Sample records for additional mediation analyses

  1. 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.

  2. 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.

  3. 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.

  4. Self-Esteem as a Mediator between Personality Traits and Body Esteem: Path Analyses across Gender and Race/Ethnicity

    PubMed Central

    Skorek, Małgorzata; Song, Anna V.; Dunham, Yarrow

    2014-01-01

    Prior literature examines the direct relationship between personality traits and body esteem. This article explores the possibility that self-esteem mediates this relationship. 165 undergraduate women and 133 men (age 18–21; 42.6% Hispanic, 28.9% Asian, 28.5% Caucasian) completed items measuring personality traits (Big Five), self-esteem, and body esteem. Path analyses were used to test for mediation. The analyses confirmed that in both men and women self-esteem mediated the relationship between three personality traits and body esteem: higher levels of conscientiousness, emotional stability, and extraversion were associated with higher self-esteem and consequently higher body esteem. Once self-esteem was included in the model the relationships between personality traits and body esteem were not significant, suggesting full mediation. In addition, the analyses revealed several racial/ethnic differences. In Asian American participants, self-esteem mediated the relationship between conscientiousness and body esteem and between emotional stability and body esteem. In Hispanic Americans, self-esteem mediated the relationship between conscientiousness and body esteem and between extraversion and body esteem. And in Caucasian Americans, self-esteem mediated the relationship between emotional stability and body esteem and between extraversion and body esteem. The most important contribution of this study is evidence for an indirect relationship between personality traits and body esteem, with this relationship being mediated by self-esteem. This has important implications for the study of personality and eating disorders in young adults, most particularly implying a need for more emphasis on self-esteem as a predictor of body image problems. PMID:25375238

  5. 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.

  6. Mediational Analyses of the Effects of Responsive Teaching on the Developmental Functioning of Preschool Children with Disabilities

    ERIC Educational Resources Information Center

    Karaaslan, Ozcan; Mahoney, Gerald

    2015-01-01

    Mediational analyses were conducted with data from two small randomized control trials of the Responsive Teaching (RT) parent-mediated developmental intervention which used nearly identical intervention and control procedures. The purpose of these analyses was to determine whether or how the changes in maternal responsiveness and children's…

  7. Genome-wide analyses of LINE–LINE-mediated nonallelic homologous recombination

    PubMed Central

    Startek, Michał; Szafranski, Przemyslaw; Gambin, Tomasz; Campbell, Ian M.; Hixson, Patricia; Shaw, Chad A.; Stankiewicz, Paweł; Gambin, Anna

    2015-01-01

    Nonallelic homologous recombination (NAHR), occurring between low-copy repeats (LCRs) >10 kb in size and sharing >97% DNA sequence identity, is responsible for the majority of recurrent genomic rearrangements in the human genome. Recent studies have shown that transposable elements (TEs) can also mediate recurrent deletions and translocations, indicating the features of substrates that mediate NAHR may be significantly less stringent than previously believed. Using >4 kb length and >95% sequence identity criteria, we analyzed of the genome-wide distribution of long interspersed element (LINE) retrotransposon and their potential to mediate NAHR. We identified 17 005 directly oriented LINE pairs located <10 Mbp from each other as potential NAHR substrates, placing 82.8% of the human genome at risk of LINE–LINE-mediated instability. Cross-referencing these regions with CNVs in the Baylor College of Medicine clinical chromosomal microarray database of 36 285 patients, we identified 516 CNVs potentially mediated by LINEs. Using long-range PCR of five different genomic regions in a total of 44 patients, we confirmed that the CNV breakpoints in each patient map within the LINE elements. To additionally assess the scale of LINE–LINE/NAHR phenomenon in the human genome, we tested DNA samples from six healthy individuals on a custom aCGH microarray targeting LINE elements predicted to mediate CNVs and identified 25 LINE–LINE rearrangements. Our data indicate that LINE–LINE-mediated NAHR is widespread and under-recognized, and is an important mechanism of structural rearrangement contributing to human genomic variability. PMID:25613453

  8. 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

  9. Electrochemical analyses of redox-active iron minerals: a review of nonmediated and mediated approaches.

    PubMed

    Sander, Michael; Hofstetter, Thomas B; Gorski, Christopher A

    2015-05-19

    Redox-active minerals are ubiquitous in the environment and are involved in numerous electron transfer reactions that significantly affect biogeochemical processes and cycles as well as pollutant dynamics. As a consequence, research in different scientific disciplines is devoted to elucidating the redox properties and reactivities of minerals. This review focuses on the characterization of mineral redox properties using electrochemical approaches from an applied (bio)geochemical and environmental analytical chemistry perspective. Establishing redox equilibria between the minerals and working electrodes is a major challenge in electrochemical measurements, which we discuss in an overview of traditional electrochemical techniques. These issues can be overcome with mediated electrochemical analyses in which dissolved redox mediators are used to increase the rate of electron transfer and to facilitate redox equilibration between working electrodes and minerals in both amperometric and potentiometric measurements. Using experimental data on an iron-bearing clay mineral, we illustrate how mediated electrochemical analyses can be employed to derive important thermodynamic and kinetic data on electron transfer to and from structural iron. We summarize anticipated methodological advancements that will further contribute to advance an improved understanding of electron transfer to and from minerals in environmentally relevant redox processes.

  10. Improving phylogenetic analyses by incorporating additional information from genetic sequence databases.

    PubMed

    Liang, Li-Jung; Weiss, Robert E; Redelings, Benjamin; Suchard, Marc A

    2009-10-01

    Statistical analyses of phylogenetic data culminate in uncertain estimates of underlying model parameters. Lack of additional data hinders the ability to reduce this uncertainty, as the original phylogenetic dataset is often complete, containing the entire gene or genome information available for the given set of taxa. Informative priors in a Bayesian analysis can reduce posterior uncertainty; however, publicly available phylogenetic software specifies vague priors for model parameters by default. We build objective and informative priors using hierarchical random effect models that combine additional datasets whose parameters are not of direct interest but are similar to the analysis of interest. We propose principled statistical methods that permit more precise parameter estimates in phylogenetic analyses by creating informative priors for parameters of interest. Using additional sequence datasets from our lab or public databases, we construct a fully Bayesian semiparametric hierarchical model to combine datasets. A dynamic iteratively reweighted Markov chain Monte Carlo algorithm conveniently recycles posterior samples from the individual analyses. We demonstrate the value of our approach by examining the insertion-deletion (indel) process in the enolase gene across the Tree of Life using the phylogenetic software BALI-PHY; we incorporate prior information about indels from 82 curated alignments downloaded from the BAliBASE database.

  11. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

    PubMed

    Day, Felix R; Ruth, Katherine S; Thompson, Deborah J; Lunetta, Kathryn L; Pervjakova, Natalia; Chasman, Daniel I; Stolk, Lisette; Finucane, Hilary K; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D; Elks, Cathy E; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A; Franke, Lude L; Huffman, Jennifer E; Keller, Margaux F; McArdle, Patrick F; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M; Schick, Ursula M; Smith, Jennifer A; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Arndt, Volker; Arnold, Alice M; Barbieri, Caterina; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J; Chapman, J Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J; Coviello, Andrea D; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eicher, John D; Fasching, Peter A; Faul, Jessica D; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E; García-Closas, Montserrat; Giles, Graham G; Girotto, Giorgia G; Goldberg, Mark S; González-Neira, Anna; Goodarzi, Mark O; Grove, Megan L; Gudbjartsson, Daniel F; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A; Hall, Per; Hamann, Ute; Henderson, Brian E; Hocking, Lynne J; Hofman, Albert; Homuth, Georg; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Huang, Jinyan; Humphreys, Keith; Hunter, David J; Jakubowska, Anna; Jones, Samuel E; Kabisch, Maria; Karasik, David; Knight, Julia A; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian'an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B; Nordestgaard, Børge G; Olson, Janet E; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D P; Pirastu, Nicola N; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F; Sanna, Serena; Sawyer, Elinor J; Schlessinger, David; Schmidt, Marjanka K; Schmidt, Frank; Schmutzler, Rita K; Schoemaker, Minouk J; Scott, Robert A; Seynaeve, Caroline M; Simard, Jacques; Sorice, Rossella; Southey, Melissa C; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D; Thorsteinsdottir, Unnur; Toland, Amanda E; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F; Winqvist, Robert; Wolffenbuttel, Bruce B H R; Wright, Alan F; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I; Buring, Julie E; Ferrucci, Luigi; Montgomery, Grant W; Gudnason, Vilmundur; Spector, Tim D; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F; Gasparini, Paolo P; Gieger, Christian; Harris, Tamara B; Hayward, Caroline; Kardia, Sharon L R; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C; Reiner, Alex P; Ridker, Paul M; Rotter, Jerome I; Toniolo, Daniela; Uitterlinden, André G; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J; Weir, David R; Yerges-Armstrong, Laura M; Price, Alkes L; Stefansson, Kari; Visser, Jenny A; Ong, Ken K; Chang-Claude, Jenny; Murabito, Joanne M; Perry, John R B; Murray, Anna

    2015-11-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

  12. Large-scale genomic analyses link reproductive ageing to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

    PubMed Central

    Lunetta, Kathryn L.; Pervjakova, Natalia; Chasman, Daniel I.; Stolk, Lisette; Finucane, Hilary K.; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D.; Elks, Cathy E.; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A.; Franke, Lude L.; Huffman, Jennifer E.; Keller, Margaux F.; McArdle, Patrick F.; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M.; Schick, Ursula M.; Smith, Jennifer A.; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V.; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arndt, Volker; Arnold, Alice M.; Barbieri, Caterina; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J.; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J.; Chapman, J. Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J.; Coviello, Andrea D.; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dörk, Thilo; dos-Santos-Silva, Isabel; Dunning, Alison M.; Eicher, John D.; Fasching, Peter A.; Faul, Jessica D.; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E.; García-Closas, Montserrat; Giles, Graham G.; Girotto, Giorgia G.; Goldberg, Mark S.; González-Neira, Anna; Goodarzi, Mark O.; Grove, Megan L.; Gudbjartsson, Daniel F.; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Henderson, Brian E.; Hocking, Lynne J.; Hofman, Albert; Homuth, Georg; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Huang, Jinyan; Humphreys, Keith; Hunter, David J.; Jakubowska, Anna; Jones, Samuel E.; Kabisch, Maria; Karasik, David; Knight, Julia A.; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian’an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G.; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M.; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B.; Nordestgaard, Børge G.; Olson, Janet E.; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D.P.; Pirastu, Nicola N.; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M.; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J.; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F.; Sanna, Serena; Sawyer, Elinor J.; Schlessinger, David; Schmidt, Marjanka K.; Schmidt, Frank; Schmutzler, Rita K.; Schoemaker, Minouk J.; Scott, Robert A.; Seynaeve, Caroline M.; Simard, Jacques; Sorice, Rossella; Southey, Melissa C.; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D.; Thorsteinsdottir, Unnur; Toland, Amanda E.; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T.; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F.; Winqvist, Robert; Wolffenbuttel, Bruce B.H.R.; Wright, Alan F.; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I.; Buring, Julie E.; Ferrucci, Luigi; Montgomery, Grant W.; Gudnason, Vilmundur; Spector, Tim D.; van Duijn, Cornelia M; Alizadeh, Behrooz Z.; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F.; Gasparini, Paolo P.; Gieger, Christian; Harris, Tamara B.; Hayward, Caroline; Kardia, Sharon L.R.; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C.; Reiner, Alex P.; Ridker, Paul M.; Rotter, Jerome I.; Toniolo, Daniela; Uitterlinden, André G.; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J.; Weir, David R.; Yerges-Armstrong, Laura M.; Price, Alkes L.; Stefansson, Kari; Visser, Jenny A.; Ong, Ken K.; Chang-Claude, Jenny; Murabito, Joanne M.; Perry, John R.B.; Murray, Anna

    2015-01-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ~70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two harbouring additional rare missense alleles of large effect. We found enrichment of signals in/near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses revealed a major association with DNA damage-response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomisation analyses supported a causal effect of later ANM on breast cancer risk (~6% risk increase per-year, P=3×10−14), likely mediated by prolonged sex hormone exposure, rather than DDR mechanisms. PMID:26414677

  13. Applied mediation analyses: a review and tutorial.

    PubMed

    Lange, Theis; Hansen, Kim Wadt; Sørensen, Rikke; Galatius, Søren

    2017-01-01

    In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation in the R package medflex. All results are illustrated using a recent study on the causal pathways stemming from the early invasive treatment of acute coronary syndrome, for which the rich Danish population registers allow us to follow patients' medication use and more after being discharged from hospital.

  14. How and for whom does web-based acceptance and commitment therapy work? Mediation and moderation analyses of web-based ACT for depressive symptoms.

    PubMed

    Pots, Wendy T M; Trompetter, Hester R; Schreurs, Karlein M G; Bohlmeijer, Ernst T

    2016-05-23

    Acceptance and Commitment Therapy (ACT) has been demonstrated to be effective in reducing depressive symptoms. However, little is known how and for whom therapeutic change occurs, specifically in web-based interventions. This study focuses on the mediators, moderators and predictors of change during a web-based ACT intervention. Data from 236 adults from the general population with mild to moderate depressive symptoms, randomized to either web-based ACT (n = 82) or one of two control conditions (web-based Expressive Writing (EW; n = 67) and a waiting list (n = 87)), were analysed. Single and multiple mediation analyses, and exploratory linear regression analyses were performed using PROCESS and linear regression analyses, to examine mediators, moderators and predictors on pre- to post- and follow-up treatment change of depressive symptoms. The treatment effect of ACT versus the waiting list was mediated by psychological flexibility and two mindfulness facets. The treatment effect of ACT versus EW was not significantly mediated. The moderator analyses demonstrated that the effects of web-based ACT did not vary according to baseline patient characteristics when compared to both control groups. However, higher baseline depressive symptoms and positive mental health and lower baseline anxiety were identified as predictors of outcome across all conditions. Similar results are found for follow-up. The findings of this study corroborate the evidence that psychological flexibility and mindfulness are distinct process mechanisms that mediate the effects of web-based ACT intervention. The results indicate that there are no restrictions to the allocation of web-based ACT intervention and that web-based ACT can work for different subpopulations. Netherlands Trial Register NTR2736 . Registered 6 February 2011.

  15. APOC3 Loss-of-Function Mutations, Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Cardiovascular Risk: Mediation- and Meta-Analyses of 137 895 Individuals.

    PubMed

    Wulff, Anders B; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2018-03-01

    Loss-of-function mutations in APOC3 associate with low remnant cholesterol levels and low risk of ischemic vascular disease (IVD). Because some studies show an additional association with low levels of low-density lipoprotein cholesterol (LDL-C), low LDL-C may explain the low risk of IVD in APOC3 loss-of-function heterozygotes. We tested to what extent the low risk of IVD in APOC3 loss-of-function heterozygotes is mediated by low plasma remnant cholesterol and LDL-C. In APOC3 loss-of-function heterozygotes versus noncarriers, we first determined remnant cholesterol and LDL-C levels in meta-analyses of 137 895 individuals. Second, we determined whether the association with LDL-C was masked by lipid-lowering therapy. Finally, using mediation analysis, we determined the fraction of the low risk of IVD and ischemic heart disease mediated by remnant cholesterol and LDL-C. In meta-analyses, remnant cholesterol was 43% lower (95% confidence interval, 40%-47%), and LDL-C was 4% lower (1%-6%) in loss-of-function heterozygotes (n=776) versus noncarriers. In the general population, LDL-C was 3% lower in loss-of-function heterozygotes versus noncarriers, 4% lower when correcting for lipid-lowering therapy, and 3% lower in untreated individuals ( P values, 0.06-0.008). Remnant cholesterol mediated 37% of the observed 41% lower risk of IVD and 54% of the observed 36% lower risk of ischemic heart disease; corresponding values mediated by LDL-C were 1% and 2%. The low risk of IVD observed in APOC3 loss-of-function heterozygotes is mainly mediated by the associated low remnant cholesterol and not by low LDL-C. Furthermore, the contribution of LDL-C to IVD risk was not masked by lipid-lowering therapy. This suggests APOC3 and remnant cholesterol as important new targets for reducing cardiovascular risk. © 2018 American Heart Association, Inc.

  16. 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…

  17. 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.

  18. Lessons learned from additional research analyses of unsolved clinical exome cases.

    PubMed

    Eldomery, Mohammad K; Coban-Akdemir, Zeynep; Harel, Tamar; Rosenfeld, Jill A; Gambin, Tomasz; Stray-Pedersen, Asbjørg; Küry, Sébastien; Mercier, Sandra; Lessel, Davor; Denecke, Jonas; Wiszniewski, Wojciech; Penney, Samantha; Liu, Pengfei; Bi, Weimin; Lalani, Seema R; Schaaf, Christian P; Wangler, Michael F; Bacino, Carlos A; Lewis, Richard Alan; Potocki, Lorraine; Graham, Brett H; Belmont, John W; Scaglia, Fernando; Orange, Jordan S; Jhangiani, Shalini N; Chiang, Theodore; Doddapaneni, Harsha; Hu, Jianhong; Muzny, Donna M; Xia, Fan; Beaudet, Arthur L; Boerwinkle, Eric; Eng, Christine M; Plon, Sharon E; Sutton, V Reid; Gibbs, Richard A; Posey, Jennifer E; Yang, Yaping; Lupski, James R

    2017-03-21

    Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery. We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease. Pilot project data included 74 families, consisting mostly of parent-offspring trios. Analyses performed on a research basis employed both WES from additional family members and complementary bioinformatics approaches and protocols. Analysis of all possible modes of Mendelian inheritance, focusing on both single nucleotide variants (SNV) and copy number variant (CNV) alleles, yielded a likely contributory variant in 36% (27/74) of cases. If one includes candidate genes with variants identified within a single family, a potential contributory variant was identified in a total of ~51% (38/74) of cases enrolled in this pilot study. The molecular diagnosis was achieved in 30/63 trios (47.6%). Besides this, the analysis workflow yielded evidence for pathogenic variants in disease-associated genes in 4/6 singleton cases (66.6%), 1/1 multiplex family involving three affected siblings, and 3/4 (75%) quartet families. Both the analytical pipeline and the collaborative efforts between the diagnostic and research laboratories provided insights that allowed recent disease gene discoveries (PURA, TANGO2, EMC1, GNB5, ATAD3A, and MIPEP) and increased the number of novel genes, defined in this study as genes identified in more than one family (DHX30 and EBF3). An efficient genomics pipeline in which

  19. Mediation analysis in nursing research: a methodological review.

    PubMed

    Liu, Jianghong; Ulrich, Connie

    2016-12-01

    Mediation statistical models help clarify the relationship between independent predictor variables and dependent outcomes of interest by assessing the impact of third variables. This type of statistical analysis is applicable for many clinical nursing research questions, yet its use within nursing remains low. Indeed, mediational analyses may help nurse researchers develop more effective and accurate prevention and treatment programs as well as help bridge the gap between scientific knowledge and clinical practice. In addition, this statistical approach allows nurse researchers to ask - and answer - more meaningful and nuanced questions that extend beyond merely determining whether an outcome occurs. Therefore, the goal of this paper is to provide a brief tutorial on the use of mediational analyses in clinical nursing research by briefly introducing the technique and, through selected empirical examples from the nursing literature, demonstrating its applicability in advancing nursing science.

  20. Redox mediators in visible light photocatalysis: photocatalytic radical thiol-ene additions.

    PubMed

    Tyson, Elizabeth L; Niemeyer, Zachary L; Yoon, Tehshik P

    2014-02-07

    Synthetically useful radical thiol-ene reactions can be initiated by visible light irradiation in the presence of transition metal polypyridyl photocatalysts. The success of this method relies upon the use of p-toluidine as an essential additive. Using these conditions, high-yielding thiol-ene reactions of cysteine-containing biomolecules can be accomplished using biocompatibile wavelengths of visible light, under aqueous conditions, and with the thiol component as the limiting reagent. We present evidence that p-toluidine serves as a redox mediator that is capable of catalyzing the otherwise inefficient photooxidation of thiols to the key thiyl radical intermediate. Thus, we show that co-catalytic oxidants can be important in the design of synthetic reactions involving visible light photoredox catalysis.

  1. 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

  2. Mediation analysis in nursing research: a methodological review

    PubMed Central

    Liu, Jianghong; Ulrich, Connie

    2017-01-01

    Mediation statistical models help clarify the relationship between independent predictor variables and dependent outcomes of interest by assessing the impact of third variables. This type of statistical analysis is applicable for many clinical nursing research questions, yet its use within nursing remains low. Indeed, mediational analyses may help nurse researchers develop more effective and accurate prevention and treatment programs as well as help bridge the gap between scientific knowledge and clinical practice. In addition, this statistical approach allows nurse researchers to ask – and answer – more meaningful and nuanced questions that extend beyond merely determining whether an outcome occurs. Therefore, the goal of this paper is to provide a brief tutorial on the use of mediational analyses in clinical nursing research by briefly introducing the technique and, through selected empirical examples from the nursing literature, demonstrating its applicability in advancing nursing science. PMID:26176804

  3. Childhood trauma and problem behavior: Examining the mediating roles of experiential avoidance and mindfulness processes.

    PubMed

    Roche, Anne I; Kroska, Emily B; Miller, Michelle L; Kroska, Sydney K; O'Hara, Michael W

    2018-03-22

    Childhood trauma is associated with a variety of risky, unhealthy, or problem behaviors. The current study aimed to explore experiential avoidance and mindfulness processes as mechanisms through which childhood trauma and problem behavior are linked in a college sample. The sample consisted of college-aged young adults recruited November-December, 2016 (N = 414). Participants completed self-report measures of childhood trauma, current problem behavior, experiential avoidance, and mindfulness processes. Bootstrapped mediation analyses examined the mechanistic associations of interest. Mediation analyses indicated that experiential avoidance was a significant mediator of the association between childhood trauma and problem behavior. Additionally, multiple mediation analyses indicated that specific mindfulness facets-act with awareness and nonjudgment of inner experience-significantly mediated the same association. Interventions for college students who have experienced childhood trauma might profitably target mechanisms such as avoidance and mindfulness in order to minimize engagement in problem behavior.

  4. 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

  5. Additional Measurements and Analyses of H217O and H218O

    NASA Astrophysics Data System (ADS)

    Pearson, John; Yu, Shanshan; Walters, Adam; Daly, Adam M.

    2015-06-01

    Historically the analysis of the spectrum of water has been a balance between the quality of the data set and the applicability of the Hamiltonian to a highly non-rigid molecule. Recently, a number of different non-rigid analysis approaches have successfully been applied to 16O water resulting in a self-consistent set of transitions and energy levels to high J which allowed the spectrum to be modeled to experimental precision. The data set for 17O and 18O water was previously reviewed and many of the problematic measurements identified, but Hamiltonian modeling of the remaining data resulted in significantly poorer quality fits than that for the 16O parent. As a result, we have made additional microwave measurements and modeled the existing 17O and 18O data sets with an Euler series model. This effort has illuminated a number of additional problematic measurements in the previous data sets and has resulted in analyses of 17O and 18O water that are of similar quality to the 16O analysis. We report the new lines, the analyses and make recommendations on the quality of the experimental data sets. SS. Yu, J.C. Pearson, B.J. Drouin et al. J. Mol. Spectrosc. 279,~16-25 (2012) J. Tennyson, P.F. Bernath, L.R. Brown et al. J. Quant. Spectrosc. Rad. Trans. 117, 29-58 (2013) J. Tennyson, P.F. Bernath, L.R. Brown et al. J. Quant. Spectrosc. Rad. Trans. 110, 573-596 (2009) H.M. Pickett, J.C. Pearson, C.E. Miller J. Mol. Spectrosc. 233, 174-179 (2005)

  6. 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.

  7. ADDITIONAL STRESS AND FRACTURE MECHANICS ANALYSES OF PRESSURIZED WATER REACTOR PRESSURE VESSEL NOZZLES

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

    Walter, Matthew; Yin, Shengjun; Stevens, Gary

    2012-01-01

    In past years, the authors have undertaken various studies of nozzles in both boiling water reactors (BWRs) and pressurized water reactors (PWRs) located in the reactor pressure vessel (RPV) adjacent to the core beltline region. Those studies described stress and fracture mechanics analyses performed to assess various RPV nozzle geometries, which were selected based on their proximity to the core beltline region, i.e., those nozzle configurations that are located close enough to the core region such that they may receive sufficient fluence prior to end-of-life (EOL) to require evaluation of embrittlement as part of the RPV analyses associated with pressure-temperaturemore » (P-T) limits. In this paper, additional stress and fracture analyses are summarized that were performed for additional PWR nozzles with the following objectives: To expand the population of PWR nozzle configurations evaluated, which was limited in the previous work to just two nozzles (one inlet and one outlet nozzle). To model and understand differences in stress results obtained for an internal pressure load case using a two-dimensional (2-D) axi-symmetric finite element model (FEM) vs. a three-dimensional (3-D) FEM for these PWR nozzles. In particular, the ovalization (stress concentration) effect of two intersecting cylinders, which is typical of RPV nozzle configurations, was investigated. To investigate the applicability of previously recommended linear elastic fracture mechanics (LEFM) hand solutions for calculating the Mode I stress intensity factor for a postulated nozzle corner crack for pressure loading for these PWR nozzles. These analyses were performed to further expand earlier work completed to support potential revision and refinement of Title 10 to the U.S. Code of Federal Regulations (CFR), Part 50, Appendix G, Fracture Toughness Requirements, and are intended to supplement similar evaluation of nozzles presented at the 2008, 2009, and 2011 Pressure Vessels and Piping (PVP

  8. Ligand functionalization as a deactivation pathway in a fac-Ir(ppy)3-mediated radical addition.

    PubMed

    Devery Iii, James J; Douglas, James J; Nguyen, John D; Cole, Kevin P; Flowers Ii, Robert A; Stephenson, Corey R J

    2015-01-01

    Knowledge of the kinetic behavior of catalysts under synthetically relevant conditions is vital for the efficient use of compounds that mediate important transformations regardless of their composition or driving force. In particular, these data are of great importance to add perspective to the growing number of applications of photoactive transition metal complexes. Here we present kinetic, synthetic, and spectroscopic evidence of the mechanistic behavior of fac -Ir(ppy) 3 in a visible light-mediated radical addition to 3-methylindole, demonstrating the instability of fac -Ir(ppy) 3 under these conditions. During the reaction, rapid in situ functionalization of the photocatalyst occurs, eventually leading to deactivation. These findings demonstrate a conceivable deactivation process for catalytic single electron reactions in the presence of radicophilic ligands. Attempts to inhibit photocatalyst deactivation through structural modification provide further insight into catalyst selection for a given system of interest.

  9. Production of cellobionate from cellulose using an engineered Neurospora crassa strain with laccase and redox mediator addition

    USDA-ARS?s Scientific Manuscript database

    We report a novel production process for cellobionic acid from cellulose using an engineered fungal strain with the exogenous addition of laccase and a redox mediator. A previously engineered strain of Neurospora crassa (F5'ace-1'cre-1'ndvB) was shown to produce cellobionate directly from cellulose ...

  10. 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…

  11. Binge eating & childhood emotional abuse: The mediating role of anger.

    PubMed

    Feinson, Marjorie C; Hornik-Lurie, Tzipi

    2016-10-01

    Recent studies reveal that childhood emotional abuse (CEA) is the trauma most clearly associated with adult eating pathology. Yet, relatively little is understood about psychological mechanisms linking these distal experiences. Anger's mediational role in the relationship between CEA and adult binge eating (BE) is explored in a community-based sample of 498 adult women (mean age 44). Detailed telephone interviews assess BE (7 items), CEA (single item), and unresolved anger (single item) along with self-criticism (modified Rosenberg self-esteem scale), depression and anxiety symptoms (BSI sub-scales). Statistical analyses include Pearson correlations, Baron and Kenny's steps for mediation, and Preacher and Hayes bootstrapping method to test proposed multiple mediators simultaneously. Findings reveal significantly more respondents (n = 476 with complete data) with serious BE behaviors report a history of CEA compared to women with considerable and/or minimal BE (53% vs 37%, p = 0.002 respectively). Significant correlations are found among all study variables. Mediation analyses focus on anger together with self-criticism, depression and anxiety. Findings reveal anger and self-criticism fully mediate the CEA-BE relationship. In contrast, depression and anxiety symptoms are not significant mediators in a model that includes anger and self-criticism. Although additional research is warranted to more fully understand complex causal processes, in the interim, treatment interventions should be broadened to include assessments of anger among adult women with BE behaviors, especially those with histories of childhood abuse. Additionally, prevention strategies that incorporate learning how to express anger directly and positively may be particularly effective in reducing various disordered eating behaviors among women and girls. Copyright © 2016. Published by Elsevier Ltd.

