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Sample records for multiple mediational effects

  1. Interventional Effects for Mediation Analysis with Multiple Mediators.

    Vansteelandt, Stijn; Daniel, Rhian M

    2017-03-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

  2. Interventional effects for mediation analysis with multiple mediators

    Vansteelandt, Stijn; Daniel, Rhian M.

    2017-01-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that...

  3. Mediation Analysis with Multiple Mediators

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  4. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets ...

  5. Mediation Analysis with Multiple Mediators.

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  6. Estimation of causal mediation effects for a dichotomous outcome in multiple-mediator models using the mediation formula.

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M

    2013-10-30

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a nonzero total mediation effect increases as the correlation coefficient between two mediators increases, whereas power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a non-zero total mediation effect increases as the correlation coefficient between two mediators increases, while power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. PMID:23650048

  8. Decomposition of the Total Effect in the Presence of Multiple Mediators and Interactions.

    Bellavia, Andrea; Valeri, Linda

    2018-06-01

    Mediation analysis allows decomposing a total effect into a direct effect of the exposure on the outcome and an indirect effect operating through a number of possible hypothesized pathways. Recent studies have provided formal definitions of direct and indirect effects when multiple mediators are of interest and have described parametric and semiparametric methods for their estimation. Investigating direct and indirect effects with multiple mediators, however, can be challenging in the presence of multiple exposure-mediator and mediator-mediator interactions. In this paper we derive a decomposition of the total effect that unifies mediation and interaction when multiple mediators are present. We illustrate the properties of the proposed framework in a secondary analysis of a pragmatic trial for the treatment of schizophrenia. The decomposition is employed to investigate the interplay of side effects and psychiatric symptoms in explaining the effect of antipsychotic medication on quality of life in schizophrenia patients. Our result offers a valuable tool to identify the proportions of total effect due to mediation and interaction when more than one mediator is present, providing the finest decomposition of the total effect that unifies multiple mediators and interactions.

  9. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

    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.

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

    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.

  11. Causal mediation analysis with multiple mediators.

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

    2015-03-01

    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 causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  12. Flexible Mediation Analysis With Multiple Mediators.

    Steen, Johan; Loeys, Tom; Moerkerke, Beatrijs; Vansteelandt, Stijn

    2017-07-15

    The advent of counterfactual-based mediation analysis has triggered enormous progress on how, and under what assumptions, one may disentangle path-specific effects upon combining arbitrary (possibly nonlinear) models for mediator and outcome. However, current developments have largely focused on single mediators because required identification assumptions prohibit simple extensions to settings with multiple mediators that may depend on one another. In this article, we propose a procedure for obtaining fine-grained decompositions that may still be recovered from observed data in such complex settings. We first show that existing analytical approaches target specific instances of a more general set of decompositions and may therefore fail to provide a comprehensive assessment of the processes that underpin cause-effect relationships between exposure and outcome. We then outline conditions for obtaining the remaining set of decompositions. Because the number of targeted decompositions increases rapidly with the number of mediators, we introduce natural effects models along with estimation methods that allow for flexible and parsimonious modeling. Our procedure can easily be implemented using off-the-shelf software and is illustrated using a reanalysis of the World Health Organization's Large Analysis and Review of European Housing and Health Status (WHO-LARES) study on the effect of mold exposure on mental health (2002-2003). © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. mma: An R Package for Mediation Analysis with Multiple Mediators

    Qingzhao Yu; Bin Li

    2017-01-01

    Mediation refers to the effect transmitted by mediators that intervene in the relationship between an exposure and a response variable. Mediation analysis has been broadly studied in many fields. However, it remains a challenge for researchers to consider complicated associations among variables and to differentiate individual effects from multiple mediators. [1] proposed general definitions of mediation effects that were adaptable to all different types of response (categorical or continuous...

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

    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.

  15. Causal mediation analysis with multiple causally non-ordered mediators.

    Taguri, Masataka; Featherstone, John; Cheng, Jing

    2018-01-01

    In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

  16. Mediation analysis with multiple versions of the mediator.

    Vanderweele, Tyler J

    2012-05-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well-defined hypothetical interventions on the mediator. In many settings, there may be multiple ways to fix the mediator to a particular value, and these various hypothetical interventions may have very different implications for the outcome of interest. In this paper, we consider mediation analysis when multiple versions of the mediator are present. Specifically, we consider the problem of attempting to decompose a total effect of an exposure on an outcome into the portion through the intermediate and the portion through other pathways. We consider the setting in which there are multiple versions of the mediator but the investigator has access only to data on the particular measurement, not information on which version of the mediator may have brought that value about. We show that the quantity that is estimated as a natural indirect effect using only the available data does indeed have an interpretation as a particular type of mediated effect; however, the quantity estimated as a natural direct effect, in fact, captures both a true direct effect and an effect of the exposure on the outcome mediated through the effect of the version of the mediator that is not captured by the mediator measurement. The results are illustrated using 2 examples from the literature, one in which the versions of the mediator are unknown and another in which the mediator itself has been dichotomized.

  17. mma: An R Package for Mediation Analysis with Multiple Mediators

    Qingzhao Yu

    2017-04-01

    Full Text Available Mediation refers to the effect transmitted by mediators that intervene in the relationship between an exposure and a response variable. Mediation analysis has been broadly studied in many fields. However, it remains a challenge for researchers to consider complicated associations among variables and to differentiate individual effects from multiple mediators. [1] proposed general definitions of mediation effects that were adaptable to all different types of response (categorical or continuous, exposure, or mediation variables. With these definitions, multiple mediators of different types can be considered simultaneously, and the indirect effects carried by individual mediators can be separated from the total effect. Moreover, the derived mediation analysis can be performed with general predictive models. That is, the relationships among variables can be modeled using not only generalized linear models but also nonparametric models such as the Multiple Additive Regression Trees. Therefore, more complicated variable transformations and interactions can be considered in analyzing the mediation effects. The proposed method is realized by the R package 'mma'. We illustrate in this paper the proposed method and how to use 'mma' to estimate mediation effects and make inferences.

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

    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%.

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

    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

  20. Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

    Huang, Yen-Tsung; Yang, Hwai-I

    2017-05-01

    Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

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

    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…

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

    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...

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

    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.

  4. Mediation analysis with multiple versions of the mediator

    VanderWeele, Tyler J.

    2012-01-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well defined hypothetical interventions on the mediator. In many settings there may be multiple ways to fix the mediator to a particular value and these different hypothetical interventions may have very different implications for the outcome of interest. In this paper we cons...

  5. Education and health and well-being: direct and indirect effects with multiple mediators and interactions with multiple imputed data in Stata.

    Sheikh, Mashhood Ahmed; Abelsen, Birgit; Olsen, Jan Abel

    2017-11-01

    Previous methods for assessing mediation assume no multiplicative interactions. The inverse odds weighting (IOW) approach has been presented as a method that can be used even when interactions exist. The substantive aim of this study was to assess the indirect effect of education on health and well-being via four indicators of adult socioeconomic status (SES): income, management position, occupational hierarchy position and subjective social status. 8516 men and women from the Tromsø Study (Norway) were followed for 17 years. Education was measured at age 25-74 years, while SES and health and well-being were measured at age 42-91 years. Natural direct and indirect effects (NIE) were estimated using weighted Poisson regression models with IOW. Stata code is provided that makes it easy to assess mediation in any multiple imputed dataset with multiple mediators and interactions. Low education was associated with lower SES. Consequently, low SES was associated with being unhealthy and having a low level of well-being. The effect (NIE) of education on health and well-being is mediated by income, management position, occupational hierarchy position and subjective social status. This study contributes to the literature on mediation analysis, as well as the literature on the importance of education for health-related quality of life and subjective well-being. The influence of education on health and well-being had different pathways in this Norwegian sample. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

    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.

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

    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.

  8. Mediatization: a concept, multiple voices

    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.

  9. Causal Mediation Analysis with Multiple Mediators

    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...

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

    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

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

    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.

  12. Depression and pain: testing of serial multiple mediators.

    Wongpakaran, Tinakon; Wongpakaran, Nahathai; Tanchakvaranont, Sitthinant; Bookkamana, Putipong; Pinyopornpanish, Manee; Wannarit, Kamonporn; Satthapisit, Sirina; Nakawiro, Daochompu; Hiranyatheb, Thanita; Thongpibul, Kulvadee

    2016-01-01

    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. 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. Perceived stress, self-sacrificing interpersonal style, and cognitive function were found to significantly mediate the relationship between depression and pain, while controlling for demographic variables. The total effect of depression on pain was significant. This model, with an additional three mediators, accounted for 15% of the explained variance in pain compared to 9% without mediators. For the alternative model, after controlling for the mediators, a nonsignificant total direct effect level of self-sacrificing was found, suggesting that the effect of self-sacrificing on pain was based only on an indirect effect and that perceived stress was found to be the strongest mediator. Serial mediation may help us to see how depression and pain are linked and what the fundamental mediators are in the chain. No significant, indirect effect of self-sacrificing on pain was observed, if perceived stress was not part of the depression and/or cognitive function mediational chain. The results shown here have implications for future research, both in terms of testing the model and in

  13. Causal mediation analysis with multiple mediators in the presence of treatment noncompliance.

    Park, Soojin; Kürüm, Esra

    2018-05-20

    Randomized experiments are often complicated because of treatment noncompliance. This challenge prevents researchers from identifying the mediated portion of the intention-to-treated (ITT) effect, which is the effect of the assigned treatment that is attributed to a mediator. One solution suggests identifying the mediated ITT effect on the basis of the average causal mediation effect among compliers when there is a single mediator. However, considering the complex nature of the mediating mechanisms, it is natural to assume that there are multiple variables that mediate through the causal path. Motivated by an empirical analysis of a data set collected in a randomized interventional study, we develop a method to estimate the mediated portion of the ITT effect when both multiple dependent mediators and treatment noncompliance exist. This enables researchers to make an informed decision on how to strengthen the intervention effect by identifying relevant mediators despite treatment noncompliance. We propose a nonparametric estimation procedure and provide a sensitivity analysis for key assumptions. We conduct a Monte Carlo simulation study to assess the finite sample performance of the proposed approach. The proposed method is illustrated by an empirical analysis of JOBS II data, in which a job training intervention was used to prevent mental health deterioration among unemployed individuals. Copyright © 2018 John Wiley & Sons, Ltd.

  14. Practical guidance for conducting mediation analysis with multiple mediators using inverse odds ratio weighting.

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

    2015-03-01

    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 between the exposure (treatment) and multiple mediators, conditional on covariates, by regressing exposure on mediators and covariates. The inverse of the covariate-adjusted exposure-mediator odds ratio association is used to weight the primary analytical regression of the outcome on treatment. The treatment coefficient in such a weighted regression estimates the natural direct effect of treatment on the outcome, and indirect effects are identified by subtracting direct effects from total effects. Weighting renders treatment and mediators independent, thereby deactivating indirect pathways of the mediators. This new mediation technique accommodates multiple discrete or continuous mediators. IORW is easily implemented and is appropriate for any standard regression model, including quantile regression and survival analysis. An empirical example is given using data from the Moving to Opportunity (1994-2002) experiment, testing whether neighborhood context mediated the effects of a housing voucher program on obesity. Relevant Stata code (StataCorp LP, College Station, Texas) is provided. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis.

    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.

  16. Depression and pain: testing of serial multiple mediators

    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

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

    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.

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

    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

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

    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...

  20. Multiple functions of the S-phase checkpoint mediator.

    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.

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

    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.

  2. Efficient nonparametric estimation of causal mediation effects

    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...

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

    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.

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

    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…

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

    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.

  6. Multifunctional Curcumin Mediate Multitherapeutic Effects.

    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®.

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

    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.

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

    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.

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

    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.

  10. 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

    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.

  11. 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.

    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.

  12. Semiotic mediation: from multiplication properties to arithmetical expressions

    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.

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

    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.

  14. Immunomodulatory Effects Mediated by Dopamine

    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

  15. Immunomodulatory Effects Mediated by Dopamine

    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.

  16. Photon-mediated electron multiplication in liquid xenon doped with trimethylamine

    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.)

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

    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...

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

    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.

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

    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.

  20. Determination of multiple scattering effects

    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

  1. Stress Effects on Multiple Memory System Interactions

    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

  2. Stress Effects on Multiple Memory System Interactions

    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.

  3. Stress Effects on Multiple Memory System Interactions.

    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.

  4. Simultaneous presence of endogenous retrovirus and herpes virus antigens has profound effect on cell-mediated immune responses: implications for multiple sclerosis

    Brudek, T.; Christensen, T.; Hansen, H.J.

    2004-01-01

    Retroviruses have been suggested as possible pathogenic factors in multiple sclerosis (MS), supported by the observation that endogenous retroviruses are activated in MS patients. Different members of the herpes family of which several are neurotropic have also been suggested as factors in MS pat...

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

    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.

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

    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.

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

    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.

  8. The Multiple Roles of the Task Design Mediator in Telecollaboration

    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…

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

    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.

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

    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....

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

    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.

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

    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.

  13. Filipino Americans and Racism: A Multiple Mediation Model of Coping

    Alvarez, Alvin N.; Juang, Linda P.

    2010-01-01

    Although the literature on Asian Americans and racism has been emerging, few studies have examined how coping influences one's encounters with racism. To advance the literature, the present study focused on the psychological impact of Filipino Americans' experiences with racism and the role of coping as a mediator using a community-based sample of…

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

    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…

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

    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

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

    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…

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

    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)

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

    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.

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

    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.

  20. Regeneration and Agrobacterium-mediated transformation of multiple lily cultivars

    Wang, Yue; Kronenburg-van de Ven, van B.C.E.; Menzel, T.R.; Maliepaard, C.A.; Shen, X.; Krens, F.A.

    2012-01-01

    To pursue genetic improvement of lily, efficiency of both regeneration and transformation from callus cultures induced from different explants were evaluated in multiple cultivars. Thirty-five callus lines induced from filaments or styles and one control callus line derived from bulb scales of in

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

    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.

  2. Lysophosphatidic acid as a lipid mediator with multiple biological actions.

    Aikawa, Shizu; Hashimoto, Takafumi; Kano, Kuniyuki; Aoki, Junken

    2015-02-01

    Lysophosphatidic acid (LPA) is one of the simplest glycerophospholipids with one fatty acid chain and a phosphate group as a polar head. Although LPA had been viewed just as a metabolic intermediate in de novo lipid synthetic pathways, it has recently been paid much attention as a lipid mediator. LPA exerts many kinds of cellular processes, such as cell proliferation and smooth muscle contraction, through cognate G protein-coupled receptors. Because lipids are not coded by the genome directly, it is difficult to know their patho- and physiological roles. However, recent studies have identified several key factors mediating the biological roles of LPA, such as receptors and producing enzymes. In addition, studies of transgenic and gene knockout animals for these LPA-related genes, have revealed the biological significance of LPA. In this review we will summarize recent advances in the studies of LPA production and its roles in both physiological and pathological conditions. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

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

    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.

  4. Mediatization

    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...

  5. Multiple mediation analysis of the relationship between rapid naming and reading

    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...

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

    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.

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

    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...

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  13. Assessing Natural Direct and Indirect Effects Through Multiple Pathways

    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...

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

    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.

  15. Retinal dopamine mediates multiple dimensions of light-adapted vision.

    Jackson, Chad R; Ruan, Guo-Xiang; Aseem, Fazila; Abey, Jane; Gamble, Karen; Stanwood, Greg; Palmiter, Richard D; Iuvone, P Michael; McMahon, Douglas G

    2012-07-04

    Dopamine is a key neuromodulator in the retina and brain that supports motor, cognitive, and visual function. Here, we developed a mouse model on a C57 background in which expression of the rate-limiting enzyme for dopamine synthesis, tyrosine hydroxylase, is specifically disrupted in the retina. This model enabled assessment of the overall role of retinal dopamine in vision using electrophysiological (electroretinogram), psychophysical (optokinetic tracking), and pharmacological techniques. Significant disruptions were observed in high-resolution, light-adapted vision caused by specific deficits in light responses, contrast sensitivity, acuity, and circadian rhythms in this retinal dopamine-depleted mouse model. These global effects of retinal dopamine on vision are driven by the differential actions of dopamine D1 and D4 receptors on specific retinal functions and appear to be due to the ongoing bioavailability of dopamine rather than developmental effects. Together, our data indicate that dopamine is necessary for the circadian nature of light-adapted vision as well as optimal contrast detection and acuity.

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

    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.

  17. Comments: Causal Interpretations of Mediation Effects

    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…

  18. Ketone Bodies Mediate Antiseizure Effects

    Jena M. Krueger

    2015-10-01

    Full Text Available Investigators from The Barrow Neurological Institute, Creighton University, University of Kentucky and the University of Calgary Faculty of Medicine investigated the effect of ketone bodies and the ketogenic diet on epileptic Kcna1-null mice.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

  5. Immunomodulatory Effects Mediated by Serotonin

    Rodrigo Arreola

    2015-01-01

    Full Text Available Serotonin (5-HT induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b downstream signaling transduction proteins; and (c enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines. This review covers the clinical and experimental mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell-specific and depend on the expression of serotonergic components in immune cells. Consequently, 5-HT can modulate several immunological events, such as chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis. The effects of 5-HT on immune cells may be relevant in the clinical outcome of pathologies with an inflammatory component. Major depression, fibromyalgia, Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated with changes in the serotonergic system associated with leukocytes. Thus, pharmacological regulation of the serotonergic system may modulate immune function and provide therapeutic alternatives for these diseases.

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

    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…

  7. Identification as a Mediator of Celebrity Effects.

    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…

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

    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.

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

    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.

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

    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.

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

    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.

  12. Multiple interdependencies and workgroup effectiveness

    Rispens, Sonja

    2006-01-01

    In this thesis I focus on the question how the alignment of interdependency leads to an effective level of performance in work groups or teams. For the continuance of every organization it is important to organize individuals so that their actions are aligned (Heath & Staudenmayer, 2000). In this

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

    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.

  14. Estimating and Testing Mediation Effects with Censored Data

    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…

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

    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.

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

    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 ...

  17. Brain mediators of the effects of noxious heat on pain.

    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.

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

    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.

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

    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.

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

    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.

  1. Estimating scaled treatment effects with multiple outcomes.

    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.

  2. Opioid receptor mediated anticonvulsant effect of pentazocine.

    Khanna, N; Khosla, R; Kohli, J

    1998-01-01

    Intraperitoneal (i.p.) administration of (+/-) pentazocine (10, 30 & 50 mg/kg), a Sigma opioid agonist, resulted in a dose dependent anticonvulsant action against maximal electroshock seizures in mice. This anticonvulsant effect of pentazocine was not antagonized by both the doses of naloxone (1 and 10 mg/kg) suggesting thereby that its anticonvulsant action is probably mediated by Sigma opiate binding sites. Its anticonvulsant effect was potentiated by both the anticonvulsant drugs viz. diazepam and diphenylhydantoin. Morphine, mu opioid agonist, on the other hand, failed to protect the animals against maximal electroshock seizures when it was given in doses of 10-40 mg/kg body wt.

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

    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.

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

    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

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

    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...

  6. Glucocorticoids as mediators of developmental programming effects.

    Khulan, Batbayar; Drake, Amanda J

    2012-10-01

    Epidemiological evidence suggests that exposure to an adverse environment in early life is associated with an increased risk of cardio-metabolic and behavioral disorders in adulthood, a phenomenon termed 'early life programming'. One major hypothesis for early life programming is fetal glucocorticoid overexposure. In animal studies, prenatal glucocorticoid excess as a consequence of maternal stress or through exogenous administration to the mother or fetus is associated with programming effects on cardiovascular and metabolic systems and on the brain. These effects can be transmitted to subsequent generations. Studies in humans provide some evidence that prenatal glucocorticoid exposure may exert similar programming effects on glucose/insulin homeostasis, blood pressure and neurodevelopment. The mechanisms by which glucocorticoids mediate these effects are unclear but may include a role for epigenetic modifications. This review discusses the evidence for glucocorticoid programming in animal models and in humans. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    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

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

    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.

  9. Stress Effects on Multiple Memory System Interactions

    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 syst...

  10. Multiple-state Feshbach resonances mediated by high-order couplings

    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

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

    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.

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

    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

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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

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

    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)

  3. Alcohol: A Nutrient with Multiple Salutary Effects

    Henry J. Pownall

    2015-03-01

    Full Text Available Numerous studies have shown that cardiovascular disease is lower among alcohol consumers than among nonconsumers. Many of the metabolic effects of alcohol are mediated by its terminal metabolite, acetate, which has reported insulinemic properties. There have been few rational metabolic targets that underly its cardioprotective effects until it was reported that acetate, the terminal product of alcohol metabolism, is the ligand for G-protein coupled receptor 43 (GPCR43, which is highly expressed in adipose tissue. Here, we recast much of some of the major lipid and lipoprotein effects of alcohol in the context of this newly discovered G-protein and develop a mechanistic model connecting the interaction of acetate with adipose tissue-GPCR43 with these effects. According to our model, ingestions of acetate could replace alcohol as a means of improving plasma lipid risk factors, improving glucose disposal, and reducing cardiovascular disease. Future studies should include biochemical, cell, animal, and human tests of acetate on energy metabolism.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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/.

  9. Possible Lingering Effects of Multiple Past Concussions

    Grant L. Iverson

    2012-01-01

    Full Text Available Background. The literature on lingering or “cumulative” effects of multiple concussions is mixed. The purpose of this study was to examine whether athletes with a history of three or more concussions perform more poorly on neuropsychological testing or report more subjective symptoms during a baseline, preseason evaluation. Hypothesis. Athletes reporting three or more past concussions would perform more poorly on preseason neurocognitive testing. Study Design. Case-control study. Methods. An archival database including 786 male athletes who underwent preseason testing with a computerized battery (ImPACT was used to select the participants. Twenty-six athletes, between the ages of 17 and 22 with a history of three or more concussions, were identified. Athletes with no history of concussion were matched, in a case-control fashion, on age, education, self-reported ADHD, school, sport, and, when possible, playing position and self-reported academic problems. Results. The two groups were compared on the four neuropsychological composite scores from ImPACT using multivariate analysis of variance followed by univariate ANOVAs. MANOVA revealed no overall significant effect. Exploratory ANOVAs were conducted using Verbal Memory, Visual Memory, Reaction Time, Processing Speed, and Postconcussion Scale composite scores as dependent variables. There was a significant effect for only the Verbal Memory composite. Conclusions. Although inconclusive, the results suggest that some athletes with multiple concussions could have lingering memory deficits.

  10. Emergent and multiplicative effect in a cluster

    I. V. Linev

    2016-01-01

    Full Text Available The concept “Cluster” of domestic and foreign literature traditionally is considered as administrative and organizational education. At the same time he represents the social and economic object created for life support of the person. The cluster is considered as system object. The main signs are defined and his life cycle is considered. Cluster self-organization takes place stages: growth of organizational weight and effects, market threats and restrictions interfering growth of organizational weight. Development of clusters requires the state support in various forms which is offered to be carried out at various stages depending on his type. The cluster is considered as the economic system possessing an emergent which dynamic aspect is the synergy, the receiving multiplicative effect causing an opportunity. The quantitative assessment of size of the listed effects represents rather complex challenge, at the same time there is a number of the factors which are with her in directly proportional dependence. The synergy which is present at a cluster allows to gain social and economic effect of his functioning by means of integration of effects of all structural elements bigger, than their simple sum. The emergent in a cluster causes increase of productivity at the expense of innovations in technological and organizational spheres and stimulations of the birth of new businesses. The multiplicative effect arising in a cluster provides incremental nature of economic results. It is possible to refer the following to the main economic results received from creation and development of clusters: decrease in transactional and transformational expenses and costs of formation and further use of infrastructure, economy of costs of introduction and development of the high and innovative technologies, optimization of logistic and information expenses, increase of business reputation and investment appeal.

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

    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

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

    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…

  13. Insecticide resistance is mediated by multiple mechanisms in recently introduced Aedes aegypti from Madeira Island (Portugal).

    Seixas, Gonçalo; Grigoraki, Linda; Weetman, David; Vicente, José Luís; Silva, Ana Clara; Pinto, João; Vontas, John; Sousa, Carla Alexandra

    2017-07-01

    Aedes aegypti is a major mosquito vector of arboviruses, including dengue, chikungunya and Zika. In 2005, Ae. aegypti was identified for the first time in Madeira Island. Despite an initial insecticide-based vector control program, the species expanded throughout the Southern coast of the island, suggesting the presence of insecticide resistance. Here, we characterized the insecticide resistance status and the underlying mechanisms of two populations of Ae. aegypti from Madeira Island, Funchal and Paúl do Mar. WHO susceptibility bioassays indicated resistance to cyfluthrin, permethrin, fenitrothion and bendiocarb. Use of synergists significantly increased mortality rates, and biochemical assays indicated elevated activities of detoxification enzymes, suggesting the importance of metabolic resistance. Microarray-based transcriptome analysis detected significant upregulation in both populations of nine cytochrome P450 oxidase genes (including four known pyrethroid metabolizing enzymes), the organophosphate metabolizer CCEae3a, Glutathione-S-transferases, and multiple putative cuticle proteins. Genotyping of knockdown resistance loci linked to pyrethroid resistance revealed fixation of the 1534C mutation, and presence with moderate frequencies of the V1016I mutation in each population. Significant resistance to three major insecticide classes (pyrethroid, carbamate and organophosphate) is present in Ae. aegypti from Madeira Island, and appears to be mediated by multiple mechanisms. Implementation of appropriate resistance management strategies including rotation of insecticides with alternative modes of action, and methods other than chemical-based vector control are strongly advised to delay or reverse the spread of resistance and achieve efficient control.

  14. Searching for Variables and Models to Investigate Mediators of Learning from Multiple Representations

    Rau, Martina A.; Scheines, Richard

    2012-01-01

    Although learning from multiple representations has been shown to be effective in a variety of domains, little is known about the mechanisms by which it occurs. We analyzed log data on error-rate, hint-use, and time-spent obtained from two experiments with a Cognitive Tutor for fractions. The goal of the experiments was to compare learning from…

  15. Membrane Transporters as Mediators of Cisplatin Effects and Side Effects

    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.

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

    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

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

    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.

  18. Effects of Sport Climbing on Multiple Sclerosis

    Julia Steimer

    2017-12-01

    Full Text Available Multiple sclerosis (MS is an autoimmune and neurodegenerative disease of the central nervous system (CNS with different types of disease courses (relapsing-remitting, secondary-progressive, primary progressive that leads to physical as well as mental disability. The symptoms comprise paresis or/and paralysis, ataxia, bladder dysfunction, visual problems as well as effects on cognition. There is limited data regarding the possible effects of sport climbing respectively therapeutic climbing on patients with MS. Sport climbing offers many potentially beneficial effects for patients with MS since there are effects on coordination, muscular strength, and cognition to name the most relevant ones. Also, disease models in rodents point toward such positive outcomes of climbing. Therefore, we assessed the currently available research literature on general effects of physical exercise, impact of climbing on body and mind and therapeutic climbing for prevention or therapy for the treatment of MS. The sparse published controlled trials that investigated this sport activity on different groups of patients with neurological or geriatric diseases grossly differ in study design and outcome parameters. Nevertheless, it appears that climbing offers the opportunity to improve some of the symptoms of patients with MS and can contribute to an enhanced quality of life.

  19. School Processes Mediate School Compositional Effects: Model Specification and Estimation

    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…

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

    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...

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

    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)

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

    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

  3. The Effect of Fearful Expressions on Multiple Face Tracking

    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.

