mediation: Topics by Science.gov

Sample records for mediation

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

PubMed Central

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

PubMed

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.
Mediation Analysis with Multiple Mediators

PubMed Central

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. PMID:25580377
Mediation Analysis with Multiple Mediators.

PubMed

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

PubMed

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.
Sensitivity analysis for mistakenly adjusting for mediators in estimating total effect in observational studies.

PubMed

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

2017-11-20

In observational studies, epidemiologists often attempt to estimate the total effect of an exposure on an outcome of interest. However, when the underlying diagram is unknown and limited knowledge is available, dissecting bias performances is essential to estimating the total effect of an exposure on an outcome when mistakenly adjusting for mediators under logistic regression. Through simulation, we focused on six causal diagrams concerning different roles of mediators. Sensitivity analysis was conducted to assess the bias performances of varying across exposure-mediator effects and mediator-outcome effects when adjusting for the mediator. Based on the causal relationships in the real world, we compared the biases of varying across the effects of exposure-mediator with those of varying across the effects of mediator-outcome when adjusting for the mediator. The magnitude of the bias was defined by the difference between the estimated effect (using logistic regression) and the total effect of the exposure on the outcome. In four scenarios (a single mediator, two series mediators, two independent parallel mediators or two correlated parallel mediators), the biases of varying across the effects of exposure-mediator were greater than those of varying across the effects of mediator-outcome when adjusting for the mediator. In contrast, in two other scenarios (a single mediator or two independent parallel mediators in the presence of unobserved confounders), the biases of varying across the effects of exposure-mediator were less than those of varying across the effects of mediator-outcome when adjusting for the mediator. The biases were more sensitive to the variation of effects of exposure-mediator than the effects of mediator-outcome when adjusting for the mediator in the absence of unobserved confounders, while the biases were more sensitive to the variation of effects of mediator-outcome than those of exposure-mediator in the presence of an unobserved confounder. © 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.
77 FR 31677 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-29

... With Discretion to Determine Whether Parties to a FINRA Mediation May Select a Mediator Who Is Not on... Director'') with discretion to determine whether parties to a FINRA mediation may select a mediator who is... mediation to select a mediator either from a list of FINRA mediators supplied by the Mediation Director, or...
7 CFR 785.9 - Access to program records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... mediations opened and closed; issues mediated; dates of sessions with mediators; names of mediators... results and supporting documentation. (b) State mediators will notify all participants in writing at the... acknowledgment of receipt of such notice from the mediator. The certified State mediation program shall maintain...
45 CFR 16.18 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Mediation. 16.18 Section 16.18 Public Welfare... BOARD § 16.18 Mediation. (a) In cases pending before the Board. If the Board decides that mediation... mediation techniques and will provide or assist in selecting a mediator. The mediator may take any steps...
7 CFR 785.3 - Annual certification of State mediation programs.

Code of Federal Regulations, 2010 CFR

2010-01-01

... program; (ii) An identification of issues available for mediation under the program; (iii) Management of... requirements for mediators including: (A) Training in mediation skills and in USDA programs; (B) Identification... mediation program provides for training of mediators in mediation skills and in all issues covered by the...
Mediation analysis with time varying exposures and mediators

PubMed Central

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

2016-01-01

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

PubMed

VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

2017-06-01

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

PubMed

Morris, Megan; Halford, W Kim; Petch, Jemima; Hardwick, David

2018-03-01

An important limitation to the effectiveness of family mediation in assisting separated parents is parents failing to engage in the mediation process. In 524 parents who presented to a telephone-based mediation service, 113 (22%) initiating parents withdrew from mediation before the other parent was invited to participate, 241 (46%) initiating parents had respondent parents who declined to participate in mediation, and 170 cases (33%) completed mediation. We tested whether socio-demographic variables, psychological distress, coparental acrimony, parenting problems, or children's behavioral difficulties predicted mediation engagement. High interparental acrimony predicted failure to engage in mediation, but none of the other variables predicted mediation engagement. We followed a sample of 131 families that did not mediate and found they showed elevated psychological distress, acrimony, parenting problems and child adjustment difficulties, which remained unchanged 6 months later. Further research is needed to explore strategies to enhance respondent parent engagement with mediation, and to address the negative outcomes for those separated families not proceeding with mediation. © 2016 Family Process Institute.
77 FR 12098 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-28

... Change FINRA is proposing to amend FINRA Rule 14107 of the Code of Mediation Procedure (``Mediation Code'') to provide the Director of Mediation (``Mediation Director'') with discretion to determine whether parties to a FINRA mediation may select a mediator who is not on FINRA's mediator roster. The text of the...
When the Test of Mediation is More Powerful than the Test of the Total Effect

PubMed Central

O'Rourke, Holly P.; MacKinnon, David P.

2014-01-01

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. First, a study compared analytical power of the mediated effect to the total effect in a single mediator model to identify the situations in which the inclusion of one mediator increased statistical power. Results from the 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 non-zero and equal across models. Next, a study identified conditions where power was greater for the test of the total mediated effect compared to the test of the total effect in the parallel two mediator model. 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 found in the first study. Finally, a study assessed analytical power for a sequential (three-path) two mediator model and compared power to detect the three-path mediated effect to power to detect both the test of the total effect and the test of the mediated effect for the single mediator model. 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. PMID:24903690
A Bifactor Approach to Model Multifaceted Constructs in Statistical Mediation Analysis.

PubMed

Gonzalez, Oscar; MacKinnon, David P

Statistical mediation analysis allows researchers to identify the most important mediating constructs in the causal process studied. Identifying specific mediators is especially relevant when the hypothesized mediating construct consists of multiple related facets. The general definition of the construct and its facets might relate differently to an outcome. However, current methods do not allow researchers to study the relationships between general and specific aspects of a construct to an outcome simultaneously. This study proposes a bifactor measurement model for the mediating construct as a way to parse variance and represent the general aspect and specific facets of a construct simultaneously. Monte Carlo simulation results are presented to help determine the properties of mediated effect estimation when the mediator has a bifactor structure and a specific facet of a construct is the true mediator. This study also investigates the conditions when researchers can detect the mediated effect when the multidimensionality of the mediator is ignored and treated as unidimensional. Simulation results indicated that the mediation model with a bifactor mediator measurement model had unbiased and adequate power to detect the mediated effect with a sample size greater than 500 and medium a - and b -paths. Also, results indicate that parameter bias and detection of the mediated effect in both the data-generating model and the misspecified model varies as a function of the amount of facet variance represented in the mediation model. This study contributes to the largely unexplored area of measurement issues in statistical mediation analysis.
Interventional Effects for Mediation Analysis with Multiple Mediators.

PubMed

Vansteelandt, Stijn; Daniel, Rhian M

2017-03-01

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

PubMed

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.
Mediation of the Relationship between Maternal Phthalate Exposure and Preterm Birth by Oxidative Stress with Repeated Measurements across Pregnancy.

PubMed

Ferguson, Kelly K; Chen, Yin-Hsiu; VanderWeele, Tyler J; McElrath, Thomas F; Meeker, John D; Mukherjee, Bhramar

2017-03-01

Mediation analysis is useful for understanding mechanisms and has been used minimally in the study of the environment and disease. We examined mediation of the association between phthalate exposure during pregnancy and preterm birth by oxidative stress. This nested case-control study of preterm birth ( n = 130 cases, 352 controls) included women who delivered in Boston, Massachusestts, from 2006 through 2008. Phthalate metabolites and 8-isoprostane, an oxidative stress biomarker, were measured in urine from three visits in pregnancy. We applied four counterfactual mediation methods: method 1, utilizing exposure and mediator averages; method 2, using averages but allowing for an exposure-mediator interaction; method 3, incorporating longitudinal measurements of the exposure and mediator; and method 4, using longitudinal measurements and allowing for an exposure-mediator interaction. We observed mediation of the associations between phthalate metabolites and all preterm birth by 8-isoprostane, with the greatest estimated proportion mediated observed for spontaneous preterm births specifically. Fully utilizing repeated measures of the exposure and mediator improved precision of indirect (i.e., mediated) effect estimates, and including an exposure-mediator interaction increased the estimated proportion mediated. For example, for mono(2-ethyl-carboxy-propyl) phthalate (MECPP), a metabolite of di(2-ethylhexyl) phthalate (DEHP), the percent of the total effect mediated by 8-isoprostane increased from 47% to 60% with inclusion of an exposure-mediator interaction term, in reference to a total adjusted odds ratio of 1.67 or 1.48, respectively. This demonstrates mediation of the phthalate-preterm birth relationship by oxidative stress, and the utility of complex regression models in capturing mediated associations when repeated measures of exposure and mediator are available and an exposure-mediator interaction may exist. Citation: Ferguson KK, Chen YH, VanderWeele TJ, McElrath TF, Meeker JD, Mukherjee B. 2017. Mediation of the relationship between maternal phthalate exposure and preterm birth by oxidative stress with repeated measurements across pregnancy. Environ Health Perspect 125:488-494; http://dx.doi.org/10.1289/EHP282.
POWER ANALYSIS FOR COMPLEX MEDIATIONAL DESIGNS USING MONTE CARLO METHODS

PubMed Central

Thoemmes, Felix; MacKinnon, David P.; Reiser, Mark R.

2013-01-01

Applied researchers often include mediation effects in applications of advanced methods such as latent variable models and linear growth curve models. Guidance on how to estimate statistical power to detect mediation for these models has not yet been addressed in the literature. We describe a general framework for power analyses for complex mediational models. The approach is based on the well known technique of generating a large number of samples in a Monte Carlo study, and estimating power as the percentage of cases in which an estimate of interest is significantly different from zero. Examples of power calculation for commonly used mediational models are provided. Power analyses for the single mediator, multiple mediators, three-path mediation, mediation with latent variables, moderated mediation, and mediation in longitudinal designs are described. Annotated sample syntax for Mplus is appended and tabled values of required sample sizes are shown for some models. PMID:23935262

32 CFR 776.38 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Mediation. 776.38 Section 776.38 National... Professional Conduct § 776.38 Mediation. (a) Mediation: (1) A covered attorney may act as a mediator between... mediation, including the advantages and risks involved, and the effect on the attorney-client...
29 CFR 1202.1 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Mediation. 1202.1 Section 1202.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.1 Mediation. The mediation..., or where conferences are refused. The National Mediation Board may proffer its services in case any...
44 CFR 7.942 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Mediation. 7.942 Section 7..., Conciliation, and Enforcement Procedures § 7.942 Mediation. (a) FEMA will promptly refer to a mediation agency... participate in the mediation process to the extent necessary to reach an agreement or for the mediator to make...
24 CFR 3288.35 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Mediation. 3288.35 Section 3288.35...-Administered States § 3288.35 Mediation. (a) Mediator. The dispute resolution provider will provide for the... identifies any other party that should be included in the mediation, the mediator will contact the other...
22 CFR 143.33 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Mediation. 143.33 Section 143.33 Foreign... Mediation. (a) Referral of complaints for mediation. The agency will refer to the Federal Mediation and... participate in the mediation process to the extent necessary to reach an agreement or make an informed...
29 CFR 1203.1 - Mediation services.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Mediation services. 1203.1 Section 1203.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD APPLICATIONS FOR SERVICE § 1203.1 Mediation services. Applications for the mediation services of the National Mediation Board under section 5, First, of the Railway...
29 CFR 35.32 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Mediation. 35.32 Section 35.32 Labor Office of the Secretary... Mediation. (a) Referral to mediation. CRC will promptly refer to the Federal Mediation and Conciliation Service or the mediation agency designated by the Secretary of Health and Human Services under 45 CFR part...
Mediators and Metaphorical Analysis: A Phenomenological Study of Florida Family Court Mediators

ERIC Educational Resources Information Center

Storrow, Rebecca A.

2012-01-01

Florida family court mediation programs have typically been assessed with quantitative analysis. To understand the complexity of the experience of being a family mediator, it was necessary to explore how mediators practiced through qualitative research. Metaphors have been considered to be representations of mediators' mental models regarding…
Hypothesis test of mediation effect in causal mediation model with high-dimensional continuous mediators.

PubMed

Huang, Yen-Tsung; Pan, Wen-Chi

2016-06-01

Causal mediation modeling has become a popular approach for studying the effect of an exposure on an outcome through a mediator. However, current methods are not applicable to the setting with a large number of mediators. We propose a testing procedure for mediation effects of high-dimensional continuous mediators. We characterize the marginal mediation effect, the multivariate component-wise mediation effects, and the L2 norm of the component-wise effects, and develop a Monte-Carlo procedure for evaluating their statistical significance. To accommodate the setting with a large number of mediators and a small sample size, we further propose a transformation model using the spectral decomposition. Under the transformation model, mediation effects can be estimated using a series of regression models with a univariate transformed mediator, and examined by our proposed testing procedure. Extensive simulation studies are conducted to assess the performance of our methods for continuous and dichotomous outcomes. We apply the methods to analyze genomic data investigating the effect of microRNA miR-223 on a dichotomous survival status of patients with glioblastoma multiforme (GBM). We identify nine gene ontology sets with expression values that significantly mediate the effect of miR-223 on GBM survival. © 2015, The International Biometric Society.
Interventional effects for mediation analysis with multiple mediators

PubMed Central

Vansteelandt, Stijn; Daniel, Rhian M.

2016-01-01

The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins21 introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal in order to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when – as often – the structural dependence between the multiple mediators is unknown; for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators. PMID:27922534
Design approaches to experimental mediation.

PubMed

Pirlott, Angela G; MacKinnon, David P

2016-09-01

Identifying causal mechanisms has become a cornerstone of experimental social psychology, and editors in top social psychology journals champion the use of mediation methods, particularly innovative ones when possible (e.g. Halberstadt, 2010, Smith, 2012). Commonly, studies in experimental social psychology randomly assign participants to levels of the independent variable and measure the mediating and dependent variables, and the mediator is assumed to causally affect the dependent variable. However, participants are not randomly assigned to levels of the mediating variable(s), i.e., the relationship between the mediating and dependent variables is correlational. Although researchers likely know that correlational studies pose a risk of confounding, this problem seems forgotten when thinking about experimental designs randomly assigning participants to levels of the independent variable and measuring the mediator (i.e., "measurement-of-mediation" designs). Experimentally manipulating the mediator provides an approach to solving these problems, yet these methods contain their own set of challenges (e.g., Bullock, Green, & Ha, 2010). We describe types of experimental manipulations targeting the mediator (manipulations demonstrating a causal effect of the mediator on the dependent variable and manipulations targeting the strength of the causal effect of the mediator) and types of experimental designs (double randomization, concurrent double randomization, and parallel), provide published examples of the designs, and discuss the strengths and challenges of each design. Therefore, the goals of this paper include providing a practical guide to manipulation-of-mediator designs in light of their challenges and encouraging researchers to use more rigorous approaches to mediation because manipulation-of-mediator designs strengthen the ability to infer causality of the mediating variable on the dependent variable.
34 CFR 81.13 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Mediation. 81.13 Section 81.13 Education Office of the... Mediation. (a) Voluntary mediation is available for proceedings that are pending before the OALJ. (b) A... mediation by filing a motion with the ALJ assigned to the case. The OALJ arranges for a mediator if the...
7 CFR 785.5 - Fees for mediation services.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Fees for mediation services. 785.5 Section 785.5... AGRICULTURE SPECIAL PROGRAMS CERTIFIED STATE MEDIATION PROGRAM § 785.5 Fees for mediation services. A requirement that non-USDA parties who elect to participate in mediation pay a fee for mediation services will...
Standardized Effect Size Measures for Mediation Analysis in Cluster-Randomized Trials

ERIC Educational Resources Information Center

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…
Does parental mediation of media influence child outcomes? A meta-analysis on media time, aggression, substance use, and sexual behavior.

PubMed

Collier, Kevin M; Coyne, Sarah M; Rasmussen, Eric E; Hawkins, Alan J; Padilla-Walker, Laura M; Erickson, Sage E; Memmott-Elison, Madison K

2016-05-01

The current study examined how parental mediation of media (restrictive mediation, active mediation, and coviewing) influenced child outcomes. Three meta-analyses, 1 for each type of mediation, were conducted on a total of 57 studies. Each analysis assessed the effectiveness of parental mediation on 4 pertinent child outcomes: media use, aggression, substance use, and sexual behavior. The overall results indicated small, but significant relationships between child outcomes and restrictive mediation (r+ = -.06), and coviewing (r+ = .09). Overall active mediation was nonsignificant, though active mediation was individually related to lower levels of aggression (r+ = -.08), sexual behavior (r+ = -.06), and substance use (r+ = -.11). This analysis revealed that parents may have the ability to mitigate some of the adverse effects of the media by using certain mediation strategies. Overall, a cooperative effort from the communication and parenting fields is necessary for a comprehensive analysis of parental mediation as well as a disentanglement of the various parental mediation measures. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
What carries a mediation process? Configural analysis of mediation.

PubMed

von Eye, Alexander; Mun, Eun Young; Mair, Patrick

2009-09-01

Mediation is a process that links a predictor and a criterion via a mediator variable. Mediation can be full or partial. This well-established definition operates at the level of variables even if they are categorical. In this article, two new approaches to the analysis of mediation are proposed. Both of these approaches focus on the analysis of categorical variables. The first involves mediation analysis at the level of configurations instead of variables. Thus, mediation can be incorporated into the arsenal of methods of analysis for person-oriented research. Second, it is proposed that Configural Frequency Analysis (CFA) can be used for both exploration and confirmation of mediation relationships among categorical variables. The implications of using CFA are first that mediation hypotheses can be tested at the level of individual configurations instead of variables. Second, this approach leaves the door open for different types of mediation processes to exist within the same set. Using a data example, it is illustrated that aggregate-level analysis can overlook mediation processes that operate at the level of individual configurations.
Bayesian dynamic mediation analysis.

PubMed

Huang, Jing; Yuan, Ying

2017-12-01

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

PubMed

Jeronimo, Célia; Langelier, Marie-France; Bataille, Alain R; Pascal, John M; Pugh, B Franklin; Robert, François

2016-11-03

Mediator is a highly conserved transcriptional coactivator organized into four modules, namely Tail, Middle, Head, and Kinase (CKM). Previous work suggests regulatory roles for Tail and CKM, but an integrated model for these activities is lacking. Here, we analyzed the genome-wide distribution of Mediator subunits in wild-type and mutant yeast cells in which RNA polymerase II promoter escape is blocked, allowing detection of transient Mediator forms. We found that although all modules are recruited to upstream activated regions (UAS), assembly of Mediator within the pre-initiation complex is accompanied by the release of CKM. Interestingly, our data show that CKM regulates Mediator-UAS interaction rather than Mediator-promoter association. In addition, although Tail is required for Mediator recruitment to UAS, Tailless Mediator nevertheless interacts with core promoters. Collectively, our data suggest that the essential function of Mediator is mediated by Head and Middle at core promoters, while Tail and CKM play regulatory roles. Copyright © 2016 Elsevier Inc. All rights reserved.
Conservation and Divergence of Mediator Structure and Function: Insights from Plants.

PubMed

Dolan, Whitney L; Chapple, Clint

2017-01-01

The Mediator complex is a large, multisubunit, transcription co-regulator that is conserved across eukaryotes. Studies of the Arabidopsis Mediator complex and its subunits have shown that it functions in nearly every aspect of plant development and fitness. In addition to revealing mechanisms of regulation of plant-specific pathways, studies of plant Mediator complexes have the potential to shed light on the conservation and divergence of Mediator structure and function across Kingdoms and plant lineages. The majority of insights into plant Mediator function have come from Arabidopsis because it is the only plant from which Mediator has been purified and from which an array of Mediator mutants have been isolated by forward and reverse genetics. So far, these studies indicate that, despite low sequence similarity between many orthologous subunits, the overall structure and function of Mediator is well conserved between Kingdoms. Several studies have also expanded our knowledge of Mediator to other plant species, opening avenues of investigation into the role of Mediator in plant adaptation and fitness.
A unification of mediation and interaction: a four-way decomposition

PubMed Central

VanderWeele, Tyler J.

2014-01-01

It is shown that the overall effect of an exposure on an outcome, in the presence of a mediator with which the exposure may interact, can be decomposed into four components: (i) the effect of the exposure in the absence of the mediator, (ii) the interactive effect when the mediator is left to what it would be in the absence of exposure, (iii) a mediated interaction, and (iv) a pure mediated effect. These four components, respectively, correspond to the portion of the effect that is due to neither mediation nor interaction, to just interaction (but not mediation), to both mediation and interaction, and to just mediation (but not interaction). This four-way decomposition unites methods that attribute effects to interactions and methods that assess mediation. Certain combinations of these four components correspond to measures for mediation, while other combinations correspond to measures of interaction previously proposed in the literature. Prior decompositions in the literature are in essence special cases of this four-way decomposition. The four-way decomposition can be carried out using standard statistical models, and software is provided to estimate each of the four components. The four-way decomposition provides maximum insight into how much of an effect is mediated, how much is due to interaction, how much is due to both mediation and interaction together, and how much is due to neither. PMID:25000145

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

ERIC Educational Resources Information Center

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

2015-01-01

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

ERIC Educational Resources Information Center

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

2015-01-01

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

PubMed Central

Michael, Benedict D.; Griffiths, Michael J.; Granerod, Julia; Brown, David; Davies, Nicholas W. S.; Borrow, Ray; Solomon, Tom

2016-01-01

Background Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15–60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause. Methods We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology. Results Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001). Conclusions Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation. PMID:26808276
Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology.

PubMed

Michael, Benedict D; Griffiths, Michael J; Granerod, Julia; Brown, David; Davies, Nicholas W S; Borrow, Ray; Solomon, Tom

2016-01-01

Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause. We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology. Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001). Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.
Measurement error, time lag, unmeasured confounding: Considerations for longitudinal estimation of the effect of a mediator in randomised clinical trials.

PubMed

Goldsmith, K A; Chalder, T; White, P D; Sharpe, M; Pickles, A

2018-06-01

Clinical trials are expensive and time-consuming and so should also be used to study how treatments work, allowing for the evaluation of theoretical treatment models and refinement and improvement of treatments. These treatment processes can be studied using mediation analysis. Randomised treatment makes some of the assumptions of mediation models plausible, but the mediator-outcome relationship could remain subject to bias. In addition, mediation is assumed to be a temporally ordered longitudinal process, but estimation in most mediation studies to date has been cross-sectional and unable to explore this assumption. This study used longitudinal structural equation modelling of mediator and outcome measurements from the PACE trial of rehabilitative treatments for chronic fatigue syndrome (ISRCTN 54285094) to address these issues. In particular, autoregressive and simplex models were used to study measurement error in the mediator, different time lags in the mediator-outcome relationship, unmeasured confounding of the mediator and outcome, and the assumption of a constant mediator-outcome relationship over time. Results showed that allowing for measurement error and unmeasured confounding were important. Contemporaneous rather than lagged mediator-outcome effects were more consistent with the data, possibly due to the wide spacing of measurements. Assuming a constant mediator-outcome relationship over time increased precision.
Subunit architecture and functional modular rearrangements of the transcriptional Mediator complex

PubMed Central

Tsai, Kuang-Lei; Tomomori-Sato, Chieri; Sato, Shigeo; Conaway, Ronald C.; Conaway, Joan W.; Asturias, Francisco J.

2014-01-01

SUMMARY The multisubunit Mediator comprising ~30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. PMID:24882805
The contribution of mediator-based deficiencies to age differences in associative learning.

PubMed

Dunlosky, John; Hertzog, Christopher; Powell-Moman, Amy

2005-03-01

Production, mediational, and utilization deficiencies, which describe how strategy use may contribute to developmental trends in episodic memory, have been intensively investigated. Using a mediator report-and-retrieval method, the authors present evidence concerning the degree to which 2 previously unexplored mediator-based deficits--retrieval and decoding deficiencies--account for age deficits in learning. During study, older and younger adults were instructed to use a strategy (imagery or sentence generation) to associate words within paired associates. They also reported each mediator and later attempted to retrieve each response and the mediator produced at study. Substantial deficits occurred in mediator recall, and small differences were observed in decoding mediators. Mediator recall also accounted for a substantial proportion of the age deficits in criterion recall independently of fluid or crystallized intelligence. Discussion focuses on mediator-based deficiencies and their implications for theories of age deficits in episodic memory. Copyright 2005 APA, all rights reserved.
Does Parental Mediation of Media Influence Child Outcomes? A Meta-Analysis on Media Time, Aggression, Substance Use, and Sexual Behavior

ERIC Educational Resources Information Center

Collier, Kevin M.; Coyne, Sarah M.; Rasmussen, Eric E.; Hawkins, Alan J.; Padilla-Walker, Laura M.; Erickson, Sage E.; Memmott-Elison, Madison K.

2016-01-01

The current study examined how parental mediation of media (restrictive mediation, active mediation, and coviewing) influenced child outcomes. Three meta-analyses, 1 for each type of mediation, were conducted on a total of 57 studies. Each analysis assessed the effectiveness of parental mediation on 4 pertinent child outcomes: media use,…
Integrating mediation and moderation to advance theory development and testing.

PubMed

Karazsia, Bryan T; Berlin, Kristoffer S; Armstrong, Bridget; Janicke, David M; Darling, Katherine E

2014-03-01

The concepts and associated analyses of mediation and moderation are important to the field of psychology. Although pediatric psychologists frequently incorporate mediation and moderation in their theories and empirical research, on few occasions have we integrated mediation and moderation. In this article, conceptual reasons for integrating mediation and moderation are offered. We illustrate a model that integrates mediation and moderation. In our illustration, the strength of an indirect or a mediating effect varied as a function of a moderating variable. Clinical implications of the integration of mediation and moderation are discussed, as is the potential of integrated models to advance research programs in pediatric psychology.
Guidelines for the Investigation of Mediating Variables in Business Research.

PubMed

MacKinnon, David P; Coxe, Stefany; Baraldi, Amanda N

2012-03-01

Business theories often specify the mediating mechanisms by which a predictor variable affects an outcome variable. In the last 30 years, investigations of mediating processes have become more widespread with corresponding developments in statistical methods to conduct these tests. The purpose of this article is to provide guidelines for mediation studies by focusing on decisions made prior to the research study that affect the clarity of conclusions from a mediation study, the statistical models for mediation analysis, and methods to improve interpretation of mediation results after the research study. Throughout this article, the importance of a program of experimental and observational research for investigating mediating mechanisms is emphasized.
Incorporating nonlinearity into mediation analyses.

PubMed

Knafl, George J; Knafl, Kathleen A; Grey, Margaret; Dixon, Jane; Deatrick, Janet A; Gallo, Agatha M

2017-03-21

Mediation is an important issue considered in the behavioral, medical, and social sciences. It addresses situations where the effect of a predictor variable X on an outcome variable Y is explained to some extent by an intervening, mediator variable M. Methods for addressing mediation have been available for some time. While these methods continue to undergo refinement, the relationships underlying mediation are commonly treated as linear in the outcome Y, the predictor X, and the mediator M. These relationships, however, can be nonlinear. Methods are needed for assessing when mediation relationships can be treated as linear and for estimating them when they are nonlinear. Existing adaptive regression methods based on fractional polynomials are extended here to address nonlinearity in mediation relationships, but assuming those relationships are monotonic as would be consistent with theories about directionality of such relationships. Example monotonic mediation analyses are provided assessing linear and monotonic mediation of the effect of family functioning (X) on a child's adaptation (Y) to a chronic condition by the difficulty (M) for the family in managing the child's condition. Example moderated monotonic mediation and simulation analyses are also presented. Adaptive methods provide an effective way to incorporate possibly nonlinear monotonicity into mediation relationships.
Decomposition of the Total Effect in the Presence of Multiple Mediators and Interactions.

PubMed

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

PubMed

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.
Mediation analysis with multiple versions of the mediator.

PubMed

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.
Mediation analysis with multiple versions of the mediator

PubMed Central

VanderWeele, Tyler J.

2013-01-01

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 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 only has access to data on the particular measurement, not 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 two examples from the literature, one in which the versions of the mediator are unknown and another in which the mediator itself has been dichotomized. PMID:22475830
Comparison of methods for the analysis of relatively simple mediation models.

PubMed

Rijnhart, Judith J M; Twisk, Jos W R; Chinapaw, Mai J M; de Boer, Michiel R; Heymans, Martijn W

2017-09-01

Statistical mediation analysis is an often used method in trials, to unravel the pathways underlying the effect of an intervention on a particular outcome variable. Throughout the years, several methods have been proposed, such as ordinary least square (OLS) regression, structural equation modeling (SEM), and the potential outcomes framework. Most applied researchers do not know that these methods are mathematically equivalent when applied to mediation models with a continuous mediator and outcome variable. Therefore, the aim of this paper was to demonstrate the similarities between OLS regression, SEM, and the potential outcomes framework in three mediation models: 1) a crude model, 2) a confounder-adjusted model, and 3) a model with an interaction term for exposure-mediator interaction. Secondary data analysis of a randomized controlled trial that included 546 schoolchildren. In our data example, the mediator and outcome variable were both continuous. We compared the estimates of the total, direct and indirect effects, proportion mediated, and 95% confidence intervals (CIs) for the indirect effect across OLS regression, SEM, and the potential outcomes framework. OLS regression, SEM, and the potential outcomes framework yielded the same effect estimates in the crude mediation model, the confounder-adjusted mediation model, and the mediation model with an interaction term for exposure-mediator interaction. Since OLS regression, SEM, and the potential outcomes framework yield the same results in three mediation models with a continuous mediator and outcome variable, researchers can continue using the method that is most convenient to them.
Induction of Hypozincemia and Hepatic Metallothionein Synthesis in Hypersensitivity Reactions.

DTIC Science & Technology

1978-06-19

cells to produce endogenous pyrogen (EP), the mediator of febrile response. Controversial evidence exists, however , concerning the differentiation of LEM...hypersensitivity reactions, Kampschmid t and Pulliam (1) proposed that leukocytic endogenous mediator (LEN) is released from phagocytic cells after... endogenous mediator(s) such as LEN, no conclusive evidence is available to indicate a mRNA requirement for the production of potential mediator(s
Mediation Works: An Action Research Study Evaluating the Peer Mediation Program from the Eyes of Mediators and Faculty

ERIC Educational Resources Information Center

Cook, Jacqueline Yvonne; Boes, Susan R.

2013-01-01

A literature review was conducted to understand how mediators and faculty view a Peer Mediation Program (PMP). The review identified four subgroups: mediators, teachers, administrators, and school counselors as well as their views on the success or lack of success of PMPs. The research also reflects how to best engage stakeholders in the mediation…
7 CFR 900.108 - Mediator's report.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Mediator's report. 900.108 Section 900.108 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Mediator's report. The mediator, upon the completion of mediation proceedings, shall submit to the...
Monte Carlo based statistical power analysis for mediation models: methods and software.

PubMed

Zhang, Zhiyong

2014-12-01

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

On the (In)Validity of Tests of Simple Mediation: Threats and Solutions

PubMed Central

Pek, Jolynn; Hoyle, Rick H.

2015-01-01

Mediation analysis is a popular framework for identifying underlying mechanisms in social psychology. In the context of simple mediation, we review and discuss the implications of three facets of mediation analysis: (a) conceptualization of the relations between the variables, (b) statistical approaches, and (c) relevant elements of design. We also highlight the issue of equivalent models that are inherent in simple mediation. The extent to which results are meaningful stem directly from choices regarding these three facets of mediation analysis. We conclude by discussing how mediation analysis can be better applied to examine causal processes, highlight the limits of simple mediation, and make recommendations for better practice. PMID:26985234
Guidelines for the Investigation of Mediating Variables in Business Research

PubMed Central

Coxe, Stefany; Baraldi, Amanda N.

2013-01-01

Business theories often specify the mediating mechanisms by which a predictor variable affects an outcome variable. In the last 30 years, investigations of mediating processes have become more widespread with corresponding developments in statistical methods to conduct these tests. The purpose of this article is to provide guidelines for mediation studies by focusing on decisions made prior to the research study that affect the clarity of conclusions from a mediation study, the statistical models for mediation analysis, and methods to improve interpretation of mediation results after the research study. Throughout this article, the importance of a program of experimental and observational research for investigating mediating mechanisms is emphasized. PMID:25237213
24 CFR 146.35 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Mediation. 146.35 Section 146.35... ASSISTANCE Investigation, Settlement, and Enforcement Procedures § 146.35 Mediation. (a) HUD shall refer to the Federal Mediation and Conciliation Service, a mediation agency designated by the Secretary of...
Statistical properties of four effect-size measures for mediation models.

PubMed

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

PubMed

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.
Lipid mediators and their metabolism in the nucleous: implications for Alzheimer's disease.

PubMed

Farooqui, Akhlaq A

2012-01-01

Lipid mediators are important endogenous regulators derived from enzymatic degradation of glycerophospholipids, sphingolipids, and cholesterol by phospholipases, sphingomyelinases, and cytochrome P450 hydroxylases, respectively. In neural cells, lipid mediators are associated with proliferation, differentiation, oxidative stress, inflammation, and apoptosis. A major group of lipid mediators, which originates from the enzymatic oxidation of arachidonic acid, is called eicosanoids (i.e., prostaglandins, leukotrienes, thromboxanes, and lipoxins). The corresponding lipid mediators of docosahexaenoic acid metabolism are named as docosanoids. They include resolvins, protectins (neuroprotectins), and maresins. Docosanoids produce antioxidant, anti-inflammatory, and antiapoptotic effects in brain tissue. Other glycerophospholipid-derived lipid mediators are platelet activating factor, lysophosphatidic acid, and endocannabinoids. Degradation of sphingolipids also results in the generation of sphingolipid-derived lipid mediators, such as ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. These mediators are involved in differentiation, growth, cell migration, and apoptosis. Similarly, cholesterol-derived lipid mediators, hydroxycholesterol, produce apoptosis. Abnormal metabolism of lipid mediators may be closely associated with pathogenesis of Alzheimer's disease.
Methods for integrating moderation and mediation: a general analytical framework using moderated path analysis.

PubMed

Edwards, Jeffrey R; Lambert, Lisa Schurer

2007-03-01

Studies that combine moderation and mediation are prevalent in basic and applied psychology research. Typically, these studies are framed in terms of moderated mediation or mediated moderation, both of which involve similar analytical approaches. Unfortunately, these approaches have important shortcomings that conceal the nature of the moderated and the mediated effects under investigation. This article presents a general analytical framework for combining moderation and mediation that integrates moderated regression analysis and path analysis. This framework clarifies how moderator variables influence the paths that constitute the direct, indirect, and total effects of mediated models. The authors empirically illustrate this framework and give step-by-step instructions for estimation and interpretation. They summarize the advantages of their framework over current approaches, explain how it subsumes moderated mediation and mediated moderation, and describe how it can accommodate additional moderator and mediator variables, curvilinear relationships, and structural equation models with latent variables. (c) 2007 APA, all rights reserved.
Mindfulness facets, trait emotional intelligence, emotional distress, and multiple health behaviors: A serial two-mediator model.

PubMed

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.
Subunit architecture and functional modular rearrangements of the transcriptional mediator complex.

PubMed

Tsai, Kuang-Lei; Tomomori-Sato, Chieri; Sato, Shigeo; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

2014-06-05

The multisubunit Mediator, comprising ∼30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA-binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.
Mediator Undergoes a Compositional Change during Transcriptional Activation.

PubMed

Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

2016-11-03

Mediator is a transcriptional co-activator recruited to enhancers by DNA-binding activators, and it also interacts with RNA polymerase (Pol) II as part of the preinitiation complex (PIC). We demonstrate that a single Mediator complex associates with the enhancer and core promoter in vivo, indicating that it can physically bridge these transcriptional elements. However, the Mediator kinase module associates strongly with the enhancer, but not with the core promoter, and it dissociates from the enhancer upon depletion of the TFIIH kinase. Severing the kinase module from Mediator by removing the connecting subunit Med13 does not affect Mediator association at the core promoter but increases occupancy at enhancers. Thus, Mediator undergoes a compositional change in which the kinase module, recruited via Mediator to the enhancer, dissociates from Mediator to permit association with Pol II and the PIC. As such, Mediator acts as a dynamic bridge between the enhancer and core promoter. Copyright © 2016 Elsevier Inc. All rights reserved.
Distinguishing Mediational Models and Analyses in Clinical Psychology: Atemporal Associations Do Not Imply Causation.

PubMed

Winer, E Samuel; Cervone, Daniel; Bryant, Jessica; McKinney, Cliff; Liu, Richard T; Nadorff, Michael R

2016-09-01

A popular way to attempt to discern causality in clinical psychology is through mediation analysis. However, mediation analysis is sometimes applied to research questions in clinical psychology when inferring causality is impossible. This practice may soon increase with new, readily available, and easy-to-use statistical advances. Thus, we here provide a heuristic to remind clinical psychological scientists of the assumptions of mediation analyses. We describe recent statistical advances and unpack assumptions of causality in mediation, underscoring the importance of time in understanding mediational hypotheses and analyses in clinical psychology. Example analyses demonstrate that statistical mediation can occur despite theoretical mediation being improbable. We propose a delineation of mediational effects derived from cross-sectional designs into the terms temporal and atemporal associations to emphasize time in conceptualizing process models in clinical psychology. The general implications for mediational hypotheses and the temporal frameworks from within which they may be drawn are discussed. © 2016 Wiley Periodicals, Inc.
Examining the role of unmeasured confounding in mediation analysis with genetic and genomic applications.

PubMed

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

2017-07-19

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

PubMed

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.
Design approaches to experimental mediation☆

PubMed Central

Pirlott, Angela G.; MacKinnon, David P.

2016-01-01

Identifying causal mechanisms has become a cornerstone of experimental social psychology, and editors in top social psychology journals champion the use of mediation methods, particularly innovative ones when possible (e.g. Halberstadt, 2010, Smith, 2012). Commonly, studies in experimental social psychology randomly assign participants to levels of the independent variable and measure the mediating and dependent variables, and the mediator is assumed to causally affect the dependent variable. However, participants are not randomly assigned to levels of the mediating variable(s), i.e., the relationship between the mediating and dependent variables is correlational. Although researchers likely know that correlational studies pose a risk of confounding, this problem seems forgotten when thinking about experimental designs randomly assigning participants to levels of the independent variable and measuring the mediator (i.e., “measurement-of-mediation” designs). Experimentally manipulating the mediator provides an approach to solving these problems, yet these methods contain their own set of challenges (e.g., Bullock, Green, & Ha, 2010). We describe types of experimental manipulations targeting the mediator (manipulations demonstrating a causal effect of the mediator on the dependent variable and manipulations targeting the strength of the causal effect of the mediator) and types of experimental designs (double randomization, concurrent double randomization, and parallel), provide published examples of the designs, and discuss the strengths and challenges of each design. Therefore, the goals of this paper include providing a practical guide to manipulation-of-mediator designs in light of their challenges and encouraging researchers to use more rigorous approaches to mediation because manipulation-of-mediator designs strengthen the ability to infer causality of the mediating variable on the dependent variable. PMID:27570259
Causal mediation analysis for longitudinal data with exogenous exposure

PubMed Central

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

2016-01-01

Mediation analysis is a valuable approach to examine pathways in epidemiological research. Prospective cohort studies are often conducted to study biological mechanisms and often collect longitudinal measurements on each participant. Mediation formulae for longitudinal data have been developed. Here, we formalize the natural direct and indirect effects using a causal framework with potential outcomes that allows for an interaction between the exposure and the mediator. To allow different types of longitudinal measures of the mediator and outcome, we assume two generalized mixed-effects models for both the mediator and the outcome. The model for the mediator has subject-specific random intercepts and random exposure slopes for each cluster, and the outcome model has random intercepts and random slopes for the exposure, the mediator, and their interaction. We also expand our approach to settings with multiple mediators and derive the mediated effects, jointly through all mediators. Our method requires the absence of time-varying confounding with respect to the exposure and the mediator. This assumption is achieved in settings with exogenous exposure and mediator, especially when exposure and mediator are not affected by variables measured at earlier time points. We apply the methodology to data from the Normative Aging Study and estimate the direct and indirect effects, via DNA methylation, of air pollution, and temperature on intercellular adhesion molecule 1 (ICAM-1) protein levels. Our results suggest that air pollution and temperature have a direct effect on ICAM-1 protein levels (i.e. not through a change in ICAM-1 DNA methylation) and that temperature has an indirect effect via a change in ICAM-1 DNA methylation. PMID:26272993
Method for evaluating multiple mediators: mediating effects of smoking and COPD on the association between the CHRNA5-A3 variant and lung cancer risk.

PubMed

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%.
7 CFR 785.7 - Distribution of Federal grant funds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... mediation services (historical and projected); (2) Scope of mediation services; (3) Service record of the... mediation services, historical and projected, as applicable; (iii) Number of mediations resulting in signed... of mediation; (4) Historic use of program funds (budgeted versus actual); and (5) Material changes in...
Mediation and Counseling Services: A Viable Partnership

ERIC Educational Resources Information Center

Hodges, Shannon

2009-01-01

Mediation has become common in many areas of society, including marital dissolution, community disputes, governmental agencies, and business and industry. Though higher education has been slower than society to adopt mediation services, campus mediation is becoming increasingly more common. This article explains why mediation is a viable…
38 CFR 18.543 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Mediation. 18.543 Section... Enforcement Procedures § 18.543 Mediation. (a) Referral of complaints for mediation. VA will refer to the Federal Mediation and Conciliation Service all complaints that: (1) Fall within the jurisdiction of the...
7 CFR 614.11 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Mediation. 614.11 Section 614.11 Agriculture... AGRICULTURE CONSERVATION OPERATIONS NRCS APPEAL PROCEDURES § 614.11 Mediation. (a) A participant who wishes to pursue mediation must file request for mediation under this part with the NRCS official designated in the...

22 CFR 218.33 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Mediation. 218.33 Section 218.33 Foreign... § 218.33 Mediation. (a) Referral of complaints for mediation. The agency will refer to the Federal Mediation and Conciliation Service all complaints that: (1) fall within the jurisdiction of these...
15 CFR 930.111 - OCRM mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false OCRM mediation. 930.111 Section 930... FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.111 OCRM mediation. The availability of mediation does not preclude use by the parties of alternative means for...
34 CFR 110.32 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Mediation. 110.32 Section 110.32 Education Regulations..., Conciliation, and Enforcement Procedures § 110.32 Mediation. (a) ED promptly refers to the Federal Mediation and Conciliation Service or to the mediation agency designated by the Secretary of Health and Human...
43 CFR 17.332 - Mediation.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., and Enforcement Procedures § 17.332 Mediation. (a) Referral of complaints for mediation. DOI will... it. The FMCS shall send the agreement to DOI. DOI, however, retains the right to monitor the... process without prior approval of the head of the mediation agency. (e) DOI will use the mediation process...
A State Space Modeling Approach to Mediation Analysis

ERIC Educational Resources Information Center

Gu, Fei; Preacher, Kristopher J.; Ferrer, Emilio

2014-01-01

Mediation is a causal process that evolves over time. Thus, a study of mediation requires data collected throughout the process. However, most applications of mediation analysis use cross-sectional rather than longitudinal data. Another implicit assumption commonly made in longitudinal designs for mediation analysis is that the same mediation…
7 CFR 900.102 - Filing of applications for mediation or arbitration.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Filing of applications for mediation or arbitration... Sales of Milk or Its Products § 900.102 Filing of applications for mediation or arbitration. All applications for mediation or arbitration, all submissions, and all correspondence regarding mediation or...
14 CFR 1252.402 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Mediation. 1252.402 Section 1252.402... Procedures § 1252.402 Mediation. (a) Referral of complaints for mediation. NASA will refer to the Federal Mediation and Conciliation Service all complaints that: (1) Fall within the jurisdiction of the Act and...
45 CFR 91.43 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Mediation. 91.43 Section 91.43 Public Welfare... Enforcement Procedures § 91.43 Mediation. (a) HHS will promptly refer to a mediation agency designated by the... mediation process to the extent necessary to reach an agreement or make an informed judgment that an...
29 CFR 1209.03 - Conduct of National Mediation Board business.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Conduct of National Mediation Board business. 1209.03 Section 1209.03 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD PUBLIC OBSERVATION OF NATIONAL MEDIATION BOARD MEETINGS § 1209.03 Conduct of National Mediation Board business...
29 CFR 1207.2 - Requests for Mediation Board action.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Requests for Mediation Board action. 1207.2 Section 1207.2 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD ESTABLISHMENT OF SPECIAL ADJUSTMENT BOARDS § 1207.2 Requests for Mediation Board action. (a) Requests for the National Mediation Board...
10 CFR 4.333 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Mediation. 4.333 Section 4.333 Energy NUCLEAR REGULATORY... Investigation, Conciliation, and Enforcement Procedures § 4.333 Mediation. (a) Referral of complaints for mediation. NRC will refer to a mediation agency designated by the Secretary of the Department of Health and...
7 CFR 780.9 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Mediation. 780.9 Section 780.9 Agriculture Regulations... PROGRAMS APPEAL REGULATIONS § 780.9 Mediation. (a) Any request for mediation must be submitted after... once: (1) If resolution of an adverse decision is not achieved in mediation, a participant may exercise...
Estimating and Testing Mediation Effects with Censored Data

ERIC Educational Resources Information Center

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…
Forms of Mediation: The Case of Interpreter-Mediated Interactions in Medical Systems

ERIC Educational Resources Information Center

Baraldi, Claudio

2009-01-01

This paper analyses the forms of mediation in interlinguistic interactions performed in Italian healthcare services and in contexts of migration. The literature encourages dialogic transformative mediation, empowering participants' voices and changing cultural presuppositions in social systems. It may be doubtful, however, whether mediation can…
15 CFR 20.12 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Mediation. 20.12 Section 20.12... Procedures § 20.12 Mediation. (a) DOC will refer to a mediation service designated by the Secretary all... further processing. (b) Both the complainant and the recipient shall participate in the mediation process...
Reducing Levels of Elementary School Violence with Peer Mediation

ERIC Educational Resources Information Center

Schellenberg, Rita Cantrell; Parks-Savage, Agatha; Rehfuss, Mark

2007-01-01

The effectiveness of an existing peer mediation program in a diverse, suburban elementary school was examined. Peer mediation was available to all students (N = 825). Three-year longitudinal data showed significant reductions in the school's out-of-school suspensions after implementation of the peer mediation program. Mediation training also…
43 CFR 17.332 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Mediation. 17.332 Section 17.332 Public..., and Enforcement Procedures § 17.332 Mediation. (a) Referral of complaints for mediation. DOI will... participate in the mediation process to the extent necessary to reach an agreement or make an informed...
15 CFR 923.83 - Mediation of amendments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Mediation of amendments. 923.83... Programs § 923.83 Mediation of amendments. (a) Section 307(h)(2) of the Act provides for mediation of... management program. Accordingly mediation is available to states or federal agencies when a serious...
15 CFR 930.45 - Availability of mediation for previously reviewed activities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Availability of mediation for... PROGRAMS Consistency for Federal Agency Activities § 930.45 Availability of mediation for previously..., either party may request the Secretarial mediation or OCRM mediation services provided for in subpart G...
15 CFR 930.115 - Termination of mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Termination of mediation. 930.115... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.115 Termination of mediation. Mediation shall terminate: (a) At any time the Federal and State agencies agree to a...