  12. Addition of glycosylation to influenza A virus hemagglutinin modulates antibody-mediated recognition of H1N1 2009 pandemic viruses.

    PubMed

    Job, Emma R; Deng, Yi-Mo; Barfod, Kenneth K; Tate, Michelle D; Caldwell, Natalie; Reddiex, Scott; Maurer-Stroh, Sebastian; Brooks, Andrew G; Reading, Patrick C

    2013-03-01

    Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the viral hemagglutinin (HA). Glycans on the head of HA promote virus survival by shielding antigenic sites, but highly glycosylated seasonal IAV are inactivated by soluble lectins of the innate immune system. In 2009, human strains of pandemic H1N1 [A(H1N1)pdm] expressed a single glycosylation site (Asn(104)) on the head of HA. Since then, variants with additional glycosylation sites have been detected, and the location of these sites has been distinct to those of recent seasonal H1N1 strains. We have compared wild-type and reverse-engineered A(H1N1)pdm IAV with differing potential glycosylation sites on HA for sensitivity to collectins and to neutralizing Abs. Addition of a glycan (Asn(136)) to A(H1N1)pdm HA was associated with resistance to neutralizing Abs but did not increase sensitivity to collectins. Moreover, variants expressing Asn(136) showed enhanced growth in A(H1N1)pdm-vaccinated mice, consistent with evasion of Ab-mediated immunity in vivo. Thus, a fine balance exists regarding the optimal pattern of HA glycosylation to facilitate evasion of Ab-mediated immunity while maintaining resistance to lectin-mediated defenses of the innate immune system.

  13. Indium-mediated asymmetric barbier-type allylations: additions to aldehydes and ketones and mechanistic investigation of the organoindium reagents.

    PubMed

    Haddad, Terra D; Hirayama, Lacie C; Singaram, Bakthan

    2010-02-05

    We report a simple, efficient, and general method for the indium-mediated enantioselective allylation of aromatic and aliphatic aldehydes and ketones under Barbier-type conditions in a one-pot synthesis affording the corresponding chiral alcohol products in very good yield (up to 99%) and enantiomeric excess (up to 93%). Our method is able to tolerate various functional groups, such as esters, nitriles, and phenols. Additionally, more substituted allyl bromides, such as crotyl and cinnamyl bromide, can be used providing moderate enantioselectivity (72% and 56%, respectively) and excellent diastereoselectivity when employing cinnamyl bromide (>95/5 anti/syn). However, the distereoselectivity when using crotyl bromide was poor and other functionalized allyl bromides under our method afforded low enantioselectivities for the alcohol products. In these types of indium-mediated additions, solvent plays a major role in determining the nature of the organoindium intermediate and we observed the susceptibility of some allylindium intermediates to hydrolysis in protic solvents. Under our reaction conditions using a polar aprotic solvent, we suggest that an allylindium(III) species is the active allylating intermediate. In addition, we have observed the presence of a shiny, indium(0) nugget throughout the reaction, irrespective of the stoichiometry, indicating disproportionation of indium halide byproduct formed during the reaction.

  14. Prototype Willingness Model Drinking Cognitions Mediate Personalized Normative Feedback Efficacy.

    PubMed

    Lewis, Melissa A; Litt, Dana M; Tomkins, Mary; Neighbors, Clayton

    2017-05-01

    Personalized normative feedback (PNF) interventions have been shown to be efficacious at reducing college student drinking. Because descriptive norms have been shown to mediate PNF efficacy, the current study focused on examining additional prototype willingness model social reaction cognitions, namely, prototypes and willingness, as mediators of intervention efficacy. We expected the PNF interventions to be associated with increased prototype favorability of students who do not drink, which would in turn be associated with decreased willingness to drink and subsequently, less drinking. The current study included 622 college students (53.2% women; 62% Caucasian) who reported one or more heavy drinking episodes in the past month and completed baseline and three-month follow-up assessments. As posited by the framework of the prototype willingness model, sequential mediation analyses were conducted to evaluate increases in abstainer prototype favorability on willingness on drinking, and subsequently willingness to drink on drinking behavior. Mediation results revealed significant indirect effects of PNF on three-month drinking through three-month prototypes and willingness, indicating that the social reaction pathway of the prototype willingness model was supported. Findings have important implications for PNF interventions aiming to reduce high-risk drinking among college students. Study findings suggest that we should consider looking at additional socially-based mediators of PNF efficacy in addition to perceived descriptive norms.

  15. Prototype Willingness Model Drinking Cognitions Mediate Personalized Normative Feedback Efficacy

    PubMed Central

    Litt, Dana M.; Tomkins, Mary; Neighbors, Clayton

    2017-01-01

    Personalized normative feedback (PNF) interventions have been shown to be efficacious at reducing college student drinking. Because descriptive norms have been shown to mediate PNF efficacy, the current study focused on examining additional prototype willingness model social reaction cognitions, namely, prototypes and willingness, as mediators of intervention efficacy. We expected the PNF interventions to be associated with increased prototype favorability of students who do not drink, which would in turn be associated with decreased willingness to drink and subsequently, less drinking. The current study included 622 college students (53.2% women; 62% Caucasian) who reported one or more heavy drinking episodes in the past month and completed baseline and three-month follow-up assessments. As posited by the framework of the prototype willingness model, sequential mediation analyses were conducted to evaluate increases in abstainer prototype favorability on willingness on drinking, and subsequently willingness to drink on drinking behavior. Mediation results revealed significant indirect effects of PNF on three-month drinking through three-month prototypes and willingness, indicating that the social reaction pathway of the prototype willingness model was supported. Findings have important implications for PNF interventions aiming to reduce high-risk drinking among college students. Study findings suggest that we should consider looking at additional socially-based mediators of PNF efficacy in addition to perceived descriptive norms. PMID:27995431

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. [Effects of nurses' perception of servant leadership on leader effectiveness, satisfaction and additional effort: focused on the mediating effects of leader trust and value congruence].

    PubMed

    Han, Sang Sook; Kim, Nam Eun

    2012-02-01

    This study was done to examine the effects of nurses' perception of servant leadership on leader effectiveness, satisfaction and promoting additional effort. The focus was the mediating effects of leader trust and value congruence. Data were collected from 361 RN-BSN students and nurses participating in nationally attended in-service training programs. Data were analyzed using descriptive statistics and structural analysis with SPSS 17.0 windows program and Amos 7.0. Direct effects of nurses' perception of servant leadership were negative, but mediating effects of trust and value congruency were positively correlated with leader effectiveness, satisfaction and additional effort, that is servant leadership should be effective through mediating factors. The study results indicate that if the middle managers of nurses can build leader trust and value congruency between nurses through servant leadership, leader effectiveness, satisfaction and additional effort on the part of the nurses could result in a positive change in the long term.

  1. 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.

  2. Effects of Food Additives on Immune Cells As Contributors to Body Weight Gain and Immune-Mediated Metabolic Dysregulation.

    PubMed

    Paula Neto, Heitor A; Ausina, Priscila; Gomez, Lilian S; Leandro, João G B; Zancan, Patricia; Sola-Penna, Mauro

    2017-01-01

    Food additives are compounds used in order to improve food palatability, texture, and shelf life. Despite a significant effort to assure safety of use, toxicological analysis of these substances, generally, rely on their direct toxicity to target organs (liver and kidney) or their genotoxic effects. Much less attention is paid to the effects of these compounds on cells of the immune system. This is of relevance given that metabolic dysregulation and obesity have a strong immune-mediated component. Obese individuals present a state of chronic low-grade inflammation that contributes to the establishment of insulin resistance and other metabolic abnormalities known as the metabolic syndrome. Obesity and metabolic syndrome are currently recognized as worldwide epidemics that pose a profound socioeconomic impact and represent a concern to public health. Cells of the immune system contribute to both the maintenance of "lean homeostasis" and the metabolic dysregulation observed in obese individuals. Although much attention has been drawn in the past decades to obesity and metabolic syndrome as a result of ingesting highly processed food containing large amounts of fat and simple sugars, mounting evidence suggest that food additives may also be important contributors to metabolic derangement. Herein, we review pieces of evidence from the literature showing that food additives have relevant effects on cells of the immune system that could contribute to immune-mediated metabolic dysregulation. Considering their potential to predispose individuals to develop obesity and metabolic syndrome, their use should be taken with caution or maybe revisited.

  3. Family functioning mediates adaptation in caregivers of individuals with Rett syndrome.

    PubMed

    Lamb, Amanda E; Biesecker, Barbara B; Umstead, Kendall L; Muratori, Michelle; Biesecker, Leslie G; Erby, Lori H

    2016-11-01

    The objective of this study was to investigate factors related to family functioning and adaptation in caregivers of individuals with Rett syndrome (RS). A cross-sectional quantitative survey explored the relationships between demographics, parental self-efficacy, coping methods, family functioning and adaptation. A forward-backward, step-wise model selection procedure was used to evaluate variables associated with both family functioning and adaptation. Analyses also explored family functioning as a mediator of the relationship between other variables and adaptation. Bivariate analyses (N=400) revealed that greater parental self-efficacy, a greater proportion of problem-focused coping, and a lesser proportion of emotion-focused coping were associated with more effective family functioning. In addition, these key variables were significantly associated with greater adaptation, as was family functioning, while controlling for confounders. Finally, regression analyses suggest family functioning as a mediator of the relationships between three variables (parental self-efficacy, problem-focused coping, and emotion-focused coping) with adaptation. This study demonstrates the potentially predictive roles of expectations and coping methods and the mediator role of family functioning in adaptation among caregivers of individuals with RS, a chronic developmental disorder. A potential target for intervention is strengthening of caregiver competence in the parenting role to enhance caregiver adaptation. Published by Elsevier Ireland Ltd.

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

    ERIC Educational Resources Information Center

    Li, Spencer D.

    2011-01-01

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

  5. Proteomic Analyses of Cellular Events Mediating/Inhibiting Chemical-Induced Injury

    DTIC Science & Technology

    2009-07-21

    cells in patients with sarcoidosis , an innammatory disease which is onen located in the lungs [27,28J. Cell signaling in the NRF-2 Mediated Oxidative...bronchoalveolar lavage cells in sarcoidosis . J Clin Invest 2007, 117:3576-3582. 28. Yang Y, Fujita J, Bandoh 5, Ohtsuki Y, Yamadori I, Yoshinouchi T

  6. Effects of Food Additives on Immune Cells As Contributors to Body Weight Gain and Immune-Mediated Metabolic Dysregulation

    PubMed Central

    Paula Neto, Heitor A.; Ausina, Priscila; Gomez, Lilian S.; Leandro, João G. B.; Zancan, Patricia; Sola-Penna, Mauro

    2017-01-01

    Food additives are compounds used in order to improve food palatability, texture, and shelf life. Despite a significant effort to assure safety of use, toxicological analysis of these substances, generally, rely on their direct toxicity to target organs (liver and kidney) or their genotoxic effects. Much less attention is paid to the effects of these compounds on cells of the immune system. This is of relevance given that metabolic dysregulation and obesity have a strong immune-mediated component. Obese individuals present a state of chronic low-grade inflammation that contributes to the establishment of insulin resistance and other metabolic abnormalities known as the metabolic syndrome. Obesity and metabolic syndrome are currently recognized as worldwide epidemics that pose a profound socioeconomic impact and represent a concern to public health. Cells of the immune system contribute to both the maintenance of “lean homeostasis” and the metabolic dysregulation observed in obese individuals. Although much attention has been drawn in the past decades to obesity and metabolic syndrome as a result of ingesting highly processed food containing large amounts of fat and simple sugars, mounting evidence suggest that food additives may also be important contributors to metabolic derangement. Herein, we review pieces of evidence from the literature showing that food additives have relevant effects on cells of the immune system that could contribute to immune-mediated metabolic dysregulation. Considering their potential to predispose individuals to develop obesity and metabolic syndrome, their use should be taken with caution or maybe revisited. PMID:29163542

  7. Perceived Interpersonal Burdensomeness as a Mediator between Nightmare Distress and Suicidal Ideation in Nightmare Sufferers

    PubMed Central

    Suh, Sooyeon; Schneider, Matthew; Lee, Ruda; Joiner, Thomas

    2016-01-01

    Previous studies have supported the significant association between nightmares and suicidal ideation, but the underlying mechanisms are largely unknown. The purpose of the present study was to investigate perceived burdensomeness and thwarted belongingness as mediators in the relationship between nightmare distress and suicidal ideation. This sample consisted of 301 undergraduate students who endorsed experiencing nightmares (mean age 21.87 ± 2.17, 78.1% female). All participants completed questionnaires on nightmare distress (Nightmare Distress Questionnaire), unmet interpersonal needs (Interpersonal Needs Questionnaire), and suicidal ideation (Depressive Symptom Inventory – Suicidality Subscale). Analyses were performed using multiple mediation regression. Results indicated that nightmare distress was associated with perceived burdensomeness (r = 0.17, p < 0.001) and suicidal ideation (r = 0.24, p < 0.001), but was not related to thwarted belongingness (r = 0.10, p = 0.06). Multiple mediation analyses revealed that perceived burdensomeness partially mediated the relationship between nightmares and suicidal ideation, but thwarted belongingness did not. Additionally, this mediating relationship for perceived burdensomeness was moderated by gender, being significant only for females. These findings highlight the important role of interpersonal factors in the relationship between nightmares and suicidal ideation. PMID:27917142

  8. Infant SES as a Predictor of Personality—Is the Association Mediated by Intelligence?

    PubMed Central

    Flensborg-Madsen, Trine; Mortensen, Erik Lykke

    2014-01-01

    Background Although research into the continuity and change of personality traits during a lifespan has been fairly extensive, little research has been conducted on childhood predictors of adult personality. Purpose We aimed to investigate the association between infant socioeconomic status (SES), and Eysenck personality traits in adulthood. An additional aim was to investigate whether intelligence and education may mediate this association. Methods SES of 9125 children in the Copenhagen Perinatal Cohort was recorded at a 1-year examination. A subsample of this cohort, comprising 1182 individuals, participated in a follow-up at 20–34 years and was administered the Eysenck Personality Questionnaire (EPQ) which includes measures of neuroticism, extraversion, psychoticism and the so-called lie-scale. Associations of SES with each of the four personality traits were analysed by bivariate and partial correlations, and the mediating effects of intelligence and years of education were analysed. Results Higher SES in infancy was associated with lower neuroticism (r = −0.06; p = 0.05), lower lie-scale scores (r = −0.11; p = 0.0002), and higher psychoticism (r = 0.09; p = 0.003). However, analyses of mediation revealed no direct effect of infant SES on any of the adult personality traits, but only indirect effects mediated by intelligence and years of education, with intelligence being the main mediating factor. Conclusion Only weak associations were observed between infant SES and personality in young adulthood, and the observed associations were mediated by adult intelligence and educational level. Thus, factors associated with infant SES or family background appears to have weak direct effects on personality development. PMID:25078408

  9. 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…

  10. Cytoskeletal dynamics in interphase, mitosis and cytokinesis analysed through Agrobacterium-mediated transient transformation of tobacco BY-2 cells.

    PubMed

    Buschmann, H; Green, P; Sambade, A; Doonan, J H; Lloyd, C W

    2011-04-01

    Transient transformation with Agrobacterium is a widespread tool allowing rapid expression analyses in plants. However, the available methods generate expression in interphase and do not allow the routine analysis of dividing cells. Here, we present a transient transformation method (termed 'TAMBY2') to enable cell biological studies in interphase and cell division. Agrobacterium-mediated transient gene expression in tobacco BY-2 was analysed by Western blotting and quantitative fluorescence microscopy. Time-lapse microscopy of cytoskeletal markers was employed to monitor cell division. Double-labelling in interphase and mitosis enabled localization studies. We found that the transient transformation efficiency was highest when BY-2/Agrobacterium co-cultivation was performed on solid medium. Transformants produced in this way divided at high frequency. We demonstrated the utility of the method by defining the behaviour of a previously uncharacterized microtubule motor, KinG, throughout the cell cycle. Our analyses demonstrated that TAMBY2 provides a flexible tool for the transient transformation of BY-2 with Agrobacterium. Fluorescence double-labelling showed that KinG localizes to microtubules and to F-actin. In interphase, KinG accumulates on microtubule lagging ends, suggesting a minus-end-directed function in vivo. Time-lapse studies of cell division showed that GFP-KinG strongly labels preprophase band and phragmoplast, but not the metaphase spindle. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.

  11. 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…

  12. 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.

  13. A unified model exploring parenting practices as mediators of marital conflict and children's adjustment.

    PubMed

    Coln, Kristen L; Jordan, Sara S; Mercer, Sterett H

    2013-06-01

    We examined positive and negative parenting practices and psychological control as mediators of the relations between constructive and destructive marital conflict and children's internalizing and externalizing problems in a unified model. Married mothers of 121 children between the ages of 6 and 12 completed questionnaires measuring marital conflict, parenting practices, and child adjustment. Analyses revealed significant direct paths from destructive marital conflict to negative parenting practices, psychological control, and both children's internalizing and externalizing behavior. In addition, psychological control was found to partially mediate relations between destructive marital conflict and children's internalizing and externalizing behavior.

  14. Examining the stress-burnout relationship: the mediating role of negative thoughts

    PubMed Central

    Chyi, Theresa; Hsu, Ya-Wen; Chan, Shi-Wei; Wang, Erica T.W.

    2017-01-01

    Background Using Smith’s (1986) cognitive-affective model of athletic burnout as a guiding framework, the purpose of this study was to examine the relationships among athletes’ stress in life, negative thoughts, and the mediating role of negative thoughts on the stress-burnout relationship. Methods A total of 300 college student-athletes (males = 174; females = 126, Mage = 20.43 y, SD = 1.68) completed the College Student Athlete’s Life Stress Scale (CSALSS; Lu et al., 2012), the Automatic Thoughts Questionnaire (ATQ; Hollon & Kendall, 1980), and the Athlete Burnout Questionnaire (ABQ; Raedeke & Smith, 2001). Results Correlational analyses found that two types of life stress and four types of negative thoughts correlated with burnout. Additionally, hierarchical regression analyses found that four types of negative thoughts partially mediated the stress-burnout relationship. Discussion We concluded that an athlete’s negative thoughts play a pivotal role in predicting athletes’ stress-burnout relationship. Future study may examine how irrational cognition influences athletes’ motivation and psychological well-being. PMID:29302397

  15. Examining the stress-burnout relationship: the mediating role of negative thoughts.

    PubMed

    Chang, Ko-Hsin; Lu, Frank J H; Chyi, Theresa; Hsu, Ya-Wen; Chan, Shi-Wei; Wang, Erica T W

    2017-01-01

    Using Smith's (1986) cognitive-affective model of athletic burnout as a guiding framework, the purpose of this study was to examine the relationships among athletes' stress in life, negative thoughts, and the mediating role of negative thoughts on the stress-burnout relationship. A total of 300 college student-athletes (males = 174; females = 126, M age  = 20.43 y, SD = 1.68) completed the College Student Athlete's Life Stress Scale (CSALSS; Lu et al., 2012), the Automatic Thoughts Questionnaire (ATQ; Hollon & Kendall, 1980), and the Athlete Burnout Questionnaire (ABQ; Raedeke & Smith, 2001). Correlational analyses found that two types of life stress and four types of negative thoughts correlated with burnout. Additionally, hierarchical regression analyses found that four types of negative thoughts partially mediated the stress-burnout relationship. We concluded that an athlete's negative thoughts play a pivotal role in predicting athletes' stress-burnout relationship. Future study may examine how irrational cognition influences athletes' motivation and psychological well-being.

  16. Theory of mind deficits partly mediate impaired social decision-making in schizophrenia.

    PubMed

    Yang, Liuqing; Li, Peifu; Mao, Haiying; Wang, Huiling; Shu, Chang; Bliksted, Vibeke; Zhou, Yuan

    2017-05-05

    Using paradigms from game theory, researchers have reported abnormal decision-making in social context in patients with schizophrenia. However, less is known about the underpinnings of the impairment. This study aimed to test whether theory of mind (ToM) deficits and/or neurocognitive dysfunctions mediate impaired social decision-making in patients with schizophrenia. We compared thirty-five patients with schizophrenia to thirty-eight matched healthy controls with regard to social decision-making using the mini Ultimatum Game (mini UG), a paradigm from game theory. Additionally, we assessed ToM using the Theory of Mind Picture Stories Task, a mental state attribution task, and assessed neurocognition using the Brief Assessment of Cognition in Schizophrenia. Mediation analyses were performed on the data. In contrast to the behavioral pattern of healthy controls in the mini UG, the patients with schizophrenia significantly accepted more disadvantageous offers and rejected more advantageous offers, and showed reduced sensitivity to the fairness-related context changes in the mini UG. Impaired ToM and neurocognition were also found in the patients. Mediation analyses indicated that ToM but not neurocognition partially mediated the group differences on the disadvantageous and advantageous offers in the mini UG. Patients with schizophrenia exhibited impaired social decision-making. This impairment can be partly explained by their ToM deficits rather than neurocognitive deficits. However, the exact nature of the ToM deficits that mediate impaired social decision-making needs to be identified in future.

  17. 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

  18. 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

  19. Design and synthesis of inositolphosphoglycan putative insulin mediators.

    PubMed

    López-Prados, Javier; Cuevas, Félix; Reichardt, Niels-Christian; de Paz, José-Luis; Morales, Ezequiel Q; Martín-Lomas, Manuel

    2005-03-07

    The binding modes of a series of molecules, containing the glucosamine (1-->6) myo-inositol structural motif, into the ATP binding site of the catalytic subunit of cAMP-dependent protein kinase (PKA) have been analysed using molecular docking. These calculations predict that the presence of a phosphate group at the non-reducing end in pseudodisaccharide and pseudotrisaccharide structures properly orientate the molecule into the binding site and that pseudotrisaccharide structures present the best shape complementarity. Therefore, pseudodisaccharides and pseudotrisaccharides have been synthesised from common intermediates using effective synthetic strategies. On the basis of this synthetic chemistry, the feasibility of constructing small pseudotrisaccharide libraries on solid-phase using the same intermediates has been explored. The results from the biological evaluation of these molecules provide additional support to an insulin-mediated signalling system which involves the intermediacy of inositolphosphoglycans as putative insulin mediators.

  20. Emotion dysregulation mediates the relationship between child maltreatment and psychopathology: A structural equation model.

    PubMed

    Jennissen, Simone; Holl, Julia; Mai, Hannah; Wolff, Sebastian; Barnow, Sven

    2016-12-01

    The present study investigated the mediating effects of emotion dysregulation on the relationship between child maltreatment and psychopathology. An adult sample (N=701) from diverse backgrounds of psychopathology completed the Childhood Trauma Questionnaire (CTQ), the Difficulties in Emotion Regulation Scale (DERS), the Brief Symptom Inventory (BSI), and the negative affect subscale of the Positive and Negative Affect Schedule (PANAS) in a cross-sectional online survey. Correlational analyses showed that all types of child maltreatment were uniformly associated with emotion dysregulation, and dimensions of emotion dysregulation were strongly related to psychopathology. Limited access to strategies for emotion regulation emerged as the most powerful predictor. Structural equation modeling analyses revealed that emotion dysregulation partially mediated the relationship between child maltreatment and psychopathology, even after controlling for shared variance with negative affect. These findings emphasize the importance of emotion dysregulation as a possible mediating mechanism in the association between child maltreatment and later psychopathology. Additionally, interventions targeting specific emotion regulation strategies may be effective to reduce psychopathology in victims of child maltreatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. ETHICAL LEADERSHIP AND EMPLOYEE VOICE: EMPLOYEE SELF-EFFICACY AND SELF-IMPACT AS MEDIATORS.

    PubMed

    Wang, Duanxu; Gan, Chenjing; Wu, Chaoyan; Wang, Danqi

    2015-06-01

    Previous studies have used social learning theory to explain the influence of ethical leadership. This study continues the previous research by using social learning theory to explain the mediating effect of self-efficacy on the relationship between ethical leadership and employee voice. In addition, this study extends previous studies by introducing expectancy theory to explore whether self-impact also mediates the relationship between ethical leadership and employee voice. Ethical leadership, self-efficacy, self-impact, and employee voice were assessed using paired surveys among 59 supervisors and 295 subordinates employed at nine firms in the People's Republic of China. Using HLM and SEM analyses, the results revealed that ethical leadership was positively related to employee voice and that this relationship was partially mediated by both self-efficacy and self-impact.

  2. 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.

  3. A Statistical Method for Synthesizing Mediation Analyses Using the Product of Coefficient Approach Across Multiple Trials

    PubMed Central

    Huang, Shi; MacKinnon, David P.; Perrino, Tatiana; Gallo, Carlos; Cruden, Gracelyn; Brown, C Hendricks

    2016-01-01

    Mediation analysis often requires larger sample sizes than main effect analysis to achieve the same statistical power. Combining results across similar trials may be the only practical option for increasing statistical power for mediation analysis in some situations. In this paper, we propose a method to estimate: 1) marginal means for mediation path a, the relation of the independent variable to the mediator; 2) marginal means for path b, the relation of the mediator to the outcome, across multiple trials; and 3) the between-trial level variance-covariance matrix based on a bivariate normal distribution. We present the statistical theory and an R computer program to combine regression coefficients from multiple trials to estimate a combined mediated effect and confidence interval under a random effects model. Values of coefficients a and b, along with their standard errors from each trial are the input for the method. This marginal likelihood based approach with Monte Carlo confidence intervals provides more accurate inference than the standard meta-analytic approach. We discuss computational issues, apply the method to two real-data examples and make recommendations for the use of the method in different settings. PMID:28239330

  4. Understanding and Using Mediators and Moderators

    ERIC Educational Resources Information Center

    Wu, Amery D.; Zumbo, Bruno D.

    2008-01-01

    Mediation and moderation are two theories for refining and understanding a causal relationship. Empirical investigation of mediators and moderators requires an integrated research design rather than the data analyses driven approach often seen in the literature. This paper described the conceptual foundation, research design, data analysis, as…

  5. Cultural Predictors of Physical and Mental Health Status among Mexican American Women: A Mediation Model

    PubMed Central

    Dinh, Khanh T.; Castro, Felipe González; Tein, Jenn-Yun; Kim, Su Yeong

    2016-01-01

    This study, using secondary data analysis, examined a mediation model of acculturation and ethnic pride as predictors of physical and mental health outcomes in a sample of 561 Mexican American women. Factors postulated as mediators were family support and religiosity. Systematic across-group comparison analyses were conducted to examine sources of differences in the mediation model between immigrant and non-immigrant women. The results partially supported the hypothesized mediation model, indicating that family support, but not religiosity, was a significant mediator in the relationship between ethnic pride and mental health problems. In addition, as differences between immigrant and non-immigrant women were observed only in the variables means, but not in the factor loadings or regression paths, the model tested may capture a common psychosocial process that affects these women and their health outcomes. Overall, this study offers important implications for future research and the design of intervention programs for Mexican American women. PMID:19130212

  6. Smokers' increased risk for disability pension: social confounding or health-mediated effects? Gender-specific analyses of the Hordaland Health Study cohort.