  4. Effects of multiple spreaders in community networks

    Hu, Zhao-Long; Ren, Zhuo-Ming; Yang, Guang-Yong; Liu, Jian-Guo

    2014-12-01

    Human contact networks exhibit the community structure. Understanding how such community structure affects the epidemic spreading could provide insights for preventing the spreading of epidemics between communities. In this paper, we explore the spreading of multiple spreaders in community networks. A network based on the clustering preferential mechanism is evolved, whose communities are detected by the Girvan-Newman (GN) algorithm. We investigate the spreading effectiveness by selecting the nodes as spreaders in the following ways: nodes with the largest degree in each community (community hubs), the same number of nodes with the largest degree from the global network (global large-degree) and randomly selected one node within each community (community random). The experimental results on the SIR model show that the spreading effectiveness based on the global large-degree and community hubs methods is the same in the early stage of the infection and the method of community random is the worst. However, when the infection rate exceeds the critical value, the global large-degree method embodies the worst spreading effectiveness. Furthermore, the discrepancy of effectiveness for the three methods will decrease as the infection rate increases. Therefore, we should immunize the hubs in each community rather than those hubs in the global network to prevent the outbreak of epidemics.

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

    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

  6. Gambogic acid inhibits multiple myeloma mediated osteoclastogenesis through suppression of chemokine receptor CXCR4 signaling pathways.

    Pandey, Manoj K; Kale, Vijay P; Song, Chunhua; Sung, Shen-shu; Sharma, Arun K; Talamo, Giampaolo; Dovat, Sinisa; Amin, Shantu G

    2014-10-01

    Bone disease, characterized by the presence of lytic lesions and osteoporosis is the hallmark of multiple myeloma (MM). Stromal cell-derived factor 1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4), has been implicated as a regulator of bone resorption, suggesting that agents that can suppress SDF1α/CXCR4 signaling might inhibit osteoclastogenesis, a process closely linked to bone resorption. We, therefore, investigated whether gambogic acid (GA), a xanthone, could inhibit CXCR4 signaling and suppress osteoclastogenesis induced by MM cells. Through docking studies we predicted that GA directly interacts with CXCR4. This xanthone down-regulates the expression of CXCR4 on MM cells in a dose- and time-dependent manner. The down-regulation of CXCR4 was not due to proteolytic degradation, but rather GA suppresses CXCR4 mRNA expression by inhibiting nuclear factor-kappa B (NF-κB) DNA binding. This was further confirmed by quantitative chromatin immunoprecipitation assay, as GA inhibits p65 binding at the CXCR4 promoter. GA suppressed SDF-1α-induced chemotaxis of MM cells and downstream signaling of CXCR4 by inhibiting phosphorylation of Akt, p38, and Erk1/2 in MM cells. GA abrogated the RANKL-induced differentiation of macrophages to osteoclasts in a dose- and time-dependent manner. In addition, we found that MM cells induced differentiation of macrophages to osteoclasts, and that GA suppressed this process. Importantly, suppression of osteoclastogenesis by GA was mediated through IL-6 inhibition. Overall, our results show that GA is a novel inhibitor of CXCR4 expression and has a strong potential to suppress osteoclastogenesis mediated by MM cells. Published by Elsevier Inc.

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

    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.

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

    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...

  9. Proteins mediating DNA loops effectively block transcription.

    Vörös, Zsuzsanna; Yan, Yan; Kovari, Daniel T; Finzi, Laura; Dunlap, David

    2017-07-01

    Loops are ubiquitous topological elements formed when proteins simultaneously bind to two noncontiguous DNA sites. While a loop-mediating protein may regulate initiation at a promoter, the presence of the protein at the other site may be an obstacle for RNA polymerases (RNAP) transcribing a different gene. To test whether a DNA loop alters the extent to which a protein blocks transcription, the lac repressor (LacI) was used. The outcome of in vitro transcription along templates containing two LacI operators separated by 400 bp in the presence of LacI concentrations that produced both looped and unlooped molecules was visualized with scanning force microscopy (SFM). An analysis of transcription elongation complexes, moving for 60 s at an average of 10 nt/s on unlooped DNA templates, revealed that they more often surpassed LacI bound to the lower affinity O2 operator than to the highest affinity Os operator. However, this difference was abrogated in looped DNA molecules where LacI became a strong roadblock independently of the affinity of the operator. Recordings of transcription elongation complexes, using magnetic tweezers, confirmed that they halted for several minutes upon encountering a LacI bound to a single operator. The average pause lifetime is compatible with RNAP waiting for LacI dissociation, however, the LacI open conformation visualized in the SFM images also suggests that LacI could straddle RNAP to let it pass. Independently of the mechanism by which RNAP bypasses the LacI roadblock, the data indicate that an obstacle with looped topology more effectively interferes with transcription. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

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

    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.

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

    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.

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

    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...

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

    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…

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

    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…

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

    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

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

    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.

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

    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

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

    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.

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

    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.

  20. Genetic transformation and gene silencing mediated by multiple copies of a transgene in eastern white pine.

    Tang, Wei; Newton, Ronald J; Weidner, Douglas A

    2007-01-01

    An efficient transgenic eastern white pine (Pinus strobus L.) plant regeneration system has been established using Agrobacterium tumefaciens strain GV3850-mediated transformation and the green fluorescent protein (gfp) gene as a reporter in this investigation. Stable integration of transgenes in the plant genome of pine was confirmed by polymerase chain reaction (PCR), Southern blot, and northern blot analyses. Transgene expression was analysed in pine T-DNA transformants carrying different numbers of copies of T-DNA insertions. Post-transcriptional gene silencing (PTGS) was mostly obtained in transgenic lines with more than three copies of T-DNA, but not in transgenic lines with one copy of T-DNA. In situ hybridization chromosome analysis of transgenic lines demonstrated that silenced transgenic lines had two or more T-DNA insertions in the same chromosome. These results suggest that two or more T-DNA insertions in the same chromosome facilitate efficient gene silencing in transgenic pine cells expressing green fluorescent protein. There were no differences in shoot differentiation and development between transgenic lines with multiple T-DNA copies and transgenic lines with one or two T-DNA copies.

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

    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.

  2. Atrial natriuretic peptide: a possible mediator involved in dexamethasone's inhibition of cell proliferation in multiple myeloma.

    Ding, Jiang-Hua; Chang, Yu-Sui

    2012-08-01

    Atrial natriuretic peptide (ANP) has been recognized for several decades for its role of regulating blood pressure. Recently, cumulating evidences show that ANP plays an anticancer role in various solid tumors via blocking the kinase cascade of Ras-MEK1/2-ERK1/2 with the result of inhibition of DNA synthesis. ANP, as well as its receptors (NPR-A and NPR-C) has been identified present in the embryonic stem cell and a wide range of cancer cells. Various lymphoid organs, such as lymph nodes, have been detected the presence of ANP. Multiple myeloma (MM), though the therapies have evolved significantly, is still an incurable disease as B lymphocyte cell neoplasm. Dexamethasone is the cornerstone in treatment of MM via inactivation of Ras-MEK1/2-ERK1/2 cascade reaction. Coincidently, dexamethasone can increase the expression of ANP markedly. Nevertheless, the role of ANP in MM is unclear. Based on these results above, we raise the hypothesis that ANP is involved in mediating dexamethasone's inhibition of proliferation in MM cells, which suggests that ANP may be a potential agent to treat MM. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

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

    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.

  4. The influence of multiple trials and computer-mediated communication on collaborative and individual semantic recall.

    Hinds, Joanne M; Payne, Stephen J

    2018-04-01

    Collaborative inhibition is a phenomenon where collaborating groups experience a decrement in recall when interacting with others. Despite this, collaboration has been found to improve subsequent individual recall. We explore these effects in semantic recall, which is seldom studied in collaborative retrieval. We also examine "parallel CMC", a synchronous form of computer-mediated communication that has previously been found to improve collaborative recall [Hinds, J. M., & Payne, S. J. (2016). Collaborative inhibition and semantic recall: Improving collaboration through computer-mediated communication. Applied Cognitive Psychology, 30(4), 554-565]. Sixty three triads completed a semantic recall task, which involved generating words beginning with "PO" or "HE" across three recall trials, in one of three retrieval conditions: Individual-Individual-Individual (III), Face-to-face-Face-to-Face-Individual (FFI) and Parallel-Parallel-Individual (PPI). Collaborative inhibition was present across both collaborative conditions. Individual recall in Recall 3 was higher when participants had previously collaborated in comparison to recalling three times individually. There was no difference between face-to-face and parallel CMC recall, however subsidiary analyses of instance repetitions and subjective organisation highlighted differences in group members' approaches to recall in terms of organisation and attention to others' contributions. We discuss the implications of these findings in relation to retrieval strategy disruption.

  5. Direct and indirect associations between social anxiety and nicotine dependence and cessation problems: multiple mediator analyses.

    Buckner, Julia D; Farris, Samantha G; Schmidt, Norman B; Zvolensky, Michael J

    2014-06-01

    Little empirical work has evaluated why socially anxious smokers are especially vulnerable to more severe nicotine dependence and cessation failure. Presumably, these smokers rely on cigarettes to help them manage their chronically elevated negative affect elicited by a wide array of social contexts. The current study examined the direct and indirect effects of social anxiety cross-sectionally in regard to a range of smoking processes among 466 treatment-seeking smokers. Negative affect and negative affect reduction motives were examined as mediators of the relations of social anxiety with nicotine dependence and cessation problems. Social anxiety was directly and robustly associated with perceived barriers to smoking cessation and problems experienced during past quit attempts. Social anxiety was also associated with greater nicotine dependence and smoking inflexibility indirectly through negative affect and negative affect smoking motives. Negative affect and smoking to reduce negative affect mediated these relations. These findings document the important role of negative affect and negative affect reduction motives in the relationships of social anxiety with nicotine dependence and cessation problems.

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

    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.

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

    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.

  8. Multiple scattering effects in 7Li

    Cox, A.J.; Warner, P.C.

    1985-01-01

    The differential cross-sections for the production of 0.478 MeV γ-rays following the inelastic scattering of 14 MeV neutrons in large samples of LiF, which will be used in fusion reactor blankets, have been measured. The neutrons were produced using the 3 H(d,n) 4 α reaction, with the deuterons being accelerated by a 150 kV SAMES type accelerator. In order to reduce the background level the γ-ray signal was gated, using a time of flight technique based on the α-particle associated with neutron production. Measurements of the γ-ray production differential cross-sections were made for various thicknesses of LiF. The results were compared to the predictions of the Monte Carlo Computer Code, MORSE, with an agreement of +-11% being achieved. In addition a phenomenological expression was found which is capable of predicting the variation in cross-sections with thickness due to multiple scattering effects to within +-12%. (author)

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

    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.

  10. Effective capacity of multiple antenna channels: Correlation and keyhole

    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

  11. A General Model for Testing Mediation and Moderation Effects

    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

  12. Gastrointestinal stimulatory and uterotonic activities of dietary radish leaves extract are mediated through multiple pathways.

    Ghayur, Muhammad Nabeel; Gilani, Anwarul Hassan

    2005-09-01

    Raphanus sativus, commonly known as radish, is a food plant known worldwide for its culinary and medicinal properties especially as a laxative and abortifacient. This study reports the gastrointestinal and uterine tone modulatory activities of the crude extract (Rl.Cr) of radish leaves. Rl.Cr, showing the presence of saponins and alkaloids, exhibited a spasmogenic effect (0.03-10 mg/mL) in isolated rabbit jejunum, rat stomach fundus and uterus which was partially blocked by atropine. In contrast, Rl.Cr was found to be devoid of any stimulatory effect in rat ileum, instead showed an inhibitory effect (0.1 mg/mL) on the ACh dose-response curves. A mild relaxant effect was also observed in rabbit jejunum at the lower doses (0.1-0.3 mg/mL) but not against K(+)-induced contractions, ruling out a calcium channel blocking effect. In guinea-pig ileum, Rl.Cr exhibited a stimulant effect resistant to atropine while sensitive to pyrilamine pretreatment. The aqueous fraction, showing a strong presence of saponins, was found to be more efficacious than the non-polar fractions in its spasmogenic effect. This study shows the presence of species-dependent gastrointestinal effects of radish mediated partially through cholinergic receptors in rabbit and rat tissues, but through histaminergic activation in the guinea-pig, providing a scientific basis for its use in gut and uterine affections while also giving a wider picture of the activity profile of radish by using different species of animals. Copyright 2005 John Wiley & Sons, Ltd.

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

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C.A.; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D’alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A.C.; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I.W.; Debouverie, Marc; D’hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F.A.; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L.; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M.A.; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N.A.; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair

    2011-01-01

    Multiple sclerosis (OMIM 126200) 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.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 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 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis. PMID:21833088

  14. R2 effect-size measures for mediation analysis

    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

  15. R2 effect-size measures for mediation analysis.

    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.

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

    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.

  17. Investigation of Fatigability during Repetitive Robot-Mediated Arm Training in People with Multiple Sclerosis.

    Deborah Severijns

    Full Text Available People with multiple sclerosis (MS are encouraged to engage in exercise programs but an increased experience of fatigue may impede sustained participation in training sessions. A high number of movements is, however, needed for obtaining optimal improvements after rehabilitation.This cross-sectional study investigated whether people with MS show abnormal fatigability during a robot-mediated upper limb movement trial. Sixteen people with MS and sixteen healthy controls performed five times three minutes of repetitive shoulder anteflexion movements. Movement performance, maximal strength, subjective upper limb fatigue and surface electromyography (median frequency and root mean square of the amplitude of the electromyography (EMG signal of the anterior deltoid were recorded during or in-between these exercises. After fifteen minutes of rest, one extra movement bout was performed to investigate how rest influences performance.A fifteen minutes upper limb movement protocol increased the perceived upper limb fatigue and induced muscle fatigue, given a decline in maximal anteflexion strength and changes of both the amplitude and the median frequency of EMG the anterior deltoid. In contrast, performance during the 3 minutes of anteflexion movements did not decline. There was no relation between changes in subjective fatigue and the changes in the amplitude and the median frequency of the anterior deltoid muscle, however, there was a correlation between the changes in subjective fatigue and changes in strength in people with MS. People with MS with upper limb weakness report more fatigue due to the repetitive movements, than people with MS with normal upper limb strength, who are comparable to healthy controls. The weak group could, however, keep up performance during the 15 minutes of repetitive movements.Albeit a protocol of repetitive shoulder anteflexion movements did not elicit a performance decline, fatigue feelings clearly increased in both

  18. Effect of multiple scattering on lidar measurements

    Cohen, A.

    1977-01-01

    The lidar equation in its standard form involves the assumption that the scattered irradiance reaching the lidar receiver has been only singly scattered. However, in the cases of scattering from clouds and thick aerosol layers, it is shown that multiple scattering cannot be neglected. An experimental method for the detection of multiple scattering by depolarization measurement techniques is discussed. One method of theoretical calculations of double-scattering is presented and discussed

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

    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...

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

    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.

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

    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.

  2. Multiple Mediation Analysis of the Relationship between Rapid Naming and Reading

    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…

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

    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…

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

    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.

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

    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...

  6. (ajst) additive main effects and multiplicative

    2013-08-02

    Aug 2, 2013 ... genotypes assessed by biplot analysis showed that the most stable ... biplot is a useful tool for the analysis of multi-environment trial (MET) data. ... multiplicative components, extracting first the additive ... The AMMI analysis of variance of cassava harvest index of the 8 .... wheat mega-environments in Iran.

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

    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.

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

    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.

  9. Testing Moderator and Mediator Effects in Counseling Psychology Research

    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…

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

    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...

  11. Reinjury anxiety, coping, and return-to-sport outcomes: a multiple mediation analysis.

    Wadey, Ross; Podlog, Leslie; Hall, Morgan; Hamson-Utley, Jordan; Hicks-Little, Charlie; Hammer, Chris

    2014-08-01

    This study aimed to examine whether the dimensions of reinjury anxiety (i.e., intensity, frequency, and direction) predicted perceived return-to-sport outcomes and whether coping mediated this relationship. Using a cross-sectional research design, 335 participants (M age = 23.5; SD = 6.6) who had sustained a sports-related injury preventing participation in training and competition for a minimum of 4 weeks (M time loss = 98 days; SD = 96.8) completed measures of reinjury anxiety (RIA-RE subscale of the Reinjury Anxiety Inventory (RIAI); Walker, Thatcher, & Lavallee, 2010), coping (MCOPE; Crocker & Graham, 1995), and perceived return-to-sport outcomes (RSSIQ; Podlog & Eklund, 2005). Pearson product-moment correlation and Preacher and Hayes's (2008) bootstrapping procedure were used to analyze the data. Consistent with our hypotheses, results indicated a positive relationship between reinjury anxiety (intensity and frequency) and heightened return concerns, whereas reinjury anxiety interpreted as facilitative toward postinjury performance was associated with a positive renewed perspective on sport participation. Significant indirect effects for coping were found for wishful thinking, venting of emotions, denial, and behavioral disengagement. Future avenues of research that aim to provide a greater knowledge and understanding of the relationship between reinjury anxiety and return-to-sport outcomes are discussed, including the need for alternative theoretical perspectives and diverse methodologies.

  12. Nuclear import of Nkx2-2 is mediated by multiple pathways

    Lin, Wenbo; Xu, PengPeng; Guo, YingYing; Jia, Qingjie; Tao, Tao

    2017-01-01

    Nkx2-2 homeoprotein is essential for the development of the central nervous system and pancreas. Although the nuclear localization signals of Nkx2-2 have been identified, the responsible transport receptor is still unknown. Here, we demonstrate that imp α1 not only interacts with Nkx2-2 but also transports it into the nucleus in vitro by acting together with imp β1. However, the nuclear import of Nkx2-2 in cells was not inhibited in response to knockdown expression of endogenous imp β1 or over-expression of Bimax2. Furthermore, imp β1 and imp 13, but not imp 4, directly interact with Nkx2-2 and are capable of transporting Nkx2-2 in an in vitro import assay. By GST pull-down assay, we demonstrate that mutation of NLS1 or NLS2 has no effect on interaction with imp α1 or imp 13, but significantly reduced binding to imp β1. Thus, the nuclear import of Nkx2-2 is mediated not only by the classical import pathway but also directly by imp β1 or imp 13.

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

    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.

  14. Grandparental effects in marine sticklebacks: transgenerational plasticity across multiple generations.

    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.

  15. Hemifield effects in multiple identity tracking.

    Charlotte Hudson

    Full Text Available In everyday life, we often need to attentively track moving objects. A previous study has claimed that this tracking occurs independently in the left and right visual hemifields (Alvarez & Cavanagh, 2005, Psychological Science,16, 637-647. Specifically, it was shown that observers were much more accurate at tracking objects that were spread over both visual hemifields as opposed to when all were confined to a single visual hemifield. In that study, observers were not required to remember the identities of the objects. Conversely, in real life, there is seldom any benefit to tracking an object unless you can also recall its identity. It has been predicted that when observers are required to remember the identities of the tracked objects a bilateral advantage should no longer be observed (Oksama & Hyönä, 2008, Cognitive Psychology, 56, 237-283. We tested this prediction and found that a bilateral advantage still occurred, though it was not as strong as when observers were not required to remember the identities of the targets. Even in the later case we found that tracking was not completely independent in the two visual hemifields. We present a combined model of multiple object tracking and multiple identity tracking that can explain our data.

  16. Multiple repair pathways mediate cellular tolerance to resveratrol-induced DNA damage.

    Liu, Ying; Wu, Xiaohua; Hu, Xiaoqing; Chen, Ziyuan; Liu, Hao; Takeda, Shunichi; Qing, Yong

    2017-08-01

    Resveratrol (RSV) has been reported to exert health benefits for the prevention and treatment of many diseases, including cancer. The anticancer mechanisms of RSV seem to be complex and may be associated with genotoxic potential. To better understand the genotoxic mechanisms, we used wild-type (WT) and a panel of isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects and molecular mechanisms of cellular tolerance to RSV. Our results showed that RSV induced significant formation of γ-H2AX foci and chromosome aberrations (CAs) in WT cells, suggesting direct DNA damage effects. Comparing the survival of WT with isogenic DNA-repair deficient DT40 cell lines demonstrated that single strand break repair (SSBR) deficient cell lines of Parp1 -/- , base excision repair (BER) deficient cell lines of Polβ -/- , homologous recombination (HR) mutants of Brca1 -/- and Brca2 -/- and translesion DNA synthesis (TLS) mutants of Rev3 -/- and Rad18 -/- were more sensitive to RSV. The sensitivities of cells were associated with enhanced DNA damage comparing the accumulation of γ-H2AX foci and number of CAs of isogenic DNA-repair deficient DT40 cell lines with WT cells. These results clearly demonstrated that RSV-induced DNA damage in DT40 cells, and multiple repair pathways including BER, SSBR, HR and TLS, play critical roles in response to RSV- induced genotoxicity. Copyright © 2017. Published by Elsevier Ltd.

  17. 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

    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...

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

    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.

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

    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.

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

    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.

  1. Parental Mediation of Television Advertising Effects.

    Robertson, Thomas S.

    1979-01-01

    Reviews the current research on the effects of television advertising on children and the interaction between parent and child regarding the child's consumer behavior. Suggests areas for future research. (JMF)

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

    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.

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

    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.

  4. Mediating role of activity level in the depressive realism effect.

    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.

  5. Mediating role of activity level in the depressive realism effect.

    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.

  6. Mediating Role of Activity Level in the Depressive Realism Effect

    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

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

    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

  8. Relationship between Academic Stress and Suicidal Ideation: Testing for Depression as a Mediator Using Multiple Regression

    Ang, Rebecca P.; Huan, Vivien S.

    2006-01-01

    Relations among academic stress, depression, and suicidal ideation were examined in 1,108 Asian adolescents 12-18 years old from a secondary school in Singapore. Using Baron and Kenny's [J Pers Soc Psychol 51:1173-1192, 1986] framework, this study tested the prediction that adolescent depression mediated the relationship between academic stress…

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

    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 that g...

  10. Training Effects on Computer-Mediated Peer Review

    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…

  11. Teacher Judgment, Student Motivation, and the Mediating Effect of Attributions

    Zhou, Ji; Urhahne, Detlef

    2013-01-01

    Based on Weiner's attributional theory of intrapersonal motivation, the mediating effect of attributions between teacher judgment and student motivation was examined. In two studies, 144 German and 272 Chinese fourth-grade elementary school students were tested on their mathematical achievement, causal ascriptions for success and failure,…

  12. Effective capacity of multiple antenna channels: Correlation and keyhole

    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.

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

    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…

  14. Exploring the relationship between socioeconomic status, control beliefs and exercise behavior: a multiple mediator model.

    Murray, Terra C; Rodgers, Wendy M; Fraser, Shawn N

    2012-02-01

    The purpose of this study was to examine the relationship between control beliefs, socioeconomic status and exercise intentions and behavior. Specifically, we examined whether distal and proximal control beliefs mediated the association between socioeconomic status and exercise intentions and behavior. A one time, cross sectional mail out survey (N = 350) was conducted in a large urban Canadian city. Distal (i.e., personal constraints) and proximal (i.e., scheduling self-efficacy) control beliefs mediated the association between socioeconomic status and exercise, explaining approximately 30% of the variance. Proximal control beliefs (i.e., scheduling self-efficacy) partially mediated the association between socioeconomic status and intentions, with the models explaining approximately 50% of the variance. Compared to individuals with lower socioeconomic status, individuals with higher socioeconomic status reported more exercise and stronger intentions to exercise. This was at least partly because higher socioeconomic status respondents reported fewer barriers in their lives, and were more confident to cope with the scheduling demands of exercise.

  15. Multiple proviral integration events after virological synapse-mediated HIV-1 spread

    Russell, Rebecca A.; Martin, Nicola; Mitar, Ivonne; Jones, Emma; Sattentau, Quentin J.

    2013-01-01

    HIV-1 can move directly between T cells via virological synapses (VS). Although aspects of the molecular and cellular mechanisms underlying this mode of spread have been elucidated, the outcomes for infection of the target cell remain incompletely understood. We set out to determine whether HIV-1 transfer via VS results in productive, high-multiplicity HIV-1 infection. We found that HIV-1 cell-to-cell spread resulted in nuclear import of multiple proviruses into target cells as seen by fluorescence in-situ hybridization. Proviral integration into the target cell genome was significantly higher than that seen in a cell-free infection system, and consequent de novo viral DNA and RNA production in the target cell detected by quantitative PCR increased over time. Our data show efficient proviral integration across VS, implying the probability of multiple integration events in target cells that drive productive T cell infection. - Highlights: • Cell-to-cell HIV-1 infection delivers multiple vRNA copies to the target cell. • Cell-to-cell infection results in productive infection of the target cell. • Cell-to-cell transmission is more efficient than cell-free HIV-1 infection. • Suggests a mechanism for recombination in cells infected with multiple viral genomes

  16. The effect of exercise therapy on fatigue in multiple sclerosis

    Andreasen, A; Stenager, E; Dalgas, U

    2011-01-01

    Fatigue occurs in the majority of patients with multiple sclerosis (MS) and therapeutic possibilities are few. Exercise therapy is a therapeutic option but no studies have systematically reviewed the existing literature evaluating the effect of exercise therapy on MS fatigue.......Fatigue occurs in the majority of patients with multiple sclerosis (MS) and therapeutic possibilities are few. Exercise therapy is a therapeutic option but no studies have systematically reviewed the existing literature evaluating the effect of exercise therapy on MS fatigue....

  17. Modelling of rate effects at multiple scales

    Pedersen, R.R.; Simone, A.; Sluys, L. J.

    2008-01-01

    , the length scale in the meso-model and the macro-model can be coupled. In this fashion, a bridging of length scales can be established. A computational analysis of  a Split Hopkinson bar test at medium and high impact load is carried out at macro-scale and meso-scale including information from  the micro-scale.......At the macro- and meso-scales a rate dependent constitutive model is used in which visco-elasticity is coupled to visco-plasticity and damage. A viscous length scale effect is introduced to control the size of the fracture process zone. By comparison of the widths of the fracture process zone...

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

    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.

  19. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    Groen, Richard W. J.; de Rooij, Martin F. M.; Kocemba, Kinga A.; Reijmers, Rogier M.; de Haan-Kramer, Anneke; Overdijk, Marije B.; Aalders, Linda; Rozemuller, Henk; Martens, Anton C. M.; Bergsagel, P. Leif; Kersten, Marie José; Pals, Steven T.; Spaargaren, Marcel

    2011-01-01

    Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow microenvironment plays

  20. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    Groen, R.W.J.; de Rooij, M.F.M.; Kocemba, K.A.; Reijmers, R.M.; de Haan-Kramer, A.; Overdijk, M.B.; Aalders, L.; Rozemuller, H.; Martens, A.C.M.; Bergsagel, P.L.; Kersten, M.J.; Pals, S.T.; Spaargaren, M.

    2011-01-01

    Background Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow

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

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

    2017-01-01

    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

  2. Multiple myeloma-derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease

    Fu, Jing; Li, Shirong; Feng, Rentian

    2016-01-01

    Multiple myeloma (MM) cells secrete osteoclastogenic factors that promote osteolytic lesions; however, the identity of these factors is largely unknown. Here, we performed a screen of human myeloma cells to identify pro-osteoclastogenic agents that could potentially serve as therapeutic targets...

  3. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    Wong, Mei Mei Jaslyn Elizabeth; Midtgaard, Søren Roi; Gysel, Kira

    2015-01-01

    of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering...

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

    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.

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

    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.