29 CFR 1425.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE MEDIATION ASSISTANCE IN THE FEDERAL SERVICE § 1425.1 Definitions. As used in this part: (a) The Service means Federal Mediation and... organization as that term is defined in 5 U.S.C. 7103(4). (c) Third-party mediation assistance means mediation...
15 CFR 930.55 - Availability of mediation for license or permit disputes.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Availability of mediation for license... Consistency for Activities Requiring a Federal License or Permit § 930.55 Availability of mediation for... consistency requirement, either party may request the OCRM mediation or Secretarial mediation services...
45 CFR 1156.16 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Mediation. 1156.16 Section 1156.16 Public Welfare... Procedures § 1156.16 Mediation. (a) Referral of complaints for mediation. The Endowment will promptly refer all complaints to the agency designated by the Secretary of HHS to manage the mediation process that...
A Bifactor Approach to Model Multifaceted Constructs in Statistical Mediation Analysis

ERIC Educational Resources Information Center

Gonzalez, Oscar; MacKinnon, David P.

2018-01-01

Statistical mediation analysis allows researchers to identify the most important mediating constructs in the causal process studied. Identifying specific mediators is especially relevant when the hypothesized mediating construct consists of multiple related facets. The general definition of the construct and its facets might relate differently to…
29 CFR 1403.4 - Assignment of mediators.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Assignment of mediators. 1403.4 Section 1403.4 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE FUNCTIONS AND DUTIES § 1403.4 Assignment of mediators. The Federal Service will assign one or more mediators to each labor...
Tests of Mediation: Paradoxical Decline in Statistical Power as a Function of Mediator Collinearity

ERIC Educational Resources Information Center

Beasley, T. Mark

2014-01-01

Increasing the correlation between the independent variable and the mediator ("a" coefficient) increases the effect size ("ab") for mediation analysis; however, increasing a by definition increases collinearity in mediation models. As a result, the standard error of product tests increase. The variance inflation caused by…
Surveying Parental Mediation: Connections, Challenges and Questions for Media Literacy

ERIC Educational Resources Information Center

Mendoza, Kelly

2009-01-01

This paper examines three strategies of parental mediation--coviewing, restrictive mediation, and active mediation--in order to make connections, challenge, and raise questions for media literacy. Coviewing, whether it is intentional practice, or whether it functions to promote media literacy, is explored. Restrictive mediation, how it connects to…
The art of the chart note in clinical ethics consultation and bioethics mediation: conveying information that can be understood and evaluated.

PubMed

Dubler, Nancy Neveloff

2013-01-01

Unlike bioethics mediators who are employed by healthcare organizations as outside consultants, mediators who are embedded in an institution must be authorized to chronicle a clinical ethics consultation (CEC) or a mediation in a patient's medical chart. This is an important privilege, as the chart is a legal document. In this article I discuss this important part of a bioethics mediator's tool kit in my presentation of a case illustrating how bioethics mediation may proceed, and what this approach using both bioethics and mediation may add.
Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros

PubMed Central

Valeri, Linda; VanderWeele, Tyler J.

2012-01-01

Mediation analysis is a useful and widely employed approach to studies in the field of psychology and in the social and biomedical sciences. The contributions of this paper are several-fold. First we seek to bring the developments in mediation analysis for non linear models within the counterfactual framework to the psychology audience in an accessible format and compare the sorts of inferences about mediation that are possible in the presence of exposure-mediator interaction when using a counterfactual versus the standard statistical approach. Second, the work by VanderWeele and Vansteelandt (2009, 2010) is extended here to allow for dichotomous mediators and count outcomes. Third, we provide SAS and SPSS macros to implement all of these mediation analysis techniques automatically and we compare the types of inferences about mediation that are allowed by a variety of software macros. PMID:23379553
Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros.

PubMed

Valeri, Linda; Vanderweele, Tyler J

2013-06-01

Mediation analysis is a useful and widely employed approach to studies in the field of psychology and in the social and biomedical sciences. The contributions of this article are several-fold. First we seek to bring the developments in mediation analysis for nonlinear models within the counterfactual framework to the psychology audience in an accessible format and compare the sorts of inferences about mediation that are possible in the presence of exposure-mediator interaction when using a counterfactual versus the standard statistical approach. Second, the work by VanderWeele and Vansteelandt (2009, 2010) is extended here to allow for dichotomous mediators and count outcomes. Third, we provide SAS and SPSS macros to implement all of these mediation analysis techniques automatically, and we compare the types of inferences about mediation that are allowed by a variety of software macros. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
Cognitive mediation of clinical improvement after intensive exposure therapy of agoraphobia and social phobia.

PubMed

Vögele, Claus; Ehlers, Anke; Meyer, Andrea H; Frank, Monika; Hahlweg, Kurt; Margraf, Jürgen

2010-03-01

The present study investigated cognitive mediation of clinical improvement in patients with agoraphobia (N=427) or social phobia (N=98) receiving high-density exposure therapy in a naturalistic clinical treatment setting. Patients were assessed before therapy, 6 weeks after the end of therapy, and 1 year thereafter, using a self-report assessment battery. Lower level mediation analyses provided support for the notion that cognitive changes partially mediate clinical improvement after exposure therapy. Changes in cognitions relating to physical catastrophes mediated treatment outcome only for patients with agoraphobia, whereas changes in cognitions about loss of control mediated outcome for both agoraphobia and social phobia patients. Changes in relationship satisfaction did not mediate symptomatic improvement. The results extend previous findings by demonstrating mediation in an unselected clinical sample and by providing evidence for the specificity of mediation effects. They further support the importance of cognitive changes in cognitive-behavior therapy. (c) 2009 Wiley-Liss, Inc.
A Tutorial in Bayesian Potential Outcomes Mediation Analysis.

PubMed

Miočević, Milica; Gonzalez, Oscar; Valente, Matthew J; MacKinnon, David P

2018-01-01

Statistical mediation analysis is used to investigate intermediate variables in the relation between independent and dependent variables. Causal interpretation of mediation analyses is challenging because randomization of subjects to levels of the independent variable does not rule out the possibility of unmeasured confounders of the mediator to outcome relation. Furthermore, commonly used frequentist methods for mediation analysis compute the probability of the data given the null hypothesis, which is not the probability of a hypothesis given the data as in Bayesian analysis. Under certain assumptions, applying the potential outcomes framework to mediation analysis allows for the computation of causal effects, and statistical mediation in the Bayesian framework gives indirect effects probabilistic interpretations. This tutorial combines causal inference and Bayesian methods for mediation analysis so the indirect and direct effects have both causal and probabilistic interpretations. Steps in Bayesian causal mediation analysis are shown in the application to an empirical example.
Best (but oft-forgotten) practices: mediation analysis.

PubMed

Fairchild, Amanda J; McDaniel, Heather L

2017-06-01

This contribution in the "Best (but Oft-Forgotten) Practices" series considers mediation analysis. A mediator (sometimes referred to as an intermediate variable, surrogate endpoint, or intermediate endpoint) is a third variable that explains how or why ≥2 other variables relate in a putative causal pathway. The current article discusses mediation analysis with the ultimate intention of helping nutrition researchers to clarify the rationale for examining mediation, avoid common pitfalls when using the model, and conduct well-informed analyses that can contribute to improving causal inference in evaluations of underlying mechanisms of effects on nutrition-related behavioral and health outcomes. We give specific attention to underevaluated limitations inherent in common approaches to mediation. In addition, we discuss how to conduct a power analysis for mediation models and offer an applied example to demonstrate mediation analysis. Finally, we provide an example write-up of mediation analysis results as a model for applied researchers. © 2017 American Society for Nutrition.
Best (but oft-forgotten) practices: mediation analysis12

PubMed Central

McDaniel, Heather L

2017-01-01

This contribution in the “Best (but Oft-Forgotten) Practices” series considers mediation analysis. A mediator (sometimes referred to as an intermediate variable, surrogate endpoint, or intermediate endpoint) is a third variable that explains how or why ≥2 other variables relate in a putative causal pathway. The current article discusses mediation analysis with the ultimate intention of helping nutrition researchers to clarify the rationale for examining mediation, avoid common pitfalls when using the model, and conduct well-informed analyses that can contribute to improving causal inference in evaluations of underlying mechanisms of effects on nutrition-related behavioral and health outcomes. We give specific attention to underevaluated limitations inherent in common approaches to mediation. In addition, we discuss how to conduct a power analysis for mediation models and offer an applied example to demonstrate mediation analysis. Finally, we provide an example write-up of mediation analysis results as a model for applied researchers. PMID:28446497
Cross-Sectional Analysis of Longitudinal Mediation Processes.

PubMed

O'Laughlin, Kristine D; Martin, Monica J; Ferrer, Emilio

2018-01-01

Statistical mediation analysis can help to identify and explain the mechanisms behind psychological processes. Examining a set of variables for mediation effects is a ubiquitous process in the social sciences literature; however, despite evidence suggesting that cross-sectional data can misrepresent the mediation of longitudinal processes, cross-sectional analyses continue to be used in this manner. Alternative longitudinal mediation models, including those rooted in a structural equation modeling framework (cross-lagged panel, latent growth curve, and latent difference score models) are currently available and may provide a better representation of mediation processes for longitudinal data. The purpose of this paper is twofold: first, we provide a comparison of cross-sectional and longitudinal mediation models; second, we advocate using models to evaluate mediation effects that capture the temporal sequence of the process under study. Two separate empirical examples are presented to illustrate differences in the conclusions drawn from cross-sectional and longitudinal mediation analyses. Findings from these examples yielded substantial differences in interpretations between the cross-sectional and longitudinal mediation models considered here. Based on these observations, researchers should use caution when attempting to use cross-sectional data in place of longitudinal data for mediation analyses.
Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

PubMed

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.
Causal mediation analysis for longitudinal data with exogenous exposure.

PubMed

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

2016-01-01

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

PubMed

Bergman, Edward J

2013-01-01

This article describes, analyzes, and advocates for management of clinical healthcare conflict by a process commonly referred to as bioethics mediation. Section I provides a brief introduction to classical mediation outside the realm of clinical healthcare. Section II highlights certain distinguishing characteristics of bioethics mediation. Section III chronicles the history of bioethics mediation and references a number of seminal writings on the subject. Finally, Section IV analyzes barriers that have, thus far, limited the widespread implementation of bioethics mediation.
Practical Guidance for Conducting Mediation Analysis With Multiple Mediators Using Inverse Odds Ratio Weighting

PubMed Central

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 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. PMID:25693776
Assessing mediation using marginal structural models in the presence of confounding and moderation

PubMed Central

Coffman, Donna L.; Zhong, Wei

2012-01-01

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

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

PubMed

Coffman, Donna L; Zhong, Wei

2012-12-01

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

ERIC Educational Resources Information Center

Hendry, Richard

2010-01-01

This article explores the developing role of mediation as a conflict resolution process in schools. It gives an accepted definition and clarifies the purposes of mediation, outlining the range of contexts in and beyond schools in which mediation is already offered as a formal intervention. The typical process of mediation itself is described. The…
36 CFR 251.103 - Mediation of term grazing permit disputes.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Mediation of term grazing... Lands § 251.103 Mediation of term grazing permit disputes. (a) Decisions subject to mediation. In those States with Department of Agriculture certified mediation programs, any holder of a term grazing permit...
12 CFR 617.7430 - Are institutions required to participate in state agricultural loan mediation programs?

Code of Federal Regulations, 2010 CFR

2010-01-01

... state agricultural loan mediation programs? 617.7430 Section 617.7430 Banks and Banking FARM CREDIT... Mediation Programs § 617.7430 Are institutions required to participate in state agricultural loan mediation programs? (a) If initiated by a borrower, System institutions must participate in state mediation programs...
15 CFR 930.44 - Availability of mediation for disputes concerning proposed activities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Availability of mediation for disputes... PROGRAMS Consistency for Federal Agency Activities § 930.44 Availability of mediation for disputes..., either party may request the Secretarial mediation or OCRM mediation services provided for in subpart G. ...
10 CFR 1040.89-6 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Mediation. 1040.89-6 Section 1040.89-6 Energy DEPARTMENT... Enforcement Procedures § 1040.89-6 Mediation. (a) Referral of complaints for mediation. DOE will refer to the Federal Mediation and Conciliation Service, in accordance with 45 CFR 90.43(c)(3), all complaints that: (1...
15 CFR 930.99 - Availability of mediation for federal assistance disputes.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Availability of mediation for federal... Consistency for Federal Assistance to State and Local Governments § 930.99 Availability of mediation for... party may request the OCRM mediation or Secretarial mediation services provided for in subpart G of this...
29 CFR 1425.6 - Use of third-party mediation assistance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Use of third-party mediation assistance. 1425.6 Section 1425.6 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE MEDIATION ASSISTANCE IN THE FEDERAL SERVICE § 1425.6 Use of third-party mediation assistance. If the parties...
Pure Mediated Priming: A Retrospective Semantic Matching Model

ERIC Educational Resources Information Center

Jones, Lara L.

2010-01-01

Mediated priming refers to the activation of a target (e.g., "stripes") by a prime (e.g., "lion") that is related indirectly via a connecting mediator (e.g., tiger). In previous mediated priming studies (e.g., McNamara & Altarriba, 1988), the mediator was associatively related to the prime. In contrast, pure mediated…
Assessing Mediation Using Marginal Structural Models in the Presence of Confounding and Moderation

ERIC Educational Resources Information Center

Coffman, Donna L.; Zhong, Wei

2012-01-01

This article presents marginal structural models with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW…
Parental mediation and cyberbullying - a longitudinal study.

PubMed

Chng, Grace S; Liau, Albert; Khoo, Angeline; Li, Dongdong

2014-01-01

Parents use active and restrictive mediation strategies to guide and regulate children's online participation and the online risks they encounter. However, changes in parental mediation do occur over time and the effectiveness of these strategies on cyberbullying demands for further empirical investigation. The current study addresses these issues with a sample of 1084 students (49% girls) in a longitudinal, three-wave design. Gender differences were tested via multi-group analyses. Longitudinal growth models showed that parental use of both active and restrictive mediation decreased over time. For both types of mediation, the mean rate of change had a significant effect on boys' engagement in cyberbullying, but not for girls. Initial levels of restrictive mediation, but not active mediation, were found to be significantly predictive of cyberbullying in both genders. Girls had higher initial levels of both parental mediation types in comparison to boys. The results reveal that the effectiveness of active and restrictive mediation in relation to students' cyberbullying differs and informs us on gender differences. The implications of these results for parental education in online mediation are discussed.
Causal Models for Mediation Analysis: An Introduction to Structural Mean Models.

PubMed

Zheng, Cheng; Atkins, David C; Zhou, Xiao-Hua; Rhew, Isaac C

2015-01-01

Mediation analyses are critical to understanding why behavioral interventions work. To yield a causal interpretation, common mediation approaches must make an assumption of "sequential ignorability." The current article describes an alternative approach to causal mediation called structural mean models (SMMs). A specific SMM called a rank-preserving model (RPM) is introduced in the context of an applied example. Particular attention is given to the assumptions of both approaches to mediation. Applying both mediation approaches to the college student drinking data yield notable differences in the magnitude of effects. Simulated examples reveal instances in which the traditional approach can yield strongly biased results, whereas the RPM approach remains unbiased in these cases. At the same time, the RPM approach has its own assumptions that must be met for correct inference, such as the existence of a covariate that strongly moderates the effect of the intervention on the mediator and no unmeasured confounders that also serve as a moderator of the effect of the intervention or the mediator on the outcome. The RPM approach to mediation offers an alternative way to perform mediation analysis when there may be unmeasured confounders.
Siblings' mediated learning strategies in families with and without children with intellectual disabilities.

PubMed

Tzuriel, David; Hanuka-Levy, Dikla

2014-11-01

Dyads of siblings in which the younger sibling had an intellectual disability (ID, n = 25) were videotaped interacting. The ID group was compared with typically developing sibling dyads matched on mental age (n = 25) and chronological age (n = 25). We observed the mediation strategies, activation, and antimediation behaviors of older siblings and younger siblings' responsiveness to mediation. Mediation strategies were analyzed by the Observation of Mediation Interaction scale. The ID group scored highest on mediation strategies and lowest on activation and antimediation behaviors. Younger siblings' responsiveness to mediation was highest among the ID group. Mediation for Intentionality and Reciprocity and Meaning were positively associated with the verbal responsiveness of the younger siblings. Activation and antimediation behaviors were negatively associated with the verbal responsiveness.
What works in school-based energy balance behaviour interventions and what does not? A systematic review of mediating mechanisms.

PubMed

van Stralen, M M; Yildirim, M; te Velde, S J; Brug, J; van Mechelen, W; Chinapaw, M J M

2011-10-01

Obesity prevention requires effective interventions targeting the so-called energy balance-related behaviours (that is, physical activity, sedentary and dietary behaviours). To improve (cost-)effectiveness of these interventions, one needs to know the working mechanisms underlying behavioural change. Mediation analyses evaluates whether an intervention works via hypothesised working mechanisms. Identifying mediators can prompt intervention developers to strengthen effective intervention components and remove/adapt ineffective components. This systematic review aims to identify psychosocial and environmental mediators of energy balance-related behaviours interventions for youth. Studies were identified by a systematic search of electronic databases (PubMed, Embase, PsycINFO, ERIC and SPORTDiscus). Studies were included if they (1) were school-based randomised controlled or quasi-experimental studies; (2) targeted energy balance behaviours; (3) conducted among children and adolescents (4-18 years of age); (4) written in English; and (5) conducted mediation analyses. A total of 24 studies were included. We found strong evidence for self-efficacy and moderate evidence for intention as mediators of physical activity interventions. Indications were found for attitude, knowledge and habit strength to be mediators of dietary behaviour interventions. The few sedentary behaviour interventions reporting on mediating effects prevented us from forming strong conclusions regarding mediators of sedentary behaviour interventions. The majority of interventions failed to significantly change hypothesised mediators because of ineffective intervention strategies, low power and/or use of insensitive measures. Despite its importance, few studies published results of mediation analysis, and more high-quality research into relevant mediators is necessary. On the basis of the limited number of published studies, self-efficacy and intention appear to be relevant mediators for physical activity interventions. Future intervention developers are advised to provide information on the theoretical base of their intervention including the strategies applied to provide insight into which strategies are effective in changing relevant mediators. In addition, future research is advised to focus on the development, validity, reliability and sensitivity of mediator measures.
What works in school-based energy balance behaviour interventions and what does not? A systematic review of mediating mechanisms

PubMed Central

van Stralen, M M; Yildirim, M; Velde, SJ te; Brug, J; van Mechelen, W; Chinapaw, M J M

2011-01-01

Objective: Obesity prevention requires effective interventions targeting the so-called energy balance-related behaviours (that is, physical activity, sedentary and dietary behaviours). To improve (cost-)effectiveness of these interventions, one needs to know the working mechanisms underlying behavioural change. Mediation analyses evaluates whether an intervention works via hypothesised working mechanisms. Identifying mediators can prompt intervention developers to strengthen effective intervention components and remove/adapt ineffective components. This systematic review aims to identify psychosocial and environmental mediators of energy balance-related behaviours interventions for youth. Method: Studies were identified by a systematic search of electronic databases (Pubmed, Embase, PsycINFO, ERIC and SPORTDiscus). Studies were included if they (1) were school-based randomised controlled or quasi-experimental studies; (2) targeted energy balance behaviours; (3) conducted among children and adolescents (4–18 years of age); (4) written in English; and (5) conducted mediation analyses. Results: A total of 24 studies were included. We found strong evidence for self-efficacy and moderate evidence for intention as mediators of physical activity interventions. Indications were found for attitude, knowledge and habit strength to be mediators of dietary behaviour interventions. The few sedentary behaviour interventions reporting on mediating effects prevented us from forming strong conclusions regarding mediators of sedentary behaviour interventions. The majority of interventions failed to significantly change hypothesised mediators because of ineffective intervention strategies, low power and/or use of insensitive measures. Conclusion: Despite its importance, few studies published results of mediation analysis, and more high-quality research into relevant mediators is necessary. On the basis of the limited number of published studies, self-efficacy and intention appear to be relevant mediators for physical activity interventions. Future intervention developers are advised to provide information on the theoretical base of their intervention including the strategies applied to provide insight into which strategies are effective in changing relevant mediators. In addition, future research is advised to focus on the development, validity, reliability and sensitivity of mediator measures. PMID:21487398
Virus Infection and Death Receptor-Mediated Apoptosis.

PubMed

Zhou, Xingchen; Jiang, Wenbo; Liu, Zhongshun; Liu, Shuai; Liang, Xiaozhen

2017-10-27

Virus infection can trigger extrinsic apoptosis. Cell-surface death receptors of the tumor necrosis factor family mediate this process. They either assist persistent viral infection or elicit the elimination of infected cells by the host. Death receptor-mediated apoptosis plays an important role in viral pathogenesis and the host antiviral response. Many viruses have acquired the capability to subvert death receptor-mediated apoptosis and evade the host immune response, mainly by virally encoded gene products that suppress death receptor-mediated apoptosis. In this review, we summarize the current information on virus infection and death receptor-mediated apoptosis, particularly focusing on the viral proteins that modulate death receptor-mediated apoptosis.
Virus Infection and Death Receptor-Mediated Apoptosis

PubMed Central

Zhou, Xingchen; Jiang, Wenbo; Liu, Zhongshun; Liu, Shuai; Liang, Xiaozhen

2017-01-01

Virus infection can trigger extrinsic apoptosis. Cell-surface death receptors of the tumor necrosis factor family mediate this process. They either assist persistent viral infection or elicit the elimination of infected cells by the host. Death receptor-mediated apoptosis plays an important role in viral pathogenesis and the host antiviral response. Many viruses have acquired the capability to subvert death receptor-mediated apoptosis and evade the host immune response, mainly by virally encoded gene products that suppress death receptor-mediated apoptosis. In this review, we summarize the current information on virus infection and death receptor-mediated apoptosis, particularly focusing on the viral proteins that modulate death receptor-mediated apoptosis. PMID:29077026
Elder mediation in theory and practice: study results from a national caregiver mediation demonstration project.

PubMed

Crampton, Alexandra

2013-01-01

Mediation is a process through which a third party facilitates discussion among disputing parties to help them identify interests and ideally reach an amicable solution. Elder mediation is a growing subspecialty to address conflicts involving older adults, primarily involving caregiving or finances. Mediation is theorized to empower participants but critics argue that it can exacerbate power imbalances among parties and coerce consensus. These contested claims are examined through study of a national caregiver mediation demonstration project. Study implications underscore the importance of gerontological social work expertise to ensure the empowerment of vulnerable older adults in mediation sessions.
Elder Mediation in Theory and Practice: Study Results From a National Caregiver Mediation Demonstration Project

PubMed Central

Crampton, Alexandra

2014-01-01

Mediation is a process through which a third party facilitates discussion among disputing parties to help them identify interests and ideally reach an amicable solution. Elder mediation is a growing subspecialty to address conflicts involving older adults, primarily involving caregiving or finances. Mediation is theorized to empower participants but critics argue that it can exacerbate power imbalances among parties and coerce consensus. These contested claims are examined through study of a national caregiver mediation demonstration project. Study implications underscore the importance of gerontological social work expertise to ensure the empowerment of vulnerable older adults in mediation sessions. PMID:23767767
Deflected mirage mediation: a phenomenological framework for generalized supersymmetry breaking.

PubMed

Everett, Lisa L; Kim, Ian-Woo; Ouyang, Peter; Zurek, Kathryn M

2008-09-05

We present a general phenomenological framework for dialing between gravity mediation, gauge mediation, and anomaly mediation. The approach is motivated from recent developments in moduli stabilization, which suggest that gravity mediated terms can be effectively loop suppressed and thus comparable to gauge and anomaly mediated terms. The gauginos exhibit a mirage unification behavior at a "deflected" scale, and gluinos are often the lightest colored sparticles. The approach provides a rich setting in which to explore generalized supersymmetry breaking at the CERN Large Hadron Collider.

[Parents' and Children's Perspectives of Parental Mediation Strategies in Association with Children's Internet Skills].

PubMed

Glüer, Michael; Lohaus, Arnold

2018-02-01

Parents' and Children's Perspectives of Parental Mediation Strategies in Association with Children's Internet Skills The purpose of this study was to examine the association of parental mediation strategies (from parents' and children's perspective) and children's internet skills. In total 194 parent-child dyads were questioned about their parent's mediation strategies. The children (fifth to ninth grade) additionally answered questions about their internet skills and the amount of time they spent daily on the internet. Parents' and children's ratings of the parental mediation strategies showed moderate associations. Parents reported to use more often mediation strategies than was perceived by their children. The mediation strategies had only limited value for the prediction of the children's internet skills. Parents' and children's perspective about restrictive content mediation were both negatively associated to children's internet skills. After controlling for children's age, sex and time spent daily on the internet, results showed that only congruencies between children's and parental perspectives regarding the parental restrictive content mediation were associated with decreased technical and social internet skills. Additionally, discrepancies between the children's and parental perspectives regarding the parental use of technical mediation were associated with decreased technical internet skills. Discrepancies regarding the parental mediation strategy monitoring were related to increased information navigation skills.
Rumination mediates the relationship between overgeneral autobiographical memory and depression in patients with major depressive disorder.

PubMed

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

2017-03-21

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

PubMed

Appleyard, Karen; Yang, Chongming; Runyan, Desmond K

2010-05-01

The current study investigated concurrent and longitudinal mediated and mediated moderation pathways among maltreatment, self-perception (i.e., loneliness and self-esteem), social support, and internalizing and externalizing behavior problems. For both genders, early childhood maltreatment (i.e., ages 0-6) was related directly to internalizing and externalizing behavior problems at age 6, and later maltreatment (i.e., ages 6-8) was directly related to internalizing and externalizing behavior problems at age 8. Results of concurrent mediation and mediated moderation indicated that early maltreatment was significantly related to internalizing and externalizing behavior problems at age 6 indirectly both through age 6 loneliness and self-esteem for boys and through age 6 loneliness for girls. Significant moderation of the pathway from early maltreatment to self-esteem, and for boys, significant mediated moderation to emotional and behavioral problems were found, such that the mediated effect through self-esteem varied across levels of social support, though in an unexpected direction. No significant longitudinal mediation or mediated moderation was found, however, between the age 6 mediators and moderator and internalizing or externalizing problems at age 8. The roles of the hypothesized mediating and moderating mechanisms are discussed, with implications for designing intervention and prevention programs.
Delineating the Maladaptive Pathways of Child Maltreatment: A Mediated Moderation Analysis of the Roles of Self Perception and Social Support

PubMed Central

Appleyard, Karen; Yang, Chongming; Runyan, Desmond K.

2014-01-01

The current study investigated concurrent and longitudinal mediated and mediated moderation pathways among maltreatment, self perception (i.e., loneliness and self esteem), social support, and internalizing and externalizing behavior problems. For both genders, early childhood maltreatment (i.e., ages 0–6) was related directly to internalizing and externalizing behavior problems at age 6, and later maltreatment (i.e., ages 6–8) was directly related to internalizing and externalizing behavior problems at age 8. Results of concurrent mediation and mediated moderation indicated that early maltreatment was significantly related to internalizing and externalizing behavior problems at age 6 indirectly both through age 6 loneliness and self esteem for boys and through age 6 loneliness for girls. Significant moderation of the pathway from early maltreatment to self esteem, and, for boys, significant mediated moderation to emotional and behavioral problems were found, such that the mediated effect through self esteem varied across levels of social support, though in an unexpected direction. No significant longitudinal mediation or mediated moderation was found, however, between the age 6 mediators and moderator and internalizing or externalizing problems at age 8. The roles of the hypothesized mediating and moderating mechanisms are discussed, with implications for designing intervention and prevention programs. PMID:20423545
Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians

PubMed Central

Pierce, Brandon L.; Tong, Lin; Chen, Lin S.; Rahaman, Ronald; Argos, Maria; Jasmine, Farzana; Roy, Shantanu; Paul-Brutus, Rachelle; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Zaman, Rakibuz; Islam, Tariqul; Rahman, Mahfuzar; Baron, John A.; Kibriya, Muhammad G.; Ahsan, Habibul

2014-01-01

A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes (trans-eQTLs) and their biological mechanisms. In this work, we use genome-wide data on SNPs and array-based expression measures from mononuclear cells obtained from a population-based cohort of 1,799 Bangladeshi individuals to characterize cis- and trans-eQTLs and determine if observed trans-eQTL associations are mediated by expression of transcripts in cis with the SNPs showing trans-association, using Sobel tests of mediation. We observed 434 independent trans-eQTL associations at a false-discovery rate of 0.05, and 189 of these trans-eQTLs were also cis-eQTLs (enrichment P<0.0001). Among these 189 trans-eQTL associations, 39 were significantly attenuated after adjusting for a cis-mediator based on Sobel P<10-5. We attempted to replicate 21 of these mediation signals in two European cohorts, and while only 7 trans-eQTL associations were present in one or both cohorts, 6 showed evidence of cis-mediation. Analyses of simulated data show that complete mediation will be observed as partial mediation in the presence of mediator measurement error or imperfect LD between measured and causal variants. Our data demonstrates that trans-associations can become significantly stronger or switch directions after adjusting for a potential mediator. Using simulated data, we demonstrate that this phenomenon is expected in the presence of strong cis-trans confounding and when the measured cis-transcript is correlated with the true (unmeasured) mediator. In conclusion, by applying mediation analysis to eQTL data, we show that a substantial fraction of observed trans-eQTL associations can be explained by cis-mediation. Future studies should focus on understanding the mechanisms underlying widespread cis-mediation and their relevance to disease biology, as well as using mediation analysis to improve eQTL discovery. PMID:25474530
Parental Mediation of Children's Videogame Playing: A Comparison of the Reports by Parents and Children

ERIC Educational Resources Information Center

Nikken, Peter; Jansz, Jeroen

2006-01-01

Through an Internet survey of 536 parent-child dyads, the authors researched which mediation strategies parents used to regulate videogaming by their children (8-18 years). Factor analyses revealed that both parents and children distinguished three types of parental mediation: (1) "restrictive mediation", (2) "active mediation", and (3)…
Bias in Cross-Sectional Analyses of Longitudinal Mediation: Partial and Complete Mediation under an Autoregressive Model

ERIC Educational Resources Information Center

Maxwell, Scott E.; Cole, David A.; Mitchell, Melissa A.

2011-01-01

Maxwell and Cole (2007) showed that cross-sectional approaches to mediation typically generate substantially biased estimates of longitudinal parameters in the special case of complete mediation. However, their results did not apply to the more typical case of partial mediation. We extend their previous work by showing that substantial bias can…
Mediator binding to UASs is broadly uncoupled from transcription and cooperative with TFIID recruitment to promoters.

PubMed

Grünberg, Sebastian; Henikoff, Steven; Hahn, Steven; Zentner, Gabriel E

2016-11-15

Mediator is a conserved, essential transcriptional coactivator complex, but its in vivo functions have remained unclear due to conflicting data regarding its genome-wide binding pattern obtained by genome-wide ChIP Here, we used ChEC-seq, a method orthogonal to ChIP, to generate a high-resolution map of Mediator binding to the yeast genome. We find that Mediator associates with upstream activating sequences (UASs) rather than the core promoter or gene body under all conditions tested. Mediator occupancy is surprisingly correlated with transcription levels at only a small fraction of genes. Using the same approach to map TFIID, we find that TFIID is associated with both TFIID- and SAGA-dependent genes and that TFIID and Mediator occupancy is cooperative. Our results clarify Mediator recruitment and binding to the genome, showing that Mediator binding to UASs is widespread, partially uncoupled from transcription, and mediated in part by TFIID. © 2016 The Authors.
Does mediator use contribute to the spacing effect for cued recall? Critical tests of the mediator hypothesis.

PubMed

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.
Mediator structure and rearrangements required for holoenzyme formation.

PubMed

Tsai, Kuang-Lei; Yu, Xiaodi; Gopalan, Sneha; Chao, Ti-Chun; Zhang, Ying; Florens, Laurence; Washburn, Michael P; Murakami, Kenji; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

2017-04-13

The conserved Mediator co-activator complex has an essential role in the regulation of RNA polymerase II transcription in all eukaryotes. Understanding the structure and interactions of Mediator is crucial for determining how the complex influences transcription initiation and conveys regulatory information to the basal transcription machinery. Here we present a 4.4 Å resolution cryo-electron microscopy map of Schizosaccharomyces pombe Mediator in which conserved Mediator subunits are individually resolved. The essential Med14 subunit works as a central backbone that connects the Mediator head, middle and tail modules. Comparison with a 7.8 Å resolution cryo-electron microscopy map of a Mediator-RNA polymerase II holoenzyme reveals that changes in the structure of Med14 facilitate a large-scale Mediator rearrangement that is essential for holoenzyme formation. Our study suggests that access to different conformations and crosstalk between structural elements are essential for the Mediator regulation mechanism, and could explain the capacity of the complex to integrate multiple regulatory signals.
Predicting the decision to pursue mediation in civil disputes: a hierarchical classes analysis.

PubMed

Reich, Warren A; Kressel, Kenneth; Scanlon, Kathleen M; Weiner, Gary A

2007-11-01

Clients (N = 185) involved in civil court cases completed the CPR Institute's Mediation Screen, which is designed to assist in making a decision about pursuing mediation. The authors modeled data using hierarchical classes analysis (HICLAS), a clustering algorithm that places clients into 1 set of classes and CPRMS items into another set of classes. HICLAS then links the sets of classes so that any class of clients can be identified in terms of the classes of items they endorsed. HICLAS-derived item classes reflected 2 underlying themes: (a) suitability of the dispute for a problem-solving process and (b) potential benefits of mediation. All clients who perceived that mediation would be beneficial also believed that the context of their conflict was favorable to mediation; however, not all clients who saw a favorable context believed they would benefit from mediation. The majority of clients who agreed to pursue mediation endorsed items reflecting both contextual suitability and perceived benefits of mediation.
Causal mediation analysis with a binary outcome and multiple continuous or ordinal mediators: Simulations and application to an alcohol intervention.

PubMed

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.
Peer victimization as a mediator of the relationship between disability status and psychosocial distress.

PubMed

McGee, Marjorie G

2015-04-01

Youth with disabilities experience greater levels of peer victimization and psychosocial distress than non-disabled youth. However, the extent to which exposure to peer victimization mediates the relationship between disability status and psychosocial distress is unknown. To determine whether the relationship between disability status and psychological distress was mediated by exposure to peer victimization, and if so, whether the mediation effects of peer victimization on psychosocial distress was moderated by sex. This cross-sectional study involved a series of regressions to test for mediation and moderated mediation using complex survey data from 6664 Oregon 11th graders. Peer victimization partially mediated the relationship between disability status and psychosocial distress. Sex, however, did not significantly moderate the mediating effects of peer victimization on psychosocial distress. Exposure to peer victimization mediated the relationship between disability status and psychosocial distress; there was little support for sex as a moderator. Copyright © 2015 Elsevier Inc. All rights reserved.
[Adolescent Use of Digital Media and Parental Mediation - A Research Review].

PubMed

Pfetsch, Jan

2018-02-01

Adolescent Use of Digital Media and Parental Mediation - A Research Review Digital media are wide spread, frequently used, and highly relevant in the lives of children, adolescents and their parents. Because parents aim to reduce or prevent potential risks of media use for their children, many parents apply different strategies of parental mediation of children's media use: restrictive parental mediation, active parental mediation, co-media use, technical monitoring, and participatory learning. These forms of parental mediation have differential impact on children and adolescents. Different types of media (e. g. television, video games, internet, and mobile phones) have common features but also specific characteristics that lead to partially inconsistent research findings that are not only due to age differences of children and adolescents. Concerning an impact model of parental mediation, the current contribution presents overarching and divergent empirical findings, approaches the effectiveness of parental mediation for cyberbullying, and discusses practical implications as well as research gaps in the analysis of parental mediation.
The Mediator Complex and Transcription Elongation

PubMed Central

Conaway, Ronald C.; Conaway, Joan Weliky

2013-01-01

Background Mediator is an evolutionarily conserved multisubunit RNA polymerase II (Pol II) coregulatory complex. Although Mediator was initially found to play a critical role in regulation of the initiation of Pol II transcription, recent studies have brought to light an expanded role for Mediator at post-initiation stages of transcription. Scope of review We provide a brief description of the structure of Mediator and its function in the regulation of Pol II transcription initiation, and we summarize recent findings implicating Mediator in the regulation of various stages of Pol II transcription elongation. Major conclusions Emerging evidence is revealing new roles for Mediator in nearly all stages of Pol II transcription, including initiation, promoter escape, elongation, pre-mRNA processing, and termination. General significance Mediator plays a central role in the regulation of gene expression by impacting nearly all stages of mRNA synthesis. PMID:22983086
Mediators of the effects on fatigue of pragmatic rehabilitation for chronic fatigue syndrome.

PubMed

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.
Learning the names of people: the role of image mediators.

PubMed

Groninger, L D; Groninger, D H; Stiens, J

1995-06-01

Four experiments are reported involving the effects of bizarre and common imagery mediation techniques on the learning and 1-week retention of surnames, given videotaped faces as cues. The videotapes contained 24 undergraduates who were photographed from about the chest up, and who introduced themselves at a 20-second rate. Experiment 1 showed that for both concrete and abstract names, immediate recall of the list was better under imagery mediation instructions than under control instructions. Experiment 2 studied the same conditions using immediate recognition memory of the list as a retrieval measure for the names, and found, despite ceiling effects, that bizarre imagery instructions facilitated recognition for concrete names. Experiment 3 showed that immediate recall could be improved if subjects were given an image mediator for every face-name pair as opposed to generating their own image mediators. Experiment 4 yielded three important findings: (a) 84% of the variance in the 1-week retention of initially recalled names was explained by the presence of absence of the original mediator during 1-week recall; (b) instructions to form image mediators facilitate recall not because image mediators are more effective than other types of mediators, but because they increase the likelihood that a mediator will be formed; (c) 1-week retention could be enhanced with an increased focus during encoding on the points where the mediation process is most likely to fail. The results of these studies are discussed within the context of mediation model wherein recall can fail at any of four stages.
Estimation of indirect effect when the mediator is a censored variable.

PubMed

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.
Code-Switching: L1-Coded Mediation in a Kindergarten Foreign Language Classroom

ERIC Educational Resources Information Center

Lin, Zheng

2012-01-01

This paper is based on a qualitative inquiry that investigated the role of teachers' mediation in three different modes of coding in a kindergarten foreign language classroom in China (i.e. L2-coded intralinguistic mediation, L1-coded cross-lingual mediation, and L2-and-L1-mixed mediation). Through an exploratory examination of the varying effects…
29 CFR 37.89 - May the Director offer the parties to a complaint the option of mediation?

Code of Federal Regulations, 2010 CFR

2010-07-01

... of mediation? 37.89 Section 37.89 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE... Procedures § 37.89 May the Director offer the parties to a complaint the option of mediation? Yes. The..., the following rules apply: (a) Mediation is voluntary; the parties must consent before the mediation...

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

PubMed Central

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

2016-01-01

Mediation analysis requires a number of strong assumptions be met in order to make valid causal inferences. Failing to account for violations of these assumptions, such as not modeling measurement error or omitting a common cause of the effects in the model, can bias the parameter estimates of the mediated effect. When the independent variable is perfectly reliable, for example when participants are randomly assigned to levels of treatment, measurement error in the mediator tends to underestimate the mediated effect, while the omission of a confounding variable of the mediator to outcome relation tends to overestimate the mediated effect. Violations of these two assumptions often co-occur, however, in which case the mediated effect could be overestimated, underestimated, or even, in very rare circumstances, unbiased. In order to explore the combined effect of measurement error and omitted confounders in the same model, the impact of each violation on the single-mediator model is first examined individually. Then the combined effect of having measurement error and omitted confounders in the same model is discussed. Throughout, an empirical example is provided to illustrate the effect of violating these assumptions on the mediated effect. PMID:27739903
Med5(Nut1) and Med17(Srb4) Are Direct Targets of Mediator Histone H4 Tail Interactions

PubMed Central

Liu, Zhongle; Myers, Lawrence C.

2012-01-01

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. In addition to its canonical role in transcriptional activation, recent studies have demonstrated that S. cerevisiae Mediator can interact directly with nucleosomes, and their histone tails. Mutations in Mediator subunits have shown that Mediator and certain chromatin structures mutually impact each other structurally and functionally in vivo. We have taken a UV photo cross-linking approach to further delineate the molecular basis of Mediator chromatin interactions and help determine whether the impact of certain Mediator mutants on chromatin is direct. Specifically, by using histone tail peptides substituted with an amino acid analog that is a UV activatible crosslinker, we have identified specific subunits within Mediator that participate in histone tail interactions. Using Mediator purified from mutant yeast strains we have evaluated the impact of these subunits on histone tail binding. This analysis has identified the Med5 subunit of Mediator as a target for histone tail interactions and suggests that the previously observed effect of med5 mutations on telomeric heterochromatin and silencing is direct. PMID:22693636
Identification and Sensitivity Analysis for Average Causal Mediation Effects with Time-Varying Treatments and Mediators: Investigating the Underlying Mechanisms of Kindergarten Retention Policy.

PubMed

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

2018-06-01

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

PubMed

Soutourina, Julie

2018-04-01

Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.
Mediator binds to boundaries of chromosomal interaction domains and to proteins involved in DNA looping, RNA metabolism, chromatin remodeling, and actin assembly

PubMed Central

Chereji, Răzvan V.; Bharatula, Vasudha; Elfving, Nils; Blomberg, Jeanette; Larsson, Miriam; Morozov, Alexandre V.; Broach, James R.

2017-01-01

Abstract Mediator is a multi-unit molecular complex that plays a key role in transferring signals from transcriptional regulators to RNA polymerase II in eukaryotes. We have combined biochemical purification of the Saccharomyces cerevisiae Mediator from chromatin with chromatin immunoprecipitation in order to reveal Mediator occupancy on DNA genome-wide, and to identify proteins interacting specifically with Mediator on the chromatin template. Tandem mass spectrometry of proteins in immunoprecipitates of mediator complexes revealed specific interactions between Mediator and the RSC, Arp2/Arp3, CPF, CF 1A and Lsm complexes in chromatin. These factors are primarily involved in chromatin remodeling, actin assembly, mRNA 3′-end processing, gene looping and mRNA decay, but they have also been shown to enter the nucleus and participate in Pol II transcription. Moreover, we have found that Mediator, in addition to binding Pol II promoters, occupies chromosomal interacting domain (CID) boundaries and that Mediator in chromatin associates with proteins that have been shown to interact with CID boundaries, such as Sth1, Ssu72 and histone H4. This suggests that Mediator plays a significant role in higher-order genome organization. PMID:28575439
Causal mediation analysis with a latent mediator.