    PubMed

    Haukenes, Inger; Riise, Trond; Haug, Kjell; Farbu, Erlend; Maeland, John Gunnar

    2013-09-01

    Studies indicate that cigarette smokers have an increased risk for disability pension, presumably mediated by adverse health effects. However, smoking is also related to socioeconomic status. The current study examined the association between smoking and subsequent disability pension, and whether the association is explained by social confounding and/or health-related mediation. A subsample of 7934 men and 8488 women, aged 40-46, from the Hordaland Health Study, Norway (1997-1999), provided baseline information on smoking status, self-reported health measures and socioeconomic status. Outcome was register-based disability pension from 12 months after baseline to end of 2004. Gender stratified Cox regression analyses were used adjusted for socioeconomic status, physical activity, self-reported health and musculoskeletal pain sites. A total of 155 (2%) men and 333 (3.9%) women were granted disability pension during follow-up. The unadjusted disability risk associated with heavy smoking versus non-smoking was 1.88 (95% CI 1.23 to 2.89) among men and 3.06 (95% CI 2.23 to 4.20) among women. In multivariate analyses, adjusting for socioeconomic status, HRs were 1.33 (95% CI 0.84 to 2.11) among men and 2.22 (95% CI 1.58 to 3.13) among women. Final adjustment for physical activity, self-reported health and musculoskeletal pain further reduced the effect of heavy smoking in women (HR=1.53, 95% CI 1.09 to 2.16). Socioeconomic status confounded the smoking-related risk for disability pension; for female heavy smokers, however, a significant increased risk persisted after adjustment. Women may be particularly vulnerable to heavy smoking and to its sociomedical consequences, such as disability pension.

  7. Mediation analysis: a retrospective snapshot of practice and more recent directions.

    PubMed

    Gelfand, Lois A; Mensinger, Janell L; Tenhave, Thomas

    2009-04-01

    R. Baron and D. A. Kenny's (1986) paper introducing mediation analysis has been cited over 9,000 times, but concerns have been expressed about how this method is used. The authors review past and recent methodological literature and make recommendations for how to address 3 main issues: association, temporal order, and the no omitted variables assumption. The authors briefly visit the topics of reliability and the confirmatory-exploratory distinction. In addition, to provide a sense of the extent to which the earlier literature had been absorbed into practice, the authors examined a sample of 50 articles from 2002 citing R. Baron and D. A. Kenny and containing at least 1 mediation analysis via ordinary least squares regression. A substantial proportion of these articles included problematic reporting; as of 2002, there appeared to be room for improvement in conducting such mediation analyses. Future literature reviews will demonstrate the extent to which the situation has improved.

  8. 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.

  9. Grignard reagent/CuI/LiCl-mediated stereoselective cascade addition/cyclization of diynes: a novel pathway for the construction of 1-methyleneindene derivatives.

    PubMed

    Li, De-Yao; Wei, Yin; Shi, Min

    2013-11-11

    Diynes containing a cyclopropane group smoothly undergo a novel intramolecular and stereoselective cascade addition/cyclization reaction to produce the corresponding 1-methyleneindene derivatives in moderate to good yields. This interesting transformation is mediated by Grignard reagent/CuI with LiCl as an additive under mild conditions. The obtained product can easily be further functionalized through cyclopropyl ring opening. A plausible reaction mechanism has also been presented on the basis of deuterium labeling and control experiments. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Glycosaminoglycan-Mediated Downstream Signaling of CXCL8 Binding to Endothelial Cells

    PubMed Central

    Derler, Rupert; Weber, Corinna; Strutzmann, Elisabeth; Miller, Ingrid; Kungl, Andreas

    2017-01-01

    The recruitment of leukocytes, mediated by endothelium bound chemokine gradients, is a vital process in inflammation. The highly negatively charged, unbranched polysaccharide family of glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate mediate chemokine immobilization. Specifically the binding of CXCL8 (interleukin 8) to GAGs on endothelial cell surfaces is known to regulate neutrophil recruitment. Currently, it is not clear if binding of CXCL8 to GAGs leads to endothelial downstream signaling in addition to the typical CXCR1/CXCR2 (C-X-C motif chemokine receptor 1 and 2)-mediated signaling which activates neutrophils. Here we have investigated the changes in protein expression of human microvascular endothelial cells induced by CXCL8. Tumor necrosis factor alpha (TNFα) stimulation was used to mimic an inflammatory state which allowed us to identify syndecan-4 (SDC4) as the potential proteoglycan co-receptor of CXCL8 by gene array, real-time PCR and flow cytometry experiments. Enzymatic GAG depolymerization via heparinase III and chondroitinase ABC was used to emulate the effect of glycocalyx remodeling on CXCL8-induced endothelial downstream signaling. Proteomic analyses showed changes in the expression pattern of a number of endothelial proteins such as Zyxin and Caldesmon involved in cytoskeletal organization, cell adhesion and cell mobility. These results demonstrate for the first time a potential role of GAG-mediated endothelial downstream signaling in addition to the well-known CXCL8-CXCR1/CXCR2 signaling pathways in neutrophils. PMID:29207576

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

    PubMed Central

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

    2017-01-01

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

  12. Mother–Adolescent Conflict as a Mediator Between Adolescent Problem Behaviors and Maternal Psychological Control

    PubMed Central

    Steeger, Christine M.; Gondoli, Dawn M.

    2014-01-01

    This study examined mother–adolescent conflict as a mediator of longitudinal reciprocal relations between adolescent aggression and depressive symptoms and maternal psychological control. Motivated by family systems theory and the transactions that occur between individual and dyadic levels of the family system, we examined the connections among these variables during a developmental period when children and parents experience significant psychosocial changes. Three years of self-report data were collected from 168 mother–adolescent dyads, beginning when the adolescents (55.4% girls) were in 6th grade. Models were tested using longitudinal path analysis. Results indicated that the connection between adolescent aggression (and depressive symptoms) and maternal psychological control was best characterized as adolescent-driven, indirect, and mediated by mother–adolescent conflict; there were no indications of parent-driven indirect effects. That is, prior adolescent aggression and depressive symptoms were associated with increased conflict. In turn, conflict was associated with increased psychological control. Within our mediation models, reciprocal direct effects between both problem behaviors and conflict and between conflict and psychological control were also found. Additionally, exploratory analyses regarding the role of adolescent gender as a moderator of variable relations were conducted. These analyses revealed no gender-related patterns of moderation, whether moderated mediation or specific path tests for moderation were considered. This study corroborates prior research finding support for child effects on parenting behaviors during early adolescence. PMID:22612432

  13. The effects of mediator and granular activated carbon addition on degradation of trace organic contaminants by an enzymatic membrane reactor.

    PubMed

    Nguyen, Luong N; Hai, Faisal I; Price, William E; Leusch, Frederic D L; Roddick, Felicity; Ngo, Hao H; Guo, Wenshan; Magram, Saleh F; Nghiem, Long D

    2014-09-01

    The removal of four recalcitrant trace organic contaminants (TrOCs), namely carbamazepine, diclofenac, sulfamethoxazole and atrazine by laccase in an enzymatic membrane reactor (EMR) was studied. Laccases are not effective for degrading non-phenolic compounds; nevertheless, 22-55% removal of these four TrOCs was achieved by the laccase EMR. Addition of the redox-mediator syringaldehyde (SA) to the EMR resulted in a notable dose-dependent improvement (15-45%) of TrOC removal affected by inherent TrOC properties and loading rates. However, SA addition resulted in a concomitant increase in the toxicity of the treated effluent. A further 14-25% improvement in aqueous phase removal of the TrOCs was consistently observed following a one-off dosing of 3g/L granular activated carbon (GAC). Mass balance analysis reveals that this improvement was not due solely to adsorption but also enhanced biodegradation. GAC addition also reduced membrane fouling and the SA-induced toxicity of the effluent. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Interpersonal and intrapersonal factors as parallel independent mediators in the association between internalized HIV stigma and ART adherence

    PubMed Central

    Seghatol-Eslami, Victoria C.; Dark, Heather; Raper, James L.; Mugavero, Michael J.; Turan, Janet M.; Turan, Bulent

    2016-01-01

    Introduction People living with HIV (PLWH) need to adhere to antiretroviral therapy (ART) to achieve optimal health. One reason for ART non-adherence is HIV-related stigma. Objectives We aimed to examine whether HIV treatment self-efficacy (an intrapersonal mechanism) mediates the stigma – adherence association. We also examined whether self-efficacy and the concern about being seen while taking HIV medication (an interpersonal mechanism) are parallel mediators independent of each other. Methods 180 PLWH self-reported internalized HIV stigma, ART adherence, HIV treatment self-efficacy, and concerns about being seen while taking HIV medication. We calculated bias-corrected 95% confidence intervals (CIs) for indirect effects using bootstrapping to conduct mediation analyses. Results Adherence self-efficacy mediated the relationship between internalized stigma and ART adherence. Additionally, self-efficacy and concern about being seen while taking HIV medication uniquely mediated and explained almost all of the stigma – adherence association in independent paths (parallel mediation). Conclusion These results can inform intervention strategies to promote ART adherence. PMID:27926668

  15. Negative Body Attitudes and Sexual Dissatisfaction in Men: The Mediating Role of Body Self-Consciousness During Physical Intimacy.

    PubMed

    van den Brink, Femke; Vollmann, Manja; Sternheim, Lot C; Berkhout, Lotte J; Zomerdijk, Renée A; Woertman, Liesbeth

    2018-04-01

    Previous research indicated that negative attitudes about the body and appearance are common among men and demonstrated that negative body attitudes are associated with negative sexual experiences. The present study investigated the association between body attitudes and sexual dissatisfaction and the mediating role of body self-consciousness during physical intimacy. In a cross-sectional design, 201 Dutch men completed an online survey regarding body attitudes toward muscularity, body fat, height, and genitals, body self-consciousness during physical intimacy, and sexual dissatisfaction. Hypotheses were tested using correlation analyses and a mediation analysis with body attitudes as predictors, body self-consciousness as mediator, and sexual dissatisfaction as outcome. Correlation analyses showed that negative body attitudes and body self-consciousness during physical intimacy were significantly related to sexual dissatisfaction. The mediation analysis revealed that negative attitudes toward muscularity, body fat, and genitals had indirect effects on sexual dissatisfaction through body self-consciousness during physical intimacy. Negative attitudes toward genitals additionally had a direct effect on sexual dissatisfaction. These findings indicate that body image interventions focused on male body attitudes may be beneficial in improving men's body image, which may ultimately increase sexual satisfaction.

  16. Rainbow: A Framework for Analysing Computer-Mediated Pedagogical Debates

    ERIC Educational Resources Information Center

    Baker, Michael; Andriessen, Jerry; Lund, Kristine; van Amelsvoort, Marie; Quignard, Matthieu

    2007-01-01

    In this paper we present a framework for analysing when and how students engage in a specific form of interactive knowledge elaboration in CSCL environments: broadening and deepening understanding of a space of debate. The framework is termed "Rainbow," as it comprises seven principal analytical categories, to each of which a colour is assigned,…

  17. The interplay between customer participation and difficulty of design examples in the online designing process and its effect on customer satisfaction: mediational analyses.

    PubMed

    Chang, Chia-Chi; Chen, Hui-Yun; Huang, I-Chiang

    2009-04-01

    In the current consumer-centric economy, consumers increasingly desire the opportunity to design their own products in order to express more effectively their self-image. Mass customization, based on efficient and flexible modulization designs, has provided individualized products to satisfy this desire. This work presents an experiment employed to demonstrate that customer participation leads to higher satisfaction. Specifically, the increment in customer satisfaction due to participation is greater when an easy example is provided than when either no example or a difficult one is provided. Additionally, self-congruity plays a mediating role on the customer participation-satisfaction relationship, and this mediating effect varies across different levels of the design example provided in the design process. When an easy design example is present, customer participation has a direct effect on satisfaction, in addition to the indirect effect of self-congruity. When a difficult example is provided, customer participation does not have incremental effects on either self-congruity or customer satisfaction. Finally, when no design example is shown to customers, contrary to our expectation, participation still enhances customer satisfaction due to an increased sense of self-congruity.

  18. Psychological Vulnerability and Problem Gambling: The Mediational Role of Cognitive Distortions.

    PubMed

    Lévesque, David; Sévigny, Serge; Giroux, Isabelle; Jacques, Christian

    2018-01-03

    Despite numerous studies demonstrating the influence of cognitive distortions on gambling problem severity, empirical data regarding the role of psychological vulnerability on the latter is limited. Hence, this study assesses the mediating effect of cognitive distortions between psychological vulnerability (personality and mood), and gambling problem severity. It also verifies whether the relationships between these variables differs according to the preferred gambling activity. The sample is composed of 272 male gamblers [191 poker players; 81 video lottery terminal (VLT) players] aged between 18 and 82 years (M = 35.2). Bootstrap analysis results revealed that cognitive distortions mediate the effect of narcissism on gambling problem severity for both groups. The level of depression for VLT players significantly predicted gambling problem severity, both directly and indirectly via the mediating effect of cognitive distortions. Mediation analyses also indicated that narcissism had an indirect impact on problem gambling through cognitive distortions for both groups. These findings suggest that certain vulnerabilities related to personality and mood may influence cognitive distortion intensity and gambling problem severity. In addition, psychological vulnerabilities could differ based on preferred gambling activity. These results may be useful for prevention policies, identifying high risk gamblers and planning psychological interventions.

  19. Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes.

    PubMed

    Carvallo, Loreto; Lopez, Lillie; Che, Fa-Yun; Lim, Jihyeon; Eugenin, Eliseo A; Williams, Dionna W; Nieves, Edward; Calderon, Tina M; Madrid-Aliste, Carlos; Fiser, Andras; Weiss, Louis; Angeletti, Ruth Hogue; Berman, Joan W

    2015-04-01

    Despite successful combined antiretroviral therapy, ∼ 60% of HIV-infected people exhibit HIV-associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV-infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9 were identified and had not been shown previously to be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction. Copyright © 2015 by The American Association of Immunologists, Inc.

  20. Hopelessness Mediates the Relation between Insomnia and Suicidal Ideation

    PubMed Central

    Woosley, Julie A.; Lichstein, Kenneth L.; Taylor, Daniel J.; Riedel, Brant W.; Bush, Andrew J.

    2014-01-01

    Introduction: A growing body of literature indicates that insomnia is related to suicidality. However, the mechanism through which insomnia correlates with suicide risk is unclear. The goal of the present research was to determine whether hopelessness, a robust predictor of suicidality, mediates the relation between insomnia and suicidal ideation (SI). Methods: The present study used archival data from community-dwelling adults. Participants (n = 766) completed a Health Survey, two weeks of daily sleep diaries, and five measures of daytime functioning, including the Beck Depression Inventory (BDI). BDI item 2 was used to assess hopelessness, and BDI item 9 was used to assess SI. Criteria from the DSM-5 as well as quantitative criteria were used to identify participants with insomnia (n = 135). Results: The analyses revealed that hopelessness is a significant mediator of the relation between insomnia and SI. After adding depression as an additional mediator, hopelessness remained a significant predictor of SI. Conclusion: The present research suggests the need for clinicians to routinely screen clients who have insomnia for hopelessness and SI, and to treat hopelessness when it is present. Further research should address the limitations in this sample and should also consider other potential mediators of the insomnia-SI link. Citation: Woosley JA, Lichstein KL, Taylor DJ, Riedel BW, Bush AJ. Hopelessness mediates the relation between insomnia and suicidal ideation. J Clin Sleep Med 2014;10(11):1223-1230. PMID:25325598

  1. Integrated genomic analyses identify WEE1 as a critical mediator of cell fate and novel therapeutic target in acute myeloid leukemia

    PubMed Central

    Porter, Christopher C.; Kim, Jihye; Fosmire, Susan; Gearheart, Christy M.; van Linden, Annemie; Baturin, Dmitry; Zaberezhnyy, Vadym; Patel, Purvi R.; Gao, Dexiang; Tan, Aik Choon; DeGregori, James

    2011-01-01

    Acute myeloid leukemia (AML) remains a therapeutic challenge despite increasing knowledge about the molecular origins of the disease, as the mechanisms of AML cell escape from chemotherapy remain poorly defined. We hypothesized that AML cells are addicted to molecular pathways in the context of chemotherapy and used complementary approaches to identify these addictions. Using novel molecular and computational approaches, we performed genome-wide shRNA screens to identify proteins that mediate AML cell fate after cytarabine exposure, gene expression profiling of AML cells exposed to cytarabine to identify genes with induced expression in this context, and examination of existing gene expression data from primary patient samples. The integration of these independent analyses strongly implicates cell cycle checkpoint proteins, particularly WEE1, as critical mediators of AML cell survival after cytarabine exposure. Knockdown of WEE1 in a secondary screen confirmed its role in AML cell survival. Pharmacologic inhibition of WEE1 in AML cell lines and primary cells is synergistic with cytarabine. Further experiments demonstrate that inhibition of WEE1 prevents S-phase arrest induced by cytarabine, broadening the functions of WEE1 that may be exploited therapeutically. These data highlight the power of integrating functional and descriptive genomics, and identify WEE1 as potential therapeutic target in AML. PMID:22289989

  2. 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

  3. Asymmetric Michael Addition Mediated by Chiral Ionic Liquids.

    PubMed

    Suzuki, Yumiko

    2018-06-01

    Chiral ionic liquids with a focus on their applications in asymmetric Michael additions and related reactions were reviewed. The examples were classified on the basis of the mode of asymmetric induction (e.g., external induction/non-covalent interaction or internal induction/covalent bond formation), the roles in reactions (as a solvent or catalyst), and their structural features (e.g., imidazolium-based chiral cations, other chiral oniums; proline derivatives). Most of the reactions with high chiral induction are Michael addition of ketones or aldehydes to chalcones or nitrostyrenes where proline-derived chiral ionic liquids catalyze the reaction through enamine/ iminium formation. Many reports demonstrate the recyclability of ionic liquid-tagged pyrrolidines.

  4. Phosphoproteomics analyses show subnetwork systems in T-cell receptor signaling.

    PubMed

    Hatano, Atsushi; Matsumoto, Masaki; Nakayama, Keiichi I

    2016-10-01

    A key issue in the study of signal transduction is how multiple signaling pathways are systematically integrated into the cell. We have now performed multiple phosphoproteomics analyses focused on the dynamics of the T-cell receptor (TCR) signaling network and its subsystem mediated by the Ca 2+ signaling pathway. Integration of these phosphoproteomics data sets and extraction of components of the TCR signaling network dependent on Ca 2+ signaling showed unexpected phosphorylation kinetics for candidate substrates of the Ca 2+ -dependent phosphatase calcineurin (CN) during TCR stimulation. Detailed characterization of the TCR-induced phosphorylation of a novel CN substrate, Itpkb, showed that phosphorylation of this protein is regulated by both CN and the mitogen-activated protein kinase Erk in a competitive manner. Phosphorylation of additional CN substrates was also found to be regulated by Erk and CN in a similar manner. The combination of multiple phosphoproteomics approaches thus showed two major subsystems mediated by Erk and CN in the TCR signaling network, with these subsystems regulating the phosphorylation of a group of proteins in a competitive manner. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  5. Changes in depression mediate the effects of AA attendance on alcohol use outcomes.

    PubMed

    Wilcox, Claire E; Tonigan, J Scott

    2018-01-01

    Depression may contribute to increased drinking in individuals with alcohol use disorder. Although Alcoholics Anonymous (AA) attendance predicts drinking reductions, there is conflicting information regarding the intermediary role played by reductions in depression. We explored whether AA attendance reduces depressive symptoms, the degree to which improvement in depression results in reductions in drinking, and in which subgroups these effects occur. 253 early AA affiliates (63% male) were recruited and assessed at baseline 3, 6, 9, 12, 18, and 24 months. Depression was measured using the Beck Depression Inventory (BDI) and was administered at baseline 3, 6, 12, 18, and 24 months. AA attendance and alcohol use outcomes were obtained with the Form 90. Mediation analyses were performed at early (3, 6, and 9 months) and late (12, 18, and 24 months) follow-up to investigate the degree to which reductions in depression mediated the effect of AA attendance on drinking, controlling for concurrent drinking. In addition, a series of moderated mediation analyses were performed using baseline depression severity as a moderator. At early follow-up, reductions in depression (6 months) mediated the effects of AA attendance (3 months) on later drinking (drinks per drinking day) (9 months) (b = -0.02, boot CI [-0.055, -0.0004]), controlling for drinking at 6 months. Baseline depression severity did not moderate the degree to which BDI mediated the effects of AA attendance on alcohol use (ps > .05). These findings provide further evidence that depression reduction is a mechanism by which AA attendance leads to reductions in alcohol use. Improving depression may help reduce alcohol use in individuals with AUD, and AA attendance may be an effective way to achieve that goal.

  6. Asymmetric Michael Addition Mediated by Chiral Ionic Liquids

    PubMed Central

    Suzuki, Yumiko

    2018-01-01

    Chiral ionic liquids with a focus on their applications in asymmetric Michael additions and related reactions were reviewed. The examples were classified on the basis of the mode of asymmetric induction (e.g., external induction/non-covalent interaction or internal induction/covalent bond formation), the roles in reactions (as a solvent or catalyst), and their structural features (e.g., imidazolium-based chiral cations, other chiral oniums; proline derivatives). Most of the reactions with high chiral induction are Michael addition of ketones or aldehydes to chalcones or nitrostyrenes where proline-derived chiral ionic liquids catalyze the reaction through enamine/ iminium formation. Many reports demonstrate the recyclability of ionic liquid-tagged pyrrolidines. PMID:29861702

  7. 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.

  8. Mother-adolescent conflict as a mediator between adolescent problem behaviors and maternal psychological control.

    PubMed

    Steeger, Christine M; Gondoli, Dawn M

    2013-04-01

    This study examined mother-adolescent conflict as a mediator of longitudinal reciprocal relations between adolescent aggression and depressive symptoms and maternal psychological control. Motivated by family systems theory and the transactions that occur between individual and dyadic levels of the family system, we examined the connections among these variables during a developmental period when children and parents experience significant psychosocial changes. Three years of self-report data were collected from 168 mother-adolescent dyads, beginning when the adolescents (55.4% girls) were in 6th grade. Models were tested using longitudinal path analysis. Results indicated that the connection between adolescent aggression (and depressive symptoms) and maternal psychological control was best characterized as adolescent-driven, indirect, and mediated by mother-adolescent conflict; there were no indications of parent-driven indirect effects. That is, prior adolescent aggression and depressive symptoms were associated with increased conflict. In turn, conflict was associated with increased psychological control. Within our mediation models, reciprocal direct effects between both problem behaviors and conflict and between conflict and psychological control were also found. Additionally, exploratory analyses regarding the role of adolescent gender as a moderator of variable relations were conducted. These analyses revealed no gender-related patterns of moderation, whether moderated mediation or specific path tests for moderation were considered. This study corroborates prior research finding support for child effects on parenting behaviors during early adolescence. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  9. Aggressive Marital Conflict, Maternal Harsh Punishment, and Child Aggressive-Disruptive Behavior: Evidence for Direct and Mediated Relations

    PubMed Central

    Erath, Stephen A.; Bierman, Karen L.

    2009-01-01

    Direct associations between aggressive marital conflict and child aggressive-disruptive behavior at home and school were explored in this cross-sectional study of 360 kindergarten children. In addition, mediated pathways linking aggressive marital conflict to maternal harsh punishment to child aggressive-disruptive behavior were examined. Moderation analyses explored how the overall frequency of marital disagreement might buffer or exacerbate the impact of aggressive marital conflict on maternal harsh punishment and child aggressive-disruptive behavior. Hierarchical regressions revealed direct pathways linking aggressive marital conflict to child aggressive-disruptive behavior at home and school and a partially mediated pathway linking aggressive marital conflict to child aggressive-disruptive behavior at home. Further analyses revealed that rates of marital disagreement moderated the association between aggressive marital conflict and child aggressive-disruptive behavior at home, with an attenuated association at high rates of marital disagreement as compared with low rates of marital disagreement. PMID:16756397

  10. 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.

  11. Mutation Detection with Next-Generation Resequencing through a Mediator Genome

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

    Wurtzel, Omri; Dori-Bachash, Mally; Pietrokovski, Shmuel

    2010-12-31

    The affordability of next generation sequencing (NGS) is transforming the field of mutation analysis in bacteria. The genetic basis for phenotype alteration can be identified directly by sequencing the entire genome of the mutant and comparing it to the wild-type (WT) genome, thus identifying acquired mutations. A major limitation for this approach is the need for an a-priori sequenced reference genome for the WT organism, as the short reads of most current NGS approaches usually prohibit de-novo genome assembly. To overcome this limitation we propose a general framework that utilizes the genome of relative organisms as mediators for comparing WTmore » and mutant bacteria. Under this framework, both mutant and WT genomes are sequenced with NGS, and the short sequencing reads are mapped to the mediator genome. Variations between the mutant and the mediator that recur in the WT are ignored, thus pinpointing the differences between the mutant and the WT. To validate this approach we sequenced the genome of Bdellovibrio bacteriovorus 109J, an obligatory bacterial predator, and its prey-independent mutant, and compared both to the mediator species Bdellovibrio bacteriovorus HD100. Although the mutant and the mediator sequences differed in more than 28,000 nucleotide positions, our approach enabled pinpointing the single causative mutation. Experimental validation in 53 additional mutants further established the implicated gene. Our approach extends the applicability of NGS-based mutant analyses beyond the domain of available reference genomes.« less

  12. 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

  13. 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

  14. Structural Equation Model of Smartphone Addiction Based on Adult Attachment Theory: Mediating Effects of Loneliness and Depression.

    PubMed

    Kim, EunYoung; Cho, Inhyo; Kim, Eun Joo

    2017-06-01

    This study investigated the mediating effects of loneliness and depression on the relationship between adult attachment and smartphone addiction in university students. A total of 200 university students participated in this study. The data was analysed using descriptive statistics, correlation analysis, and structural equation modeling. There were significant positive relationships between attachment anxiety, loneliness, depression, and smartphone addiction. However, attachment anxiety was not significantly correlated with smartphone addiction. The results also showed that loneliness did not directly mediate between attachment anxiety and smartphone addiction. In addition, loneliness and depression serially mediated between attachment anxiety and smartphone addiction. The results suggest there are mediating effects of loneliness and depression in the relationship between attachment anxiety and smartphone addiction. The hypothesized model was found to be a suitable model for predicting smartphone addiction among university students. Future study is required to find a causal path to prevent smartphone addiction among university students. Copyright © 2017. Published by Elsevier B.V.

  15. 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.