  6. Drinking to Cope With Depressive Symptoms and Ruminative Thinking: A Multiple Mediation Model Among College Students.

    Bravo, Adrian J; Pearson, Matthew R; Henson, James M

    2017-01-02

    Understanding the potential psychosocial mechanisms that explain (i.e., mediate) the associations between depressive symptoms and alcohol-related problems can improve interventions targeting college students. The current research examined four distinct facets of rumination (e.g., problem-focused thoughts, counterfactual thinking, repetitive thoughts, and anticipatory thoughts) and drinking to cope motives as potential explanatory mechanisms by which depressive symptoms are associated with increased alcohol-related problems. Participants were undergraduate students from a large, southeastern university in the United States that consumed at least one drink per typical week in the previous month (n = 403). The majority of participants were female (n = 291; 72.2%), identified as being either White, non-Hispanic (n = 210; 52.1%), or African American (n = 110; 27.3%), and reported a mean age of 21.92 (SD = 5.75) years. Structural equation modeling was conducted examining the concurrent associations between depressive symptoms, rumination facets, drinking to cope motives, and alcohol-related problems (i.e., cross-sectional). There was one significant double-mediated association that suggested that increased depressive symptoms is associated with increased problem-focused thoughts, which is associated with higher drinking to cope motives and alcohol-related problems. Conclusions/Importance: Our results suggests that problem-focused thoughts at least partially explains the associations between depression and maladaptive coping (i.e., drinking to cope), which in turn is related to problematic drinking among college students. Limitations and future directions are discussed.

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

    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.

  8. Linguistic ostracism causes prejudice: Support for a serial mediation effect.

    Hitlan, Robert Thomas; A Zárate, Michael; Kelly, Kristine M; Catherine DeSoto, M

    2016-01-01

    This research investigated the effects of linguistic ostracism, defined as any communication setting in which a target individual (or group) is ostracized by another individual (or group) in a language that the target has extremely limited ability to understand. Participants were included or ostracized by their group members during a computer-mediated group discussion. Half of the ostracized participants were linguistically ostracized via their group members conversing with one another in a language the participant did not know well (Spanish Ostracism: SO), or in a language the participant did know well (English Ostracism: EO). SO participants reported feeling less similar than both included and EO participants. SO participants also reported being angrier and expressed more prejudice than included participants (and EO participants using effect size estimates). Results also provided support for the hypothesized serial mediation model. Findings are discussed in terms of implications for intergroup relations.

  9. Microstructure-mediated Optical Effects in Southern African Snakes

    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.

  10. Monte Carlo simulations of multiple scattering effects in ERD measurements

    Doyle, Barney Lee; Arstila, Kai.; Nordlumd, K.; Knapp, James Arthur

    2003-01-01

    Multiple scattering effects in ERD measurements are studied by comparing two Monte Carlo simulation codes, representing different approaches to obtain acceptable statistics, to experimental spectra measured from a HfO 2 sample with a time-of-flight-ERD setup. The results show that both codes can reproduce the absolute detection yields and the energy distributions in an adequate way. The effect of the choice of the interatomic potential in multiple scattering effects is also studied. Finally the capabilities of the MC simulations in the design of new measurement setups are demonstrated by simulating the recoil energy spectra from a WC x N y sample with a low energy heavy ion beam.

  11. Does Multiple Leadership Styles Mediated by Job Satisfaction Influence Better Business Performance? Perception of MNC Employees in Malaysia

    Kader Ali Noor Nasir

    2016-01-01

    Full Text Available One of the biggest challenges facing leaders today is the need to develop new business models that stress on effective leadership styles, employee job satisfaction and sustainability without sacrificing the financial and non-financial performance. The objective of this study is to examine the relationship between leadership styles and business performance of multinational companies operating in Malaysia mediated by job satisfaction. A quantitative study, using self-administered structured questionnaire, are issued using purposive sampling via direct distribution to 150 employees working in MNC. Analysis using Statistical Package for the Social Sciences (SPSS and Partial Least Square (PLS indicated that spiritual leadership style has the highest significant influence on job satisfaction, followed by authentic leadership style, transformational leadership style, and transactional leadership style. In addition, job satisfaction has a mediating effect on the relationship between each of the leadership styles, namely, transactional, transformational, authentic, and spiritual on business performance.

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

    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.

  13. Multiple scattering effects in depth resolution of elastic recoil detection

    Wielunski, L.S.; Harding, G.L.

    1998-01-01

    Elastic Recoil Detection (ERD) is used to profile hydrogen and other low mass elements in thin films at surface and interfaces in a similar way that Rutherford Backscattering Spectroscopy (RBS) is used to detect and profile heavy elements. It is often assumed that the depth resolutions of these two techniques are similar. However, in contrast to typical RBS, the depth resolution of ERD is limited substantially by multiple scattering. In experimental data analysis and/or spectra simulations of a typical RBS measurement multiple scattering effects are often ignored. Computer programs used in IBA, such as RUMP, HYPRA or RBX do not include multiple scattering effects at all. In this paper, using practical thin metal structures with films containing intentionally introduced hydrogen, we demonstrate experimental ERD depth resolution and sensitivity limitations. The effects of sample material and scattering angle are also discussed. (authors)

  14. Multiple scattering effects in depth resolution of elastic recoil detection

    Wielunski, L.S.; Harding, G.L. [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Lindfield, NSW (Australia). Telecommunications and Industrial Physics; Szilagyi, E. [KFKI Research Institute for Particle and Nuclear Physics, Budapest, (Hungary)

    1998-06-01

    Elastic Recoil Detection (ERD) is used to profile hydrogen and other low mass elements in thin films at surface and interfaces in a similar way that Rutherford Backscattering Spectroscopy (RBS) is used to detect and profile heavy elements. It is often assumed that the depth resolutions of these two techniques are similar. However, in contrast to typical RBS, the depth resolution of ERD is limited substantially by multiple scattering. In experimental data analysis and/or spectra simulations of a typical RBS measurement multiple scattering effects are often ignored. Computer programs used in IBA, such as RUMP, HYPRA or RBX do not include multiple scattering effects at all. In this paper, using practical thin metal structures with films containing intentionally introduced hydrogen, we demonstrate experimental ERD depth resolution and sensitivity limitations. The effects of sample material and scattering angle are also discussed. (authors). 19 refs., 4 figs.

  15. Positive emotional change: mediating effects of forgiveness and spirituality.

    Levenson, Michael R; Aldwin, Carolyn M; Yancura, Loriena

    2006-01-01

    We evaluated the efficacy of an emotional education program that seeks to reduce the intergenerational transmission of negative interaction patterns by increasing forgiveness and spirituality. We examined both reduction of psychological symptoms and increase in positive psychological outcomes over the course of a year, as well as the mediators of this change. At baseline, the sample consisted of 99 participants and 47 waiting list controls. Comparisons of scores from baseline (Time 1) to one week after the Hoffman Quadrinity Process (Time 2) showed large declines in negative affect (depressive symptoms) and increases in both positive outcomes (mastery, empathy, emotional intelligence, life satisfaction, forgiveness, and spiritual experience) and health and well-being. Over the course of a year, most of these gains were sustained, in comparison with the control group. Further, increases in forgiveness and spirituality mediated the effect of program participation on depressive symptoms.

  16. Membrane cholesterol mediates the cellular effects of monolayer graphene substrates.

    Kitko, Kristina E; Hong, Tu; Lazarenko, Roman M; Ying, Da; Xu, Ya-Qiong; Zhang, Qi

    2018-02-23

    Graphene possesses extraordinary properties that promise great potential in biomedicine. However, fully leveraging these properties requires close contact with the cell surface, raising the concern of unexpected biological consequences. Computational models have demonstrated that graphene preferentially interacts with cholesterol, a multifunctional lipid unique to eukaryotic membranes. Here we demonstrate an interaction between graphene and cholesterol. We find that graphene increases cell membrane cholesterol and potentiates neurotransmission, which is mediated by increases in the number, release probability, and recycling rate of synaptic vesicles. In fibroblasts grown on graphene, we also find an increase in cholesterol, which promotes the activation of P2Y receptors, a family of receptor regulated by cholesterol. In both cases, direct manipulation of cholesterol levels elucidates that a graphene-induced cholesterol increase underlies the observed potentiation of each cell signaling pathway. These findings identify cholesterol as a mediator of graphene's cellular effects, providing insight into the biological impact of graphene.

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

    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

  18. Effect of multiple austenitizing treatments on HT-9 steels

    Emigh, R.A.

    1985-12-01

    The effect of multiple austenitizing treatments on the toughness of an Fe-12Cr-1.0Mo-0.5W-0.3V (HT-9) steel was studied. The resulting microstructures were characterized by their mechanical properties, precipitated carbide distribution, and fracture surface appearance. It was proposed that multiple transformations would refine the martensite structure and improve toughness. Optical and scanning electron microscopic observations revealed that the martensite packet structure was somewhat refined by a second austenite transformation. Transmission electron microscopy studies of carbon extraction replicas showed that this multiple step treatment had eliminated grain boundary carbide films seen in single treated specimens on prior austenite grain boundaries. The 0.2% yield strength, tensile strength, and elongation were relatively unchanged, but the toughness measured by fatigue pre-cracked Charpy impact tests increased for the multiple step specimens

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

    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.

  20. Involvement of Multiple Transporters-mediated Transports in Mizoribine and Methotrexate Pharmacokinetics

    Teruo Murakami

    2012-08-01

    Full Text Available Mizoribine is administered orally and excreted into urine without being metabolized. Many research groups have reported a linear relationship between the dose and peak serum concentration, between the dose and AUC, and between AUC and cumulative urinary excretion of mizoribine. In contrast, a significant interindividual variability, with a small intraindividual variability, in oral bioavailability of mizoribine is also reported. The interindividual variability is mostly considered to be due to the polymophisms of transporter genes. Methotrexate (MTX is administered orally and/or by parenteral routes, depending on the dose. Metabolic enzymes and multiple transporters are involved in the pharmacokinetics of MTX. The oral bioavailability of MTX exhibits a marked interindividual variability and saturation with increase in the dose of MTX, with a small intraindividual variability, where the contribution of gene polymophisms of transporters and enzymes is suggested. Therapeutic drug monitoring of both mizoribine and MTX is expected to improve their clinical efficacy in the treatment of rheumatoid arthritis.

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

    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.

  2. 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.

    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.

  3. Tariff-Mediated Network Effects Versus Strategic Disounting

    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...

  4. GSK3-mediated MAF phosphorylation in multiple myeloma as a potential therapeutic target

    Herath, N I; Rocques, N; Garancher, A; Eychène, A; Pouponnot, C

    2014-01-01

    Multiple myeloma (MM) is an incurable haematological malignancy characterised by the proliferation of mature antibody-secreting plasma B cells in the bone marrow. MM can arise from initiating translocations, of which the musculoaponeurotic fibrosarcoma (MAF) family is implicated in ∼5%. MMs bearing Maf translocations are of poor prognosis. These translocations are associated with elevated Maf expression, including c-MAF, MAFB and MAFA, and with t(14;16) and t(14;20) translocations, involving c-MAF and MAFB, respectively. c-MAF is also overexpressed in MM through MEK/ERK activation, bringing the number of MMs driven by the deregulation of a Maf gene close to 50%. Here we demonstrate that MAFB and c-MAF are phosphorylated by the Ser/Thr kinase GSK3 in human MM cell lines. We show that LiCl-induced GSK3 inhibition targets these phosphorylations and specifically decreases proliferation and colony formation of Maf-expressing MM cell lines. Interestingly, bortezomib induced stabilisation of Maf phosphorylation, an observation that could explain, at least partially, the low efficacy of bortezomib for patients carrying Maf translocations. Thus, GSK3 inhibition could represent a new therapeutic approach for these patients

  5. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    Wong, Jaslyn E. M. M. [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Midtgaard, Søren Roi [University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark); Gysel, Kira [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Thygesen, Mikkel B.; Sørensen, Kasper K.; Jensen, Knud J. [University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Stougaard, Jens; Thirup, Søren; Blaise, Mickaël, E-mail: mickael.blaise@cpbs.cnrs.fr [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)

    2015-03-01

    The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

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

    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

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

    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.

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

    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

  9. Statistical Power in Evaluations That Investigate Effects on Multiple Outcomes: A Guide for Researchers

    Porter, Kristin E.

    2018-01-01

    Researchers are often interested in testing the effectiveness of an intervention on multiple outcomes, for multiple subgroups, at multiple points in time, or across multiple treatment groups. The resulting multiplicity of statistical hypothesis tests can lead to spurious findings of effects. Multiple testing procedures (MTPs) are statistical…

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

    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.

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

    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.

  12. Cumulative effect in multiple production processes on nuclei

    Golubyatnikova, E.S.; Shmonin, V.L.; Kalinkin, B.N.

    1989-01-01

    It is shown that the cumulative effect is a natural result of the process of hadron multiple production in nuclear reactions. Interpretation is made of the universality of slopes of inclusive spectra and other characteristics of cumulative hadrons. The character of information from such reactions is discussed, which could be helpful in studying the mechanism of multiparticle production. 27 refs.; 4 figs

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

    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.

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

    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.

  15. Analysis of multiple scattering effects in optical Doppler tomography

    Yura, H.T.; Thrane, L.; Andersen, Peter E.

    2005-01-01

    Optical Doppler tomography (ODT) combines Doppler velocimetry and optical coherence tomography (OCT) to obtain high-resolution cross-sectional imaging of particle flow velocity in scattering media such as the human retina and skin. Here, we present the results of a theoretical analysis of ODT where...... multiple scattering effects are included. The purpose of this analysis is to determine how multiple scattering affects the estimation of the depth-resolved localized flow velocity. Depth-resolved velocity estimates are obtained directly from the corresponding mean or standard deviation of the observed...

  16. Effects of multiple scattering and target structure on photon emission

    Blankenbecler, R.

    1996-05-01

    The Landau-Pomeranchuk-Migdal effect is the suppression of Bethe-Heitler radiation caused by multiple scattering in the target medium. The quantum treatment given by S.D. Drell and the author for homogeneous targets of finite thickness will be reviewed. It will then be extended to structured targets. In brief, it is shown that radiators composed of separated plates or of a medium with a spatially varying radiation length can exhibit unexpected structure, even coherence maxima and minima, in their photon spectra. Finally, a functional integral method for performing the averaging implicit in multiple scattering will be briefly discussed and the leading corrections to previous results evaluated

  17. Multiple-Machine Scheduling with Learning Effects and Cooperative Games

    Yiyuan Zhou

    2015-01-01

    Full Text Available Multiple-machine scheduling problems with position-based learning effects are studied in this paper. There is an initial schedule in this scheduling problem. The optimal schedule minimizes the sum of the weighted completion times; the difference between the initial total weighted completion time and the minimal total weighted completion time is the cost savings. A multiple-machine sequencing game is introduced to allocate the cost savings. The game is balanced if the normal processing times of jobs that are on the same machine are equal and an equal number of jobs are scheduled on each machine initially.

  18. Systematic review of nutrient intake and growth in children with multiple IgE-mediated food allergies.

    Sova, Cassandra; Feuling, Mary Beth; Baumler, Megan; Gleason, Linda; Tam, Jonathan S; Zafra, Heidi; Goday, Praveen S

    2013-12-01

    Food allergies affect up to 8% of American children. The current recommended treatment for food allergies is strict elimination of the allergens from the diet. Dietary elimination of nutrient-dense foods may result in inadequate nutrient intake and impaired growth. The purpose of this review was to critically analyze available research on the effect of an elimination diet on nutrient intake and growth in children with multiple food allergies. A systematic review of the literature was conducted and a workgroup was established to critically analyze each relevant article. The findings were summarized and a conclusion was generated. Six studies were analyzed. One study found that children with food allergies are more likely to be malnourished than children without food allergies. Three studies found that children with multiple food allergies were shorter than children with 1 food allergy. Four studies assessed nutrient intake of children with multiple food allergies, but the inclusion and comparison criteria were different in each of the studies and the findings were conflicting. One study found that children with food allergies who did not receive nutrition counseling were more likely to have inadequate intake of calcium and vitamin D. Children with multiple food allergies have a higher risk of impaired growth and may have a higher risk of inadequate nutrient intake than children without food allergies. Until more research is available, we recommend monitoring of nutrition and growth of children with multiple food allergies to prevent possible nutrient deficiencies and to optimize growth.

  19. Effects of applying hydrotherapy on fatigue in multiple sclerosis patients

    Somaiyeh Ghafari; Fazlolah Ahmadi; Masood Nabavi

    2008-01-01

    (Received 10 May, 2008 ; Accepted 3 Oct, 2008) Abstract Background and purpose: Fatigue is a common symptom of Multiple Sclerosis (MS) that is purported to cause significant distress and have detrimental effects on daily living functioning, social and occupational obligations, and overall well-being. Complementary therapies are widely used by people with MS and Progressive Hydrotherapy is a form of complementary therapies. The aim of this study is to assess the effects of applying Hydrotherap...

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

    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.

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

    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

  2. Cognitive Load Mediates the Effect of Emotion on Analytical Thinking.

    Trémolière, Bastien; Gagnon, Marie-Ève; Blanchette, Isabelle

    2016-11-01

    Although the detrimental effect of emotion on reasoning has been evidenced many times, the cognitive mechanism underlying this effect remains unclear. In the present paper, we explore the cognitive load hypothesis as a potential explanation. In an experiment, participants solved syllogistic reasoning problems with either neutral or emotional contents. Participants were also presented with a secondary task, for which the difficult version requires the mobilization of cognitive resources to be correctly solved. Participants performed overall worse and took longer on emotional problems than on neutral problems. Performance on the secondary task, in the difficult version, was poorer when participants were reasoning about emotional, compared to neutral contents, consistent with the idea that processing emotion requires more cognitive resources. Taken together, the findings afford evidence that the deleterious effect of emotion on reasoning is mediated by cognitive load.

  3. Dynamic Interaction of Stress Granules, DDX3X, and IKK-α Mediates Multiple Functions in Hepatitis C Virus Infection.

    Pène, Véronique; Li, Qisheng; Sodroski, Catherine; Hsu, Ching-Sheng; Liang, T Jake

    2015-05-01

    The ubiquitous ATP-dependent RNA helicase DDX3X is involved in many cellular functions, including innate immunity, and is a pivotal host factor for hepatitis C virus (HCV) infection. Recently, we showed that DDX3X specifically recognizes the HCV 3' untranslated region (UTR), leading to the activation of IKK-α and a cascade of lipogenic signaling to facilitate lipid droplet biogenesis and viral assembly (Q. Li, V. Pene, S. Krishnamurthy, H. Cha, and T. J. Liang, Nat Med 19:722-729, 2013, http://dx.doi.org/10.1038/nm.3190). The interaction of DDX3X with HCV core protein seems to be dispensable for its proviral role. In this study, through systematic imaging and biochemical and virologic approaches, we identified a dynamic association between DDX3X and various cellular compartments and viral elements mediating multiple functions of DDX3X in productive HCV infection. Upon HCV infection, the HCV 3'UTR interacts with DDX3X and IKK-α, which redistribute to speckle-like cytoplasmic structures shown to be stress granules (SGs). As viral proteins accumulate in infected cells, DDX3X granules together with SG-associated proteins redistribute and colocalize with HCV core protein around lipid droplets (LDs). IKK-α, however, does not relocate to the LD but translocates to the nucleus. In HCV-infected cells, various HCV nonstructural proteins also interact or colocalize with DDX3X in close proximity to SGs and LDs, consistent with the tight juxtaposition of the replication complex and the assembly site at the surface of LDs. Short interfering RNA (siRNA)-mediated silencing of DDX3X and multiple SG components markedly inhibits HCV infection. Our data suggest that DDX3X initiates a multifaceted cellular program involving dynamic associations with HCV RNA and proteins, IKK-α, SG, and LD surfaces for its crucial role in the HCV life cycle. IMPORTANCE DDX3X is a proviral host factor for HCV infection. Recently, we showed that DDX3X binds to the HCV 3'UTR, activating IKK-α and

  4. Lipocalin 2 is a novel immune mediator of experimental autoimmune encephalomyelitis pathogenesis and is modulated in multiple sclerosis.

    Berard, Jennifer L; Zarruk, Juan G; Arbour, Nathalie; Prat, Alexandre; Yong, V Wee; Jacques, Francois H; Akira, Shizuo; David, Samuel

    2012-07-01

    Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of multiple sclerosis (MS), an inflammatory, demyelinating disease of the central nervous system (CNS). EAE pathogenesis involves various cell types, cytokines, chemokines, and adhesion molecules. Given the complexity of the inflammatory response in EAE, it is likely that many immune mediators still remain to be discovered. To identify novel immune mediators of EAE pathogenesis, we performed an Affymetrix gene array screen on the spinal cords of mice at the onset stage of disease. This screening identified the gene encoding lipocalin 2 (Lcn2) as being significantly upregulated. Lcn2 is a multi-functional protein that plays a role in glial activation, matrix metalloproteinase (MMP) stabilization, and cellular iron flux. As many of these processes have been implicated in EAE, we characterized the expression and role of Lcn2 in this disease in C57BL/6 mice. We show that Lcn2 is significantly upregulated in the spinal cord throughout EAE and is expressed predominantly by monocytes and reactive astrocytes. The Lcn2 receptor, 24p3R, is also expressed on monocytes, macrophages/microglia, and astrocytes in EAE. In addition, we show that EAE severity is increased in Lcn2(-/-) mice as compared with wild-type controls. Finally, we demonstrate that elevated levels of Lcn2 are detected in the plasma and cerebrospinal fluid (CSF) in MS and in immune cells in CNS lesions in MS tissue sections. These data indicate that Lcn2 is a modulator of EAE pathogenesis and suggest that it may also play a role in MS. Copyright © 2012 Wiley Periodicals, Inc.

  5. Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.

    Nojima, Kuniharu; Hochegger, Helfrid; Saberi, Alihossein; Fukushima, Toru; Kikuchi, Koji; Yoshimura, Michio; Orelli, Brian J; Bishop, Douglas K; Hirano, Seiki; Ohzeki, Mioko; Ishiai, Masamichi; Yamamoto, Kazuhiko; Takata, Minoru; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Yamazoe, Mitsuyoshi; Kawamoto, Takuo; Araki, Kasumi; Takahashi, Jun A; Hashimoto, Nobuo; Takeda, Shunichi; Sonoda, Eiichiro

    2005-12-15

    Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair pathways is distinctively different from the situation in yeast, where NER seems to play a major role in dealing with ICL. Cells deficient in Rev3, the catalytic subunit of TLS polymerase Polzeta, showed the highest sensitivity to cisplatin followed by fanc-c. Furthermore, epistasis analysis revealed that these two mutants work in the same pathway. Our genetic comprehensive study reveals a critical role for DNA repair pathways that release DNA replication block at ICLs in cellular tolerance to cross-linking agents and could be directly exploited in designing an effective chemotherapy.

  6. Aspirin-Mediated Acetylation Protects Against Multiple Neurodegenerative Pathologies by Impeding Protein Aggregation.

    Ayyadevara, Srinivas; Balasubramaniam, Meenakshisundaram; Kakraba, Samuel; Alla, Ramani; Mehta, Jawahar L; Shmookler Reis, Robert J

    2017-12-10

    Many progressive neurological disorders, including Alzheimer's disease (AD), Huntington's disease, and Parkinson's disease (PD), are characterized by accumulation of insoluble protein aggregates. In prospective trials, the cyclooxygenase inhibitor aspirin (acetylsalicylic acid) reduced the risk of AD and PD, as well as cardiovascular events and many late-onset cancers. Considering the role played by protein hyperphosphorylation in aggregation and neurodegenerative diseases, and aspirin's known ability to donate acetyl groups, we asked whether aspirin might reduce both phosphorylation and aggregation by acetylating protein targets. Aspirin was substantially more effective than salicylate in reducing or delaying aggregation in human neuroblastoma cells grown in vitro, and in Caenorhabditis elegans models of human neurodegenerative diseases in vivo. Aspirin acetylates many proteins, while reducing phosphorylation, suggesting that acetylation may oppose phosphorylation. Surprisingly, acetylated proteins were largely excluded from compact aggregates. Molecular-dynamic simulations indicate that acetylation of amyloid peptide energetically disfavors its association into dimers and octamers, and oligomers that do form are less compact and stable than those comprising unacetylated peptides. Hyperphosphorylation predisposes certain proteins to aggregate (e.g., tau, α-synuclein, and transactive response DNA-binding protein 43 [TDP-43]), and it is a critical pathogenic marker in both cardiovascular and neurodegenerative diseases. We present novel evidence that acetylated proteins are underrepresented in protein aggregates, and that aggregation varies inversely with acetylation propensity after diverse genetic and pharmacologic interventions. These results are consistent with the hypothesis that aspirin inhibits protein aggregation and the ensuing toxicity of aggregates through its acetyl-donating activity. This mechanism may contribute to the neuro-protective, cardio

  7. Stanniocalcin-1 Protects a Mouse Model from Renal Ischemia-Reperfusion Injury by Affecting ROS-Mediated Multiple Signaling Pathways.

    Liu, Dajun; Shang, Huiping; Liu, Ying

    2016-07-12

    Stanniocalcin-1 (STC-1) protects against renal ischemia-reperfusion injury (RIRI). However, the molecular mechanisms remain widely unknown. STC-1 inhibits reactive oxygen species (ROS), whereas most ROS-mediated pathways are associated with ischemic injury. Therefore, to explore the mechanism, the effects of STC-1 on ROS-medicated pathways were studied. Non-traumatic vascular clamps were used to establish RIRI mouse models. The serum levels of STC-1, interleukin-6 (IL-6), interferon (IFN) γ, P53, and capase-3 were measured by ELISA kits. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by fluorescence spectrofluorometer. All these molecules changed significantly in a RIRI model mouse when compared with those in a sham control. Kidney cells were isolated from sham and model mice. STC-1 was overexpressed or knockout in these kidney cells. The molecules in ROS-medicated pathways were measured by real-time quantitative PCR and Western blot. The results showed that STC-1 is an effective ROS scavenger. The serum levels of STC-1, MDA and SOD activity were increased while the serum levels of IL-6, iIFN-γ, P53, and capase-3 were decreased in a model group when compared with a sham control (p ROS-mediated molecules. Therefore, STC-1 maybe improve anti-inflammation, anti-oxidant and anti-apoptosis activities by affecting ROS-mediated pathways, especially the phospho-modifications of the respective proteins, resulting in the increase of SOD and reduce of capase-3, p53, IL-6 and IFN-γ.

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

    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.

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

    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

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

    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.

  11. [Body image dissatisfaction as a mediator of the association between BMI, self-esteem and mental health in early adolescents: a multiple-group path analysis across gender].

    Jang, Mi Heui; Lee, Gyungjoo

    2013-04-01

    This study was done to examine not only the relationships between body mass index (BMI), self-esteem, body image dissatisfaction (BID) and mental health, according to gender, but the mediating role of BID on mental health in relation to BMI and self-esteem among early adolescents. Data from 576 (296 boys and 280 girls) elementary school students in grades 5 to 6 were collected. A multiple-group path analysis was utilized to examine the relationships between BMI, self-esteem, BID and mental health by gender. In the path analysis for all students, poor mental health was related directly to BID, while it was indirectly related to BMI and self-esteem. In the multiple-group path analysis of both genders, BID was found to have a significant direct and indirect effect on mental health for girls alone. The findings suggested that BID should be examined early to prevent poor mental health in early adolescent girls. This study helps to elucidate the role of early adolescent BID on mental health and provides insight for further prevention and intervention programs in school and community mental health settings.

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

    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.

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

    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.

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

    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...