PubMed

Albert, Jeffrey M; Geng, Cuiyu; Nelson, Suchitra

2016-05-01

Health researchers are often interested in assessing the direct effect of a treatment or exposure on an outcome variable, as well as its indirect (or mediation) effect through an intermediate variable (or mediator). For an outcome following a nonlinear model, the mediation formula may be used to estimate causally interpretable mediation effects. This method, like others, assumes that the mediator is observed. However, as is common in structural equations modeling, we may wish to consider a latent (unobserved) mediator. We follow a potential outcomes framework and assume a generalized structural equations model (GSEM). We provide maximum-likelihood estimation of GSEM parameters using an approximate Monte Carlo EM algorithm, coupled with a mediation formula approach to estimate natural direct and indirect effects. The method relies on an untestable sequential ignorability assumption; we assess robustness to this assumption by adapting a recently proposed method for sensitivity analysis. Simulation studies show good properties of the proposed estimators in plausible scenarios. Our method is applied to a study of the effect of mother education on occurrence of adolescent dental caries, in which we examine possible mediation through latent oral health behavior. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Nitroglycerin mediated dilation evaluated by ultrasound is associated with sTWEAK in hemodialysis patients.

PubMed

Rusu, Crina Claudia; Ghervan, Liviu; Racasan, Simona; Kacsa, Ina; Moldovan, Diana; Potra, Alina; Bondor, Cosmina; Anton, Florin; Patiu, Ioan Mihai; Caprioara, Mirela Gherman

2016-03-01

The main cause of death in hemodialysis (HD) patients is cardiovascular disease. Ultrasound assessment of the brachial artery dysfunction is easily achievable and can non-invasively detect atherosclerosis in various stages. In HD patients the cardiovascular risk profile is different and the determinants of brachial arterial function can be distinct comparing with general population. The aim of the study is to assess the determinants of arterial brachial function (flow-mediated and nitroglycerin-mediated dilation) evaluated by ultrasound in HD patients and their relation with tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) described as atherosclerotic marker in chronic kidney disease patients. We conducted a cross-sectional observational study on 54 hemodialysis patients. We recorded clinical and biological data and we measured sTWEAK serum levels by ELISA. We evaluated the arterial brachial function by measurement of flow-mediated and nitroglycerin-mediated dilation, using B mode ultrasound. The determinants of flow-mediated dilation were: Kt/V (r=0.47, p<0.001), LDL-cholesterol (r=0.29, p=0.04), and total cholesterol (r=0.31, p=0.02). Flow-mediated dilation correlated with nitroglycerin-mediated dilation (r=0.70, p<0.001). In multivariate analysis kt/V was the only significant predictor for flow-mediated dilation (p=0.04). Nitroglycerin-mediated dilation correlates with sTWEAK (r=-0.30, p=0.03), systolic blood pressure (r=-0.28, p=0.04) and pulse pressure (r=-0.31, p=0.02). In multivariate analysis sTWEAK was the only significant predictor for nitroglycerin-mediated dilation (p=0.04). The main determinant of nitroglycerin-mediated dilation was sTWEAK. In addition, decreased nitroglycerin-mediated dilation was associated with higher systolic blood pressure and pulse pressure. The main determinant of FMD was Kt/V. Increased flow-mediated dilation was associated with better dialysis efficiency and high total cholesterol and LDL-cholesterol.
Mediators of the relationship between maternal education and children's TV viewing.

PubMed

Hesketh, Kylie; Ball, Kylie; Crawford, David; Campbell, Karen; Salmon, Jo

2007-07-01

Maternal education is consistently found to be inversely related to children's television viewing and is associated with aspects of the family television environment. This study investigates whether family television environment mediates the relationship between maternal education and children's television viewing. Parents of 1484 children reported maternal education, time their child spends watching television, and 21 aspects of the family television environment (potential mediators) during 2002 and 2003. Separate regression analyses were conducted in 2006 for each potential mediator that met two initial conditions for mediation (associated with both maternal education and children's television viewing (p<0.10)), to assess whether inclusion reduced the association between maternal education and children's television viewing. Multivariable regression assessed the combined impact of all mediators. Twelve of 21 potential mediators met the initial conditions for mediation. Inclusion of each resulted in decreased beta values (3.2% to 15.2%) for the association between maternal education and television viewing. Number and placement of televisions in the home appeared to have the greatest mediating effect, followed by frequency of eating dinner in front of the television with the child and rules about television viewing during mealtimes. Together, the 12 mediators accounted for more than one-third of the association between maternal education and children's television viewing time. This study suggests the strong inverse relationship between maternal education and children's television viewing is partly mediated by aspects of the family television environment.
The four-principle formulation of common morality is at the core of bioethics mediation method.

PubMed

Ahmadi Nasab Emran, Shahram

2015-08-01

Bioethics mediation is increasingly used as a method in clinical ethics cases. My goal in this paper is to examine the implicit theoretical assumptions of the bioethics mediation method developed by Dubler and Liebman. According to them, the distinguishing feature of bioethics mediation is that the method is useful in most cases of clinical ethics in which conflict is the main issue, which implies that there is either no real ethical issue or if there were, they are not the key to finding a resolution. I question the tacit assumption of non-normativity of the mediation method in bioethics by examining the various senses in which bioethics mediation might be non-normative or neutral. The major normative assumption of the mediation method is the existence of common morality. In addition, the four-principle formulation of the theory articulated by Beauchamp and Childress implicitly provides the normative content for the method. Full acknowledgement of the theoretical and normative assumptions of bioethics mediation helps clinical ethicists better understand the nature of their job. In addition, the need for a robust philosophical background even in what appears to be a purely practical method of mediation cannot be overemphasized. Acknowledgement of the normative nature of bioethics mediation method necessitates a more critical attitude of the bioethics mediators towards the norms they usually take for granted uncritically as valid.
Assessing moderated mediation in linear models requires fewer confounding assumptions than assessing mediation.

PubMed

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

2016-11-01

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

PubMed Central

Poss, Zachary C.; Ebmeier, Christopher C.

2013-01-01

The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module. PMID:24088064
Applying causal mediation analysis to personality disorder research.

PubMed

Walters, Glenn D

2018-01-01

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

PubMed

Morgan-Lopez, Antonio A; MacKinnon, David P

2006-02-01

Mediated moderation occurs when the interaction between two variables affects a mediator, which then affects a dependent variable. In this article, we describe the mediated moderation model and evaluate it with a statistical simulation using an adaptation of product-of-coefficients methods to assess mediation. We also demonstrate the use of this method with a substantive example from the adolescent tobacco literature. In the simulation, relative bias (RB) in point estimates and standard errors did not exceed problematic levels of +/- 10% although systematic variability in RB was accounted for by parameter size, sample size, and nonzero direct effects. Power to detect mediated moderation effects appears to be severely compromised under one particular combination of conditions: when the component variables that make up the interaction terms are correlated and partial mediated moderation exists. Implications for the estimation of mediated moderation effects in experimental and nonexperimental research are discussed.
Social cognitive and emotional mediators link violence exposure and parental nurturance to adolescent aggression.

PubMed

Su, Wei; Mrug, Sylvie; Windle, Michael

2010-01-01

This study examined aggressive fantasies, violence-approving attitudes, and empathy as mediators of the effects of violence exposure and parental nurturance on aggression. A total of 603 early adolescents (M age = 11.8 years; SD = 0.8) participated in a two-wave study, reporting on violence exposure and parental nurturance at Wave 1 and the three mediators and aggression at Wave 2. Violence-approving attitudes mediated the effects of both violence exposure and low parental nurturance on aggression. Aggressive fantasies also mediated the effects of violence exposure and empathy mediated the effects of parental nurturance. The mediation pathways through which parental nurturance were linked to aggression differed across levels of violence exposure. In the context of high violence exposure, parental nurturance was related to lower aggression through higher social emotional empathy, but under low violence exposure, the effect was mediated by greater disapproval of violence.
The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF.

PubMed

Cheng, Ying; Shao, Can; Lathrop, Quinn N

2016-02-01

Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable or multiple variables that may completely or partially mediate the DIF effect. If complete mediation effect is found, the DIF effect is fully accounted for. Through our simulation study, we find that the mediated MIMIC model is very successful in detecting the mediation effect that completely or partially accounts for DIF, while keeping the Type I error rate well controlled for both balanced and unbalanced sample sizes between focal and reference groups. Because it is successful in detecting such mediation effects, the mediated MIMIC model may help explain DIF and give guidance in the revision of a DIF item.
The practice of mediation to resolve clinical, bioethical, and medical malpractice disputes.

PubMed

Lee, Danny W H; Lai, Paul B S

2015-12-01

Mediation is a voluntary process whereby a neutral and impartial third party-t-he mediator--is present to facilitate communication and negotiation between the disputing parties so that amicable settlements can be agreed. Being confidential and non-adversarial in nature, the mediation process and skills are particularly applicable in clinical practice to facilitate challenging communications following adverse events, to assist bioethical decision making and to resolve disputes. Mediation is also a more effective and efficient means of dispute resolution in medical malpractice claims when compared with civil litigation. Health care mediation teams should be set up at individual facilities to provide education and consultation services to frontline staff and patients. At a community level, the Government, the mediation community, and the health care professionals should join forces to promote mediation as a means to settle medical malpractice claims outside of the courtroom.
The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

PubMed Central

Cheng, Ying; Shao, Can; Lathrop, Quinn N.

2015-01-01

Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable or multiple variables that may completely or partially mediate the DIF effect. If complete mediation effect is found, the DIF effect is fully accounted for. Through our simulation study, we find that the mediated MIMIC model is very successful in detecting the mediation effect that completely or partially accounts for DIF, while keeping the Type I error rate well controlled for both balanced and unbalanced sample sizes between focal and reference groups. Because it is successful in detecting such mediation effects, the mediated MIMIC model may help explain DIF and give guidance in the revision of a DIF item.
Effect of gamma-oryzanol on cytochrome P450 activities in human liver microsomes.

PubMed

Umehara, Ken; Shimokawa, Yoshihiko; Miyamoto, Gohachiro

2004-07-01

The effects of gamma-oryzanol, a drug mainly used for the treatment of hyperlipidaemia, on several cytochrome P450 (CYP) specific reactions in human liver microsomes were investigated to predict drug interactions with gamma-oryzanol in vivo from in vitro data. The following eight CYP catalytic reactions were used in this study: CYP1A1/2-mediated 7-ethoxyresorufin O-deethylation, CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6-mediated 7-benzyloxyresorufin O-debenzylation, CYP2C8/9-mediated tolbutamide methylhydroxylation, CYP2C19-mediated S-mephenytoin 4'-hydroxylation, CYP2D6-mediated bufuralol 1'-hydroxylation, CYP2E1-mediated chlorzoxazone 6-hydroxylation, and CYP3A4-mediated testosterone 6beta-hydroxylation. gamma-Oryzanol had little inhibitory effects on CYP activities, indicating that this compound would not be expected to cause clinically significant interactions with other CYP-metabolized drugs at expected therapeutic concentrations.
Mediated moderation or moderated mediation: relationship between length of unemployment, resilience, coping and health.

PubMed

Sojo, Víctor; Guarino, Leticia

2011-05-01

The aim of the present research was to evaluate a model of mediated moderation vs. moderated mediation that could explain the relationship between length of unemployment, dispositional resilience, coping styles and depression and social functioning of Venezuelan unemployed individuals. Self-report measures were administered to a sample of 328 unemployed residents in Caracas, Venezuela. Results indicated that emotional coping acted as a mediator in the relationship between resilience and depression. Individuals with greater resilience used more detachment coping when unemployment was longer, while individuals with poorer resilience in the same situation used less avoidance coping. Resilience acted as a protective moderating factor between longer periods of unemployment and social functioning, a process mediated by detachment coping. Overall, results supported a mediated moderation model, with resilience as the moderating factor and coping as the mediator in the relation between stress due to the length of unemployment and well-being.
Role for the MED21-MED7 Hinge in Assembly of the Mediator-RNA Polymerase II Holoenzyme*

PubMed Central

Sato, Shigeo; Tomomori-Sato, Chieri; Tsai, Kuang-Lei; Yu, Xiaodi; Sardiu, Mihaela; Saraf, Anita; Washburn, Michael P.; Florens, Laurence; Asturias, Francisco J.; Conaway, Ronald C.

2016-01-01

Mediator plays an integral role in activation of RNA polymerase II (Pol II) transcription. A key step in activation is binding of Mediator to Pol II to form the Mediator-Pol II holoenzyme. Here, we exploit a combination of biochemistry and macromolecular EM to investigate holoenzyme assembly. We identify a subset of human Mediator head module subunits that bind Pol II independent of other subunits and thus probably contribute to a major Pol II binding site. In addition, we show that binding of human Mediator to Pol II depends on the integrity of a conserved “hinge” in the middle module MED21-MED7 heterodimer. Point mutations in the hinge region leave core Mediator intact but lead to increased disorder of the middle module and markedly reduced affinity for Pol II. These findings highlight the importance of Mediator conformation for holoenzyme assembly. PMID:27821593

Mediator phosphorylation prevents stress response transcription during non-stress conditions.

PubMed

Miller, Christian; Matic, Ivan; Maier, Kerstin C; Schwalb, Björn; Roether, Susanne; Strässer, Katja; Tresch, Achim; Mann, Matthias; Cramer, Patrick

2012-12-28

The multiprotein complex Mediator is a coactivator of RNA polymerase (Pol) II transcription that is required for the regulated expression of protein-coding genes. Mediator serves as an end point of signaling pathways and regulates Pol II transcription, but the mechanisms it uses are not well understood. Here, we used mass spectrometry and dynamic transcriptome analysis to investigate a functional role of Mediator phosphorylation in gene expression. Affinity purification and mass spectrometry revealed that Mediator from the yeast Saccharomyces cerevisiae is phosphorylated at multiple sites of 17 of its 25 subunits. Mediator phosphorylation levels change upon an external stimulus set by exposure of cells to high salt concentrations. Phosphorylated sites in the Mediator tail subunit Med15 are required for suppression of stress-induced changes in gene expression under non-stress conditions. Thus dynamic and differential Mediator phosphorylation contributes to gene regulation in eukaryotic cells.
A Mediator-Based Approach to Resolving Interface Heterogeneity of Web Services

NASA Astrophysics Data System (ADS)

Leitner, Philipp; Rosenberg, Florian; Michlmayr, Anton; Huber, Andreas; Dustdar, Schahram

In theory, service-oriented architectures are based on the idea of increasing flexibility in the selection of internal and external business partners using loosely-coupled services. However, in practice this flexibility is limited by the fact that partners need not only to provide the same service, but to do so via virtually the same interface in order to actually be interchangeable easily. Invocation-level mediation may be used to overcome this issue — by using mediation interface differences can be resolved transparently at runtime. In this chapter we discuss the basic ideas of mediation, with a focus on interface-level mediation. We show how interface mediation is integrated into our dynamic Web service invocation framework DAIOS, and present three different mediation strategies, one based on structural message similarity, one based on semantically annotated WSDL, and one which is embedded into the VRESCo SOA runtime, a larger research project with explicit support for service mediation.
Social Cognitive and Emotional Mediators Link Violence Exposure and Parental Nurturance to Adolescent Aggression

PubMed Central

Su, Wei; Mrug, Sylvie; Windle, Michael

2013-01-01

This study examined aggressive fantasies, violence-approving attitudes, and empathy as mediators of the effects of violence exposure and parental nurturance on aggression. A total of 603 early adolescents participated in a two-wave study, reporting on violence exposure and parental nurturance at Wave 1 and the three mediators and aggression at Wave 2. Violence-approving attitudes mediated the effects of both violence exposure and low parental nurturance on aggression. Aggressive fantasies also mediated the effects of violence exposure and empathy mediated the effects of parental nurturance. The mediation pathways via which parental nurturance was linked to aggression differed across levels of violence exposure. In the context of high violence exposure, parental nurturance was related to lower aggression through higher social emotional empathy, but under low violence exposure, the effect was mediated by greater disapproval of violence. PMID:21058128
Current Directions in Mediation Analysis

PubMed Central

MacKinnon, David P.; Fairchild, Amanda J.

2010-01-01

Mediating variables continue to play an important role in psychological theory and research. A mediating variable transmits the effect of an antecedent variable on to a dependent variable, thereby providing more detailed understanding of relations among variables. Methods to assess mediation have been an active area of research for the last two decades. This paper describes the current state of methods to investigate mediating variables. PMID:20157637
Music Technology-Mediated Teaching and Learning Approach for Music Education: A Case Study from an Elementary School in South Korea

ERIC Educational Resources Information Center

Kim, Eunjin

2013-01-01

This study aims to show how music technology mediated (or music software mediated) music teaching and learning can provide an effective pedagogy in music education. It also seeks to demonstrate that music technology mediated teaching is in accordance with socio-educational trends for both postmodern values and IT mediated learning. The new…
Determinants of lifestyle behavior change to prevent type 2 diabetes in high-risk individuals.

PubMed

den Braver, N R; de Vet, E; Duijzer, G; Ter Beek, J; Jansen, S C; Hiddink, G J; Feskens, E J M; Haveman-Nies, A

2017-06-12

Although there are many effective lifestyle interventions for type 2 diabetes (T2DM) prevention, insight into effective intervention pathways, especially of long-term interventions, is often lacking. This study aims to provide insight into the effective intervention pathways of the SLIMMER diabetes prevention intervention using mediation analyses. In total, 240 participants at increased risk of T2DM were included in the analyses over 18 months. The intervention was a combined lifestyle intervention with a dietary and a physical activity (PA) component. The primary and secondary outcomes were change in fasting insulin (pmol/L) and change in body weight (kg) after 18 months, respectively. Firstly, in a multiple mediator model, we investigated whether significant changes in these outcomes were mediated by changes in dietary and PA behavior. Secondly, in multiple single mediator models, we investigated whether changes in dietary and PA behavior were mediated by changes in behavioral determinants and the participants' psychological profile. The mediation analyses used linear regression models, where significance of indirect effects was calculated with bootstrapping. The effect of the intervention on decreased fasting insulin was 40% mediated by change in dietary and PA behavior, where dietary behavior was an independent mediator of the association (34%). The effect of the intervention on decreased body weight was 20% mediated by change in dietary and PA behavior, where PA behavior was an independent mediator (17%). The intervention significantly changed intake of fruit, fat from bread spread, and fiber from bread. Change in fruit intake was mediated by change in action control (combination of consciousness, self-control, and effort), motivation, self-efficacy, intention, and skills. Change in fat intake was mediated by change in action control and psychological profile. No mediators could be identified for change in fiber intake. The change in PA behavior was mediated by change in action control, motivation, and psychological profile. The effect of the SLIMMER intervention on fasting insulin and body weight was mediated by changes in dietary and PA behavior, in distinct ways. These results indicate that changing dietary as well as PA behavior is important in T2DM prevention.
Statistical grand rounds: understanding the mechanism: mediation analysis in randomized and nonrandomized studies.

PubMed

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

2013-10-01

In comparative clinical studies, a common goal is to assess whether an exposure, or intervention, affects the outcome of interest. However, just as important is to understand the mechanism(s) for how the intervention affects outcome. For example, if preoperative anemia was shown to increase the risk of postoperative complications by 15%, it would be important to quantify how much of that effect was due to patients receiving intraoperative transfusions. Mediation analysis attempts to quantify how much, if any, of the effect of an intervention on outcome goes though prespecified mediator, or "mechanism" variable(s), that is, variables sitting on the causal pathway between exposure and outcome. Effects of an exposure on outcome can thus be divided into direct and indirect, or mediated, effects. Mediation is claimed when 2 conditions are true: the exposure affects the mediator and the mediator (adjusting for the exposure) affects the outcome. Understanding how an intervention affects outcome can validate or invalidate one's original hypothesis and also facilitate further research to modify the responsible factors, and thus improve patient outcome. We discuss the proper design and analysis of studies investigating mediation, including the importance of distinguishing mediator variables from confounding variables, the challenge of identifying potential mediators when the exposure is chronic versus acute, and the requirements for claiming mediation. Simple designs are considered, as well as those containing multiple mediators, multiple outcomes, and mixed data types. Methods are illustrated with data collected by the National Surgical Quality Improvement Project (NSQIP) and utilized in a companion paper which assessed the effects of preoperative anemic status on postoperative outcomes.
Mediator Recruitment to Heat Shock Genes Requires Dual Hsf1 Activation Domains and Mediator Tail Subunits Med15 and Med16*

PubMed Central

Kim, Sunyoung; Gross, David S.

2013-01-01

The evolutionarily conserved Mediator complex is central to the regulation of gene transcription in eukaryotes because it serves as a physical and functional interface between upstream regulators and the Pol II transcriptional machinery. Nonetheless, its role appears to be context-dependent, and the detailed mechanism by which it governs the expression of most genes remains unknown. Here we investigate Mediator involvement in HSP (heat shock protein) gene regulation in the yeast Saccharomyces cerevisiae. We find that in response to thermal upshift, subunits representative of each of the four Mediator modules (Head, Middle, Tail, and Kinase) are rapidly, robustly, and selectively recruited to the promoter regions of HSP genes. Their residence is transient, returning to near-background levels within 90 min. Hsf1 (heat shock factor 1) plays a central role in recruiting Mediator, as indicated by the fact that truncation of either its N- or C-terminal activation domain significantly reduces Mediator occupancy, whereas removal of both activation domains abolishes it. Likewise, ablation of either of two Mediator Tail subunits, Med15 or Med16, reduces Mediator recruitment to HSP promoters, whereas deletion of both abolishes it. Accompanying the loss of Mediator, recruitment of RNA polymerase II is substantially diminished. Interestingly, Mediator antagonizes Hsf1 occupancy of non-induced promoters yet facilitates enhanced Hsf1 association with activated ones. Collectively, our observations indicate that Hsf1, via its dual activation domains, recruits holo-Mediator to HSP promoters in response to acute heat stress through cooperative physical and/or functional interactions with the Tail module. PMID:23447536
Relate it! Objective and subjective evaluation of mediator-based strategies for improving source memory in younger and older adults.

PubMed

Kuhlmann, Beatrice G; Touron, Dayna R

2017-06-01

The present study examined younger and older adults' ability to improve their source memory for different types of sources through imaginal and verbal (sentence) mediators. Younger (18-29 years) and older (60-75 years) adults' strategy use and source memory for either text-type (bold vs italic) or person (woman vs man) sources was assessed; strategy use was either spontaneous or the generation of imaginal mediators was instructed before encoding. Younger and older adults did not differ in spontaneous use of mediator-based strategies; however, older adults generated more images but fewer verbal mediators than younger adults. Participants were able to increase mediator generation when instructed to, resulting in substantial increases in both item and source memory for the instructed conditions in both age groups. Use of verbal mediators was more likely for the more concrete person sources for which source memory was generally better. Importantly, these objective benefits of mediator-based strategies translated into subjective benefits for both younger and older adults: Increased use of either mediator type was correlated with lower experienced task difficulty; the instructions to use imaginal mediators resulted in a significant decrease in difficulty ratings on the group level. Participants were generally able to monitor mediator benefits to both item and source memory and accurately judged mediator strategies (especially imagery) as more effective than repetition; older adults, however, rated all strategies as less effective than younger adults. Implications of these findings, especially for neuropsychological studies on source monitoring, are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.
Practical guidance for conducting mediation analysis with multiple mediators using inverse odds ratio weighting.

PubMed

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.
Kin28 regulates the transient association of Mediator with core promoters.

PubMed

Jeronimo, Célia; Robert, François

2014-05-01

Mediator is an essential, broadly used eukaryotic transcriptional coactivator. How and what Mediator communicates from activators to RNA polymerase II (RNAPII) remains an open question. Here we performed genome-wide location profiling of Saccharomyces cerevisiae Mediator subunits. Mediator is not found at core promoters but rather occupies the upstream activating sequence, upstream of the pre-initiation complex. In the absence of Kin28 (CDK7) kinase activity or in cells in which the RNAPII C-terminal domain is mutated to replace Ser5 with alanine, however, Mediator accumulates at core promoters together with RNAPII. We propose that Mediator is released quickly from promoters after phosphorylation of Ser5 by Kin28 (CDK7), which also allows for RNAPII to escape from the promoter.
78 FR 18631 - Notice of Proposed Information Collection Requests

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-27

... NATIONAL MEDIATION BOARD Notice of Proposed Information Collection Requests AGENCY: National Mediation Board. SUMMARY: The Director, Office of Administration, invites comments on the proposed... Mediation Board is soliciting comments concerning the proposed extension of the Application for Mediation...
Mediator: A key regulator of plant development.

PubMed

Buendía-Monreal, Manuel; Gillmor, C Stewart

2016-11-01

Mediator is a multiprotein complex that regulates transcription at the level of RNA pol II assembly, as well as through regulation of chromatin architecture, RNA processing and recruitment of epigenetic marks. Though its modular structure is conserved in eukaryotes, its subunit composition has diverged during evolution and varies in response to environmental and tissue-specific inputs, suggesting different functions for each subunit and/or Mediator conformation. In animals, Mediator has been implicated in the control of differentiation and morphogenesis through modulation of numerous signaling pathways. In plants, studies have revealed roles for Mediator in regulation of cell division, cell fate and organogenesis, as well as developmental timing and hormone responses. We begin this review with an overview of biochemical mechanisms of yeast and animal Mediator that are likely to be conserved in all eukaryotes, as well as a brief discussion of the role of Mediator in animal development. We then present a comprehensive review of studies of the role of Mediator in plant development. Finally, we point to important questions for future research on the role of Mediator as a master coordinator of development. Copyright © 2016 Elsevier Inc. All rights reserved.
Characterization of Mediator Complex and its Associated Proteins from Rice.

PubMed

Samanta, Subhasis; Thakur, Jitendra Kumar

2017-01-01

The Mediator complex is a multi-protein complex that acts as a molecular bridge conveying transcriptional messages from the cis element-bound transcription factor to the RNA Polymerase II machinery. It is found in all eukaryotes including members of the plant kingdom. Increasing number of reports from plants regarding different Mediator subunits involved in a multitude of processes spanning from plant development to environmental interactions have firmly established it as a central hub of plant regulatory networks. Routine isolation of Mediator complex in a particular species is a necessity because of many reasons. First, composition of the Mediator complex varies from species to species. Second, the composition of the Mediator complex in a particular species is not static under all developmental and environmental conditions. Besides this, at times, Mediator complex is used in in vitro transcription systems. Rice, a staple food crop of the world, is used as a model monocot crop. Realizing the need of a reliable protocol for the isolation of Mediator complex from plants, we describe here the isolation of Mediator complex from rice.
Generalized causal mediation and path analysis: Extensions and practical considerations.

PubMed

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

2018-01-01

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

PubMed

Roth, Wolff-Michael; Jornet, Alfredo

2017-01-05

Mediation is one of the most often cited concepts in current cultural-historical theory literature, in which cultural actions and artifacts are often characterized as mediators standing between situational stimuli and behavioral responses. Most often presented as a means to overcome Cartesian dualism between subject and object, and between individual and society, some scholars have nonetheless raised criticism suggesting that such mediators are problematic for a dialectical psychology that takes a unit analysis (monist) approach. In fact, Spinoza develops a monist theory of mind and body that goes without and even excludes every form of mediation. In this study, we follow up on the latter criticisms and explore what we consider to be problematic uses of the notion of mediation as an analytical construct in the literature. We elaborate an empirically grounded discussion on the ways the concept of mediation may lead to dualistic readings; and we offer an alternative account where the notion of mediator is not needed. We conclude discussing prospects for and implications of a cultural-historical theory where the notion of mediation no longer is invoked to account for human action and development.
Causal mediation analysis with a binary outcome and multiple continuous or ordinal mediators: Simulations and application to an alcohol intervention

PubMed Central

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 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. PMID:27158217
Defining and estimating causal direct and indirect effects when setting the mediator to specific values is not feasible

PubMed Central

Lok, Judith J.

2016-01-01

Natural direct and indirect effects decompose the effect of a treatment into the part that is mediated by a covariate (the mediator) and the part that is not. Their definitions rely on the concept of outcomes under treatment with the mediator “set” to its value without treatment. Typically, the mechanism through which the mediator is set to this value is left unspecified, and in many applications it may be challenging to fix the mediator to particular values for each unit or patient. Moreover, how one sets the mediator may affect the distribution of the outcome. This article introduces “organic” direct and indirect effects, which can be defined and estimated without relying on setting the mediator to specific values. Organic direct and indirect effects can be applied for example to estimate how much of the effect of some treatments for HIV/AIDS on mother-to-child transmission of HIV infection is mediated by the effect of the treatment on the HIV viral load in the blood of the mother. PMID:27229743
Bayesian Mediation Analysis

ERIC Educational Resources Information Center

Yuan, Ying; MacKinnon, David P.

2009-01-01

In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…
29 CFR 1430.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE FEDERAL MEDIATION AND CONCILIATION... Mediation and Conciliation Service employee or his delegee, officially designated to perform the advisory committee management functions delineated in this part; (e) The term Service means the Federal Mediation and...

78 FR 35055 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-11

... NATIONAL MEDIATION BOARD Submission for OMB Review; Comment Request AGENCY: National Mediation...) Reporting and/or Record keeping burden. OMB invites public comment. Currently, the National Mediation Board is soliciting comments concerning the proposed extension of the Application for Mediation Services...
78 FR 30341 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

... NATIONAL MEDIATION BOARD Submission for OMB Review; Comment Request AGENCY: National Mediation...) Reporting and/or Record keeping burden. OMB invites public comment. Currently, the National Mediation Board... Mediation Board. Application for Investigation of Representation Dispute Type of Review: Extension. Title...
Mediation With Muscle: Understanding When Mediators Commit Resources to Civil War Negotiations

DTIC Science & Technology

2015-12-01

MEDIATION STRATEGIES Mediators’ involvement in civil wars varies in intensity, and the various strategies require introduction (Bercovitch et al ., 1991...Kreutz, 2010; Regan et al ., 2009).15 To identify mediation events, the CWM uses the UCDP Conflict Termination dataset (Kreutz, 2010), the...Diplomatic Intervention and Civil War (Regan et al ., 2009), and public sources to identify individual civil war mediation events (DeRouen et al ., 2011). It
Estimation of Indirect Effects in the Presence of Unmeasured Confounding for the Mediator-Outcome Relationship in a Multilevel 2-1-1 Mediation Model

ERIC Educational Resources Information Center

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…
Maturation trajectories of cortical resting-state networks depend on the mediating frequency band.

PubMed

Khan, Sheraz; Hashmi, Javeria A; Mamashli, Fahimeh; Michmizos, Konstantinos; Kitzbichler, Manfred G; Bharadwaj, Hari; Bekhti, Yousra; Ganesan, Santosh; Garel, Keri-Lee A; Whitfield-Gabrieli, Susan; Gollub, Randy L; Kong, Jian; Vaina, Lucia M; Rana, Kunjan D; Stufflebeam, Steven M; Hämäläinen, Matti S; Kenet, Tal

2018-07-01

The functional significance of resting state networks and their abnormal manifestations in psychiatric disorders are firmly established, as is the importance of the cortical rhythms in mediating these networks. Resting state networks are known to undergo substantial reorganization from childhood to adulthood, but whether distinct cortical rhythms, which are generated by separable neural mechanisms and are often manifested abnormally in psychiatric conditions, mediate maturation differentially, remains unknown. Using magnetoencephalography (MEG) to map frequency band specific maturation of resting state networks from age 7 to 29 in 162 participants (31 independent), we found significant changes with age in networks mediated by the beta (13-30 Hz) and gamma (31-80 Hz) bands. More specifically, gamma band mediated networks followed an expected asymptotic trajectory, but beta band mediated networks followed a linear trajectory. Network integration increased with age in gamma band mediated networks, while local segregation increased with age in beta band mediated networks. Spatially, the hubs that changed in importance with age in the beta band mediated networks had relatively little overlap with those that showed the greatest changes in the gamma band mediated networks. These findings are relevant for our understanding of the neural mechanisms of cortical maturation, in both typical and atypical development. Copyright © 2018. Published by Elsevier Inc.
Redefining the modular organization of the core Mediator complex.

PubMed

Wang, Xuejuan; Sun, Qianqian; Ding, Zhenrui; Ji, Jinhua; Wang, Jianye; Kong, Xiao; Yang, Jianghong; Cai, Gang

2014-07-01

The Mediator complex plays an essential role in the regulation of eukaryotic transcription. The Saccharomyces cerevisiae core Mediator comprises 21 subunits, which are organized into Head, Middle and Tail modules. Previously, the Head module was assigned to a distinct dense domain at the base, and the Middle and Tail modules were identified to form a tight structure above the Head module, which apparently contradicted findings from many biochemical and functional studies. Here, we compared the structures of the core Mediator and its subcomplexes, especially the first 3D structure of the Head + Middle modules, which permitted an unambiguous assignment of the three modules. Furthermore, nanogold labeling pinpointing four Mediator subunits from different modules conclusively validated the modular assignment, in which the Head and Middle modules fold back on one another and form the upper portion of the core Mediator, while the Tail module forms a distinct dense domain at the base. The new modular model of the core Mediator has reconciled the previous inconsistencies between the structurally and functionally defined Mediator modules. Collectively, these analyses completely redefine the modular organization of the core Mediator, which allow us to integrate the structural and functional information into a coherent mechanism for the Mediator's modularity and regulation in transcription initiation.
Mediator binds to boundaries of chromosomal interaction domains and to proteins involved in DNA looping, RNA metabolism, chromatin remodeling, and actin assembly.

PubMed

Chereji, Razvan V; Bharatula, Vasudha; Elfving, Nils; Blomberg, Jeanette; Larsson, Miriam; Morozov, Alexandre V; Broach, James R; Björklund, Stefan

2017-09-06

Mediator is a multi-unit molecular complex that plays a key role in transferring signals from transcriptional regulators to RNA polymerase II in eukaryotes. We have combined biochemical purification of the Saccharomyces cerevisiae Mediator from chromatin with chromatin immunoprecipitation in order to reveal Mediator occupancy on DNA genome-wide, and to identify proteins interacting specifically with Mediator on the chromatin template. Tandem mass spectrometry of proteins in immunoprecipitates of mediator complexes revealed specific interactions between Mediator and the RSC, Arp2/Arp3, CPF, CF 1A and Lsm complexes in chromatin. These factors are primarily involved in chromatin remodeling, actin assembly, mRNA 3'-end processing, gene looping and mRNA decay, but they have also been shown to enter the nucleus and participate in Pol II transcription. Moreover, we have found that Mediator, in addition to binding Pol II promoters, occupies chromosomal interacting domain (CID) boundaries and that Mediator in chromatin associates with proteins that have been shown to interact with CID boundaries, such as Sth1, Ssu72 and histone H4. This suggests that Mediator plays a significant role in higher-order genome organization. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
Mediator complex cooperatively regulates transcription of retinoic acid target genes with Polycomb Repressive Complex 2 during neuronal differentiation.

PubMed

Fukasawa, Rikiya; Iida, Satoshi; Tsutsui, Taiki; Hirose, Yutaka; Ohkuma, Yoshiaki

2015-11-01

The Mediator complex (Mediator) plays key roles in transcription and functions as the nexus for integration of various transcriptional signals. Previously, we screened for Mediator cyclin-dependent kinase (CDK)-interacting factors and identified three proteins related to chromatin regulation. One of them, SUZ12 is required for both stability and activity of Polycomb Repressive Complex 2 (PRC2). PRC2 primarily suppresses gene expression through histone H3 lysine 27 trimethylation, resulting in stem cell maintenance and differentiation; perturbation of this process leads to oncogenesis. Recent work showed that Mediator contributes to the embryonic stem cell state through DNA loop formation, which is strongly associated with chromatin architecture; however, it remains unclear how Mediator regulates gene expression in cooperation with chromatin regulators (i.e. writers, readers and remodelers). We found that Mediator CDKs interact directly with the PRC2 subunit EZH2, as well as SUZ12. Known PRC2 target genes were deregulated by Mediator CDK knockdown during neuronal differentiation, and both Mediator and PRC2 complexes co-occupied the promoters of developmental genes regulated by retinoic acid. Our results provide a mechanistic link between Mediator and PRC2 during neuronal differentiation. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
Redefining the modular organization of the core Mediator complex

PubMed Central

Wang, Xuejuan; Sun, Qianqian; Ding, Zhenrui; Ji, Jinhua; Wang, Jianye; Kong, Xiao; Yang, Jianghong; Cai, Gang

2014-01-01

The Mediator complex plays an essential role in the regulation of eukaryotic transcription. The Saccharomyces cerevisiae core Mediator comprises 21 subunits, which are organized into Head, Middle and Tail modules. Previously, the Head module was assigned to a distinct dense domain at the base, and the Middle and Tail modules were identified to form a tight structure above the Head module, which apparently contradicted findings from many biochemical and functional studies. Here, we compared the structures of the core Mediator and its subcomplexes, especially the first 3D structure of the Head + Middle modules, which permitted an unambiguous assignment of the three modules. Furthermore, nanogold labeling pinpointing four Mediator subunits from different modules conclusively validated the modular assignment, in which the Head and Middle modules fold back on one another and form the upper portion of the core Mediator, while the Tail module forms a distinct dense domain at the base. The new modular model of the core Mediator has reconciled the previous inconsistencies between the structurally and functionally defined Mediator modules. Collectively, these analyses completely redefine the modular organization of the core Mediator, which allow us to integrate the structural and functional information into a coherent mechanism for the Mediator's modularity and regulation in transcription initiation. PMID:24810298
The mediator complex in genomic and non-genomic signaling in cancer.

PubMed

Weber, Hannah; Garabedian, Michael J

2018-05-01

Mediator is a conserved, multi-subunit macromolecular machine divided structurally into head, middle, and tail modules, along with a transiently associating kinase module. Mediator functions as an integrator of transcriptional regulatory activity by interacting with DNA-bound transcription factors and with RNA polymerase II (Pol II) to both activate and repress gene expression. Mediator has been shown to affect multiple steps in transcription, including chromatin looping between enhancers and promoters, pre-initiation complex formation, transcriptional elongation, and mRNA splicing. Individual Mediator subunits participate in regulation of gene expression by the estrogen and androgen receptors and are altered in a number of endocrine cancers, including breast and prostate cancer. In addition to its role in genomic signaling, MED12 has been implicated in non-genomic signaling by interacting with and activating TGF-beta receptor 2 in the cytoplasm. Recent structural studies have revealed extensive inter-domain interactions and complex architecture of the Mediator-Pol II complex, suggesting that Mediator is capable of reorganizing its conformation and composition to fit cellular needs. We propose that alterations in Mediator subunit expression that occur in various cancers could impact the organization and function of Mediator, resulting in changes in gene expression that promote malignancy. A better understanding of the role of Mediator in cancer could reveal new approaches to the diagnosis and treatment of Mediator-dependent endocrine cancers, especially in settings of therapy resistance. Copyright © 2017 Elsevier Inc. All rights reserved.
7 CFR 900.109 - Mediation agreement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 8 2012-01-01 2012-01-01 false Mediation agreement. 900.109 Section 900.109... Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS Procedure... Mediation agreement. An agreement arrived at by mediation shall not become effective until approved by the...
7 CFR 900.109 - Mediation agreement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Mediation agreement. 900.109 Section 900.109... Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS Procedure... Mediation agreement. An agreement arrived at by mediation shall not become effective until approved by the...
76 FR 19310 - Information Collection; Certified State Mediation Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... DEPARTMENT OF AGRICULTURE Farm Service Agency Information Collection; Certified State Mediation... supports the Certified State Mediation Program. The information collection is necessary to ensure the grant... submit comments by any of the following methods: Mail: Carol Wagner, Certified State Mediation Program...
78 FR 51751 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-21

... NATIONAL MEDIATION BOARD Submission for OMB Review; Comment Request AGENCY: National Mediation... should be addressed to June D. W. King, Director, Office of Administration, National Mediation Board...: August 15, 2013. June D.W. King, Director, Office of Administration, National Mediation Board. Request...
MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana

PubMed Central

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

2017-01-01

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

PubMed

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 clinical application.
Mediated electrochemical oxidation of organic wastes without electrode separators

DOEpatents

Farmer, Joseph C.; Wang, Francis T.; Hickman, Robert G.; Lewis, Patricia R.

1996-01-01

An electrochemical cell/electrolyte/mediator combination for the efficient destruction of organic contaminants using metal salt mediators in a sulfuric acid electrolyte, wherein the electrodes and mediator are chosen such that hydrogen gas is produced at the cathode and no cell membrane is required.
34 CFR 303.419 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false Mediation. 303.419 Section 303.419 Education... DISABILITIES Procedural Safeguards Mediation and Due Process Procedures for Parents and Children § 303.419 Mediation. (a) General. Each State shall ensure that procedures are established and implemented to allow...
7 CFR 900.103 - Application for mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Application for mediation. 900.103 Section 900.103 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Application for mediation. An application for mediation by a cooperative, shall be in writing and shall...
Is Parenting the Mediator of Change in Behavioral Parent Training for Externalizing Problems of Youth?

PubMed Central

Forehand, Rex; Lafko, Nicole; Parent, Justin; Burt, Keith

2014-01-01

Change in parenting behavior is theorized to be the mediator accounting for change in child and adolescent externalizing problems in behavioral parent training (BPT). The purpose of this review is to examine this assumption in BPT prevention and intervention programs. Eight intervention and 17 prevention studies were identified as meeting all criteria or all but one criterion for testing mediation. Parenting behaviors were classified as positive, negative, discipline, monitoring/supervision, or a composite measure. Forty-five percent of the tests performed across studies to test mediation supported parenting as a mediator. A composite measure of parenting and discipline received the most support, whereas monitoring/supervision was rarely examined. More support for the mediating role of parenting emerged for prevention than intervention studies and when meeting all criteria for testing mediation was not required. Although the findings do not call BPT into question as an efficacious treatment, they do suggest more attention should be focused on examining parenting as a putative mediator in BPT. PMID:25455625

Satisfaction with Life Scale (SWLS) in Caregivers of Clinically-Referred Youth: Psychometric Properties and Mediation Analysis

PubMed Central

Athay, M. Michele

2012-01-01

This paper presents the psychometric evaluation of the Satisfaction with Life Scale (SWLS; Diener, Emmons, Larson & Griffen, 1985) used with a large sample (N = 610) of caregivers for youth receiving mental health services. Methods from classical test theory, factor analysis and item response theory are utilized. Additionally, this paper investigates whether caregiver strain mediates the effect of youth symptom severity on caregiver life satisfaction (N = 356). Bootstrapped confidence intervals are used to determine the significance of the mediated effects. Results indicate that the SWLS is a psychometrically sound instrument to be used with caregivers of clinically-referred youth. Mediation analyses found that the effect of youth symptom severity on caregiver life satisfaction is mediated by caregiver strain but that the mediation effect differs based on the type of youth symptoms. Caregiver strain is a partial mediator when externalizing symptoms are measured and a full mediator when internalizing symptoms are measured. Implications for future research and clinical practice are discussed. PMID:22407554
Mediators of Change in Psychosocial Interventions for Cancer Patients: A Systematic Review

PubMed Central

Moyer, Anne; Goldenberg, Matthew; Hall, Matthew A.; Knapp-Oliver, Sarah K.; Sohl, Stephanie J.; Sarma, Elizabeth A.; Schneider, Stefan

2012-01-01

Careful reviews and meta-analyses have made valuable contributions to understanding the efficacy of psychosocial interventions for cancer patients. An important next step is to determine the mediators that explain the influence of efficacious interventions on outcomes. This systematic review summarizes tests of mediating variables from twenty-two projects conducted from 1989–2010. Although all authors provided some type of rationale for considering particular mediating relationships, the investigations varied widely with respect to the extent to which formal theoretical constructs were tested, the type and goals of the interventions studied, and the broad types of outcomes and potential mediators examined. Although there was some evidence supporting selected mediating relationships, with positive findings often found when mediating variables represented behaviors targeted by an intervention, the findings were mixed. Expanding the focus of research to include mechanisms in psychosocial oncology intervention research is necessary for providing a unified picture of how mediating relationships may be operating in this field. PMID:22873734
Role for the MED21-MED7 Hinge in Assembly of the Mediator-RNA Polymerase II Holoenzyme.

PubMed

Sato, Shigeo; Tomomori-Sato, Chieri; Tsai, Kuang-Lei; Yu, Xiaodi; Sardiu, Mihaela; Saraf, Anita; Washburn, Michael P; Florens, Laurence; Asturias, Francisco J; Conaway, Ronald C; Conaway, Joan W

2016-12-23

Mediator plays an integral role in activation of RNA polymerase II (Pol II) transcription. A key step in activation is binding of Mediator to Pol II to form the Mediator-Pol II holoenzyme. Here, we exploit a combination of biochemistry and macromolecular EM to investigate holoenzyme assembly. We identify a subset of human Mediator head module subunits that bind Pol II independent of other subunits and thus probably contribute to a major Pol II binding site. In addition, we show that binding of human Mediator to Pol II depends on the integrity of a conserved "hinge" in the middle module MED21-MED7 heterodimer. Point mutations in the hinge region leave core Mediator intact but lead to increased disorder of the middle module and markedly reduced affinity for Pol II. These findings highlight the importance of Mediator conformation for holoenzyme assembly. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Architecture of the RNA polymerase II-Mediator core initiation complex.