  16. Mediating pathways and gender differences between shift work and subjective cognitive function.

    PubMed

    Wong, Imelda S; Smith, Peter M; Ibrahim, Selahadin; Mustard, Cameron A; Gignac, Monique A M

    2016-11-01

    Increased injury risk among shift workers is often attributed to cognitive function deficits that come about as a result of sleep disruptions. However, little is known about the intermediate influences of other factors (eg, work stress, health) which may affect this relationship. In addition, gender differences in these the complex relationships have not been fully explored. The purpose of this study is to (1) identify the extent to which work and non-work factors mediate the relationship between shift work, sleep and subsequent subjective cognitive function; and (2) determine if the mediating pathways differ for men and women. Data from the 2010 National Population Health Survey was used to create a cross-sectional sample of 4255 employed Canadians. Using path modelling, we examined the direct and indirect relationships between shift work, sleep duration, sleep quality and subjective cognitive function. Multigroup analyses tested for significantly different pathways between men and women. Potential confounding effects of age and self-reported health and potential mediating effects of work stress were simultaneously examined. Work stress and sleep quality significantly mediated the effects of shift work on cognition. Age and health confounded the relationship between sleep quality and subjective cognition. No differences were found between men and women. Occupational health and safety programmes are needed to address stress and health factors, in addition to sleep hygiene, to effectively address cognitive function among shift workers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. Density- and trait-mediated effects of a parasite and a predator in a tri-trophic food web

    PubMed Central

    Banerji, Aabir; Duncan, Alison B; Griffin, Joanne S; Humphries, Stuart; Petchey, Owen L; Kaltz, Oliver

    2015-01-01

    1. Despite growing interest in ecological consequences of parasitism in food webs, relatively little is known about effects of parasites on long-term population dynamics of non-host species or about whether such effects are density or trait mediated. 2. We studied a tri-trophic food chain comprised of (i) a bacterial basal resource (Serratia fonticola), (ii) an intermediate consumer (Paramecium caudatum), (iii) a top predator (Didinium nasutum) and (iv) a parasite of the intermediate consumer (Holospora undulata). A fully factorial experimental manipulation of predator and parasite presence/absence was combined with analyses of population dynamics, modelling and analyses of host (Paramecium) morphology and behaviour. 3. Predation and parasitism each reduced the abundance of the intermediate consumer (Paramecium), and parasitism indirectly reduced the abundance of the basal resource (Serratia). However, in combination, predation and parasitism had non-additive effects on the abundance of the intermediate consumer, as well as on that of the basal resource. In both cases, the negative effect of parasitism seemed to be effaced by predation. 4. Infection of the intermediate consumer reduced predator abundance. Modelling and additional experimentation revealed that this was most likely due to parasite reduction of intermediate host abundance (a density-mediated effect), as opposed to changes in predator functional or numerical response. 5. Parasitism altered morphological and behavioural traits, by reducing host cell length and increasing the swimming speed of cells with moderate parasite loads. Additional tests showed no significant difference in Didinium feeding rate on infected and uninfected hosts, suggesting that the combination of these modifications does not affect host vulnerability to predation. However, estimated rates of encounter with Serratia based on these modifications were higher for infected Paramecium than for uninfected Paramecium. 6. A mixture of

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

    PubMed

    Terlecki, Meredith A; Buckner, Julia D

    2015-01-01

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

  19. Social Anxiety and Heavy Situational Drinking: Coping and Conformity Motives as Multiple Mediators

    PubMed Central

    Terlecki, Meredith A.; Buckner, Julia D.

    2014-01-01

    Individuals with clinically elevated social anxiety are at greater risk for alcohol use disorder, and the relation between social anxiety and drinking problems is at least partially accounted for by drinking more in negative emotional (e.g., feeling sad or angry) and personal/intimate (e.g., before sexual intercourse) situations. Identification of cognitive/motivational factors related to drinking in these high-risk situations could inform the development of treatment and prevention interventions for these high-risk drinkers. The current study examined the mediating effect of drinking motives on the relationship between social anxiety and drinking these high-risk situations amongst undergraduates (N = 232). Clinically elevated social anxiety was associated with greater coping and conformity motives. Both coping and conformity motives mediated the relation between social anxiety and heavier alcohol consumption in negative emotional and personal/intimate contexts. Multiple mediation analyses indicated that these motives work additively to mediate the social anxiety-drinking situations relationship, such that that heavy situational drinking amongst undergraduates with clinically elevated social anxiety can be jointly attributed to desire to cope with negative affect and to avoid social scrutiny. PMID:25233446

  20. 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.

  1. [Interrelations Between Adolescent Problematic Internet Use and Parental Internet Mediation].

    PubMed

    Kammerl, Rudolf; Wartberg, Lutz

    2018-02-01

    Interrelations Between Adolescent Problematic Internet Use and Parental Internet Mediation Everyday life of adolescents and their parents is increasingly characterized by digital media usage (also referred to as "process of mediatization"). In the current study, associations between problematic Internet use of the adolescents (as a possible consequence of the process of mediatization) and parental media education were explored. For this purpose, throughout Germany 1,095 family dyads (an adolescent and a related parent) were investigated with a standardized questionnaire measuring different aspects of parental media education and adolescent problematic Internet use. We conducted two multiple linear regression analyses (dimensional approach) with adolescent problematic Internet use based on self-ratings (model 1, corrected R 2 = 0.18) and parental assessment (model 2, corrected R 2 = 0.24) as response variables. Consistently for self- and parental ratings, adolescent problematic Internet use was statistically significant related to male gender (of the adolescent), a more frequent inconsistent media education (adolescents' and parents' perspective) and a stronger monitoring (parents' perspective). Additionally, we observed associations between the parental rating of adolescent problematic Internet use and a less frequent active and restrictive Internet Mediation (parents' perspective). The findings of the present study show the importance of parental media education for problematic Internet use in adolescence and especially, the role of inconsistent media education should be investigated again in further studies.

  2. One-Year Outcomes and Mediators of a Brief Intervention for Drug Abusing Adolescents

    PubMed Central

    Winters, Ken C.; Lee, Susanne; Botzet, Andria; Fahnhorst, Tamara; Nicholson, Ali

    2014-01-01

    Two manually-guided brief interventions were evaluated with a randomized controlled trial. Adolescents (aged 13-17 years) suspected of abusing alcohol and other drugs and their parent were randomly assigned to receive either a 2-session adolescent only (BI-A), 2-session adolescent and additional parent session (BI-AP), or assessment only control condition (CON). Adolescents were identified in a school setting and the intervention was delivered by trained counselors. Outcome analyses (N=284; 90% of those enrolled) of relative change (from intake to 12-months) and absolute status (at 12-months) revealed a general pattern of reductions in drug use behaviors, particularly with the cannabis outcome measures, in both active conditions (BI-A and BI-AP). Students in the control condition showed worse outcome compared to the BI-A and BI-AP groups. Among the four mediating variables measured at 6-months, use of additional services, motivation to change and parenting practices had significant influences on 12-month outcome; problem solving skills approached significance as a mediator. The potential value of a brief intervention for drug abusing adolescents is discussed. PMID:24955669

  3. 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.

  4. Soybean peroxidase-mediated degradation of an azo dye– a detailed mechanistic study

    PubMed Central

    2013-01-01

    Background Peroxidases are emerging as an important class of enzymes that can be used for the efficient degradation of organic pollutants. However, detailed studies identifying the various intermediates produced and the mechanisms involved in the enzyme-mediated pollutant degradation are not widely published. Results In the present study, the enzymatic degradation of an azo dye (Crystal Ponceau 6R, CP6R) was studied using commercially available soybean peroxidase (SBP) enzyme. Several operational parameters affecting the enzymatic degradation of dye were evaluated and optimized, such as initial dye concentration, H2O2 dosage, mediator amount and pH of the solution. Under optimized conditions, 40 ppm dye solution could be completely degraded in under one minute by SBP in the presence of H2O2 and a redox mediator. Dye degradation was also confirmed using HPLC and TOC analyses, which showed that most of the dye was being mineralized to CO2 in the process. Conclusions Detailed analysis of metabolites, based on LC/MS results, showed that the enzyme-based degradation of the CP6R dye proceeded in two different reaction pathways- via symmetric azo bond cleavage as well as asymmetric azo bond breakage in the dye molecule. In addition, various critical transformative and oxidative steps such as deamination, desulfonation, keto-oxidation are explained on an electronic level. Furthermore, LC/MS/MS analyses confirmed that the end products in both pathways were small chain aliphatic carboxylic acids. PMID:24308857

  5. 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.

  6. 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.

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

    PubMed

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

    2018-03-01

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

  8. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial.

    PubMed

    Keohane, Denis; Schwartz, Jeffrey; Gundapaneni, Balarama; Stewart, Michelle; Amass, Leslie

    2017-03-01

    Tafamidis, a non-NSAID highly specific transthyretin stabilizer, delayed neurologic disease progression as measured by Neuropathy Impairment Score-Lower Limbs (NIS-LL) in an 18-month, double-blind, placebo-controlled randomized trial in 128 patients with early-stage transthyretin V30M familial amyloid polyneuropathy (ATTRV30M-FAP). The current post hoc analyses aimed to further evaluate the effects of tafamidis in delaying ATTRV30M-FAP progression in this trial. Pre-specified, repeated-measures analysis of change from baseline in NIS-LL in this trial (ClinicalTrials.gov NCT00409175) was repeated with addition of baseline as covariate and multiple imputation analysis for missing data by treatment group. Change in NIS-LL plus three small-fiber nerve tests (NIS-LL + Σ3) and NIS-LL plus seven nerve tests (NIS-LL + Σ7) were assessed without baseline as covariate. Treatment outcomes over the NIS-LL, Σ3, Σ7, modified body mass index and Norfolk Quality of Life-Diabetic Neuropathy Total Quality of Life Score were also examined using multivariate analysis techniques. Neuropathy progression based on NIS-LL change from baseline to Month 18 remained significantly reduced for tafamidis versus placebo in the baseline-adjusted and multiple imputation analyses. NIS-LL + Σ3 and NIS-LL + Σ7 captured significant treatment group differences. Multivariate analyses provided strong statistical evidence for a superior tafamidis treatment effect. These supportive analyses confirm that tafamidis delays neurologic progression in early-stage ATTRV30M-FAP. NCT00409175.

  9. Childhood stress and birth timing among African American women: Cortisol as biological mediator.

    PubMed

    Gillespie, Shannon L; Christian, Lisa M; Alston, Angela D; Salsberry, Pamela J

    2017-10-01

    Preterm birth (PTB) occurs among 1:11U.S. white women and 1:7.5 African American women and is a significant driver of racial disparities in infant mortality. Maternal stress is the most common clinical phenotype underlying spontaneous PTB. Specific patterns of stress and biological mediators driving PTB remain unclear. We examined the effect of childhood stress on birth timing among African American women and evaluated maternal cortisol elevation as a biological mediator. A prospective observational design was employed, with a single study visit at 28-32 weeks gestation and medical record review. The Stress and Adversity Inventory was administered, which provides a comprehensive estimate of childhood stress, stress in adulthood, and five core characteristic subscales (interpersonal loss, physical danger, humiliation, entrapment, role disruption). Venipuncture was performed between 11:00am and 4:00pm and plasma cortisol quantified by ELISA. Analyses controlled for stress in adulthood. Among a final sample of 89, cumulative childhood stress predicted birth timing (p=0.01). The association was driven by stress related to interpersonal loss and physical danger, with support for maternal cortisol as a biological mediator (ab=0.02, 95% CI [0.001, 0.045]; ab=0.02, 95% CI [0.001, 0.043], respectively). Results were similar, overall, in sub-group analyses among spontaneously laboring women (n=53); however, role disruption arose as an additional predictor, as mediated by cortisol elevations (ab=0.03, 95% CI [0.005, 0.074]). Of note, cortisol was no longer supported as a mediator linking physical danger to birth timing after adjusting for sleep quality and hours awake prior to venipuncture (ab=0.02, 95% CI [-0.0001, 0.046]). We provide preliminary evidence that, independent of stress in adulthood, childhood stress of specific core characteristics may shape birth timing, with cortisol elevation as a biological mediator. Further investigation is warranted and may bolster the

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

    PubMed

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

    2013-08-01

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

  11. Secondary mediation and regression analyses of the PTClinResNet database: determining causal relationships among the International Classification of Functioning, Disability and Health levels for four physical therapy intervention trials.

    PubMed

    Mulroy, Sara J; Winstein, Carolee J; Kulig, Kornelia; Beneck, George J; Fowler, Eileen G; DeMuth, Sharon K; Sullivan, Katherine J; Brown, David A; Lane, Christianne J

    2011-12-01

    Each of the 4 randomized clinical trials (RCTs) hosted by the Physical Therapy Clinical Research Network (PTClinResNet) targeted a different disability group (low back disorder in the Muscle-Specific Strength Training Effectiveness After Lumbar Microdiskectomy [MUSSEL] trial, chronic spinal cord injury in the Strengthening and Optimal Movements for Painful Shoulders in Chronic Spinal Cord Injury [STOMPS] trial, adult stroke in the Strength Training Effectiveness Post-Stroke [STEPS] trial, and pediatric cerebral palsy in the Pediatric Endurance and Limb Strengthening [PEDALS] trial for children with spastic diplegic cerebral palsy) and tested the effectiveness of a muscle-specific or functional activity-based intervention on primary outcomes that captured pain (STOMPS, MUSSEL) or locomotor function (STEPS, PEDALS). The focus of these secondary analyses was to determine causal relationships among outcomes across levels of the International Classification of Functioning, Disability and Health (ICF) framework for the 4 RCTs. With the database from PTClinResNet, we used 2 separate secondary statistical approaches-mediation analysis for the MUSSEL and STOMPS trials and regression analysis for the STEPS and PEDALS trials-to test relationships among muscle performance, primary outcomes (pain related and locomotor related), activity and participation measures, and overall quality of life. Predictive models were stronger for the 2 studies with pain-related primary outcomes. Change in muscle performance mediated or predicted reductions in pain for the MUSSEL and STOMPS trials and, to some extent, walking speed for the STEPS trial. Changes in primary outcome variables were significantly related to changes in activity and participation variables for all 4 trials. Improvement in activity and participation outcomes mediated or predicted increases in overall quality of life for the 3 trials with adult populations. Variables included in the statistical models were limited to those

  12. Mediation Analysis with Survival Outcomes: Accelerated Failure Time vs. Proportional Hazards Models

    PubMed Central

    Gelfand, Lois A.; MacKinnon, David P.; DeRubeis, Robert J.; Baraldi, Amanda N.

    2016-01-01

    Objective: Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored) events. We present considerations for choosing an approach, using a comparison of semi-parametric proportional hazards (PH) and fully parametric accelerated failure time (AFT) approaches for illustration. Method: We compare PH and AFT models and procedures in their integration into mediation models and review their ability to produce coefficients that estimate causal effects. Using simulation studies modeling Weibull-distributed survival times, we compare statistical properties of mediation analyses incorporating PH and AFT approaches (employing SAS procedures PHREG and LIFEREG, respectively) under varied data conditions, some including censoring. A simulated data set illustrates the findings. Results: AFT models integrate more easily than PH models into mediation models. Furthermore, mediation analyses incorporating LIFEREG produce coefficients that can estimate causal effects, and demonstrate superior statistical properties. Censoring introduces bias in the coefficient estimate representing the treatment effect on outcome—underestimation in LIFEREG, and overestimation in PHREG. With LIFEREG, this bias can be addressed using an alternative estimate obtained from combining other coefficients, whereas this is not possible with PHREG. Conclusions: When Weibull assumptions are not violated, there are compelling advantages to using LIFEREG over PHREG for mediation analyses involving survival-time outcomes. Irrespective of the procedures used, the interpretation of coefficients, effects of censoring on coefficient estimates, and statistical properties should be taken into account when reporting results. PMID:27065906

  13. Mediation Analysis with Survival Outcomes: Accelerated Failure Time vs. Proportional Hazards Models.

    PubMed

    Gelfand, Lois A; MacKinnon, David P; DeRubeis, Robert J; Baraldi, Amanda N

    2016-01-01

    Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored) events. We present considerations for choosing an approach, using a comparison of semi-parametric proportional hazards (PH) and fully parametric accelerated failure time (AFT) approaches for illustration. We compare PH and AFT models and procedures in their integration into mediation models and review their ability to produce coefficients that estimate causal effects. Using simulation studies modeling Weibull-distributed survival times, we compare statistical properties of mediation analyses incorporating PH and AFT approaches (employing SAS procedures PHREG and LIFEREG, respectively) under varied data conditions, some including censoring. A simulated data set illustrates the findings. AFT models integrate more easily than PH models into mediation models. Furthermore, mediation analyses incorporating LIFEREG produce coefficients that can estimate causal effects, and demonstrate superior statistical properties. Censoring introduces bias in the coefficient estimate representing the treatment effect on outcome-underestimation in LIFEREG, and overestimation in PHREG. With LIFEREG, this bias can be addressed using an alternative estimate obtained from combining other coefficients, whereas this is not possible with PHREG. When Weibull assumptions are not violated, there are compelling advantages to using LIFEREG over PHREG for mediation analyses involving survival-time outcomes. Irrespective of the procedures used, the interpretation of coefficients, effects of censoring on coefficient estimates, and statistical properties should be taken into account when reporting results.

  14. Commentary: Mediation Analysis, Causal Process, and Cross-Sectional Data

    ERIC Educational Resources Information Center

    Shrout, Patrick E.

    2011-01-01

    Maxwell, Cole, and Mitchell (2011) extended the work of Maxwell and Cole (2007), which raised important questions about whether mediation analyses based on cross-sectional data can shed light on longitudinal mediation process. The latest article considers longitudinal processes that can only be partially explained by an intervening variable, and…

  15. Psychological Detachment Mediating the Daily Relationship between Workload and Marital Satisfaction

    PubMed Central

    Germeys, Lynn; De Gieter, Sara

    2017-01-01

    Scholars already demonstrated that psychologically detaching from work after workhours can diminish or avoid the negative effects of job demands on employees' well-being. In this study, we examined a curvilinear relationship between workload and psychological detachment. Moreover, we investigated the moderating influence of an employee's work-home segmentation preference on the relation between detachment and marital satisfaction. In addition, we applied and extended the stressor-detachment model by examining detachment as a mediator of the relation between workload and marital satisfaction. A total of 136 employees participated in our daily diary survey study during 10 consecutive working days. The results of the Bayesian 2-level path analyses revealed a negative linear and curvilinear relationship between workload and psychological detachment on a daily basis. Daily detachment positively related to marital satisfaction, with one's preference to segment work from home reinforcing this relationship. Moreover, psychological detachment fully mediated the daily relationship between workload and marital satisfaction. Implications for practice and suggestions for future research are discussed. PMID:28101076

  16. 24 CFR 81.65 - Other information and analyses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Other information and analyses. 81... information and analyses. When deemed appropriate and requested in writing, on a case by-case basis, by the... conduct additional analyses concerning any such report. A GSE shall submit additional reports or other...

  17. 24 CFR 81.65 - Other information and analyses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Other information and analyses. 81... information and analyses. When deemed appropriate and requested in writing, on a case by-case basis, by the... conduct additional analyses concerning any such report. A GSE shall submit additional reports or other...

  18. 24 CFR 81.65 - Other information and analyses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Other information and analyses. 81... information and analyses. When deemed appropriate and requested in writing, on a case by-case basis, by the... conduct additional analyses concerning any such report. A GSE shall submit additional reports or other...

  19. 24 CFR 81.65 - Other information and analyses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Other information and analyses. 81... information and analyses. When deemed appropriate and requested in writing, on a case by-case basis, by the... conduct additional analyses concerning any such report. A GSE shall submit additional reports or other...

  20. 24 CFR 81.65 - Other information and analyses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Other information and analyses. 81... information and analyses. When deemed appropriate and requested in writing, on a case by-case basis, by the... conduct additional analyses concerning any such report. A GSE shall submit additional reports or other...

  1. When ab ≠ c - c': published errors in the reports of single-mediator models.

    PubMed

    Petrocelli, John V; Clarkson, Joshua J; Whitmire, Melanie B; Moon, Paul E

    2013-06-01

    Accurate reports of mediation analyses are critical to the assessment of inferences related to causality, since these inferences are consequential for both the evaluation of previous research (e.g., meta-analyses) and the progression of future research. However, upon reexamination, approximately 15% of published articles in psychology contain at least one incorrect statistical conclusion (Bakker & Wicherts, Behavior research methods, 43, 666-678 2011), disparities that beget the question of inaccuracy in mediation reports. To quantify this question of inaccuracy, articles reporting standard use of single-mediator models in three high-impact journals in personality and social psychology during 2011 were examined. More than 24% of the 156 models coded failed an equivalence test (i.e., ab = c - c'), suggesting that one or more regression coefficients in mediation analyses are frequently misreported. The authors cite common sources of errors, provide recommendations for enhanced accuracy in reports of single-mediator models, and discuss implications for alternative methods.

  2. Efficient and rapid Agrobacterium-mediated genetic transformation of durum wheat (Triticum turgidum L. var. durum) using additional virulence genes.

    PubMed

    Wu, Huixia; Doherty, Angela; Jones, Huw D

    2008-06-01

    Genetic transformation of wheat, using biolistics or Agrobacterium, underpins a range of specific research methods for identifying genes and studying their function in planta. Transgenic approaches to study and modify traits in durum wheat have lagged behind those for bread wheat. Here we report the use of Agrobacterium strain AGL1, with additional vir genes housed in a helper plasmid, to transform and regenerate the durum wheat variety Ofanto. The use of the basic pSoup helper plasmid with no additional vir genes failed to generate transformants, whereas the presence of either virG542 or the 15 kb Komari fragment containing virB, virC and virG542 produced transformation efficiencies of between 0.6 and 9.7%. Of the 42 transgenic plants made, all but one (which set very few seeds) appeared morphologically normal and produced between 100 and 300 viable seeds. The transgene copy number and the segregation ratios were found to be very similar to those previously reported for bread wheat. We believe that this is the first report describing successful genetic transformation of tetraploid durum wheat (Triticum turgidum L. var. durum) mediated by Agrobacterium tumefaciens using immature embryos as the explant.

  3. Domain General Mediators of the Relation between Kindergarten Number Sense and First-Grade Mathematics Achievement

    PubMed Central

    Hassinger-Das, Brenna; Jordan, Nancy C.; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

    2013-01-01

    Domain general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that attention problems and executive functioning both were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance while executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. PMID:24237789

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

    PubMed

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

    2017-11-01

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

  5. Does Emotion Dysregulation Mediate the Association Between Sluggish Cognitive Tempo and College Students' Social Impairment?

    PubMed

    Flannery, Andrew J; Becker, Stephen P; Luebbe, Aaron M

    2016-09-01

    Studies demonstrate an association between sluggish cognitive tempo (SCT) and social impairment, although no studies have tested possible mechanisms of this association. This study aimed to (a) examine SCT in relation to college students' social functioning; (b) test if SCT is significantly associated with emotion dysregulation beyond depressive, anxious, and ADHD symptoms; and (c) test if emotion dysregulation mediates the association between SCT symptoms and social impairment. College students (N = 158) completed measures of psychopathology symptoms, emotion dysregulation, and social functioning. Participants with elevated SCT (12%) had higher ADHD, depressive, and anxious symptoms in addition to poorer emotion regulation and social adjustment than participants without elevated SCT. Above and beyond other psychopathologies, SCT was significantly associated with social impairment but not general interpersonal functioning. SCT was also associated with emotion dysregulation, even after accounting for the expectedly strong association between depression and emotion dysregulation. Further analyses supported emotion dysregulation as a mediator of the association between SCT and social impairment. These findings are important for theoretical models of SCT and underscore the need for additional, longitudinal research. © The Author(s) 2014.

  6. Religiosity and decreased risk of substance use disorders: is the effect mediated by social support or mental health status?

    PubMed Central

    Harris, Katherine M.; Koenig, Harold G.; Han, Xiaotong; Sullivan, Greer; Mattox, Rhonda; Tang, Lingqi

    2009-01-01

    Objective The negative association between religiosity (religious beliefs and church attendance) and the likelihood of substance use disorders is well established, but the mechanism(s) remain poorly understood. We investigated whether this association was mediated by social support or mental health status. Method We utilized cross-sectional data from the 2002 National Survey on Drug Use and Health (n = 36,370). We first used logistic regression to regress any alcohol use in the past year on sociodemographic and religiosity variables. Then, among individuals who drank in the past year, we regressed past year alcohol abuse/dependence on sociodemographic and religiosity variables. To investigate whether social support mediated the association between religiosity and alcohol use and alcohol abuse/dependence we repeated the above models, adding the social support variables. To the extent that these added predictors modified the magnitude of the effect of the religiosity variables, we interpreted social support as a possible mediator. We also formally tested for mediation using path analysis. We investigated the possible mediating role of mental health status analogously. Parallel sets of analyses were conducted for any drug use, and drug abuse/dependence among those using any drugs as the dependent variables. Results The addition of social support and mental health status variables to logistic regression models had little effect on the magnitude of the religiosity coefficients in any of the models. While some of the tests of mediation were significant in the path analyses, the results were not always in the expected direction, and the magnitude of the effects was small. Conclusions The association between religiosity and decreased likelihood of a substance use disorder does not appear to be substantively mediated by either social support or mental health status. PMID:19714282

  7. 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)…

  8. Sleep Disturbance and Depression Symptoms Mediate the Relationship between Pain and Cognitive Dysfunction in Lupus Patients.

    PubMed

    Lillis, Teresa A; Tirone, Vanessa; Gandhi, Nisarg; Weinberg, Stacy; Nika, Ailda; Sequeira, Winston; Hobfoll, Stevan E; Block, Joel A; Jolly, Meenakshi

    2018-05-04

    The current study explored whether sleep disturbance and depression symptoms mediated the relationship between pain and Cognitive Dysfunction (CD) in a sample of 115 patients with Systemic Lupus Erythematosus (SLE). 115 consenting SLE patients completed questionnaires on pain, perceived stress, depression, sleep, and CD. Relationships among pain, sleep, depression and CD were assessed with bootstrapped mediation models controlling for race/ethnicity, fibromyalgia diagnosis, current corticosteroid use, disease activity and damage, and perceived stress. Mediation analyses indicated that the effect of pain on CD was mediated by sleep disturbance (β = 0.30) and depression symptoms (β = 0.33). These effects were maintained even after controlling for aforementioned covariates, of which, only disease activity (β= 0.20) and stress (β=.22) remained significantly linked to CD [Overall Model R 2 = .53; all p's <.05). Even after controlling for disease activity and perceived stress, the relationship between pain and CD was explained by sleep disturbance and depression symptoms. Although these relationships need validation in longitudinal studies with additional measurement modalities, our findings may indicate promising, non-pharmacologic intervention avenues for SLE patients with pain and CD. Specifically, cognitive-behavioral therapies for depression and sleep are known to reduce distress and enhance functioning across various psychosocial domains. Given the symptom burden of SLE, interventions that maximize potential benefits without additional pharmacologic treatments may be of particular utility. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Differentiation of Xylella fastidiosa Strains via Multilocus Sequence Analysis of Environmentally Mediated Genes (MLSA-E)

    PubMed Central

    Parker, Jennifer K.; Havird, Justin C.

    2012-01-01

    Isolates of the plant pathogen Xylella fastidiosa are genetically very similar, but studies on their biological traits have indicated differences in virulence and infection symptomatology. Taxonomic analyses have identified several subspecies, and phylogenetic analyses of housekeeping genes have shown broad host-based genetic differences; however, results are still inconclusive for genetic differentiation of isolates within subspecies. This study employs multilocus sequence analysis of environmentally mediated genes (MLSA-E; genes influenced by environmental factors) to investigate X. fastidiosa relationships and differentiate isolates with low genetic variability. Potential environmentally mediated genes, including host colonization and survival genes related to infection establishment, were identified a priori. The ratio of the rate of nonsynonymous substitutions to the rate of synonymous substitutions (dN/dS) was calculated to select genes that may be under increased positive selection compared to previously studied housekeeping genes. Nine genes were sequenced from 54 X. fastidiosa isolates infecting different host plants across the United States. Results of maximum likelihood (ML) and Bayesian phylogenetic (BP) analyses are in agreement with known X. fastidiosa subspecies clades but show novel within-subspecies differentiation, including geographic differentiation, and provide additional information regarding host-based isolate variation and specificity. dN/dS ratios of environmentally mediated genes, though <1 due to high sequence similarity, are significantly greater than housekeeping gene dN/dS ratios and correlate with increased sequence variability. MLSA-E can more precisely resolve relationships between closely related bacterial strains with low genetic variability, such as X. fastidiosa isolates. Discovering the genetic relationships between X. fastidiosa isolates will provide new insights into the epidemiology of populations of X. fastidiosa, allowing

  10. Differentiation of Xylella fastidiosa strains via multilocus sequence analysis of environmentally mediated genes (MLSA-E).