  15. Nicotinic Acid-Mediated Activation of Both Membrane and Nuclear Receptors towards Therapeutic Glucocorticoid Mimetics for Treating Multiple Sclerosis

    W. Todd Penberthy

    2009-01-01

    Full Text Available Acute attacks of multiple sclerosis (MS are most commonly treated with glucocorticoids, which can provide life-saving albeit only temporary symptomatic relief. The mechanism of action (MOA is now known to involve induction of indoleamine 2,3-dioxygenase (IDO and interleukin-10 (IL-10, where IL-10 requires subsequent heme oxygenase-1 (HMOX-1 induction. Ectopic expression studies reveal that even small changes in expression of IDO, HMOX-1, or mitochondrial superoxide dismutase (SOD2 can prevent demyelination in experimental autoimmune encephalomyelitis (EAE animal models of MS. An alternative to glucocorticoids is needed for a long-term treatment of MS. A distinctly short list of endogenous activators of both membrane G-protein-coupled receptors and nuclear peroxisome proliferating antigen receptors (PPARs demonstrably ameliorate EAE pathogenesis by MOAs resembling that of glucocorticoids. These dual activators and potential MS therapeutics include endocannabinoids and the prostaglandin 15-deoxy-Δ12,14-PGJ2. Nicotinamide profoundly ameliorates and prevents autoimmune-mediated demyelination in EAE via maintaining levels of nicotinamide adenine dinucleotide (NAD, without activating PPAR nor any G-protein-coupled receptor. By comparison, nicotinic acid provides even greater levels of NAD than nicotinamide in many tissues, while additionally activating the PPAR-dependent pathway already shown to provide relief in animal models of MS after activation of GPR109a/HM74a. Thus nicotinic acid is uniquely suited for providing therapeutic relief in MS. However nicotinic acid is unexamined in MS research. Nicotinic acid penetrates the blood brain barrier, cures pellagric dementia, has been used for over 50 years clinically without toxicity, and raises HDL concentrations to a greater degree than any pharmaceutical, thus providing unparalleled benefits against lipodystrophy. Summary analysis reveals that the expected therapeutic benefits of high-dose nicotinic

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

    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...

  17. Attentional bias mediates the effect of neurostimulation on emotional vulnerability.

    Chen, Nigel T M; Basanovic, Julian; Notebaert, Lies; MacLeod, Colin; Clarke, Patrick J F

    2017-10-01

    Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which has garnered recent interest in the potential treatment for emotion-based psychopathology. While accumulating evidence suggests that tDCS may attenuate emotional vulnerability, critically, little is known about underlying mechanisms of this effect. The present study sought to clarify this by examining the possibility that tDCS may affect emotional vulnerability via its capacity to modulate attentional bias towards threatening information. Fifty healthy participants were randomly assigned to receive either anodal tDCS (2 mA/min) stimulation to the left dorsolateral prefrontal cortex (DLPFC), or sham. Participants were then eye tracked during a dual-video stressor task designed to elicit emotional reactivity, while providing a concurrent in-vivo measure of attentional bias. Greater attentional bias towards threatening information was associated with greater emotional reactivity to the stressor task. Furthermore, the active tDCS group showed reduced attentional bias to threat, compared to the sham group. Importantly, attentional bias was found to statistically mediate the effect of tDCS on emotional reactivity, while no direct effect of tDCS on emotional reactivity was observed. The findings are consistent with the notion that the effect of tDCS on emotional vulnerability may be mediated by changes in attentional bias, holding implications for the application of tDCS in emotion-based psychopathology. The findings also highlight the utility of in-vivo eye tracking measures in the examination of the mechanisms associated with DLPFC neuromodulation in emotional vulnerability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Performance effect of multiple control forms in a Lean organization

    Kristensen, Thomas Borup; Israelsen, Poul

    2012-01-01

    Over the last decades Lean has developed into a prominent management philosophy reaching beyond shop floor tools. However, substantial support of performance effects from Lean is still scarce and at best with mixed results. Recently, research has turned its focus towards perceiving Lean...... as a control package. In this paper we present statistical support for enhanced performance coming from Lean. Furthermore, our results strongly support the perception of Lean as a set of multiple control forms (output, behavioral, and social controls) that complement each other. Therefore, performance...... is increased if the average level of control forms is increased, and performance is further increased if the control forms are balanced at the same level representing a complementary effect between them. Our data are archival data spanning multiple years in a strong Lean organization. The dependent performance...

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

    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

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

    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.

  1. Cumulative organic anion transporter-mediated drug-drug interaction potential of multiple components in salvia miltiorrhiza (danshen) preparations.

    Wang, Li; Venitz, Jürgen; Sweet, Douglas H

    2014-12-01

    To evaluate organic anion transporter-mediated drug-drug interaction (DDI) potential for individual active components of Danshen (Salvia miltiorrhiza) vs. combinations using in vitro and in silico approaches. Inhibition profiles for single Danshen components and combinations were generated in stably-expressing human (h)OAT1 and hOAT3 cells. Plasma concentration-time profiles for compounds were estimated from in vivo human data using an i.v. two-compartment model (with first-order elimination). The cumulative DDI index was proposed as an indicator of DDI potential for combination products. This index was used to evaluate the DDI potential for Danshen injectables from 16 different manufacturers and 14 different lots from a single manufacturer. The cumulative DDI index predicted in vivo inhibition potentials, 82% (hOAT1) and 74% (hOAT3), comparable with those observed in vitro, 72 ± 7% (hOAT1) and 81 ± 10% (hOAT3), for Danshen component combinations. Using simulated unbound Cmax values, a wide range in cumulative DDI index between manufacturers, and between lots, was predicted. Many products exhibited a cumulative DDI index > 1 (50% inhibition). Danshen injectables will likely exhibit strong potential to inhibit hOAT1 and hOAT3 function in vivo. The proposed cumulative DDI index might improve prediction of DDI potential of herbal medicines or pharmaceutical preparations containing multiple components.

  2. The high risk HPV16 L2 minor capsid protein has multiple transport signals that mediate its nucleocytoplasmic traffic

    Mamoor, Shahan; Onder, Zeynep; Karanam, Balasubramanyam; Kwak, Kihyuck; Bordeaux, Jennifer; Crosby, Lauren; Roden, Richard B.S.; Moroianu, Junona

    2012-01-01

    In this study we examined the transport signals contributing to HPV16 L2 nucleocytoplasmic traffic using confocal microscopy analysis of enhanced green fluorescent protein—L2 (EGFP-L2) fusions expressed in HeLa cells. We confirmed that both nuclear localization signals (NLSs), the nNLS (1MRHKRSAKRTKR12) and cNLS (456RKRRKR461), previously characterized in vitro (Darshan et al., 2004), function independently in vivo. We discovered that a middle region rich in arginine residues (296SRRTGIRYSRIGNKQTLRTRS316) functions as a nuclear retention sequence (NRS), as mutagenesis of critical arginine residues within this NRS reduced the fraction of L2 in the nucleus despite the presence of both NLSs. Significantly, the infectivity of HPV16 pseudoviruses containing either RR297AA or RR297EE within the L2 NRS was strongly reduced both in HaCaT cells and in a murine challenge model. Experiments using Ratjadone A nuclear export inhibitor and mutation-localization analysis lead to the discovery of a leucine-rich nuclear export signal ( 462 LPYFFSDVSL) mediating 16L2 nuclear export. These data indicate that HPV16 L2 nucleocytoplasmic traffic is dependent on multiple functional transport signals.

  3. The high risk HPV16 L2 minor capsid protein has multiple transport signals that mediate its nucleocytoplasmic traffic

    Mamoor, Shahan; Onder, Zeynep [Biology Department, Boston College, Chestnut Hill, MA 02467 (United States); Karanam, Balasubramanyam; Kwak, Kihyuck [Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231 (United States); Bordeaux, Jennifer; Crosby, Lauren [Biology Department, Boston College, Chestnut Hill, MA 02467 (United States); Roden, Richard B.S. [Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231 (United States); Moroianu, Junona, E-mail: moroianu@bc.edu [Biology Department, Boston College, Chestnut Hill, MA 02467 (United States)

    2012-01-20

    In this study we examined the transport signals contributing to HPV16 L2 nucleocytoplasmic traffic using confocal microscopy analysis of enhanced green fluorescent protein-L2 (EGFP-L2) fusions expressed in HeLa cells. We confirmed that both nuclear localization signals (NLSs), the nNLS (1MRHKRSAKRTKR12) and cNLS (456RKRRKR461), previously characterized in vitro (Darshan et al., 2004), function independently in vivo. We discovered that a middle region rich in arginine residues (296SRRTGIRYSRIGNKQTLRTRS316) functions as a nuclear retention sequence (NRS), as mutagenesis of critical arginine residues within this NRS reduced the fraction of L2 in the nucleus despite the presence of both NLSs. Significantly, the infectivity of HPV16 pseudoviruses containing either RR297AA or RR297EE within the L2 NRS was strongly reduced both in HaCaT cells and in a murine challenge model. Experiments using Ratjadone A nuclear export inhibitor and mutation-localization analysis lead to the discovery of a leucine-rich nuclear export signal ({sub 462}LPYFFSDVSL) mediating 16L2 nuclear export. These data indicate that HPV16 L2 nucleocytoplasmic traffic is dependent on multiple functional transport signals.

  4. Team effectiveness in academic medical libraries: a multiple case study.

    Martin, Elaine Russo

    2006-07-01

    The objective of this study is to apply J. Richard Hackman's framework on team effectiveness to academic medical library settings. The study uses a qualitative, multiple case study design, employing interviews and focus groups to examine team effectiveness in three academic medical libraries. Another site was selected as a pilot to validate the research design, field procedures, and methods to be used with the cases. In all, three interviews and twelve focus groups, with approximately seventy-five participants, were conducted at the case study libraries. Hackman identified five conditions leading to team effectiveness and three outcomes dimensions that defined effectiveness. The participants in this study identified additional characteristics of effectiveness that focused on enhanced communication, leadership personality and behavior, and relationship building. The study also revealed an additional outcome dimension related to the evolution of teams. Introducing teams into an organization is not a trivial matter. Hackman's model of effectiveness has implications for designing successful library teams.

  5. A Multiple Mediational Test of the Relationship between Childhood Maltreatment and Non-Suicidal Self-Injury

    Shenk, Chad E.; Noll, Jennie G.; Cassarly, Jennifer A.

    2010-01-01

    Post-traumatic stress symptoms, depressive symptoms, and psychological dysregulation have been shown to mediate the relationship between child maltreatment and non-suicidal self-injury. However, these proposed mediators often co-occur and previous research has not tested mediation when all variables are assessed simultaneously. The current study…

  6. Mediator and moderator effects in developmental and behavioral pediatric research.

    Rose, Brigid M; Holmbeck, Grayson N; Coakley, Rachael Millstein; Franks, Elizabeth A

    2004-02-01

    The terms mediation and moderation are defined and clarified with particular emphasis on the role of mediational and moderational analyses in developmental and behavioral pediatric research. The article highlights the applicability of mediational and moderational analyses to longitudinal, intervention, and risk and protective factor research, and it provides basic information about how these analyses might be conducted. Also included is a discussion of various ways that both mediator and moderator variables can be incorporated into a single model. The article concludes with extended examples of both types of analyses using a longitudinal pediatric study for illustration. The article provides recommendations for applying mediational and moderational research in clinical practice.

  7. Statistical Power in Evaluations That Investigate Effects on Multiple Outcomes: A Guide for Researchers

    Porter, Kristin E.

    2016-01-01

    In education research and in many other fields, researchers are often interested in testing the effectiveness of an intervention on multiple outcomes, for multiple subgroups, at multiple points in time, or across multiple treatment groups. The resulting multiplicity of statistical hypothesis tests can lead to spurious findings of effects. Multiple…

  8. Peer Mediation and Its Effects on Elementary Student Perceptions of Self-Esteem and Social Competence

    Cardoza, Deanna Janine

    2013-01-01

    The purpose of this research study was to examine the effectiveness of training students in peer mediation (Mediator Mentors Curriculum), and how peer mediation-training influences third- through fifth-grade student perceptions of self-esteem, resiliency, and social competence. The research was a mixed-methods design with both quantitative and…

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

    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.

  10. A nutritionally mediated risk effect of wolves on elk.

    Christianson, David; Creel, Scott

    2010-04-01

    Though it is widely argued that antipredator responses carry nutritional costs, or risk effects, these costs are rarely measured in wild populations. To quantify risk effects in elk, a species that strongly responds to the presence of wolves, we noninvasively monitored diet selection and nutrient balance in wintering elk in the Upper Gallatin, Montana, USA, over three winters while quantifying the local presence of wolves at a fine spatiotemporal scale. Standard nutritional indices based on the botanical and chemical composition of 786 fecal samples, 606 snow urine samples, and 224 forage samples showed that elk were generally malnourished throughout winter. Increased selection for dietary nitrogen within forage types (e.g., grasses) led to approximately 8% higher fecal nitrogen in the presence of wolves. However, urinary allantoin : creatinine and potassium : creatinine ratios decreased in the presence of wolves, suggesting large declines in energy intake, equal to 27% of maintenance requirements. Urinary nitrogen : creatinine ratios confirmed that deficiencies in nitrogen and/or energy were exacerbated in the presence of wolves, leading to increased endogenous protein catabolism. Overall, the nutritional effects of wolf presence may be of sufficient magnitude to reduce survival and reproduction in wintering elk. Nutritionally mediated risk effects may be important for understanding predator-prey dynamics in wild populations, but such effects could be masked as bottom-up forces if antipredator responses are not considered.

  11. ATF3 mediates inhibitory effects of ethanol on hepatic gluconeogenesis.

    Tsai, Wen-Wei; Matsumura, Shigenobu; Liu, Weiyi; Phillips, Naomi G; Sonntag, Tim; Hao, Ergeng; Lee, Soon; Hai, Tsonwin; Montminy, Marc

    2015-03-03

    Increases in circulating glucagon during fasting maintain glucose balance by stimulating hepatic gluconeogenesis. Acute ethanol intoxication promotes fasting hypoglycemia through an increase in hepatic NADH, which inhibits hepatic gluconeogenesis by reducing the conversion of lactate to pyruvate. Here we show that acute ethanol exposure also lowers fasting blood glucose concentrations by inhibiting the CREB-mediated activation of the gluconeogenic program in response to glucagon. Ethanol exposure blocked the recruitment of CREB and its coactivator CRTC2 to gluconeogenic promoters by up-regulating ATF3, a transcriptional repressor that also binds to cAMP-responsive elements and thereby down-regulates gluconeogenic genes. Targeted disruption of ATF3 decreased the effects of ethanol in fasted mice and in cultured hepatocytes. These results illustrate how the induction of transcription factors with overlapping specificity can lead to cross-coupling between stress and hormone-sensitive pathways.

  12. Involvement of Astrocytes in Mediating the Central Effects of Ghrelin

    Frago, Laura M.; Chowen, Julie A.

    2017-01-01

    Although astrocytes are the most abundant cells in the mammalian brain, much remains to be learned about their molecular and functional features. Astrocytes express receptors for numerous hormones and metabolic factors, including the appetite-promoting hormone ghrelin. The metabolic effects of ghrelin are largely opposite to those of leptin, as it stimulates food intake and decreases energy expenditure. Ghrelin is also involved in glucose-sensing and glucose homeostasis. The widespread expression of the ghrelin receptor in the central nervous system suggests that this hormone is not only involved in metabolism, but also in other essential functions in the brain. In fact, ghrelin has been shown to promote cell survival and neuroprotection, with some studies exploring the use of ghrelin as a therapeutic agent against metabolic and neurodegenerative diseases. In this review, we highlight the possible role of glial cells as mediators of ghrelin’s actions within the brain. PMID:28257088

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

    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.

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

    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

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

    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.

  16. Evidence for multiple stressor interactions and effects on coral reefs.

    Ban, Stephen S; Graham, Nicholas A J; Connolly, Sean R

    2014-03-01

    Concern is growing about the potential effects of interacting multiple stressors, especially as the global climate changes. We provide a comprehensive review of multiple stressor interactions in coral reef ecosystems, which are widely considered to be one of the most sensitive ecosystems to global change. First, we synthesized coral reef studies that examined interactions of two or more stressors, highlighting stressor interactions (where one stressor directly influences another) and potentially synergistic effects on response variables (where two stressors interact to produce an effect that is greater than purely additive). For stressor-stressor interactions, we found 176 studies that examined at least 2 of the 13 stressors of interest. Applying network analysis to analyze relationships between stressors, we found that pathogens were exacerbated by more costressors than any other stressor, with ca. 78% of studies reporting an enhancing effect by another stressor. Sedimentation, storms, and water temperature directly affected the largest number of other stressors. Pathogens, nutrients, and crown-of-thorns starfish were the most-influenced stressors. We found 187 studies that examined the effects of two or more stressors on a third dependent variable. The interaction of irradiance and temperature on corals has been the subject of more research (62 studies, 33% of the total) than any other combination of stressors, with many studies reporting a synergistic effect on coral symbiont photosynthetic performance (n = 19). Second, we performed a quantitative meta-analysis of existing literature on this most-studied interaction (irradiance and temperature). We found that the mean effect size of combined treatments was statistically indistinguishable from a purely additive interaction, although it should be noted that the sample size was relatively small (n = 26). Overall, although in aggregate a large body of literature examines stressor effects on coral reefs and coral

  17. 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.

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

  5. 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.

    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.

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

    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.

  7. Habitat structure mediates biodiversity effects on ecosystem properties.

    Godbold, J A; Bulling, M T; Solan, M

    2011-08-22

    Much of what we know about the role of biodiversity in mediating ecosystem processes and function stems from manipulative experiments, which have largely been performed in isolated, homogeneous environments that do not incorporate habitat structure or allow natural community dynamics to develop. Here, we use a range of habitat configurations in a model marine benthic system to investigate the effects of species composition, resource heterogeneity and patch connectivity on ecosystem properties at both the patch (bioturbation intensity) and multi-patch (nutrient concentration) scale. We show that allowing fauna to move and preferentially select patches alters local species composition and density distributions, which has negative effects on ecosystem processes (bioturbation intensity) at the patch scale, but overall positive effects on ecosystem functioning (nutrient concentration) at the multi-patch scale. Our findings provide important evidence that community dynamics alter in response to localized resource heterogeneity and that these small-scale variations in habitat structure influence species contributions to ecosystem properties at larger scales. We conclude that habitat complexity forms an important buffer against disturbance and that contemporary estimates of the level of biodiversity required for maintaining future multi-functional systems may need to be revised.

  8. Climate mediates the effects of disturbance on ant assemblage structure

    Gibb, Heloise; Sanders, Nathan J.; Dunn, Robert R.; Watson, Simon; Photakis, Manoli; Abril, Silvia; Andersen, Alan N.; Angulo, Elena; Armbrecht, Inge; Arnan, Xavier; Baccaro, Fabricio B.; Bishop, Tom R.; Boulay, Raphael; Castracani, Cristina; Del Toro, Israel; Delsinne, Thibaut; Diaz, Mireia; Donoso, David A.; Enríquez, Martha L.; Fayle, Tom M.; Feener, Donald H.; Fitzpatrick, Matthew C.; Gómez, Crisanto; Grasso, Donato A.; Groc, Sarah; Heterick, Brian; Hoffmann, Benjamin D.; Lach, Lori; Lattke, John; Leponce, Maurice; Lessard, Jean-Philippe; Longino, John; Lucky, Andrea; Majer, Jonathan; Menke, Sean B.; Mezger, Dirk; Mori, Alessandra; Munyai, Thinandavha C.; Paknia, Omid; Pearce-Duvet, Jessica; Pfeiffer, Martin; Philpott, Stacy M.; de Souza, Jorge L. P.; Tista, Melanie; Vasconcelos, Heraldo L.; Vonshak, Merav; Parr, Catherine L.

    2015-01-01

    Many studies have focused on the impacts of climate change on biological assemblages, yet little is known about how climate interacts with other major anthropogenic influences on biodiversity, such as habitat disturbance. Using a unique global database of 1128 local ant assemblages, we examined whether climate mediates the effects of habitat disturbance on assemblage structure at a global scale. Species richness and evenness were associated positively with temperature, and negatively with disturbance. However, the interaction among temperature, precipitation and disturbance shaped species richness and evenness. The effect was manifested through a failure of species richness to increase substantially with temperature in transformed habitats at low precipitation. At low precipitation levels, evenness increased with temperature in undisturbed sites, peaked at medium temperatures in disturbed sites and remained low in transformed sites. In warmer climates with lower rainfall, the effects of increasing disturbance on species richness and evenness were akin to decreases in temperature of up to 9°C. Anthropogenic disturbance and ongoing climate change may interact in complicated ways to shape the structure of assemblages, with hot, arid environments likely to be at greatest risk. PMID:25994675

  9. Social networks as mediators of the effect of Alcoholics Anonymous.

    Kaskutas, Lee Ann; Bond, Jason; Humphreys, Keith

    2002-07-01

    This study tested the hypothesis that the relationship between Alcoholics Anonymous (AA) involvement and reduced substance use is partially explained (or 'mediated') by changes in social networks. This is a naturalistic longitudinal study of the course of alcohol problems. Study sites were the 10 largest public and private alcohol treatment programs in a northern California county. Three hundred and seventy-seven men and 277 women were recruited upon seeking treatment at study sites. At baseline and 1-year follow-up, we assessed alcohol consequences and dependence symptoms, consumption, social support for abstinence, pro-drinking social influences and AA involvement. In the structural equation model, AA involvement was a significant predictor of lower alcohol consumption and fewer related problems. The size of this effect decreased by 36% when network size and support for drinking were included as mediators. In logistic regression models predicting abstinence at follow-up, AA remained highly significant after including social network variables but was again reduced in magnitude. Thirty-day abstinence was predicted by AA involvement (OR=2.9), not having pro-drinking influences in one's network (OR=0.7) and having support for reducing consumption from people met in AA (versus no support; OR=3.4). In contrast, having support from non-AA members was not a significant predictor of abstinence. For alcohol-related outcomes other than abstinence, significant relationships were found for both AA-based and non-AA-based support. The type of social support specifically given by AA members, such as 24-hour availability, role modeling and experientially based advice for staying sober, may help to explain AA's mechanism of action. Results highlight the value of focusing on outcomes reflective of AA's goals (such as abstinence) when studying how AA works.

  10. Exploring transcriptional signalling mediated by OsWRKY13, a potential regulator of multiple physiological processes in rice

    Li Xianghua

    2009-06-01

    Full Text Available Abstract Background Rice transcription regulator OsWRKY13 influences the functioning of more than 500 genes in multiple signalling pathways, with roles in disease resistance, redox homeostasis, abiotic stress responses, and development. Results To determine the putative transcriptional regulation mechanism of OsWRKY13, the putative cis-acting elements of OsWRKY13-influenced genes were analyzed using the whole genome expression profiling of OsWRKY13-activated plants generated with the Affymetrix GeneChip Rice Genome Array. At least 39 transcription factor genes were influenced by OsWRKY13, and 30 of them were downregulated. The promoters of OsWRKY13-upregulated genes were overrepresented with W-boxes for WRKY protein binding, whereas the promoters of OsWRKY13-downregulated genes were enriched with cis-elements putatively for binding of MYB and AP2/EREBP types of transcription factors. Consistent with the distinctive distribution of these cis-elements in up- and downregulated genes, nine WRKY genes were influenced by OsWRKY13 and the promoters of five of them were bound by OsWRKY13 in vitro; all seven differentially expressed AP2/EREBP genes and six of the seven differentially expressed MYB genes were suppressed by in OsWRKY13-activated plants. A subset of OsWRKY13-influenced WRKY genes were involved in host-pathogen interactions. Conclusion These results suggest that OsWRKY13-mediated signalling pathways are partitioned by different transcription factors. WRKY proteins may play important roles in the monitoring of OsWRKY13-upregulated genes and genes involved in pathogen-induced defence responses, whereas MYB and AP2/EREBP proteins may contribute most to the control of OsWRKY13-downregulated genes.

  11. The flexible C-terminal arm of the Lassa arenavirus Z-protein mediates interactions with multiple binding partners.

    May, Eric R; Armen, Roger S; Mannan, Aristotle M; Brooks, Charles L

    2010-08-01

    The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation, and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics (MD) was used to refine the structures, which were then subsequently clustered. Population-weighted ensembles of low-energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was identified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during MD trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein-binding recognition motifs for Tsg101 and eIF4E and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein. (c) 2010 Wiley-Liss, Inc.

  12. Klotho: a humeral mediator in CSF and plasma that influences longevity and susceptibility to multiple complex disorders, including depression.

    Pavlatou, M G; Remaley, A T; Gold, P W

    2016-08-30

    Klotho is a hormone secreted into human cerebrospinal fluid (CSF), plasma and urine that promotes longevity and influences the onset of several premature senescent phenotypes in mice and humans, including atherosclerosis, cardiovascular disease, stroke and osteoporosis. Preliminary studies also suggest that Klotho possesses tumor suppressor properties. Klotho's roles in these phenomena were first suggested by studies demonstrating that a defect in the Klotho gene in mice results in a significant decrease in lifespan. The Klotho-deficient mouse dies prematurely at 8-9 weeks of age. At 4-5 weeks of age, a syndrome resembling human ageing emerges consisting of atherosclerosis, osteoporosis, cognitive disturbances and alterations of hippocampal architecture. Several deficits in Klotho-deficient mice are likely to contribute to these phenomena. These include an inability to defend against oxidative stress in the central nervous system and periphery, decreased capacity to generate nitric oxide to sustain normal endothelial reactivity, defective Klotho-related mediation of glycosylation and ion channel regulation, increased insulin/insulin-like growth factor signaling and a disturbed calcium and phosphate homeostasis accompanied by altered vitamin D levels and ectopic calcification. Identifying the mechanisms by which Klotho influences multiple important pathways is an emerging field in human biology that will contribute significantly to understanding basic physiologic processes and targets for the treatment of complex diseases. Because many of the phenomena seen in Klotho-deficient mice occur in depressive illness, major depression and bipolar disorder represent illnesses potentially associated with Klotho dysregulation. Klotho's presence in CSF, blood and urine should facilitate its study in clinical populations.

  13. Effects of mathematics computer games on special education students' multiplicative reasoning ability

    Bakker, M.; Heuvel-Panhuizen, M.H.A.M. van den; Robitzsch, A.

    2016-01-01

    This study examined the effects of a teacher-delivered intervention with online mathematics mini-games on special education students' multiplicative reasoning ability (multiplication and division). The games involved declarative, procedural, as well as conceptual knowledge of multiplicative

  14. Rapid Exercise-Induced Mobilization of Dendritic Cells Is Potentially Mediated by a Flt3L- and MMP-9-Dependent Process in Multiple Sclerosis

    Nathalie Deckx

    2015-01-01

    Full Text Available In healthy individuals, one exercise bout induces a substantial increase in the number of circulating leukocytes, while their function is transiently suppressed. The effect of one exercise bout in multiple sclerosis (MS is less studied. Since recent evidence suggests a role of dendritic cells (DC in the pathogenesis of MS, we investigated the effect of one combined endurance/resistance exercise bout on the number and function of DC in MS patients and healthy controls. Our results show a rapid increase in the number of DC in response to physical exercise in both MS patients and controls. Further investigation revealed that in particular DC expressing the migratory molecules CCR5 and CD62L were increased upon acute physical activity. This may be mediated by Flt3L- and MMP-9-dependent mobilization of DC, as demonstrated by increased circulating levels of Flt3L and MMP-9 following one exercise bout. Circulating DC display reduced TLR responsiveness after acute exercise, as evidenced by a less pronounced upregulation of activation markers, HLA-DR and CD86, on plasmacytoid DC and conventional DC, respectively. Our results indicate mobilization of DC, which may be less prone to drive inflammatory processes, following exercise. This may present a negative feedback mechanism for exercise-induced tissue damage and inflammation.