PubMed

Plaschka, C; Larivière, L; Wenzeck, L; Seizl, M; Hemann, M; Tegunov, D; Petrotchenko, E V; Borchers, C H; Baumeister, W; Herzog, F; Villa, E; Cramer, P

2015-02-19

The conserved co-activator complex Mediator enables regulated transcription initiation by RNA polymerase (Pol) II. Here we reconstitute an active 15-subunit core Mediator (cMed) comprising all essential Mediator subunits from Saccharomyces cerevisiae. The cryo-electron microscopic structure of cMed bound to a core initiation complex was determined at 9.7 Å resolution. cMed binds Pol II around the Rpb4-Rpb7 stalk near the carboxy-terminal domain (CTD). The Mediator head module binds the Pol II dock and the TFIIB ribbon and stabilizes the initiation complex. The Mediator middle module extends to the Pol II foot with a 'plank' that may influence polymerase conformation. The Mediator subunit Med14 forms a 'beam' between the head and middle modules and connects to the tail module that is predicted to bind transcription activators located on upstream DNA. The Mediator 'arm' and 'hook' domains contribute to a 'cradle' that may position the CTD and TFIIH kinase to stimulate Pol II phosphorylation.
Intrinsic motivation as a mediator of relationships between symptoms and functioning among individuals with schizophrenia spectrum disorders in a diverse urban community.

PubMed

Yamada, Ann-Marie; Lee, Karen K; Dinh, Tam Q; Barrio, Concepción; Brekke, John S

2010-01-01

This study investigated intrinsic motivation as a mediator of the relationship between clinical symptoms and functioning. The mediation model was tested with a sample of 166 adults with schizophrenia spectrum disorders attending psychosocial rehabilitation programs in a diverse urban community. Ethnic minority status was examined as a moderator of the mediation model. Motivation was measured using items reflecting intrapsychic drive. Symptoms were assessed with the expanded Brief Psychiatric Rating Scale and functioning with the Role Functioning Scale. Motivation was a significant mediator of the relationship between functioning and all symptom scores; fully mediating the relationship between functioning and negative, disorganized, and global symptoms, and partially mediating the relationship between positive symptoms and functioning. Motivation scores between ethnic minority and nonminority individuals differed significantly (p < 0.05), but no moderation effect was indicated. The strong mediation effect schizophrenia of motivation on the symptoms-functioning relationship supports future work to translate findings into effective recovery-oriented services.
Intrinsic Motivation as a Mediator of Relationships Between Symptoms and Functioning Among Individuals With Schizophrenia Spectrum Disorders in a Diverse Urban Community

PubMed Central

Yamada, Ann-Marie; Lee, Karen K.; Dinh, Tam Q.; Barrio, Concepción; Brekke, John S.

2010-01-01

This study investigated intrinsic motivation as a mediator of the relationship between clinical symptoms and functioning. The mediation model was tested with a sample of 166 adults with schizophrenia spectrum disorders attending psychosocial rehabilitation programs in a diverse urban community. Ethnic minority status was examined as a moderator of the mediation model. Motivation was measured using items reflecting intrapsychic drive. Symptoms were assessed with the expanded Brief Psychiatric Rating Scale and functioning with the Role Functioning Scale. Motivation was a significant mediator of the relationship between functioning and all symptom scores; fully mediating the relationship between functioning and negative, disorganized, and global symptoms, and partially mediating the relationship between positive symptoms and functioning. Motivation scores between ethnic minority and nonminority individuals differed significantly (p < 0.05), but no moderation effect was indicated. The strong mediation effect schizophrenia of motivation on the symptoms-functioning relationship supports future work to translate findings into effective recovery-oriented services. PMID:20061866
Function and regulation of the Mediator complex.

PubMed

Conaway, Ronald C; Conaway, Joan Weliky

2011-04-01

Over the past few years, advances in biochemical and genetic studies of the structure and function of the Mediator complex have shed new light on its subunit architecture and its mechanism of action in transcription by RNA polymerase II (pol II). The development of improved methods for reconstitution of recombinant Mediator subassemblies is enabling more in-depth analyses of basic features of the mechanisms by which Mediator interacts with and controls the activity of pol II and the general initiation factors. The discovery and characterization of multiple, functionally distinct forms of Mediator characterized by the presence or absence of the Cdk8 kinase module have led to new insights into how Mediator functions in both Pol II transcription activation and repression. Finally, progress in studies of the mechanisms by which the transcriptional activation domains (ADs) of DNA binding transcription factors target Mediator have brought to light unexpected complexities in the way Mediator participates in signal transduction. Copyright © 2011 Elsevier Ltd. All rights reserved.
Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture.

PubMed

Eychenne, Thomas; Novikova, Elizaveta; Barrault, Marie-Bénédicte; Alibert, Olivier; Boschiero, Claire; Peixeiro, Nuno; Cornu, David; Redeker, Virginie; Kuras, Laurent; Nicolas, Pierre; Werner, Michel; Soutourina, Julie

2016-09-15

Mediator is a large coregulator complex conserved from yeast to humans and involved in many human diseases, including cancers. Together with general transcription factors, it stimulates preinitiation complex (PIC) formation and activates RNA polymerase II (Pol II) transcription. In this study, we analyzed how Mediator acts in PIC assembly using in vivo, in vitro, and in silico approaches. We revealed an essential function of the Mediator middle module exerted through its Med10 subunit, implicating a key interaction between Mediator and TFIIB. We showed that this Mediator-TFIIB link has a global role on PIC assembly genome-wide. Moreover, the amplitude of Mediator's effect on PIC formation is gene-dependent and is related to the promoter architecture in terms of TATA elements, nucleosome occupancy, and dynamics. This study thus provides mechanistic insights into the coordinated function of Mediator and TFIIB in PIC assembly in different chromatin contexts. © 2016 Eychenne et al.; Published by Cold Spring Harbor Laboratory Press.
Predictors of Parental Mediation Regarding Children's Smartphone Use.

PubMed

Hwang, Yoori; Jeong, Se-Hoon

2015-12-01

Children's addiction to smartphones has become a serious issue, and parental mediation could help prevent children's problematic use of smartphones. This research examined the factors that predict and explain parents' intention to mediate children's behavior over smartphone use. Based on a survey of 460 parents of elementary school students, we found that parental mediation was predicted by (a) parent's own addiction to smartphones, (b) perceived severity of smartphone addiction, and (c) personality traits such as neuroticism, openness, and agreeableness. To the best of our knowledge, this study is the first to examine the predictors of parental mediation regarding children's smartphone addiction, and the findings suggest some strategies to increase parental mediation.
Establishment of Stable, Cell-Mediated Immunity that Makes "Susceptible" Mice Resistant to Leishmania major

NASA Astrophysics Data System (ADS)

Bretscher, Peter A.; Wei, Guojian; Menon, Juthika N.; Bielefeldt-Ohmann, Helle

1992-07-01

Cell-mediated, but not antibody-mediated, immune responses protect humans against certain pathogens that produce chronic diseases such as leishmaniasis. Effective vaccination against such pathogens must therefore produce an immunological "imprint" so that stable, cell-mediated immunity is induced in all individuals after natural infection. BALB/c mice "innately susceptible" to Leishmania major produce antibodies after substantial infection. In the present study, "susceptible" mice injected with a small number of parasites mounted a cell-mediated response and acquired resistance to a larger, normally pathogenic, challenge. This vaccination strategy may be applicable in diseases in which protection is dependent on cell-mediated immunity.
Mediator and moderator effects in developmental and behavioral pediatric research.

PubMed

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.
Odor-mediated taste learning requires dorsal hippocampus, but not basolateral amygdala activity

PubMed Central

Wheeler, Daniel S.; Chang, Stephen E.; Holland, Peter C.

2013-01-01

Mediated learning is a unique cognitive phenomenon in which mental representations of physically absent stimuli enter into associations with directly-activated representations of physically present stimuli. Three experiments investigated the functional physiology of mediated learning involving the use of odor-taste associations. In Experiments 1a and 1b, basolateral amygdala lesions failed to attenuate mediated taste aversion learning. In Experiment 2, dorsal hippocampus inactivation impaired mediated learning, but left direct learning intact. Considered with past studies, the results implicate the dorsal hippocampus in mediated learning generally, and suggest a limit on the importance of the basolateral amygdala. PMID:23274135
Histone modifications influence mediator interactions with chromatin

PubMed Central

Zhu, Xuefeng; Zhang, Yongqiang; Bjornsdottir, Gudrun; Liu, Zhongle; Quan, Amy; Costanzo, Michael; Dávila López, Marcela; Westholm, Jakub Orzechowski; Ronne, Hans; Boone, Charles; Gustafsson, Claes M.; Myers, Lawrence C.

2011-01-01

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization. PMID:21742760
Childhood Maltreatment and PTSD: Spiritual Well-Being and Intimate Partner Violence as Mediators

PubMed Central

Zhang, Huaiyu; Pittman, Delishia M.; Lamis, Dorian A.; Fischer, Nicole L.; Schwenke, Tomina J.; Carr, Erika R.; Shah, Sanjay; Kaslow, Nadine J.

2016-01-01

Childhood maltreatment places individuals, including African American women who are undereducated and economically disadvantaged, at risk for developing posttraumatic stress disorder (PTSD) symptoms. Participants were 192 African American women with a history in the prior year of both a suicide attempt and intimate partner violence (IPV) exposure. They were recruited from a public hospital that provides medical and mental health treatment to mostly low-income patients. A simple mediator model was used to examine if (1) existential well-being (sense of purpose) and/or religious well-being (relationship with God) mediated the link between childhood maltreatment and adult PTSD symptoms. Sequential multiple mediator models determined if physical and nonphysical IPV enhanced our understanding of the mediational association among the aforementioned variables. Findings suggest that existential well-being mediated the association between childhood maltreatment and adult PTSD symptoms in a simple mediator model, and existential well-being and recent nonphysical IPV served as sequential multiple mediators of this link. However, religious well-being and physical IPV were not significant mediators. Findings underscore the importance of enhancing existential well-being in the treatment of suicidal African American women with a history of childhood maltreatment and IPV. PMID:26989343
Defining and estimating causal direct and indirect effects when setting the mediator to specific values is not feasible.

PubMed

Lok, Judith J

2016-09-30

Natural direct and indirect effects decompose the effect of a treatment into the part that is mediated by a covariate (the mediator) and the part that is not. Their definitions rely on the concept of outcomes under treatment with the mediator 'set' to its value without treatment. Typically, the mechanism through which the mediator is set to this value is left unspecified, and in many applications, it may be challenging to fix the mediator to particular values for each unit or patient. Moreover, how one sets the mediator may affect the distribution of the outcome. This article introduces 'organic' direct and indirect effects, which can be defined and estimated without relying on setting the mediator to specific values. Organic direct and indirect effects can be applied, for example, to estimate how much of the effect of some treatments for HIV/AIDS on mother-to-child transmission of HIV infection is mediated by the effect of the treatment on the HIV viral load in the blood of the mother. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
A mediator effect size in randomized clinical trials.

PubMed

Kraemer, Helena Chmura

2014-12-01

To understand the process by which a treatment (T) achieves an effect on outcome (O) and thus to improve the effect of T on O, it is vital to detect mediators, to compare the impact of different mediators, and to develop hypotheses about the causal factors (all mediators) linking T and O. An index is needed to facilitate interpretation of the potential clinical importance of a mediator (M) of choice of T on treatment O in randomized clinical trials (RCTs). Ideally such a mediator effect size should (1) be invariant under any rescaling of M and O consistent with the model used, and (2) reflect the difference between the overall observed effect of T on O and what the maximal effect of T on O could be were the association between T and M broken. A mediator effect size is derived first for the traditional linear model, and then more generally for any categorical (ordered or non-ordered) potential mediator. Issues such as the problem of multiple treatments, outcomes and mediators, and of causal inferences, and the correspondence between this approach and earlier ones, are discussed. Illustrations are given of the application of the approach. Copyright © 2014 John Wiley & Sons, Ltd.
Is Technology-Mediated Parental Monitoring Related to Adolescent Substance Use?

PubMed

Rudi, Jessie; Dworkin, Jodi

2018-01-03

Prevention researchers have identified parental monitoring leading to parental knowledge to be a protective factor against adolescent substance use. In today's digital society, parental monitoring can occur using technology-mediated communication methods, such as text messaging, email, and social networking sites. The current study aimed to identify patterns, or clusters, of in-person and technology-mediated monitoring behaviors, and examine differences between the patterns (clusters) in adolescent substance use. Cross-sectional survey data were collected from 289 parents of adolescents using Facebook and Amazon Mechanical Turk (MTurk). Cluster analyses were computed to identify patterns of in-person and technology-mediated monitoring behaviors, and chi-square analyses were computed to examine differences in substance use between the identified clusters. Three monitoring clusters were identified: a moderate in-person and moderate technology-mediated monitoring cluster (moderate-moderate), a high in-person and high technology-mediated monitoring cluster (high-high), and a high in-person and low technology-mediated monitoring cluster (high-low). Higher frequency of technology-mediated parental monitoring was not associated with lower levels of substance use. Results show that higher levels of technology-mediated parental monitoring may not be associated with adolescent substance use.
Causal Mediation Analysis for the Cox Proportional Hazards Model with a Smooth Baseline Hazard Estimator.

PubMed

Wang, Wei; Albert, Jeffrey M

2017-08-01

An important problem within the social, behavioral, and health sciences is how to partition an exposure effect (e.g. treatment or risk factor) among specific pathway effects and to quantify the importance of each pathway. Mediation analysis based on the potential outcomes framework is an important tool to address this problem and we consider the estimation of mediation effects for the proportional hazards model in this paper. We give precise definitions of the total effect, natural indirect effect, and natural direct effect in terms of the survival probability, hazard function, and restricted mean survival time within the standard two-stage mediation framework. To estimate the mediation effects on different scales, we propose a mediation formula approach in which simple parametric models (fractional polynomials or restricted cubic splines) are utilized to approximate the baseline log cumulative hazard function. Simulation study results demonstrate low bias of the mediation effect estimators and close-to-nominal coverage probability of the confidence intervals for a wide range of complex hazard shapes. We apply this method to the Jackson Heart Study data and conduct sensitivity analysis to assess the impact on the mediation effects inference when the no unmeasured mediator-outcome confounding assumption is violated.
A classical regression framework for mediation analysis: fitting one model to estimate mediation effects.

PubMed

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.
Mediation analysis when a continuous mediator is measured with error and the outcome follows a generalized linear model

PubMed Central

Valeri, Linda; Lin, Xihong; VanderWeele, Tyler J.

2014-01-01

Mediation analysis is a popular approach to examine the extent to which the effect of an exposure on an outcome is through an intermediate variable (mediator) and the extent to which the effect is direct. When the mediator is mis-measured the validity of mediation analysis can be severely undermined. In this paper we first study the bias of classical, non-differential measurement error on a continuous mediator in the estimation of direct and indirect causal effects in generalized linear models when the outcome is either continuous or discrete and exposure-mediator interaction may be present. Our theoretical results as well as a numerical study demonstrate that in the presence of non-linearities the bias of naive estimators for direct and indirect effects that ignore measurement error can take unintuitive directions. We then develop methods to correct for measurement error. Three correction approaches using method of moments, regression calibration and SIMEX are compared. We apply the proposed method to the Massachusetts General Hospital lung cancer study to evaluate the effect of genetic variants mediated through smoking on lung cancer risk. PMID:25220625

Attachment, emotion regulation, and adaptation to breast cancer: assessment of a mediational hypothesis.

PubMed

Ávila, Marisa; Brandão, Tânia; Teixeira, Joana; Coimbra, Joaquim Luis; Matos, Paula Mena

2015-11-01

This study examines the links between attachment, adaptation to breast cancer, and the mediating role played by emotional regulation processes. Participants were 127 women with breast cancer recruited in two public hospitals of Porto and at the Portuguese Cancer League. Women completed measures of attachment, quality of life, and emotion regulation. Path models were used to examine the associations between the constructs and to test the mediational hypotheses. Significant associations were found between attachment and adaptation. Dimensions of emotion regulation totally or partially mediated the associations between attachment and adaptation outcomes. Attachment security effects on interpersonal relations were totally mediated by communicating emotions. Also, attachment anxiety effect on physical well-being was totally mediated by rumination. Attachment avoidance effects on psychological outcomes were totally mediated by emotional control and partially mediated by communicating emotions for the case of interpersonal relations. This study highlights the importance of addressing emotional regulation jointly with attachment to deepen the comprehension of the relational processes implicated in adaptation to breast cancer. Results supported a mediational hypothesis, presenting emotional regulation processes as relevant dimensions for the understanding of attachment associations with adaptation to breast cancer. Copyright © 2015 John Wiley & Sons, Ltd.
77 FR 23208 - Assessment of Mediation and Arbitration Procedures

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-18

... No. EP 699] Assessment of Mediation and Arbitration Procedures AGENCY: Surface Transportation Board... Mediation and Arbitration Procedures, EP 699 (STB served Mar. 28, 2012),\\1\\ the Surface Transportation Board... favors the resolution of disputes through the use of mediation and arbitration procedures, in lieu of...
77 FR 19591 - Assessment of Mediation and Arbitration Procedures

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-02

..., 1111, and 1115 [Docket No. EP 699] Assessment of Mediation and Arbitration Procedures AGENCY: Surface... STB) proposes regulations that would require parties to participate in mediation in certain types of cases and would modify its existing regulations that permit parties to engage voluntarily in mediation...
15 CFR 930.114 - Secretarial mediation efforts.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Secretarial mediation efforts. 930.114... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.114 Secretarial mediation efforts. (a) Following the close of the hearing, the hearing officer shall transmit the...
29 CFR 1208.5 - Material relating to mediation function-confidential.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Material relating to mediation function-confidential. 1208.5 Section 1208.5 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD AVAILABILITY OF INFORMATION § 1208.5 Material relating to mediation function—confidential. (a) All files...
7 CFR 900.106 - Assignment of mediator.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Assignment of mediator. 900.106 Section 900.106 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Assignment of mediator. The Director of the Division shall assign a mediator, from the group designated by...
The Use of Propensity Scores in Mediation Analysis

ERIC Educational Resources Information Center

Jo, Booil; Stuart, Elizabeth A.; MacKinnon, David P.; Vinokur, Amiram D.

2011-01-01

Mediation analysis uses measures of hypothesized mediating variables to test theory for how a treatment achieves effects on outcomes and to improve subsequent treatments by identifying the most efficient treatment components. Most current mediation analysis methods rely on untested distributional and functional form assumptions for valid…
Mediator-assisted decolorization and detoxification of textile dyes/dye mixture by Cyathus bulleri laccase.

PubMed

Chhabra, Meenu; Mishra, Saroj; Sreekrishnan, T R

2008-12-01

Laccase from basidiomycete fungus Cyathus bulleri was evaluated for its ability to decolorize a number of reactive and acidic dyes in the presence of natural and synthetic mediators. The extent of decolorization was monitored at different mediator/dye concentrations and incubation time. Among the synthetic mediators, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) was effective at low mediator/dye ratios and resulted in 80-95% decolorization at rates that varied from 226 +/- 4 nmol min(-1) mg(-1) for Reactive Orange 1 to 1,333 +/- 15 nmol min(-1) mg(-1) for Reactive Red 198. Other synthetic mediators like 1-hydroxybenzotriazole and violuric acid showed both concentration- and time-dependent increases in percent decolorization. Natural mediators like vanillin, on the other hand, were found to be less effective on all the dyes except Reactive Orange 1. Computed rates of decolorization were about twofold lower than that with ABTS. The laccase-ABTS system also led to nearly 80% decolorization for the simulated dye mixture. No clear correlation between laccase activity on the mediator and its ability to decolorize dyes was found, but pH had a significant effect: Optimum pH for decolorization coincided with the optimum pH for mediator oxidation. The treated samples were also evaluated for toxicity in model microbial systems. The laccase-mediator system appears promising for treatment of textile wastewaters.
Mediating processes between stress and problematic marijuana use.

PubMed

Ketcherside, Ariel; Filbey, Francesca M

2015-06-01

The literature widely reports that stress is associated with marijuana use, yet, to date, the path from stress to marijuana-related problems has not been tested. In this study, we evaluated whether negative affect mediates the relationship between stress and marijuana use. To that end, we tested models to determine mediators between problems with marijuana use (via Marijuana Problem Scale), stress (via Early Life Stress Questionnaire, Perceived Stress Scale), and negative affect (via Beck Depression Inventory; Beck Anxiety Inventory) in 157 current heavy marijuana users. Mediation tests and bootstrap confidence intervals were carried out via the "Mediation" package in R. Depression and anxiety scores both significantly mediated the relationship between perceived stress and problematic marijuana use. Only depression significantly mediated the relationship between early life stress and problematic marijuana use. Early life stress, perceived stress and problematic marijuana use were significant only as independent variables and dependent variables. These findings demonstrate that (1) depression mediated both early life stress and perceived stress, and problematic marijuana use, and, (2) anxiety mediated perceived stress and problematic marijuana use. This mediation analysis represents a strong first step toward understanding the relationship between these variables; however, longitudinal studies are needed to determine causality between these variables. To conclude, addressing concomitant depression and anxiety in those who report either perceived stress or early life stress is important for the prevention of cannabis use disorders. Copyright © 2015. Published by Elsevier Ltd.
PIC Activation through Functional Interplay between Mediator and TFIIH.

PubMed

Malik, Sohail; Molina, Henrik; Xue, Zhu

2017-01-06

The multiprotein Mediator coactivator complex functions in large part by controlling the formation and function of the promoter-bound preinitiation complex (PIC), which consists of RNA polymerase II and general transcription factors. However, precisely how Mediator impacts the PIC, especially post-recruitment, has remained unclear. Here, we have studied Mediator effects on basal transcription in an in vitro transcription system reconstituted from purified components. Our results reveal a close functional interplay between Mediator and TFIIH in the early stages of PIC development. We find that under conditions when TFIIH is not normally required for transcription, Mediator actually represses transcription. TFIIH, whose recruitment to the PIC is known to be facilitated by the Mediator, then acts to relieve Mediator-induced repression to generate an active form of the PIC. Gel mobility shift analyses of PICs and characterization of TFIIH preparations carrying mutant XPB translocase subunit further indicate that this relief of repression is achieved through expending energy via ATP hydrolysis, suggesting that it is coupled to TFIIH's established promoter melting activity. Our interpretation of these results is that Mediator functions as an assembly factor that facilitates PIC maturation through its various stages. Whereas the overall effect of the Mediator is to stimulate basal transcription, its initial engagement with the PIC generates a transcriptionally inert PIC intermediate, which necessitates energy expenditure to complete the process. Copyright © 2016 Elsevier Ltd. All rights reserved.
The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator.

PubMed

Grants, Jennifer M; Goh, Grace Y S; Taubert, Stefan

2015-02-27

The Mediator multiprotein complex ('Mediator') is an important transcriptional coregulator that is evolutionarily conserved throughout eukaryotes. Although some Mediator subunits are essential for the transcription of all protein-coding genes, others influence the expression of only subsets of genes and participate selectively in cellular signaling pathways. Here, we review the current knowledge of Mediator subunit function in the nematode Caenorhabditis elegans, a metazoan in which established and emerging genetic technologies facilitate the study of developmental and physiological regulation in vivo. In this nematode, unbiased genetic screens have revealed critical roles for Mediator components in core developmental pathways such as epidermal growth factor (EGF) and Wnt/β-catenin signaling. More recently, important roles for C. elegans Mediator subunits have emerged in the regulation of lipid metabolism and of systemic stress responses, engaging conserved transcription factors such as nuclear hormone receptors (NHRs). We emphasize instances where similar functions for individual Mediator subunits exist in mammals, highlighting parallels between Mediator subunit action in nematode development and in human cancer biology. We also discuss a parallel between the association of the Mediator subunit MED12 with several human disorders and the role of its C. elegans ortholog mdt-12 as a regulatory hub that interacts with numerous signaling pathways. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
Genome-wide association of mediator and RNA polymerase II in wild-type and mediator mutant yeast.

PubMed

Paul, Emily; Zhu, Z Iris; Landsman, David; Morse, Randall H

2015-01-01

Mediator is a large, multisubunit complex that is required for essentially all mRNA transcription in eukaryotes. In spite of the importance of Mediator, the range of its targets and how it is recruited to these is not well understood. Previous work showed that in Saccharomyces cerevisiae, Mediator contributes to transcriptional activation by two distinct mechanisms, one depending on the tail module triad and favoring SAGA-regulated genes, and the second occurring independently of the tail module and favoring TFIID-regulated genes. Here, we use chromatin immunoprecipitation sequencing (ChIP-seq) to show that dependence on tail module subunits for Mediator recruitment and polymerase II (Pol II) association occurs preferentially at SAGA-regulated over TFIID-regulated genes on a genome-wide scale. We also show that recruitment of tail module subunits to active gene promoters continues genome-wide when Mediator integrity is compromised in med17 temperature-sensitive (ts) yeast, demonstrating the modular nature of the Mediator complex in vivo. In addition, our data indicate that promoters exhibiting strong and stable occupancy by Mediator have a wide range of activity and are enriched for targets of the Tup1-Cyc8 repressor complex. We also identify a number of strong Mediator occupancy peaks that overlap dubious open reading frames (ORFs) and are likely to include previously unrecognized upstream activator sequences. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Genome-Wide Association of Mediator and RNA Polymerase II in Wild-Type and Mediator Mutant Yeast

PubMed Central

Paul, Emily; Zhu, Z. Iris

2014-01-01

Mediator is a large, multisubunit complex that is required for essentially all mRNA transcription in eukaryotes. In spite of the importance of Mediator, the range of its targets and how it is recruited to these is not well understood. Previous work showed that in Saccharomyces cerevisiae, Mediator contributes to transcriptional activation by two distinct mechanisms, one depending on the tail module triad and favoring SAGA-regulated genes, and the second occurring independently of the tail module and favoring TFIID-regulated genes. Here, we use chromatin immunoprecipitation sequencing (ChIP-seq) to show that dependence on tail module subunits for Mediator recruitment and polymerase II (Pol II) association occurs preferentially at SAGA-regulated over TFIID-regulated genes on a genome-wide scale. We also show that recruitment of tail module subunits to active gene promoters continues genome-wide when Mediator integrity is compromised in med17 temperature-sensitive (ts) yeast, demonstrating the modular nature of the Mediator complex in vivo. In addition, our data indicate that promoters exhibiting strong and stable occupancy by Mediator have a wide range of activity and are enriched for targets of the Tup1-Cyc8 repressor complex. We also identify a number of strong Mediator occupancy peaks that overlap dubious open reading frames (ORFs) and are likely to include previously unrecognized upstream activator sequences. PMID:25368384
Potential Mediators in Parenting and Family Intervention: Quality of Mediation Analyses

PubMed Central

Patel, Chandni C.; Fairchild, Amanda J.; Prinz, Ronald J.

2017-01-01

Parenting and family interventions have repeatedly shown effectiveness in preventing and treating a range of youth outcomes. Accordingly, investigators in this area have conducted a number of studies using statistical mediation to examine some of the potential mechanisms of action by which these interventions work. This review examined from a methodological perspective in what ways and how well the family-based intervention studies tested statistical mediation. A systematic search identified 73 published outcome studies that tested mediation for family-based interventions across a wide range of child and adolescent outcomes (i.e., externalizing, internalizing, and substance-abuse problems; high-risk sexual activity; and academic achievement), for putative mediators pertaining to positive and negative parenting, family functioning, youth beliefs and coping skills, and peer relationships. Taken as a whole, the studies used designs that adequately addressed temporal precedence. The majority of studies used the product of coefficients approach to mediation, which is preferred, and less limiting than the causal steps approach. Statistical significance testing did not always make use of the most recently developed approaches, which would better accommodate small sample sizes and more complex functions. Specific recommendations are offered for future mediation studies in this area with respect to full longitudinal design, mediation approach, significance testing method, documentation and reporting of statistics, testing of multiple mediators, and control for Type I error. PMID:28028654
Environmentally relevant metal and transition metal ions enhance Fc epsilon RI-mediated mast cell activation.

PubMed Central

Walczak-Drzewiecka, Aurelia; Wyczólkowska, Janina; Dastych, Jaroslaw

2003-01-01

Upon contact with allergen, sensitized mast cells release highly active proinflammatory mediators. Allergen-mediated mast cell activation is an important mechanism in the pathogenesis of atopic asthma. Asthmatic patients are especially susceptible to air pollution. Epidemiologic studies found a positive correlation between severity of symptoms among asthmatic patients and the level of particulate matter (PM) in the air. Among the constituents of PM are metals and transition metals, which could mediate some of its adverse effects on human health. We sought to determine the effect of metal and transition metal ions on allergen-mediated mast cell activation. We observed that several metal and transition metal ions activated mast cells and enhanced allergen-mediated mast cell activation. Thus, Al(3+), Cd(2+), and Sr(2+) induced release of granule-associated N-acetyl-ss-d-hexosaminidase, and Al(3+) and Ni(2+) enhanced antigen-mediated release. Metal and transition metal ions also induced significant secretion of interleukin (IL)-4 and increased antigen-mediated IL-4 secretion in mast cells. These effects of metal and transition metal ions on mast cells were observed at concentrations that do not result in direct cytotoxicity and might be relevant for environmental exposure. Thus, metals and transition metals could increase the level of allergen-mediated mast cell activation, which might be one of the mechanisms mediating exacerbation of allergen-driven asthma symptoms by air pollution. PMID:12727598
Anxiety, affect, self-esteem, and stress: mediation and moderation effects on depression.

PubMed

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.
Within-subject mediation analysis for experimental data in cognitive psychology and neuroscience.

PubMed

Vuorre, Matti; Bolger, Niall

2017-12-15

Statistical mediation allows researchers to investigate potential causal effects of experimental manipulations through intervening variables. It is a powerful tool for assessing the presence and strength of postulated causal mechanisms. Although mediation is used in certain areas of psychology, it is rarely applied in cognitive psychology and neuroscience. One reason for the scarcity of applications is that these areas of psychology commonly employ within-subjects designs, and mediation models for within-subjects data are considerably more complicated than for between-subjects data. Here, we draw attention to the importance and ubiquity of mediational hypotheses in within-subjects designs, and we present a general and flexible software package for conducting Bayesian within-subjects mediation analyses in the R programming environment. We use experimental data from cognitive psychology to illustrate the benefits of within-subject mediation for theory testing and comparison.
Natural Mediators in the Oxidation of Polycyclic Aromatic Hydrocarbons by Laccase Mediator Systems

PubMed Central

Johannes, Christian; Majcherczyk, Andrzej

2000-01-01

The oxidation of polycyclic aromatic compounds was studied in systems consisting of laccase from Trametes versicolor and so-called mediator compounds. The enzymatic oxidation of acenaphthene, acenaphthylene, anthracene, and fluorene was mediated by various laccase substrates (phenols and aromatic amines) or compounds produced and secreted by white rot fungi. The best natural mediators, such as phenol, aniline, 4-hydroxybenzoic acid, and 4-hydroxybenzyl alcohol were as efficient as the previously described synthetic compounds ABTS [2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)] and 1-hydroxybenzotriazole. The oxidation efficiency increased proportionally with the redox potentials of the phenolic mediators up to a maximum value of 0.9 V and decreased thereafter with redox potentials exceeding this value. Natural compounds such as methionine, cysteine, and reduced glutathione, containing sulfhydryl groups, were also active as mediator compounds. PMID:10653713
The power of mediation.

PubMed

Zerkin, A J

1999-01-01

There is a range of intervention strategies and procedures designed to assist parties in reaching agreement, from negotiation, over which parties have complete control, to arbitration, the process over which they have the least control. In the middle of this spectrum is mediation. Simply put, mediation is assisted negotiation. A mediator is an impartial person (or team) that works with the parties, mostly together and sometimes separately, to help them reach an agreement to resolve a dispute. The cornerstones of mediation are impartiality and confidentiality. The logic of mediation is that disputants can easily fall into many pitfalls trying to resolve a dispute without help. This article explores these common barriers to effective direct negotiations--such as overestimating the likelihood of prevailing through power, litigation, or arbitration--and presents a case study describing how a complex set of problems was resolved through mediation.
Regulation of metabolism by the Mediator complex.

PubMed

Youn, Dou Yeon; Xiaoli, Alus M; Pessin, Jeffrey E; Yang, Fajun

2016-01-01

The Mediator complex was originally discovered in yeast, but it is conserved in all eukaryotes. Its best-known function is to regulate RNA polymerase II-dependent gene transcription. Although the mechanisms by which the Mediator complex regulates transcription are often complicated by the context-dependent regulation, this transcription cofactor complex plays a pivotal role in numerous biological pathways. Biochemical, molecular, and physiological studies using cancer cell lines or model organisms have established the current paradigm of the Mediator functions. However, the physiological roles of the mammalian Mediator complex remain poorly defined, but have attracted a great interest in recent years. In this short review, we will summarize some of the reported functions of selective Mediator subunits in the regulation of metabolism. These intriguing findings suggest that the Mediator complex may be an important player in nutrient sensing and energy balance in mammals.

Transformational Leadership and Organizational Citizenship Behavior: A Meta-Analytic Test of Underlying Mechanisms.

PubMed

Nohe, Christoph; Hertel, Guido

2017-01-01

Based on social exchange theory, we examined and contrasted attitudinal mediators (affective organizational commitment, job satisfaction) and relational mediators (trust in leader, leader-member exchange; LMX) of the positive relationship between transformational leadership and organizational citizenship behavior (OCB). Hypotheses were tested using meta-analytic path models with correlations from published meta-analyses (761 samples with 227,419 individuals overall). When testing single-mediator models, results supported our expectations that each of the mediators explained the relationship between transformational leadership and OCB. When testing a multi-mediator model, LMX was the strongest mediator. When testing a model with a latent attitudinal mechanism and a latent relational mechanism, the relational mechanism was the stronger mediator of the relationship between transformational leadership and OCB. Our findings help to better understand the underlying mechanisms of the relationship between transformational leadership and OCB.
The healthy donor profile of immunoregulatory soluble mediators is altered by stem cell mobilization and apheresis.

PubMed

Melve, Guro Kristin; Ersvaer, Elisabeth; Paulsen Rye, Kristin; Bushra Ahmed, Aymen; Kristoffersen, Einar K; Hervig, Tor; Reikvam, Håkon; Hatfield, Kimberley Joanne; Bruserud, Øystein

2018-05-01

Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and thereafter harvested by leukapheresis are commonly used for allogeneic stem cell transplantation. Plasma levels of 38 soluble mediators (cytokines, soluble adhesion molecules, proteases, protease inhibitors) were analyzed in samples derived from healthy stem cell donors before G-CSF treatment and after 4 days, both immediately before and after leukapheresis. Donors could be classified into two main subsets based on their plasma mediator profile before G-CSF treatment. Seventeen of 36 detectable mediators were significantly altered by G-CSF; generally an increase in mediator levels was seen, including pro-inflammatory cytokines, soluble adhesion molecules and proteases. Several leukocyte- and platelet-released mediators were increased during apheresis. Both plasma and graft mediator profiles were thus altered and showed correlations to graft concentrations of leukocytes and platelets; these concentrations were influenced by the apheresis device used. Finally, the mediator profile of the allotransplant recipients was altered by graft infusion, and based on their day +1 post-transplantation plasma profile our recipients could be divided into two major subsets that differed in overall survival. G-CSF alters the short-term plasma mediator profile of healthy stem cell donors. These effects together with the leukocyte and platelet levels in the graft determine the mediator profile of the stem cell grafts. Graft infusion also alters the systemic mediator profile of the recipients, but further studies are required to clarify whether such graft-induced alterations have a prognostic impact. Copyright © 2018. Published by Elsevier Inc.
40 CFR 7.180 - Mediation of age discrimination complaints.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Mediation of age discrimination... Discrimination Prohibited on the Basis of Age § 7.180 Mediation of age discrimination complaints. (a) The OCR will refer all accepted complaints alleging age discrimination to the Mediation Agency designated by...
40 CFR 7.180 - Mediation of age discrimination complaints.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Mediation of age discrimination... Discrimination Prohibited on the Basis of Age § 7.180 Mediation of age discrimination complaints. (a) The OCR will refer all accepted complaints alleging age discrimination to the Mediation Agency designated by...
40 CFR 7.180 - Mediation of age discrimination complaints.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Mediation of age discrimination... Discrimination Prohibited on the Basis of Age § 7.180 Mediation of age discrimination complaints. (a) The OCR will refer all accepted complaints alleging age discrimination to the Mediation Agency designated by...
40 CFR 7.180 - Mediation of age discrimination complaints.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Mediation of age discrimination... Discrimination Prohibited on the Basis of Age § 7.180 Mediation of age discrimination complaints. (a) The OCR will refer all accepted complaints alleging age discrimination to the Mediation Agency designated by...
40 CFR 7.180 - Mediation of age discrimination complaints.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Mediation of age discrimination... Discrimination Prohibited on the Basis of Age § 7.180 Mediation of age discrimination complaints. (a) The OCR will refer all accepted complaints alleging age discrimination to the Mediation Agency designated by...
Mediated electrochemical oxidation of organic wastes without electrode separators

DOEpatents

Farmer, J.C.; Wang, F.T.; Hickman, R.G.; Lewis, P.R.

1996-05-14

An electrochemical cell/electrolyte/mediator combination is described for the efficient destruction of organic contaminants using metal salt mediators in a sulfuric acid electrolyte, wherein the electrodes and mediator are chosen such that hydrogen gas is produced at the cathode and no cell membrane is required. 3 figs.
Parental Mediation of Children's Viewing in a Changing Television Environment.

ERIC Educational Resources Information Center

Tidhar, Chava E.; Levinsohn, Hanna

1997-01-01

This study surveyed the effects of cable television on Israeli parents' mediation of their childrens' viewing. Results indicate the introduction of cable television changed strategies of parental control and mediation and parents' assessment of television's influence on children. Active parental mediation was closely related to the attribution of…
Methods for Mediation Analysis with Missing Data

ERIC Educational Resources Information Center

Zhang, Zhiyong; Wang, Lijuan

2013-01-01

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

ERIC Educational Resources Information Center

Keele, Luke

2015-01-01

In policy evaluations, interest may focus on why a particular treatment works. One tool for understanding why treatments work is causal mediation analysis. In this essay, I focus on the assumptions needed to estimate mediation effects. I show that there is no "gold standard" method for the identification of causal mediation effects. In…
29 CFR 1425.5 - Referral to FSIP.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE MEDIATION ASSISTANCE IN THE FEDERAL SERVICE § 1425.5 Referral to FSIP. If the mediation process has been completed and the parties are... Federal Services Impasses Panel. The Service shall not refer a case to FSIP until the mediation process...
41 CFR 101-8.717 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Mediation. 101-8.717... FINANCIAL ASSISTANCE 8.7-Discrimination Prohibited on the Basis of Age § 101-8.717 Mediation. (a) GSA promptly refers to the mediation agency designated by the Secretary, HHS, all sufficient complaints that...
13 CFR 117.12 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Mediation. 117.12 Section 117.12... Mediation. (a) SBA shall, after ensuring that the complaint falls within the coverage of this Act and all... clearly within an exception, promptly refer the complaint to the Federal Mediation and Conciliation...
15 CFR 930.112 - Request for Secretarial mediation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Request for Secretarial mediation. 930... RESOURCE MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.112 Request for Secretarial mediation. (a) The Secretary or other head of a Federal agency, or the...
29 CFR 1202.2 - Interpretation of mediation agreements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Interpretation of mediation agreements. 1202.2 Section 1202.2 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.2 Interpretation of mediation agreements. Under section 5, Second, of title I of the Railway Labor...
45 CFR 617.10 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Mediation. 617.10 Section 617.10 Public Welfare... OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF § 617.10 Mediation. (a) NSF will refer to the Federal Mediation and Conciliation Service all complaints that fall within...
29 CFR 1203.3 - Interpretation of mediation agreements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Interpretation of mediation agreements. 1203.3 Section 1203.3 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD APPLICATIONS FOR SERVICE § 1203.3 Interpretation of mediation agreements. (a) Applications may be filed with the Board's Chief of...
The Merits of Using Longitudinal Mediation

ERIC Educational Resources Information Center

Jose, Paul E.

2016-01-01

Many of the mediation analyses reported in the literature are based on concurrent or single-occasion data sets. The 2 overarching themes of the present article are: Results of concurrent mediations are inherently ambiguous, and researchers would be wise to conduct mediations on longitudinal data sets instead. An example included here demonstrates…
Single-Level and Multilevel Mediation Analysis

ERIC Educational Resources Information Center

Tofighi, Davood; Thoemmes, Felix

2014-01-01

Mediation analysis is a statistical approach used to examine how the effect of an independent variable on an outcome is transmitted through an intervening variable (mediator). In this article, we provide a gentle introduction to single-level and multilevel mediation analyses. Using single-level data, we demonstrate an application of structural…

Assessing Mediational Models: Testing and Interval Estimation for Indirect Effects

ERIC Educational Resources Information Center

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

2010-01-01

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…
The Contribution of Mediator-Based Deficiencies to Age Differences in Associative Learning

ERIC Educational Resources Information Center

Dunlosky, John; Hertzog, Christopher; Powell-Moman, Amy

2005-01-01

Production, mediational, and utilization deficiencies, which describe how strategy use may contribute to developmental trends in episodic memory, have been intensively investigated. Using a mediator report-and-retrieval method, the authors present evidence concerning the degree to which 2 previously unexplored mediator-based deficits--retrieval…
School-Based Peer Mediation Programs: A Natural Extension of Developmental Guidance Programs.

ERIC Educational Resources Information Center

Robertson, Gwendolyn

School-based peer mediation programs are natural extensions of the kindergarten-grade 12 developmental guidance programs. Peer mediation programs not only provide schools with alternatives to traditional discipline practices, but also teach students important life skills. Existing research on peer mediation is very limited, yet promising. This…
Sample Size Limits for Estimating Upper Level Mediation Models Using Multilevel SEM

ERIC Educational Resources Information Center

Li, Xin; Beretvas, S. Natasha

2013-01-01

This simulation study investigated use of the multilevel structural equation model (MLSEM) for handling measurement error in both mediator and outcome variables ("M" and "Y") in an upper level multilevel mediation model. Mediation and outcome variable indicators were generated with measurement error. Parameter and standard…
Mediator assessment, documentation, and disposition of child custody cases involving intimate partner abuse: a naturalistic evaluation of one county's practices.

PubMed

Beck, Connie J A; Walsh, Michele E; Mechanic, Mindy B; Taylor, Caitilin S

2010-06-01

The contentious and costly nature of the adversarial process for resolving child custody disputes has prompted scholars, practitioners, and policy makers to advocate for the development and implementation of less divisive forms of dispute resolution, notably, mediation. Mediation has been championed for its potential to resolve disputes with less acrimony among disputants, reduced economic costs, increased satisfaction with outcomes, and fewer adverse consequences for family members. Despite the increasing popularity, arguments have cautioned against the use of mandated mediation when intimate partner abuse (IPA) is alleged. This research documents a mediation screening process and models mediators' decision-making process as instantiated, naturally, in one jurisdiction.
The multitalented Mediator complex.

PubMed

Carlsten, Jonas O P; Zhu, Xuefeng; Gustafsson, Claes M

2013-11-01

The Mediator complex is needed for regulated transcription of RNA polymerase II (Pol II)-dependent genes. Initially, Mediator was only seen as a protein bridge that conveyed regulatory information from enhancers to the promoter. Later studies have added many other functions to the Mediator repertoire. Indeed, recent findings show that Mediator influences nearly all stages of transcription and coordinates these events with concomitant changes in chromatin organization. We review the multitude of activities associated with Mediator and discuss how this complex coordinates transcription with other cellular events. We also discuss the inherent difficulties associated with in vivo characterization of a coactivator complex that can indirectly affect diverse cellular processes via changes in gene transcription. Copyright © 2013 Elsevier Ltd. All rights reserved.
Frontal EEG asymmetry as a moderator and mediator of emotion.