    PubMed

    Parker, Jennifer K; Havird, Justin C; De La Fuente, Leonardo

    2012-03-01

    Isolates of the plant pathogen Xylella fastidiosa are genetically very similar, but studies on their biological traits have indicated differences in virulence and infection symptomatology. Taxonomic analyses have identified several subspecies, and phylogenetic analyses of housekeeping genes have shown broad host-based genetic differences; however, results are still inconclusive for genetic differentiation of isolates within subspecies. This study employs multilocus sequence analysis of environmentally mediated genes (MLSA-E; genes influenced by environmental factors) to investigate X. fastidiosa relationships and differentiate isolates with low genetic variability. Potential environmentally mediated genes, including host colonization and survival genes related to infection establishment, were identified a priori. The ratio of the rate of nonsynonymous substitutions to the rate of synonymous substitutions (dN/dS) was calculated to select genes that may be under increased positive selection compared to previously studied housekeeping genes. Nine genes were sequenced from 54 X. fastidiosa isolates infecting different host plants across the United States. Results of maximum likelihood (ML) and Bayesian phylogenetic (BP) analyses are in agreement with known X. fastidiosa subspecies clades but show novel within-subspecies differentiation, including geographic differentiation, and provide additional information regarding host-based isolate variation and specificity. dN/dS ratios of environmentally mediated genes, though <1 due to high sequence similarity, are significantly greater than housekeeping gene dN/dS ratios and correlate with increased sequence variability. MLSA-E can more precisely resolve relationships between closely related bacterial strains with low genetic variability, such as X. fastidiosa isolates. Discovering the genetic relationships between X. fastidiosa isolates will provide new insights into the epidemiology of populations of X. fastidiosa, allowing

  11. Understanding the connection between self-esteem and aggression: The mediating role of emotion dysregulation.

    PubMed

    Garofalo, Carlo; Holden, Christopher J; Zeigler-Hill, Virgil; Velotti, Patrizia

    2016-01-01

    The purpose of the present study was to extend previous knowledge concerning the link between self-esteem and aggression by examining the mediating role of emotion dysregulation among offenders and community participants. A sample of 153 incarcerated violent offenders and a community sample of 197 individuals completed self-report measures of self-esteem level, emotion dysregulation, and trait aggression. Offenders reported lower levels of self-esteem than community participants, as well as greater levels of emotional nonacceptance and hostility. Bootstrapping analyses were performed to test whether emotion dysregulation mediated the association between self-esteem level and aggression. In the offender sample, mediation models were significant for three of the four aspects of trait aggression that were considered. Emotion dysregulation fully mediated the links that low self-esteem had with physical aggression, anger, and hostility. The same pattern (with the addition of full mediation for verbal aggression) was confirmed in the community sample. Our findings suggest that emotion dysregulation may play an important role in the connection between low self-esteem and aggression. Alternative models of the associations among these variables were tested and discussed. As a whole, the present results are consistent with those of other studies and suggest that it may be beneficial to include emotion regulation modules as part of prevention and treatment programs for violent offenders. © 2015 Wiley Periodicals, Inc.

  12. 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.

  13. Childhood social withdrawal, interpersonal impairment, and young adult depression: a mediational model.

    PubMed

    Katz, Shaina J; Conway, Christopher C; Hammen, Constance L; Brennan, Patricia A; Najman, Jake M

    2011-11-01

    Building on interpersonal theories of depression, the current study sought to explore whether early childhood social withdrawal serves as a risk factor for depressive symptoms and diagnoses in young adulthood. The researchers hypothesized that social impairment at age 15 would mediate the association between social withdrawal at age 5 and depression by age 20. This mediational model was tested in a community sample of 702 Australian youth followed from mother's pregnancy to youth age 20. Structural equation modeling analyses found support for a model in which childhood social withdrawal predicted adolescent social impairment, which, in turn, predicted depression in young adulthood. Additionally, gender was found to moderate the relationship between adolescent social impairment and depression in early adulthood, with females exhibiting a stronger association between social functioning and depression at the symptom and diagnostic level. This study illuminates one potential pathway from early developing social difficulties to later depressive symptoms and disorders.

  14. Childhood Social Withdrawal, Interpersonal Impairment, and Young Adult Depression: A Mediational Model

    PubMed Central

    Katz, Shaina J.; Conway, Christopher C.; Hammen, Constance L.; Brennan, Patricia A.; Najman, Jake M.

    2012-01-01

    Building on interpersonal theories of depression, the current study sought to explore whether early childhood social withdrawal serves as a risk factor for depressive symptoms and diagnoses in young adulthood. The researchers hypothesized that social impairment at age 15 would mediate the association between social withdrawal at age 5 and depression by age 20. This mediational model was tested in a community sample of 702 Australian youth followed from mother’s pregnancy to youth age 20. Structural equation modeling analyses found support for a model in which childhood social withdrawal predicted adolescent social impairment, which, in turn, predicted depression in young adulthood. Additionally, gender was found to moderate the relationship between adolescent social impairment and depression in early adulthood, with females exhibiting a stronger association between social functioning and depression at the symptom and diagnostic level. This study illuminates one potential pathway from early developing social difficulties to later depressive symptoms and disorders. PMID:21744059

  15. A default Bayesian hypothesis test for mediation.

    PubMed

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

    2015-03-01

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

  16. DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood

    PubMed Central

    Tobi, Elmar W.; Slieker, Roderick C.; Luijk, René; Dekkers, Koen F.; Stein, Aryeh D.; Xu, Kate M.; Slagboom, P. Eline; van Zwet, Erik W.; Lumey, L. H.; Heijmans, Bastiaan T.

    2018-01-01

    Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342,596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formal mediation analysis. DNAm mediated the association of prenatal famine exposure with adult BMI and TG but not with glucose. DNAm at PIM3 (cg09349128), a gene involved in energy metabolism, mediated 13.4% [95% confidence interval (CI), 5 to 28%] of the association between famine exposure and BMI. DNAm at six CpGs, including TXNIP (cg19693031), influencing β cell function, and ABCG1 (cg07397296), affecting lipid metabolism, together mediated 80% (95% CI, 38.5 to 100%) of the association between famine exposure and TG. Analyses restricted to those exposed to famine during early gestation identified additional CpGs mediating the relationship with TG near PFKFB3 (glycolysis) and METTL8 (adipogenesis). DNAm at the CpGs involved was associated with gene expression in an external data set and correlated with DNAm levels in fat depots in additional postmortem data. Our data are consistent with the hypothesis that epigenetic mechanisms mediate the influence of transient adverse environmental factors in early life on long-term metabolic health. The specific mechanism awaits elucidation. PMID:29399631

  17. Power Analysis for Complex Mediational Designs Using Monte Carlo Methods

    ERIC Educational Resources Information Center

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

    2010-01-01

    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…

  18. Mediating and moderating processes in the relationship between multicultural ideology and attitudes towards immigrants in emerging adults.

    PubMed

    Musso, Pasquale; Inguglia, Cristiano; Lo Coco, Alida; Albiero, Paolo; Berry, John W

    2017-12-01

    Few studies examine intercultural relations in emerging adulthood. Framed from the perspective of the Mutual Intercultural Relations in Plural Societies (MIRIPS) project, the current paper examined the mediating role of tolerance and perceived consequences of immigration in the relationship between multicultural ideology and attitudes towards immigrants. Additionally, the moderating role of context was analysed. A two-group structural equation modelling was performed on data collected from 305 Italian emerging adults living both in northern and in southern Italy with different socio-political climates towards immigrants. In both groups, tolerance and perceived consequences of immigration mediated the relationship between multicultural ideology and attitudes towards immigrants. Also, this indirect relationship was significantly higher for the northern than southern Italians. These findings provide provisional evidence of mediating and moderating processes in the relationship between multicultural ideology and attitudes towards immigrants and suggest important implications for practitioners interested in promoting intercultural relations among emerging adults. © 2016 International Union of Psychological Science.

  19. Sequence- and structure-based computational analyses of Gram-negative tripartite efflux pumps in the context of bacterial membranes

    DOE PAGES

    Travers, Timothy; Wang, Katherine J.; Lopez, Cesar A.; ...

    2018-02-09

    Gram-negative multidrug resistance currently presents a serious threat to public health with infections effectively rendered untreatable. Multiple molecular mechanisms exist that cause antibiotic resistance and in addition, the last three decades have seen slowing rates of new drug development. In this paper, we summarize the use of various computational techniques for investigating the mechanisms of multidrug resistance mediated by Gram-negative tripartite efflux pumps and membranes. Recent work in our lab combines data-driven sequence and structure analyses to study the interactions and dynamics of these bacterial components. Computational studies can complement experimental methodologies for gaining crucial insights into combatting multidrug resistance.

  20. Sequence- and structure-based computational analyses of Gram-negative tripartite efflux pumps in the context of bacterial membranes

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

    Travers, Timothy; Wang, Katherine J.; Lopez, Cesar A.

    Gram-negative multidrug resistance currently presents a serious threat to public health with infections effectively rendered untreatable. Multiple molecular mechanisms exist that cause antibiotic resistance and in addition, the last three decades have seen slowing rates of new drug development. In this paper, we summarize the use of various computational techniques for investigating the mechanisms of multidrug resistance mediated by Gram-negative tripartite efflux pumps and membranes. Recent work in our lab combines data-driven sequence and structure analyses to study the interactions and dynamics of these bacterial components. Computational studies can complement experimental methodologies for gaining crucial insights into combatting multidrug resistance.

  1. A novel derivative of decursin, CSL-32, blocks migration and production of inflammatory mediators and modulates PI3K and NF-κB activities in HT1080 cells.

    PubMed

    Lee, Seung-Hee; Lee, Jee Hyun; Kim, Eun-Ju; Kim, Won-Jung; Suk, Kyoungho; Kim, Joo-Hwan; Song, Gyu Yong; Lee, Won-Ha

    2012-07-01

    Decursin and related coumarin compounds in herbal extracts have a number of biological activities against inflammation, angiogenesis and cancer. We have analysed a derivative of decursin (CSL-32) for activity against inflammatory activation of cancer cells, such as migration, invasion and expression of pro-inflammatory mediators. The human fibrosarcoma cell line, HT1080, was treated with TNFα (tumour necrosis factor α) in the presence or absence of CSL-32. The cellular responses and modification of signalling adapters were analysed with respect to the production of pro-inflammatory mediators, as also migration, adhesion and invasion. Treatment of HT1080 cells with CSL-32 inhibited their proliferation, without affecting cell viability, and TNFα-induced expression of pro-inflammatory mediators, such as MMP-9 (matrix metalloproteinase-9) and IL-8 (interleukin-8). CSL-32 also suppressed phosphorylation and degradation of IκB (inhibitory κB), phosphorylation of p65 subunit of NF-κB (nuclear factor-κB) and nuclear translocation of NF-κB, which are required for the expression of pro-inflammatory mediators. In addition, CSL-32 inhibited invasion and migration of HT1080 cells, as also cellular adhesion to fibronectin, an ECM (extracellular matrix) protein. CSL-32 treatment resulted in a dose-dependent inhibition of PI3K (phosphoinositide 3-kinase) activity, required for the cellular migration. The analyses show that CSL-32 inhibits processes associated with inflammation, such as the production of pro-inflammatory mediators, as well as adhesion, migration and invasion in HT1080 cells.

  2. Collective efficacy, group potency, and group performance: meta-analyses of their relationships, and test of a mediation model.

    PubMed

    Stajkovic, Alexander D; Lee, Dongseop; Nyberg, Anthony J

    2009-05-01

    The authors examined relationships among collective efficacy, group potency, and group performance. Meta-analytic results (based on 6,128 groups, 31,019 individuals, 118 correlations adjusted for dependence, and 96 studies) reveal that collective efficacy was significantly related to group performance (.35). In the proposed nested 2-level model, collective efficacy assessment (aggregation and group discussion) was tested as the 1st-level moderator. It showed significantly different average correlations with group performance (.32 vs. .45), but the group discussion assessment was homogeneous, whereas the aggregation assessment was heterogeneous. Consequently, there was no 2nd-level moderation for the group discussion, and heterogeneity in the aggregation group was accounted for by the 2nd-level moderator, task interdependence (high, moderate, and low levels were significant; the higher the level, the stronger the relationship). The 2nd and 3rd meta-analyses indicated that group potency was related to group performance (.29) and to collective efficacy (.65). When tested in a structural equation modeling analysis based on meta-analytic findings, collective efficacy fully mediated the relationship between group potency and group performance. The authors suggest future research and convert their findings to a probability of success index to help facilitate practice. (c) 2009 APA, all rights reserved.

  3. Additive effects of inflammation and stress reaction on Toll-like receptor 4-mediated growth of endometriotic stromal cells.

    PubMed

    Khan, Khaleque Newaz; Kitajima, Michio; Inoue, Tsuneo; Tateishi, Seiko; Fujishita, Akira; Nakashima, Masahiro; Masuzaki, Hideaki

    2013-10-01

    for ESCs from control women. Exogenous treatment with either HSP70 or LPS significantly stimulated the production of IL-6 and TNFα by M[Symbol: see text] and promoted the proliferation of ESCs, and a significant additive effect between LPS and HSP70 was observed. While individual treatment with either polymyxin B, an LPS antagonist, or anti-HSP70 antibody was unable to suppress the combined effects of LPS and HSP70 on cytokine secretion or ESC proliferation, pretreatment of cells with the anti-TLR4 antibody was able to significantly suppress their combined effects. Further studies are needed to examine the mutual role between other secondary inflammatory mediators and endogenous stress proteins in promoting pelvic inflammation and growth of endometriotic stromal cells. Our findings suggest that endotoxin and HSP70 are mutually involved in a stress reaction and in inflammation. A combined effect between local inflammation and a stress reaction in pelvic environment may be involved in TLR4-mediated growth of endometriotic cells. Since endometriosis is a multi-factorial disease, it is difficult to explain uniformly its growth regulation by a single factor. Our findings may provide some new insights in understanding the physiopathology or pathogenesis of endometriosis and may hold new therapeutic potential. This work was supported by Grants-in-Aid for Scientific Research (grant no. 16591671 and 18591837) from the Ministry of Education, Sports, Culture, Science and Technology of Japan (to K.N.K.). There is no conflict of interest related to this study. Not applicable.

  4. When mothers have serious mental health problems: parenting as a proximal mediator.

    PubMed

    Oyserman, Daphna; Bybee, Deborah; Mowbray, Carol; Hart-Johnson, Tamera

    2005-08-01

    Maternal mental health (MMH) problems are associated with lack of confidence in one's parenting, overly lax or too harsh discipline, and child academic underperformance. We asked if parenting mediates the effect of MMH problems on academic outcomes even among mothers with serious mental illness (n=164). Structural equation analyses show a significant association between MMH problems and permissive (lack of parenting confidence, lack of follow through) parenting and verbal hostility as well as worse academic outcomes (school recorded grades, teacher reported behaviour). Permissive parenting completely mediated the direct effect of MMH on academic outcomes. Further analyses showed that the mediation effect was attributed to a single component of permissive parenting-lack of parenting confidence.

  5. Does perfectionism in bipolar disorder pedigrees mediate associations between anxiety/stress and mood symptoms?

    PubMed

    Corry, Justine; Green, Melissa; Roberts, Gloria; Fullerton, Janice M; Schofield, Peter R; Mitchell, Philip B

    2017-10-06

    Bipolar disorder (BD) and the anxiety disorders are highly comorbid. The present study sought to examine perfectionism and goal attainment values as potential mechanisms of known associations between anxiety, stress and BD symptomatology. Measures of perfectionism and goal attainment values were administered to 269 members of BD pedigrees, alongside measures of anxiety and stress, and BD mood symptoms. Regression analyses were used to determine whether perfectionism and goal attainment values were related to depressive and (hypo)manic symptoms; planned mediation models were then used to test the potential for perfectionism to mediate associations between anxiety/stress and BD symptoms. Self-oriented perfectionism was associated with chronic depressive symptoms; socially-prescribed perfectionism was associated with chronic (hypo)manic symptoms. Self-oriented perfectionism mediated relationships between anxiety/stress and chronic depressive symptoms even after controlling for chronic hypomanic symptoms. Similarly, socially-prescribed perfectionism mediated associations between anxiety/stress and chronic hypomanic symptoms after controlling for chronic depressive symptoms. Goal attainment beliefs were not uniquely associated with chronic depressive or (hypo)manic symptoms. Cognitive styles of perfectionism may explain the co-occurrence of anxiety and stress symptoms and BD symptoms. Psychological interventions for anxiety and stress symptoms in BD might therefore address perfectionism in attempt to reduce depression and (hypo)manic symptoms in addition to appropriate pharmacotherapy.

  6. Three WRKY transcription factors additively repress abscisic acid and gibberellin signaling in aleurone cells.

    PubMed

    Zhang, Liyuan; Gu, Lingkun; Ringler, Patricia; Smith, Stanley; Rushton, Paul J; Shen, Qingxi J

    2015-07-01

    Members of the WRKY transcription factor superfamily are essential for the regulation of many plant pathways. Functional redundancy due to duplications of WRKY transcription factors, however, complicates genetic analysis by allowing single-mutant plants to maintain wild-type phenotypes. Our analyses indicate that three group I WRKY genes, OsWRKY24, -53, and -70, act in a partially redundant manner. All three showed characteristics of typical WRKY transcription factors: each localized to nuclei and yeast one-hybrid assays indicated that they all bind to W-boxes, including those present in their own promoters. Quantitative real time-PCR (qRT-PCR) analyses indicated that the expression levels of the three WRKY genes varied in the different tissues tested. Particle bombardment-mediated transient expression analyses indicated that all three genes repress the GA and ABA signaling in a dosage-dependent manner. Combination of all three WRKY genes showed additive antagonism of ABA and GA signaling. These results suggest that these WRKY proteins function as negative transcriptional regulators of GA and ABA signaling. However, different combinations of these WRKY genes can lead to varied strengths in suppression of their targets. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Idiosyncratic deals and employee outcomes: the mediating roles of social exchange and self-enhancement and the moderating role of individualism.

    PubMed

    Liu, Jun; Lee, Cynthia; Hui, Chun; Kwan, Ho Kwong; Wu, Long-Zeng

    2013-09-01

    The majority of studies on idiosyncratic employment arrangements ("i-deals") are based on social exchange theory. The authors suggest that self-enhancement theory, in addition to social exchange, can be used to explain the effects of i-deals. Using a multisource sample including 230 employees and 102 supervisors from 2 Chinese companies, the authors adopt a 3-wave lagged design to examine the mediating roles of social exchange and self-enhancement and the moderating role of individualism in the relationships between i-deals and employee outcomes, as indicated by proactive behaviors and affective commitment. The results of bootstrapping analyses confirm the mediating effects of social exchange and self-enhancement. In addition, employees with high levels of individualism are more receptive to self-enhancement effects; in contrast, employees with low levels of individualism are more receptive to social exchange effects. PsycINFO Database Record (c) 2013 APA, all rights reserved

  8. [Childhood Traumas and Attachment Style-Associated Depression Symptoms: The Mediator Role of Alexithymia].

    PubMed

    Şenkal, İpek; Işıklı, Sedat

    2015-01-01

    The aim of this study was to investigate the mediator role of alexithymia and its relationship with childhood traumas (sexual abuse, physical abuse, emotional abuse, emotional neglect, physical neglect) and attachment style (anxiety and avoidance dimensions of attachment) associated depression symptoms in adulthood. The sample of this study included 417 undergraduate university students from different departments that studied at Hacettepe University during the 2012-2013 school years with a final analysis done over 369 participants. The Demographic Information Form, Experiences in Close Relationship Inventory-II (ECR-R), Childhood Trauma Questionnaire (CTQ), Toronto Alexithymia Scale (TAS-20), and Beck Depression Inventory (BDI) were administered to the undergraduate students who participated in this study. Mediator analyses were applied to the data. The results revealed that the total score of the Toronto Alexithymia Scale had a partial mediating role in the relationship of childhood traumas (the total score of Childhood Trauma Questionnaire), childhood emotional abuse and emotional neglect with depressive symptom levels in university students. Besides, the total score of the Toronto Alexithymia Scale had a full mediating role in the relationship between childhood physical neglect and depressive symptom levels in adulthood. Additionally, it was found that the total score of the Toronto Alexithymia Scale had a partial mediating role between the anxiety dimension of the attachment and the depressive symptom levels. This study revealed that alexithymia should be considered as a significant variable in the relationship of childhood traumas and attachment patterns with depression symptoms in adulthood.

  9. 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

  10. 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.

  11. [Mediator effect of resilience between burnout and health in nursing staff].

    PubMed

    Arrogante, Óscar

    2014-01-01

    To determine the relationships between 3 burnout dimensions (Emotional Exhaustion, Depersonalization, and Reduced Personal Accomplishment), health (physical and mental health), and resilience, as well as to analyse the mediator role of resilience in relationships between burnout and health in a sample of Nursing staff. A correlational and cross-sectional study with probabilistic sampling was conducted on a sample of 194 Nursing staff of University Hospital of Fuenlabrada (Madrid), and composed of nurses (n=133) and nursing assistants (n=61). MBI-HSS (burnout syndrome), SF-12v1 (physical and mental components of health), 10-Item CD-RISC (resilience), and sociodemographic variables. Correlational analyses showed that mental health was negatively related with 3 burnout dimensions and positively with resilience. Furthermore, physical health was only negatively related with Emotional Exhaustion, and positively with resilience. Mediational analyses revealed that resilience mediated, on one hand, the relationship between Emotional Exhaustion and Depersonalization with mental health (partial mediation) and, on the other hand, the relationship between Reduced Personal Accomplishment and mental health (total mediation). Resilience is not only important to improve the mental health of Nursing staff, but also to buffer and minimize the negative consequences of the occupational stress to which they are at risk, with its most adverse result being signs of burnout. Therefore, resilience training should be promoted to improve nursing clinical practice. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  12. Domain-general mediators of the relation between kindergarten number sense and first-grade mathematics achievement.

    PubMed

    Hassinger-Das, Brenna; Jordan, Nancy C; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

    2014-02-01

    Domain-general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that both attention problems and executive functioning were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance, whereas executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Reduction of dioxin-like toxicity in effluents by additional wastewater treatment and related effects in fish.

    PubMed

    Maier, Diana; Benisek, Martin; Blaha, Ludek; Dondero, Francesco; Giesy, John P; Köhler, Heinz-R; Richter, Doreen; Scheurer, Marco; Triebskorn, Rita

    2016-10-01

    Efficiency of advanced wastewater treatment technologies to reduce micropollutants which mediate dioxin-like toxicity was investigated. Technologies compared included ozonation, powdered activated carbon and granular activated carbon. In addition to chemical analyses in samples of effluents, surface waters, sediments, and fish, (1) dioxin-like potentials were measured in paired samples of effluents, surface waters, and sediments by use of an in vitro biotest (reporter gene assay) and (2) dioxin-like effects were investigated in exposed fish by use of in vivo activity of the mixed-function, monooxygenase enzyme, ethoxyresorufin O-deethylase (EROD) in liver. All advanced technologies studied, based on degradation or adsorption, significantly reduced dioxin-like potentials in samples and resulted in lesser EROD activity in livers of fish. Results of in vitro and in vivo biological responses were not clearly related to quantification of targeted analytes by use of instrumental analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

    Walters, Glenn D

    2014-02-01

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

  15. Does anger regulation mediate the discrimination-mental health link among Mexican-origin adolescents? A longitudinal mediation analysis using multilevel modeling.

    PubMed

    Park, Irene J K; Wang, Lijuan; Williams, David R; Alegría, Margarita

    2017-02-01

    [Correction Notice: An Erratum for this article was reported in Vol 53(2) of Developmental Psychology (see record 2017-04475-001). In the article, there were several typographical errors in the Recruitment and Procedures section. The percentage of mothers who responded to survey items should have been 99.3%. Additionally, the youths surveyed at T2 and T3 should have been n 246. Accordingly, the percentage of youths surveyed in T2 and T3 should have been 91.4% and the percentage of mothers surveyed at T2 and T3 should have been 90.7%. Finally, the youths missing at T2 should have been n 23, and therefore the attrition rate for youth participants should have been 8.6. All versions of this article have been corrected.] Although prior research has consistently documented the association between racial/ethnic discrimination and poor mental health outcomes, the mechanisms that underlie this link are still unclear. The present 3-wave longitudinal study tested the mediating role of anger regulation in the discrimination-mental health link among 269 Mexican-origin adolescents ( M age = 14.1 years, SD = 1.6; 57% girls), 12 to 17 years old. Three competing anger regulation variables were tested as potential mediators: outward anger expression, anger suppression, and anger control. Longitudinal mediation analyses were conducted using multilevel modeling that disaggregated within-person effects from between-person effects. Results indicated that outward anger expression was a significant mediator; anger suppression and anger control were not significant mediators. Within a given individual, greater racial/ethnic discrimination was associated with more frequent outward anger expression. In turn, more frequent outward anger expression was associated with higher levels of anxiety and depression at a given time point. Gender, age, and nativity status were not significant moderators of the hypothesized mediation models. By identifying outward anger expression as an explanatory

  16. Influence of Goal Contents on Exercise Addiction: Analysing the Mediating Effect of Passion for Exercise

    PubMed Central

    Sicilia, Álvaro; Alcaraz-Ibáñez, Manuel; Lirola, María-Jesús; Burgueño, Rafael

    2017-01-01

    Abstract Based on the self-determination theory (Deci and Ryan, 1985, 2000), the purpose of this study was to examine the effects of exercise goal contents on exercise addiction, taking into account the mediating effects of passion for exercise. A total of 384 university students (284 men and 100 women; Mage = 20.31, SD = 3.10) completed a questionnaire that measured exercise frequency and intensity, exercise goal contents (e.g. intrinsic: social affiliation, health management, skill development; extrinsic: image and social recognition), passion for exercise (e.g. harmonious and obsessive), and exercise addiction. After controlling the exercise frequency and intensity effects, results showed that goal contents did not directly predict exercise addiction. However, mediation analysis showed that goal contents predicted addiction through passion for exercise. These results support a motivational sequence in which extrinsic versus intrinsic goals influence exercise addiction because such goals are positively associated with obsessive passion for exercise and negatively associated with harmonious passion. PMID:29134055

  17. Influence of Goal Contents on Exercise Addiction: Analysing the Mediating Effect of Passion for Exercise.

    PubMed

    Sicilia, Álvaro; Alcaraz-Ibáñez, Manuel; Lirola, María-Jesús; Burgueño, Rafael

    2017-10-01

    Based on the self-determination theory (Deci and Ryan, 1985, 2000), the purpose of this study was to examine the effects of exercise goal contents on exercise addiction, taking into account the mediating effects of passion for exercise. A total of 384 university students (284 men and 100 women; M age = 20.31, SD = 3.10) completed a questionnaire that measured exercise frequency and intensity, exercise goal contents (e.g. intrinsic: social affiliation, health management, skill development; extrinsic: image and social recognition), passion for exercise (e.g. harmonious and obsessive), and exercise addiction. After controlling the exercise frequency and intensity effects, results showed that goal contents did not directly predict exercise addiction. However, mediation analysis showed that goal contents predicted addiction through passion for exercise. These results support a motivational sequence in which extrinsic versus intrinsic goals influence exercise addiction because such goals are positively associated with obsessive passion for exercise and negatively associated with harmonious passion.

  18. 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

  19. Specificity in mediated pathways by anxiety symptoms linking adolescent stress profiles to depressive symptoms: Results of a moderated mediation approach.

    PubMed

    Anyan, Frederick; Bizumic, Boris; Hjemdal, Odin

    2018-03-01

    We investigated the specificity in mediated pathways that separately link specific stress dimensions through anxiety to depressive symptoms and the protective utility of resilience. Thus, this study goes beyond lumping together potential mediating and moderating processes that can explain the relations between stress and (symptoms of) psychopathology and the buffering effect of resilience. Ghanaian adolescents between 13 and 17 years (female = 285; male = 244) completed the Adolescent Stress Questionnaire (ASQ), Spielberger State Anxiety Inventory (STAI), Short Mood Feeling Questionnaire (SMFQ) and the Resilience Scale for Adolescents (READ). Independent samples t-test, multivariate analysis of covariance with follow-up tests and moderated mediation analyses were performed. Evidences were found for specificity in the associations between dimensions of adolescent stressors and depressive symptoms independent of transient anxiety. Transient anxiety partly accounted for the indirect effects of eight stress dimensions on depressive symptoms. Except stress of school attendance and school/leisure conflict, resilience moderated the indirect effects of specific stress dimensions on depressive symptoms. Results suggested differences in how Ghanaian adolescents view the various stress dimensions, and mediated pathways associated with anxiety and depressive symptoms. Use of cross-sectional data does not show causal process and temporal changes over time. Findings support and clarify the specificity in the interrelations and mediated pathways among dimensions of adolescent stress, transient anxiety, and depressive symptoms. Conditional process analyses shows that resilience does not only buffer direct, but also indirect psychological adversities. Interventions for good mental health may focus on low resilience subgroups in specific stress dimensions while minimizing transient anxiety. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Risk factors and mediating pathways of loneliness and social support in community-dwelling older adults.