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

    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

  16. Multiplicity counting from fission detector signals with time delay effects

    Nagy, L.; Pázsit, I.; Pál, L.

    2018-03-01

    In recent work, we have developed the theory of using the first three auto- and joint central moments of the currents of up to three fission chambers to extract the singles, doubles and triples count rates of traditional multiplicity counting (Pázsit and Pál, 2016; Pázsit et al., 2016). The objective is to elaborate a method for determining the fissile mass, neutron multiplication, and (α, n) neutron emission rate of an unknown assembly of fissile material from the statistics of the fission chamber signals, analogous to the traditional multiplicity counting methods with detectors in the pulse mode. Such a method would be an alternative to He-3 detector systems, which would be free from the dead time problems that would be encountered in high counting rate applications, for example the assay of spent nuclear fuel. A significant restriction of our previous work was that all neutrons born in a source event (spontaneous fission) were assumed to be detected simultaneously, which is not fulfilled in reality. In the present work, this restriction is eliminated, by assuming an independent, identically distributed random time delay for all neutrons arising from one source event. Expressions are derived for the same auto- and joint central moments of the detector current(s) as in the previous case, expressed with the singles, doubles, and triples (S, D and T) count rates. It is shown that if the time-dispersion of neutron detections is of the same order of magnitude as the detector pulse width, as they typically are in measurements of fast neutrons, the multiplicity rates can still be extracted from the moments of the detector current, although with more involved calibration factors. The presented formulae, and hence also the performance of the proposed method, are tested by both analytical models of the time delay as well as with numerical simulations. Methods are suggested also for the modification of the method for large time delay effects (for thermalised neutrons).

  17. Prevalence and effects of multiple chemical sensitivities in Australia

    Anne Steinemann

    2018-06-01

    Full Text Available Multiple chemical sensitivities (MCS is a medical condition associated with exposure to common chemical pollutants. The aims of this study are to assess the prevalence of MCS, its overlaps with asthma and fragrance sensitivity, and its health and societal effects in Australia. Data were collected in June 2016 using an on-line survey with a representative national sample (N = 1098 of adults (ages 18–65 in Australia. Results found that, across the country, 6.5% report medically diagnosed MCS, 18.9% report chemical sensitivity (being unusually sensitive to everyday chemicals and chemically formulated products, and 19.9% either or both. Among people with MCS, 74.6% also have diagnosed asthma or an asthma-like condition, and 91.5% have fragrance sensitivity, reporting health problems (such as migraine headaches when exposed to fragranced consumer products (such as air fresheners and cleaning supplies. In addition, among people with MCS, 77.5% are prevented from access to places because of fragranced products, 52.1% lost workdays or a job in the past year due to fragranced product exposure in the workplace, and 55.4% report health effects considered potentially disabling. Results indicate that MCS is a widespread disease, affecting an estimated 1 million adult Australians, with chemical sensitivity affecting another 2 million. Reducing chemical exposure to problematic sources, such as fragranced consumer products, is critical to reduce adverse effects. Keywords: MCS, Multiple chemical sensitivities, Chemical sensitivity, Asthma, Fragrance sensitivity, Fragranced consumer products

  18. Effects of dependence in high-dimensional multiple testing problems

    van de Wiel Mark A

    2008-02-01

    Full Text Available Abstract Background We consider effects of dependence among variables of high-dimensional data in multiple hypothesis testing problems, in particular the False Discovery Rate (FDR control procedures. Recent simulation studies consider only simple correlation structures among variables, which is hardly inspired by real data features. Our aim is to systematically study effects of several network features like sparsity and correlation strength by imposing dependence structures among variables using random correlation matrices. Results We study the robustness against dependence of several FDR procedures that are popular in microarray studies, such as Benjamin-Hochberg FDR, Storey's q-value, SAM and resampling based FDR procedures. False Non-discovery Rates and estimates of the number of null hypotheses are computed from those methods and compared. Our simulation study shows that methods such as SAM and the q-value do not adequately control the FDR to the level claimed under dependence conditions. On the other hand, the adaptive Benjamini-Hochberg procedure seems to be most robust while remaining conservative. Finally, the estimates of the number of true null hypotheses under various dependence conditions are variable. Conclusion We discuss a new method for efficient guided simulation of dependent data, which satisfy imposed network constraints as conditional independence structures. Our simulation set-up allows for a structural study of the effect of dependencies on multiple testing criterions and is useful for testing a potentially new method on π0 or FDR estimation in a dependency context.

  19. Effect of total lymphoid irradiation in chronic progressive multiple sclerosis

    Cook, S.D.; Devereux, C.; Troiano, R.; Hafstein, M.P.; Zito, G.; Hernandez, E.; Lavenhar, M.; Vidaver, R.; Dowling, P.C.

    1986-01-01

    Total lymphoid irradiation (TLI; 1980 cGy) or sham irradiation was given to 40 patients with chronic progressive multiple sclerosis (MS) in a prospective, randomised, double-blind study. During mean follow-up of 21 months, MS patients treated with TLI has less functional decline than sham-irradiated MS patients (p<0.01). A significant relation was noted between absolute blood lymphocyte counts in the first year after TLI and subsequent course, patients with higher lymphocyte counts generally having a worse prognosis (p<0.01). TLI was well tolerated and associated with only mild short-term, and to date, long-term side-effects. (author)

  20. Multiplicity of effects and health benefits of resveratrol

    Lolita Kuršvietienė

    2016-01-01

    Full Text Available Resveratrol is mainly found in grapes and red wine, also in some plants and fruits, such as peanuts, cranberries, pistachios, blueberries and bilberries. Moreover, nowadays this compound is available as purified preparation and dietary supplement. Resveratrol provides a wide range of benefits, including cardiovascular protective, antiplatelet, antioxidant, anti-inflammatory, blood glucose-lowering and anticancer activities, hence it exhibits a complex mode of action. During the recent years, these properties have been widely studied in animal and human models, both in vitro and in vivo. This paper is intended to present information published during the recent years on the biological activities and multiple effects of resveratrol.

  1. Supplementation of Nigella sativa fixed and essential oil mediates potassium bromate induced oxidative stress and multiple organ toxicity.

    Sultan, Muhammad Tauseef; Butt, Masood Sadiq; Ahmad, Rabia Shabeer; Pasha, Imran; Ahmad, Atif Nisar; Qayyum, Mir Muhammad Nasir

    2012-01-01

    The plants and their functional ingredients hold potential to cure various maladies and number of plants hold therapeutic potential. The present research was designed study the health promoting potential of black cumin (Nigella sativa) fixed oil (BCFO) and essential oil (BCEO) against oxidative stress with special reference to multiple organ toxicity. For the purpose, thirty rats (Strain: Sprague Dawley) were procured and divided into three groups (10 rats/group). The groups were fed on their respective diets i.e. D1 (control), D2 (BCFO @ 4.0%) and D3 (BCEO @ 0.30%) for a period of 56 days. Mild oxidative stress was induced with the help of potassium bromate injection @ 45 mg/Kg body weight. Furthermore, the levels of cardiac and liver enzymes were assayed. The results indicated that oxidative stress increased the activities of cardiac and liver enzymes. However, supplementation of BCFO and BCEO was effective in reducing the abnormal values of enzymes. Elevated levels of lactate dehydrogenase (LDH), CPK and CPK-MB were reduced from 456 to 231, 176 to 122 and 45 to 36mg/dL, respectively. Similarly, liver enzymes were also reduced. However, the results revealed that BCEO supplementation @ 0.30% is more effectual in ameliorating the multiple organ toxicity in oxidative stressed animal modelling. In the nutshell, it can be assumed that black cumin essential oil is more effective in reducing the extent of potassium bromate induced multiple organ toxicity (cardiac and liver enzymes imbalance) that will ultimately helpful in reducing the extent of myocardial and liver necrosis.

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

    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

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

    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

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

    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…

  5. 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.

    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.

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

    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.

  7. Effects of radiotherapy in the treatment of multiple myeloma

    Ochtrop, Thomas Alexander

    2015-01-01

    Palliative irradiation of osteolytic lesions is a considerable component in the treatment for patients with multiple myeloma. In this study, we analyzed the efficacy of irradiation in these patients. Patients and methods: We retrospectively analyzed 153 patients with multiple myeloma who were admitted to our department between 1989 and 2013. According to the staging system of Durie and Salmon 116 patients were classified as stage III. 107/153 patients were treated with radiotherapy of at least one and up to 6 bony lesions at different times. In order to evaluate the effect of local radiotherapy on pain relief and bone recalcification a uni- and multivariate analysis was performed using a binary logistic regression model to correct for multiple measurements. Complete information on dose, fractionation and volume of radiotherapy was available from 81 patients treated in 136 target volumes for pain relief, and from 69 patients treated in 108 target volumes for recalcification. Total radiation doses varied between 8 Gy to 50 Gy (median dose 25 Gy in 2.5 Gy fractions, 5 times a week). Results: Radiotherapy resulted in complete local pain relief in 31% and partial local pain relief in 54% of the patients. In the univariate analysis, higher total radiation doses (p = 0.023) and higher age (p = 0.014) at the time of radiotherapy were significantly associated with a higher likelihood of pain relief, whereas no significant association was detected for concurrent systemic treatment, type and stage of myeloma and location of bone lesions. The same variables were independent predictors for pain relief in the multivariate analysis. Recalcification was observed in 48% of irradiated bone lesions. In the uni- and multivariate analysis higher radiation doses were significantly associated (p = 0.048) with an increased likelihood of recalcification. Side effects of radiotherapy were generally mild. Conclusions: Higher total biological radiation doses were associated with better pain

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

    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…

  9. Therapeutic Effect of Gamma Knife Radiosurgery for Multiple Brain Metastases

    Lee, Chul-Kyu; Lee, Sang Ryul; Cho, Jin Mo; Yang, Kyung Ah

    2011-01-01

    Objective The aim of this study is to evaluate the therapeutic effects of gamma knife radiosurgery (GKRS) in patients with multiple brain metastases and to investigate prognostic factors related to treatment outcome. Methods We retrospectively reviewed clinico-radiological and dosimetric data of 36 patients with 4-14 brain metastases who underwent GKRS for 264 lesions between August 2008 and April 2011. The most common primary tumor site was the lung (n=22), followed by breast (n=7). At GKRS, the median Karnofsky performance scale score was 90 and the mean tumor volume was 1.2 cc (0.002-12.6). The mean prescription dose of 17.8 Gy was delivered to the mean 61.1% isodose line. Among 264 metastases, 175 lesions were assessed for treatment response by at least one imaging follow-up. Results The overall median survival after GKRS was 9.1±1.7 months. Among various factors, primary tumor control was a significant prognostic factor (11.1±1.3 months vs. 3.3±2.4 months, p=0.031). The calculated local tumor control rate at 6 and 9 months after GKRS were 87.9% and 84.2%, respectively. Paddick's conformity index (>0.75) was significantly related to local tumor control. The actuarial peritumoral edema reduction rate was 22.4% at 6 months. Conclusion According to our results, GKRS can provide beneficial effect for the patients with multiple (4 or more) brain metastases, when systemic cancer is controlled. And, careful dosimetry is essential for local tumor control. Therefore, GKRS can be considered as one of the treatment modalities for multiple brain metastase. PMID:22102945

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

    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.

  11. Study of multiple scattering effects in heavy ion RBS

    Fang, Z; O` Connor, D J [Newcastle Univ., NSW (Australia). Dept. of Physics

    1997-12-31

    Multiple scattering effect is normally neglected in conventional Rutherford Backscattering (RBS) analysis. The backscattered particle yield normally agrees well with the theory based on the single scattering model. However, when heavy incident ions are used such as in heavy ion Rutherford backscattering (HIRBS), or the incident ion energy is reduced, multiple scattering effect starts to play a role in the analysis. In this paper, the experimental data of 6MeV C ions backscattered from a Au target are presented. In measured time of flight spectrum a small step in front of the Au high energy edge is observed. The high energy edge of the step is about 3.4 ns ahead of the Au signal which corresponds to an energy {approx} 300 keV higher than the 135 degree single scattering energy. This value coincides with the double scattering energy of C ion undergoes two consecutive 67.5 degree scattering. Efforts made to investigate the origin of the high energy step observed lead to an Monte Carlo simulation aimed to reproduce the experimental spectrum on computer. As a large angle scattering event is a rare event, two consecutive large angle scattering is extremely hard to reproduce in a random simulation process. Thus, the simulation has not found a particle scattering into 130-140 deg with an energy higher than the single scattering energy. Obviously faster algorithms and a better physical model are necessary for a successful simulation. 16 refs., 3 figs.

  12. Study of multiple scattering effects in heavy ion RBS

    Fang, Z.; O`Connor, D.J. [Newcastle Univ., NSW (Australia). Dept. of Physics

    1996-12-31

    Multiple scattering effect is normally neglected in conventional Rutherford Backscattering (RBS) analysis. The backscattered particle yield normally agrees well with the theory based on the single scattering model. However, when heavy incident ions are used such as in heavy ion Rutherford backscattering (HIRBS), or the incident ion energy is reduced, multiple scattering effect starts to play a role in the analysis. In this paper, the experimental data of 6MeV C ions backscattered from a Au target are presented. In measured time of flight spectrum a small step in front of the Au high energy edge is observed. The high energy edge of the step is about 3.4 ns ahead of the Au signal which corresponds to an energy {approx} 300 keV higher than the 135 degree single scattering energy. This value coincides with the double scattering energy of C ion undergoes two consecutive 67.5 degree scattering. Efforts made to investigate the origin of the high energy step observed lead to an Monte Carlo simulation aimed to reproduce the experimental spectrum on computer. As a large angle scattering event is a rare event, two consecutive large angle scattering is extremely hard to reproduce in a random simulation process. Thus, the simulation has not found a particle scattering into 130-140 deg with an energy higher than the single scattering energy. Obviously faster algorithms and a better physical model are necessary for a successful simulation. 16 refs., 3 figs.

  13. Sensitivity analysis for the effects of multiple unmeasured confounders.

    Groenwold, Rolf H H; Sterne, Jonathan A C; Lawlor, Debbie A; Moons, Karel G M; Hoes, Arno W; Tilling, Kate

    2016-09-01

    Observational studies are prone to (unmeasured) confounding. Sensitivity analysis of unmeasured confounding typically focuses on a single unmeasured confounder. The purpose of this study was to assess the impact of multiple (possibly weak) unmeasured confounders. Simulation studies were performed based on parameters estimated from the British Women's Heart and Health Study, including 28 measured confounders and assuming no effect of ascorbic acid intake on mortality. In addition, 25, 50, or 100 unmeasured confounders were simulated, with various mutual correlations and correlations with measured confounders. The correlated unmeasured confounders did not need to be strongly associated with exposure and outcome to substantially bias the exposure-outcome association at interest, provided that there are sufficiently many unmeasured confounders. Correlations between unmeasured confounders, in addition to the strength of their relationship with exposure and outcome, are key drivers of the magnitude of unmeasured confounding and should be considered in sensitivity analyses. However, if the unmeasured confounders are correlated with measured confounders, the bias yielded by unmeasured confounders is partly removed through adjustment for the measured confounders. Discussions of the potential impact of unmeasured confounding in observational studies, and sensitivity analyses to examine this, should focus on the potential for the joint effect of multiple unmeasured confounders to bias results. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Team effectiveness in academic medical libraries: a multiple case study*

    Russo Martin, Elaine

    2006-01-01

    Objectives: The objective of this study is to apply J. Richard Hackman's framework on team effectiveness to academic medical library settings. Methods: The study uses a qualitative, multiple case study design, employing interviews and focus groups to examine team effectiveness in three academic medical libraries. Another site was selected as a pilot to validate the research design, field procedures, and methods to be used with the cases. In all, three interviews and twelve focus groups, with approximately seventy-five participants, were conducted at the case study libraries. Findings: Hackman identified five conditions leading to team effectiveness and three outcomes dimensions that defined effectiveness. The participants in this study identified additional characteristics of effectiveness that focused on enhanced communication, leadership personality and behavior, and relationship building. The study also revealed an additional outcome dimension related to the evolution of teams. Conclusions: Introducing teams into an organization is not a trivial matter. Hackman's model of effectiveness has implications for designing successful library teams. PMID:16888659

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

    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.

  16. National Prevalence and Effects of Multiple Chemical Sensitivities.

    Steinemann, Anne

    2018-03-01

    The aim of this study was to assess the prevalence of multiple chemical sensitivities (MCS), its co-occurrence with asthma and fragrance sensitivity, and effects from exposure to fragranced consumer products. A nationally representative cross-sectional population-based sample of adult Americans (n = 1137) was surveyed in June 2016. Among the population, 12.8% report medically diagnosed MCS and 25.9% report chemical sensitivity. Of those with MCS, 86.2% experience health problems, such as migraine headaches, when exposed to fragranced consumer products; 71.0% are asthmatic; 70.3% cannot access places that use fragranced products such as air fresheners; and 60.7% lost workdays or a job in the past year due to fragranced products in the workplace. Prevalence of diagnosed MCS has increased over 300%, and self-reported chemical sensitivity over 200%, in the past decade. Reducing exposure to fragranced products could help reduce adverse health and societal effects.

  17. Effective field theories for superconducting systems with multiple Fermi surfaces

    Braga, P.R., E-mail: pedro.rangel.braga@gmail.com [Departamento de Física Teórica, Instituto de Física, UERJ - Universidade do Estado do Rio de Janeiro, Rua São Francisco Xavier 524, 20550-013 Maracanã, Rio de Janeiro (Brazil); Granado, D.R., E-mail: diegorochagrana@uerj.br [Departamento de Física Teórica, Instituto de Física, UERJ - Universidade do Estado do Rio de Janeiro, Rua São Francisco Xavier 524, 20550-013 Maracanã, Rio de Janeiro (Brazil); Department of Physics and Astronomy, Ghent University, Krijgslaan 281-S9, 9000 Gent (Belgium); Guimaraes, M.S., E-mail: msguimaraes@uerj.br [Departamento de Física Teórica, Instituto de Física, UERJ - Universidade do Estado do Rio de Janeiro, Rua São Francisco Xavier 524, 20550-013 Maracanã, Rio de Janeiro (Brazil); Wotzasek, C., E-mail: clovis@if.ufrj.br [Instituto de Física, Universidade Federal do Rio de Janeiro, 21941-972, Rio de Janeiro (Brazil)

    2016-11-15

    In this work we investigate the description of superconducting systems with multiple Fermi surfaces. For the case of one Fermi surface we re-obtain the result that the superconductor is more precisely described as a topological state of matter. Studying the case of more than one Fermi surface, we obtain the effective theory describing a time reversal symmetric topological superconductor. These results are obtained by employing a general procedure to construct effective low energy actions describing states of electromagnetic systems interacting with charges and defects. The procedure consists in taking into account the proliferation or dilution of these charges and defects and its consequences for the low energy description of the electromagnetic response of the system. We find that the main ingredient entering the low energy characterization of the system with more than one Fermi surface is a non-conservation of the canonical supercurrent triggered by particular vortex configurations.

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

    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.

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

    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…

  20. Role of Transformational Leadership in Effective Organizational Knowledge Creation Practices: Mediating Effects of Employees' Work Engagement

    Song, Ji Hoon; Kolb, Judith A.; Lee, Ung Hee; Kim, Hye Kyoung

    2012-01-01

    Engagement as an area of increasing interest has been discussed in terms of a wide array of organizational policies, practices, and outcomes. This study focuses on a specific aspect of work engagement and its relationship with leadership practices and the outcome of knowledge creation. The mediating effect of employees' work engagement level was…

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

    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

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

    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

  3. Using Functional Electrical Stimulation Mediated by Iterative Learning Control and Robotics to Improve Arm Movement for People With Multiple Sclerosis.

    Sampson, Patrica; Freeman, Chris; Coote, Susan; Demain, Sara; Feys, Peter; Meadmore, Katie; Hughes, Ann-Marie

    2016-02-01

    Few interventions address multiple sclerosis (MS) arm dysfunction but robotics and functional electrical stimulation (FES) appear promising. This paper investigates the feasibility of combining FES with passive robotic support during virtual reality (VR) training tasks to improve upper limb function in people with multiple sclerosis (pwMS). The system assists patients in following a specified trajectory path, employing an advanced model-based paradigm termed iterative learning control (ILC) to adjust the FES to improve accuracy and maximise voluntary effort. Reaching tasks were repeated six times with ILC learning the optimum control action from previous attempts. A convenience sample of five pwMS was recruited from local MS societies, and the intervention comprised 18 one-hour training sessions over 10 weeks. The accuracy of tracking performance without FES and the amount of FES delivered during training were analyzed using regression analysis. Clinical functioning of the arm was documented before and after treatment with standard tests. Statistically significant results following training included: improved accuracy of tracking performance both when assisted and unassisted by FES; reduction in maximum amount of FES needed to assist tracking; and less impairment in the proximal arm that was trained. The system was well tolerated by all participants with no increase in muscle fatigue reported. This study confirms the feasibility of FES combined with passive robot assistance as a potentially effective intervention to improve arm movement and control in pwMS and provides the basis for a follow-up study.

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

    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.

  5. Effect of ARA9 on dioxin receptor mediated transcription

    Lees, M.J.; Whitelaw, M.L.

    2002-01-01

    The dioxin (Aryl hydrocarbon) receptor (DR) is a unique bHLH transcription factor which is activated by binding of planar aromatic hydrocarbons typified by dioxin (TCDD). The active receptor is key to metabolism of aryl hydrocarbon xenobiotics by being a potent inducer of CYP1A1 gene activity. Chlorinated dioxins are inert to metabolism and initiate multifarious toxicities, including potent tumour promotion. These ill-effects are mediated by the activated DR and we are studying the mechanisms by which the ligand binding domain of the DR controls activity of the protein. The DR ligand binding domain resides within a PAS (Per/Arnt/Sim homology) region which is contiguous with the bHLH. The latent bHLH/PAS dioxin receptor (DR) is found in the cytoplasm of most mammalian cell types in a complex with heat shock protein 90, a novel immunophilin like protein termed ARA9/XAP2/AIP, and the co-chaperone p23. Here we use antisense ARA9 constructs to reveal that in the absence of ARA9, the DR is unable to form a transcriptionally active complex. Co-expression of antisense ARA9 with a form of the DR which is constitutively targeted to the nucleus leads to dramatically decreased levels of the nuclear DR protein, implying that ARA9 may function beyond its currently proposed role in cytoplasmic retention of the latent DR

  6. Predicting the cumulative effect of multiple disturbances on seagrass connectivity.

    Grech, Alana; Hanert, Emmanuel; McKenzie, Len; Rasheed, Michael; Thomas, Christopher; Tol, Samantha; Wang, Mingzhu; Waycott, Michelle; Wolter, Jolan; Coles, Rob

    2018-03-15

    The rate of exchange, or connectivity, among populations effects their ability to recover after disturbance events. However, there is limited information on the extent to which populations are connected or how multiple disturbances affect connectivity, especially in coastal and marine ecosystems. We used network analysis and the outputs of a biophysical model to measure potential functional connectivity and predict the impact of multiple disturbances on seagrasses in the central Great Barrier Reef World Heritage Area (GBRWHA), Australia. The seagrass networks were densely connected, indicating that seagrasses are resilient to the random loss of meadows. Our analysis identified discrete meadows that are important sources of seagrass propagules and that serve as stepping stones connecting various different parts of the network. Several of these meadows were close to urban areas or ports and likely to be at risk from coastal development. Deep water meadows were highly connected to coastal meadows and may function as a refuge, but only for non-foundation species. We evaluated changes to the structure and functioning of the seagrass networks when one or more discrete meadows were removed due to multiple disturbance events. The scale of disturbance required to disconnect the seagrass networks into two or more components was on average >245 km, about half the length of the metapopulation. The densely connected seagrass meadows of the central GBRWHA are not limited by the supply of propagules; therefore, management should focus on improving environmental conditions that support natural seagrass recruitment and recovery processes. Our study provides a new framework for assessing the impact of global change on the connectivity and persistence of coastal and marine ecosystems. Without this knowledge, management actions, including coastal restoration, may prove unnecessary and be unsuccessful. © 2018 John Wiley & Sons Ltd.

  7. Intergroup differentiation in computer-mediated communication : Effects of depersonalization

    Postmes, T; Spears, R; Lea, M

    Two studies examined intergroup discussions via computer-mediated communication systems. It was hypothesized that depersonalization, in comparison with individuated interaction, would increase the tendency for intergroup differentiation in attitudes and stereotypes, In Study 1, 24 groups

  8. Mediation Analysis Using the Hierarchical Multiple Regression Technique: A Study of the Mediating Roles of World-Class Performance in Operations

    Wakhid S. Ciptono

    2010-05-01

    mediating roles of the contextual factors of world-class performance in operations (i.e., world-class company practices or WCC, operational excellence practices or OE, company nonfinancial performance or CNFP, and the company financial performance would enable the company to facilitate the sustainability of TQM implementation model. This empirical study aims to assess how TQM—a holistic management philosophy initially developed by W. Edward Deming, which integrates improvement strategy, management practices, and organizational performance—is specifically implemented in the oil and gas companies operating in Indonesia. Relevant literature on the TQM, the world-class performance in operations (world-class company and operational performance, the company performance (financial and non-financial performances, and the amendments of the Law of the Republic of Indonesia concerning the oil and gas industry, and related research on how the oil and gas industry in Indonesia develops sustainable competitive advantage and sustainable development programs are reviewed in details in our study. The findings from data analysis provide evidence that there is a strong positive relationship between the critical factors of quality management practices and the company financial performance mediated by the three mediating variables, i.e., world-class company practices, operational excellence practices, and company non-financial performance.

  9. 创业失败经验与新产品开发绩效的倒U形关系:创业导向的多重中介作用%An Inverted U-Shape Relationship between Entrepreneurial Failure Experiences and New Product Development Performance:The Multiple Mediating Effects of Entrepreneurial Orientation

    于晓宇; 陶向明

    2015-01-01

    Prior empirical studies on the relationship between entrepreneur′s prior experience and the new venture performance are mixed.Some scholars argue that entrepreneur′s prior experience may enhance new venture performance primarily based on the human-capital theory.However, many scholars hold the viewpoint that more prior experience may not guarantee better new ven-ture performance, since prior experience can shape his/her cognitive profile and lead to his/her bias in thinking, which may re-tard the entrepreneurs′learning behaviors and thus negatively affect performance of new ventures.Previous studies failed to con-jointly consider both the positive and negative effects of entrepreneurial failure experience on new venture performance, and have not addressed whether and how entrepreneurial failure experience influences the New Product Development( NPD) performance of new ventures.To address these research gaps, this study provides fresh insights into the relationship between entrepreneurial fail-ure experience and NPD performance.This study integrates experience learning theory and cognitive theories and builds a con-ceptual model to explore an inverted U-shaped relationship between entrepreneurial failure experience and NPD performance and the underlying mechanism. Hypotheses were tested using data from 231 habitual entrepreneurs of high-technology new ventures.The study results, based on hierarchical regression analysis and bootstrapping method, showed that:①There was an inverted U-shaped relationship between entrepreneurial failure experience and the NPD performance; ②There were inverted U-shaped relationships between entrepre-neurial failure experience and the three dimensions of entrepreneurial orientation, namely, proactiveness, innovativeness and risk-taking;③proactiveness, innovativeness and risk-taking partially mediate the relationship between entrepreneurial failure ex-perience and NPD performance respectively. The study demonstrates a nonlinear

  10. Income as mediator of the effect of occupation on the risk of myocardial infarction

    Andersen, Ingelise; Gamborg, Michael; Osler, Merete

    2005-01-01

    To investigate whether the effect of occupational grade on the risk of myocardial infarction (MI) is mediated by income with different aspects of income taken into account.......To investigate whether the effect of occupational grade on the risk of myocardial infarction (MI) is mediated by income with different aspects of income taken into account....