PubMed

Coan, James A; Allen, John J B

2004-10-01

Frontal EEG asymmetry appears to serve as (1) an individual difference variable related to emotional responding and emotional disorders, and (2) a state-dependent concomitant of emotional responding. Such findings, highlighted in this review, suggest that frontal EEG asymmetry may serve as both a moderator and a mediator of emotion- and motivation-related constructs. Unequivocal evidence supporting frontal EEG asymmetry as a moderator and/or mediator of emotion is lacking, as insufficient attention has been given to analyzing the frontal EEG asymmetries in terms of moderators and mediators. The present report reviews the frontal EEG asymmetry literature from the framework of moderators and mediators, and overviews data analytic strategies that would support claims of moderation and mediation.
Effect of NaI/I 2 mediators on properties of PEO/LiAlO 2 based all-solid-state supercapacitors

NASA Astrophysics Data System (ADS)

Yin, Yijing; Zhou, Juanjuan; Mansour, Azzam N.; Zhou, Xiangyang

NaI/I 2 mediators and activated carbon were added into poly(ethylene oxide) (PEO)/lithium aluminate (LiAlO 2) electrolyte to fabricate composite electrodes. All solid-state supercapacitors were fabricated using the as prepared composite electrodes and a Nafion 117 membrane as a separator. Cyclic voltammetry, electrochemical impedance spectroscopy, and galvanostatic charge/discharge measurements were conducted to evaluate the electrochemical properties of the supercapacitors. With the addition of NaI/I 2 mediators, the specific capacitance increased by 27 folds up to 150 F g -1. The specific capacitance increased with increases in the concentration of mediators in the electrodes. The addition of mediators also reduced the electrode resistance and rendered a higher electron transfer rate between mediator and mediator. The stability of the all-solid-state supercapacitor was tested over 2000 charge/discharge cycles.
Polyoxometalate active charge-transfer material for mediated redox flow battery

DOEpatents

Anderson, Travis Mark; Hudak, Nicholas; Staiger, Chad; Pratt, Harry

2017-01-17

Redox flow batteries including a half-cell electrode chamber coupled to a current collecting electrode are disclosed herein. In a general embodiment, a separator is coupled to the half-cell electrode chamber. The half-cell electrode chamber comprises a first redox-active mediator and a second redox-active mediator. The first redox-active mediator and the second redox-active mediator are circulated through the half-cell electrode chamber into an external container. The container includes an active charge-transfer material. The active charge-transfer material has a redox potential between a redox potential of the first redox-active mediator and a redox potential of the second redox-active mediator. The active charge-transfer material is a polyoxometalate or derivative thereof. The redox flow battery may be particularly useful in energy storage solutions for renewable energy sources and for providing sustained power to an electrical grid.
Evaluation of 16 measures of mental workload using a simulated flight task emphasizing mediational activity

NASA Technical Reports Server (NTRS)

Wierwille, W. W.; Rahimi, M.; Casali, J. G.

1985-01-01

As aircraft and other systems become more automated, a shift is occurring in human operator participation in these systems. This shift is away from manual control and toward activities that tap the higher mental functioning of human operators. Therefore, an experiment was performed in a moving-base flight simulator to assess mediational (cognitive) workload measurement. Specifically, 16 workload estimation techniques were evaluated as to their sensitivity and intrusion in a flight task emphasizing mediational behavior. Task loading, using navigation problems presented on a display, was treated as an independent variable, and workload-measure values were treated as dependent variables. Results indicate that two mediational task measures, two rating scale measures, time estimation, and two eye behavior measures were reliably sensitive to mediational loading. The time estimation measure did, however, intrude on mediational task performance. Several of the remaining measures were completely insensitive to mediational load.
Relationship between mediation analysis and the structured life course approach

PubMed Central

Howe, Laura D; Smith, Andrew D; Macdonald-Wallis, Corrie; Anderson, Emma L; Galobardes, Bruna; Lawlor, Debbie A; Ben-Shlomo, Yoav; Hardy, Rebecca; Cooper, Rachel; Tilling, Kate; Fraser, Abigail

2016-01-01

Abstract Many questions in life course epidemiology involve mediation and/or interaction because of the long latency period between exposures and outcomes. In this paper, we explore how mediation analysis (based on counterfactual theory and implemented using conventional regression approaches) links with a structured approach to selecting life course hypotheses. Using theory and simulated data, we show how the alternative life course hypotheses assessed in the structured life course approach correspond to different combinations of mediation and interaction parameters. For example, an early life critical period model corresponds to a direct effect of the early life exposure, but no indirect effect via the mediator and no interaction between the early life exposure and the mediator. We also compare these methods using an illustrative real-data example using data on parental occupational social class (early life exposure), own adult occupational social class (mediator) and physical capability (outcome). PMID:27681097
Robust Mediation Analysis Based on Median Regression

PubMed Central

Yuan, Ying; MacKinnon, David P.

2014-01-01

Mediation analysis has many applications in psychology and the social sciences. The most prevalent methods typically assume that the error distribution is normal and homoscedastic. However, this assumption may rarely be met in practice, which can affect the validity of the mediation analysis. To address this problem, we propose robust mediation analysis based on median regression. Our approach is robust to various departures from the assumption of homoscedasticity and normality, including heavy-tailed, skewed, contaminated, and heteroscedastic distributions. Simulation studies show that under these circumstances, the proposed method is more efficient and powerful than standard mediation analysis. We further extend the proposed robust method to multilevel mediation analysis, and demonstrate through simulation studies that the new approach outperforms the standard multilevel mediation analysis. We illustrate the proposed method using data from a program designed to increase reemployment and enhance mental health of job seekers. PMID:24079925
Current options in the treatment of mast cell mediator-related symptoms in mastocytosis.

PubMed

Escribano, Luis; Akin, Cem; Castells, Mariana; Schwartz, Lawrence B

2006-01-01

Patients with mastocytosis have symptoms related to the tissue response to the release of mediators from mast cells (MC), local mast cell burden or associated non-mast cell hematological disorders. MC contain an array of biologically active mediators in their granules, which are preformed and stored. MC are also able to produce newly generated membrane-derived lipid mediators and are a source of multifunctional cytokines. Mediator-related symptoms can include pruritus, flushing, syncope, gastric distress, nausea and vomiting, diarrhea, bone pain and neuropsychiatric disturbances; these symptoms are variably controlled by adequate medications. Management of patients within all categories of mastocytosis includes: a) a careful counseling of patients (parents in pediatric cases) and care providers, b) avoidance of factors triggering acute mediator release, c) treatment of acute and chronic MC-mediator symptoms and, if indicated, d) an attempt for cytoreduction and treatment of organ infiltration by mast cells.
Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture

PubMed Central

Eychenne, Thomas; Novikova, Elizaveta; Barrault, Marie-Bénédicte; Alibert, Olivier; Boschiero, Claire; Peixeiro, Nuno; Cornu, David; Redeker, Virginie; Kuras, Laurent; Nicolas, Pierre; Werner, Michel; Soutourina, Julie

2016-01-01

Mediator is a large coregulator complex conserved from yeast to humans and involved in many human diseases, including cancers. Together with general transcription factors, it stimulates preinitiation complex (PIC) formation and activates RNA polymerase II (Pol II) transcription. In this study, we analyzed how Mediator acts in PIC assembly using in vivo, in vitro, and in silico approaches. We revealed an essential function of the Mediator middle module exerted through its Med10 subunit, implicating a key interaction between Mediator and TFIIB. We showed that this Mediator–TFIIB link has a global role on PIC assembly genome-wide. Moreover, the amplitude of Mediator's effect on PIC formation is gene-dependent and is related to the promoter architecture in terms of TATA elements, nucleosome occupancy, and dynamics. This study thus provides mechanistic insights into the coordinated function of Mediator and TFIIB in PIC assembly in different chromatin contexts. PMID:27688401
Transformational Leadership and Organizational Citizenship Behavior: A Meta-Analytic Test of Underlying Mechanisms

PubMed Central

Nohe, Christoph; Hertel, Guido

2017-01-01

Based on social exchange theory, we examined and contrasted attitudinal mediators (affective organizational commitment, job satisfaction) and relational mediators (trust in leader, leader-member exchange; LMX) of the positive relationship between transformational leadership and organizational citizenship behavior (OCB). Hypotheses were tested using meta-analytic path models with correlations from published meta-analyses (761 samples with 227,419 individuals overall). When testing single-mediator models, results supported our expectations that each of the mediators explained the relationship between transformational leadership and OCB. When testing a multi-mediator model, LMX was the strongest mediator. When testing a model with a latent attitudinal mechanism and a latent relational mechanism, the relational mechanism was the stronger mediator of the relationship between transformational leadership and OCB. Our findings help to better understand the underlying mechanisms of the relationship between transformational leadership and OCB. PMID:28848478
Mediation Analysis: A Practitioner's Guide.

PubMed

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.
Natural mediators in the oxidation of polycyclic aromatic hydrocarbons by laccase mediator systems

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

Johannes, C.; Majcherczyk, A.

2000-02-01

The oxidation of polycyclic aromatic compounds was studied in systems consisting of laccase from Trametes versicolor and so-called mediator compounds. The enzymatic oxidation of acenaphthene, acenaphthylene, anthracene, and fluorene was mediated by various laccase substrates (phenols and aromatic amines) or compounds produced and secreted by white rot fungi. The best natural mediators, such as phenol, aniline, 4-hydroxybenzoic acid, and 4-hydroxybenzyl alcohol were as efficient as the previously described synthetic compounds ABTS [2,2{prime}-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)] and 1-hydroxybenzotriazole. The oxidation efficiency increased proportionally with the redox potentials of the phenolic mediators up to a maximum value of 0.9 V and decreased thereafter withmore » redox potentials exceeding this value. Natural compounds such as methionine, cysteine, and reduced glutathione, containing sulfhydryl groups, were also active as mediator compounds.« less
Laccase from Pycnoporus cinnabarinus and phenolic compounds: can the efficiency of an enzyme mediator for delignifying kenaf pulp be predicted?

PubMed

Andreu, Glòria; Vidal, Teresa

2013-03-01

In this work, kenaf pulp was delignified by using laccase in combination with various redox mediators and the efficiency of the different laccase–mediator systems assessed in terms of the changes in pulp properties after bleaching. The oxidative ability of the individual mediators used (acetosyringone, syringaldehyde, p-coumaric acid, vanillin and actovanillone) and the laccase–mediator systems was determined by monitoring the oxidation–reduction potential (ORP) during process. The results confirmed the production of phenoxy radicals of variable reactivity and stressed the significant role of lignin structure in the enzymatic process. Although changes in ORP were correlated with the oxidative ability of the mediators, pulp properties as determined after the bleaching stage were also influenced by condensation and grafting reactions. As shown here, ORP measurements provide a first estimation of the delignification efficiency of a laccase–mediator system. Copyright © 2013 Elsevier Ltd. All rights reserved.
Equity by Design: Using Peer-Mediated Learning to Advance Equity for All Students

ERIC Educational Resources Information Center

Tan, Paulo; Macey, Erin M.; Thorius, Kathleen A. K.; Simon, Marsha

2013-01-01

The use of peer-mediated learning has emerged as a promising practice to transform the classroom experiences of both students with disabilities and their non-disabled peers. This brief summarizes the best practices for implementing peer-mediated learning and advocates situating peer-mediated learning in inclusive, interdependent learning…
Methods for Integrating Moderation and Mediation: A General Analytical Framework Using Moderated Path Analysis

ERIC Educational Resources Information Center

Edwards, Jeffrey R.; Lambert, Lisa Schurer

2007-01-01

Studies that combine moderation and mediation are prevalent in basic and applied psychology research. Typically, these studies are framed in terms of moderated mediation or mediated moderation, both of which involve similar analytical approaches. Unfortunately, these approaches have important shortcomings that conceal the nature of the moderated…

Effects of atopic dermatitis and gender on sebum lipid mediator and fatty acid profiles

USDA-ARS?s Scientific Manuscript database

Lipid mediator metabolism in skin is altered in some diseases. If mediators in skin secretions are influenced by skin health, they may provide useful clinical matrices with low subject burden. While lipid mediators in sweat can be altered by disease, the influences of skin diseases on sebum lipid me...
Are You Satisfied? Exploring the Mediating Effects of Mentoring Communication Strategies in Predicting Chinese International Graduate Students' Program Satisfaction

ERIC Educational Resources Information Center

Yang, Qinghua; Orrego Dunleavy, Victoria; Phillips, Jasmine Rene

2016-01-01

This study examined how mentoring initiation and maintenance strategies mediate the relationship between acculturative stress and intercultural communication competence on Chinese graduate students' program satisfaction. Results supported a partial mediation effect for mentoring maintenance strategies. By specifying the mediating effect, the model…
7 CFR 766.114 - State-certified mediation or voluntary meeting of creditors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false State-certified mediation or voluntary meeting of... Programs § 766.114 State-certified mediation or voluntary meeting of creditors. (a) A borrower who is...) State-certified mediation; or (2) Voluntary meeting of creditors when a State does not have a certified...
Causal Mediation in Educational Research: An Illustration Using International Assessment Data

ERIC Educational Resources Information Center

Caro, Daniel H.

2015-01-01

This paper applies the causal mediation framework proposed by Kosuke Imai and colleagues (Imai, Keele, & Tingley, 2010) to educational research by examining the causal mediating role of early literacy activities in parental education influences on reading performance. The paper argues that the study of causal mediation is particularly relevant…
45 CFR 400.83 - Mediation and fair hearings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false Mediation and fair hearings. 400.83 Section 400.83... Employment § 400.83 Mediation and fair hearings. (a) Mediation—(1) Public/private RCA program. The State must ensure that a mediation period prior to imposition of sanctions is provided to refugees by local...
46 CFR 502.411 - Mediation and other alternative means of dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 9 2010-10-01 2010-10-01 false Mediation and other alternative means of dispute... PROVISIONS RULES OF PRACTICE AND PROCEDURE Alternative Dispute Resolution § 502.411 Mediation and other alternative means of dispute resolution. (a) Parties are encouraged to utilize mediation or other forms of...
29 CFR 1471.635 - May the Federal Mediation and Conciliation Service settle a debarment or suspension action?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false May the Federal Mediation and Conciliation Service settle a...) FEDERAL MEDIATION AND CONCILIATION SERVICE GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) General Principles Relating to Suspension and Debarment Actions § 1471.635 May the Federal Mediation and...
29 CFR 1471.610 - What procedures does the Federal Mediation and Conciliation Service use in suspension and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false What procedures does the Federal Mediation and Conciliation... Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE GOVERNMENTWIDE DEBARMENT AND SUSPENSION... the Federal Mediation and Conciliation Service use in suspension and debarment actions? In deciding...
29 CFR 1471.135 - May the Federal Mediation and Conciliation Service exclude a person who is not currently...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false May the Federal Mediation and Conciliation Service exclude....135 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) General § 1471.135 May the Federal Mediation and...
29 CFR 1403.2 - Policies of the Federal Mediation and Conciliation Service.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Policies of the Federal Mediation and Conciliation Service. 1403.2 Section 1403.2 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE FUNCTIONS AND DUTIES § 1403.2 Policies of the Federal Mediation and Conciliation Service...
29 CFR 1403.5 - Relations with State and local mediation agencies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Relations with State and local mediation agencies. 1403.5 Section 1403.5 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE FUNCTIONS AND DUTIES § 1403.5 Relations with State and local mediation agencies. (a) If under State or local...
Parent-School Involvement and School Performance: Mediated Pathways among Socioeconomically Comparable African American and Euro-American Families.

ERIC Educational Resources Information Center

Hill, Nancy E.; Craft, Stacie A.

2003-01-01

Examines children's social and academic competencies as mediators to explain the often positive relation between parent-school involvement and achievement. Ethnic variation was examined. For African Americans, academic skills mediated the relations between school involvement and math performance. For Euro-Americans, social competence mediated the…
Mediation in the Schools. ERIC Digest.

ERIC Educational Resources Information Center

Trevaskis, David Keller

This digest discusses mediation as a form of conflict management that is receiving widespread attention in schools. Mediation involves a neutral third person, called a mediator, who assists the disputants in resolving their problem with the consent of all parties. It offers a risk-free way to settle disputes for the parties involved. Unresolved…
A Multiple Mediational Test of the Relationship between Childhood Maltreatment and Non-Suicidal Self-Injury

ERIC Educational Resources Information Center

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…
Prospective and Retrospective Processing in Associative Mediated Priming

ERIC Educational Resources Information Center

Jones, Lara L.

2012-01-01

Mediated priming refers to the faster word recognition of a target (e.g., milk) following presentation of a prime (e.g., pasture) that is related indirectly via a connecting "mediator" (e.g., cow). Association strength may be an important factor in whether mediated priming occurs prospectively (with target activation prior to its presentation) or…
Elaborative retrieval: Do semantic mediators improve memory?

PubMed

Lehman, Melissa; Karpicke, Jeffrey D

2016-10-01

The elaborative retrieval account of retrieval-based learning proposes that retrieval enhances retention because the retrieval process produces the generation of semantic mediators that link cues to target information. We tested 2 assumptions that form the basis of this account: that semantic mediators are more likely to be generated during retrieval than during restudy and that the generation of mediators facilitates later recall of targets. Although these assumptions are often discussed in the context of retrieval processes, we noted that there was little prior empirical evidence to support either assumption. We conducted a series of experiments to measure the generation of mediators during retrieval and restudy and to examine the effect of the generation of mediators on later target recall. Across 7 experiments, we found that the generation of mediators was not more likely during retrieval (and may be more likely during restudy), and that the activation of mediators was unrelated to subsequent free recall of targets and was negatively related to cued recall of targets. The results pose challenges for both assumptions of the elaborative retrieval account. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein.

PubMed

Lee, Na-Rae; Shin, Han-Bo; Kim, Hye-In; Choi, Myung-Soo; Inn, Kyung-Soo

2013-07-19

RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways. Copyright © 2013 Elsevier Inc. All rights reserved.
SPSS and SAS procedures for estimating indirect effects in simple mediation models.

PubMed

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/.
Is parenting the mediator of change in behavioral parent training for externalizing problems of youth?

PubMed

Forehand, Rex; Lafko, Nicole; Parent, Justin; Burt, Keith B

2014-12-01

Change in parenting behavior is theorized to be the mediator accounting for change in child and adolescent externalizing problems in behavioral parent training (BPT). The purpose of this review is to examine this assumption in BPT prevention and intervention programs. Eight intervention and 17 prevention studies were identified as meeting all criteria or all but one criterion for testing mediation. Parenting behaviors were classified as positive, negative, discipline, monitoring/supervision, or a composite measure. Forty-five percent of the tests performed across studies to test mediation supported parenting as a mediator. A composite measure of parenting and discipline received the most support, whereas monitoring/supervision was rarely examined. More support for the mediating role of parenting emerged for prevention than intervention studies and when meeting all criteria for testing mediation was not required. Although the findings do not call BPT into question as an efficacious treatment, they do suggest more attention should be focused on examining parenting as a putative mediator in BPT. Copyright © 2014 Elsevier Ltd. All rights reserved.
The function of the Mediator complex in plant immunity.

PubMed

An, Chuanfu; Mou, Zhonglin

2013-03-01

Upon pathogen infection, plants undergo dramatic transcriptome reprogramming to shift from normal growth and development to immune response. During this rapid process, the multiprotein Mediator complex has been recognized as an important player to fine-tune gene-specific and pathway-specific transcriptional reprogramming by acting as an adaptor/coregulator between sequence-specific transcription factor and RNA polymerase II (RNAPII). Here, we review current understanding of the role of five functionally characterized Mediator subunits (MED8, MED15, MED16, MED21 and MED25) in plant immunity. All these Mediator subunits positively regulate resistance against leaf-infecting biotrophic bacteria or necrotrophic fungi. While MED21 appears to regulate defense against fungal pathogens via relaying signals from upstream regulators and chromatin modification to RNAPII, the other four Mediator subunits locate at different positions of the defense network to convey phytohormone signal(s). Fully understanding the role of Mediator in plant immunity needs to characterize more Mediator subunits in both Arabidopsis and other plant species. Identification of interacting proteins of Mediator subunits will further help to reveal their specific regulatory mechanisms in plant immunity.

Mediators and moderators in early intervention research.

PubMed

Breitborde, Nicholas J K; Srihari, Vinod H; Pollard, Jessica M; Addington, Donald N; Woods, Scott W

2010-05-01

The goal of this paper is to provide clarification with regard to the nature of mediator and moderator variables and the statistical methods used to test for the existence of these variables. Particular attention will be devoted to discussing the ways in which the identification of mediator and moderator variables may help to advance the field of early intervention in psychiatry. We completed a literature review of the methodological strategies used to test for mediator and moderator variables. Although several tests for mediator variables are currently available, recent evaluations suggest that tests which directly evaluate the indirect effect are superior. With regard to moderator variables, two approaches ('pick-a-point' and regions of significance) are available, and we provide guidelines with regard to how researchers can determine which approach may be most appropriate to use for their specific study. Finally, we discuss how to evaluate the clinical importance of mediator and moderator relationships as well as the methodology to calculate statistical power for tests of mediation and moderation. Further exploration of mediator and moderator variables may provide valuable information with regard to interventions provided early in the course of a psychiatric illness.
Testing a multiple mediator model of the effect of childhood sexual abuse on adolescent sexual victimization.

PubMed

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.
Longitudinal Mediation Analysis with Time-varying Mediators and Exposures, with Application to Survival Outcomes

PubMed Central

Zheng, Wenjing; van der Laan, Mark

2017-01-01

In this paper, we study the effect of a time-varying exposure mediated by a time-varying intermediate variable. We consider general longitudinal settings, including survival outcomes. At a given time point, the exposure and mediator of interest are influenced by past covariates, mediators and exposures, and affect future covariates, mediators and exposures. Right censoring, if present, occurs in response to past history. To address the challenges in mediation analysis that are unique to these settings, we propose a formulation in terms of random interventions based on conditional distributions for the mediator. This formulation, in particular, allows for well-defined natural direct and indirect effects in the survival setting, and natural decomposition of the standard total effect. Upon establishing identifiability and the corresponding statistical estimands, we derive the efficient influence curves and establish their robustness properties. Applying Targeted Maximum Likelihood Estimation, we use these efficient influence curves to construct multiply robust and efficient estimators. We also present an inverse probability weighted estimator and a nested non-targeted substitution estimator for these parameters. PMID:29387520
Mediators of the Relationship Between Racial Identity and Life Satisfaction in a Community Sample of African American Women and Men

PubMed Central

Yap, Stevie C. Y.; Settles, Isis H.; Pratt-Hyatt, Jennifer S.

2017-01-01

Few empirical studies have explored the mechanisms through which racial identity, the importance of racial group membership, affects well-being for racial/ethnic minorities. Using a community sample of 161 African American adults, the present study examined whether the association between racial identity (centrality, public regard, and private regard) and life satisfaction is mediated by two identity functions, belongingness and discrimination. Our results indicated that the relationships of centrality and private regard with life satisfaction were mediated by perceptions of belongingness. Furthermore, gender moderated the strength of each of these mediating effects, such that belongingness mediated these relationships for women but not for men. Our results also indicated that the relationship between public regard and life satisfaction was mediated by perceptions of discrimination. Furthermore, higher public regard was related to lower perceptions of discrimination for women but not men. However, a combined model for public regard and life satisfaction as mediated by discrimination failed to show moderated mediation. We discuss these results in relation to research and theory on racial identity and intersectionality. PMID:21341901
Mediators of the relationship between racial identity and life satisfaction in a community sample of African American women and men.

PubMed

Yap, Stevie C Y; Settles, Isis H; Pratt-Hyatt, Jennifer S

2011-01-01

Few empirical studies have explored the mechanisms through which racial identity, the importance of racial group membership, affects well-being for racial/ethnic minorities. Using a community sample of 161 African American adults, the present study examined whether the association between racial identity (centrality, public regard, and private regard) and life satisfaction is mediated by two identity functions, belongingness and discrimination. Our results indicated that the relationships of centrality and private regard with life satisfaction were mediated by perceptions of belongingness. Furthermore, gender moderated the strength of each of these mediating effects, such that belongingness mediated these relationships for women but not for men. Our results also indicated that the relationship between public regard and life satisfaction was mediated by perceptions of discrimination. Furthermore, higher public regard was related to lower perceptions of discrimination for women but not men. However, a combined model for public regard and life satisfaction as mediated by discrimination failed to show moderated mediation. We discuss these results in relation to research and theory on racial identity and intersectionality.
The Care of Our Hybrid Selves: Ethics in Times of Technical Mediation.

PubMed

Dorrestijn, Steven

2017-01-01

What can the art of living after Foucault contribute to ethics in relation to the mediation of human existence by technology? To develop the relation between technical mediation and ethics, firstly the theme of technical mediation is elaborated in line with Foucault's notion of ethical problematization. Every view of what technology does to us at the same time expresses an ethical concern about technology. The contemporary conception of technical mediation tends towards the acknowledgement of ongoing hybridization, not ultimately good or bad but ambivalent, which means for us the challenge of taking care of ourselves as hybrid beings. Secondly, the work of Foucault provides elements for imagining this care for our hybrid selves, notably his notions of freedom as a practice and of the care of the self. A conclusions about technical mediation and ethics is that whereas the approaches of the delegation of morality to technology by Latour and mediated morality by Verbeek see technical mediation of behavior and moral outlook as an answer in ethics, this should rather be considered the problem that ethics is about.
Association between sleep difficulties as well as duration and hypertension: is BMI a mediator?

PubMed

Carrillo-Larco, R M; Bernabe-Ortiz, A; Sacksteder, K A; Diez-Canseco, F; Cárdenas, M K; Gilman, R H; Miranda, J J

2017-01-01

Sleep difficulties and short sleep duration have been associated with hypertension. Though body mass index (BMI) may be a mediator variable, the mediation effect has not been defined. We aimed to assess the association between sleep duration and sleep difficulties with hypertension, to determine if BMI is a mediator variable, and to quantify the mediation effect. We conducted a mediation analysis and calculated prevalence ratios with 95% confidence intervals. The exposure variables were sleep duration and sleep difficulties, and the outcome was hypertension. Sleep difficulties were statistically significantly associated with a 43% higher prevalence of hypertension in multivariable analyses; results were not statistically significant for sleep duration. In these analyses, and in sex-specific subgroup analyses, we found no strong evidence that BMI mediated the association between sleep indices and risk of hypertension. Our findings suggest that BMI does not appear to mediate the association between sleep patterns and hypertension. These results highlight the need to further study the mechanisms underlying the relationship between sleep patterns and cardiovascular risk factors.
The Mediating Role of Loneliness in the Relation Between Social Engagement and Depressive Symptoms Among Older Korean Americans: Do Men and Women Differ?

PubMed Central

2013-01-01

Objectives. This study conceptualized loneliness as a mediator in the relation between social engagement and depressive symptoms and explored gender differences in the mediation model. Various indices of social engagement were considered including living arrangement, social network, and activity participation. Method. Using data from 674 community-dwelling Korean American older adults, we first examined the mediation effect of loneliness in the relation between each of 3 indices of social engagement (not living alone, social network, and activity participation) and depressive symptoms. Subsequently, gender differences in the mediation model were examined. Results. As hypothesized, loneliness was found to mediate the relation between each of the indices of social engagement and depressive symptoms in both men and women. We also observed gender differences in the strength of mediating effects; the effect of living alone was more likely to be mediated by loneliness among men, whereas women showed greater levels of mediation in the models with social network and activity participation. Discussion. Our findings suggest that loneliness may explain the mechanism by which deficits in social engagement exerts its effect on depressive symptoms and that gender differences should be considered in interventions targeting social engagement for mental health promotion. PMID:22929386
The development of CotA mediator cocktail system for dyes decolorization.

PubMed

Luo, S; Xie, T; Liu, Z; Sun, F; Wang, G

2018-05-01

The increasing use of dyes leads to serious environmental concerns, it is significant to explore eco-friendly and economic approaches for dye decolorization. This study aimed to develop mediator cocktail (AS and ABTS) for enhancing the capability of laccase-mediator system in the removal of dyes. By mediator screening, the mediators of ABTS and AS (ABTS, 2, 2'-azino-bis-(3-ethylbenzothiazo-thiazoline-6-sulphonic acid); AS, acetosyringone) were combined for dyes decolorization. The Box-Behnken Design and response surface analysis was performed to optimize experiment conditions. Comparing the CotA-ABTS-AS cocktail system with CotA-single mediator system showed that the coupling of ABTS and AS could increase the decolorization rate 15 times higher, save a third of the cost and shorten the reaction time by 50%. In addition, our studies revealed that sequential oxidation may occur in CotA-ABTS-AS system. Compared with CotA laccase-single mediator system, the CotA-ABTS-AS cocktail system showed advantages including higher efficiency, lower cost and shorter reaction time. This was the first report on the dyes decolorization by laccase mediator cocktail system. These results paved the curb for the application of laccase mediator system in various industrial processes. © 2018 The Society for Applied Microbiology.
The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator

PubMed Central

Grants, Jennifer M.; Goh, Grace Y. S.; Taubert, Stefan

2015-01-01

The Mediator multiprotein complex (‘Mediator’) is an important transcriptional coregulator that is evolutionarily conserved throughout eukaryotes. Although some Mediator subunits are essential for the transcription of all protein-coding genes, others influence the expression of only subsets of genes and participate selectively in cellular signaling pathways. Here, we review the current knowledge of Mediator subunit function in the nematode Caenorhabditis elegans, a metazoan in which established and emerging genetic technologies facilitate the study of developmental and physiological regulation in vivo. In this nematode, unbiased genetic screens have revealed critical roles for Mediator components in core developmental pathways such as epidermal growth factor (EGF) and Wnt/β-catenin signaling. More recently, important roles for C. elegans Mediator subunits have emerged in the regulation of lipid metabolism and of systemic stress responses, engaging conserved transcription factors such as nuclear hormone receptors (NHRs). We emphasize instances where similar functions for individual Mediator subunits exist in mammals, highlighting parallels between Mediator subunit action in nematode development and in human cancer biology. We also discuss a parallel between the association of the Mediator subunit MED12 with several human disorders and the role of its C. elegans ortholog mdt-12 as a regulatory hub that interacts with numerous signaling pathways. PMID:25634893
Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor

PubMed Central

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

2016-01-01

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. PMID:27185874
Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo

PubMed Central

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

2015-01-01

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 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. PMID:26240385
Mediating pathways from central obesity to childhood asthma: a population-based longitudinal study.

PubMed

Chih, An-Hsuan; Chen, Yang-Ching; Tu, Yu-Kang; Huang, Kuo-Chin; Chiu, Tai-Yuan; Lee, Yungling Leo

2016-09-01

The mediating pathways linking obesity and asthma are largely unknown. We aimed to investigate the mediating pathways and to search for the most prominent pathological mechanism between central obesity and childhood asthma.In the Taiwan Children Health Study, we collected data on an open cohort of children aged 9-13 years. Children's respiratory outcomes, atopic conditions, obesity measures and pulmonary function were surveyed annually between 2010 and 2012. Exhaled nitric oxide fraction concentrations were recorded in 2012. Generalised estimating equations and general linear models were used to examine the associations between central obesity, possible mediators and asthma. Structural equation models were applied to investigate the pathways that mediate the link between central obesity and asthma.Central obesity (waist-to-hip ratio) most accurately predicted childhood asthma. In the active asthma model, the percentage of mediation was 28.6% for pulmonary function, 18.1% for atopy and 5.7% for airway inflammation. The percentage of mediation for pulmonary function was 40.2% in the lifetime wheeze model. Pulmonary function was responsible for the greatest percentage of mediation among the three mediators in both models.Decline in pulmonary function is the most important pathway in central obesity related asthma. Pulmonary function screening should be applied to obese children for asthma risk prediction. Copyright ©ERS 2016.
Nonlinear Predictive Models for Multiple Mediation Analysis: With an Application to Explore Ethnic Disparities in Anxiety and Depression Among Cancer Survivors.

PubMed

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

2018-04-02

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

PubMed

Zou, Zhi-Yong; Yang, Yi-de; Wang, Shuo; Dong, Bin; Li, Xiao-Hui; Ma, Jun

2016-07-01

We aimed to examine the contribution of blood lipids to the association between BMI and blood pressure (BP) in children with overweight and obesity. Data were collected in elementary and high schools of Chaoyang District, Beijing, China in 2012. Participants' weight, height, BP and fasting plasma lipid profile were measured by standard protocols. Mediation analysis was used to examine the mediation role of blood lipids on the relation between BMI and BP, with age included as a covariate. We found that in boys 8·29 % (mediation effect=0·106, P=0·012) of the association between BMI and systolic BP was mediated through TAG. TAG mediated 12·53 % (mediation effect=0·093, P=0·018) and LDL-cholesterol mediated 7·75 % (mediation effect=0·57, P=0·046) of the association between BMI and diastolic BP was mediated by TAG and LDL-cholesterol, respectively. However, blood lipids did not show the mediation effect in girls. Our findings suggested that there was a sex difference in the contribution of blood lipids to the association between BMI and BP. Controlling TAG or LDL-cholesterol may be beneficial for reducing the risk of the BMI-related high BP in overweight boys; however, this outcome is not the case when controlling TAG or LDL-cholesterol in girls. This study may provide clues to explore the underlying mechanism of the association between obesity and hypertension.
Anxiety, Affect, Self-Esteem, and Stress: Mediation and Moderation Effects on Depression

PubMed Central

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

PubMed

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.
Cognitive and affective mechanisms of pain and fatigue in multiple sclerosis.

PubMed

Arewasikporn, Anne; Turner, Aaron P; Alschuler, Kevin N; Hughes, Abbey J; Ehde, Dawn M

2018-06-01

To examine the extent to which pain catastrophizing, fatigue catastrophizing, positive affect, and negative affect simultaneously mediated the associations between common symptoms of multiple sclerosis (MS; i.e., pain, fatigue) and impact on daily life, depressive symptoms, and resilience. Participants were community-dwelling adults with MS (N = 163) reporting chronic pain, fatigue, and/or moderate depressive symptoms. Multiple mediation path analysis was used to model potential mediators of pain and fatigue separately, using baseline data from a randomized controlled trial comparing two symptom self-management interventions. In the pain model, pain catastrophizing was a mediator of pain intensity with pain interference and depression. Negative affect was a mediator of pain intensity with depression and resilience. In the fatigue model, fatigue catastrophizing was a mediator of fatigue intensity with fatigue impact and depression. Positive affect was a mediator of fatigue intensity with depression and resilience. These findings provide preliminary support for the presence of differential effects of cognitive-affective mediators and suggest potential targets for psychological interventions based on an individual's clinical presentation. The differential mediating effects also support the inclusion of both positive and negative aspects of psychological health in models of pain and fatigue, which would not be otherwise apparent if negative constructs were examined in isolation. To our knowledge, this is the first study to utilize a multivariate path analysis approach to examine cognitive-affective mediators of pain and fatigue in MS, while also examining positive and negative constructs concurrently. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Psychological distress longitudinally mediates the effect of vertigo symptoms on vertigo-related handicap.

PubMed

Probst, Thomas; Dinkel, Andreas; Schmid-Mühlbauer, Gabriele; Radziej, Katharina; Limburg, Karina; Pieh, Christoph; Lahmann, Claas

2017-02-01

Vertigo symptoms can lead to more or less vertigo-related handicap. This longitudinal study investigated whether depression, anxiety, and/or somatization mediate the relationship between vertigo symptoms and vertigo-related handicap. N=111 patients with vertigo/dizziness provided complete data on the following measures: Vertigo symptoms at baseline, depression at 6-month follow-up, anxiety at 6-month follow-up, somatization at 6-month follow-up, and vertigo handicap at 12-month follow-up. Mediation analyses with bootstrapping were performed to investigate the mediating role of anxiety, depression, and somatization in the relationship between vertigo symptoms and vertigo-related handicap. When the mediating role of anxiety, depression, and somatization was evaluated separately from each other in single mediation models, the effect vertigo symptoms at baseline exerted on vertigo-related handicap at 12-month follow-up was significantly mediated by depression at 6-month follow-up (p<0.05), by anxiety at 6-month follow-up (p<0.05), as well as by somatization at 6-month follow-up (p<0.05). When statistically controlling for the other mediators in a multiple mediator model, only depression at 6-month follow-up mediated the effect of vertigo symptoms at baseline on vertigo-related handicap at 12-month follow-up (p<0.05). Psychological distress is an important mechanism in the process how vertigo symptoms lead to vertigo-related handicap. Copyright © 2016 Elsevier Inc. All rights reserved.
Efficacy of family mediation and the role of family violence: study protocol.

PubMed

Cleak, Helen; Schofield, Margot; Bickerdike, Andrew

2014-01-21

Family law reforms in Australia require separated parents in dispute to attempt mandatory family dispute resolution (FDR) in community-based family services before court attendance. However, there are concerns about such services when clients present with a history of high conflict and family violence. This study protocol describes a longitudinal study of couples presenting for family mediation services. The study aims to describe the profile of family mediation clients, including type of family violence, and determine the impact of violence profiles on FDR processes and outcomes, such as the type and durability of shared parenting arrangements and clients' satisfaction with mediated agreements. A mixed method, naturalistic longitudinal design is used. The sampling frame is clients presenting at nine family mediation centres across metropolitan, outer suburban, and regional/rural sites in Victoria, Australia. Data are collected at pre-test, completion of mediation, and six months later. Self-administered surveys are administered at the three time points, and a telephone interview at the final post-test. The key study variable is family violence. Key outcome measures are changes in the type and level of acrimony and violent behaviours, the relationship between violence and mediated agreements, the durability of agreements over six months, and client satisfaction with mediation. Family violence is a major risk to the physical and mental health of women and children. This study will inform debates about the role of family violence and how to manage it in the family mediation context. It will also inform decision-making about mediation practices by better understanding how mediation impacts on parenting agreements, and the implications for children, especially in the context of family violence.

Body mass index, depression, and suicidality: The role of self-esteem in bariatric surgery candidates.

PubMed

Yusufov, Miryam; Dalrymple, Kristy; Bernstein, Michael H; Walsh, Emily; Rosenstein, Lia; Chelminski, Iwona; Zimmerman, Mark

2017-01-15

Previous research suggests a relationship between weight and depression/suicidality, although few studies have examined the mechanisms underlying this association. This study examined the mediating role of self-esteem in the relationship between BMI and depression/suicidality, as well as the moderating role of gender in the mediated pathways. As part of a screening process in consideration for bariatric surgery, 3,101 adults (81.4% female, 18.6% male) were assessed one time. Five univariate mediation and five univariate moderated-mediation models were hypothesized and analyzed. For the mediation models, we entered five outcome variables separately: 1) severity of depressed mood, 2) diagnosis of Major Depressive Disorder, 3) lifetime history of suicide attempts, 4) suicidal ideation at the time of evaluation, and 5) severity of suicidality, BMI as the independent variable, and self-esteem as the mediator. For the moderated-mediated models, gender was examined as a moderator to examine whether self-esteem was a stronger mediator for one gender, compared to the other. Findings supported the mediating role of self-esteem across all five outcomes. Further, the mediated effect was moderated by gender, such that the mediation effect was stronger for males, compared to females. The majority of the sample consisted of White females, limiting broad applicability of findings. All variables were assessed simultaneously, at baseline, limiting the ability to make causal attributions. Study findings suggest that self-esteem may help explain the relationship between BMI and depression/suicidality, particularly for men. Thus, interventions targeting self-esteem may be useful for improving psychological outcomes among those presenting for bariatric surgery. Copyright © 2016 Elsevier B.V. All rights reserved.
The Tlo Proteins Are Stoichiometric Components of Candida albicans Mediator Anchored via the Med3 Subunit

PubMed Central

Zhang, Anda; Petrov, Kostadin O.; Hyun, Emily R.; Liu, Zhongle; Gerber, Scott A.

2012-01-01

The amplification of the TLO (for telomere-associated) genes in Candida albicans, compared to its less pathogenic, close relative Candida dubliniensis, suggests a role in virulence. Little, however, is known about the function of the Tlo proteins. We have purified the Mediator coactivator complex from C. albicans (caMediator) and found that Tlo proteins are a stoichiometric component of caMediator. Many members of the Tlo family are expressed, and each is a unique member of caMediator. Protein expression analysis of individual Tlo proteins, as well as the purification of tagged Tlo proteins, demonstrate that there is a large free population of Tlo proteins in addition to the Mediator-associated population. Coexpression and copurification of Tloα12 and caMed3 in Escherichia coli established a direct physical interaction between the two proteins. We have also made a C. albicans med3Δ/Δ strain and purified an intact Mediator from this strain. The analysis of the composition of the med3Δ Mediator shows that it lacks a Tlo subunit. Regarding Mediator function, the med3Δ/Δ strain serves as a substitute for the difficult-to-make tloΔ/Δ C. albicans strain. A potential role of the TLO and MED3 genes in virulence is supported by the inability of the med3Δ/Δ strain to form normal germ tubes. This study of caMediator structure provides initial clues to the mechanism of action of the Tlo genes and a platform for further mechanistic studies of caMediator's involvement in gene regulatory patterns that underlie pathogenesis. PMID:22562472
Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis.

PubMed

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

2017-11-01

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

PubMed

Lett, Tristram A; Waller, Lea; Tost, Heike; Veer, Ilya M; Nazeri, Arash; Erk, Susanne; Brandl, Eva J; Charlet, Katrin; Beck, Anne; Vollstädt-Klein, Sabine; Jorde, Anne; Kiefer, Falk; Heinz, Andreas; Meyer-Lindenberg, Andreas; Chakravarty, M Mallar; Walter, Henrik

2017-06-01

Threshold-free cluster enhancement (TFCE) is a sensitive means to incorporate spatial neighborhood information in neuroimaging studies without using arbitrary thresholds. The majority of methods have applied TFCE to voxelwise data. The need to understand the relationship among multiple variables and imaging modalities has become critical. We propose a new method of applying TFCE to vertexwise statistical images as well as cortexwise (either voxel- or vertexwise) mediation analysis. Here we present TFCE_mediation, a toolbox that can be used for cortexwise multiple regression analysis with TFCE, and additionally cortexwise mediation using TFCE. The toolbox is open source and publicly available (https://github.com/trislett/TFCE_mediation). We validated TFCE_mediation in healthy controls from two independent multimodal neuroimaging samples (N = 199 and N = 183). We found a consistent structure-function relationship between surface area and the first independent component (IC1) of the N-back task, that white matter fractional anisotropy is strongly associated with IC1 N-back, and that our voxel-based results are essentially identical to FSL randomise using TFCE (all P FWE <0.05). Using cortexwise mediation, we showed that the relationship between white matter FA and IC1 N-back is mediated by surface area in the right superior frontal cortex (P FWE < 0.05). We also demonstrated that the same mediation model is present using vertexwise mediation (P FWE < 0.05). In conclusion, cortexwise analysis with TFCE provides an effective analysis of multimodal neuroimaging data. Furthermore, cortexwise mediation analysis may identify or explain a mechanism that underlies an observed relationship among a predictor, intermediary, and dependent variables in which one of these variables is assessed at a whole-brain scale. Hum Brain Mapp 38:2795-2807, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Efficacy of family mediation and the role of family violence: study protocol

PubMed Central

2014-01-01

Background Family law reforms in Australia require separated parents in dispute to attempt mandatory family dispute resolution (FDR) in community-based family services before court attendance. However, there are concerns about such services when clients present with a history of high conflict and family violence. This study protocol describes a longitudinal study of couples presenting for family mediation services. The study aims to describe the profile of family mediation clients, including type of family violence, and determine the impact of violence profiles on FDR processes and outcomes, such as the type and durability of shared parenting arrangements and clients’ satisfaction with mediated agreements. Methods A mixed method, naturalistic longitudinal design is used. The sampling frame is clients presenting at nine family mediation centres across metropolitan, outer suburban, and regional/rural sites in Victoria, Australia. Data are collected at pre-test, completion of mediation, and six months later. Self-administered surveys are administered at the three time points, and a telephone interview at the final post-test. The key study variable is family violence. Key outcome measures are changes in the type and level of acrimony and violent behaviours, the relationship between violence and mediated agreements, the durability of agreements over six months, and client satisfaction with mediation. Discussion Family violence is a major risk to the physical and mental health of women and children. This study will inform debates about the role of family violence and how to manage it in the family mediation context. It will also inform decision-making about mediation practices by better understanding how mediation impacts on parenting agreements, and the implications for children, especially in the context of family violence. PMID:24443936
GPER-independent effects of estrogen in rat aortic vascular endothelial cells.

PubMed

Ding, Q; Hussain, Y; Chorazyczewski, J; Gros, R; Feldman, R D

2015-01-05

GPER (aka GPR30) has been identified as an important mechanism by which estrogen mediates its effects. Previous studies from our laboratories and those of others have demonstrated that GPER activation mediates a range of vascular contractile and growth regulatory responses. However, the importance of GPER in mediating the actions of estradiol (E2) in rat aortic endothelial cells is unclear. Therefore, we sought to determine the importance of GPER vs. the "classical" estrogen receptor (ER) in mediating the endothelial growth regulatory effects of E2. To do this we assessed the effect of E2 in regulating phosphoERK content and apoptotic rates in rat aortic endothelial cells and the role of GPER in mediating these effects. E2 mediated a concentration-dependent inhibition of both ERK phosphorylation and serum deprivation-induced apoptosis with a maximal effect at a concentration of 10 nM. Pretreatment with the ER antagonist ICI 182780 abolished E2-mediated inhibition of both ERK phosphorylation and apoptosis. In contrast, pretreatment with GPER antagonist G15 had no significant effect on E2-mediated inhibition of ERK phosphorylation or on apoptosis. Further, downregulation of GPER expression with a GPER shRNA adenovirus did not block E2-mediated inhibitory effects on ERK phosphorylation and apoptosis. In fact, these inhibitory effects of E2 were further enhanced by GPER downregulation. Downregulation of ERα expression reversed the E2-mediated inhibitory effects to stimulatory effects. E2's phosphoERK and apoptosis stimulatory effects seen with ERα downregulation are attenuated by pretreatment with G15. In conclusion, in rat aortic endothelial cells, E2-mediated endothelial effects are predominantly driven by ER and not by GPER. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
A systematic review: can one prescribe carbapenems to patients with IgE-mediated allergy to penicillins or cephalosporins?