    PubMed

    Schnittger, Rebecca I B; Wherton, Joseph; Prendergast, David; Lawlor, Brian A

    2012-01-01

    To develop biopsychosocial models of loneliness and social support thereby identifying their key risk factors in an Irish sample of community-dwelling older adults. Additionally, to investigate indirect effects of social support on loneliness through mediating risk factors. A total of 579 participants (400 females; 179 males) were given a battery of biopsychosocial assessments with the primary measures being the De Jong Gierveld Loneliness Scale and the Lubben Social Network Scale along with a broad range of secondary measures. Bivariate correlation analyses identified items to be included in separate psychosocial, cognitive, biological and demographic multiple regression analyses. The resulting model items were then entered into further multiple regression analyses to obtain overall models. Following this, bootstrapping mediation analyses was conducted to examine indirect effects of social support on the subtypes (emotional and social) of loneliness. The overall model for (1) emotional loneliness included depression, neuroticism, perceived stress, living alone and accommodation type, (2) social loneliness included neuroticism, perceived stress, animal naming and number of grandchildren and (3) social support included extraversion, executive functioning (Trail Making Test B-time), history of falls, age and whether the participant drives or not. Social support influenced emotional loneliness predominantly through indirect means, while its effect on social loneliness was more direct. These results characterise the biopsychosocial risk factors of emotional loneliness, social loneliness and social support and identify key pathways by which social support influences emotional and social loneliness. These findings highlight issues with the potential for consideration in the development of targeted interventions.

  1. Planning Abilities in Bilingual and Monolingual Children: Role of Verbal Mediation.

    PubMed

    Gangopadhyay, Ishanti; McDonald, Margarethe; Ellis Weismer, Susan; Kaushanskaya, Margarita

    2018-01-01

    We examined the role of verbal mediation in planning performance of English-Spanish-speaking bilingual children and monolingual English-speaking children, between the ages of 9 and 12 years. To measure planning, children were administered the Tower of London (ToL) task. In a dual-task paradigm, children completed ToL problems under three conditions: with no secondary task (baseline), with articulatory suppression, and with non-verbal motor suppression. Analyses revealed generally shorter planning times for bilinguals than monolinguals but both groups performed similarly on number of moves and execution times. Additionally, bilingual children were more efficient at planning throughout the duration of the task while monolingual children showed significant gains with more practice. Children's planning times under articulatory suppression were significantly shorter than under motor suppression as well as the baseline condition, and there was no difference in planning times between monolingual and bilingual children during articulatory suppression. These results demonstrate that bilingualism influences performance on a complex EF measure like planning, and that these effects are not related to verbal mediation.

  2. Planning Abilities in Bilingual and Monolingual Children: Role of Verbal Mediation

    PubMed Central

    Gangopadhyay, Ishanti; McDonald, Margarethe; Ellis Weismer, Susan; Kaushanskaya, Margarita

    2018-01-01

    We examined the role of verbal mediation in planning performance of English–Spanish-speaking bilingual children and monolingual English-speaking children, between the ages of 9 and 12 years. To measure planning, children were administered the Tower of London (ToL) task. In a dual-task paradigm, children completed ToL problems under three conditions: with no secondary task (baseline), with articulatory suppression, and with non-verbal motor suppression. Analyses revealed generally shorter planning times for bilinguals than monolinguals but both groups performed similarly on number of moves and execution times. Additionally, bilingual children were more efficient at planning throughout the duration of the task while monolingual children showed significant gains with more practice. Children’s planning times under articulatory suppression were significantly shorter than under motor suppression as well as the baseline condition, and there was no difference in planning times between monolingual and bilingual children during articulatory suppression. These results demonstrate that bilingualism influences performance on a complex EF measure like planning, and that these effects are not related to verbal mediation. PMID:29593620

  3. Approaches to Dispute Resolution in Additional Support Needs in Scotland

    ERIC Educational Resources Information Center

    Riddell, Sheila; Weedon, Elisabet

    2009-01-01

    The Education (Additional Support for Learning) (Scotland) Act 2004 aimed, among other things, to increase parents' rights in relation to the education of their children. In addition to the creation of the Additional Supports Needs Tribunals for Scotland, parents were given new rights to challenge local authority decisions through mediation and…

  4. How job demands affect absenteeism? The mediating role of work-family conflict and exhaustion.

    PubMed

    Vignoli, Michela; Guglielmi, Dina; Bonfiglioli, Roberta; Violante, Francesco Saverio

    2016-01-01

    To investigate how psychosocial factors (such as job demands and work-family conflict) produce absenteeism in the workplace, using the health impairment process of the job demands-resources model. According to this model, job demands lead to burnout (often measured with the emotional exhaustion component), which in turn could lead to outcomes (such as absenteeism). Work-family conflict (WFC) was also studied, because of contradictory results collected in the existing literature on absenteeism in the workplace, regarding the role of WFC in causing absenteeism. Data were collected on 245 workers using both subjective (questionnaire on psychological risk factors and work-related health) and objective data (sickness leave frequency records). To test the hypothesis that job demands and WFC contribute to absenteeism in the workplace, a subsequent mediation analysis was used, which analysed both (a) the subsequent mediation of WFC and emotional exhaustion and (b) the separate roles played by the mediators proposed (WFC and emotional exhaustion). Job demands affect absenteeism through the subsequent mediation of WFC and emotional exhaustion. In addition, emotional exhaustion mediates the relationship between job demands and absenteeism, while WFC does not. In conclusion, subsequent mediation highlights the role of emotional exhaustion in causing absenteeism; in fact, when emotional exhaustion is included in the analysis, job demands are associated with higher levels of absenteeism. The results of this study suggest that without the concurrent contribution of emotional exhaustion, WFC does not influence absenteeism in the workplace. Our findings are useful for organizations that aim to reduce absenteeism.

  5. The effect of corporal punishment and verbal abuse on delinquency: mediating mechanisms.

    PubMed

    Evans, Sara Z; Simons, Leslie Gordon; Simons, Ronald L

    2012-08-01

    While the link between parenting and delinquency is well established, there is less consensus among scholars with regards to the processes that account for this link. The current study had two objectives. The first was to disentangle the effects of African American parents' use of corporal punishment and verbal abuse on the conduct problems of their preteen children. The second was to investigate the mechanisms that explain this relationship, such as having low self-control or a hostile view of relationships, whereby these harsh parenting practices increase a youth's involvement in problem behavior. Further, we are interested in specifically addressing how these mechanisms may operate differently for males versus females. Analyses utilized structural equation modeling and longitudinal data spanning approximately 2.5 years from a sample of 704 (54.2 % female) African American children ages 10-12. The results indicated that verbal abuse was a more important predictor of conduct problems than corporal punishment. Additionally, we found that the mechanisms that mediated the impact of verbal abuse and corporal punishment on conduct problems varied by gender. For males, most of the effect of verbal abuse was mediated by low self-control, whereas anger/frustration was the primary mediator for females. Implications of these results and directions for future study are also discussed.

  6. Morphine-induced antinociception in the rat: supra-additive interactions with imidazoline I₂ receptor ligands.

    PubMed

    Li, Jun-Xu; Zhang, Yanan; Winter, Jerrold C

    2011-11-01

    Pain remains a significant clinical challenge and currently available analgesics are not adequate to meet clinical needs. Emerging evidence suggests the role of imidazoline I(2) receptors in pain modulation primarily from studies of the non-selective imidazoline receptor ligand, agmatine. However, little is known of the generality of the effect to selective I(2) receptor ligands. This study examined the antinociceptive effects of two selective I(2) receptor ligands 2-BFI and BU224 (>2000-fold selectivity for I(2) receptors over α(2) adrenoceptors) in a hypertonic (5%) saline-induced writhing test and analyzed their interaction with morphine using a dose-addition analysis. Morphine, 2-BFI and BU224 but not agmatine produced a dose-dependent antinociceptive effect. Both composite additive curve analyses and isobolographical plots revealed a supra-additive interaction between morphine and 2-BFI or BU224, whereas the interaction between 2-BFI and BU224 was additive. The antinociceptive effect of 2-BFI and BU224 was attenuated by the I(2) receptor antagonist/α(2) adrenoceptor antagonist idazoxan but not by the selective α(2) adrenoceptor antagonist yohimbine, suggesting an I(2) receptor-mediated mechanism. Agmatine enhanced the antinociceptive effect of morphine, 2-BFI and BU224 and the enhancement was prevented by yohimbine, suggesting that the effect was mediated by α(2) adrenoceptors. Taken together, these data represent the first report that selective I(2) receptor ligands have substantial antinociceptive activity and produce antinociceptive synergy with opioids in a rat model of acute pain. These data suggest that drugs acting on imidazoline I(2) receptors may be useful either alone or in combination with opioids for the treatment of pain. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Spacelab Charcoal Analyses

    NASA Technical Reports Server (NTRS)

    Slivon, L. E.; Hernon-Kenny, L. A.; Katona, V. R.; Dejarme, L. E.

    1995-01-01

    This report describes analytical methods and results obtained from chemical analysis of 31 charcoal samples in five sets. Each set was obtained from a single scrubber used to filter ambient air on board a Spacelab mission. Analysis of the charcoal samples was conducted by thermal desorption followed by gas chromatography/mass spectrometry (GC/MS). All samples were analyzed using identical methods. The method used for these analyses was able to detect compounds independent of their polarity or volatility. In addition to the charcoal samples, analyses of three Environmental Control and Life Support System (ECLSS) water samples were conducted specifically for trimethylamine.

  8. Ticagrelor and Rosuvastatin Have Additive Cardioprotective Effects via Adenosine.

    PubMed

    Birnbaum, Yochai; Birnbaum, Gilad D; Birnbaum, Itamar; Nylander, Sven; Ye, Yumei

    2016-12-01

    Ticagrelor inhibits the equilibrative-nucleoside-transporter-1 and thereby, adenosine cell re-uptake. Ticagrelor limits infarct size (IS) in non-diabetic rats and the effect is adenosine-dependent. Statins, via ecto-5'-nucleotidase activation, also increase adenosine levels and limit IS. Ticagrelor and rosuvastatin have additive effects on myocardial adenosine levels, and therefore, on IS and post-reperfusion activation of the NLRP3-inflammasome. Diabetic ZDF rats received via oral gavage; water (control), ticagrelor (150 mg/kg/d), prasugrel (7.5 mg/kg/d), rosuvastatin (5 mg/kg/d), ticagrelor + rosuvastatin and prasugrel + rosuvastatin for 3d. On day 4, rats underwent 30 min coronary artery occlusion and 24 h of reperfusion. Two additional groups received, ticagrelor + rosuvastatin or water in combination with CGS15943 (CGS, an adenosine receptor antagonist, 10 mg/kg i.p. 1 h before ischemia). Both ticagrelor and rosuvastatin increased myocardial adenosine levels with an additive effect of the combination whereas prasugrel had no effect. Similarly, both ticagrelor and rosuvastatin significantly reduced IS with an additive effect of the combination whereas prasugrel had no effect. The effect on IS was adenosine dependent as CGS15943 reversed the effect of ticagrelor + rosuvastatin. The ischemia-reperfusion injury increased myocardial mRNA levels of NLRP3, ASC, IL-1β and IL-6. Ticagrelor and rosuvastatin, but not prasugrel, significantly decreased these pro-inflammatory mediators with a trend to an additive effect of the combination. The combination also increased the levels of anti-inflammatory 15-epilipoxin A 4 . Ticagrelor and rosuvastatin when given in combination have an additive effect on local myocardial adenosine levels in the setting of ischemia reperfusion. This translates into an additive cardioprotective effect mediated by adenosine-induced effects including downregulation of pro- but upregulation of anti-inflammatory mediators.

  9. Effect of Caring for an Abusive Parent on Mental Health: The Mediating Role of Self-Esteem.

    PubMed

    Kong, Jooyoung

    2018-05-08

    This study examines a sample of filial caregivers to investigate whether and how a history of childhood abuse is associated with caregivers' mental health (i.e., depressed affect, psychological well-being, and life satisfaction). This study also investigates the mediational role of self-esteem between caring for an abusive parent and the mental health outcomes. Using the 2004-2006 National Survey of Midlife Development in the United States, data from 219 filial caregivers were analyzed. A series of ordinary least squares (OLS) regression and mediational analyses were conducted to estimate the direct and indirect effects of providing care to an abusive parent on negative affect, psychological well-being, and levels of life satisfaction. Key results showed that providing care to an abusive parent was associated with greater depressed affect and lower levels of life satisfaction. In addition, self-esteem served as a significant mediator: providing care to an abusive parent was associated with lower self-esteem, which was, in turn, ultimately associated with greater depressed affect, diminished psychological well-being, and lower levels of life satisfaction. Filial caregivers with a history of childhood abuse should be acknowledged as a high-risk group of caregivers so that they can gain attention and support for targeted interventions. Additionally, evidence-based intervention programs (e.g., improving self-esteem issues) should be designed and implemented to address this group's unique challenges and concerns.

  10. Metacognitions as Mediators of Gender Identity-related Anxiety.

    PubMed

    Fernie, Bruce A; Wright, Talen; Caselli, Gabriele; Nikčević, Ana V; Spada, Marcantonio M

    2017-01-01

    Research has found that the prevalence of psychological distress is substantially higher in transgender compared to cisgender populations. This study explored the role of metacognitions as mediators of anxiety in a sample comprising of cisgender and transgender individuals. One-hundred and twenty-five individuals (19 trans-male; 24 male; 25 trans-female; 57 female) completed a series of measures that assessed metacognitions, worry and anxiety. Correlation analyses were used to identify potential mediators of the relationship between gender identity and anxiety. A mediation model indicated that beliefs about thoughts concerning uncontrollability and danger entirely mediated the relationship between gender identity and anxiety (b = 2.00, bias corrected and accelerated confidence interval [0.68, 3.49]). Metacognitions play an important role in anxiety in transgender individuals. -Metacognitions were found to mediate anxiety in transgender and cisgender individuals. -The exploration of metacognitions in transgender individuals experiencing psychological distress may have clinical utility. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Mediation, identification, and plausibility: an illustration using children's mental health services.

    PubMed

    Foster, E Michael

    2014-10-01

    Analyses of mediation are important for understanding the effects of mental health services and treatments. The most common approach is to add potential mediators as regressors and to estimate the direct and indirect effects of the treatment of interest. This practice makes the strong assumption that the mediator itself does not suffer from unobserved confounding--that it is as if randomly assigned. In many instances, this assumption seems rather implausible. The objective of this article is to describe the identification problem that represents the fundamental challenge of causal inference. It outlines how mediation complicates identification and considers several identification strategies. The goal of this article is not to propose a new method for handling mediation or to identify a best method for doing so. The latter, in fact, is impossible. The contribution of the article is to illustrate how one can think about possible approaches to mediation in the context of a specific empirical study. Using data from a large evaluation of a demonstration project in children's mental health services (n = 763), the article illustrates identification strategies. That demonstration improved service delivery in several ways but primarily by offering services "intermediate" between inpatient and outpatient. These analyses focus on the impact of these intermediate services on 6-month improvement in a behavior checklist commonly used to measure psychopathology and competence among children and youths. The results highlight how different identification strategies produce different answers to key questions. These alternative findings have to be assessed in light of substantive knowledge of the program involved. The analyses generally support the notion that children and youths treated at the demonstration site who received intermediate services benefited from them. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  12. 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.

  13. 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

  14. Indium-mediated asymmetric Barbier-type propargylations: additions to aldehydes and ketones and mechanistic investigation of the organoindium reagents.

    PubMed

    Haddad, Terra D; Hirayama, Lacie C; Buckley, Jannise J; Singaram, Bakthan

    2012-01-20

    We report a simple, efficient, and general method for the indium-mediated enantioselective propargylation of aromatic and aliphatic aldehydes under Barbier-type conditions in a one-pot synthesis affording the corresponding chiral alcohol products in very good yield (up to 90%) and enantiomeric excess (up to 95%). The extension of this methodology to ketones demonstrated the need for electrophilic ketones more reactive than acetophenone as the reaction would not proceed with just acetophenone. Using the Lewis acid indium triflate [In(OTf)(3)] induced regioselective formation of the corresponding homoallenic alcohol product from acetophenone. However, this methodology demonstrated excellent chemoselectivity in formation of only the corresponding secondary homopropargylic alcohol product in the presence of a ketone functionality. Investigation of the organoindium intermediates under our reaction conditions shows the formation of allenylindium species, and we suggest that these species contain an indium(III) center. In addition, we have observed the presence of a shiny, indium(0) nugget throughout the reaction, irrespective of the stoichiometry, indicating disproportionation of indium halide byproduct formed during the reaction.

  15. Estimating and testing mediation and moderation in within-subject designs.

    PubMed

    Judd, C M; Kenny, D A; McClelland, G H

    2001-06-01

    Analyses designed to detect mediation and moderation of treatment effects are increasingly prevalent in research in psychology. The mediation question concerns the processes that produce a treatment effect. The moderation question concerns factors that affect the magnitude of that effect. Although analytic procedures have been reasonably well worked out in the case in which the treatment varies between participants, no systematic procedures for examining mediation and moderation have been developed in the case in which the treatment varies within participants. The authors present an analytic approach to these issues using ordinary least squares estimation.

  16. The relationship between alexithymia and maladaptive perfectionism in eating disorders: a mediation moderation analysis methodology.

    PubMed

    Marsero, S; Ruggiero, G M; Scarone, S; Bertelli, S; Sassaroli, S

    2011-09-01

    This work aimed to explore the relationship between alexithymia and maladaptive perfectionism in the psychological process leading to eating disorders (ED). Forty-nine individuals with ED and 49 controls completed the Concern over Mistakes subscale of the Frost Multidimensional Perfectionism Scale, the Perfectionism subscale of the Eating Disorders Inventory, the total score of the Toronto Alexithymia Scale, and the Drive for Thinness, Bulimia, and Body Dissatisfaction subscales of the Eating Disorders Inventory. We tested a model in which alexythimia is the independent variable and perfectionism is the possible mediator or moderator. Analyses confirmed the assumed model. In addition, it emerged that perfectionism played a mediating or moderating role when measured by different instruments. This result suggested that different instruments measured subtly different aspects of the same construct. Results could suggest that alexithymia is a predisposing factor for perfectionism, which in turn may lead to the development of eating disorders.

  17. The Impact of Homophobia and HIV Stigma on HIV Testing Uptake among Chinese Men Who Have Sex with Men: A Mediation Analysis

    PubMed Central

    Wei, Chongyi; Cheung, Doug H.; Yan, Hongjing; Li, Jianjun; Shi, Ling-en; Raymond, H. Fisher

    2015-01-01

    BACKGROUND Gay and HIV-related stigma and discrimination are major barriers to accessing HIV prevention services among MSM worldwide. We aimed to identify modifiable factors that mediate the relationships between gay and HIV-related stigma and discrimination and HIV testing uptake among Chinese MSM. METHODS We conducted a cross-sectional survey study of 523 HIV-uninfected or unknown MSM in Jiangsu Province, China between November 2013 and January 2014. Multivariable analyses were conducted to examine the associations among experienced homophobia, HIV stigma, and recent HIV testing. Causal mediation parametric analyses were conducted to assess whether depression and social norms mediated hypothesized associations. RESULTS Stronger subjective norms toward testing was associated with higher odds of recent HIV testing (AOR: 1.10, 95% CI: 1.01, 1.21) while increasing levels of depression and HIV stigma were both associated with lower odds of recent testing (AOR: 0.96, 95% CI: 0.92, 0.99; and AOR: 0.91, 95% CI: 0.84, 0.99, respectively). There was an indirect relationship (natural indirect effect) of experienced homophobia on recent testing (ORNIE: 0.96, 95% CI: 0.93, 0.98) mediated (35.0%) through depression. Furthermore, there was an indirect relationship of HIV stigma on recent testing (ORNIE: 0.98, 95% CI: 0.95, 0.99) mediated (19.2%) through subjective norms. CONCLUSIONS Depression and social norms are important mediators of HIV testing uptake among stigmatized Chinese MSM. Therefore, in addition to advocacy efforts and policies that address social-level stigma and discrimination, HIV prevention programs should also address mental health issues and incorporate community-based approaches to changing social norms toward HIV testing. PMID:26334742

  18. Do nurses who work in a fair organization sleep and perform better and why? Testing potential psychosocial mediators of organizational justice.

    PubMed

    Hietapakka, Laura; Elovainio, Marko; Heponiemi, Tarja; Presseau, Justin; Eccles, Martin; Aalto, Anna-Mari; Pekkarinen, Laura; Kuokkanen, Liisa; Sinervo, Timo

    2013-10-01

    We examined whether organizational justice is associated with sleep quality and performance in a population-based sample of 1,729 Finnish registered nurses working full time. In addition, we tested psychological mechanisms mediating the potential association. The results of multivariate linear regression analyses showed higher organizational justice to be associated with fewer sleeping problems (β values range from -.20 to -.11) and higher self-reported performance (β values range from .05 to .35). Furthermore, psychological distress (related to the psychological stress model) and job involvement (related to the psychosocial resource model) mediated the association between organizational justice and sleep. Sleeping problems partly mediated the association between organizational justice and performance. Psychological distress explained 51% to 83% and job involvement explained 10% to 15% of the total effects of justice variables on sleeping problems. The findings provide support for the psychological stress model and offer practical implications for reducing nurses' sleeping problems.

  19. Anterior insular cortex mediates bodily sensibility and social anxiety

    PubMed Central

    Shibata, Midori; Moriguchi, Yoshiya; Umeda, Satoshi

    2013-01-01

    Studies in psychiatry and cognitive neuroscience have reported an important relationship between individual interoceptive accuracy and anxiety level. This indicates that greater attention to one’s bodily state may contribute to the development of intense negative emotions and anxiety disorders. We hypothesized that reactivity in the anterior insular cortex underlies the intensity of interoceptive awareness and anxiety. To elucidate this triadic mechanism, we conducted functional magnetic resonance imaging (fMRI) and mediation analyses to examine the relationship between emotional disposition and activation in the anterior insular cortex while participants evaluated their own emotional and bodily states. Our results indicated that right anterior insular activation was positively correlated with individual levels of social anxiety and neuroticism and negatively correlated with agreeableness and extraversion. The results of the mediation analyses revealed that activity in the right anterior insula mediated the activity of neural correlates of interoceptive sensibility and social fear. Our findings suggest that attention to interoceptive sensation affects personality traits through how we feel emotion subjectively in various situations. PMID:22977199

  20. 10 CFR 436.24 - Uncertainty analyses.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Procedures for Life Cycle Cost Analyses § 436.24 Uncertainty analyses. If particular items of cost data or... impact of uncertainty on the calculation of life cycle cost effectiveness or the assignment of rank order... and probabilistic analysis. If additional analysis casts substantial doubt on the life cycle cost...

  1. 10 CFR 436.24 - Uncertainty analyses.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Procedures for Life Cycle Cost Analyses § 436.24 Uncertainty analyses. If particular items of cost data or... impact of uncertainty on the calculation of life cycle cost effectiveness or the assignment of rank order... and probabilistic analysis. If additional analysis casts substantial doubt on the life cycle cost...

  2. 10 CFR 436.24 - Uncertainty analyses.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Procedures for Life Cycle Cost Analyses § 436.24 Uncertainty analyses. If particular items of cost data or... impact of uncertainty on the calculation of life cycle cost effectiveness or the assignment of rank order... and probabilistic analysis. If additional analysis casts substantial doubt on the life cycle cost...

  3. 10 CFR 436.24 - Uncertainty analyses.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Procedures for Life Cycle Cost Analyses § 436.24 Uncertainty analyses. If particular items of cost data or... impact of uncertainty on the calculation of life cycle cost effectiveness or the assignment of rank order... and probabilistic analysis. If additional analysis casts substantial doubt on the life cycle cost...

  4. Self-Esteem and Problematic Drinking in China: A Mediated Model.

    PubMed

    Zhai, Hui; Yang, Yanjie; Sui, Hong; Wang, Wenbo; Chen, Lu; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Wang, Lin; Zhu, Xiongzhao; Yang, Jiarun

    2015-01-01

    Although self-esteem is related to problematic drinking, the mechanisms by which it affects drinking remain unclear. The purpose of this study was to determine whether coping mechanisms mediate the relationship between self-esteem and problematic drinking among Chinese men and women with alcohol use disorders and to recommend appropriate interventions for drinking problems. A cross-sectional survey was conducted in Harbin, Heilongjiang Province, China. A sample of 5,689 community residents was screened, and 517 male and 172 female problematic drinkers were chosen to participate in this study. A self-esteem scale, a coping questionnaire and an alcohol use disorder identification test were completed in order to assess participants' self-esteem, coping mechanisms and alcohol use disorders, respectively. Participants' socio-demographic data were also gathered at this stage. The resulting data were examined via descriptive statistics, correlations and bootstrap analyses. Lower self-esteem levels were related to problematic drinking, and there were no gender differences in the relationship between self-esteem and problematic drinking. A relationship between low self-esteem and negative coping was observed only in men. Negative coping thus mediated the relationship between self-esteem and problematic drinking among men, but this was not the case for women. Positive coping did not mediate the relationship between self-esteem and problematic drinking among the participants, regardless of gender. Self-esteem and coping strategies are correlated among problematic drinkers. In addition, there are gender differences in the manners in which negative coping mediates the relationship between self-esteem and problematic drinking. Problematic drinking interventions directed at males should simultaneously address low self-esteem and negative coping.

  5. Self-Esteem and Problematic Drinking in China: A Mediated Model

    PubMed Central

    Zhai, Hui; Yang, Yanjie; Sui, Hong; Wang, Wenbo; Chen, Lu; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Wang, Lin; Zhu, Xiongzhao; Yang, Jiarun

    2015-01-01

    Background Although self-esteem is related to problematic drinking, the mechanisms by which it affects drinking remain unclear. The purpose of this study was to determine whether coping mechanisms mediate the relationship between self-esteem and problematic drinking among Chinese men and women with alcohol use disorders and to recommend appropriate interventions for drinking problems. Methods A cross-sectional survey was conducted in Harbin, Heilongjiang Province, China. A sample of 5,689 community residents was screened, and 517 male and 172 female problematic drinkers were chosen to participate in this study. A self-esteem scale, a coping questionnaire and an alcohol use disorder identification test were completed in order to assess participants’ self-esteem, coping mechanisms and alcohol use disorders, respectively. Participants’ socio-demographic data were also gathered at this stage. The resulting data were examined via descriptive statistics, correlations and bootstrap analyses. Results Lower self-esteem levels were related to problematic drinking, and there were no gender differences in the relationship between self-esteem and problematic drinking. A relationship between low self-esteem and negative coping was observed only in men. Negative coping thus mediated the relationship between self-esteem and problematic drinking among men, but this was not the case for women. Positive coping did not mediate the relationship between self-esteem and problematic drinking among the participants, regardless of gender. Conclusions Self-esteem and coping strategies are correlated among problematic drinkers. In addition, there are gender differences in the manners in which negative coping mediates the relationship between self-esteem and problematic drinking. Problematic drinking interventions directed at males should simultaneously address low self-esteem and negative coping. PMID:26451595

  6. Attitudes toward healthy eating: a mediator of the educational level-diet relationship.

    PubMed

    Lê, J; Dallongeville, J; Wagner, A; Arveiler, D; Haas, B; Cottel, D; Simon, C; Dauchet, L

    2013-08-01

    A higher educational level is associated with a healthier diet. The goal of this study was to establish whether this association is mediated by attitudes toward healthy eating. The cross-sectional MONA LISA-NUT study was performed in 2005-2007 on adults aged 35-64 years from northern and north-eastern France. Diet quality was assessed on the basis of a 3-day food record and a validated score based on French national dietary guidelines. Specific questions investigated attitudes toward healthy eating. Multivariate analyses were used to quantify the proportion of the educational level-diet relationship that was mediated by attitudes toward healthy eating. Among the 1631 subjects, favourable attitudes toward healthy eating were associated with both higher educational level and diet quality. In the mediation analysis, 'organic food consumption' explained 14% (95% confidence interval (8;24)) of the educational level-diet relationship and 'attention paid to health when buying food' explained 9% (3;16). In contrast, 'attention to food choice', 'searching for information about food' and 'perceived role of eating' were not mediators of the association between educational level and diet. In a multivariate model, the attitude items together accounted for 25% (10;45) of the relationship. The mediation was more pronounced in women than in men (37% (15;54) vs 16% (1;27), respectively) and was significant for consumption of fruits and vegetables (23% (13;37)), whole-grain food (32% (15;58)) and seafood (22% (9;55)). Our results suggest that poor attitudes toward healthy eating in groups with low socioeconomic status constitute an additional factor (along with cost constraints) in the choice of unhealthy foods.