  11. Moderators of the Mediated Effect of Intentions, Planning, and Saturated-Fat Intake in Obese Individuals

    Soureti, A.; Hurling, R.; van Mechelen, W.; Cobain, M.; Chin A Paw, M.J.M.

    2012-01-01

    Objective: The present study aimed to advance our understanding of health-related theory, that is, the alleged intention-behavior gap in an obese population. It examined the mediating effects of planning on the intention-behavior relationship and the moderated mediation effects of age, self-efficacy

  12. Direction of Effects in Multiple Linear Regression Models.

    Wiedermann, Wolfgang; von Eye, Alexander

    2015-01-01

    Previous studies analyzed asymmetric properties of the Pearson correlation coefficient using higher than second order moments. These asymmetric properties can be used to determine the direction of dependence in a linear regression setting (i.e., establish which of two variables is more likely to be on the outcome side) within the framework of cross-sectional observational data. Extant approaches are restricted to the bivariate regression case. The present contribution extends the direction of dependence methodology to a multiple linear regression setting by analyzing distributional properties of residuals of competing multiple regression models. It is shown that, under certain conditions, the third central moments of estimated regression residuals can be used to decide upon direction of effects. In addition, three different approaches for statistical inference are discussed: a combined D'Agostino normality test, a skewness difference test, and a bootstrap difference test. Type I error and power of the procedures are assessed using Monte Carlo simulations, and an empirical example is provided for illustrative purposes. In the discussion, issues concerning the quality of psychological data, possible extensions of the proposed methods to the fourth central moment of regression residuals, and potential applications are addressed.

  13. Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

    Milo, Ron

    2015-04-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

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

    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.

  15. Effective arithmetic in finite fields based on Chudnovsky's multiplication algorithm

    Atighehchi , Kévin; Ballet , Stéphane; Bonnecaze , Alexis; Rolland , Robert

    2016-01-01

    International audience; Thanks to a new construction of the Chudnovsky and Chudnovsky multiplication algorithm, we design efficient algorithms for both the exponentiation and the multiplication in finite fields. They are tailored to hardware implementation and they allow computations to be parallelized, while maintaining a low number of bilinear multiplications.À partir d'une nouvelle construction de l'algorithme de multiplication de Chudnovsky et Chudnovsky, nous concevons des algorithmes ef...

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

    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.

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

    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.

  18. Implications of astrocytes in mediating the protective effects of Selective Estrogen Receptor Modulators upon brain damage

    George E. Barreto

    2015-04-01

    Full Text Available Selective Estrogen Receptor Modulators (SERMs are steroidal or non-steroidal compounds that are already used in clinical practice for the treatment of breast cancer, osteoporosis and menopausal symptoms. While SERMs actions in the breast, bone, and uterus have been well characterized, their actions in the brain are less well understood. Previous works have demonstrated the beneficial effects of SERMs in different chronic neurodegenerative diseases like Alzheimer, Parkinson’s disease and Multiple sclerosis, as well as acute degeneration as stroke and traumatic brain injury. Moreover, these compounds exhibit similar protective actions as those of estradiol in the Central Nervous System, overt any secondary effect. For these reasons, in the past few years, there has been a growing interest in the neuroprotective effects exerted directly or indirectly by SERMs in the SNC. In this context, astrocytes play an important role in the maintenance of brain metabolism, and antioxidant support to neurons, thus indicating that better protection of astrocytes are an important asset targeting neuronal protection. Moreover, various clinical and experimental studies have reported that astrocytes are essential for the neuroprotective effects of SERMs during neuronal injuries, as these cells express different estrogen receptors in cell membrane, demonstrating that part of SERMs effects upon injury may be mediated by astrocytes. The present work highlights the current evidence on the protective mechanisms of SERMs, such as tamoxifen and raloxifene, in the SNC, and their modulation of astrocytic properties as promising therapeutic targets during brain damage.

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

    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...

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

    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.

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

    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...

  2. Neuroprotective effects of testosterone treatment in men with multiple sclerosis

    Florian Kurth

    2014-01-01

    Full Text Available Multiple sclerosis (MS is an inflammatory and neurodegenerative disease of the central nervous system. While current medication reduces relapses and inflammatory activity, it has only a modest effect on long-term disability and gray matter atrophy. Here, we have characterized the potential neuroprotective effects of testosterone on cerebral gray matter in a pilot clinical trial. Ten men with relapsing–remitting MS were included in this open-label phase II trial. Subjects were observed without treatment for 6 months, followed by testosterone treatment for another 12 months. Focal gray matter loss as a marker for neurodegeneration was assessed using voxel-based morphometry. During the non-treatment phase, significant voxel-wise gray matter decreases were widespread (p≤ 0.05 corrected. However, during testosterone treatment, gray matter loss was no longer evident. In fact, a significant gray matter increase in the right frontal cortex was observed (p≤ 0.05 corrected. These observations support the potential of testosterone treatment to stall (and perhaps even reverse neurodegeneration associated with MS. Furthermore, they warrant the investigation of testosterone's neuroprotective effects in larger, placebo controlled MS trials as well as in other neurodegenerative diseases. This is the first report of gray matter increase as the result of treatment in MS.

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

    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.

  4. Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.

    Peter C Cook

    2011-03-01

    Full Text Available Infection of the mammalian host by schistosome larvae occurs via the skin, although nothing is known about the development of immune responses to multiple exposures of schistosome larvae, and/or their excretory/secretory (E/S products. Here, we show that multiple (4x exposures, prior to the onset of egg laying by adult worms, modulate the skin immune response and induce CD4(+ cell hypo-responsiveness in the draining lymph node, and even modulate the formation of hepatic egg-induced granulomas. Compared to mice exposed to a single infection (1x, dermal cells from multiply infected mice (4x, were less able to support lymph node cell proliferation. Analysis of dermal cells showed that the most abundant in 4x mice were eosinophils (F4/80(+MHC-II(-, but they did not impact the ability of antigen presenting cells (APC to support lymphocyte proliferation to parasite antigen in vitro. However, two other cell populations from the dermal site of infection appear to have a critical role. The first comprises arginase-1(+, Ym-1(+ alternatively activated macrophage-like cells, and the second are functionally compromised MHC-II(hi cells. Through the administration of exogenous IL-12 to multiply infected mice, we show that these suppressive myeloid cell phenotypes form as a consequence of events in the skin, most notably an enrichment of IL-4 and IL-13, likely resulting from an influx of RELMα-expressing eosinophils. We further illustrate that the development of these suppressive dermal cells is dependent upon IL-4Rα signalling. The development of immune hypo-responsiveness to schistosome larvae and their effect on the subsequent response to the immunopathogenic egg is important in appreciating how immune responses to helminth infections are modulated by repeated exposure to the infective early stages of development.

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

    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,…

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

    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.

  7. Impulse purchases and trust: the mediating effect of stickiness and the mental budgeting account.

    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.

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

    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.

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

    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.

  10. Diffusion of multiple species with excluded-volume effects

    Bruna, Maria; Chapman, S. Jonathan

    2012-01-01

    Stochastic models of diffusion with excluded-volume effects are used to model many biological and physical systems at a discrete level. The average properties of the population may be described by a continuum model based on partial differential equations. In this paper we consider multiple interacting subpopulations/species and study how the inter-species competition emerges at the population level. Each individual is described as a finite-size hard core interacting particle undergoing Brownian motion. The link between the discrete stochastic equations of motion and the continuum model is considered systematically using the method of matched asymptotic expansions. The system for two species leads to a nonlinear cross-diffusion system for each subpopulation, which captures the enhancement of the effective diffusion rate due to excluded-volume interactions between particles of the same species, and the diminishment due to particles of the other species. This model can explain two alternative notions of the diffusion coefficient that are often confounded, namely collective diffusion and self-diffusion. Simulations of the discrete system show good agreement with the analytic results. © 2012 American Institute of Physics.

  11. Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects.

    Zheng, Bin; Yang, Liu; Wen, Caixia; Huang, Xiuwang; Xu, Chenxia; Lee, Kuan-Han; Xu, Jianhua

    2016-03-15

    L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    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.

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

    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.

  14. Bias and Bias Correction in Multi-Site Instrumental Variables Analysis of Heterogeneous Mediator Effects

    Reardon, Sean F.; Unlu, Faith; Zhu, Pei; Bloom, Howard

    2013-01-01

    We explore the use of instrumental variables (IV) analysis with a multi-site randomized trial to estimate the effect of a mediating variable on an outcome in cases where it can be assumed that the observed mediator is the only mechanism linking treatment assignment to outcomes, as assumption known in the instrumental variables literature as the…

  15. Bias and Bias Correction in Multisite Instrumental Variables Analysis of Heterogeneous Mediator Effects

    Reardon, Sean F.; Unlu, Fatih; Zhu, Pei; Bloom, Howard S.

    2014-01-01

    We explore the use of instrumental variables (IV) analysis with a multisite randomized trial to estimate the effect of a mediating variable on an outcome in cases where it can be assumed that the observed mediator is the only mechanism linking treatment assignment to outcomes, an assumption known in the IV literature as the exclusion restriction.…

  16. Academic Achievement, Self-Concept and Depression in Taiwanese Children: Moderated Mediation Effect

    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…

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

    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.

  18. mediation: R Package for Causal Mediation Analysis

    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.

  19. Effects of organizational justice on organizational citizenship behaviors: mediating effects of institutional trust and affective commitment.

    Guh, Wei-Yuan; Lin, Shang-Ping; Fan, Chwei-Jen; Yang, Chin-Fang

    2013-06-01

    This study investigated the mediating role of institutional trust and affective commitment on the relationship between organizational justice and organizational citizenship behaviors. The study participants were 315 faculty members at 67 public/private universities of technology and vocational colleges in Taiwan. Structural equation modeling was used to analyze the relationships between the variables and assess the goodness of fit of the overall model. Organizational justice was positively related to institutional trust and there was an indirect effect of organizational justice on affective commitment through institutional trust. In addition, the relation between institutional trust and affective commitment was positive and affective commitment was shown to have a positive relation to organizational citizenship behaviors. Institutional trust was found to indirectly affect organizational citizenship behaviors through affective commitment. Most importantly, this study suggested a mediating effect of institutional trust and affective commitment on the relation between organizational justice and organizational citizenship behaviors. Implications, limitations, and future research were also discussed.

  20. Mediation Effects of Internet Addiction on Shame and Social Networking

    Dogan, Ugur; Kaya, Sinem

    2016-01-01

    A survey of 488 college students was conducted in Turkey to investigate the relationship between social network usage, shame and Internet addiction. It was hypothesized that a relationship between shame and social network usage was mediated by Internet addiction. First of all, according to simple regression analysis, it was found that shame…

  1. Stimulus effects and the mediation of recognition memory.

    McAdoo, Ryan M; Key, Kylie N; Gronlund, Scott D

    2018-04-19

    Two broad approaches characterize the type of evidence that mediates recognition memory: discrete state and continuous. Discrete-state models posit a thresholded memory process that provides accurate information about an item (it is detected) or, failing that, no mnemonic information about the item. Continuous models, in contrast, posit the existence of graded mnemonic information about an item. Evidence favoring 1 approach over the other has been mixed, suggesting the possibility that the mediation of recognition memory may be adaptable and influenced by other factors. We tested this possibility with 2 experiments that varied the semantic similarity of word targets and fillers. Experiment 1, which used semantically similar fillers, displayed evidence of continuous mediation (contrary to Kellen & Klauer, 2015), whereas Experiment 2, which used semantically dissimilar fillers, displayed evidence of discrete mediation. The results have implications for basic theories of recognition memory, as well as for theories of applied domains like eyewitness identification. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  2. The mediating effect of sustainability control system on reverse ...

    This paper analyses part of the viability of green supply chain management practices created for fisheries industry to implement sustainability control system adoption as mediating on reverse logistics innovation and customer environmental collaboration towards sustainability performance. It examines reverse logistics ...

  3. Trust, Knowledge Creation and Mediating Effects of Knowledge Transfer Processes

    Anna Sankowska

    2016-01-01

    Full Text Available This paper investigates how organizational trust contributes to knowledge transfer processes and knowledge creation both directly and indirectly. The mediation analyses were used. The findings using cross-sectional data from Polish companies suggest a new way of thinking in respect of how crucial is trust to creation of knowledge unconnected to organizational memory.

  4. Effects of mediated social touch on affective experiences and trust

    Erk, S.M.; Toet, A.; Erp, J.B.F. van

    2015-01-01

    This study investigated whether communication via mediated hand pressure during a remotely shared experience (watching an amusing video) can (1) enhance recovery from sadness, (2) enhance the affective quality of the experience, and (3) increase trust towards the communication partner. Thereto

  5. Effects of mediated social touch on affective experiences and trust.

    Erk, Stefanie M.; Toet, Alexander; van Erp, Johannes Bernardus Fransiscus

    2015-01-01

    This study investigated whether communication via mediated hand pressure during a remotely shared experience (watching an amusing video) can (1) enhance recovery from sadness, (2) enhance the affective quality of the experience, and (3) increase trust towards the communication partner. Thereto

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

    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

  7. Microscopic theory of multiple-phonon-mediated dephasing and relaxation of quantum dots near a photonic band gap

    Roy, Chiranjeeb; John, Sajeev

    2010-02-01

    We derive a quantum theory of the role of acoustic and optical phonons in modifying the optical absorption line shape, polarization dynamics, and population dynamics of a two-level atom (quantum dot) in the “colored” electromagnetic vacuum of a photonic band-gap (PBG) material. This is based on a microscopic Hamiltonian describing both radiative and vibrational processes quantum mechanically. We elucidate the extent to which phonon-assisted decay limits the lifetime of a single photon-atom bound state and derive the modified spontaneous emission dynamics due to coupling to various phonon baths. We demonstrate that coherent interaction with undamped phonons can lead to an enhanced lifetime of a photon-atom bound state in a PBG. This results in reduction of the steady-state atomic polarization but an increase in the fractionalized upper state population in the photon-atom bound state. We demonstrate, on the other hand, that the lifetime of the photon-atom bound state in a PBG is limited by the lifetime of phonons due to lattice anharmonicities (breakup of phonons into lower energy phonons) and purely nonradiative decay. We also derive the modified polarization decay and dephasing rates in the presence of such damping. This leads to a microscopic, quantum theory of the optical absorption line shapes. Our model and formalism provide a starting point for describing dephasing and relaxation in the presence of external coherent fields and multiple quantum dot interactions in electromagnetic reservoirs with radiative memory effects.

  8. Microscopic theory of multiple-phonon-mediated dephasing and relaxation of quantum dots near a photonic band gap

    Roy, Chiranjeeb; John, Sajeev

    2010-01-01

    We derive a quantum theory of the role of acoustic and optical phonons in modifying the optical absorption line shape, polarization dynamics, and population dynamics of a two-level atom (quantum dot) in the ''colored'' electromagnetic vacuum of a photonic band-gap (PBG) material. This is based on a microscopic Hamiltonian describing both radiative and vibrational processes quantum mechanically. We elucidate the extent to which phonon-assisted decay limits the lifetime of a single photon-atom bound state and derive the modified spontaneous emission dynamics due to coupling to various phonon baths. We demonstrate that coherent interaction with undamped phonons can lead to an enhanced lifetime of a photon-atom bound state in a PBG. This results in reduction of the steady-state atomic polarization but an increase in the fractionalized upper state population in the photon-atom bound state. We demonstrate, on the other hand, that the lifetime of the photon-atom bound state in a PBG is limited by the lifetime of phonons due to lattice anharmonicities (breakup of phonons into lower energy phonons) and purely nonradiative decay. We also derive the modified polarization decay and dephasing rates in the presence of such damping. This leads to a microscopic, quantum theory of the optical absorption line shapes. Our model and formalism provide a starting point for describing dephasing and relaxation in the presence of external coherent fields and multiple quantum dot interactions in electromagnetic reservoirs with radiative memory effects.

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

    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.

  10. College Alcohol Beliefs and Drinking Consequences: A Multiple Mediation Analysis of Norms, Expectancies, and Willingness to Experience Drinking Consequences

    Osberg, Timothy M.; Boyer, Amber

    2018-01-01

    Objective: We explored the potential mediating role of willingness to experience drinking consequences and other traditional alcohol outcome predictors (descriptive norms, injunctive norms, positive alcohol expectancies) in explaining the association between college alcohol beliefs1 (CABs) and the actual experience of drinking consequences among…

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

    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

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

    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.

  13. EFFECTIVE INDICES FOR MONITORING MENTAL WORKLOAD WHILE PERFORMING MULTIPLE TASKS.

    Hsu, Bin-Wei; Wang, Mao-Jiun J; Chen, Chi-Yuan; Chen, Fang

    2015-08-01

    This study identified several physiological indices that can accurately monitor mental workload while participants performed multiple tasks with the strategy of maintaining stable performance and maximizing accuracy. Thirty male participants completed three 10-min. simulated multitasks: MATB (Multi-Attribute Task Battery) with three workload levels. Twenty-five commonly used mental workload measures were collected, including heart rate, 12 HRV (heart rate variability), 10 EEG (electroencephalography) indices (α, β, θ, α/θ, θ/β from O1-O2 and F4-C4), and two subjective measures. Analyses of index sensitivity showed that two EEG indices, θ and α/θ (F4-C4), one time-domain HRV-SDNN (standard deviation of inter-beat intervals), and four frequency-domain HRV: VLF (very low frequency), LF (low frequency), %HF (percentage of high frequency), and LF/HF were sensitive to differentiate high workload. EEG α/θ (F4-C4) and LF/HF were most effective for monitoring high mental workload. LF/HF showed the highest correlations with other physiological indices. EEG α/θ (F4-C4) showed strong correlations with subjective measures across different mental workload levels. Operation strategy would affect the sensitivity of EEG α (F4-C4) and HF.

  14. Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT and lysosomal trafficking regulator (LYST induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study

    Ivyna Pau Ni Bong

    2016-11-01

    Full Text Available Multiple myeloma (MM is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM phosphoribosyltransferase (NAMPT and lysosomal trafficking regulator (LYST genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05. NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05. Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01. Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM.

  15. Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study

    Bong, Ivyna Pau Ni; Ng, Ching Ching; Fakiruddin, Shaik Kamal; Lim, Moon Nian; Zakaria, Zubaidah

    2016-01-01

    Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the fprotein expression in unctions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA)-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05). NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05). Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01). Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM. PMID:27754828

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

    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.

  17. Proactive sustainability strategy and corporate sustainability performance: The mediating effect of sustainability control systems.

    Wijethilake, Chaminda

    2017-07-01

    This study examines to what extent corporations use sustainability control systems (SCS) to translate proactive sustainability strategy into corporate sustainability performance. The study investigates the mediating effect of SCS on the relationship between proactive sustainability strategy and corporate sustainability performance. Survey data were collected from top managers in 175 multinational and local corporations operating in Sri Lanka and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). SCS were observed to only partially mediate the relationship between proactive sustainability strategy and corporate sustainability performance. The mediating effect of SCS is further examined under three sustainability strategies; environmental and social strategies reveal a partial mediation, while the economic strategy exhibits no mediation. The study also finds that (i) a proactive sustainability strategy is positively associated with SCS and corporate sustainability performance and (ii) SCS are positively associated with corporate sustainability performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Sensitivity analysis in multiple imputation in effectiveness studies of psychotherapy.

    Crameri, Aureliano; von Wyl, Agnes; Koemeda, Margit; Schulthess, Peter; Tschuschke, Volker

    2015-01-01

    The importance of preventing and treating incomplete data in effectiveness studies is nowadays emphasized. However, most of the publications focus on randomized clinical trials (RCT). One flexible technique for statistical inference with missing data is multiple imputation (MI). Since methods such as MI rely on the assumption of missing data being at random (MAR), a sensitivity analysis for testing the robustness against departures from this assumption is required. In this paper we present a sensitivity analysis technique based on posterior predictive checking, which takes into consideration the concept of clinical significance used in the evaluation of intra-individual changes. We demonstrate the possibilities this technique can offer with the example of irregular longitudinal data collected with the Outcome Questionnaire-45 (OQ-45) and the Helping Alliance Questionnaire (HAQ) in a sample of 260 outpatients. The sensitivity analysis can be used to (1) quantify the degree of bias introduced by missing not at random data (MNAR) in a worst reasonable case scenario, (2) compare the performance of different analysis methods for dealing with missing data, or (3) detect the influence of possible violations to the model assumptions (e.g., lack of normality). Moreover, our analysis showed that ratings from the patient's and therapist's version of the HAQ could significantly improve the predictive value of the routine outcome monitoring based on the OQ-45. Since analysis dropouts always occur, repeated measurements with the OQ-45 and the HAQ analyzed with MI are useful to improve the accuracy of outcome estimates in quality assurance assessments and non-randomized effectiveness studies in the field of outpatient psychotherapy.

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

    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/.

  20. Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling

    Zeis, T.; Allaman, I.; Gentner, M.; Schroder, K.; Tschopp, J.; Magistretti, Pierre J.; Schaeren-Wiemers, N.

    2015-01-01

    Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction

  1. Effect of thermohydraulic parameter on the flux distribution and the effective multiplication factor

    Mello, J.C.; Valladares, G.L.

    1990-01-01

    The influence of two thermohydraulics parameters; the coolant flow velocity along the reactor channels and the increase of the average water temperature through the core, on the thermal flux distribution and on the effective multiplication factor, was studied in a radioisotopes production reactor. The results show that, for a fixed values of the thermohydraulics parameters reffered above, there are limits for the reactor core volume reduction for each value of the V sub(mod)/V sub(comb) ratio. These thermohydraulics conditions determine the higher termal flux value in the flux-trap and the lower value of the reactor effective multiplication factor. It is also show that there is a V sub(mod)/V sub(comb) ratio value that correspond to the higher value of the lower effective multiplication factor. These results was interpreted and comment using fundamentals concepts and relations of reactor physics. (author)

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

    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.

  3. Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma.

    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.

  4. Effects of mediated social touch on affective experiences and trust

    Stefanie M. Erk

    2015-10-01

    Full Text Available This study investigated whether communication via mediated hand pressure during a remotely shared experience (watching an amusing video can (1 enhance recovery from sadness, (2 enhance the affective quality of the experience, and (3 increase trust towards the communication partner. Thereto participants first watched a sad movie clip to elicit sadness, followed by a funny one to stimulate recovery from sadness. While watching the funny clip they signaled a hypothetical fellow participant every time they felt amused. In the experimental condition the participants responded by pressing a hand-held two-way mediated touch device (a Frebble, which also provided haptic feedback via simulated hand squeezes. In the control condition they responded by pressing a button and they received abstract visual feedback. Objective (heart rate, galvanic skin conductance, number and duration of joystick or Frebble presses and subjective (questionnaires data were collected to assess the emotional reactions of the participants. The subjective measurements confirmed that the sad movie successfully induced sadness while the funny movie indeed evoked more positive feelings. Although their ranking agreed with the subjective measurements, the physiological measurements confirmed this conclusion only for the funny movie. The results show that recovery from movie induced sadness, the affective experience of the amusing movie, and trust towards the communication partner did not differ between both experimental conditions. Hence, feedback via mediated hand touching did not enhance either of these factors compared to visual feedback. Further analysis of the data showed that participants scoring low on Extraversion (i.e., persons that are more introvert or low on Touch Receptivity (i.e., persons who do not like to be touched by others felt better understood by their communication partner when receiving mediated touch feedback instead of visual feedback, while the opposite was

  5. Effects of mediated social touch on affective experiences and trust.

    Erk, Stefanie M; Toet, Alexander; Van Erp, Jan B F

    2015-01-01

    This study investigated whether communication via mediated hand pressure during a remotely shared experience (watching an amusing video) can (1) enhance recovery from sadness, (2) enhance the affective quality of the experience, and (3) increase trust towards the communication partner. Thereto participants first watched a sad movie clip to elicit sadness, followed by a funny one to stimulate recovery from sadness. While watching the funny clip they signaled a hypothetical fellow participant every time they felt amused. In the experimental condition the participants responded by pressing a hand-held two-way mediated touch device (a Frebble), which also provided haptic feedback via simulated hand squeezes. In the control condition they responded by pressing a button and they received abstract visual feedback. Objective (heart rate, galvanic skin conductance, number and duration of joystick or Frebble presses) and subjective (questionnaires) data were collected to assess the emotional reactions of the participants. The subjective measurements confirmed that the sad movie successfully induced sadness while the funny movie indeed evoked more positive feelings. Although their ranking agreed with the subjective measurements, the physiological measurements confirmed this conclusion only for the funny movie. The results show that recovery from movie induced sadness, the affective experience of the amusing movie, and trust towards the communication partner did not differ between both experimental conditions. Hence, feedback via mediated hand touching did not enhance either of these factors compared to visual feedback. Further analysis of the data showed that participants scoring low on Extraversion (i.e., persons that are more introvert) or low on Touch Receptivity (i.e., persons who do not like to be touched by others) felt better understood by their communication partner when receiving mediated touch feedback instead of visual feedback, while the opposite was found for

  6. Effect of 12-Week Pilates Trainning on EDSS in Women Suffering fromMultiple Sclerosis

    Z Shanazari; SM Marandi; S Samie

    2013-01-01

    Abstract Background & aim: Multiple sclerosis is a debilitating disease that strikes the immune system. Multiple sclerosis is a chronic disease which debilitates the nervous system. The study was evaluated the effects of Pilates exercise on women with physical disabilities suffering from multiple sclerosis for 12 weeks .The aim of this study was to investigating the effects of Pilates trainning on EDSS of women suffering from Multiple Sclerosis (MS) for 12 weeks. Methods: In the pres...

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

    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

  8. Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health.

    Bansal, Amita; Henao-Mejia, Jorge; Simmons, Rebecca A

    2018-01-01

    The incidence of metabolic disorders like type 2 diabetes and obesity continues to increase. In addition to the well-known contributors to these disorders, such as food intake and sedentary lifestyle, recent research in the exposure science discipline provides evidence that exposure to endocrine-disrupting chemicals like bisphenol A and phthalates via multiple routes (e.g., food, drink, skin contact) also contribute to the increased risk of metabolic disorders. Endocrine-disrupting chemicals (EDCs) can disrupt any aspect of hormone action. It is becoming increasingly clear that EDCs not only affect endocrine function but also adversely affect immune system function. In this review, we focus on human, animal, and in vitro studies that demonstrate EDC exposure induces dysfunction of the immune system, which, in turn, has detrimental effects on metabolic health. These findings highlight how the immune system is emerging as a novel player by which EDCs may mediate their effects on metabolic health. We also discuss studies highlighting mechanisms by which EDCs affect the immune system. Finally, we consider that a better understanding of the immunomodulatory roles of EDCs will provide clues to enhance metabolic function and contribute toward the long-term goal of reducing the burden of environmentally induced diabetes and obesity. Copyright © 2018 Endocrine Society.

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

    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.

  10. Depressive symptoms, ruminative thinking, drinking motives, and alcohol outcomes: A multiple mediation model among college students in three countries.