PubMed

Kula, Brittany; Djordjevic, Gordana; Robinson, Joan L

2014-10-15

Cross-reactivity between penicillins or cephalosporins and carbapenems is anticipated as all have a beta lactam ring. However, the true incidence of immunoglobulin (Ig)E-mediated cross-reactivity is not known. A systematic review was conducted to collect and combine all published data on children and adults reported to have a clinical history of IgE-mediated hypersensitivity to a penicillin and/or cephalosporin who were subsequently given a carbapenem. Reactions were classified as proven, suspected, or possible IgE-mediated and non-IgE-mediated. Ten studies and 12 case reports describing 854 participants fit the study criteria. For patients with previous proven, suspected, or possible IgE-mediated penicillin reactions (N = 838), the incidence of any type of suspected hypersensitivity reaction to a carbapenem was 36/838 (4.3%; 95% confidence interval [CI], 3.1%-5.9%) and the incidence of proven (1/838), suspected (0/838), or possible (19/838) IgE-mediated reactions was 20/838 (2.4%; 95% CI, 1.6%-3.7%). Of the subset of patients with positive penicillin skin tests (n = 295), only 1 had a hypersensitivity reaction (0.3%; 95% CI, .06%-1.9%), and this was a possible IgE-mediated reaction. For patients with previous proven, suspected, or possible IgE-mediated cephalosporin reactions (N = 12), the incidence of any type of hypersensitivity reaction to a carbapenem was 3/12 (25%); this included 2 non-IgE-mediated reactions and 1 possible IgE-mediated reaction. The cross-reactivity between penicillins and carbapenems for IgE-mediated reactions is very low, but caution is still advised. Cross-reactivity rates may be higher between cephalosporins and carbapenems; however, minimal data are available. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
The Effects of Constraints and Mastery on Mental and Physical Health: Conceptual and Methodological Considerations

PubMed Central

Infurna, Frank J.; Mayer, Axel

2015-01-01

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

PubMed

Springvloet, Linda; Lechner, Lilian; Candel, Math J J M; de Vries, Hein; Oenema, Anke

2016-03-01

This study explored whether the determinants that were targeted in two versions of a Web-based computer-tailored nutrition education intervention mediated the effects on fruit, high-energy snack, and saturated fat intake among adults who did not comply with dietary guidelines. A RCT was conducted with a basic (tailored intervention targeting individual cognitions and self-regulation), plus (additionally targeting environmental-level factors), and control group (generic nutrition information). Participants were recruited from the general Dutch adult population and randomly assigned to one of the study groups. Online self-reported questionnaires assessed dietary intake and potential mediating variables (behavior-specific cognitions, action- and coping planning, environmental-level factors) at baseline and one (T1) and four (T2) months post-intervention (i.e. four and seven months after baseline). The joint-significance test was used to establish mediating variables at different time points (T1-mediating variables - T2-intake; T1-mediating variables - T1-intake; T2-mediating variables - T2-intake). Educational differences were examined by testing interaction terms. The effect of the plus version on fruit intake was mediated (T2-T2) by intention and fruit availability at home and for high-educated participants also by attitude. Among low/moderate-educated participants, high-energy snack availability at home mediated (T1-T1) the effect of the basic version on high-energy snack intake. Subjective norm mediated (T1-T1) the effect of the basic version on fat intake among high-educated participants. Only some of the targeted determinants mediated the effects of both intervention versions on fruit, high-energy snack, and saturated fat intake. A possible reason for not finding a more pronounced pattern of mediating variables is that the educational content was tailored to individual characteristics and that participants only received feedback for relevant and not for all assessed mediating variables. Netherlands Trial Registry NTR3396. Copyright © 2015. Published by Elsevier Ltd.
The effects of constraints and mastery on mental and physical health: Conceptual and methodological considerations.

PubMed

Infurna, Frank J; Mayer, Axel

2015-06-01

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

PubMed

Dzhambov, Angel; Hartig, Terry; Markevych, Iana; Tilov, Boris; Dimitrova, Donka

2018-01-01

Urban greenspace can benefit mental health through multiple mechanisms. They may work together, but previous studies have treated them as independent. We aimed to compare single and parallel mediation models, which estimate the independent contributions of different paths, to several models that posit serial mediation components in the pathway from greenspace to mental health. We collected cross-sectional survey data from 399 participants (15-25 years of age) in the city of Plovdiv, Bulgaria. Objective "exposure" to urban residential greenspace was defined by the Normalized Difference Vegetation Index (NDVI), Soil Adjusted Vegetation Index, tree cover density within the 500-m buffer, and Euclidean distance to the nearest urban greenspace. Self-reported measures of availability, access, quality, and usage of greenspace were also used. Mental health was measured with the General Health Questionnaire. The following potential mediators were considered in single and parallel mediation models: restorative quality of the neighborhood, neighborhood social cohesion, commuting and leisure time physical activity, road traffic noise annoyance, and perceived air pollution. Four models were tested with the following serial mediation components: (1) restorative quality → social cohesion; (2) restorative quality → physical activity; (3) perceived traffic pollution → restorative quality; (4) and noise annoyance → physical activity. There was no direct association between objectively-measured greenspace and mental health. For the 500-m buffer, the tests of the single mediator models suggested that restorative quality mediated the relationship between NDVI and mental health. Tests of parallel mediation models did not find any significant indirect effects. In line with theory, tests of the serial mediation models showed that higher restorative quality was associated with more physical activity and more social cohesion, and in turn with better mental health. As for self-reported greenspace measures, single mediation through restorative quality was significant only for time in greenspace, and there was no mediation though restorative quality in the parallel mediation models; however, serial mediation through restorative quality and social cohesion/physical activity was indicated for all self-reported measures except for greenspace quality. Statistical models should adequately address the theoretically indicated interdependencies between mechanisms underlying association between greenspace and mental health. If such causal relationships hold, testing mediators alone or in parallel may lead to incorrect inferences about the relative contribution of specific paths, and thus to inappropriate intervention strategies. Copyright © 2017 Elsevier Inc. All rights reserved.
Brain region and epilepsy-associated differences in inflammatory mediator levels in medically refractory mesial temporal lobe epilepsy.

PubMed

Strauss, Kenneth I; Elisevich, Kost V

2016-10-13

Epilepsy patients have distinct immune/inflammatory cell profiles and inflammatory mediator levels in the blood. Although the neural origin of inflammatory cells and mediators has been implied, few studies have measured these inflammatory components in the human brain itself. This study examines the brain levels of chemokines (8), cytokines (14), and vascular injury mediators (3) suspected of being altered in epilepsy. Soluble protein extracts of fresh frozen resected hippocampus, entorhinal cortex, and temporal cortex from 58 medically refractory mesial temporal lobe epilepsy subjects and 4 nonepileptic neurosurgical subjects were assayed for 25 inflammation-related mediators using ultrasensitive low-density arrays. Brain mediator levels were compared between regions and between epileptic and nonepileptic cases, showing a number of regional and possible epilepsy-associated differences. Eotaxin, interferon-γ, interleukin (IL)-2, IL-4, IL-12 p70, IL-17A, tumor necrosis factor-α, and intercellular adhesion molecule (ICAM)-1 levels were highest in the hippocampus, the presumptive site of epileptogenesis. Surprisingly, IL-1β and IL-1α were lowest in the hippocampus, compared to cortical regions. In the temporal cortex, IL-1β, IL-8, and MIP-1α levels were highest, compared to the entorhinal cortex and the hippocampus. The most pronounced epilepsy-associated differences were decreased levels of eotaxin, IL-1β, C-reactive protein, and vascular cell adhesion molecule (VCAM)-1 and increased IL-12 p70 levels. Caution must be used in interpreting these results, however, because nonepileptic subjects were emergent neurosurgical cases, not a control group. Correlation analyses of each mediator in each brain region yielded valuable insights into the regulation of these mediator levels in the brain. Over 70 % of the associations identified were between different mediators in a single brain region, providing support for local control of mediator levels. Correlations of different mediators in different brain regions suggested more distributed control mechanisms, particularly in the hippocampus. Interestingly, only four mediators showed robust correlations between the brain regions, yet levels in three of these were significantly different between regions, indicating both global and local controls for these mediators. Both brain region-specific and epilepsy-associated changes in inflammation-related mediators were detected. Correlations in mediator levels within and between brain regions indicated local and global regulation, respectively. The hippocampus showed the majority of interregional associations, suggesting a focus of inflammatory control between these regions.
Training Parents to Mediate Sibling Disputes Affects Children's Negotiation and Conflict Understanding

ERIC Educational Resources Information Center

Smith, Julie; Ross, Hildy

2007-01-01

The effects of training parents to use formal mediation procedures in sibling disputes were examined in 48 families with 5- to 10-years-old children, randomly assigned to mediation and control conditions. Children whose parents were trained in mediation were compared with those whose parents intervened normally. Parents reported that children used…
29 CFR 1471.615 - How does the Federal Mediation and Conciliation Service notify a person of a suspension or...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false How does the Federal Mediation and Conciliation Service... to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE GOVERNMENTWIDE DEBARMENT AND... does the Federal Mediation and Conciliation Service notify a person of a suspension or debarment action...
10 CFR 708.27 - May the Hearing Officer recommend mediation to the parties?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false May the Hearing Officer recommend mediation to the parties... Investigation, Hearing and Decision Process § 708.27 May the Hearing Officer recommend mediation to the parties... complaint through mediation or other informal means at any time before issuance of an initial agency...
Peer Mediation and Its Effects on Elementary Student Perceptions of Self-Esteem and Social Competence

ERIC Educational Resources Information Center

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…
Ten Ways to Improve the Use of Statistical Mediation Analysis in the Practice of Child and Adolescent Treatment Research

ERIC Educational Resources Information Center

Maric, Marija; Wiers, Reinout W.; Prins, Pier J. M.

2012-01-01

Despite guidelines and repeated calls from the literature, statistical mediation analysis in youth treatment outcome research is rare. Even more concerning is that many studies that "have" reported mediation analyses do not fulfill basic requirements for mediation analysis, providing inconclusive data and clinical implications. As a result, after…
29 CFR 1471.645 - Do other Federal agencies know if the Federal Mediation and Conciliation Service agrees to a...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Do other Federal agencies know if the Federal Mediation and... Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE GOVERNMENTWIDE DEBARMENT AND SUSPENSION... agencies know if the Federal Mediation and Conciliation Service agrees to a voluntary exclusion? (a) Yes...
Mediacion en educacion especial: Una guia para los padres (Special Education Mediation: A Guide for Parents).

ERIC Educational Resources Information Center

Consortium for Appropriate Dispute Resolution in Special Education (CADRE), Eugene, OR.

Designed for Spanish-speaking parents of students with disabilities living in Oregon, this brochure describes the general mediation process that parents can use to resolve special education services disputes with schools. It begins by discussing what mediation is and the characteristics of a trained mediator. It addresses the requirement for…
29 CFR 1400.735-20 - Code of Professional Conduct for Labor Mediators.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Code of Professional Conduct for Labor Mediators. 1400.735... Conduct and Responsibilities § 1400.735-20 Code of Professional Conduct for Labor Mediators. In 1964, a Code of Professional Conduct for Labor Mediators was drafted by a Federal-State Liaison Committee and...

34 CFR 361.57 - Review of determinations made by designated State unit personnel.

Code of Federal Regulations, 2010 CFR

2010-07-01

... filed; (iv) The manner in which a mediator or impartial hearing officer may be selected consistent with... rights provided under this part. At any point during the mediation process, either party or the mediator... impartial mediator, as defined in § 361.5(b)(43), who must be selected from a list of qualified and...
Social Support as a Mediator between Internalized Stigma and Coping Behaviors of Individuals with Substance Abuse Issues

ERIC Educational Resources Information Center

Chou, Chih-Chin; Robb, Jayci Lynn; Clay, Matthew Christopher; Chronister, Julie Ann

2013-01-01

In this study, 51 individuals from online substance abuse support groups were surveyed to investigate the mediating role of social support on the relationship between internalized stigma and coping. Regression and bootstrapping were conducted to perform mediation analysis. Findings suggest that social support mediates the negative impact of…
Mediation and the "Chilling" Effect of Med-Arb in a Simulated Labor-Management Dispute.

ERIC Educational Resources Information Center

Carnevale, Peter J. D.; Leatherwood, Marya L.

Mediation and mediation-arbitration (med-arb) are two forms of third-party conflict intervention that can affect integrative agreements in labor-management negotiation. In an attempt to evaluate the relative value of each of these two methods, 160 volunteers, almost all business students, were randomly placed into a mediation triad, a med-arb…
Let's talk conflict: using mediation in healthcare security disputes.

PubMed

Armstrong, Brad

2013-01-01

Healthcare security administrators face weekly, if not daily challenges and conflict. This article considers that security leaders must anticipate disputes in highly complex healthcare systems. When disputes cannot be resolved by organizational efforts, security administrators may be in a position to recommend or participate in mediation. Here the concept of mediation is introduced to healthcare security leaders as a viable means to resolve disputes with patients, visitors, and the community. This includes a description of the facilitative versus evaluative mediation processes, as well as pragmatic guidance when preparing for mediation.
The mediational role of identification in the relationship between experience mode and self-efficacy: Enactive role-playing versus passive observation.

PubMed

Peng, Wei

2008-12-01

Abstract Based on Social Cognitive Theory, this study proposes a new concept-mediated enactive experience to understand game playing effects on self-efficacy in the context of a health promotion role-playing game. An experiment demonstrated that a mediated enactive experience afforded by game playing was more effective than a mediated observational experience provided by game watching in influencing self-efficacy. It was found that identification with the game character partially mediated the relationship between experience mode and self-efficacy.
THE RELATIONSHIP BETWEEN FAMILY-OF-ORIGIN VIOLENCE, HOSTILITY, AND INTIMATE PARTNER VIOLENCE IN MEN ARRESTED FOR DOMESTIC VIOLENCE: TESTING A MEDIATIONAL MODEL

PubMed Central

Elmquist, JoAnna; Shorey, Ryan C.; Labrecque, Lindsay; Ninnemann, Andrew; Zapor, Heather; Febres, Jeniimarie; Wolford-Clevenger, Caitlin; Plasencia, Maribel; Temple, Jeff R.; Stuart, Gregory L.

2015-01-01

Although research has shown links between family-of-origin violence (FOV), intimate partner violence (IPV), and hostility, research has not examined whether hostility mediates the relationship between FOV and IPV. The current study examined whether hostility mediates FOV and IPV perpetration in 302 men arrested for domestic violence. Results demonstrated that hostility fully mediated the relationship between father-to-participant FOV and physical and psychological IPV and the relationship between mother-to-participant FOV and physical IPV. Results indicated that hostility fully mediated the relationship between experiencing and witnessing FOV and physical IPV (composite FOV), and partially mediated the relationship between composite FOV and psychological aggression. PMID:26712239
The Relationship Between Family-of-Origin Violence, Hostility, and Intimate Partner Violence in Men Arrested for Domestic Violence: Testing a Mediational Model.

PubMed

Elmquist, JoAnna; Shorey, Ryan C; Labrecque, Lindsay; Ninnemann, Andrew; Zapor, Heather; Febres, Jeniimarie; Wolford-Clevenger, Caitlin; Plasencia, Maribel; Temple, Jeff R; Stuart, Gregory L

2016-09-01

Although research has shown links between family-of-origin violence (FOV), intimate partner violence (IPV), and hostility, research has not examined whether hostility mediates the relationship between FOV and IPV. The current study examined whether hostility mediates FOV and IPV perpetration in 302 men arrested for domestic violence. Results demonstrated that hostility fully mediated the relationship between father-to-participant FOV and physical and psychological IPV, and the relationship between mother-to-participant FOV and physical IPV. Results indicated that hostility fully mediated the relationship between experiencing and witnessing FOV and physical IPV (composite FOV), and partially mediated the relationship between composite FOV and psychological aggression. © The Author(s) 2015.
Parentally Bereaved Children’s Grief: Self-system Beliefs as Mediators of the Relations between Grief and Stressors and Caregiver-child Relationship Quality

PubMed Central

Wolchik, Sharlene A.; Ma, Yue; Tein, Jenn-Yun; Sandler, Irwin N.; Ayers, Tim S.

2009-01-01

We investigated whether three self-system beliefs -- fear of abandonment, coping efficacy, and self-esteem -- mediated the relations between stressors and caregiver-child relationship quality and parentally bereaved youths’ general grief and intrusive grief thoughts. Cross-sectional (n=340 youth) and longitudinal (n=100 youth) models were tested. In the cross-sectional model, fear of abandonment mediated the effects of stressors and relationship quality on both measures of grief and coping efficacy mediated the path from relationship quality to general grief. Fear of abandonment showed a marginal prospective mediational relation between stressors and intrusive grief thoughts. After excluding the mediators, relationship quality showed a direct prospective relation to intrusive grief thoughts. PMID:18924290
Parental dysphoria and children's internalizing symptoms: marital conflict styles as mediators of risk.

PubMed

Du Rocher Schudlich, Tina D; Cummings, E Mark

2003-01-01

Parents' marital conflict styles were investigated as mediators in the associations between parental dysphoria and children's internalizing symptoms. A community sample of 267 children, ages 8 to 16, participated with their parents. Behavioral observations were made of parents' interactions during marital conflict resolution tasks. Questionnaires assessed parents' dysphoria and children's internalizing problems. Structural equation modeling indicated that marital discord, in particular, depressive conflict styles, mediated the relationship between parental dysphoria and children's internalizing problems. Furthermore, whereas for dysphoric mothers, depressive conflict styles partially mediated the links with children's internalizing, for fathers, depressive conflict styles fully mediated the links. Destructive and constructive marital conflict were associated with parental dysphoria (positively and negatively, respectively) but did not mediate the relations with children's internalizing.
Training parents to mediate sibling disputes affects children's negotiation and conflict understanding.

PubMed

Smith, Julie; Ross, Hildy

2007-01-01

The effects of training parents to use formal mediation procedures in sibling disputes were examined in 48 families with 5- to 10-years-old children, randomly assigned to mediation and control conditions. Children whose parents were trained in mediation were compared with those whose parents intervened normally. Parents reported that children used more constructive conflict resolution strategies, compromised more often, and controlled the outcomes of conflicts more often in mediation families than in control families. Observations indicated less negativity in children's independent negotiations of recurrent conflicts, better understanding of the role of interpretation in assessing blame, and better knowledge of their siblings' perspectives in the mediation group. Thus, both social and social-cognitive gains resulted from experience with constructive conflict resolution.
Plant Mediator complex and its critical functions in transcription regulation.

PubMed

Yang, Yan; Li, Ling; Qu, Li-Jia

2016-02-01

The Mediator complex is an important component of the eukaryotic transcriptional machinery. As an essential link between transcription factors and RNA polymerase II, the Mediator complex transduces diverse signals to genes involved in different pathways. The plant Mediator complex was recently purified and comprises conserved and specific subunits. It functions in concert with transcription factors to modulate various responses. In this review, we summarize the recent advances in understanding the plant Mediator complex and its diverse roles in plant growth, development, defense, non-coding RNA production, response to abiotic stresses, flowering, genomic stability and metabolic homeostasis. In addition, the transcription factors interacting with the Mediator complex are also highlighted. © 2015 Institute of Botany, Chinese Academy of Sciences.
Social cognition as a mediator variable between neurocognition and functional outcome in schizophrenia: empirical review and new results by structural equation modeling.

PubMed

Schmidt, Stefanie J; Mueller, Daniel R; Roder, Volker

2011-09-01

Cognitive impairments are currently regarded as important determinants of functional domains and are promising treatment goals in schizophrenia. Nevertheless, the exact nature of the interdependent relationship between neurocognition and social cognition as well as the relative contribution of each of these factors to adequate functioning remains unclear. The purpose of this article is to systematically review the findings and methodology of studies that have investigated social cognition as a mediator variable between neurocognitive performance and functional outcome in schizophrenia. Moreover, we carried out a study to evaluate this mediation hypothesis by the means of structural equation modeling in a large sample of 148 schizophrenia patients. The review comprised 15 studies. All but one study provided evidence for the mediating role of social cognition both in cross-sectional and in longitudinal designs. Other variables like motivation and social competence additionally mediated the relationship between social cognition and functional outcome. The mean effect size of the indirect effect was 0.20. However, social cognitive domains were differentially effective mediators. On average, 25% of the variance in functional outcome could be explained in the mediation model. The results of our own statistical analysis are in line with these conclusions: Social cognition mediated a significant indirect relationship between neurocognition and functional outcome. These results suggest that research should focus on differential mediation pathways. Future studies should also consider the interaction with other prognostic factors, additional mediators, and moderators in order to increase the predictive power and to target those factors relevant for optimizing therapy effects.
Socioeconomic Attainment of Extremely Low Birth Weight Survivors: The Role of Early Cognition.

PubMed

Dobson, Kathleen G; Ferro, Mark A; Boyle, Michael H; Schmidt, Louis A; Saigal, Saroj; Van Lieshout, Ryan J

2017-03-01

To determine: (1) if childhood cognitive and academic abilities mediate the association between being born at extremely low birth weight (ELBW) and socioeconomic attainment at age 29 to 36 years; (2) which cognitive abilities (IQ, verbal abilities, fluid intelligence, mathematical abilities, or academic achievement) most strongly mediate this association; and (3) if the mediating role of cognition is different in ELBW survivors with significant neurosensory impairment (NSI). A prospective, longitudinal cohort of 100 Canadian ELBW survivors born between 1977 and 1982 and 89 normal birth weight comparison participants were used to examine the mediating role of childhood cognition by using 5 cognitive mediators assessed at age 8 years (overall IQ, verbal IQ, performance IQ, quantitative ability, and academic achievement) on socioeconomic attainment at adulthood. Socioeconomic attainment was defined as personal annual earnings and full-time employment assessed via self-report at age 29 to 36 years. Mediation models revealed that childhood cognition mediated the association between ELBW status and income attainment, with mathematical abilities and overall IQ each accounting for 26% of the direct effect. Mediated effects were not statistically significant in full-time employment models. For both outcomes, the mediating effect of cognition was stronger for ELBW survivors with NSI. Childhood cognitive abilities partially mediate associations between ELBW status and adult income attainment. Early life cognition is a critical predictor of socioeconomic attainment in ELBW survivors, particularly in those born with NSI. Interventions aimed at enhancing early cognition in ELBW survivors may help optimize their later socioeconomic attainment. Copyright © 2017 by the American Academy of Pediatrics.
Differences and Similarities in TRAIL- and Tumor Necrosis Factor-Mediated Necroptotic Signaling in Cancer Cells

PubMed Central

Philipp, Stephan; Fuchslocher Chico, Johaiber; Saggau, Carina; Fritsch, Jürgen; Föll, Alexandra; Plenge, Johannes; Arenz, Christoph; Pinkert, Thomas; Kalthoff, Holger; Trauzold, Anna; Schmitz, Ingo; Schütze, Stefan; Adam, Dieter

2016-01-01

Recently, a type of regulated necrosis (RN) called necroptosis was identified to be involved in many pathophysiological processes and emerged as an alternative method to eliminate cancer cells. However, only a few studies have elucidated components of TRAIL-mediated necroptosis useful for anticancer therapy. Therefore, we have compared this type of cell death to tumor necrosis factor (TNF)-mediated necroptosis and found similar signaling through acid and neutral sphingomyelinases, the mitochondrial serine protease HtrA2/Omi, Atg5, and vacuolar H+-ATPase. Notably, executive mechanisms of both TRAIL- and TNF-mediated necroptosis are independent of poly(ADP-ribose) polymerase 1 (PARP-1), and depletion of p38α increases the levels of both types of cell death. Moreover, we found differences in signaling between TNF- and TRAIL-mediated necroptosis, e.g., a lack of involvement of ubiquitin carboxyl hydrolase L1 (UCH-L1) and Atg16L1 in executive mechanisms of TRAIL-mediated necroptosis. Furthermore, we discovered indications of an altered involvement of mitochondrial components, since overexpression of the mitochondrial protein Bcl-2 protected Jurkat cells from TRAIL- and TNF-mediated necroptosis, and overexpression of Bcl-XL diminished only TRAIL-induced necroptosis in Colo357 cells. Furthermore, TRAIL does not require receptor internalization and endosome-lysosome acidification to mediate necroptosis. Taken together, pathways described for TRAIL-mediated necroptosis and differences from those for TNF-mediated necroptosis might be unique targets to increase or modify necroptotic signaling and eliminate tumor cells more specifically in future anticancer approaches. PMID:27528614
The mediating role of pain acceptance during mindfulness-based cognitive therapy for headache.

PubMed

Day, Melissa A; Thorn, Beverly E

2016-04-01

This study aimed to determine if mindfulness-based cognitive therapy (MBCT) engenders improvement in headache outcomes via the mechanisms specified by theory: (1) change in psychological process, (i.e., pain acceptance); and concurrently (2) change in cognitive content, (i.e., pain catastrophizing; headache management self-efficacy). A secondary analysis of a randomized controlled trial comparing MBCT to a medical treatment as usual, delayed treatment (DT) control was conducted. Participants were individuals with headache pain who completed MBCT or DT (N=24) at the Kilgo Headache Clinic or psychology clinic. Standardized measures of the primary outcome (pain interference) and proposed mediators were administered at pre- and post-treatment; change scores were calculated. Bootstrap mediation models were conducted. Pain acceptance emerged as a significant mediator of the group-interference relation (p<.05). Mediation models examining acceptance subscales showed nuances in this effect, with activity engagement emerging as a significant mediator (p<.05), but pain willingness not meeting criteria for mediation due to a non-significant pathway from the mediator to outcome. Criteria for mediation was also not met for the catastrophizing or self-efficacy models as neither of these variables significantly predicted pain interference. Pain acceptance, and specifically engagement in valued activities despite pain, may be a key mechanism underlying improvement in pain outcome during a MBCT for headache pain intervention. The theorized mediating role of cognitive content factors was not supported in this preliminary study. A large, definitive trial is warranted to replicate and extend the findings in order to streamline and optimize MBCT for headache. Copyright © 2016 Elsevier Ltd. All rights reserved.
Parametric mediational g-formula approach to mediation analysis with time-varying exposures, mediators, and confounders

PubMed Central

Lin, Sheng-Hsuan; Young, Jessica; Logan, Roger; Tchetgen Tchetgen, Eric J.; VanderWeele, Tyler J.

2016-01-01

The assessment of direct and indirect effects with time-varying mediators and confounders is a common but challenging problem, and standard mediation analysis approaches are generally not applicable in this context. The mediational g-formula was recently proposed to address this problem, paired with a semi-parametric estimation approach to evaluate longitudinal mediation effects empirically. In this paper, we develop a parametric estimation approach to the mediational g-formula, including a feasible algorithm implemented in a freely available SAS macro. In the Framingham Heart Study data, we apply this method to estimate the interventional analogues of natural direct and indirect effects of smoking behaviors sustained over a 10-year period on blood pressure when considering weight change as a time-varying mediator. Compared with not smoking, smoking 20 cigarettes per day for 10 years was estimated to increase blood pressure by 1.2 (95 % CI: −0.7, 2.7) mm-Hg. The direct effect was estimated to increase blood pressure by 1.5 (95 % CI: −0.3, 2.9) mm-Hg, and the indirect effect was −0.3 (95% CI: −0.5, −0.1) mm-Hg, which is negative because smoking which is associated with lower weight is associated in turn with lower blood pressure. These results provide evidence that weight change in fact partially conceals the detrimental effects of cigarette smoking on blood pressure. Our work represents, to our knowledge, the first application of the parametric mediational g-formula in an epidemiologic cohort study. PMID:27984420
Two-condition within-participant statistical mediation analysis: A path-analytic framework.

PubMed

Montoya, Amanda K; Hayes, Andrew F

2017-03-01

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

PubMed

Francesconi, Marta; Minichino, Amedeo; Carrión, Ricardo E; Chiaie, Roberto Delle; Bevilacqua, Arturo; Parisi, Maurizio; Rullo, Santo; Bersani, Francesco Saverio; Biondi, Massimo; Cadenhead, Kristin

2016-12-30

A large body of studies provides evidence for a link between neurocognition, theory of mind (ToM) and functioning in psychotic spectrum disorders (PSDs), with ToM mediating the effect that neurocognition has on functioning. These three constructs and the related mediation effect may characterize different psychiatric syndromes other than PSDs. Structural equation modelling (SEM) was applied to baseline data from a longitudinal study of 138 young individuals with a recent-onset psychiatric disorder. Using SEM, we tested the hypothesis that ToM mediates the effect of neurocognition on functioning independent of the level of psychosis risk and the diagnostic category. In the mediation model the bootstrapping estimate revealed a significant indirect effect that was the association of social cognition with neurocognition and with functional outcome. ToM was significantly associated with neurocognition and the path from neurocognition to functioning was no longer significant as soon as the mediator (ToM) was entered into the mediation model consistent with a complete mediation effect through ToM. This mediation was independent of the psychosis-risk status and the psychiatric diagnoses. Our results provide useful information on a young psychiatric sample, in which specific therapeutic interventions have the potential to significantly limit functional disability. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Weight Stigma Mediates the Association Between BMI and Self-Reported Health

PubMed Central

Hunger, Jeffrey M.; Major, Brenda

2014-01-01

Objective Weight stigma is pervasive in the United States. We tested the hypothesis that stigma may be a mechanism through which obesity negatively affects self-reported health. Two studies examined whether perceived weight-based discrimination and concerns over weight stigma mediated the association between BMI and self-reported psychological health (Study 1) and physical health (Study 2). Method In two online studies, adult community members completed measures of stigma-relevant mediators (perceived weight discrimination, weight stigma concerns) and provided their height and weight. In Study 1 (N = 171) participants also completed measures of psychological health (depression, self-esteem, quality of life), whereas participants in Study 2 (N = 194) also completed a measure of self-reported physical health. Process modeling was used to simultaneously test for mediation through perceived discrimination and stigma concerns independently as well as for serial mediation through both variables. Results Across both studies, we hypothesized and found support for serial mediation such that BMI was indirectly related to poorer self-reported health through its effect on perceived discrimination and concerns about stigma. Additionally, concerns about stigma mediated the association between BMI and health independent of perceived discrimination. Conclusion Weight stigma is an important mediator of the association between BMI and self-reported health. Furthermore, results indicate that concerns about facing stigma in the future mediate the link between perceived past experiences of discrimination and psychological and physical health. PMID:25133837
Do attentional capacities and processing speed mediate the effect of age on executive functioning?

PubMed

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.

Interaction intensity and pollinator-mediated selection.

PubMed

Trunschke, Judith; Sletvold, Nina; Ågren, Jon

2017-05-01

In animal-pollinated plants, the opportunity for selection and the strength of pollinator-mediated selection are expected to increase with the degree of pollen limitation. However, whether differences in pollen limitation can explain variation in pollinator-mediated and net selection among animal-pollinated species is poorly understood. In the present study, we quantified pollen limitation, variance in relative fitness and pollinator-mediated selection on five traits important for pollinator attraction (flowering start, plant height, flower number, flower size) and pollination efficiency (spur length) in natural populations of 12 orchid species. Pollinator-mediated selection was quantified by subtracting estimates of selection gradients for plants receiving supplemental hand-pollination from estimates obtained for open-pollinated control plants. Mean pollen limitation ranged from zero to 0.96. Opportunity for selection, pollinator-mediated selection and net selection were all positively related to pollen limitation, whereas nonpollinator-mediated selection was not. Opportunity for selection varied five-fold, strength of pollinator-mediated selection varied three-fold and net selection varied 1.5-fold among species. Supplemental hand-pollination reduced both opportunity for selection and selection on floral traits. The results show that the intensity of biotic interactions is an important determinant of the selection regime, and indicate that the potential for pollinator-mediated selection and divergence in floral traits is particularly high in species that are strongly pollen-limited. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.
Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo.

PubMed

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.
Mediator directs co-transcriptional heterochromatin assembly by RNA interference-dependent and -independent pathways.

PubMed

Oya, Eriko; Kato, Hiroaki; Chikashige, Yuji; Tsutsumi, Chihiro; Hiraoka, Yasushi; Murakami, Yota

2013-01-01

Heterochromatin at the pericentromeric repeats in fission yeast is assembled and spread by an RNAi-dependent mechanism, which is coupled with the transcription of non-coding RNA from the repeats by RNA polymerase II. In addition, Rrp6, a component of the nuclear exosome, also contributes to heterochromatin assembly and is coupled with non-coding RNA transcription. The multi-subunit complex Mediator, which directs initiation of RNA polymerase II-dependent transcription, has recently been suggested to function after initiation in processes such as elongation of transcription and splicing. However, the role of Mediator in the regulation of chromatin structure is not well understood. We investigated the role of Mediator in pericentromeric heterochromatin formation and found that deletion of specific subunits of the head domain of Mediator compromised heterochromatin structure. The Mediator head domain was required for Rrp6-dependent heterochromatin nucleation at the pericentromere and for RNAi-dependent spreading of heterochromatin into the neighboring region. In the latter process, Mediator appeared to contribute to efficient processing of siRNA from transcribed non-coding RNA, which was required for efficient spreading of heterochromatin. Furthermore, the head domain directed efficient transcription in heterochromatin. These results reveal a pivotal role for Mediator in multiple steps of transcription-coupled formation of pericentromeric heterochromatin. This observation further extends the role of Mediator to co-transcriptional chromatin regulation.
Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor.

PubMed

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

PubMed

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.
Maternal depressive symptoms and early childhood cognitive development: a review of putative environmental mediators.

PubMed

Ahun, Marilyn N; Côté, Sylvana M

2018-06-06

Despite the abundance of research investigating the associations between maternal depressive symptoms (MDS) and children's cognitive development, little is known about the putative mechanisms through which depressive symptoms are associated with children's cognitive development. The aim of this review was to summarize the literature on family mediators (i.e., maternal parenting behaviors, mother-child interactions, and family stress) involved in this association in early childhood. The review includes seven studies, five longitudinal and two cross-sectional, which tested putative mediators of the association between MDS and children's cognitive development. Studies were selected from online databases (PubMed, PsycNet) and manual searches. Only studies which quantitatively assessed associations between MDS in the postnatal period and child cognitive development in early childhood (i.e., 0-5 years) and included mediator variables were included in the review. Six out of seven studies identified mediating variables. The mediators included maternal responsiveness, parenting style, family dysfunction, the quality of the home environment, and maternal caregiving practices. Different mediators were identified across the reviewed studies. Maternal depressive symptoms are partly associated with child cognitive development via family processes and parenting practices. Various mediating processes are at play. Further research is needed on the role of maternal and paternal mental health and gene-environment correlations in this association. A better understanding of the mediating pathways is needed for the design of preventative intervention targeting specific family processes.
Can Computer-Mediated Interventions Change Theoretical Mediators of Safer Sex? A Meta-Analysis

ERIC Educational Resources Information Center

Noar, Seth M.; Pierce, Larson B.; Black, Hulda G.

2010-01-01

The purpose of this study was to conduct a meta-analysis of computer-mediated interventions (CMIs) aimed at changing theoretical mediators of safer sex. Meta-analytic aggregation of effect sizes from k = 20 studies indicated that CMIs significantly improved HIV/AIDS knowledge, d = 0.276, p less than 0.001, k = 15, N = 6,625; sexual/condom…
Locus of Control and Self-Efficacy: Potential Mediators of Stress, Illness, and Utilization of Health Services in College Students

ERIC Educational Resources Information Center

Roddenberry, Angela; Renk, Kimberly

2010-01-01

Although many studies examine the biological phenomena that mediate the relationship between stress and illness, more research is needed regarding psychological variables that may mediate this relationship. Thus, the current study investigates the mediating effects of locus of control and self-efficacy in the relationships among stress, illness,…
25 CFR 161.603 - Can mediation be used in the event of a permit violation or dispute?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Can mediation be used in the event of a permit violation... AND WATER NAVAJO PARTITIONED LANDS GRAZING PERMITS Permit Violations § 161.603 Can mediation be used... to be resolved with the District Grazing Committee through mediation. (a) The District Grazing...
29 CFR 1425.3 - Functions of the Service under title VII of the Civil Service Reform Act.

Code of Federal Regulations, 2010 CFR

2010-07-01

... MEDIATION AND CONCILIATION SERVICE MEDIATION ASSISTANCE IN THE FEDERAL SERVICE § 1425.3 Functions of the... Service through a specific request for mediation from one or both of the parties, through notification... dispute and if, in its opinion, the need for mediation exists, the Service will use its best efforts to...
25 CFR 291.11 - What must the Secretary do upon receiving the proposal selected by the mediator?

Code of Federal Regulations, 2010 CFR

2010-04-01

... selected by the mediator? 291.11 Section 291.11 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... receiving the proposal selected by the mediator? Within 60 days of receiving the proposal selected by the mediator, the Secretary must do one of the following: (a) Notify the Indian tribe, the Governor and the...
Flexible Approaches to Computing Mediated Effects in Generalized Linear Models: Generalized Estimating Equations and Bootstrapping

ERIC Educational Resources Information Center

Schluchter, Mark D.

2008-01-01

In behavioral research, interest is often in examining the degree to which the effect of an independent variable X on an outcome Y is mediated by an intermediary or mediator variable M. This article illustrates how generalized estimating equations (GEE) modeling can be used to estimate the indirect or mediated effect, defined as the amount by…
The Quality of Mediational Teaching Practiced by Teachers in Special Education: An Observational Study in Norwegian Primary Schools

ERIC Educational Resources Information Center

Nyborg, Geir

2011-01-01

In this case study the quality of mediational teaching was evaluated for interactions between teachers and pupils in special education in regular Norwegian primary schools. Mediational teaching is interpreted as a process by which a teacher mediates a given curriculum using certain categories in interactions with a pupil. The categories are…
Brief Report: Mediation of Treatment Effect in a Communication Intervention for Pre-School Children with Autism

ERIC Educational Resources Information Center

Aldred, Catherine; Green, Jonathan; Emsley, Richard; McConachie, Helen

2012-01-01

Tests of mediation in treatment trials can illuminate processes of change and suggest causal influences in development. We conducted a mediation analysis of a previously published randomised controlled trial of parent-mediated communication-focused treatment for autism against ordinary care, with 28 children aged 2-5 years (Aldred et al. in J…
Mediators and moderators in early intervention research

PubMed Central

Breitborde, Nicholas J. K.; Srihari, Vinod H.; Pollard, Jessica M.; Addington, Donald N.; Woods, Scott W.

2015-01-01

Aim The goal of this paper is to provide clarification with regard to the nature of mediator and moderator variables and the statistical methods used to test for the existence of these variables. Particular attention will be devoted to discussing the ways in which the identification of mediator and moderator variables may help to advance the field of early intervention in psychiatry. Methods We completed a literature review of the methodological strategies used to test for mediator and moderator variables. Results Although several tests for mediator variables are currently available, recent evaluations suggest that tests which directly evaluate the indirect effect are superior. With regard to moderator variables, two approaches (‘pick-a-point’ and regions of significance) are available, and we provide guidelines with regard to how researchers can determine which approach may be most appropriate to use for their specific study. Finally, we discuss how to evaluate the clinical importance of mediator and moderator relationships as well as the methodology to calculate statistical power for tests of mediation and moderation. Conclusion Further exploration of mediator and moderator variables may provide valuable information with regard to interventions provided early in the course of a psychiatric illness. PMID:20536970
Covariate Measurement Error Correction Methods in Mediation Analysis with Failure Time Data

PubMed Central

Zhao, Shanshan

2014-01-01

Summary Mediation analysis is important for understanding the mechanisms whereby one variable causes changes in another. Measurement error could obscure the ability of the potential mediator to explain such changes. This paper focuses on developing correction methods for measurement error in the mediator with failure time outcomes. We consider a broad definition of measurement error, including technical error and error associated with temporal variation. The underlying model with the ‘true’ mediator is assumed to be of the Cox proportional hazards model form. The induced hazard ratio for the observed mediator no longer has a simple form independent of the baseline hazard function, due to the conditioning event. We propose a mean-variance regression calibration approach and a follow-up time regression calibration approach, to approximate the partial likelihood for the induced hazard function. Both methods demonstrate value in assessing mediation effects in simulation studies. These methods are generalized to multiple biomarkers and to both case-cohort and nested case-control sampling design. We apply these correction methods to the Women's Health Initiative hormone therapy trials to understand the mediation effect of several serum sex hormone measures on the relationship between postmenopausal hormone therapy and breast cancer risk. PMID:25139469
Covariate measurement error correction methods in mediation analysis with failure time data.

PubMed

Zhao, Shanshan; Prentice, Ross L

2014-12-01

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

PubMed

Tuttolomondo, Antonino; Simonetta, Irene; Pinto, Antonio

2016-11-01

Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. Areas covered: We will review recent advances in understanding the role of several receptor-mediated signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various receptor pathways), and other mechanisms mediated by micro-RNAs. We will analyze the role of some receptor mediated signaling pathways such as natriuretic peptides, mediators of glycogen synthase kinase 3 and ERK1/2 pathways, beta-adrenergic receptor subtypes and relaxin receptor signaling mechanisms, TNF/TNF receptor family and TWEAK/Fn14 axis, and some micro-RNAs as candidate target pathways in pathogenesis of heart failure. These mediators of receptor-mediated pathways and micro-RNA are the most addressed targets of emerging therapies in modern heart failure treatment strategies. Expert opinion: Future treatment strategies should address mediators involved in multiple steps within heart failure pathogenetic pathways.
Emotional states as mediators between tinnitus loudness and tinnitus distress in daily life: Results from the “TrackYourTinnitus” application

PubMed Central

Probst, Thomas; Pryss, Rüdiger; Langguth, Berthold; Schlee, Winfried

2016-01-01

The psychological process how tinnitus loudness leads to tinnitus distress remains unclear. This cross-sectional study investigated the mediating role of the emotional state “stress level” and of the two components of the emotional state “arousal” and “valence” with N = 658 users of the “TrackYourTinnitus” smartphone application. Stress mediated the relationship between tinnitus loudness and tinnitus distress in a simple mediation model and even in a multiple mediation model when arousal and valence were held constant. Arousal mediated the loudness-distress relationship when holding valence constant, but not anymore when controlling for valence as well as for stress. Valence functioned as a mediator when controlling for arousal and even when holding arousal and stress constant. The direct effect of tinnitus loudness on tinnitus distress remained significant in all models. This study demonstrates that emotional states affect the process how tinnitus loudness leads to tinnitus distress. We thereby could show that the mediating influence of emotional valence is at least equally strong as the influence of stress. Implications of the findings for future research, assessment, and clinical management of tinnitus are discussed. PMID:26853815
Physical Injury and Somatic Complaints: The Mediating Role of Posttraumatic Stress Symptoms in Young Survivors of a Terror Attack.

PubMed

Bugge, Ingrid; Dyb, Grete; Stensland, Synne Øien; Ekeberg, Øivind; Wentzel-Larsen, Tore; Diseth, Trond H

2017-06-01

Physically injured trauma survivors have particularly high risk for later somatic complaints and posttraumatic stress symptoms (PTSS). However, the potential mediating role of PTSS linking injury to later somatic complaints has been poorly investigated. In this study, survivors (N = 255) were interviewed longitudinally at 2 timepoints after the terror attack on Utøya Island, Norway, in 2011. Assessments included injury sustained during the attack, PTSS (after 4-5 months), somatic complaints (after 14-15 months), and background factors. Causal mediation analysis was conducted to evaluate the potential mediating role of PTSS in linking injury to somatic complaints comparing 2 groups of injured survivors with noninjured survivors. For the nonhospitalized injured versus the noninjured survivors, the mediated pathway was significant (average causal mediation effect; ACME = 0.09, p = .028, proportion = 55.8%). For the hospitalized versus the noninjured survivors, the mediated pathway was not significant (ACME = 0.04, p = .453, proportion = 11.6%). PTSS may play a significant mediating role in the development of somatic complaints among nonhospitalized injured trauma survivors. Intervening health professionals should be aware of this possible pathway to somatic complaints. Copyright © 2017 International Society for Traumatic Stress Studies.

Differentiating food allergies from food intolerances.

PubMed

Guandalini, Stefano; Newland, Catherine

2011-10-01

Adverse reactions to foods are extremely common, and generally they are attributed to allergy. However, clinical manifestations of various degrees of severity related to ingestion of foods can arise as a result of a number of disorders, only some of which can be defined as allergic, implying an immune mechanism. Recent epidemiological data in North America showed that the prevalence of food allergy in children has increased. The most common food allergens in the United States include egg, milk, peanut, tree nuts, wheat, crustacean shellfish, and soy. This review examines the various forms of food intolerances (immunoglobulin E [IgE] and non-IgE mediated), including celiac disease and gluten sensitivity. Immune mediated reactions can be either IgE mediated or non-IgE mediated. Among the first group, Immediate GI hypersensitivity and oral allergy syndrome are the best described. Often, but not always, IgE-mediated food allergies are entities such as eosinophilic esophagitis and eosinophilic gastroenteropathy. Non IgE-mediated immune mediated food reactions include celiac disease and gluten sensitivity, two increasingly recognized disorders. Finally, non-immune mediated reactions encompass different categories such as disorders of digestion and absorption, inborn errors of metabolism, as well as pharmacological and toxic reactions.
How Online Basic Psychological Need Satisfaction Influences Self-Disclosure Online among Chinese Adolescents: Moderated Mediation Effect of Exhibitionism and Narcissism.