  7. Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus

    PubMed Central

    Serhan, C N; Chiang, N

    2008-01-01

    Complete resolution of an acute inflammatory response and its return to homeostasis are essential for healthy tissues. Here, we overview ongoing efforts to characterize cellular and molecular mechanisms that govern the resolution of self-limited inflammation. Systematic temporal analyses of evolving inflammatory exudates using mediator lipidomics-informatics, proteomics, and cellular trafficking with murine resolving exudates demonstrate novel endogenous pathways of local-acting mediators that share both anti-inflammatory and pro-resolving properties. In murine systems, resolving-exudate leukocytes switch their phenotype to actively generate new families of mediators from major omega-3 fatty acids EPA and DHA termed resolvins and protectins. Recent advances on their biosynthesis and actions are reviewed with a focus on the E-series resolvins (RvE1, RvE2), D series resolvins (RvD1, RvD2) and the protectins including neuroprotectin D1/protectin D1 (NPD1/PD1) as well as their aspirin-triggered epimeric forms. Members of each new family demonstrate potent stereo-specific actions, joining the lipoxins as endogenous local signals that govern resolution and endogenous anti-inflammation mechanisms. In addition to their origins and roles in resolution biology in the immune system, recent findings indicate that these new mediator families also display potent protective actions in lung, kidney, and eye as well as enhance microbial clearance. Thus, these endogenous agonists of resolution pathways constitute a novel genus of chemical mediators that possess pro-resolving, anti-inflammatory, and antifibrotic as well as host-directed antimicrobial actions. These may be useful in the design of new therapeutics and treatments for diseases with the underlying trait of uncontrolled inflammation and redox organ stress. PMID:17965751

  8. The need for cognition mediates and moderates the association between depressive symptoms and impaired effortful control.

    PubMed

    Nishiguchi, Yuki; Takano, Keisuke; Tanno, Yoshihiko

    2016-07-30

    Previous studies have shown a negative correlation between effortful control (EC) and depressive symptoms. EC is defined as the efficiency of executive attention, which may be reduced by the attentional impairment associated with depression. However, the mechanism underlying this correlation is still unclear. We investigated the relationship between EC and depressive symptoms with the hypothesis that cognitive motivation, or need for cognition (NfC), is a possible mediator of this relationship. Participants were 178 Japanese university students. Each completed the Zung Self-Rating Depression Scale, Effortful Control Scale, and Need for Cognition Scale at baseline and follow-up assessments. Supporting our hypothesis, mediation analyses revealed a significant indirect effect of depressive symptoms on EC that was mediated by NfC. In addition, our data demonstrated a direct effect of depressive symptoms on EC. Longitudinal analysis indicated that an increase in depression and a decrease in NfC occurred synchronously, while NfC predicted an increase in EC over time. Depressive symptoms may decrease executive functioning and effortful control both directly and indirectly, the latter effect being mediated by motivation. These findings imply that a motivational deficit may partially explain the decreased EC found in people suffering from depression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Conserved Regulators of Nucleolar Size Revealed by Global Phenotypic Analyses

    PubMed Central

    Neumüller, Ralph A.; Gross, Thomas; Samsonova, Anastasia A.; Vinayagam, Arunachalam; Buckner, Michael; Founk, Karen; Hu, Yanhui; Sharifpoor, Sara; Rosebrock, Adam P.; Andrews, Brenda; Winston, Fred; Perrimon, Norbert

    2014-01-01

    Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I–mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I–mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry–based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules. PMID:23962978

  10. 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.

  11. 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

  12. Passion, Trait Self-Control, and Wellbeing: Comparing Two Mediation Models Predicting Wellbeing

    PubMed Central

    Briki, Walid

    2017-01-01

    Research has found that passion and trait self-control represented key determinants of wellbeing. Yet, no study to date has attempted to investigate the mediating influences of trait self-control and passion for accounting for the relationships between passion, trait self-control, and wellbeing (dependent variable). Using different frameworks, such as the dualistic model of passion and the neo-socioanalytic theory, the present study proposed two mediation models, considering either trait self-control (model 1) or passion (model 2) as the mediating variable. Five hundred nine volunteers from the United States (326 females and 183 males; Mage = 31.74, SDage = 11.05, from 18 to 70 years old), who reported being passionate about a specific activity (e.g., fishing, swimming, blogging; Mpassion = 5.94, SDpassion = 0.89), answered questionnaires assessing harmonious and obsessive passion, trait self-control, and wellbeing (measured through hedonic and eudaimonic wellbeing scales). Preliminary analyses revealed that both models were significant (model 1: absolute GoF = 0.366, relative GoF = 0.971, outer model GoF = 0.997, inner model GoF = 0.973, R2 = 18.300%, p < 0.001; model 2: absolute GoF = 0.298; relative GoF = 0.980; outer model GoF = 0.997; inner model GoF = 0.982; R2 = 12.111%, p < 0.001). Correlational analyses revealed positive relationships between harmonious passion, trait self-control, and wellbeing, and no relationships of obsessive passion with trait self-control and wellbeing. Mediation analyses revealed that trait self-control significantly mediated the relationship between harmonious passion and wellbeing (i.e., partial mediation, VAF = 33.136%). Harmonious passion appeared to significantly mediate the positive effect of trait self-control on wellbeing; however, the size of the mediating effect indicated that (almost) no mediation would take place (i.e., VAF = 11.144%). The present study is the first to examine the relationships between passion, trait

  13. Passion, Trait Self-Control, and Wellbeing: Comparing Two Mediation Models Predicting Wellbeing.

    PubMed

    Briki, Walid

    2017-01-01

    Research has found that passion and trait self-control represented key determinants of wellbeing. Yet, no study to date has attempted to investigate the mediating influences of trait self-control and passion for accounting for the relationships between passion, trait self-control, and wellbeing (dependent variable). Using different frameworks, such as the dualistic model of passion and the neo-socioanalytic theory, the present study proposed two mediation models, considering either trait self-control (model 1) or passion (model 2) as the mediating variable. Five hundred nine volunteers from the United States (326 females and 183 males; M age = 31.74, SD age = 11.05, from 18 to 70 years old), who reported being passionate about a specific activity (e.g., fishing, swimming, blogging; M passion = 5.94, SD passion = 0.89), answered questionnaires assessing harmonious and obsessive passion, trait self-control, and wellbeing (measured through hedonic and eudaimonic wellbeing scales). Preliminary analyses revealed that both models were significant ( model 1: absolute GoF = 0.366, relative GoF = 0.971, outer model GoF = 0.997, inner model GoF = 0.973, R 2 = 18.300%, p < 0.001; model 2: absolute GoF = 0.298; relative GoF = 0.980; outer model GoF = 0.997; inner model GoF = 0.982; R 2 = 12.111%, p < 0.001). Correlational analyses revealed positive relationships between harmonious passion, trait self-control, and wellbeing, and no relationships of obsessive passion with trait self-control and wellbeing. Mediation analyses revealed that trait self-control significantly mediated the relationship between harmonious passion and wellbeing (i.e., partial mediation, VAF = 33.136%). Harmonious passion appeared to significantly mediate the positive effect of trait self-control on wellbeing; however, the size of the mediating effect indicated that (almost) no mediation would take place (i.e., VAF = 11.144%). The present study is the first to examine the relationships between passion

  14. 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.

  15. Keep Up the Good Work! Age-Moderated Mediation Model on Intention to Retire

    PubMed Central

    Dordoni, Paola; Van der Heijden, Beatrice; Peters, Pascale; Kraus-Hoogeveen, Sascha; Argentero, Piergiorgio

    2017-01-01

    In European nations, the aging of the workforce is a major issue which is increasingly addressed both in national and organizational policies in order to sustain older workers' employability and to encourage longer working lives. Particularly older workers' employability can be viewed an important issue as this has the potential to motivate them for their work and change their intention to retire. Based on lifespan development theories and Van der Heijden's ‘employability enhancement model’, this paper develops and tests an age-moderated mediation model (which refers to the processes that we want to test in this model), linking older workers' (55 years old and over) perceptions of job support for learning (job-related factor) and perceptions of negative age stereotypes on productivity (organizational factor), on the one hand, and their intention to retire, on the other hand, via their participation in employability enhancing activities, being the mediator in our model. A total of 2,082 workers aged 55 years and above were included in the analyses. Results revealed that the two proposed relationships between the predictors and intention to retire were mediated by participation in employability enhancing activities, reflecting two mechanisms through which work context affects intention to retire (namely ‘a gain spiral and a loss spiral’). Multi-Group SEM analyses, distinguishing between two age groups (55–60 and 61–65 years old), revealed different paths for the two distinguished groups of older workers. Employability mediated the relationship between perceptions of job support for learning and intention to retire in both age groups, whereas it only mediated the relationship between perceptions of negative age stereotypes and intention to retire in the 55–60 group. From our empirical study, we may conclude that employability is an important factor in the light of older workers' intention to retire. In order to motivate this category of workers to

  16. Keep Up the Good Work! Age-Moderated Mediation Model on Intention to Retire.

    PubMed

    Dordoni, Paola; Van der Heijden, Beatrice; Peters, Pascale; Kraus-Hoogeveen, Sascha; Argentero, Piergiorgio

    2017-01-01

    In European nations, the aging of the workforce is a major issue which is increasingly addressed both in national and organizational policies in order to sustain older workers' employability and to encourage longer working lives. Particularly older workers' employability can be viewed an important issue as this has the potential to motivate them for their work and change their intention to retire. Based on lifespan development theories and Van der Heijden's 'employability enhancement model', this paper develops and tests an age-moderated mediation model (which refers to the processes that we want to test in this model), linking older workers' (55 years old and over) perceptions of job support for learning (job-related factor) and perceptions of negative age stereotypes on productivity (organizational factor), on the one hand, and their intention to retire, on the other hand, via their participation in employability enhancing activities, being the mediator in our model. A total of 2,082 workers aged 55 years and above were included in the analyses. Results revealed that the two proposed relationships between the predictors and intention to retire were mediated by participation in employability enhancing activities, reflecting two mechanisms through which work context affects intention to retire (namely 'a gain spiral and a loss spiral'). Multi-Group SEM analyses, distinguishing between two age groups (55-60 and 61-65 years old), revealed different paths for the two distinguished groups of older workers. Employability mediated the relationship between perceptions of job support for learning and intention to retire in both age groups, whereas it only mediated the relationship between perceptions of negative age stereotypes and intention to retire in the 55-60 group. From our empirical study, we may conclude that employability is an important factor in the light of older workers' intention to retire. In order to motivate this category of workers to participate in

  17. The Mediator Complex and Lipid Metabolism.

    PubMed

    Zhang, Yi; Xiaoli; Zhao, Xiaoping; Yang, Fajun

    2013-03-01

    The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understanding on the biological functions of Mediator remains incomplete, research in the past decade has revealed an important role of Mediator in regulating lipid metabolism. Such function of Mediator is dependent on specific transcription factors, including peroxisome proliferator-activated receptor-gamma (PPARγ) and sterol regulatory element-binding proteins (SREBPs), which represent the master regulators of lipid metabolism. The medical significance of these findings is apparent, as aberrant lipid metabolism is intimately linked to major human diseases, such as type 2 diabetes and cardiovascular disease. Here, we briefly review the functions and molecular mechanisms of Mediator in regulation of lipid metabolism.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Nonindependence and sensitivity analyses in ecological and evolutionary meta-analyses.

    PubMed

    Noble, Daniel W A; Lagisz, Malgorzata; O'dea, Rose E; Nakagawa, Shinichi

    2017-05-01

    Meta-analysis is an important tool for synthesizing research on a variety of topics in ecology and evolution, including molecular ecology, but can be susceptible to nonindependence. Nonindependence can affect two major interrelated components of a meta-analysis: (i) the calculation of effect size statistics and (ii) the estimation of overall meta-analytic estimates and their uncertainty. While some solutions to nonindependence exist at the statistical analysis stages, there is little advice on what to do when complex analyses are not possible, or when studies with nonindependent experimental designs exist in the data. Here we argue that exploring the effects of procedural decisions in a meta-analysis (e.g. inclusion of different quality data, choice of effect size) and statistical assumptions (e.g. assuming no phylogenetic covariance) using sensitivity analyses are extremely important in assessing the impact of nonindependence. Sensitivity analyses can provide greater confidence in results and highlight important limitations of empirical work (e.g. impact of study design on overall effects). Despite their importance, sensitivity analyses are seldom applied to problems of nonindependence. To encourage better practice for dealing with nonindependence in meta-analytic studies, we present accessible examples demonstrating the impact that ignoring nonindependence can have on meta-analytic estimates. We also provide pragmatic solutions for dealing with nonindependent study designs, and for analysing dependent effect sizes. Additionally, we offer reporting guidelines that will facilitate disclosure of the sources of nonindependence in meta-analyses, leading to greater transparency and more robust conclusions. © 2017 John Wiley & Sons Ltd.

  3. 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,…

  4. Coping Mediates the Association Between Marital Instability and Depression, but Not Marital Satisfaction and Depression

    PubMed Central

    Fink, Brandi C.; Shapiro, Alyson F.

    2014-01-01

    The association between marital discord and depression is well established. Marital discord is hypothesized to be a stressful life event that would evoke one’s efforts to cope with it. In an effort to further understand the nature of this association, the current study investigated coping as a mediating variable between marital dissatisfaction and depression and between marital instability and depression. Both marital dissatisfaction and instability, reflecting orthogonal dimensions of marital discord, were included in the model examined to elucidate a more complete picture of marital functioning. Structural Equation Modeling analyses revealed that coping mediated the association between marital instability and depression, but not marital dissatisfaction and depression, suggesting that coping traditionally considered adaptive for individuals in the context of controllable stressors may not be adaptive in the context of couple relationship instability. The findings also have implications for interventions focusing on decreasing maladaptive coping strategies in couples presenting for marital therapy or depression in addition to efforts directed at improving marital quality. PMID:25032063

  5. The Impact of Homophobia and HIV Stigma on HIV Testing Uptake Among Chinese Men Who Have Sex With Men: a Mediation Analysis.

    PubMed

    Wei, Chongyi; Cheung, Doug H; Yan, Hongjing; Li, Jianjun; Shi, Ling-en; Raymond, Henry F

    2016-01-01

    Gay and HIV-related stigma and discrimination are major barriers to accessing HIV prevention services among Men Who Have Sex with Men (MSM) worldwide. We aimed to identify modifiable factors that mediate the relationships between gay and HIV-related stigma and discrimination and HIV testing uptake among Chinese MSM. We conducted a cross-sectional survey study of 523 HIV-uninfected or unknown HIV status MSM in Jiangsu Province, China between November 2013 and January 2014. Multivariable analyses were conducted to examine the associations among experienced homophobia, HIV stigma, and recent HIV testing. Causal mediation parametric analyses were conducted to assess whether depression and social norms mediated hypothesized associations. Stronger subjective norms toward testing was associated with higher odds of recent HIV testing (adjusted odds ratio [AOR]: 1.10, 95% confidence interval [CI]: 1.01 to 1.21), whereas increasing levels of depression and HIV stigma were both associated with lower odds of recent testing (AOR: 0.96, 95% CI: 0.92 to 0.99; and AOR: 0.91, 95% CI: 0.84 to 0.99, respectively). There was an indirect relationship (natural indirect effect [NIE]) of experienced homophobia on recent testing (ORNIE: 0.96, 95% CI: 0.93 to 0.98) mediated (35.0%) through depression. Furthermore, there was an indirect relationship of HIV stigma on recent testing (ORNIE: 0.98, 95% CI: 0.95 to 0.99) mediated (19.2%) through subjective norms. Depression and social norms are important mediators of HIV testing uptake among stigmatized Chinese MSM. Therefore, in addition to advocacy efforts and policies that address social-level stigma and discrimination, HIV prevention programs should also address mental health issues and incorporate community-based approaches to changing social norms toward HIV testing.

  6. Burnout and health among critical care professionals: The mediational role of resilience.

    PubMed

    Arrogante, Oscar; Aparicio-Zaldivar, Eva

    2017-10-01

    To analyse the mediational role of resilience in relationships between burnout and health in critical care professionals; to determine relationships among resilience level, three burnout dimensions, and physical/mental health; and to establish demographic differences in psychological variables evaluated. Cross-sectional study. A total of 52 critical care professionals, mainly nurses, were recruited from an intensive care unit of Madrid (Spain). All participants were assessed with the questionnaires 10-item Connor-Davidson Resilience Scale, Maslach Burnout Inventory-Human Services Survey, and Short Form-12 Health Survey. No demographic differences were found. Three burnout dimensions were negatively associated with mental health and resilience. Mediational analyses revealed resilience mediated 1) the relationships between emotional exhaustion and depersonalisation with mental health (partial mediations) and 2) the relationship between personal accomplishment and mental health (total mediation). Resilience minimises and buffers the impact of negative outcomes of workplace stress on mental health of critical care professionals. As a result, resilience prevents the occurrence of burnout syndrome. Resilience improves not only their mental health, but also their ability to practice effectively. It is therefore imperative to develop resilience programs for critical care nurses in nursing schools, universities and health centres. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. 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.

  8. Trauma exposure and the mediating role of posttraumatic stress on somatic symptoms in civilian war victims.

    PubMed

    Morina, Naser; Schnyder, Ulrich; Klaghofer, Richard; Müller, Julia; Martin-Soelch, Chantal

    2018-04-10

    It has been well documented that the exposure to war has a negative effect on the psychological health of civilian. However, little is known on the impact of war exposure on the physical health of the civilian population. In addition, the link between trauma exposure and somatic symptoms remain poorly understood. This cross-sectional study examined levels of somatic symptoms in the aftermath of war, and the mediating role of posttraumatic stress symptoms in the relationship between trauma exposure and somatic symptoms. Civilian war survivors (N = 142) from Kosovo were assessed for potentially traumatic events, posttraumatic stress symptoms, and somatic symptoms. Data were analyzed using mediation analyses. Posttraumatic stress disorder (PTSD) symptoms were categorized based on King's four factor model (Psychol Assessment. 10: 90-96, 1998). Participants reported on average more than 5 types of traumatic exposure. The cut-off indicative for PTSD was exceeded by 26.1% of participants. Symptom levels of PTSD were associated with somatic symptoms. The relationship between trauma exposure and somatic symptoms was partly mediated by the active avoidance and hyperarousal symptom clusters of PTSD. Active avoidance and hyperarousal symptoms seem to play a key role in traumatized people suffering from somatic symptoms.

  9. [Mediation in schools].

    PubMed

    Mickley, Angela

    2006-01-01

    In this article the guiding questions concern the objectives and effectiveness of introducing mediation into an existing school culture of dominance, competition and selection. In addition the necessity will be shown of combining conflict resolution with organisational development and the introduction of a consensual ethics and behaviour code to attain sustainable results in creating a constructive and healthy school environment. Given scarce resources and little time the decisive role of artistic methods will be looked at in providing young people with flexible methods of expressing and negotiating their interests in a changing environment of values and power structures. Some aspects of the development of nonviolent communication, conflict resolution and mediation methods in schools in Germany will be focused on with special emphasis on the type of intervention used and its long term sustainable effects.

  10. Direct and Indirect Associations Between Social Anxiety and Nicotine Dependence and Cessation Problems: Multiple Mediator Analyses

    PubMed Central

    2014-01-01

    Introduction: Little empirical work has evaluated why socially anxious smokers are especially vulnerable to more severe nicotine dependence and cessation failure. Presumably, these smokers rely on cigarettes to help them manage their chronically elevated negative affect elicited by a wide array of social contexts. Methods: The current study examined the direct and indirect effects of social anxiety cross-sectionally in regard to a range of smoking processes among 466 treatment-seeking smokers. Negative affect and negative affect reduction motives were examined as mediators of the relations of social anxiety with nicotine dependence and cessation problems. Results: Social anxiety was directly and robustly associated with perceived barriers to smoking cessation and problems experienced during past quit attempts. Social anxiety was also associated with greater nicotine dependence and smoking inflexibility indirectly through negative affect and negative affect smoking motives. Negative affect and smoking to reduce negative affect mediated these relations. Conclusions: These findings document the important role of negative affect and negative affect reduction motives in the relationships of social anxiety with nicotine dependence and cessation problems. PMID:24492021

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

    PubMed

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

    2014-06-01

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

  12. Importance of Mediator complex in the regulation and integration of diverse signaling pathways in plants.

    PubMed

    Samanta, Subhasis; Thakur, Jitendra K

    2015-01-01

    Basic transcriptional machinery in eukaryotes is assisted by a number of cofactors, which either increase or decrease the rate of transcription. Mediator complex is one such cofactor, and recently has drawn a lot of interest because of its integrative power to converge different signaling pathways before channeling the transcription instructions to the RNA polymerase II machinery. Like yeast and metazoans, plants do possess the Mediator complex across the kingdom, and its isolation and subunit analyses have been reported from the model plant, Arabidopsis. Genetic, and molecular analyses have unraveled important regulatory roles of Mediator subunits at every stage of plant life cycle starting from flowering to embryo and organ development, to even size determination. It also contributes immensely to the survival of plants against different environmental vagaries by the timely activation of its resistance mechanisms. Here, we have provided an overview of plant Mediator complex starting from its discovery to regulation of stoichiometry of its subunits. We have also reviewed involvement of different Mediator subunits in different processes and pathways including defense response pathways evoked by diverse biotic cues. Wherever possible, attempts have been made to provide mechanistic insight of Mediator's involvement in these processes.

  13. Importance of Mediator complex in the regulation and integration of diverse signaling pathways in plants

    PubMed Central

    Samanta, Subhasis; Thakur, Jitendra K.

    2015-01-01

    Basic transcriptional machinery in eukaryotes is assisted by a number of cofactors, which either increase or decrease the rate of transcription. Mediator complex is one such cofactor, and recently has drawn a lot of interest because of its integrative power to converge different signaling pathways before channeling the transcription instructions to the RNA polymerase II machinery. Like yeast and metazoans, plants do possess the Mediator complex across the kingdom, and its isolation and subunit analyses have been reported from the model plant, Arabidopsis. Genetic, and molecular analyses have unraveled important regulatory roles of Mediator subunits at every stage of plant life cycle starting from flowering to embryo and organ development, to even size determination. It also contributes immensely to the survival of plants against different environmental vagaries by the timely activation of its resistance mechanisms. Here, we have provided an overview of plant Mediator complex starting from its discovery to regulation of stoichiometry of its subunits. We have also reviewed involvement of different Mediator subunits in different processes and pathways including defense response pathways evoked by diverse biotic cues. Wherever possible, attempts have been made to provide mechanistic insight of Mediator's involvement in these processes. PMID:26442070

  14. 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.

  15. Distress and Diabetes Treatment Adherence: A Mediating Role for Perceived Control

    PubMed Central

    Gonzalez, Jeffrey S.; Shreck, Erica; Psaros, Christina; Safren, Steven A.

    2014-01-01

    Objective To understand independent pathways linking emotional distress, medication adherence and glycemic control in adults with type 2 diabetes, as well as the potential mediating effects of perceived control over illness and self-efficacy. Methods Adults with type 2 diabetes (N = 142) were recruited for an intervention study evaluating cognitive behavioral therapy for adherence and depression. Depressive symptom severity was assessed via semi-structured interview. Validated self-reports assessed diabetes-related distress, perceived control over diabetes (perceived control), self-efficacy for diabetes self-management and medication adherence. Glycemic control was evaluated by hemoglobin A1c (A1C). Only baseline data were included in correlational and linear regression analyses. Results Perceived control was an important mediator for both medication adherence and A1C outcomes. Specifically, regression analyses demonstrated that diabetes distress, but not depression severity, was significantly related to medication adherence and A1C. Self-efficacy and perceived control were also independently associated with medication adherence and A1C. Mediation analyses demonstrated a significant indirect effect for diabetes distress and medication adherence, through perceived control and self-efficacy. The relationship between distress and A1C was accounted for by an indirect effect through perceived control. Conclusion Results demonstrate that diabetes-related emotional distress is associated with poorer treatment adherence and glycemic control among adults with type 2 diabetes; these relationships were partially mediated through perceived control over diabetes. Perceptions of one’s personal ability to influence diabetes may be important in understanding the pathway between emotional distress and poor diabetes treatment outcomes. PMID:25110840

  16. Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

    PubMed Central

    He, Liang; Kernogitski, Yelena; Kulminskaya, Irina; Loika, Yury; Arbeev, Konstantin G.; Loiko, Elena; Bagley, Olivia; Duan, Matt; Yashkin, Arseniy; Ukraintseva, Svetlana V.; Kovtun, Mikhail; Yashin, Anatoliy I.; Kulminski, Alexander M.

    2016-01-01

    Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan. Here, we performed pleiotropic meta-analyses of genetic variants using five NIH-funded datasets by integrating univariate summary statistics for age-related diseases and endophenotypes. We investigated three groups of traits: (1) endophenotypes such as blood glucose, blood pressure, lipids, hematocrit, and body mass index, (2) time-to-event outcomes such as the age-at-onset of diabetes mellitus (DM), cancer, cardiovascular diseases (CVDs) and neurodegenerative diseases (NDs), and (3) both combined. In addition to replicating previous findings, we identify seven novel genome-wide significant loci (< 5e-08), out of which five are low-frequency variants. Specifically, from Group 2, we find rs7632505 on 3q21.1 in SEMA5B, rs460976 on 21q22.3 (1 kb from TMPRSS2) and rs12420422 on 11q24.1 predominantly associated with a variety of CVDs, rs4905014 in ITPK1 associated with stroke and heart failure, rs7081476 on 10p12.1 in ANKRD26 associated with multiple diseases including DM, CVDs, and NDs. From Group 3, we find rs8082812 on 18p11.22 and rs1869717 on 4q31.3 associated with both endophenotypes and CVDs. Our follow-up analyses show that rs7632505, rs4905014, and rs8082812 have age-dependent effects on coronary heart disease or stroke. Functional annotation suggests that most of these SNPs are within regulatory regions or DNase clusters and in linkage disequilibrium with expression quantitative trait loci, implying their potential regulatory influence on

  17. 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.

  18. Streetscape greenery and health: stress, social cohesion and physical activity as mediators.

    PubMed

    de Vries, Sjerp; van Dillen, Sonja M E; Groenewegen, Peter P; Spreeuwenberg, Peter

    2013-10-01

    Several studies have shown a positive relationship between local greenspace availability and residents' health, which may offer opportunities for health improvement. This study focuses on three mechanisms through which greenery might exert its positive effect on health: stress reduction, stimulating physical activity and facilitating social cohesion. Knowledge on mechanisms helps to identify which type of greenspace is most effective in generating health benefits. In eighty neighbourhoods in four Dutch cities data on quantity and quality of streetscape greenery were collected by observations. Data on self-reported health and proposed mediators were obtained for adults by mail questionnaires (N = 1641). Multilevel regression analyses, controlling for socio-demographic characteristics, revealed that both quantity and quality of streetscape greenery were related to perceived general health, acute health-related complaints, and mental health. Relationships were generally stronger for quality than for quantity. Stress and social cohesion were the strongest mediators. Total physical activity was not a mediator. Physical activity that could be undertaken in the public space (green activity) was, but less so than stress and social cohesion. With all three mediators included in the analysis, complete mediation could statistically be proven in five out of six cases. In these analyses the contribution of green activity was often not significant. The possibility that the effect of green activity is mediated by stress and social cohesion, rather than that it has a direct health effect, is discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. 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.