    Bravo, Adrian J; Pilatti, Angelina; Pearson, Matthew R; Mezquita, Laura; Ibáñez, Manuel I; Ortet, Generós

    2018-01-01

    Recent research suggests that ruminative thinking (specifically problem-focused thoughts) may explain why individuals engage in drinking to cope (DTC) when dealing with depressive symptoms; which in turn leads to increased negative alcohol-related consequences. Cross-cultural studies addressing these phenomena are scarce. The present study cross-culturally tested whether four rumination facets (problem-focused thoughts, counterfactual thinking, repetitive thoughts, and anticipatory thoughts) uniquely mediate the relationships between depressive symptoms and drinking motives/alcohol outcomes in a multicultural sample of college student drinkers (n=1429) from Spain, Argentina, and the U.S. Structural equation modeling was conducted to test the models, controlling for sex. Further, we conducted invariance testing to determine whether our models were culturally-specific or culturally-universal. Within both proposed models, no rumination facet uniquely mediated the relationship between depressive symptoms and drinking motives. However, an exploratory model with a second-order latent factor of ruminative thinking did significantly mediate these associations (exception was conformity motives). Further, there were two significant double-mediated associations that suggested that increased depressive symptoms is associated with increased ruminative thinking, which is associated with higher DTC motives, which in turn is associated with higher alcohol consumption and negative alcohol-related consequences. All models were found to be invariant across countries and sex, suggesting that these associations may be relatively universal. Rumination is relevant to understand the increased vulnerability of college drinkers to exhibit greater alcohol consumption and negative consequences via DTC motives when dealing with depressive symptoms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Demographic consequences of predators on prey: trait and density mediated effects on mosquito larvae in containers.

    Barry W Alto

    Full Text Available Predators may affect prey population growth and community diversity through density mediated lethal and trait mediated non-lethal effects that influence phenotypic traits of prey. We tested experimentally the roles of thinning the density of prey (lethality in the absence of predator cues and density and trait mediated effects (lethality + intimidation of predatory midge Corethrella appendiculata on competing native and invasive mosquito prey. Predator-mediated reductions in prey and density reductions in the absence of C. appendiculata resulted in lower percent survivorship to adulthood and estimates of the finite rate of increase (λ' for invasive mosquito Aedes albopictus relative to that of controls. In most instances, thinning the density of prey in the absence, but not in the presence, of C. appendiculata cues resulted in lower survivorship to adulthood and λ' for native mosquito Aedes triseriatus relative to that of controls. Together, these results suggested trait mediated effects of C. appendiculata specific to each species of mosquito prey. Release from intraspecific competition attributable to density reductions in the absence, but not in the presence, of C. appendiculata enhanced growth and lengthened adult lifespan relative to that of controls for A. albopictus but not A. triseriatus. These results show the importance of predator-mediated density and trait mediated effects on phenotypic traits and populations of invasive and native mosquitoes. Species-specific differences in the phenotypic responses of prey may be due, in part, to longer evolutionary history of C. appendiculata with A. triseriatus than A. albopictus.

  12. Multiple Effects of Messages with Multiple Goals: Some Perceived Outcomes of Responses to Sexual Harassment.

    Bingham, Shereen G.; Burleson, Brant R.

    1989-01-01

    Tests the perceived effectiveness of different messages responding to sexual harassment in the organizational environment. Finds that none of the messages were perceived as being particularly effective at stopping the harasser's offensive conduct. (MM)

  13. Exploring the Relationship Between Social Anxiety and Bulimic Symptoms: Mediational Effects of Perfectionism Among Females

    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

  14. β3-adrenoceptor mediates β3-selective agonist-induced effects on ...

    β3-adrenoceptor mediates β3-selective agonist-induced effects on energy expenditure, insulin secrtion and food ... Journal of the Ghana Science Association ... is usually associated with obesity, also involves defective energy expenditure, ...

  15. Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial apoptosis in diabetic nephropathy.

    Katalin Susztak

    2005-02-01

    Full Text Available Diabetic nephropathy (DNP is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced by glycated albumins (AGE-BSA and CML-BSA and free fatty acid palmitate through sequential activation of src kinase, and proapoptotic p38 MAPK and caspase 3. In contrast, paucity of expression of CD36 in PTECs in diabetic mice with diabetic glomerulopathy was associated with normal tubular epithelium and the absence of tubular apoptosis. Mouse PTECs lacked CD36 and were resistant to AGE-BSA-induced apoptosis. Recombinant expression of CD36 in mouse PTECs conferred susceptibility to AGE-BSA-induced apoptosis.Our findings suggest a novel role for CD36 as an essential mediator of proximal tubular apoptosis in human DNP. Because CD36 expression was induced by glucose in PTECs, and because increased CD36 mediated AGE-BSA-, CML-BSA-, and palmitate-induced PTEC apoptosis, we propose a two-step metabolic hit model for TED, a hallmark of progression in DNP.

  16. The relationship among self-efficacy, negative self-referent cognitions, and social anxiety in children: a multiple mediator model.

    Rudy, Brittany M; Davis, Thompson E; Matthews, Russell A

    2012-09-01

    Evidence suggests that general self-efficacy, an individual's beliefs about his global abilities, and social self-efficacy, an individual's beliefs in his ability to navigate social situations, are strongly connected to levels of social anxiety. Negative self-statements, also known as negative self-referent cognitions, have also been linked with levels of social anxiety. Although self-efficacy and negative self-statements have been shown to be important variables in the phenomenology and maintenance of social anxiety in children, they have yet to be examined in conjunction with one another. The purpose of this study was to examine the relationship between negative self-referent cognitions and self-efficacy and to examine both general self-efficacy and social self-efficacy as mediator variables in the relationship between negative self-statements and social anxiety. Results were based on a sample of 126 children ages 11 to 14 years. A significant association between negative self-statements and both general self-efficacy and social self-efficacy was established. Results also indicated that general self-efficacy fully mediated the relationship between negative self-statements and social anxiety; however, contrary to hypotheses, social self-efficacy did not mediate the relationship between negative self-statements and social anxiety. Implications and future recommendations are discussed. Copyright © 2011. Published by Elsevier Ltd.

  17. Effects of Acupuncture on Gait of Patients with Multiple Sclerosis.

    Criado, Maria Begoña; Santos, Maria João; Machado, Jorge; Gonçalves, Arminda Manuela; Greten, Henry Johannes

    2017-11-01

    Multiple sclerosis is considered a complex and heterogeneous disease. Approximately 85% of patients with multiple sclerosis indicate impaired gait as one of the major limitations in their daily life. Acupuncture studies found a reduction of spasticity and improvement of fatigue and imbalance in patients with multiple sclerosis, but there is a lack of studies regarding gait. We designed a study of acupuncture treatment, according to the Heidelberg model of Traditional Chinese Medicine (TCM), to investigate if acupuncture can be a useful therapeutic strategy in patients with gait impairment in multiple sclerosis of relapsing-remitting type. The sample consisted of 20 individuals with diagnosis of multiple sclerosis of relapsing-remitting type. Gait impairment was evaluated by the 25-foot walk test. The results showed differences in time to walk 25 feet following true acupuncture. In contrast, there was no difference in time to walk 25 feet following sham acupuncture. When using true acupuncture, 95% of cases showed an improvement in 25-foot walk test, compared with 45% when sham acupuncture was done. Our study protocol provides evidence that acupuncture treatment can be an attractive option for patients with multiple sclerosis, with gait impairment.

  18. Utilizing inter-organizational relationships for new product development performance: A test of possible mediation effects

    Mortensen, Thomas Bøtker; Knudsen, Mette Præst

    The purpose of this paper is to investigate whether collaborative experience can act as a mediating variable on the use of inter-organizational relationships on NPD performance. The paper tests two different research questions: 1) Is there a possible mediating effect of experience on the linkage...... between inter-organizational relationships and performance? And If yes: what is the nature of the mediating effect and the resulting influence on performance? The paper is motivated by the growing literature on the importance of inter-organizational relationships created by the idea that firms operate...

  19. Semantic Information Activated during Retrieval Contributes to Later Retention: Support for the Mediator Effectiveness Hypothesis of the Testing Effect

    Carpenter, Shana K.

    2011-01-01

    Previous research has proposed that tests enhance retention more than do restudy opportunities because they promote the effectiveness of mediating information--that is, a word or concept that links a cue to a target (Pyc & Rawson, 2010). Although testing has been shown to promote retention of mediating information that participants were asked…

  20. [Multiple sclerosis: socioeconomic effects and impact on quality of life].

    Ayuso, Guillermo Izquierdo

    2014-12-01

    Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that affects young adults. Survival is long, more than 35 years, and consequently the disease has a huge socioeconomic impact. The present article discusses the enormous difficulties of carrying out economic assessments in this field but also describes the advances made in research on this topic and the advantages of performing socioeconomic evaluations with increasingly sophisticated tools. We also discuss the need to quantify indirect and intangible costs to translate them into quality of life and subsequently into economic cost, expressed in euros in the case of Spain. The available data indicate that the enormous cost of the disease (1200 million euros per year) is due more to disability-related expenditure than to treatment, which-although expensive-does not represent more than 16-18% of the total expenditure (approximately 200 million euros per year). The increase represented by the cost of MS is not based on higher treatment expenditure but on an increase in the incidence and-especially-the prevalence of the disease. Above all, in the last few years, there has been a considerable rise in the percentage of patients with an indication for treatment. Reflection is therefore needed on the use of drug therapy in MS, since a saving in the most effective products seems to increase the overall cost of MS, while expenditure on these drugs represents a saving in the long-term. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  1. The effects of multiple anaesthetic episodes on equine recovery quality.

    Platt, J P; Simon, B T; Coleman, M; Martinez, E A; Lepiz, M A; Watts, A E

    2018-01-01

    Although rare, 70% of equine fatalities during recovery from general anaesthesia (GA) are due to catastrophic fractures from poor recovery quality. To determine the effect of repeated GA recovery on GA recovery quality. Experimental blinded trial. Eight adult horses underwent six GA events on sevoflurane for distal limb MRI examination over a 14-week period. Prior to GA recovery, xylazine was administered. Randomly ordered video-recorded GA recoveries were scored by three blinded board certified veterinary anaesthesiologists, unaware of patient identity or GA event number, for nine parameters using a 100 mm visual analogue scale (VAS) where 0 = worst and 100 = best. The number of attempts to stand, duration of lateral and sternal recumbency, total recovery duration and physiologic parameters during each GA event were recorded. Repeated measures ANOVA were used to detect differences. Agreement between observer VAS scores was determined via inter-rater reliability using an intraclass correlation. With GA recovery experience, VAS scores for balance and coordination, knuckling, and overall quality of recovery were improved and the duration of lateral recumbency was increased. There were no differences in total recovery duration, number of attempts to stand, physiologic parameters other than heart rate during GA, or VAS scores for activity in lateral recumbency, move to sternal, move to stand, or strength. Each GA event was relatively short and there was no surgical stimulation. The same results may not occur if there was surgical stimulation and pain during each GA event. Recovery from GA improves with multiple anaesthetic episodes in horses. Clinicians can advise clients that horses are likely to have better GA recovery on repeated GA recovery due to improved balance and coordination and reduced knuckling. Additionally, there is no change in anaesthetic morbidity with six repeated GA events over a 14-week period. © 2017 EVJ Ltd.

  2. Mediation Analysis: A Practitioner's Guide.

    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.

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

    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 ...

  4. THE MEDIATING EFFECT OF PROACTIVE MARKET ORIENTATION CAPABILITY IN ENTREPRENEURIAL ORIENTATION AND SERVICE INNOVATION

    CANTALEANO, KAREN RAPHAELE; RODRIGUES, GRAZIELA PERRETTO; MARTINS, TOMAS SPARANO

    2018-01-01

    ABSTRACT Purpose: The purpose of this article is to verify the mediating effect of a proactive market orientation capability in the relationship between entrepreneurial orientation (EO) and service innovation in micro and small companies in the food-away from home sector. We analyzed the mediating effect of a marketing capability (proactive market capability) because, according to Morgan et al. (2009), a capability is an ability developed from a strategic orientation, and capabilities and or...

  5. Exploring the Mediating Effect of E-social Capital Between Community Members Interaction and Consumer Engagement

    Yan Bingsheng; Li Lihua; Sun Hongtao

    2017-01-01

    This article explored the effect of instrumental interaction and relational interaction on consumer engagement (community engagement and brand engagement) among community members. The mediating effect of E-social capital was investigated as well. The research results showed that: both instrumental interaction and interpersonal interaction promote the formation of E-social capital (online trust and online reciprocity); online trust plays a partial mediating role between community interaction (...

  6. Mediation pathways and effects of green structures on respiratory mortality via reducing air pollution

    Shen, Yu-Sheng; Lung, Shih-Chun Candice

    2017-01-01

    Previous studies have shown both health and environmental benefits of green spaces, especially in moderating temperature and reducing air pollution. However, the characteristics of green structures have been overlooked in previous investigations. In addition, the mediation effects of green structures on respiratory mortality have not been assessed. This study explores the potential mediation pathways and effects of green structure characteristics on respiratory mortality through temperature, ...

  7. [Effects of nurses' mentoring on turnover intention: focused on the mediating effects role stress and burnout].

    Han, Sangsook; Kim, Ohsook; Joo, Yunsu; Choi, Eunduck; Han, Jeongwon

    2013-10-01

    The purpose of this study was to investigate the casual relationship between nurses' mentoring and turnover intention and to verify the goodness of fit between a hypothetical model and actual data in order to suggest an adequate model. The survey was conducted with 434 nurses working in general hospitals in Seoul. Data were collected during February 2013, and analyzed with SPSS Windows 18.0 and AMOS 7.0. Mentoring was found to have a direct effect on decrease in role stress. Role stress had a direct effect on increase in burnout and mentoring, with role stress as a mediator, there was an indirect effect on burnout. Burnout had a direct effect on increase in turnover intention, and role stress, with burnout as a mediator, and mentoring, through role stress and burnout, an indirect effect was found on increase in turnover intention. The results of this study indicate that nursing managers should put effort into reducing role stress and burnout, while seeking to establish a more efficient mentoring system so that for nurses, there will be a lowering of turnover intention.

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

    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.

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

    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.

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

    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.

  11. Signaling via G proteins mediates tumorigenic effects of GPR87

    Arfelt, Kristine Niss; Fares, Suzan; Sparre-Ulrich, Alexander H.

    2017-01-01

    G protein-coupled receptors (GPCRs) constitute a large protein family of seven transmembrane (7TM) spanning proteins that regulate multiple physiological functions. GPR87 is overexpressed in several cancers and plays a role in tumor cell survival. Here, the basal activity of GPR87 was investigated...

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

    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.

  13. Culture in psychiatric epidemiology: using ethnography and multiple mediator models to assess the relationship of caste with depression and anxiety in Nepal.

    Kohrt, Brandon A; Speckman, Rebecca A; Kunz, Richard D; Baldwin, Jennifer L; Upadhaya, Nawaraj; Acharya, Nanda Raj; Sharma, Vidya Dev; Nepal, Mahendra K; Worthman, Carol M

    2009-01-01

    The causes of ethnic and caste-based disparities in mental health are poorly understood. The study aimed to identify mediators underlying caste-based disparities in mental health in Nepal. A mixed methods ethnographic and epidemiological study of 307 adults (Dalit/Nepali, n=75; high caste Brahman and Chhetri, n=232) was assessed with Nepali versions of Beck Depression (BDI) and Anxiety (BAI) Inventories. One-third (33.7%) of participants were classified as depressed: Dalit/Nepali 50.0%, high caste 28.4%. One quarter (27.7%) of participants were classified as anxious: Dalit/Nepali 50.7%, high caste 20.3%. Ethnographic research identified four potential mediators: Stressful life events, owning few livestock, no household income, and lack of social support. The direct effect of caste was 1.08 (95% CI -1.10-3.27) on depression score and 4.76 (95% CI 2.33-7.19) on anxiety score. All four variables had significant indirect (mediation) effects on anxiety, and all but social support had significant indirect effects on depression. Caste-based disparities in mental health in rural Nepal are statistically mediated by poverty, lack of social support, and stressful life events. Interventions should target these areas to alleviate the excess mental health burden born by Dalit/Nepali women and men.

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

    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.

  15. RITA inhibits multiple myeloma cell growth through induction of p53-mediated caspase-dependent apoptosis and synergistically enhances nutlin-induced cytotoxic responses.

    Saha, Manujendra N; Jiang, Hua; Mukai, Asuka; Chang, Hong

    2010-11-01

    Mutations or deletions of p53 are relatively rare in multiple myeloma (MM), at least in newly diagnosed patients. Thus, restoration of p53 tumor suppressor function in MM by blocking the inhibitory role of murine double minute 2 (MDM2) is a promising and applicable therapeutic strategy. RITA and nutlin are two new classes of small molecule MDM2 inhibitors that prevent the p53-MDM2 interaction. Earlier reports showed p53-dependent activity of RITA in solid tumors as well as in leukemias. We and others recently described nutlin-induced apoptosis in MM cells, but it remains unclear whether RITA exerts antimyeloma activity. Here, we found that RITA activates the p53 pathway and induces apoptosis in MM cell lines and primary MM samples, preferentially killing myeloma cells. The activation of p53 induced by RITA was mediated through modulation of multiple apoptotic regulatory proteins, including upregulation of a proapoptotic protein (NOXA), downregulation of an antiapoptotic protein, Mcl-1, and activation of caspases through extrinsic pathways. Moreover, a number of key p53-mediated apoptotic target genes were identified by gene expression profiling and further validated by quantitative real-time PCR. Importantly, the combination of RITA with nutlin displayed a strong synergism on growth inhibition with the combination index ranging from 0.56 to 0.82 in MM cells. Our data support further clinical evaluation of RITA as a potential novel therapeutic intervention in MM. ©2010 AACR.

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

    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.

  17. Epithelial V-like antigen mediates efficacy of anti-alpha₄ integrin treatment in a mouse model of multiple sclerosis.

    Erik Wright

    Full Text Available Natalizumab inhibits the transmigration of activated T lymphocytes into the brain and is highly efficacious in multiple sclerosis (MS. However, from a pharmacogenomic perspective, its efficacy and safety in specific patients remain unclear. Here our goal was to analyze the effects of epithelial V-like antigen (EVA on anti-alpha₄ integrin (VLA4 efficacy in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE. EVA has been previously characterized in human CD4 T lymphocytes, mouse thymic development, and choroid plexus epithelial cells. Further analysis here demonstrated expression in B lymphocytes and an increase in EVA⁺ lymphocytes following immunization. Following active induction of EAE using the MOG³⁵⁻⁵⁵ active immunization model, EVA deficient mice developed more severe EAE and white matter tissue injury as compared to wild type controls. This severe EAE phenotype did not respond to anti-VLA4 treatment. In both the control antibody and anti-VLA4 conditions, these mice demonstrated persistent CNS invasion of mature B lymphocyte (CD19⁺, CD21⁺, sIgG⁺, increased serum autoantibody levels, and extensive complement and IgG deposition within lesions containing CD5⁺IgG⁺ cells. Wild type mice treated with control antibody also demonstrated the presence of CD19⁺, CD21⁺, sIgG⁺ cells within the CNS during peak EAE disease severity and detectable serum autoantibody. In contrast, wild type mice treated with anti-VLA4 demonstrated reduced serum autoantibody levels as compared to wild type controls and EVA-knockout mice. As expected, anti-VLA4 treatment in wild type mice reduced the total numbers of all CNS mononuclear cells and markedly decreased CD4 T lymphocyte invasion. Treatment also reduced the frequency of CD19⁺, CD21⁺, sIgG⁺ cells in the CNS. These results suggest that anti-VLA4 treatment may reduce B lymphocyte associated autoimmunity in some individuals and that EVA expression is necessary for an

  18. The Effects of Discrimination Experience on Life Satisfaction of North Korean Refugees: Mediating Effect of Stress.

    Noh, Jin-Won; Park, Hyunchun; Kim, Minji; Kwon, Young Dae; Kim, Jin-Seok; Yu, Shieun

    2018-01-01

    This study investigated the mediation effect of stress between the experience of discrimination and life satisfaction among North Korean refugees who resettled in South Korea. The findings of the current study provide empirical evidence for the need of social interventions to mitigate adverse effects of stress on North Korean refugees who are subject to social discrimination on a daily basis. In this study, we included 500 subjects among 2,138 North Korean refugees who took refuge in South Korea in 2007. The interview started from April 6th 2009 and finished on May 25th 2009. We conducted moderator effect analysis with Path analysis was conducted because we confirm the experience of discrimination was affected by life satisfaction and stress can affected life satisfaction as a moderator. The experience of discrimination significantly affects stress and stress significantly affects life satisfaction. However, the experience of discrimination was not directly related to life satisfaction. The more stress the study respondents experienced, the lower the life satisfaction they reported. The present finding suggests that the effects of discriminating experiences on the life satisfaction of North Korean refugees in South Korea were mediated by their own perceived stress.

  19. Turnover in health care: the mediating effects of employee engagement.

    Collini, Stevie A; Guidroz, Ashley M; Perez, Lisa M

    2015-03-01

    This study aimed to understand the interaction between interpersonal respect, diversity climate, mission fulfilment and engagement to better predict turnover in health care. Registered nurse turnover has averaged 14% and current nursing shortages are expected to spread. Few studies have studied employee engagement as a mediator between organisational context and turnover. Study participants were employees working within 185 departments across ten hospitals within a large healthcare organisation in the USA. Although a total of 5443 employees work in these departments, employee opinion survey responses were aggregated by department before being linked to turnover rates gathered from company records. Engagement fully mediated the relationship between respect and turnover and the relationship between mission fulfilment and turnover. Diversity climate was not related to turnover. Turnover in health care poses a significant threat to the mission of creating a healing environment for patients and these results demonstrate that workplace respect and connection to the mission affect turnover by decreasing engagement. The findings demonstrated that to increase engagement, and improve turnover rates in health care, it would be beneficial for organisations, and nurse management to focus on improving mission fulfilment and interpersonal relationships. © 2013 John Wiley & Sons Ltd.

  20. Nanoscale effects in dendrimer-mediated targeting of neuroinflammation.

    Nance, Elizabeth; Zhang, Fan; Mishra, Manoj K; Zhang, Zhi; Kambhampati, Siva P; Kannan, Rangaramanujam M; Kannan, Sujatha

    2016-09-01

    Neuroinflammation, mediated by activated microglia and astrocytes, plays a key role in the pathogenesis of many neurological disorders. Systemically-administered dendrimers target neuroinflammation and deliver drugs with significant efficacy, without the need for ligands. Elucidating the nanoscale aspects of targeting neuroinflammation will enable superior nanodevices for eventual translation. Using a rabbit model of cerebral palsy, we studied the in vivo contributions of dendrimer physicochemical properties and disease pathophysiology on dendrimer brain uptake, diffusion, and cell specific localization. Neutral dendrimers move efficiently within the brain parenchyma and rapidly localize in glial cells in regions of injury. Dendrimer uptake is also dependent on the extent of blood-brain-barrier breakdown, glial activation, and disease severity (mild, moderate, or severe), which can lend the dendrimer to be used as an imaging biomarker for disease phenotype. This new understanding of the in vivo mechanism of dendrimer-mediated delivery in a clinically-relevant rabbit model provides greater opportunity for clinical translation of targeted brain injury therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Need satisfaction, motivational regulations and exercise: moderation and mediation effects.

    Weman-Josefsson, Karin; Lindwall, Magnus; Ivarsson, Andreas

    2015-05-20

    Based on the Self-determination theory process model, this study aimed to explore relationships between the latent constructs of psychological need satisfaction, autonomous motivation and exercise behaviour; the mediational role of autonomous motivation in the association of psychological need satisfaction with exercise behaviour; as well as gender and age differences in the aforementioned associations. Adult active members of an Internet-based exercise program (n = 1091) between 18 and 78 years of age completed a test battery on motivational aspects based on Self-determination theory. The Basic Psychological Needs in Exercise Scale and the Behavioural Regulation in Exercise Questionnaire-2 were used to measure need satisfaction and type of motivation and the Leisure Time Exercise Questionnaire to measure self-reported exercise. Need satisfaction predicted autonomous motivation, which in turn predicted exercise, especially for women. Autonomous motivation was found to mediate the association between need satisfaction and exercise. Age and gender moderated several of the paths in the model linking need satisfaction with motivation and exercise. The results demonstrated gender and age differences in the proposed sequential mechanisms between autonomous motivation and exercise in the process model. This study thus highlights a potential value in considering moderating factors and the need to further examine the underlying mechanisms between needs, autonomous motivation, and exercise behaviour.

  2. Effects of Music during Multiple Cesarean Section Delivery.

    Handan, Eren; Sahiner, Nejla Canbulat; Bal, Meltem Demirgoz; Dissiz, Melike

    2018-03-01

    This experimental study was conducted to determine the level of anxiety in women undergoing multiple cesarean section. Sixty multiple cesarean section referrals were randomly assigned to either the experimental or control groups. Data was collected at the Karaman Public Health Hospital in Turkey, from June 2015 to June 2016. Songs chosen earlier by the patients were played during the cesarean section procedure for the experimental group. The control group was studied without music. Data was collected using a questionnaire form, and Visual Analogue Scale (VAS) was used to determine the anxiety levels. The t-test and chi-square test were used to analyse statistically significant differences between the groups. The VAS scores before and during the procedure showed significantly lower scores for the experimental group, compared to the control group (p<0.05). Music therapy reduces the physiological and cognitive responses of anxiety in patients undergoing multiple cesarean section, and can be used in the clinical practice.

  3. AS3MT-mediated tolerance to arsenic evolved by multiple independent horizontal gene transfers from bacteria to eukaryotes

    Palmgren, Michael; Engström, Karin; Hallström, Björn M.

    2017-01-01

    the evolutionary origin of AS3MT and assessed the ability of different genotypes to produce methylated arsenic metabolites. Phylogenetic analysis suggests that multiple, independent horizontal gene transfers between different bacteria, and from bacteria to eukaryotes, increased tolerance to environmental arsenic...

  4. The role of helplessness as mediator between neurological disability, emotional instability, experienced fatigue and depression in patients with multiple sclerosis.

    Werf, S.P. van der; Evers, A.W.M.; Jongen, P.J.H.; Bleijenberg, G.

    2003-01-01

    The aim of this study was to test, in patients with multiple sclerosis (MS), whether the concept of helplessness might improve the understanding of the relationship between disease severity (neurological impairment) and personality characteristics (emotional instability) on one hand, and depressive

  5. Using mini-games for learning multiplication and division: A longitudinal effect study

    Bakker, M.

    2014-01-01

    This thesis reports the findings of a three-year longitudinal research project set up to investigate the effectiveness of employing online mini-games for the learning of multiplication and division, including multiplicative fact knowledge (declarative knowledge), multiplicative operation skills

  6. Effects of Mathematics Computer Games on Special Education Students' Multiplicative Reasoning Ability

    Bakker, Marjoke; van den Heuvel-Panhuizen, Marja; Robitzsch, Alexander

    2016-01-01

    This study examined the effects of a teacher-delivered intervention with online mathematics mini-games on special education students' multiplicative reasoning ability (multiplication and division). The games involved declarative, procedural, as well as conceptual knowledge of multiplicative relations, and were accompanied with teacher-led lessons…

  7. Effects of mathematics computer games on special education students’ multiplicative reasoning ability

    Bakker, M.|info:eu-repo/dai/nl/355337770; Van den Heuvel-Panhuizen, M.|info:eu-repo/dai/nl/069266255; Robitzsch, Alexander

    2016-01-01

    This study examined the effects of a teacher-delivered intervention with online math-ematics mini-games on special education students’ multiplicative reasoning ability(multiplication and division). The games involved declarative, procedural, as well asconceptual knowledge of multiplicative

  8. Suppressive effect of glucocorticoids on TNF-alpha production is associated with their clinical effect in multiple sclerosis

    van Winsen, L.M.L.; Polman, C.H.; Dijkstra, C.D.; Tilders, F.J.H.; Uitdehaag, B.M.J.