PubMed

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

2016-01-01

Under the basic framework of self-determination theory, the present study examined a moderated mediation model in which exhibitionism mediated the relationship between online basic psychological need satisfaction and self-disclosure on the mobile Internet, and this mediation effect was moderated by narcissism. A total of 296 Chinese middle school students participated in this research. The results revealed that exhibitionism fully mediated the association between online competence need satisfaction and self-disclosure on the mobile net, and partly mediated the association between online relatedness need satisfaction and self-disclosure on the mobile net. The mediating path from online basic psychological need satisfaction (competence and relatedness) to exhibitionism was moderated by narcissism. Compared to the low level of narcissism, online competence need satisfaction had a stronger predictive power on exhibitionism under the high level of narcissism condition. In contrast, online relatedness need satisfaction had a weaker predictive power on exhibitionism.
A multiple mediational test of the relationship between childhood maltreatment and non-suicidal self-injury.

PubMed

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

2010-04-01

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 sought to advance the literature on maltreatment and self-injury by estimating the mediational effects of post-traumatic stress symptoms, depressive symptoms, and psychological dysregulation in the same multiple mediator model. Both maltreated (n = 129) and non-maltreated (n = 82) adolescent females, consisting of Caucasian (55%), African-American (37%), and Bi-racial (8%) backgrounds, participated in the study. Results indicated that only post-traumatic stress symptoms mediated the relationship between maltreatment and self-injury when all variables were included in the model. Overall, post-traumatic symptoms represented a unique pathway from maltreatment to self-injury and warrant special attention when assessing and treating such behavior with adolescent females.
How Online Basic Psychological Need Satisfaction Influences Self-Disclosure Online among Chinese Adolescents: Moderated Mediation Effect of Exhibitionism and Narcissism

PubMed Central

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

2016-01-01

Under the basic framework of self-determination theory, the present study examined a moderated mediation model in which exhibitionism mediated the relationship between online basic psychological need satisfaction and self-disclosure on the mobile Internet, and this mediation effect was moderated by narcissism. A total of 296 Chinese middle school students participated in this research. The results revealed that exhibitionism fully mediated the association between online competence need satisfaction and self-disclosure on the mobile net, and partly mediated the association between online relatedness need satisfaction and self-disclosure on the mobile net. The mediating path from online basic psychological need satisfaction (competence and relatedness) to exhibitionism was moderated by narcissism. Compared to the low level of narcissism, online competence need satisfaction had a stronger predictive power on exhibitionism under the high level of narcissism condition. In contrast, online relatedness need satisfaction had a weaker predictive power on exhibitionism. PMID:27616999
Chinese Beliefs in Luck are Linked to Gambling Problems via Strengthened Cognitive Biases: A Mediation Test.

PubMed

Lim, Matthew S M; Rogers, Robert D

2017-12-01

Problematic patterns of gambling and their harms are known to have culturally specific expressions. For ethnic Chinese people, patterns of superstitious belief in this community appear to be linked to the elevated rates of gambling-related harms; however, little is known about the mediating psychological mechanisms. To address this issue, we surveyed 333 Chinese gamblers residing internationally and used a mediation analysis to explore how gambling-related cognitive biases, gambling frequency and variety of gambling forms ('scope') mediate the association between beliefs in luck and gambling problems. We found that cognitive biases and scope were significant mediators of this link but that the former is a stronger mediator than the latter. The mediating erroneous beliefs were not specific to any particular type of cognitive bias. These results suggest that Chinese beliefs in luck are expressed as gambling cognitive biases that increase the likelihood of gambling problems, and that biases that promote gambling (and its harms) are best understood within their socio-cultural context.
Potential mediators between child abuse and both violence and victimization in juvenile offenders.

PubMed

Day, David M; Hart, Trevor A; Wanklyn, Sonya G; McCay, Elizabeth; Macpherson, Alison; Burnier, Nathalie

2013-02-01

Juvenile offenders are at risk for involvement in both fighting behavior and peer victimization. Understanding the potential causal mechanisms leading to these outcomes is important to address the needs of this population. The present study tested four mediator models of violent perpetration and peer victimization in a sample of 112 incarcerated youth (68 males and 44 females). In the models, the relationship between child physical and emotional abuse and fighting and victimization was expected to be mediated by impulsiveness, depression, and drug use. Multiple mediator models were tested according to Preacher and Hayes (2008). Depression fully mediated the relation between child emotional abuse and victimization and partially mediated the relation between child physical abuse and victimization. Drug use fully mediated the relation between child emotional abuse and fighting. These results suggest that treatment of depressive symptoms and drug use among juvenile offenders with a history of child physical or emotional abuse may limit violent perpetration and peer victimization in this population.
Efficient and Provable Secure Pairing-Free Security-Mediated Identity-Based Identification Schemes

PubMed Central

Chin, Ji-Jian; Tan, Syh-Yuan; Heng, Swee-Huay; Phan, Raphael C.-W.

2014-01-01

Security-mediated cryptography was first introduced by Boneh et al. in 2001. The main motivation behind security-mediated cryptography was the capability to allow instant revocation of a user's secret key by necessitating the cooperation of a security mediator in any given transaction. Subsequently in 2003, Boneh et al. showed how to convert a RSA-based security-mediated encryption scheme from a traditional public key setting to an identity-based one, where certificates would no longer be required. Following these two pioneering papers, other cryptographic primitives that utilize a security-mediated approach began to surface. However, the security-mediated identity-based identification scheme (SM-IBI) was not introduced until Chin et al. in 2013 with a scheme built on bilinear pairings. In this paper, we improve on the efficiency results for SM-IBI schemes by proposing two schemes that are pairing-free and are based on well-studied complexity assumptions: the RSA and discrete logarithm assumptions. PMID:25207333
Efficient and provable secure pairing-free security-mediated identity-based identification schemes.

PubMed

Chin, Ji-Jian; Tan, Syh-Yuan; Heng, Swee-Huay; Phan, Raphael C-W

2014-01-01

Security-mediated cryptography was first introduced by Boneh et al. in 2001. The main motivation behind security-mediated cryptography was the capability to allow instant revocation of a user's secret key by necessitating the cooperation of a security mediator in any given transaction. Subsequently in 2003, Boneh et al. showed how to convert a RSA-based security-mediated encryption scheme from a traditional public key setting to an identity-based one, where certificates would no longer be required. Following these two pioneering papers, other cryptographic primitives that utilize a security-mediated approach began to surface. However, the security-mediated identity-based identification scheme (SM-IBI) was not introduced until Chin et al. in 2013 with a scheme built on bilinear pairings. In this paper, we improve on the efficiency results for SM-IBI schemes by proposing two schemes that are pairing-free and are based on well-studied complexity assumptions: the RSA and discrete logarithm assumptions.
In the Ethos of the Safety Net: An Expanded Role for Clinical Ethics Mediation.

PubMed

McGreevy, Jolion

2015-01-01

Clinical ethics mediation is invaluable for resolving intractable disputes in the hospital. But it is also a critical day-to-day skill for clinicians, especially those who serve a disproportionate number of vulnerable patients. While mediation is typically reserved for intractable cases, there are two important opportunities to expand its use. First is preventative mediation, in which clinicians incorporate clinical ethics mediation into their daily routine in order to address value-laden conflicts before they reach the point at which outside consultation becomes necessary. Second is guided mediation, in which clinical teams resolve conflicts with patients or surrogates with guidance from an ethics consultant, who operates at some distance from the conflict and, rather than recommending a single action, counsels clinicians on the process they can use to resolve the conflict on their own. These approaches build the capacity of all clinicians to use clinical ethics mediation to improve the care of vulnerable patients. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.
Influence of very low doses of mediators on fungal laccase activity - nonlinearity beyond imagination

PubMed Central

Malarczyk, Elzbieta; Kochmanska-Rdest, Janina; Jarosz-Wilkolazka, Anna

2009-01-01

Laccase, an enzyme responsible for aerobic transformations of natural phenolics, in industrial applications requires the presence of low-molecular substances known as mediators, which accelerate oxidation processes. However, the use of mediators is limited by their toxicity and the high costs of exploitation. The activation of extracellular laccase in growing fungal culture with highly diluted mediators, ABTS and HBT is described. Two high laccase-producing fungal strains, Trametes versicolor and Cerrena unicolor, were used in this study as a source of enzyme. Selected dilutions of the mediators significantly increased the activity of extracellular laccase during 14 days of cultivation what was distinctly visible in PAGE technique and in colorimetric tests. The same mediator dilutions increased demethylation properties of laccase, which was demonstrated during incubation of enzyme with veratric acid. It was established that the activation effect was assigned to specific dilutions of mediators. Our dose-response dilution process smoothly passes into the range of action of homeopathic dilutions and is of interest for homeopaths. PMID:19732425
Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment.

PubMed

Eyboulet, Fanny; Cibot, Camille; Eychenne, Thomas; Neil, Helen; Alibert, Olivier; Werner, Michel; Soutourina, Julie

2013-12-01

Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with DNA repair. We identified a functional contact between the Med17 Mediator subunit and Rad2/XPG, the 3' endonuclease involved in nucleotide excision DNA repair. Genome-wide location analyses revealed that Rad2 is associated with RNA polymerase II (Pol II)- and Pol III-transcribed genes and telomeric regions in the absence of exogenous genotoxic stress. Rad2 occupancy of Pol II-transcribed genes is transcription-dependent. Genome-wide Rad2 occupancy of class II gene promoters is well correlated with that of Mediator. Furthermore, UV sensitivity of med17 mutants is correlated with reduced Rad2 occupancy of class II genes and concomitant decrease of Mediator interaction with Rad2 protein. Our results suggest that Mediator is involved in DNA repair by facilitating Rad2 recruitment to transcribed genes.
Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment

PubMed Central

Eyboulet, Fanny; Cibot, Camille; Eychenne, Thomas; Neil, Helen; Alibert, Olivier; Werner, Michel; Soutourina, Julie

2013-01-01

Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with DNA repair. We identified a functional contact between the Med17 Mediator subunit and Rad2/XPG, the 3′ endonuclease involved in nucleotide excision DNA repair. Genome-wide location analyses revealed that Rad2 is associated with RNA polymerase II (Pol II)- and Pol III-transcribed genes and telomeric regions in the absence of exogenous genotoxic stress. Rad2 occupancy of Pol II-transcribed genes is transcription-dependent. Genome-wide Rad2 occupancy of class II gene promoters is well correlated with that of Mediator. Furthermore, UV sensitivity of med17 mutants is correlated with reduced Rad2 occupancy of class II genes and concomitant decrease of Mediator interaction with Rad2 protein. Our results suggest that Mediator is involved in DNA repair by facilitating Rad2 recruitment to transcribed genes. PMID:24298055
Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae.

PubMed

Uthe, Henriette; Vanselow, Jens T; Schlosser, Andreas

2017-02-27

Here we present the most comprehensive analysis of the yeast Mediator complex interactome to date. Particularly gentle cell lysis and co-immunopurification conditions allowed us to preserve even transient protein-protein interactions and to comprehensively probe the molecular environment of the Mediator complex in the cell. Metabolic 15 N-labeling thereby enabled stringent discrimination between bona fide interaction partners and nonspecifically captured proteins. Our data indicates a functional role for Mediator beyond transcription initiation. We identified a large number of Mediator-interacting proteins and protein complexes, such as RNA polymerase II, general transcription factors, a large number of transcriptional activators, the SAGA complex, chromatin remodeling complexes, histone chaperones, highly acetylated histones, as well as proteins playing a role in co-transcriptional processes, such as splicing, mRNA decapping and mRNA decay. Moreover, our data provides clear evidence, that the Mediator complex interacts not only with RNA polymerase II, but also with RNA polymerases I and III, and indicates a functional role of the Mediator complex in rRNA processing and ribosome biogenesis.
Emerging functions of multi-protein complex Mediator with special emphasis on plants.

PubMed

Malik, Naveen; Agarwal, Pinky; Tyagi, Akhilesh

2017-10-01

Mediator is a multi-subunit protein complex which is involved in transcriptional regulation in yeast and other eukaryotes. As a co-activator, it connects information from transcriptional activators/repressors to transcriptional machinery including RNA polymerase II and general transcription factors. It is not only involved in transcription initiation but also has important roles to play in transcription elongation and termination. Functional attributes of different Mediator subunits have been largely defined in yeast and mammalian systems earlier, while such studies in plants have gained momentum recently. Mediator regulates various processes related to plant development and is also involved in biotic and abiotic stress response. Thus, plant Mediator, like yeast and mammalian Mediator complex, is indispensable for plant growth and survival. Interaction of its multiple subunits with other regulatory proteins and their ectopic expression or knockdown in model plant like Arabidopsis and certain crop plants are paving the way to biochemical analysis and unravel molecular mechanisms of action of Mediator in plants.
How do physicians discuss e-health with patients? the relationship of physicians' e-health beliefs to physician mediation styles.

PubMed

Fujioka, Yuki; Stewart, Erin

2013-01-01

A survey of 104 physicians examined the role of physicians' evaluation of the quality of e-health and beliefs about the influence of patients' use of e-health in how physicians discuss e-health materials with patients. Physicians' lower (poor) evaluation of the quality of e-health content predicted more negative mediation (counter-reinforcement of e-health content). Perceived benefits of patients' e-health use predicted more positive (endorsement of e-health content). Physician's perceived concerns (negative influence) regarding patients' e-health use were not a significant predictor for their mediation styles. Results, challenging the utility of restrictive mediation, suggested reconceptualizing it as redirective mediation in a medical interaction. The study suggested that patient-generated e-health-related inquiries invite physician mediation in medical consultations. Findings and implications are discussed in light of the literature of physician-patient interaction, incorporating the theory of parental mediation of media into a medical context.
The rise and fall of the medical mediated searcher

PubMed Central

Atlas, Michel C.

2000-01-01

The relationship between the development of mediated online literature searching and the recruitment of medical librarians to fill positions as online searchers was investigated. The history of database searching by medical librarians was outlined and a content analysis of thirty-five years of job advertisements in MLA News from 1961 through 1996 was summarized. Advertisements for online searchers were examined to test the hypothesis that the growth of mediated online searching was reflected in the recruitment of librarians to fill positions as mediated online searchers in medical libraries. The advent of end-user searching was also traced to determine how this trend affected the demand for mediated online searching and job availability of online searchers. Job advertisements were analyzed to determine what skills were in demand as end-user searching replaced mediated online searching as the norm in medical libraries. Finally, the trend away from mediated online searching to support of other library services was placed in the context of new roles for medical librarians. PMID:10658961
Relationship between mediation analysis and the structured life course approach.

PubMed

Howe, Laura D; Smith, Andrew D; Macdonald-Wallis, Corrie; Anderson, Emma L; Galobardes, Bruna; Lawlor, Debbie A; Ben-Shlomo, Yoav; Hardy, Rebecca; Cooper, Rachel; Tilling, Kate; Fraser, Abigail

2016-08-01

Many questions in life course epidemiology involve mediation and/or interaction because of the long latency period between exposures and outcomes. In this paper, we explore how mediation analysis (based on counterfactual theory and implemented using conventional regression approaches) links with a structured approach to selecting life course hypotheses. Using theory and simulated data, we show how the alternative life course hypotheses assessed in the structured life course approach correspond to different combinations of mediation and interaction parameters. For example, an early life critical period model corresponds to a direct effect of the early life exposure, but no indirect effect via the mediator and no interaction between the early life exposure and the mediator. We also compare these methods using an illustrative real-data example using data on parental occupational social class (early life exposure), own adult occupational social class (mediator) and physical capability (outcome). © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.
Hybrid anomaly and gravity mediation for electroweak supersymmetry

NASA Astrophysics Data System (ADS)

Zhu, Bin; Ding, Ran; Li, Tianjun

2018-03-01

In this paper, we propose a hybrid mediation and hybrid supersymmetry breaking. In particular, the RG-invariant anomaly mediation is considered. Together with additional gravity mediation, the slepton tachyon problem of anomaly mediation is solved automatically. The special properties are that all color sparticles masses fall into several TeV regions due to the large m0 and m32 which are well beyond the scope of current LHC Run II limits. Unlike the gauge mediation, the dark matter candidate is still the lightest neutralino and the correct dark matter relic density can be realized within the framework of mixed axion-Wino dark matter. Due to the existence of multi-component axion-Wino dark matter, the direct detection cross-section is suppressed to evade the tightest LUX, PandaX bound.
Exposure to peer delinquency as a mediator between self-report pubertal timing and delinquency: A longitudinal study of mediation

PubMed Central

Negriff, Sonya; Ji, Juye; Trickett, Penelope K.

2013-01-01

This study examined exposure to peer delinquency as a mediator between pubertal timing and self-reported delinquency longitudinally and whether this mediational model was moderated by either gender or maltreatment experience. Data were obtained from Time 1, 2, and 3 of a longitudinal study of maltreatment and development. At Time 1 the sample comprised 454 children aged 9–13 years. Analyses via structural equation modeling supported full mediation. Gender did not moderate this mediational relationship, but maltreatment experience did. The results show that early maturing males and females are both at risk for being exposed to peers that may draw them into delinquent behavior. Additionally, the mechanism linking early pubertal timing to delinquency differs depending on maltreatment experience. PMID:21262055
The Mediator Complex: At the Nexus of RNA Polymerase II Transcription.

PubMed

Jeronimo, Célia; Robert, François

2017-10-01

Mediator is an essential, large, multisubunit, transcriptional co-activator highly conserved across eukaryotes. Mediator interacts with gene-specific transcription factors at enhancers as well as with the RNA polymerase II (RNAPII) transcription machinery bound at promoters. It also interacts with several other factors involved in various aspects of transcription, chromatin regulation, and mRNA processing. Hence, Mediator is at the nexus of RNAPII transcription, regulating its many steps and connecting transcription with co-transcriptional events. To achieve this flexible role, Mediator, which is divided into several functional modules, reorganizes its conformation and composition while making transient contacts with other components. Here, we review the mechanisms of action of Mediator and propose a unifying model for its function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Kin28 regulates the transient association of Mediator with core promoters

PubMed Central

Jeronimo, Célia; Robert, François

2014-01-01

Mediator is an essential, broadly utilized eukaryotic transcriptional co-activator. How and what it communicates from activators to RNA polymerase II (RNAPII) remains an open question. Here we performed genome-wide location profiling of Saccharomyces cerevisiae Mediator subunits. Mediator is not found at core promoters but rather occupies the upstream activating sequence (UAS), upstream of the pre-initiation complex. In the absence of Kin28 (CDK7) kinase activity, or in cells where the RNAPII C-terminal domain (CTD) is mutated to replace Ser5 with alanines, however, Mediator accumulates at core promoters together with RNAPII. We propose that Mediator is quickly released from promoters upon Ser5 phosphorylation by Kin28 (CDK7), which also allows for RNAPII to escape from the promoter. PMID:24704787
On the Interpretation and Use of Mediation: Multiple Perspectives on Mediation Analysis.

PubMed

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.
Social Information Processing Mediates the Intergenerational Transmission of Aggressiveness in Romantic Relationships

PubMed Central

Fite, Jennifer E.; Bates, John E.; Holtzworth-Munroe, Amy; Dodge, Kenneth A.; Nay, Sandra Y.; Pettit, Gregory S.

2012-01-01

This study explored the K. A. Dodge (1986) model of social information processing as a mediator of the association between interparental relationship conflict and subsequent offspring romantic relationship conflict in young adulthood. The authors tested 4 social information processing stages (encoding, hostile attributions, generation of aggressive responses, and positive evaluation of aggressive responses) in separate models to explore their independent effects as potential mediators. There was no evidence of mediation for encoding and attributions. However, there was evidence of significant mediation for both the response generation and response evaluation stages of the model. Results suggest that the ability of offspring to generate varied social responses and effectively evaluate the potential outcome of their responses at least partially mediates the intergenerational transmission of relationship conflict. PMID:18540765
The future of intercultural mediation in Belgium.

PubMed

Nierkens, Vera; Krumeich, Anja; de Ridder, Ri; van Dongen, Martien

2002-04-01

Intercultural mediation was developed to solve problems between western (Belgian) health professionals and Turkish, Moroccan and Italian clients. The need for intercultural mediation in Belgium Health Care was measured by asking intercultural mediators to complete a questionnaire about situations in which language, culture, social-economic and personal circumstances cause difficulties. Results show that the profession 'intercultural mediator' continues to be important in improving the quality and accessibility of the Belgian health care for ethnic minorities. Even if clients speak Flemish fluently, there are still difficulties between health professional and client caused by culture, social-economic and personal circumstances.
Social cognitive mediators of parent-child sexual communication.

PubMed

Evans, W Douglas; Blitstein, Jonathan L; Davis, Kevin C

2011-07-01

To test a social cognitive behavior change model and identify mediators of the effects of the Parents Speak Up National Campaign (PSUNC) on parent-child sexual communication. Investigators used 5 waves of data from an online randomized controlled trial. Latent variables were developed based on item response theory and confirmatory factor analysis. Structural equation modeling was used to test mediation. Outcome expectations mediated effects of social norms and self-efficacy on sexual communication. Other hypothesized mediators were not confirmed. Interventions to promote parent-child sexual communication should target outcome expectations. Future research should investigate parents' health information seeking.
The Mediator complex: a central integrator of transcription

PubMed Central

Allen, Benjamin L.; Taatjes, Dylan J.

2016-01-01

The RNA polymerase II (pol II) enzyme transcribes all protein-coding and most non-coding RNA genes and is globally regulated by Mediator, a large, conformationally flexible protein complex with variable subunit composition (for example, a four-subunit CDK8 module can reversibly associate). These biochemical characteristics are fundamentally important for Mediator's ability to control various processes important for transcription, including organization of chromatin architecture and regulation of pol II pre-initiation, initiation, re-initiation, pausing, and elongation. Although Mediator exists in all eukaryotes, a variety of Mediator functions appear to be specific to metazoans, indicative of more diverse regulatory requirements. PMID:25693131
Exploratory Mediation Analysis via Regularization

PubMed Central

Serang, Sarfaraz; Jacobucci, Ross; Brimhall, Kim C.; Grimm, Kevin J.

2017-01-01

Exploratory mediation analysis refers to a class of methods used to identify a set of potential mediators of a process of interest. Despite its exploratory nature, conventional approaches are rooted in confirmatory traditions, and as such have limitations in exploratory contexts. We propose a two-stage approach called exploratory mediation analysis via regularization (XMed) to better address these concerns. We demonstrate that this approach is able to correctly identify mediators more often than conventional approaches and that its estimates are unbiased. Finally, this approach is illustrated through an empirical example examining the relationship between college acceptance and enrollment. PMID:29225454
49 CFR 1109.4 - Mandatory mediation in rate cases to be considered under the stand-alone cost methodology.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Mandatory mediation in rate cases to be considered... § 1109.4 Mandatory mediation in rate cases to be considered under the stand-alone cost methodology. (a) A... methodology must engage in non-binding mediation of its dispute with the railroad upon filing a formal...
25 CFR 291.10 - What is the role of the mediator appointed by the Secretary?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false What is the role of the mediator appointed by the... ENTERPRISES CLASS III GAMING PROCEDURES § 291.10 What is the role of the mediator appointed by the Secretary? (a) The mediator must ask the Indian tribe and the State to submit their last best proposal for Class...
The Relationship between Psychological Contract Breach and Organizational Commitment: Exchange Imbalance as a Moderator of the Mediating Role of Violation

ERIC Educational Resources Information Center

Cassar, Vincent; Briner, Rob B.

2011-01-01

This study tested the mediating role of violation in the relationship between breach and both affective and continuance commitment and the extent to which this mediating role is moderated by exchange imbalance amongst a sample of 103 sales personnel. Results suggest that violation mediated the relationship between breach and commitment. Also,…
The systemic immune network in recent onset type 1 diabetes: central role of interleukin-1 receptor antagonist (DIATOR Trial).

PubMed

Kolb, Hubert; Lückemeyer, Kathrin; Heise, Tim; Herder, Christian; Schloot, Nanette C; Koenig, Wolfgang; Heinemann, Lutz; Martin, Stephan

2013-01-01

The hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics. All patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18-39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation) giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA) held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25-0.72), i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI). There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß) but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex. In patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and is the only mediator which correlates (positively) with residual beta cell function. ClinicalTrials.gov registration number: NCT00974740.
The mediation effect of emotional eating between depression and body mass index in the two European countries Denmark and Spain.

PubMed

van Strien, Tatjana; Winkens, Laura; Toft, Madeleine Broman; Pedersen, Susanne; Brouwer, Ingeborg; Visser, Marjolein; Lähteenmäki, Liisa

2016-10-01

In two European countries with a different prevalence of depression, namely Denmark (high) and Spain (low), we assessed whether the mediation effect of emotional eating between depression and Body Mass Index (BMI) as found in earlier studies can be replicated and whether this mediation effect is contingent on 1) change in appetite and 2) gender. Mediation and moderated mediation was assessed with Hayes' PROCESS macro in SPSS. Emotional eating (DEBQ: Dutch Eating Behavior Questionnaire), depressive symptoms (CES-D: Center for Epidemiologic Studies Depression Scale), change in appetite, weight and height were self-reported. In both countries, emotional eating acted as a mediator between depression and BMI (Denmark: B = 0.03 (SE = 0.01), 95% CI, [0.03, 0.05]; Spain: B = 0.03 (SE = 0.01), 95% CI, [0.02, 0.04]). In Denmark this mediation effect was stronger for participants with increased appetite and for females than for participants with decreases/no change in appetite and for males (more appetite: B = 0.08, (SE = 0.03), [0.03, 0.15]; decreased appetite/no change in appetite: B = 0.03 (SE = 0.01), [0.02, 0.04]); females: B = 0.05 (SE = 0.01), [0.03, 0.07]; males: B = 0.01 (SE = 0.01), [0.004, 0.04]. This supports depression with atypical features as an underlying mechanism in the mediation effect of emotional eating. In Spain there was no support for depression with atypical features as underlying mechanism because the mediation effect was neither moderated by change in appetite nor by gender. Instead, post-hoc analyses suggested 'stress of unemployment' as possible explanatory factor of the mediation effect, with stronger mediation effects for unemployed than for employed people (unemployed: B = 0.05 (SE = 0.01), [0.03, 0.07]; employed B = 0.02 (SE = 0.01), [0.01, 0.04]). The mediating effect of emotional eating between depressive symptoms and body mass index in both countries suggests that obesity interventions should take emotional eating into account. Copyright © 2016 Elsevier Ltd. All rights reserved.
Explaining the effects of a 1-year intervention promoting a low fat diet in adolescent girls: a mediation analysis.

PubMed

Haerens, Leen; Cerin, Ester; Deforche, Benedicte; Maes, Lea; De Bourdeaudhuij, Ilse

2007-11-09

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. 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. 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). 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. Alternatively, it could be argued that these constructs need not be targeted in interventions aimed at adolescents, as they may not be responsible for the intervention effects on fat intake. To draw any conclusions regarding mediators of fat-intake change in adolescent' girls and regarding optimal future intervention strategies, more systematic research on the mediating properties of psychosocial variables is needed.
Molecular architecture of the human Mediator-RNA polymerase II-TFIIF assembly.

PubMed

Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C; Nogales, Eva; Taatjes, Dylan J

2011-03-01

The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator-pol II interface is not well-characterized, whereas attempts to structurally define the Mediator-pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator-pol II-TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator-pol II-TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator-pol II-TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator-CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator-pol II complexes lacking TFIIF reveal that TFIIF plays a key role in stabilizing pol II orientation within the assembly.
Coping mediates the effects of cognitive-behavioral therapy for alcohol use disorder among out-patient clients in Project MATCH when dependence severity is high.

PubMed

Roos, Corey R; Maisto, Stephen A; Witkiewitz, Katie

2017-09-01

There is inconsistent evidence that alcohol-specific coping is a mechanism of change in cognitive-behavioral therapy (CBT) for alcohol use disorder (AUD). Our primary aim was to test whether baseline dependence severity moderates the mediational effect of CBT on drinking outcomes via coping. Secondary data analysis of Project MATCH , a multi-site alcohol treatment trial in which participants, recruited in out-patient and aftercare arms, were randomized to three treatments: CBT, motivational enhancement therapy (MET) and Twelve-Step facilitation (TSF). Nine research sites in the United States. A total of 1063 adults with AUD. The primary outcomes were percentage days abstinent and percentage heavy drinking days at the 1-year follow-up. Coping was assessed with the Processes of Change Questionnaire . Dependence severity was measured with the Alcohol Dependence Scale . Among the full available sample (across treatment arms), there were no significant moderated mediation effects. Double moderated mediation analyses indicated that several moderated mediation effects were moderated by treatment arm (all P < 0.05). In the out-patient arm, there were several significant moderated mediation effects (all P < 0.05), but no significant moderated mediation effects in the aftercare arm. For out-patient clients with high baseline dependence severity, end-of-treatment coping mediated the positive treatment effects of CBT, compared with both MET and TSF, on 1-year drinking outcomes (all P < 0.05). Coping did not mediate treatment effects of CBT among those with low or moderate dependence severity. In the Project MATCH out-patient sample, whether or not coping mediated the effects of cognitive-behavioral therapy for alcohol use disorder was conditional on dependence severity. End-of-treatment coping mediated the positive treatment effects of cognitive-behavioral therapy on 1-year drinking outcomes among out-patient clients when dependence severity was high, but not when dependence severity was low or moderate. © 2017 Society for the Study of Addiction.
Adenoviral mediated interferon-alpha 2b gene therapy suppresses the pro-angiogenic effect of vascular endothelial growth factor in superficial bladder cancer.

PubMed

Adam, Liana; Black, Peter C; Kassouf, Wassim; Eve, Beryl; McConkey, David; Munsell, Mark F; Benedict, William F; Dinney, Colin P N

2007-05-01

Intravesical adenovirus mediated interferon-alpha gene transfer has a potent therapeutic effect against superficial human bladder carcinoma xenografts growing in the bladder of athymic nude mice. We determined whether the inhibition of angiogenesis might contribute to the antitumor effect. We treated several human urothelial carcinoma cells with adenovirus mediated interferon-alpha 2b and monitored its effects on the production of angiogenic factors using real-time reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemical analysis and a gel shift based transcription factor array. To assess the role of adenovirus mediated interferon 2b in angiogenic activity we used in vitro invasion assays and evaluated the anti-angiogenic effects of adenovirus mediated interferon gene therapy in an orthotopic murine model of human superficial bladder cancer. In adenovirus mediated interferon-alpha infected 253J B-V cells vascular endothelial growth factor was decreased and anti-angiogenic interferon-gamma inducible protein 10 was up-regulated. In contrast, the addition of as much as 100,000 IU recombinant interferon had no apparent effect on vascular endothelial growth factor production. Conditioned medium derived from adenovirus mediated interferon 2b infected 253J B-V cells greatly decreased the invasive potential of human endothelial cells and down-regulated their matrix metalloproteinase 2 expression compared to controls. Furthermore, adenovirus mediated interferon 2b blocked pro-angiogenic nuclear signals, such as the transcription factors activating protein-1 and 2, stimulating protein-1, nuclear factor kappaB and c-myb. In vivo experiments revealed significant vascular endothelial growth factor down-regulation and decreased tumor vessel density in the adenovirus mediated interferon 2b treated group compared to controls. Treatment with adenovirus mediated interferon 2b increases the angiostatic activity of the bladder cancer microenvironment. This inhibition may prove beneficial for treating superficial bladder cancer with adenovirus mediated interferon-alpha and hopefully contribute to a decreased recurrence rate of this neoplasm.
48 CFR 6101.54 - Alternative dispute resolution [Rule 54].

Code of Federal Regulations, 2010 CFR

2010-10-01

... as ADR Neutrals, most commonly use a combination of facilitative and evaluative mediation approaches...) Evaluative mediation. In addition to engaging in facilitative mediation, if authorized under the terms of the...
48 CFR 6101.54 - Alternative dispute resolution [Rule 54].

Code of Federal Regulations, 2012 CFR

2012-10-01

... as ADR Neutrals, most commonly use a combination of facilitative and evaluative mediation approaches...) Evaluative mediation. In addition to engaging in facilitative mediation, if authorized under the terms of the...
48 CFR 6101.54 - Alternative dispute resolution [Rule 54].

Code of Federal Regulations, 2014 CFR

2014-10-01

... as ADR Neutrals, most commonly use a combination of facilitative and evaluative mediation approaches...) Evaluative mediation. In addition to engaging in facilitative mediation, if authorized under the terms of the...
48 CFR 6101.54 - Alternative dispute resolution [Rule 54].

Code of Federal Regulations, 2011 CFR

2011-10-01

... as ADR Neutrals, most commonly use a combination of facilitative and evaluative mediation approaches...) Evaluative mediation. In addition to engaging in facilitative mediation, if authorized under the terms of the...

48 CFR 6101.54 - Alternative dispute resolution [Rule 54].

Code of Federal Regulations, 2013 CFR

2013-10-01

... as ADR Neutrals, most commonly use a combination of facilitative and evaluative mediation approaches...) Evaluative mediation. In addition to engaging in facilitative mediation, if authorized under the terms of the...
24 CFR 3288.35 - Mediation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... commencement of the mediation to reach a mediated settlement. In every case, the dispute resolution provider... to reach a settlement. (3) For corrective repairs. Unless a longer period is agreed to in writing by...
Practicing more retrieval routes leads to greater memory retention.

PubMed

Zheng, Jun; Zhang, Wei; Li, Tongtong; Liu, Zhaomin; Luo, Liang

2016-09-01

A wealth of research has shown that retrieval practice plays a significant role in improving memory retention. The current study focused on one simple yet rarely examined question: would repeated retrieval using two different retrieval routes or using the same retrieval route twice lead to greater long-term memory retention? Participants elaborately learned 22 Japanese-Chinese translation word pairs using two different mediators. Half an hour after the initial study phase, the participants completed two retrieval sessions using either one mediator (Tm1Tm1) or two different mediators (Tm1Tm2). On the final test, which was performed 1week after the retrieval practice phase, the participants received only the cue with a request to report the mediator (M1 or M2) followed by the target (Experiment 1) or only the mediator (M1 or M2) with a request to report the target (Experiment 2). The results of Experiment 1 indicated that the participants who practiced under the Tm1Tm2 condition exhibited greater target retention than those who practiced under the Tm1Tm1 condition. This difference in performance was due to the significant disadvantage in mediator retrieval and decoding of the unpracticed mediator under the Tm1Tm1 condition. Although mediators were provided to participants on the final test in Experiment 2, decoding of the unpracticed mediators remained less effective than decoding of the practiced mediators. We conclude that practicing multiple retrieval routes leads to greater memory retention than focusing on a single retrieval route. Thus, increasing retrieval variability during repeated retrieval practice indeed significantly improves long-term retention in a delay test. Copyright © 2016 Elsevier B.V. All rights reserved.
The prevalence of eosinophilic esophagitis in pediatric patients with IgE-mediated food allergy

PubMed Central

Hill, David A.; Dudley, Jesse W.; Spergel, Jonathan M.

2017-01-01

BACKGROUND Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Recently, EoE has been identified in patients undergoing oral immunotherapy (OIT) for IgE-mediated food allergy, suggesting an association. OBJECTIVE We sought to ascertain whether significant associations exist between IgE-mediated food allergies and EoE. METHODS Utilizing analysis of EMR data and manual chart review, we examined our sub-specialty care network of 35,528 children and adolescents to identify and characterize patients with IgE-mediated, and EoE food allergy. The most common food allergens were defined, and the prevalence of EoE in patients with IgE-mediated food allergy was determined. Logistic regression was used to measure the extent to which IgE-mediated food allergy to specific foods is associated with EoE. RESULTS The most common causes of EoE were milk, grains, meats, peanut, tree nuts, egg, and soy, an allergen pattern that is distinct from that of IgE-mediated food allergy. The prevalence of EoE in patients with IgE-mediated food allergy was higher than that reported in the general population (4.7% vs 0.04%). The distribution of IgE-mediated food allergens in patients with EoE was similar to that of the general population, and IgE-mediated allergy to egg (2.27; 1.91–2.64), milk (4.19; 3.52–4.97), or shellfish (1.55; 1.24–1.92) was significantly associated with EoE diagnosis. CONCLUSIONS Our findings support a clinical association between these conditions that has implications for the management of children with food allergy, and particular relevance to patients undergoing OIT. PMID:28042003
Salivary and serum inflammatory mediators among pre-conception women with periodontal disease.

PubMed

Jiang, Hong; Zhang, Yiming; Xiong, Xu; Harville, Emily W; O, Karmin; Qian, Xu

2016-12-15

There have been inconsistent conclusions regarding the levels of inflammatory mediators in saliva and serum among people with or without periodontal disease. Although pre-conception has been put forward as the optimal time for the periodontal treatment in order to improving pregnancy outcomes, few studies have been conducted to examine inflammatory mediators in saliva and serum among pre-conception women. Pre-conception women were recruited between January 2012 and December 2014. Women were provided with an oral health examination to detect periodontal disease. Salivary and serum samples were collected at the same of examination. Inflammatory mediators includinginterleukin-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α) and beta-glucuronidase (β-glucuronidase) were tested and analyzed among women with overall periodontal disease (n = 442) or moderate/severe periodontal disease (n = 247). Results were compared to that in women with a healthy periodontium (n = 91). Significantly increased concentrations of inflammatory mediators of IL-1β, IL-6, TNF-α and β-glucuronidase in saliva and IL-1β, β-glucuronidase and TNF-α in serum were found among pre-conception women with moderate/severe periodontal disease, compared with women without periodontal disease. Significantly increased levels were also found in all the above saliva inflammatory mediators and in serum IL-1β and TNF-α among women with overall periodontal disease. The levels of all inflammatory mediators in saliva and almost all inflammatory mediators except IL-6 in serum significantly increased with severity of periodontal disease. Periodontal disease is highly associated with the elevated levels of inflammatory mediators in saliva and some mediators in serum among pre-conception women.
Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs.

PubMed

Friedenberg, Steven G; Buhrman, Greg; Chdid, Lhoucine; Olby, Natasha J; Olivry, Thierry; Guillaumin, Julien; O'Toole, Theresa; Goggs, Robert; Kennedy, Lorna J; Rose, Robert B; Meurs, Kathryn M

2016-03-01

Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher's exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.
Mediating effects of self-stigma on the relationship between perceived stigma and psychosocial outcomes among psychiatric outpatients: findings from a cross-sectional survey in Singapore

PubMed Central

Picco, Louisa; Lau, Ying Wen; Pang, Shirlene; Abdin, Edimansyah; Vaingankar, Janhavi Ajit; Chong, Siow Ann; Subramaniam, Mythily

2017-01-01

Objectives To examine whether self-stigma mediates the relationship between perceived stigma and quality of life, self-esteem and general functioning among outpatients with depression, schizophrenia, anxiety and obsessive-compulsive disorder (OCD). Design Cross-sectional survey. Setting Outpatient clinics at a tertiary psychiatric hospital in Singapore. Participants 280 outpatients with a primary clinical diagnosis of either schizophrenia, depression, anxiety or OCD. Methods Data were collected in relation to self-stigma, perceived stigma, self-esteem, functioning and quality of life. In order to examine the mediating role of self-stigma on the relationship between perceived stigma and psychosocial outcomes, bootstrapping mediation analyses were used. Results Mediation analyses revealed that the relationship between perceived stigma and psychosocial outcomes was subject to the effects of self-stigma among the overall sample. Separate mediation analyses were conducted by diagnoses and showed differences in the mediating effects of self-stigma. Among the whole sample and the subsample with OCD, self-stigma mediated the relationship between perceived stigma and all psychosocial outcomes. For those with anxiety, depression and schizophrenia, the mediating effects of self-stigma were present in all relationships except (1) perceived stigma with physical health in the anxiety sample, (2) perceived stigma with social relationships in the depression sample and (3) perceived stigma with physical health in the schizophrenia sample. Conclusions The mediating effects of self-stigma on the relationship between perceived stigma and various psychosocial outcomes are evident and differ across diagnoses. Interventions to address and reduce the effects of self-stigma along with targeted treatments and psychoeducation to assist people with mental illness overcome or better manage self-stigma while providing them the skills to counteract public stigma are needed. PMID:28851803
Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

PubMed Central

Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

2016-01-01

ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297
Developing models of how cognitive improvements change functioning: Mediation, moderation and moderated mediation

PubMed Central

Wykes, Til; Reeder, Clare; Huddy, Vyv; Taylor, Rumina; Wood, Helen; Ghirasim, Natalia; Kontis, Dimitrios; Landau, Sabine

2012-01-01

Background Cognitive remediation (CRT) affects functioning but the extent and type of cognitive improvements necessary are unknown. Aim To develop and test models of how cognitive improvement transfers to work behaviour using the data from a current service. Method Participants (N49) with a support worker and a paid or voluntary job were offered CRT in a Phase 2 single group design with three assessments: baseline, post therapy and follow-up. Working memory, cognitive flexibility, planning and work outcomes were assessed. Results Three models were tested (mediation — cognitive improvements drive functioning improvement; moderation — post treatment cognitive level affects the impact of CRT on functioning; moderated mediation — cognition drives functioning improvements only after a certain level is achieved). There was evidence of mediation (planning improvement associated with improved work quality). There was no evidence that cognitive flexibility (total Wisconsin Card Sorting Test errors) and working memory (Wechsler Adult Intelligence Scale III digit span) mediated work functioning despite significant effects. There was some evidence of moderated mediation for planning improvement if participants had poorer memory and/or made fewer WCST errors. The total CRT effect on work quality was d = 0.55, but the indirect (planning-mediated CRT effect) was d = 0.082 Conclusion Planning improvements led to better work quality but only accounted for a small proportion of the total effect on work outcome. Other specific and non-specific effects of CRT and the work programme are likely to account for some of the remaining effect. This is the first time complex models have been tested and future Phase 3 studies need to further test mediation and moderated mediation models. PMID:22503640
Cocaine induces astrocytosis through ER stress-mediated activation of autophagy.

PubMed

Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

2016-08-02

Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation.
Post-Traumatic Symptomatology and Compulsions as Potential Mediators of the Relation Between Child Sexual Abuse and Auditory Verbal Hallucinations.

PubMed

McCarthy-Jones, Simon

2018-05-01

Whilst evidence is mounting that childhood sexual abuse (CSA) can be a cause of auditory verbal hallucinations (AVH), it is unclear what factors mediate this relation. Recent evidence suggests that post-traumatic symptomatology may mediate the CSA-AVH relation in clinical populations, although this hypothesis has not yet been tested in the general population. There is also reason to believe that obsessive ideation could mediate the CSA-AVH relation. To test for evidence to falsify the hypotheses that post-traumatic symptomatology, obsessions, compulsions, anxiety and depression mediate the relation between CSA and AVH in a general population sample. Indirect effects of CSA on AVH via potential mediators were tested for, using a regression-based approach employing data from the 2007 Adult Psychiatric Morbidity Survey (n = 5788). After controlling for demographics, IQ and child physical abuse, it was found that CSA, IQ, post-traumatic symptomatology and compulsions predicted lifetime experience of AVH. Mediation analyses found significant indirect effects of CSA on AVH via post-traumatic symptomatology [odds ratio (OR): 1.11; 95% confidence interval (CI):1.00-1.29] and compulsions (OR: 1.10, 95% CI: 1.01-1.28). These findings offer further support for the hypothesis that post-traumatic symptomatology is a mediator of the CSA-AVH relation. Although no evidence was found for obsessional thoughts as a mediating variable, a potential mediating role for compulsions is theoretically intriguing. This study's findings reiterate the need to ask about experiences of childhood adversity and post-traumatic symptomology in people with AVH, as well as the likely therapeutic importance of trauma-informed and trauma-based interventions for this population.
Improving quality-of-life outcomes for patients with cancer through mediating effects of depressive symptoms and functional status: a three-path mediation model.

PubMed

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.
Direct and indirect effects of alcohol expectancies through drinking motives on alcohol outcomes among students in Vietnam.