    2010-01-01

    A reduced sensitivity to glucocorticoids can affect the clinical effect of treatment with high-dose intravenous methylprednisolone in multiple sclerosis. We prospectively studied 27 multiple sclerosis patients who were treated with intravenous methylprednisolone. Before and after treatment in vitro

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

    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.

  10. Common Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Epitopes Mediate Multiple Routes for Internalization and Function

    DeVay, Rachel M.; Yamamoto, Lynn; Shelton, David L.; Liang, Hong

    2015-01-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a soluble protein that directs membrane-bound receptors to lysosomes for degradation. In the most studied example of this, PCSK9 binding leads to the degradation of low density lipoprotein receptor (LDLR), significantly affecting circulating LDL-C levels. The mechanism mediating this degradation, however, is not completely understood. We show here that LDLR facilitates PCSK9 interactions with amyloid precursor like protein 2 (APLP2) at neutral pH leading to PCSK9 internalization, although direct binding between PCSK9 and LDLR is not required. Moreover, binding to APLP2 or LDLR is independently sufficient for PCSK9 endocytosis in hepatocytes, while LDL can compete with APLP2 for PCSK9 binding to indirectly mediate PCSK9 endocytosis. Finally, we show that APLP2 and LDLR are also required for the degradation of another PCSK9 target, APOER2, necessitating a general role for LDLR and APLP2 in PCSK9 function. Together, these findings provide evidence that PCSK9 has at least two endocytic epitopes that are utilized by a variety of internalization mechanisms and clarifies how PCSK9 may direct proteins to lysosomes. PMID:25905719

  11. Performance of Fourth-Grade Students with Learning Disabilities on Multiplication Facts Comparing Teacher-Mediated and Technology-Mediated Interventions: A Preliminary Investigation

    Bryant, Brian R.; Ok, Minwook; Kang, Eun Young; Kim, Min Kyung; Lang, Russell; Bryant, Diane Pedrotty; Pfannestiel, Kathleen

    2015-01-01

    Instructional applications (apps) are educational software programs that can be accessed via mobile technologies (e.g., iPad, smartphone) and used to help students acquire various academic skills, including mathematics. Although research suggests that app-based instruction (AI) can be effective, there is a paucity of research comparing AI, to…

  12. Caffeine reversal of ethanol effects on the multiple sleep latency test, memory, and psychomotor performance.

    Drake, Christopher L; Roehrs, Timothy; Turner, Lauren; Scofield, Holly M; Roth, Thomas

    2003-02-01

    Caffeine has been shown to reverse some of the performance-impairing effects of ethanol. However, it is not known whether this antagonistic effect of caffeine is mediated by a reduction in sleepiness. The present study assessed physiological alertness/sleepiness, memory, and psychomotor performance following the administration of placebo, ethanol, and caffeine+ethanol combinations. A total of 13 healthy individuals (21-35 years old) underwent four conditions presented in a Latin Square Design: placebo-placebo, ethanol (0.5 g/kg)-placebo, ethanol (0.5 g/kg)-caffeine 150 mg, and ethanol (0.5 g/kg)-caffeine 300-mg. The Multiple Sleep Latency Test (MSLT), psychomotor performance battery, memory test, and mood/sleepiness questionnaires were administered following each condition. The peak breadth ethanol concentration (BrEC) was 0.043+/-0.0197% and did not differ among the three caffeine treatments. As expected, ethanol reduced mean latency on the MSLT. The lowest caffeine dose reversed this effect and the highest dose increased mean latency (greater alertness) significantly beyond placebo levels. Ethanol also impaired psychomotor performance and memory. The 300-mg caffeine dose restored performance and memory measures to placebo levels. Although visual analog ratings of dizziness were increased by ethanol, they were not diminished by either caffeine dose. In conclusion, Low-dose caffeine prevented the sleepiness and performance impairment associated with a moderate dose of ethanol. Thus, caffeine, similar to other stimulants, can reverse the physiologically sedating effects of ethanol, although other negative effects remain.

  13. Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression.

    Rana, Digvijay G; Galani, Varsha J

    2014-01-01

    The effects of antidepressant treatments have traditionally been discussed primarily in terms of effects on noradrenergic and serotonergic systems. Multiple lines of investigation have also explored the role of dopaminergic systems in mental depression. Seed of Mucuna pruriens Linn. (DC) (Leguminoseae) is well-known with dopaminergic action and has several therapeutic applications in folk medicine in curing or managing a wide range of diseases including Parkinsonism. To elucidate the anti-depressent profile and possible dopaminergic modulating action of M. pruriens seeds in various experimental models of depression. In the present study, antidepressant effect of the hydroalcoholic extract of the M. pruriens seeds (MPE) (100 and 200 mg/kg, p.o.) was investigated in the Forced Swimming Test (FST), Tail Suspension Test (TST), and Chronic Unpredictable Mild Stress (CUMS) test in mice. Further, dopaminergic interaction of same doses of MPE in the FST and TST were checked by the administration of a haloperidol (0.1 mg/kg, i.p.) and bromocriptine (2 mg/kg, i.p.) on the 7(th) day of MPE treatment. Effect of MPE on locomotor activity was also checked using actophotometer. MPE produced a significant reduction of the immobility time in the FST and TST. Further, antidepressant action of MPE was significantly inhibited by haloperidol and potentiated by bromocriptine in the FST and TST. 21 days of MPE treatment produced protection in CUMS as indicated by a significant increase of sucrose intake of stressed mice. Locomotor activities of mice were not significantly changed after 1 h and 7(th) day of the MPE treatment. The results of this study indicate that hydroalcoholic extract of MPE have antidepressant action, which may be mediated by an interaction with the dopaminergic system.

  14. Are behavioral effects of early experience mediated by oxytocin?

    Karen Lisa Bales

    2011-05-01

    Full Text Available Early experiences can alter adaptive emotional responses necessary for social behavior as well as physiological reactivity in the face of challenge. In the highly social prairie vole (Microtus ochrogaster, manipulations in early life or hormonal treatments specifically targeted at the neuropeptides oxytocin (OT and arginine vasopressin (AVP, have long-lasting, often sexually-dimorphic, consequences for social behavior. Here we examine the hypothesis that behavioral changes associated with differential early experience, in this case handling the family during the first week of life, may be mediated by changes in OT or AVP or their brain receptors. Four early treatment groups were used, differing only in the amount of manipulation received during the first week of life. MAN1 animals were handled once on post-natal day 1; MAN1 treatment produces a pattern of behavior usually considered typical of this species, against which other groups were compared. MAN 1-7 animals were handled once a day for post-natal days 1-7, MAN 7 animals were handled once on post-natal day 7, and MAN0 animals received no handling during the first week of life. When tested following weaning, males in groups that had received manipulation during the first few days of life (MAN1 and MAN1-7 displayed higher alloparenting than other groups. Neuroendocrine measures, including OT receptor binding and OT and AVP immunoreactivity, varied by early treatment. In brain areas including the nucleus accumbens, bed nucleus of stria terminalis and lateral septum, MAN0 females showed increased OT receptor binding. MAN1 animals also displayed higher numbers of immunoreactive OT cell bodies in the supraoptic nucleus. Taken together these findings support the broader hypothesis that experiences in the first few days of life, mediated in part by sexually-dimorphic changes in neuropeptides, especially in the receptor for OT, may have adaptive consequences for sociality and emotion regulation.

  15. The effect of both Z and Z'-mediated flavor-changing neutral currents on Bs → μ+ μ- decay

    Sahoo, S.; Maharana, L.; Behera, B.R.

    2007-01-01

    We study the effect of both Z and Z'-mediated flavor-changing neutral currents (FCNCs) on the B s → μ + μ - rare decay process. Mixing between ordinary and exotic left-handed quarks induces Z-mediated FCNC whereas mixing of right-handed ordinary and exotic quarks induces Z'-mediated FCNC. We find the branching ratio is enhanced from its standard model (SM) value due to the effect of both Z and Z'-mediated FCNCs. (author)

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

    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

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

    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.

  18. TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis.

    Kazuya Takahashi

    2007-04-01

    Full Text Available BACKGROUND: In multiple sclerosis, inflammation can successfully be prevented, while promoting repair is still a major challenge. Microglial cells, the resident phagocytes of the central nervous system (CNS, are hematopoietic-derived myeloid cells and express the triggering receptor expressed on myeloid cells 2 (TREM2, an innate immune receptor. Myeloid cells are an accessible source for ex vivo gene therapy. We investigated whether myeloid precursor cells genetically modified to express TREM2 affect the disease course of experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis. METHODS AND FINDINGS: EAE was induced in mice by immunization with a myelin autoantigen. Intravenous application of TREM2-transduced bone marrow-derived myeloid precursor cells at the EAE peak led to an amelioration of clinical symptoms, reduction in axonal damage, and prevention of further demyelination. TREM2-transduced myeloid cells applied intravenously migrated into the inflammatory spinal cord lesions of EAE-diseased mice, showed increased lysosomal and phagocytic activity, cleared degenerated myelin, and created an anti-inflammatory cytokine milieu within the CNS. CONCLUSIONS: Intravenously applied bone marrow-derived and TREM2-tranduced myeloid precursor cells limit tissue destruction and facilitate repair within the murine CNS by clearance of cellular debris during EAE. TREM2 is a new attractive target for promotion of repair and resolution of inflammation in multiple sclerosis and other neuroinflammatory diseases.

  19. Academic self-concept, autonomous academic motivation, and academic achievement : mediating and additive effects

    Guay, Frédéric; Ratelle, Catherine; Roy, Amélie; Litalien, David

    2010-01-01

    Three conceptual models were tested to examine the relationships among academic self-concept, autonomous academic motivation, and academic achievement. This allowed us to determine whether 1) autonomous academic motivation mediates the relation between academic self-concept and achievement, 2) academic self-concept mediates the relation between autonomous academic motivation and achievement, or 3) both motivational constructs have an additive effect on academic achievement. A total of 925 hig...

  20. Mediating effect of Facebook addiction on the relationship between subjective vitality and subjective happiness.

    Uysal, Recep; Satici, Seydi Ahmet; Akin, Ahmet

    2013-12-01

    This study examined the mediating effects of Facebook addiction on the relationship between subjective vitality and subjective happiness. 297 university students (157 women, 140 men; M age = 20.1 yr., SD = 1.3) were administered the Facebook Addiction Scale, the Subjective Vitality Scale, and the Subjective Happiness Scale. Hierarchical regression analysis showed that Facebook addiction partially mediated the relationship between subjective vitality and subjective happiness.

  1. Servant Leadership and Follower Outcomes: Mediating Effects of Organizational Identification and Psychological Safety.

    Chughtai, Aamir Ali

    2016-10-02

    This study investigated the mediating role of organizational identification and psychological safety in the relationship between servant leadership and two employee outcomes: employee voice and negative feedback seeking behavior. The sample for this study comprised of 174 full-time employees drawn from a large food company based in Pakistan. Results showed that organizational identification and psychological safety partially mediated the effects of servant leadership on voice and negative feedback seeking behavior. The theoretical and practical implications of this research are discussed.

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

    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.

  3. Endocannabinoid signaling within the basolateral amygdala integrates multiple stress hormone effects on memory consolidation.

    Atsak, Piray; Hauer, Daniela; Campolongo, Patrizia; Schelling, Gustav; Fornari, Raquel V; Roozendaal, Benno

    2015-05-01

    Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory of emotionally arousing experiences. However, as the onset of these glucocorticoid actions appear often too rapid to be explained by genomic regulation, the neurobiological mechanism of how glucocorticoids could modify the memory-enhancing properties of norepinephrine and CRF remained elusive. Here, we show that the endocannabinoid system, a rapidly activated retrograde messenger system, is a primary route mediating the actions of glucocorticoids, via a glucocorticoid receptor on the cell surface, on BLA neural plasticity and memory consolidation. Furthermore, glucocorticoids recruit downstream endocannabinoid activity within the BLA to interact with both the norepinephrine and CRF systems in enhancing memory consolidation. These findings have important implications for understanding the fine-tuned crosstalk between multiple stress hormone systems in the coordination of (mal)adaptive stress and emotional arousal effects on neural plasticity and memory consolidation.

  4. The impact of workplace spirituality dimensions on organisational citizenship behaviour among nurses with the mediating effect of affective organisational commitment.

    Kazemipour, Farahnaz; Mohd Amin, Salmiah

    2012-12-01

    To investigate the relationship between workplace spirituality dimensions and organisational citizenship behaviour (OCB) among nurses through the mediating effect of affective organisational commitment. Nurses' OCB has been considered recently to improve the quality of services to patients and subsequently, their performance. As an influential attitude, affective organisational commitment has been recognized to influence OCB, and ultimately, organisational performance. Meanwhile, workplace spirituality is introduced as a new organisational behaviour concept to increase affective commitment influencing employees' OCB. The cross-sectional study and the respective data were collected with a questionnaire-based survey. The questionnaires were distributed to 305 nurses employed in four public and general Iranian hospitals. To analyse the data, descriptive statistics, Pearson coefficient, simple regression, multiple regression and path analyses were also conducted. The results indicated that workplace spirituality dimensions including meaningful work, a sense of community and an alignment with organisational values have a significant positive relationship with OCB. Moreover, affective organisational commitment mediated the impact of workplace spirituality on OCB. The concept of workplace spirituality through its dimensions predicts nurses' OCB, and affective organisational commitment partially mediated the relationship between workplace spirituality and OCB. Nurses' managers should consider the potentially positive influence of workplace spirituality on OCB and affective commitment among their nurses. With any plan to increase workplace spirituality, the respective managers can improve nurses' performance and would be of considerable importance in the healthcare system. © 2012 Blackwell Publishing Ltd.

  5. The impact of self-efficacy, alexithymia and multiple traumas on posttraumatic stress disorder and psychiatric co-morbidity following epileptic seizures: a moderated mediation analysis.

    Chung, Man Cheung; Allen, Rachel D; Dennis, Ian

    2013-12-30

    This study investigated the incidence of posttraumatic stress disorder (PTSD) and psychiatric co-morbidity following epileptic seizure, whether alexithymia mediated the relationship between self-efficacy and psychiatric outcomes, and whether the mediational effect was moderated by the severity of PTSD from other traumas. Seventy-one (M=31, F=40) people with a diagnosis of epilepsy recruited from support groups in the United Kingdom completed the Posttraumatic Stress Diagnostic Scale, the Hospital Anxiety and Depression Scale, the Toronto Alexithymia Scale-20 and the Generalized Self-Efficacy Scale. They were compared with 71 people (M=29, F=42) without epilepsy. For people with epilepsy, 51% and 22% met the diagnostic criteria for post-epileptic seizure PTSD and for PTSD following one other traumatic life event respectively. For the control group, 24% met the diagnostic criteria for PTSD following other traumatic life events. The epilepsy group reported significantly more anxiety and depression than the control. Partial least squares (PLS) analysis showed that self-efficacy was significantly correlated with alexithymia, post-epileptic seizure PTSD and psychiatric co-morbidity. Alexithymia was also significantly correlated with post-epileptic seizure PTSD and psychiatric co-morbidity. Mediation analyses confirmed that alexithymia mediated the path between self-efficacy and post-epileptic seizure PTSD and psychiatric co-morbidity. Moderated mediation also confirmed that self-efficacy and PTSD from one other trauma moderated the effect of alexithymia on outcomes. To conclude, people can develop posttraumatic stress disorder symptoms and psychiatric co-morbidity following epileptic seizure. These psychiatric outcomes are closely linked with their belief in personal competence to deal with stressful situations and regulate their own functioning, to process rather than defend against distressing emotions, and with the degree of PTSD from other traumas. © 2013 Elsevier

  6. Effect of multiple subcultures on Musa shoots derived from cassava ...

    Shoot tip explants excised from in vitro plantlets of two Musa genotypes (TM3X 15108-6 and TMBX 612-74) were seeded singly into test tubes containing twenty milliliters each of Musa multiplication medium gelled differently in 60 and 70 gL-l cassava starch as well as 5 gL-l agar and placed on shelves under 14 h photo ...

  7. Multiplex, Rapid, and Sensitive Isothermal Detection of Nucleic-Acid Sequence by Endonuclease Restriction-Mediated Real-Time Multiple Cross Displacement Amplification.

    Wang, Yi; Wang, Yan; Zhang, Lu; Liu, Dongxin; Luo, Lijuan; Li, Hua; Cao, Xiaolong; Liu, Kai; Xu, Jianguo; Ye, Changyun

    2016-01-01

    We have devised a novel isothermal amplification technology, termed endonuclease restriction-mediated real-time multiple cross displacement amplification (ET-MCDA), which facilitated multiplex, rapid, specific and sensitive detection of nucleic-acid sequences at a constant temperature. The ET-MCDA integrated multiple cross displacement amplification strategy, restriction endonuclease cleavage and real-time fluorescence detection technique. In the ET-MCDA system, the functional cross primer E-CP1 or E-CP2 was constructed by adding a short sequence at the 5' end of CP1 or CP2, respectively, and the new E-CP1 or E-CP2 primer was labeled at the 5' end with a fluorophore and in the middle with a dark quencher. The restriction endonuclease Nb.BsrDI specifically recognized the short sequence and digested the newly synthesized double-stranded terminal sequences (5' end short sequences and their complementary sequences), which released the quenching, resulting on a gain of fluorescence signal. Thus, the ET-MCDA allowed real-time detection of single or multiple targets in only a single reaction, and the positive results were observed in as short as 12 min, detecting down to 3.125 fg of genomic DNA per tube. Moreover, the analytical specificity and the practical application of the ET-MCDA were also successfully evaluated in this study. Here, we provided the details on the novel ET-MCDA technique and expounded the basic ET-MCDA amplification mechanism.

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

    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.

  9. Unravelling nocebo effect: the mediating effect of anxiety between anticipation and pain at wound dressing change.

    Woo, Kevin Y

    2015-07-01

    The purpose of this study was to examine the mediating effect of anxiety in the relationship between anticipation and pain in people with chronic wounds. Pain is common in people with chronic wounds. Anticipation or negative expectation of discomfort has been shown to have an augmenting effect on pain; also known as nocebo hyperalgesia. This was a cross-sectional study with repeated measures. Prior to dressing change, anticipatory pain level was evaluated by a 11-point numerical rating scale and anxiety by the Six-items State-Trait Anxiety Inventory (STAI-6). During wound dressing changes, pain was measured before dressing removal, at dressing removal, at cleansing and dressing application using the numerical scale. Analysis was completed based on the data from a convenience sample of 96 patients. Participants reported more pain at cleansing and dressing removal than baseline. High levels of anticipation, anxiety and pain at dressing change for wounds were related to heavy exudate and wound that were covered with necrotic tissue. Finally, the relationship between anticipation and pain perception was mediated by anxiety. Anticipation of pain triggers anxiety that can lead to increased pain. There is a need to incorporate evaluation of anxiety and personal expectations as part of comprehensive pain assessment. Clinicians should be aware of the impact of emotions and anticipation on overall pain experience. © 2015 John Wiley & Sons Ltd.

  10. Testing the Causal Direction of Mediation Effects in Randomized Intervention Studies.

    Wiedermann, Wolfgang; Li, Xintong; von Eye, Alexander

    2018-05-21

    In a recent update of the standards for evidence in research on prevention interventions, the Society of Prevention Research emphasizes the importance of evaluating and testing the causal mechanism through which an intervention is expected to have an effect on an outcome. Mediation analysis is commonly applied to study such causal processes. However, these analytic tools are limited in their potential to fully understand the role of theorized mediators. For example, in a design where the treatment x is randomized and the mediator (m) and the outcome (y) are measured cross-sectionally, the causal direction of the hypothesized mediator-outcome relation is not uniquely identified. That is, both mediation models, x → m → y or x → y → m, may be plausible candidates to describe the underlying intervention theory. As a third explanation, unobserved confounders can still be responsible for the mediator-outcome association. The present study introduces principles of direction dependence which can be used to empirically evaluate these competing explanatory theories. We show that, under certain conditions, third higher moments of variables (i.e., skewness and co-skewness) can be used to uniquely identify the direction of a mediator-outcome relation. Significance procedures compatible with direction dependence are introduced and results of a simulation study are reported that demonstrate the performance of the tests. An empirical example is given for illustrative purposes and a software implementation of the proposed method is provided in SPSS.

  11. A default Bayesian hypothesis test for mediation

    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

  12. Fundamental principles of nanostructures and multiple exciton generation effect in quantum dots

    Turaeva, N.; Oksengendler, B.; Rashidova, S.

    2011-01-01

    In this work the theoretical aspects of the effect of multiple exciton generation in QDs has been studied. The statistic theory of multiple exciton generation in quantum dots is presented based on the Fermi approach to the problem of multiple generation of elementary particles at nucleon-nucleon collisions. Our calculations show that the quantum efficiencies of multiple exciton generation in various quantum dots at absorption of single photon are in a good agreement with the experimental data. The microscopic mechanism of this effect is based on the theory of electronic 'shaking'. In the work the deviation of averaged multiplicity of MEG effect from the Poisson law of fluctuations has been investigated. Besides, the role of interface electronic states of quantum dot and ligand has been considered by means of quantum mechanics. The size optimization of quantum dot has been arranged to receive the maximum multiplicity of MEG effect. (authors)

  13. Improvements in closeness, communication, and psychological distress mediate effects of couple therapy for veterans.

    Doss, Brian D; Mitchell, Alexandra; Georgia, Emily J; Biesen, Judith N; Rowe, Lorelei Simpson

    2015-04-01

    Empirically based couple therapy results in significant improvements in relationship satisfaction for the average couple; however, further research is needed to identify mediators that lead to change and to ensure that improvements in mediators predict subsequent-not just concurrent-relationship satisfaction. In addition, given that much of the current literature on couple therapy examines outcomes in a research environment, it is important to examine mediators in a treatment-as-usual setting. To address these questions, 161 heterosexual couples (322 individuals) received treatment-as-usual couple therapy at one of two Veteran Administration Medical Centers (M = 5.0 and 13.0 sessions at the two sites) and were assessed before every session. The majority of couples were married (85%) and had been together for a median of 7.8 years (SD = 13). Participants were primarily White, non-Hispanic (69%), African American (21%), and White, Hispanic/Latino (8%). Individuals' own self-reported improvements in communication, emotional closeness, and psychological distress (but not frequency of behaviors targeted in treatment) mediated the effect of treatment on their subsequent relationship satisfaction. When all significant mediators were examined simultaneously, improvements in men's and women's emotional closeness and men's psychological distress independently mediated subsequent relationship satisfaction. In contrast, improvements in earlier relationship satisfaction mediated the effect of treatment only on subsequent psychological distress. This study identifies unique mediators of treatment effects and shows that gains in mechanisms predict subsequent relationship satisfaction. Future investigations should focus on the role of emotional closeness and psychological distress-constructs that have often been neglected-in couple therapy. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  14. The Rho Kinases: Critical Mediators of Multiple Profibrotic Processes and Rational Targets for New Therapies for Pulmonary Fibrosis

    Knipe, Rachel S.; Tager, Andrew M.

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung scarring, short median survival, and limited therapeutic options, creating great need for new pharmacologic therapies. IPF is thought to result from repetitive environmental injury to the lung epithelium, in the context of aberrant host wound healing responses. Tissue responses to injury fundamentally involve reorganization of the actin cytoskeleton of participating cells, including epithelial cells, fibroblasts, endothelial cells, and macrophages. Actin filament assembly and actomyosin contraction are directed by the Rho-associated coiled-coil forming protein kinase (ROCK) family of serine/threonine kinases (ROCK1 and ROCK2). As would therefore be expected, lung ROCK activation has been demonstrated in humans with IPF and in animal models of this disease. ROCK inhibitors can prevent fibrosis in these models, and more importantly, induce the regression of already established fibrosis. Here we review ROCK structure and function, upstream activators and downstream targets of ROCKs in pulmonary fibrosis, contributions of ROCKs to profibrotic cellular responses to lung injury, ROCK inhibitors and their efficacy in animal models of pulmonary fibrosis, and potential toxicities of ROCK inhibitors in humans, as well as involvement of ROCKs in fibrosis in other organs. As we discuss, ROCK activation is required for multiple profibrotic responses, in the lung and multiple other organs, suggesting ROCK participation in fundamental pathways that contribute to the pathogenesis of a broad array of fibrotic diseases. Multiple lines of evidence therefore indicate that ROCK inhibition has great potential to be a powerful therapeutic tool in the treatment of fibrosis, both in the lung and beyond. PMID:25395505

  15. Mediation and moderation of divorce effects on children's behavior problems.

    Weaver, Jennifer M; Schofield, Thomas J

    2015-02-01

    Using data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, we examined children's internalizing and externalizing behavior problems from age 5 to 15 years in relation to whether they had experienced a parental divorce. Children from divorced families had more behavior problems compared with a propensity-score-matched sample of children from intact families, according to both teachers and mothers. They exhibited more internalizing and externalizing problems at the first assessment after the parents' separation and at the last available assessment (age 11 years for teacher reports, or 15 years for mother reports). Divorce also predicted both short-term and long-term rank-order increases in behavior problems. Associations between divorce and child behavior problems were moderated by family income (assessed before the divorce) such that children from families with higher incomes prior to the separation had fewer internalizing problems than children from families with lower incomes prior to the separation. Higher levels of predivorce maternal sensitivity and child IQ also functioned as protective factors for children of divorce. Mediation analyses showed that children were more likely to exhibit behavior problems after the divorce if their postdivorce home environment was less supportive and stimulating, their mother was less sensitive and more depressed, and their household income was lower. We discuss avenues for intervention, particularly efforts to improve the quality of home environments in divorced families. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  16. Effects of Active Listening, Reformulation, and Imitation on Mediator Success: Preliminary Results.

    Fischer-Lokou, Jacques; Lamy, Lubomir; Guéguen, Nicolas; Dubarry, Alexandre

    2016-06-01

    An experiment with 212 students (100 men, 112 women; M age = 18.3 years, SD = 0.9) was carried out to compare the effect of four techniques used by mediators on the number of agreements contracted by negotiators. Under experimental conditions, mediators were asked either to rephrase (reformulate) negotiators' words or to imitate them or to show active listening behavior, or finally, to use a free technique. More agreements were reached in the active listening condition than in both free and rephrase conditions. Furthermore, mediators in the active listening condition were perceived, by the negotiators, as more efficient than mediators using other techniques, although there was no significant difference observed between the active listening and imitation conditions. © The Author(s) 2016.

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

    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.

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

    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.

  19. Effect of failures and repairs on multiple cell production lines

    Legato, P.; Bobbio, A.; Roberti, L.

    1989-01-01

    This paper examines a production line composed of multiple stages, or cells, which are passed in sequential order to arrive to the final product. Two possible coordination disciplines are considered, namely: the classical tandem arrangement of sequential working centers with input buffer and the kanban scheme, considered the Japanese shop floor realization of the Just-In-Time (JIT) manifacturing approach. The production line is modelled and analysed by means of Stochastic Petri Nets (SPN). Finally an analysis is made of the possibility that the working cells can incur failure/repair cycles perturbing the production flow of the line and thus reduce performance indices.

  20. Effect of multiplicative noise on stationary stochastic process

    Kargovsky, A. V.; Chikishev, A. Yu.; Chichigina, O. A.

    2018-03-01

    An open system that can be analyzed using the Langevin equation with multiplicative noise is considered. The stationary state of the system results from a balance of deterministic damping and random pumping simulated as noise with controlled periodicity. The dependence of statistical moments of the variable that characterizes the system on parameters of the problem is studied. A nontrivial decrease in the mean value of the main variable with an increase in noise stochasticity is revealed. Applications of the results in several physical, chemical, biological, and technical problems of natural and humanitarian sciences are discussed.