PubMed

Diep, Pham Bich; Schelleman-Offermans, K; Kuntsche, E; De Vries, Nanne; Knibbe, Ronald A

2016-01-01

To investigate whether the links between alcohol expectancies (tension reduction; global positive change; improved cognitive and motor abilities; and change in social behavior) and alcohol outcomes (drinking volume, 6+ drinks, alcohol problems, and symptoms of alcohol dependence) are mediated by drinking motives (social, enhancement, conformity, and coping). A multi-stage sampling strategy was used in four Vietnamese provinces, resulting in a final sample of 4756 students (43.2% females) with mean age 20.6 (SD 1.8) years. Structural equation models, including indirect effects, were estimated for women and men separately. Overall, there were many cases of full mediation (indirect effects range from -0.006 to 0.083 and p-values from <0.05 to <0.001) and little indication of partial mediation (indirect effects range from -0.009 to 0.025 and p-values from <0.05 to <0.001). In both men and women, coping motives most frequently mediated the influence of expectancies on alcohol outcomes. Among men, enhancement motives and, to a lesser extent, social motives also played a role in mediating the effects of expectancies on alcohol outcomes. Among women, full mediation was found far less often and less consistently. By confirming that, in Vietnam, motives mediate the link between expectancies and drinking behavior, this study supports the cultural robustness of a key assumption of the motivational model (i.e. that drinking motives are more closely associated with alcohol use than expectancies). Enhancement, coping and social motives are most frequently found as mediators among male students whereas coping motive only is most frequently found as a mediator among female students. As most of the effects of expectancies were mediated by motives, drinking motives appear to be a promising factor for interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.
7 CFR 785.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... mediation process in which the mediator will not disclose to any person oral or written communications... has attended a minimum of 40 hours of core mediator knowledge and skills training and, to remain in a...
7 CFR 785.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... mediation process in which the mediator will not disclose to any person oral or written communications... has attended a minimum of 40 hours of core mediator knowledge and skills training and, to remain in a...
7 CFR 785.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... mediation process in which the mediator will not disclose to any person oral or written communications... has attended a minimum of 40 hours of core mediator knowledge and skills training and, to remain in a...
Sensitivity analysis for direct and indirect effects in the presence of exposure-induced mediator-outcome confounders

PubMed Central

Chiba, Yasutaka

2014-01-01

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

PubMed

Baron, R M; Kenny, D A

1986-12-01

In this article, we attempt to distinguish between the properties of moderator and mediator variables at a number of levels. First, we seek to make theorists and researchers aware of the importance of not using the terms moderator and mediator interchangeably by carefully elaborating, both conceptually and strategically, the many ways in which moderators and mediators differ. We then go beyond this largely pedagogical function and delineate the conceptual and strategic implications of making use of such distinctions with regard to a wide range of phenomena, including control and stress, attitudes, and personality traits. We also provide a specific compendium of analytic procedures appropriate for making the most effective use of the moderator and mediator distinction, both separately and in terms of a broader causal system that includes both moderators and mediators.
Different perspectives of cultural mediation: implications for the research design on studies examining its effect on students' cognition

NASA Astrophysics Data System (ADS)

Teo, Tang Wee

2013-06-01

In this forum, I extend Tao, Oliver, and Venville's paper Chinese and Australian children's understanding of the earth: a cross cultural study of conceptual development to discuss the different views on culture and cultural mediation. I tease out nuances in the viewpoints to suggest three ways to theoretically frame studies examining cultural mediation of students' cognition. Specifically, cultural mediation may be attributed to innate psychological attributes, an accretion of cultural elements, or the social interaction process. Each of these ideas represents a theoretical lens and has implications for the research design of studies relating cultural mediation to cognition. In the final section of this forum paper, I show how a study conducted from the symbolic interactionist viewpoint underscoring cultural mediation as a social interaction process might unfold.
Curvature-Mediated Assembly of Janus Nanoparticles on Membrane Vesicles.

PubMed

Bahrami, Amir Houshang; Weikl, Thomas R

2018-02-14

Besides direct particle-particle interactions, nanoparticles adsorbed to biomembranes experience indirect interactions that are mediated by the membrane curvature arising from particle adsorption. In this Letter, we show that the curvature-mediated interactions of adsorbed Janus particles depend on the initial curvature of the membrane prior to adsorption, that is, on whether the membrane initially bulges toward or away from the particles in our simulations. The curvature-mediated interaction can be strongly attractive for Janus particles adsorbed to the outside of a membrane vesicle, which initially bulges away from the particles. For Janus particles adsorbed to the vesicle inside, in contrast, the curvature-mediated interactions are repulsive. We find that the area fraction of the adhesive Janus particle surface is an important control parameter for the curvature-mediated interaction and assembly of the particles, besides the initial membrane curvature.

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

PubMed Central

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
Job security and work performance in Chinese employees: The mediating role of organisational identification.

PubMed

Ma, Bing; Liu, Shanshi; Liu, Donglai; Wang, Hongchun

2016-04-01

This research focuses on investigating whether organisational identification mediates the effects of job security on in-role behaviour and extra-role behaviour and how these mediation mechanisms differ according to gender. Through analysing 212 supervisor-subordinate dyads from a Chinese air transportation group, the research indicated that organisational identification partially mediated the effect of job security on in-role behaviour and fully mediated the effect of job security on extra-role behaviour. A multi-group analysis also showed that there were significant differences between male and female employees in these relationships. In addition, moderated mediation analyses showed that gender moderated the indirect effects of job security on in-role behaviour and extra-role behaviour through organisational identification. Limitations and implications of these findings are discussed. © 2015 International Union of Psychological Science.
Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance.

PubMed

Yamada, Akiko; Arakaki, Rieko; Saito, Masako; Kudo, Yasusei; Ishimaru, Naozumi

2017-01-01

Fas-mediated apoptosis contributes to physiological and pathological cellular processes, such as differentiation and survival. In particular, the roles of Fas in immune cells are complex and critical for the maintenance of immune tolerance. The precise pathways and unique functions associated with Fas/FasL-mediated signaling in the immune system are known. The dual character of Fas/FasL-mediated immune regulation that induces beneficial or harmful effects is associated with the onset or development of immune disorders. Studies on mutations in genes encoding Fas and FasL gene of humans and mice contributed to our understanding of the pathogenesis of autoimmune diseases. Here, we review the opposing functions of Fas/FasL-mediated signaling, bilateral effects of Fas/FasL on in immune cells, and complex pathogenesis of autoimmunity mediated by Fas/FasL.
Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance

PubMed Central

Yamada, Akiko; Arakaki, Rieko; Saito, Masako; Kudo, Yasusei; Ishimaru, Naozumi

2017-01-01

Fas-mediated apoptosis contributes to physiological and pathological cellular processes, such as differentiation and survival. In particular, the roles of Fas in immune cells are complex and critical for the maintenance of immune tolerance. The precise pathways and unique functions associated with Fas/FasL-mediated signaling in the immune system are known. The dual character of Fas/FasL-mediated immune regulation that induces beneficial or harmful effects is associated with the onset or development of immune disorders. Studies on mutations in genes encoding Fas and FasL gene of humans and mice contributed to our understanding of the pathogenesis of autoimmune diseases. Here, we review the opposing functions of Fas/FasL-mediated signaling, bilateral effects of Fas/FasL on in immune cells, and complex pathogenesis of autoimmunity mediated by Fas/FasL. PMID:28424702
Psychological mechanism linking abusive supervision and compulsory citizenship behavior: a moderated mediation study.

PubMed

Zhao, Hongdan; Peng, Zhenglong; Han, Yong; Sheard, Geoff; Hudson, Alan

2013-01-01

This study seeks to examine the effect of abusive supervision on the "dark side" of organizational citizenship behavior (OCB) and, specifically, compulsory citizenship behavior (CCB). The study focuses on the mediating role of psychological safety underpinning the relationship between abusive supervision and CCB, and the moderating role of Chinese traditionality in influencing the mediation. The authors tested the model with data of 434 dyads (employee-coworker pairs) in a large Chinese service company. Results indicated that psychological safety fully mediated the relationship between abusive supervision and CCB. The authors also found that Chinese traditionality moderated the strength of the mediated relationship between abusive supervision and CCB via psychological safety, such that the mediated relationship is weaker under high Chinese traditionality than under low Chinese traditionality. The article also discusses the implications, limitations, and future research directions.
Protein S is inducible by interleukin 4 in T cells and inhibits lymphoid cell procoagulant activity

PubMed Central

Smiley, Stephen T.; Boyer, Sarah N.; Heeb, Mary J.; Griffin, John H.; Grusby, Michael J.

1997-01-01

Extravascular procoagulant activity often accompanies cell-mediated immune responses and systemic administration of pharmacologic anticoagulants prevents cell-mediated delayed-type hypersensitivity reactions. These observations suggest a direct association between coagulation and cell-mediated immunity. The cytokine interleukin (IL)-4 potently suppresses cell-mediated immune responses, but its mechanism of action remains to be determined. Herein we demonstrate that the physiologic anticoagulant protein S is IL-4-inducible in primary T cells. Although protein S was known to inhibit the classic factor Va-dependent prothrombinase assembled by endothelial cells and platelets, we found that protein S also inhibits the factor Va-independent prothrombinase assembled by lymphoid cells. Thus, protein S-mediated down-regulation of lymphoid cell procoagulant activity may be one mechanism by which IL-4 antagonizes cell-mediated immunity. PMID:9326636
Mediating the Maltreatment-Delinquency Relationship: The Role of Triad Gang Membership.

PubMed

Chui, Wing Hong; Khiatani, Paul Vinod

2018-02-01

The primary aim of this article is to examine the role of triad affiliation in mediating the relationship between child maltreatment (neglect, punishment, emotional abuse, and sexual abuse) and delinquency among active young gang members in Hong Kong. A sample of 177 gang members aged 12 to 24 was recruited to complete a questionnaire with the assistance of a youth outreach social work team. Neglect was identified as the most common form of maltreatment, followed by emotional abuse, punishment, and sexual abuse. Mediation analyses confirmed that triad affiliation acts as a mediating variable in the child maltreatment-delinquency relationship, except in cases of sexual abuse. Only the relationship between punishment and delinquency was found to be fully mediated by triad affiliation; partial mediation effects were found for neglect and emotional abuse. Recommendations for child protection and youth workers are provided.
Do social support, stigma, and social problem-solving skills predict depressive symptoms in people living with HIV? A mediation analysis.

PubMed

White, Worawan; Grant, Joan S; Pryor, Erica R; Keltner, Norman L; Vance, David E; Raper, James L

2012-01-01

Social support, stigma, and social problem solving may be mediators of the relationship between sign and symptom severity and depressive symptoms in people living with HIV (PLWH). However, no published studies have examined these individual variables as mediators in PLWH. This cross-sectional, correlational study of 150 PLWH examined whether social support, stigma, and social problem solving were mediators of the relationship between HIV-related sign and symptom severity and depressive symptoms. Participants completed self-report questionnaires during their visits at two HIV outpatient clinics in the Southeastern United States. Using multiple regression analyses as a part of mediation testing, social support, stigma, and social problem solving were found to be partial mediators of the relationship between sign and symptom severity and depressive symptoms, considered individually and as a set.
Retrieval activates related words more than presentation.

PubMed

Hausman, Hannah; Rhodes, Matthew G

2018-03-23

Retrieving information enhances learning more than restudying. One explanation of this effect is based on the role of mediators (e.g., sand-castle can be mediated by beach). Retrieval is hypothesised to activate mediators more than restudying, but existing tests of this hypothesis have had mixed results [Carpenter, S. K. (2011). Semantic information activated during retrieval contributes to later retention: Support for the mediator effectiveness hypothesis of the testing effect. Journal of Experimental Psychology: Learning, Memory, and Cognition, 37(6), 1547-1552. doi: 10.1037/a0024140 ; Lehman, M., & Karpicke, J. D. (2016). Elaborative retrieval: Do semantic mediators improve memory? Journal of Experimental Psychology: Learning, Memory, and Cognition, 42(10), 1573-1591. doi: 10.1037/xlm0000267 ]. The present experiments explored an explanation of the conflicting results, testing whether mediator activation during a retrieval attempt depends on the accessibility of the target information. A target was considered less versus more accessible when fewer versus more cues were given during retrieval practice (Experiments 1 and 2), when the target had been studied once versus three times initially (Experiment 3), or when the target could not be recalled versus could be recalled during retrieval practice (Experiments 1-3). A mini meta-analysis of all three experiments revealed a small effect such that retrieval activated mediators more than presentation, but mediator activation was not reliably related to target accessibility. Thus, retrieval may enhance learning by activating mediators, in part, but these results suggest the role of other processes, too.
Clinical data, clinicopathologic findings and outcome in dogs with amegakaryocytic thrombocytopenia and primary immune-mediated thrombocytopenia.

PubMed

Cooper, S A; Huang, A A; Raskin, R E; Weng, H-Y; Scott-Moncrieff, J C

2016-03-01

The aim of this study was to identify distinguishing characteristics between dogs diagnosed with amegakaryocytic thrombocytopenia and those diagnosed with presumed primary peripheral immune-mediated thrombocytopenia. Presenting clinical and clinicopathologic data and outcomes were compared between the two groups. Retrospective study performed on seven client-owned dogs diagnosed with amegakaryocytic thrombocytopenia and 34 client-owned dogs with primary peripheral immune-mediated thrombocytopenia. All dogs in the amegakaryocytic thrombocytopenia group were anaemic on presentation with a median haematocrit of 23% (range 9·4 to 36), while the primary peripheral immune-mediated thrombocytopoenia group had a median presenting haematocrit of 35% (range 10 to 53). Dogs with amegakaryocytic thrombocytopenia had a median of five (range 4 to 7) clinical signs of bleeding compared to a median of three (range 0 to 6) in the primary peripheral immune-mediated thrombocytopenia group with 86% (6 of 7) of amegakaryocytic thrombocytopenia dogs requiring a blood transfusion compared to 41% (14 of 34) of primary peripheral immune-mediated thrombocytopenia dogs. Six of the seven amegakaryocytic thrombocytopenia dogs did not survive to discharge, while only five of the 34 primary peripheral immune-mediated thrombocytopenia dogs did not survive to discharge. The clinical presentation of dogs with amegakaryocytic thrombocytopenia and primary peripheral immune-mediated thrombocytopenia is similar, but dogs with amegakaryocytic thrombocytopenia had a more severe clinical course compared to primary peripheral immune-mediated thrombocytopenia dogs. The prognosis for dogs with amegakaryocytic thrombocytopenia is poor. © 2016 British Small Animal Veterinary Association.
Auxin-dependent compositional change in Mediator in ARF7- and ARF19-mediated transcription.

PubMed

Ito, Jun; Fukaki, Hidehiro; Onoda, Makoto; Li, Lin; Li, Chuanyou; Tasaka, Masao; Furutani, Masahiko

2016-06-07

Mediator is a multiprotein complex that integrates the signals from transcription factors binding to the promoter and transmits them to achieve gene transcription. The subunits of Mediator complex reside in four modules: the head, middle, tail, and dissociable CDK8 kinase module (CKM). The head, middle, and tail modules form the core Mediator complex, and the association of CKM can modify the function of Mediator in transcription. Here, we show genetic and biochemical evidence that CKM-associated Mediator transmits auxin-dependent transcriptional repression in lateral root (LR) formation. The AUXIN/INDOLE 3-ACETIC ACID 14 (Aux/IAA14) transcriptional repressor inhibits the transcriptional activity of its binding partners AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 by making a complex with the CKM-associated Mediator. In addition, TOPLESS (TPL), a transcriptional corepressor, forms a bridge between IAA14 and the CKM component MED13 through the physical interaction. ChIP assays show that auxin induces the dissociation of MED13 but not the tail module component MED25 from the ARF7 binding region upstream of its target gene. These findings indicate that auxin-induced degradation of IAA14 changes the module composition of Mediator interacting with ARF7 and ARF19 in the upstream region of their target genes involved in LR formation. We suggest that this regulation leads to a quick switch of signal transmission from ARFs to target gene expression in response to auxin.
LDB1-mediated enhancer looping can be established independent of mediator and cohesin.

PubMed

Krivega, Ivan; Dean, Ann

2017-08-21

Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected. Additional deletion of the promoter GATA1 site eliminated LDB1 complex and mediator occupancy and resulted in loss of LCR/β-globin proximity. To separate the roles of LDB1 and mediator in LCR looping, we expressed a looping-competent but transcription-activation deficient form of LDB1 in LDB1 knock down cells: LCR/β-globin proximity was restored without mediator core occupancy. Further, Cas9-directed tethering of mutant LDB1 to the β-globin promoter forced LCR loop formation in the absence of mediator or cohesin occupancy. Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs. Thus, lineage specific factors largely mediate enhancer-promoter looping in erythroid cells independent of mediator and cohesin. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.
Implementation and reporting of causal mediation analysis in 2015: a systematic review in epidemiological studies.

PubMed

Liu, Shao-Hsien; Ulbricht, Christine M; Chrysanthopoulou, Stavroula A; Lapane, Kate L

2016-07-20

Causal mediation analysis is often used to understand the impact of variables along the causal pathway of an occurrence relation. How well studies apply and report the elements of causal mediation analysis remains unknown. We systematically reviewed epidemiological studies published in 2015 that employed causal mediation analysis to estimate direct and indirect effects of observed associations between an exposure on an outcome. We identified potential epidemiological studies through conducting a citation search within Web of Science and a keyword search within PubMed. Two reviewers independently screened studies for eligibility. For eligible studies, one reviewer performed data extraction, and a senior epidemiologist confirmed the extracted information. Empirical application and methodological details of the technique were extracted and summarized. Thirteen studies were eligible for data extraction. While the majority of studies reported and identified the effects of measures, most studies lacked sufficient details on the extent to which identifiability assumptions were satisfied. Although most studies addressed issues of unmeasured confounders either from empirical approaches or sensitivity analyses, the majority did not examine the potential bias arising from the measurement error of the mediator. Some studies allowed for exposure-mediator interaction and only a few presented results from models both with and without interactions. Power calculations were scarce. Reporting of causal mediation analysis is varied and suboptimal. Given that the application of causal mediation analysis will likely continue to increase, developing standards of reporting of causal mediation analysis in epidemiological research would be prudent.
Mediating mechanisms of a military Web-based alcohol intervention.

PubMed

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

2009-03-01

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

PubMed

Yamasaki, Syudo; Ando, Shuntaro; Koike, Shinsuke; Usami, Satoshi; Endo, Kaori; French, Paul; Sasaki, Tsukasa; Furukawa, Toshi A; Hasegawa-Hiraiwa, Mariko; Kasai, Kiyoto; Nishida, Atsushi

2016-06-01

Peer victimization increases the risk of experiencing psychotic symptoms among clinical and general populations, but the mechanism underlying this association remains unclear. Dissociation, which is related to peer victimization and hallucinatory experiences, has been demonstrated as a significant mediator in the relation between childhood victimization and hallucinatory experience among adult patients with psychosis. However, no studies have examined the mediating effect of dissociation in a general early adolescent population. We examined whether dissociation mediates the relationship between peer victimization and hallucinatory experiences among 10-year-old adolescents using a population-based cross-sectional survey of early adolescents and their main parent (Tokyo Early Adolescence Survey; N = 4478). We examined the mediating effect of dissociation, as well as external locus of control and depressive symptoms, on the relationship between peer victimization and hallucinatory experiences using path analysis. The model assuming mediation effects indicated good model fit (comparative fit index = .999; root mean square error of approximation = .015). The mediation effect between peer victimization and hallucination via dissociation (standardized indirect effect = .038, p < .001) was statistically significant, whereas the mediation effects of depressive symptoms (standardized indirect effect = -.0066, p = 0.318) and external locus of control (standardized indirect effect = .0024, p = 0.321) were not significant. These results suggest that dissociation is a mediator in the relation between peer victimization and hallucinatory experiences in early adolescence. For appropriate intervention strategies, assessing dissociation and peer victimization as they affect hallucinatory experiences is necessary.
Going Beyond the Norm: The Case for Incorporating Evaluative Mediation into Department of Defense Employment Discrimination Complaints

DTIC Science & Technology

2017-03-01

Incorporating Evaluative Mediation into Department of Defense Employment Discrimination Complaints By Thomas A...to resolve the dispute and does not evaluate the actual merits of a complaint. This can be problematic when an employee has filed a workplace...complaint based on illegal discrimination with the Equal Opportunity Office. Evaluative mediation involves having a mediator with expertise in labor and
Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.

PubMed

Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko

2017-07-17

Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.
Teen Dating Violence, Sexual Harassment, and Bullying Among Middle School Students: Examining Mediation and Moderated Mediation by Gender.

PubMed

Cutbush, Stacey; Williams, Jason; Miller, Shari

2016-11-01

This longitudinal study tested whether sexual harassment perpetration mediates the relationship between bullying perpetration and teen dating violence (TDV) perpetration and tested moderated mediation by assessing whether the developmental pathway varies by gender among middle school-aged youth. Although TDV has been associated with bullying and sexual harassment, the developmental relationship among all three behaviors has rarely been examined, especially by gender. The data were collected from one cohort of seventh grade middle school students (N = 612) from four schools. Students were surveyed every 6 months during seventh and eighth grades for a total of four waves of data collection. Structural equation modeling (SEM) was conducted to address the study aims, consisting of three stages: measurement models, mediation, and moderated mediation (otherwise known as Contrast of Mediated Effects). Results indicate no evidence of mediation. However, in the overall model, bullying and sexual harassment both emerged as significant predictors of TDV at a later time point. Among girls, only bullying significantly predicted TDV at a later time point, and, among boys, only sexual harassment significantly predicted TDV at a later time point. Prevention programs that target bullying and sexual harassment perpetration may reduce later perpetration of TDV. Further research is needed to disentangle the temporal relationships between these aggressive behaviors among youth.
Interventions to Reduce College Student Drinking: State of the Evidence for Mechanisms of Behavior Change

PubMed Central

Reid, Allecia E.; Carey, Kate B.

2015-01-01

Interventions to reduce college student drinking, although efficacious, generally yield only small effects on behavior change. Examining mechanisms of change may help to improve the magnitude of intervention effects by identifying effective and ineffective active ingredients. Informed by guidelines for establishing mechanisms of change, we conducted a systematic review of alcohol interventions for college students to identify (a) which constructs have been examined and received support as mediators, (b) circumstances that enhance the likelihood of detecting mediation, and (c) the extent of evidence for mechanisms of change. We identified 61 trials that examined 22 potential mediators of intervention efficacy. Descriptive norms consistently mediated normative feedback interventions. Motivation to change consistently failed to mediate motivational interviewing interventions. Multiple active ingredient interventions were not substantially more likely to find evidence of mediation than single ingredient interventions. Delivering intervention content remotely reduced likelihood of finding support for mediation. With the exception of descriptive norms, there is inadequate evidence for the psychosocial constructs purported as mechanisms of change in the college drinking literature. Evidence for mechanisms will be yielded by future studies that map all active ingredients to targeted psychosocial outcomes and that assess potential mediators early, inclusively, and at appropriate intervals following interventions. PMID:26164065
Relationship between Anxiety and Burnout among Chinese Physicians: A Moderated Mediation Model

PubMed Central

Zhou, Jiawei; Yang, Yanjie; Qiu, Xiaohui; Yang, Xiuxian; Pan, Hui; Ban, Bo; Qiao, Zhengxue; Wang, Lin; Wang, Wenbo

2016-01-01

Objective The main goal of this research was to investigate the complex relationships among coping styles, personality, burnout, and anxiety using a moderated mediation analysis. Methods A random cluster sampling procedure was used to select a total of 1274 physicians from two tertiary grade A hospitals in Heilongjiang Province, which is located in northeast China. The Zung Self-Rating Anxiety Scale (SAS), Chinese Maslach Burnout Inventory (CMBI), Chinese version of the EPQ-revised Short Scale, and the Trait Coping Style Questionnaire (TCSQ) were used to gather data. Moderated mediation analysis was used in this study; it was executed using the PROCESS macro so that the mediators and moderator could function together in the same model. Results The prevalence of anxiety symptoms among the physicians was 31%, and there were no differences between the sexes. The results showed that positive and negative coping styles partially mediated the association between burnout and anxiety symptoms in physicians. The mediated effect of positive coping styles was moderated by Eysenck’s Psychoticism traits. Conclusions Personality traits moderate the strength of the relationships between burnout and anxiety mediated by positive coping styles; however, personality traits do not moderate the strength of the relationships between burnout and anxiety mediated by negative coping styles. PMID:27479002

How do Housing Subsidies Improve Quality of Life Among Homeless Adults? A Mediation Analysis.

PubMed

O'Connell, Maria; Sint, Kyaw; Rosenheck, Robert

2018-03-01

Supported housing, combining rent subsidies with intensive case management, is associated with improvements in quality of life of homeless adults, but factors mediating their impact on quality of life have not been studied. Twelve-month outcome data from a randomized trial of the Housing and Urban Development- Veterans Affairs Supported Housing program (HUD-VASH) showed that access to a housing rent subsidy plus intensive case management (ICM) was associated with greater improvement in subjective quality of life than ICM alone. Multiple mediation analyses were applied to identify variables that significantly mediated the relationship between receipt of housing voucher and improvements in quality of life. Significant mediating covariates were those whose 95% bias-corrected confidence intervals, when added to the model predicting improvement in quality of life, did not overlap zero. Increases in the number of days housed, size of social network, and availability of emotional support appear to mediate improvement in quality of life and account for 71% of the benefit attributable to having a rent subsidy. Improvement in subjective quality of life though housing subsidies is mediated by gains in both material and psychosocial factors. Mediating factors deserve special attention in supported housing services. © Society for Community Research and Action 2018.
Roles of OA1 octopamine receptor and Dop1 dopamine receptor in mediating appetitive and aversive reinforcement revealed by RNAi studies

PubMed Central

Awata, Hiroko; Wakuda, Ryo; Ishimaru, Yoshiyasu; Matsuoka, Yuji; Terao, Kanta; Katata, Satomi; Matsumoto, Yukihisa; Hamanaka, Yoshitaka; Noji, Sumihare; Mito, Taro; Mizunami, Makoto

2016-01-01

Revealing reinforcing mechanisms in associative learning is important for elucidation of brain mechanisms of behavior. In mammals, dopamine neurons are thought to mediate both appetitive and aversive reinforcement signals. Studies using transgenic fruit-flies suggested that dopamine neurons mediate both appetitive and aversive reinforcements, through the Dop1 dopamine receptor, but our studies using octopamine and dopamine receptor antagonists and using Dop1 knockout crickets suggested that octopamine neurons mediate appetitive reinforcement and dopamine neurons mediate aversive reinforcement in associative learning in crickets. To fully resolve this issue, we examined the effects of silencing of expression of genes that code the OA1 octopamine receptor and Dop1 and Dop2 dopamine receptors by RNAi in crickets. OA1-silenced crickets exhibited impairment in appetitive learning with water but not in aversive learning with sodium chloride solution, while Dop1-silenced crickets exhibited impairment in aversive learning but not in appetitive learning. Dop2-silenced crickets showed normal scores in both appetitive learning and aversive learning. The results indicate that octopamine neurons mediate appetitive reinforcement via OA1 and that dopamine neurons mediate aversive reinforcement via Dop1 in crickets, providing decisive evidence that neurotransmitters and receptors that mediate appetitive reinforcement indeed differ among different species of insects. PMID:27412401
SPSS and SAS programming for the testing of mediation models.

PubMed

Dudley, William N; Benuzillo, Jose G; Carrico, Mineh S

2004-01-01

Mediation modeling can explain the nature of the relation among three or more variables. In addition, it can be used to show how a variable mediates the relation between levels of intervention and outcome. The Sobel test, developed in 1990, provides a statistical method for determining the influence of a mediator on an intervention or outcome. Although interactive Web-based and stand-alone methods exist for computing the Sobel test, SPSS and SAS programs that automatically run the required regression analyses and computations increase the accessibility of mediation modeling to nursing researchers. To illustrate the utility of the Sobel test and to make this programming available to the Nursing Research audience in both SAS and SPSS. The history, logic, and technical aspects of mediation testing are introduced. The syntax files sobel.sps and sobel.sas, created to automate the computation of the regression analysis and test statistic, are available from the corresponding author. The reported programming allows the user to complete mediation testing with the user's own data in a single-step fashion. A technical manual included with the programming provides instruction on program use and interpretation of the output. Mediation modeling is a useful tool for describing the relation between three or more variables. Programming and manuals for using this model are made available.
Cross-sectional evidence for a stress-negative affect pathway to substance use among sexual minority girls.

PubMed

Marshal, Michael P; Burton, Chad M; Chisolm, Deena J; Sucato, Gina S; Friedman, Mark S

2013-08-01

Sexual minority girls (SMGs) are four times more likely to engage in substance use than are heterosexual girls. A better understanding of the explanatory mechanisms of this disparity is needed to inform prevention and intervention programs. The goal of this study was to conduct a preliminary test of a "stress-negative affect" pathway by examining gay-related victimization and depression as mediators of substance use among SMGs. Adolescent girls (N = 156, 41% SMGs) were recruited from two urban adolescent medicine clinics to participate in an NIH-funded study of adolescent substance use. The average age was 17.0 years old and 57% were nonwhite. Mediation analyses were conducted in a multiple regression framework using SPSS and a mediation macro utilizing bias-corrected bootstrapping. Four models were estimated to test mediated pathways from sexual orientation to gay-related victimization (Mediator 1), to depression symptoms (Mediator 2), and then to each of four substance use variables: cigarettes, marijuana, alcohol, and heavy alcohol use. Significant mediated pathways (mediation tests with 95% CIs) were found for cigarette, alcohol and heavy alcohol use outcome variables. Results provide preliminary support for the minority stress hypothesis and the stress-negative affect pathway, and may inform the development of future prevention and intervention programs. © 2013 Wiley Periodicals, Inc.
Roles of OA1 octopamine receptor and Dop1 dopamine receptor in mediating appetitive and aversive reinforcement revealed by RNAi studies.

PubMed

Awata, Hiroko; Wakuda, Ryo; Ishimaru, Yoshiyasu; Matsuoka, Yuji; Terao, Kanta; Katata, Satomi; Matsumoto, Yukihisa; Hamanaka, Yoshitaka; Noji, Sumihare; Mito, Taro; Mizunami, Makoto

2016-07-14

Revealing reinforcing mechanisms in associative learning is important for elucidation of brain mechanisms of behavior. In mammals, dopamine neurons are thought to mediate both appetitive and aversive reinforcement signals. Studies using transgenic fruit-flies suggested that dopamine neurons mediate both appetitive and aversive reinforcements, through the Dop1 dopamine receptor, but our studies using octopamine and dopamine receptor antagonists and using Dop1 knockout crickets suggested that octopamine neurons mediate appetitive reinforcement and dopamine neurons mediate aversive reinforcement in associative learning in crickets. To fully resolve this issue, we examined the effects of silencing of expression of genes that code the OA1 octopamine receptor and Dop1 and Dop2 dopamine receptors by RNAi in crickets. OA1-silenced crickets exhibited impairment in appetitive learning with water but not in aversive learning with sodium chloride solution, while Dop1-silenced crickets exhibited impairment in aversive learning but not in appetitive learning. Dop2-silenced crickets showed normal scores in both appetitive learning and aversive learning. The results indicate that octopamine neurons mediate appetitive reinforcement via OA1 and that dopamine neurons mediate aversive reinforcement via Dop1 in crickets, providing decisive evidence that neurotransmitters and receptors that mediate appetitive reinforcement indeed differ among different species of insects.
Use of one- and two-mediator systems for developing a BOD biosensor based on the yeast Debaryomyces hansenii.

PubMed

Zaitseva, A S; Arlyapov, V A; Yudina, N Yu; Alferov, S V; Reshetilov, A N

2017-03-01

We investigated the use of one- and two-mediator systems in amperometric BOD biosensors (BOD, biochemical oxygen demand) based on the yeast Debaryomyces hansenii. Screening of nine mediators potentially capable of electron transfer - ferrocene, 1,1'-dimethylferrocene, ferrocenecarboxaldehyde, ferroceneacetonitrile, neutral red, 2,6-dichlorophenolindophenol, thionine, methylene blue and potassium ferricyanide - showed only ferrocene and neutral red to be efficient electron carriers for the eukaryotes studied. Two-mediator systems based on combinations of the investigated compounds were used to increase the efficiency of electron transfer. The developed two-mediator biosensors exceeded their one-mediator analogs by their characteristics. The most preferable two-mediator system for developing a BOD biosensor was a ferrocene-methylene blue combination that ensured a satisfactory long-time stability (43 days), selectivity, sensitivity (the lower limit of the determined BOD 5 concentrations, 2.5mg О 2 /dm 3 ) and speed (assay time for one sample, not greater than 10min) of BOD determination. Analysis of water samples showed that the use of a ferrocene-methylene blue two-mediator system and the yeast D. hansenii enabled registration of data that highly correlated with the results of the standard method (R=0.9913). Copyright © 2017 Elsevier Inc. All rights reserved.
Fungal mediator tail subunits contain classical transcriptional activation domains.

PubMed

Liu, Zhongle; Myers, Lawrence C

2015-04-01

Classical activation domains within DNA-bound eukaryotic transcription factors make weak interactions with coactivator complexes, such as Mediator, to stimulate transcription. How these interactions stimulate transcription, however, is unknown. The activation of reporter genes by artificial fusion of Mediator subunits to DNA binding domains that bind to their promoters has been cited as evidence that the primary role of activators is simply to recruit Mediator. We have identified potent classical transcriptional activation domains in the C termini of several tail module subunits of Saccharomyces cerevisiae, Candida albicans, and Candida dubliniensis Mediator, while their N-terminal domains are necessary and sufficient for their incorporation into Mediator but do not possess the ability to activate transcription when fused to a DNA binding domain. This suggests that Mediator fusion proteins actually are functioning in a manner similar to that of a classical DNA-bound activator rather than just recruiting Mediator. Our finding that deletion of the activation domains of S. cerevisiae Med2 and Med3, as well as C. dubliniensis Tlo1 (a Med2 ortholog), impairs the induction of certain genes shows these domains function at native promoters. Activation domains within coactivators are likely an important feature of these complexes and one that may have been uniquely leveraged by a common fungal pathogen. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
The Arabidopsis mediator complex subunits MED16, MED14, and MED2 regulate mediator and RNA polymerase II recruitment to CBF-responsive cold-regulated genes.

PubMed

Hemsley, Piers A; Hurst, Charlotte H; Kaliyadasa, Ewon; Lamb, Rebecca; Knight, Marc R; De Cothi, Elizabeth A; Steele, John F; Knight, Heather

2014-01-01

The Mediator16 (MED16; formerly termed SENSITIVE TO FREEZING6 [SFR6]) subunit of the plant Mediator transcriptional coactivator complex regulates cold-responsive gene expression in Arabidopsis thaliana, acting downstream of the C-repeat binding factor (CBF) transcription factors to recruit the core Mediator complex to cold-regulated genes. Here, we use loss-of-function mutants to show that RNA polymerase II recruitment to CBF-responsive cold-regulated genes requires MED16, MED2, and MED14 subunits. Transcription of genes known to be regulated via CBFs binding to the C-repeat motif/drought-responsive element promoter motif requires all three Mediator subunits, as does cold acclimation-induced freezing tolerance. In addition, these three subunits are required for low temperature-induced expression of some other, but not all, cold-responsive genes, including genes that are not known targets of CBFs. Genes inducible by darkness also required MED16 but required a different combination of Mediator subunits for their expression than the genes induced by cold. Together, our data illustrate that plants control transcription of specific genes through the action of subsets of Mediator subunits; the specific combination defined by the nature of the stimulus but also by the identity of the gene induced.
How Does MBCT for Depression Work? Studying Cognitive and Affective Mediation Pathways

PubMed Central

Batink, Tim; Peeters, Frenk; Geschwind, Nicole; van Os, Jim; Wichers, Marieke

2013-01-01

Mindfulness based cognitive therapy (MBCT) is a non-pharmacological intervention to reduce current symptoms and to prevent recurrence of major depressive disorder. At present, it is not well understood which underlying mechanisms during MBCT are associated with its efficacy. The current study (n = 130) was designed to examine the roles of mindfulness skills, rumination, worry and affect, and the interplay between those factors, in the mechanisms of change in MBCT for residual depressive symptoms. An exploratory but systematic approach was chosen using Sobel-Goodman mediation analyses to identify mediators on the pathway from MBCT to reduction in depressive symptoms. We replicated earlier findings that therapeutic effects of MBCT are mediated by changes in mindfulness skills and worry. Second, results showed that changes in momentary positive and negative affect significantly mediated the efficacy of MBCT, and also mediated the effect of worry on depressive symptoms. Third, within the group of patients with a prior history of ≤ 2 episodes of MDD, predominantly changes in cognitive and to a lesser extent affective processes mediated the effect of MBCT. However, within the group of patients with a prior history of ≥ 3 episodes of MDD, only changes in affect were significant mediators for the effect of MBCT. Trail Registration: Nederlands Trial Register NTR1084 PMID:24009704
Measurement error, time lag, unmeasured confounding: Considerations for longitudinal estimation of the effect of a mediator in randomised clinical trials

PubMed Central

Goldsmith, KA; Chalder, T; White, PD; Sharpe, M; Pickles, A

2016-01-01

Clinical trials are expensive and time-consuming and so should also be used to study how treatments work, allowing for the evaluation of theoretical treatment models and refinement and improvement of treatments. These treatment processes can be studied using mediation analysis. Randomised treatment makes some of the assumptions of mediation models plausible, but the mediator–outcome relationship could remain subject to bias. In addition, mediation is assumed to be a temporally ordered longitudinal process, but estimation in most mediation studies to date has been cross-sectional and unable to explore this assumption. This study used longitudinal structural equation modelling of mediator and outcome measurements from the PACE trial of rehabilitative treatments for chronic fatigue syndrome (ISRCTN 54285094) to address these issues. In particular, autoregressive and simplex models were used to study measurement error in the mediator, different time lags in the mediator–outcome relationship, unmeasured confounding of the mediator and outcome, and the assumption of a constant mediator–outcome relationship over time. Results showed that allowing for measurement error and unmeasured confounding were important. Contemporaneous rather than lagged mediator–outcome effects were more consistent with the data, possibly due to the wide spacing of measurements. Assuming a constant mediator–outcome relationship over time increased precision. PMID:27647810
Selective identification of specialized pro-resolving lipid mediators from their biosynthetic double di-oxygenation isomers.

PubMed

Hansen, Trond V; Dalli, Jesmond; Serhan, Charles N

The n-3 polyunsaturated fatty acids are substrates for lipoxygenases and cyclooxygenases. During inflammatory processes, these enzymes form several distinct families of oxygenated polyunsaturated fatty acids coined specialized pro-resolving lipid mediators. Structural elucidation of these natural products using LC-MS/MS based metabololipidomics with the pico- to nanogram amounts of biosynthetic material available have been performed. The specialized pro-resolving lipid mediators display stereospecific and potent anti-inflammatory and pro-resolving actions. Most often the different families among these mediators are chemically characterized by two or three chiral, secondary alcohols, separated by either an E,E,Z -triene or an E,Z,E,E -tetraenemoiety. The lipoxygenases also form other oxygenated polyunsaturated natural products, coined double di-oxygenation products, that are constitutional isomers of the protectin and maresin families of specialized pro-resolving lipid mediators. Very often these products exhibit similar chromatographic properties and mass spectrometrical fragment ions as the pro-resolving mediators. In addition, the double di-oxygenation products are sometimes formed in larger amounts than the specialized pro-resolving lipid mediators. Thus, it is not always possible to distinguish between the specialized pro-resolving mediators and their double di-oxygenation isomers in biological systems, using LC/MS-based techniques. Herein, a convenient and easy-to-use protocol to meet this challenge is presented.
Identifying Sources of Clinical Conflict: A Tool for Practice and Training in Bioethics Mediation.

PubMed

Bergman, Edward J

2015-01-01

Bioethics mediators manage a wide range of clinical conflict emanating from diverse sources. Parties to clinical conflict are often not fully aware of, nor willing to express, the true nature and scope of their conflict. As such, a significant task of the bioethics mediator is to help define that conflict. The ability to assess and apply the tools necessary for an effective mediation process can be facilitated by each mediator's creation of a personal compendium of sources that generate clinical conflict, to provide an orientation for the successful management of complex dilemmatic cases. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.
Influence of employees' attachment styles on their life satisfaction as mediated by job satisfaction and burnout.

PubMed

Reizer, Abira

2015-01-01

The aim of this study was to obtain better insight into the associations between attachment styles and employees' life satisfaction. This was achieved by examining the mediating roles of burnout and job satisfaction. Three hundred and thirty-nine employees, from a convenience community sample, participated in the current study. Results of the mediation model indicated that the associations between avoidance and life satisfaction were mediated by burnout and job satisfaction. However, the associations between attachment anxiety and life satisfaction were mediated by burnout but not by job satisfaction. Theoretical and practical implications for organizations and for attachment theory at work are discussed.
[Evaluation of nasal inflammation].

PubMed

De La Torre Morín, F; Sánchez Machín, I

2006-01-01

In the reaction of immediate hypersensibility to alergene is joined to its specific type IgE antibody, also united to the high affinity receptors for IgE (FccI) of the effecters cells fundamentally mastocites and basophiles. The interbreeding of these molecules Fcc to RI, after the union ofpolyvalent antigenes to IgE, active these cells, producing three biologic responses: excitosis of the preformed content of its granules, synthesization of lipidic mediators and citoquine secretion. The inflammation mediators are in last term, substances responsible of the clinic symptomatology. They can be divided generally in preformed mediators (biogene amines and macromolecules of the granules) and of new synthese mediators (lipidic and citoquine mediators).
The mediating role of interpersonal cognition on the relationships between personality and adolescent ego development.

PubMed

Liu, Yih-Lan

2013-01-01

The author investigated whether interpersonal cognition mediated the relationships between defense, social sensitivity, and ego development. Participants (N = 616; M age = 15.66 years, SD = .52 year; 276 boys) from northwestern Taiwan completed a battery of questionnaires. Structural equation modeling and mediation analyses supported the hypothesis that interpersonal cognition would mediate the path between defense and ego development, and the path between social sensitivity and ego development. Defense and social sensitivity were found to have direct effects on ego development. The study provides evidence of the mediating effect of interpersonal cognition on the association between personality and ego development.
Mood as a mediator of the link between child sexual abuse and psychosis.

PubMed

Marwaha, S; Bebbington, P

2015-04-01

The significance of affective changes in psychosis is increasingly acknowledged, as is the role of early traumatic events. In a previous paper, using data from the English Adult Psychiatric Morbidity Survey 2007 (APMS2007), strong associations between child sexual abuse (CSA) and psychosis were demonstrated, with some evidence of mediation by affect. In the current paper, we subjected the same dataset to formal tests of mediation. For CSA involving sexual intercourse, 38.5% of the link was mediated, 30.0% by depression and 8.5% by anxiety. For all forms of contact abuse, 38.2% was mediated, 29.1% by depression and 9.1% by anxiety.
Charge transfer mediator based systems for electrocatalytic oxygen reduction

DOEpatents

Stahl, Shannon S.; Gerken, James B.; Anson, Colin W.

2017-11-07

Disclosed are systems for the electrocatalytic reduction of oxygen, having redox mediator/redox catalyst pairs and an electrolyte solution in contact with an electrode. The redox mediator is included in the electrolyte solution, and the redox catalyst may be included in the electrolyte solution, or alternatively, may be in contact with the electrolyte solution. In one form a cobalt redox catalyst is used with a quinone redox mediator. In another form a nitrogen oxide redox catalyst is used with a nitroxyl type redox mediator. The systems can be used in electrochemical cells wherein neither the anode nor the cathode comprise an expensive metal such as platinum.
Charge transfer mediator based systems for electrocatalytic oxygen reduction

DOEpatents

Stahl, Shannon S.; Gerken, James B.; Anson, Colin W.

2017-07-18

Disclosed are systems for the electrocatalytic reduction of oxygen, having redox mediator/redox catalyst pairs and an electrolyte solution in contact with an electrode. The redox mediator is included in the electrolyte solution, and the redox catalyst may be included in the electrolyte solution, or alternatively, may be in contact with the electrolyte solution. In one form a cobalt redox catalyst is used with a quinone redox mediator. In another form a nitrogen oxide redox catalyst is used with a nitroxyl type redox mediator. The systems can be used in electrochemical cells wherein neither the anode nor the cathode comprise an expensive metal such as platinum.
Extraction of nonlinear waveform in turbulent plasma

NASA Astrophysics Data System (ADS)

Kin, F.; Itoh, K.; Fujisawa, A.; Kosuga, Y.; Sasaki, M.; Yamada, T.; Inagaki, S.; Itoh, S.-I.; Kobayashi, T.; Nagashima, Y.; Kasuya, N.; Arakawa, H.; Yamasaki, K.; Hasamada, K.

2018-06-01

Streamers and their mediator have been known to exist in linear cylindrical plasmas [Yamada et al., Nat. Phys. 4, 721 (2008)]. Conditional averaging is applied to extract the nonlinear characteristics of a mediator, which has been simply treated as a linear wave. This paper reports that a mediator should have higher harmonic components generated by self-couplings, and the envelope of a streamer should be generated with not only fundamental but also higher harmonic components of the mediator. Moreover, both the mediator and the envelope of the streamer have common features with solitary waves, i.e., the height should increase inversely as the square of their localization width.
Leadership and change commitment in the life insurance service context in Taiwan: the mediating-moderating role of job satisfaction.

PubMed

Yang, Yi-Feng

2011-06-01

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

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