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

    PubMed

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

    2017-11-01

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

  1. "Does anger regulation mediate the discrimination-mental health link among Mexican-origin adolescents? A longitudinal mediation analysis using multilevel modeling": Correction to Park et al. (2016).

    PubMed

    2017-02-01

    Reports an error in "Does Anger Regulation Mediate the Discrimination-Mental Health Link Among Mexican-Origin Adolescents? A Longitudinal Mediation Analysis Using Multilevel Modeling" by Irene J. K. Park, Lijuan Wang, David R. Williams and Margarita Alegría ( Developmental Psychology , Advanced Online Publication, Nov 28, 2016, np). In the article, there were several typographical errors in the Recruitment and Procedures section. The percentage of mothers who responded to survey items should have been 99.3%. Additionally, the youths surveyed at T2 and T3 should have been n=246 . Accordingly, the percentage of youths surveyed in T2 and T3 should have been 91.4% and the percentage of mothers surveyed at T2 and T3 should have been 90.7%. Finally, the youths missing at T2 should have been n= 23, and therefore the attrition rate for youth participants should have been 8.6. All versions of this article have been corrected. (The following abstract of the original article appeared in record 2016-57671-001.) Although prior research has consistently documented the association between racial/ethnic discrimination and poor mental health outcomes, the mechanisms that underlie this link are still unclear. The present 3-wave longitudinal study tested the mediating role of anger regulation in the discrimination-mental health link among 269 Mexican-origin adolescents ( M age = 14.1 years, SD = 1.6; 57% girls), 12 to 17 years old. Three competing anger regulation variables were tested as potential mediators: outward anger expression, anger suppression, and anger control. Longitudinal mediation analyses were conducted using multilevel modeling that disaggregated within-person effects from between-person effects. Results indicated that outward anger expression was a significant mediator; anger suppression and anger control were not significant mediators. Within a given individual, greater racial/ethnic discrimination was associated with more frequent outward anger expression. In turn

  2. Mediation analysis of relationships between chronic inflammation and quality of life in older adults.

    PubMed

    Nowakowski, Alexandra C H; Graves, Katelyn Y; Sumerau, J E

    2016-03-22

    This article summarizes exploratory analyses of relationships between chronic inflammation, its physical consequences, and quality of life (QoL). It summarizes key findings from preliminary analyses, and contextualizes these results with extant sociomedical literature to recommend directions for future research. Cross-sectional data from the National Social Life, Health, and Aging Project (NSHAP) were used to explore these relationships. Inflammation was assessed via the biomarker C-reactive protein (CRP). We examined associations between CRP levels and two different domains of QoL: happiness with life in general and happiness with intimate relationships. We used ordinal logistic regression with companion OLS models and Sobel-Goodman tests to assess potential mediation, and also conducted a variety of sensitivity analyses. Findings suggest that mediation pathways for the overall association between chronic inflammation and QoL may differ markedly across particular outcome constructs. Specifically, it shows mediation potential for the clinical sequelae of chronic inflammation in frameworks using happiness as an outcome measure, but not in those using relationship satisfaction. Disability appears to mediate the effect of inflammation by 27 %; chronic pain appears to exert a similar mediation effect of 21 %. Pain and disability linked to chronic inflammation appear to play a small but significant mediating role in the overall reduction in QoL observed among older adults with biomarker evidence of chronic inflammation. We note that these patterns are best framed as dynamic elements of a complex causal fabric, rather than powerful determinants that override other factors contributing to QoL. Hypotheses for further exploration using longitudinal data from the NSHAP are thus offered, pending availability of Wave III data in future years.

  3. 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.

  4. An Examination of Mediators of the Transfer of Cognitive Speed of Processing Training to Everyday Functional Performance

    PubMed Central

    Edwards, Jerri D.; Ruva, Christine L.; O’Brien, Jennifer L.; Haley, Christine B.; Lister, Jennifer J.

    2013-01-01

    The purpose of these analyses was to examine mediators of the transfer of cognitive speed of processing training to improved everyday functional performance (Edwards, Wadley, Vance, Roenker, & Ball, 2005). Cognitive speed of processing and visual attention (as measured by the Useful Field of View Test; UFOV) were examined as mediators of training transfer. Secondary data analyses were conducted from the Staying Keen in Later Life (SKILL) study, a randomized cohort study including 126 community dwelling adults 63 to 87 years of age. In the SKILL study, participants were randomized to an active control group or cognitive speed of processing training (SOPT), a non-verbal, computerized intervention involving perceptual practice of visual tasks. Prior analyses found significant effects of training as measured by the UFOV and Timed Instrumental Activities of Daily Living (TIADL) Tests. Results from the present analyses indicate that speed of processing for a divided attention task significantly mediated the effect of SOPT on everyday performance (e.g., TIADL) in a multiple mediation model accounting for 91% of the variance. These findings suggest that everyday functional improvements found from SOPT are directly attributable to improved UFOV performance, speed of processing for divided attention in particular. Targeting divided attention in cognitive interventions may be important to positively affect everyday functioning among older adults. PMID:23066808

  5. Mediator-regulated transcription through the +1 nucleosome.

    PubMed

    Nock, Adam; Ascano, Janice M; Barrero, Maria J; Malik, Sohail

    2012-12-28

    Many genes are regulated at the level of a Pol II that is recruited to a nucleosome-free region upstream of the +1 nucleosome. How the Mediator coactivator complex, which functions at multiple steps, affects transcription through the promoter proximal region, including this nucleosome, remains largely unaddressed. We have established a fully defined in vitro assay system to delineate mechanisms for Pol II transit across the +1 nucleosome. Our results reveal cooperative functions of multiple cofactors, particularly of Mediator and elongation factor SII, in transcribing into this nucleosome. This is achieved, in part, through an unusual activity of SII that alters the intrinsic catalytic properties of promoter-proximal Pol II and, in concert with the Mediator, leads to enhancement in transcription of nucleosomal DNA. Our data provide additional mechanistic bases for Mediator function after recruitment of Pol II and, potentially, for regulation of genes controlled via nucleosome-mediated promoter-proximal pausing. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Regulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation.

    PubMed

    Gaughan, Luke; Logan, Ian R; Neal, David E; Robson, Craig N

    2005-01-01

    The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors and plays a critical role in regulating the expression of genes involved in androgen-dependent and -independent tumour formation. Regulation of the AR is achieved by alternate binding of either histone acetyltransferase (HAT)-containing co-activator proteins, or histone deacetylase 1 (HDAC1). Factors that control AR stability may also constitute an important regulatory mechanism, a notion that has been confirmed with the finding that the AR is a direct target for Mdm2-mediated ubiquitylation and proteolysis. Using chromatin immunoprecipitation (ChIP) and re-ChIP analyses, we show that Mdm2 associates with AR and HDAC1 at the active androgen-responsive PSA promoter in LNCaP prostate cancer cells. Furthermore, we demonstrate that Mdm2-mediated modification of AR and HDAC1 catalyses protein destabilization and attenuates AR sactivity, suggesting that ubiquitylation of the AR and HDAC1 may constitute an additional mechanism for regulating AR function. We also show that HDAC1 and Mdm2 function co-operatively to reduce AR-mediated transcription that is attenuated by the HAT activity of the AR co-activator Tip60, suggesting interplay between acetylation status and receptor ubiquitylation in AR regulation. In all, our data indicates a novel role for Mdm2 in regulating components of the AR transcriptosome.

  7. An improved Agrobacterium-mediated transformation of recalcitrant indica rice (Oryza sativa L.) cultivars.

    PubMed

    Shri, Manju; Rai, Arti; Verma, Pankaj Kumar; Misra, Prashant; Dubey, Sonali; Kumar, Smita; Verma, Sikha; Gautam, Neelam; Tripathi, Rudra Deo; Trivedi, Prabodh Kumar; Chakrabarty, Debasis

    2013-04-01

    Agrobacterium-mediated transformation of indica rice varieties has been quite difficult as these are recalcitrant to in vitro responses. In the present study, we established a high-efficiency Agrobacterium tumefaciens-mediated transformation system of rice (Oryza sativa L. ssp. indica) cv. IR-64, Lalat, and IET-4786. Agrobacterium strain EHA-101 harboring binary vector pIG121-Hm, containing a gene encoding for β-glucuronidase (GUS) and hygromycin resistance, was used in the transformation experiments. Manipulation of different concentrations of acetosyringone, days of co-culture period, bacterial suspension of different optical densities (ODs), and the concentrations of L-cysteine in liquid followed by solid co-culture medium was done for establishing the protocol. Among the different co-culture periods, 5 days of co-culture with bacterial cells (OD600 nm = 0.5-0.8) promoted the highest frequency of transformation (83.04 %) in medium containing L-cysteine (400 mg l(-1)). Putative transformed plants were analyzed for the presence of a transgene through genomic PCR and GUS histochemical analyses. Our results also suggest that different cultural conditions and the addition of L-cysteine in the co-culture medium improve the Agrobacterium-mediated transformation frequencies from an average of 12.82 % to 33.33 % in different indica rice cultivars.

  8. 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

  9. Concanavalin A-mediated polyclonal helper assay of normal thymocytes and its use for the analysis of ontogeny.

    PubMed

    Kina, T; Nishikawa, S; Amagai, T; Katsura, Y

    1987-01-01

    A concanavalin A (Con A)-mediated polyclonal helper assay system was established by using the thymus cells or splenic T cells as a source of helper T cells. When splenic B cells were cocultured with thymus cells or splenic Lyt-2- T cells in the presence of an optimal dose of Con A, B Cells were polyclonally activated and differentiated into immunoglobulin-secreting cells. This Con A-mediated helper activity was completely inhibited by the addition of alpha-methyl-D-mannoside and could not be substituted by culture supernatant of Con A-stimulated thymocytes or splenic T cells. Almost all the activity of the thymus cells was carried by peanut agglutinin low binding population. Genetic restriction between T and B cells was not observed in this helper function. In ontogeny, Con A-mediated helper activity in the thymus was first detected at a few days after birth and reached the adult level at about 1 week of age. The polyclonal helper assay system developed in the present study provides a sensitive system to analyse the helper function of thymus cells and also to delineate the early phase of the differentiation of helper T cell population.

  10. Reaping the benefits of meaningful work: The mediating versus moderating role of work engagement.

    PubMed

    Johnson, Matthew J; Jiang, Lixin

    2017-08-01

    This study examined whether meaningful work may improve one's quality of life outside of the workplace (i.e., work-to-life enrichment). More importantly, we proposed and tested competing hypotheses regarding the role of work engagement in the relationship between meaningful work and work-to-life enrichment. Specifically, we investigated whether work engagement served as a mediator of this relationship, as suggested by the job demands-resources model, or instead a moderator, as suggested by conservation of resources theory. Two-wave survey data were collected from 194 respondents recruited via Amazon Mechanical Turk. Analyses showed that meaningful work was positively related to work-to-life enrichment over time (i.e., 3 months later). Additionally, work engagement mediated but did not moderate the relationship between meaningful work at Time 1 and work-to-life enrichment at Time 2. We suggest that organizations foster a sense of meaningfulness in employees to facilitate engagement and in turn enrich employees' lives beyond the workplace. Therefore, not only organizations, but individuals as well may reap the benefits of meaningful work. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Does Anger Regulation Mediate the Discrimination-Mental Health Link among Mexican-Origin Adolescents? A Longitudinal Mediation Analysis Using Multilevel Modeling

    PubMed Central

    Park, Irene J. K.; Wang, Lijuan; Williams, David R.; Alegría, Margarita

    2016-01-01

    Although prior research has consistently documented the association between racial/ethnic discrimination and poor mental health outcomes, the mechanisms that underlie this link are still unclear. The present three-wave longitudinal study tested the mediating role of anger regulation in the discrimination—mental health link among 269 Mexican-origin adolescents (Mage = 14.1 years, SD = 1.6; 57% girls), 12 – 17 years old. Three competing anger regulation variables were tested as potential mediators: outward anger expression, anger suppression, and anger control. Longitudinal mediation analyses were conducted using multilevel modeling that disaggregated within-person effects from between-person effects. Results indicated that outward anger expression was a significant mediator; anger suppression and anger control were not significant mediators. Within a given individual, greater racial/ethnic discrimination was associated with more frequent outward anger expression. In turn, more frequent outward anger expression was associated with higher levels of anxiety and depression at a given time point. Gender, age, and nativity status were not significant moderators of the hypothesized mediation models. By identifying outward anger expression as an explanatory mechanism in the discrimination-distress link among Latino youths, this study points to a malleable target for prevention and intervention efforts aimed at mitigating the detrimental impact of racism on Latino youths’ mental health during the developmentally critical period of adolescence. PMID:27893238

  12. Adolescent Depression and Negative Life Events, the Mediating Role of Cognitive Emotion Regulation

    PubMed Central

    Stikkelbroek, Yvonne; Bodden, Denise H. M.; Kleinjan, Marloes; Reijnders, Mirjam; van Baar, Anneloes L.

    2016-01-01

    Background Depression during adolescence is a serious mental health problem. Difficulties in regulating evoked emotions after stressful life events are considered to lead to depression. This study examined if depressive symptoms were mediated by various cognitive emotion regulation strategies after stressful life events, more specifically, the loss of a loved one, health threats or relational challenges. Methods We used a sample of 398 adolescents (Mage = 16.94, SD = 2.90), including 52 depressed outpatients, who all reported stressful life event(s). Path analyses in Mplus were used to test mediation, for the whole sample as well as separately for participants scoring high versus low on depression, using multigroup analyses. Results Health threats and relational challenging stressful life events were associated with depressive symptoms, while loss was not. More frequent use of maladaptive strategies was related to more depressive symptoms. More frequent use of adaptive strategies was related to less depressive symptoms. Specific life events were associated with specific emotion regulation strategies. The relationship between challenging, stressful life events and depressive symptoms in the whole group was mediated by maladaptive strategies (self-blame, catastrophizing and rumination). No mediation effect was found for adaptive strategies. Conclusion The association between relational challenging, stressful life events and depressive symptoms was mediated by maladaptive, cognitive emotion regulation strategies. PMID:27571274

  13. Talking about Quitting: Interpersonal Communication as a Mediator of Campaign Effects on Smokers’ Quit Behaviors

    PubMed Central

    Jeong, Michelle; Tan, Andy; Brennan, Emily; Gibson, Laura; Hornik, Robert C.

    2015-01-01

    This study examined the role of interpersonal communication in the context of a mass media anti-smoking campaign. Specifically, it explored whether conversations about campaign ads and/or about quitting mediated campaign exposure effects on two quitting behaviors (sought help to quit and tried to quit smoking completely), as well as the relationship between ad-related and quitting-related conversations. Data were collected prior to the campaign and monthly for 16 months during the campaign through cross-sectional telephone surveys among a sample of 3277 adult Philadelphian smokers. Follow-up interviews were conducted among 877 participants three months after their first survey. Cross-sectional and longitudinal mediation models with bootstrap procedures assessed the indirect effects of campaign exposure on outcomes through conversations, and of conversations about ads on outcomes through conversations about quitting. In addition, lagged regression analyses tested the causal direction of associations between the variables of interest. The results partially support hypotheses that conversations about quitting mediate campaign effects on quitting-related behaviors, and, in line with previous research, that conversations about the ads have indirect effects on quitting-related behaviors by triggering conversations about quitting. These findings demonstrate the importance of considering interpersonal communication as a route of campaign exposure effects when evaluating and designing future public health campaigns. PMID:26147367

  14. Do smoking and fruit and vegetable intake mediate the association between socio-economic status and plasma carotenoids?

    PubMed

    Kvaavik, Elisabeth; Totland, Torunn H; Bastani, Nasser; Kjøllesdal, Marte K; Tell, Grethe S; Andersen, Lene F

    2014-08-01

    The aim was to study whether the association between educational attainment and antioxidant status is mediated by smoking and fruit and vegetable intake. Cross-sectional analyses of the Oslo Youth Study 2006 wave were carried out. Information about education, smoking habits and diet was collected by questionnaire for 261 subjects (142 women and 119 men aged 38-42 years). Blood samples, height and weight measurements were taken by the participants' General Practitioner. Blood were analysed for plasma carotenoids. Linear regression analyses were used to examine whether smoking and fruit and vegetable intake mediate the association between education and plasma carotenoids. Educational level was positively associated with β-cryptoxanthin, α-carotene and lutein/zeaxanthin, but not with total carotenoids, β-carotene or lycopene. Education was negatively associated with smoking and positively associated with fruit and vegetable intake. Smoking was negatively associated with β-cryptoxanthin, and fruit and vegetable intake was positively associated with β-cryptoxanthin (adjusted for educational level). Moreover, cigarette consumption mediated the association between education and β-cryptoxanthin by 37%, while fruit and vegetable intake mediated this association by 18%. The total mediation effect was 55%. Smoking seemed to be more important as a mediator between education and plasma levels of β-cryptoxanthin than the intake of fruit and vegetables, but more studies are needed to establish the relative importance of smoking and diet as mediators of the association between education and antioxidant status. © The Author 2013. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  15. Agrobacterium tumefaciens-mediated transformation of Mucor circinelloides.

    PubMed

    Nyilasi, I; Acs, K; Papp, T; Nagy, E; Vágvölgyi, C

    2005-01-01

    The Agrobacterium tumefaciens-mediated transformation of the zygomycetous fungus Mucor circinelloides is described. A method was also developed for the hygromycin B-based selection of Mucor transformants. Transformation with the hygromycin B phosphotransferase gene of Escherichia coli controlled by the heterologous Aspergillus nidulans trpC promoter resulted in hygromycin B-resistant clones. The presence of the hygromycin resistance gene in the genome of the transformants was verified by polymerase chain reaction and Southern hybridization: the latter analyses revealed integrations in the host genome at different sites in different transformants. The stability of transformants remained questionable during the latter analyses.

  16. E3 Ubiquitin Ligase CHIP and NBR1-Mediated Selective Autophagy Protect Additively against Proteotoxicity in Plant Stress Responses

    PubMed Central

    Qi, Jingxia; Chi, Yingjin; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

    2014-01-01

    Plant stress responses require both protective measures that reduce or restore stress-inflicted damage to cellular structures and mechanisms that efficiently remove damaged and toxic macromolecules, such as misfolded and damaged proteins. We have recently reported that NBR1, the first identified plant autophagy adaptor with a ubiquitin-association domain, plays a critical role in plant stress tolerance by targeting stress-induced, ubiquitinated protein aggregates for degradation by autophagy. Here we report a comprehensive genetic analysis of CHIP, a chaperone-associated E3 ubiquitin ligase from Arabidopsis thaliana implicated in mediating degradation of nonnative proteins by 26S proteasomes. We isolated two chip knockout mutants and discovered that they had the same phenotypes as the nbr1 mutants with compromised tolerance to heat, oxidative and salt stresses and increased accumulation of insoluble proteins under heat stress. To determine their functional interactions, we generated chip nbr1 double mutants and found them to be further compromised in stress tolerance and in clearance of stress-induced protein aggregates, indicating additive roles of CHIP and NBR1. Furthermore, stress-induced protein aggregates were still ubiquitinated in the chip mutants. Through proteomic profiling, we systemically identified heat-induced protein aggregates in the chip and nbr1 single and double mutants. These experiments revealed that highly aggregate-prone proteins such as Rubisco activase and catalases preferentially accumulated in the nbr1 mutant while a number of light-harvesting complex proteins accumulated at high levels in the chip mutant after a relatively short period of heat stress. With extended heat stress, aggregates for a large number of intracellular proteins accumulated in both chip and nbr1 mutants and, to a greater extent, in the chip nbr1 double mutant. Based on these results, we propose that CHIP and NBR1 mediate two distinct but complementary anti

  17. Trends in Mediation Analysis in Nursing Research: Improving Current Practice.

    PubMed

    Hertzog, Melody

    2018-06-01

    The purpose of this study was to describe common approaches used by nursing researchers to test mediation models and evaluate them within the context of current methodological advances. MEDLINE was used to locate studies testing a mediation model and published from 2004 to 2015 in nursing journals. Design (experimental/correlation, cross-sectional/longitudinal, model complexity) and analysis (method, inclusion of test of mediated effect, violations/discussion of assumptions, sample size/power) characteristics were coded for 456 studies. General trends were identified using descriptive statistics. Consistent with findings of reviews in other disciplines, evidence was found that nursing researchers may not be aware of the strong assumptions and serious limitations of their analyses. Suggestions for strengthening the rigor of such studies and an overview of current methods for testing more complex models, including longitudinal mediation processes, are presented.

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

    PubMed

    Negriff, Sonya; Trickett, Penelope K

    2012-11-01

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

  19. Genome-Wide Analyses of Calcium Sensors Reveal Their Involvement in Drought Stress Response and Storage Roots Deterioration after Harvest in Cassava.

    PubMed

    Hu, Wei; Yan, Yan; Tie, Weiwei; Ding, Zehong; Wu, Chunlai; Ding, Xupo; Wang, Wenquan; Xia, Zhiqiang; Guo, Jianchun; Peng, Ming

    2018-04-19

    Calcium (Ca 2+ ) plays a crucial role in plant development and responses to environmental stimuli. Currently, calmodulins (CaMs), calmodulin-like proteins (CMLs), and calcineurin B-like proteins (CBLs), such as Ca 2+ sensors, are not well understood in cassava ( Manihot esculenta Crantz), an important tropical crop. In the present study, 8 CaMs, 48 CMLs, and 9 CBLs were genome-wide identified in cassava, which were divided into two, four, and four groups, respectively, based on evolutionary relationship, protein motif, and gene structure analyses. Transcriptomic analysis revealed the expression diversity of cassava CaMs-CMLs-CBLs in distinct tissues and in response to drought stress in different genotypes. Generally, cassava CaMs-CMLs-CBLs showed different expression profiles between cultivated varieties (Arg7 and SC124) and wild ancestor (W14) after drought treatment. In addition, numerous CaMs-CMLs-CBLs were significantly upregulated at 6 h, 12 h, and 48 h after harvest, suggesting their possible role during storage roots (SR) deterioration. Further interaction network and co-expression analyses suggested that a CBL-mediated interaction network was widely involved in SR deterioration. Taken together, this study provides new insights into CaMs-CMLs-CBLs-mediated drought adaption and SR deterioration at the transcription level in cassava, and identifies some candidates for the genetic improvement of cassava.

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

    ERIC Educational Resources Information Center

    Yang, Hongfei; Li, Juan

    2016-01-01

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

  1. Prospective association of childhood receptive vocabulary and conduct problems with self-reported adolescent delinquency: tests of mediation and moderation in sibling-comparison analyses.

    PubMed

    Lahey, Benjamin B; D'Onofrio, Brian M; Van Hulle, Carol A; Rathouz, Paul J

    2014-11-01

    Associations among receptive vocabulary measured at 4-9 years, mother-reported childhood conduct problems at 4-9 years, and self-reported adolescent delinquency at 14-17 years were assessed using data from a prospective study of the offspring of a large U.S. nationally representative sample of women. A novel quasi-experimental strategy was used to rule out family-level confounding by estimating path-analytic associations within families in a sibling comparison design. This allowed simultaneous tests of the direct and indirect effects of receptive vocabulary and childhood conduct problems, and of their joint moderation, on adolescent delinquency without family-level environmental confounding. The significant association of receptive vocabulary with later adolescent delinquency was indirect, mediated by childhood conduct problems. Furthermore, a significant interaction between receptive vocabulary and childhood conduct problems reflected a steeper slope for the predictive association between childhood conduct problems and adolescent delinquency when receptive vocabulary scores were higher. These findings of significant indirect association were qualitatively identical in both population-level and within-family analyses, suggesting that they are not the result of family-level confounds.

  2. Physical Activity and Bone Health in Schoolchildren: The Mediating Role of Fitness and Body Fat

    PubMed Central

    Torres-Costoso, Ana; Gracia-Marco, Luis; Sánchez-López, Mairena; Notario-Pacheco, Blanca; Arias-Palencia, Natalia; Martínez-Vizcaíno, Vicente

    2015-01-01

    Background The relationship between physical activity (PA) and bone health is well known, although the role of percent body fat (%BF) and fitness as confounders or mediators in this relationship remains uncertain. Objective To examine whether the association between PA and bone mineral content (BMC) is mediated by %BF and cardiorespiratory fitness (CRF). Methods In this cross sectional study, BMC, total %BF (by DXA), vigorous PA (VPA), CRF, age and height were measured in 132 schoolchildren (62 boys, aged 8–11 years). ANCOVA was used to test differences in BMC by %BF, CRF and VPA, controlling for different sets of confounders. Simple mediation analyses and serial multiple mediation analyses were fitted to examine whether the relationship between PA and BMC is mediated by %BF and fitness. Results Children with high %BF had higher total body BMC than their peers after controlling for all sets of confounders. Children with good CRF or VPA had significantly less total body BMC after controlling for age and sex but in children with good CRF this inverse relation disappeared after adjusting by %BF. %BF and CRF both act as a full mediator in the association between VPA and BMC, after inclusion of the potential confounders in the models. Conclusion Fitness and %BF seem to have a mediator role on the relationship between physical activity and bone mass. PMID:25915941

  3. Motivation toward Physical Exercise and Subjective Wellbeing: The Mediating Role of Trait Self-Control

    PubMed Central

    Briki, Walid

    2016-01-01

    Motivation toward physical exercise (MPE) and trait self-control (TSC) were identified as key predictors of subjective wellbeing (SWB). However, there has not been any research designed to examine the mediating role of TSC in the relationship between MPE and SWB. The present study utilizes self-determination theory, control-process theory of self-regulation, and theory of multiple pathways of TSC in order to examine whether TSC mediates the relationships of autonomous MPE (A-MPE), controlled MPE (C-MPE), and impersonal MPE (NO-MPE) with SWB using structural equation modeling (XLSTAT PLS). Three hundred seventeen adult American individuals (Mage = 32.97, SDage = 11.30), who reported to be regular exercisers, voluntarily answered questionnaires assessing MPE, TSC, and SWB. Correlational analyses revealed positive relationships between A-MPE, TSC, and SWB, and negative relationships of C-MPE and NO-MPE with TSC and SWB. Mediation analyses revealed that TSC mediated the relationships of A-MPE (partial mediation) and C-MPE (full mediation) with SWB, but did not mediate the relationship between NO-MPE and SWB. The estimates of the quality of the hypothesized model were acceptable (outer model GoF = 0.935; absolute GoF = 0.330; relative GoF = 0.942; inner model GoF = 1.008; R2 = 36.947%). Finally, this study supports the view that MPE can influence SWB through TSC, and incites to pursue the examination of the relationships between self-determined motivation, self-regulation mechanisms, and health-related outcomes. PMID:27761126

  4. Parent training for young Norwegian children with ODD and CD problems: predictors and mediators of treatment outcome.

    PubMed

    Fossum, Sturla; Mørch, Willy-Tore; Handegård, Bjørn H; Drugli, May B; Larsson, Bo

    2009-04-01

    Participants were 121 children, aged 4-8 years referred for conduct problems, and their mothers. A parent training intervention was implemented in two outpatient clinics in Norway. Treatment responders were defined as children scoring below a cut-off on the Eyberg Child Behavior Inventory, a score below an optimal cut-off for children in day-care and school as reported by teachers, in addition to a 30% reduction or greater in observed negative parenting. Self-reported parenting practices were explored as potential mediators. The results of logistic regression analyses showed that high levels of maternal stress, clinical levels of ADHD, and being a girl predicted a poorer outcome in conduct problems at home, while pretreatment clinical levels of ADHD predicted a poorer outcome as perceived by the teachers. Harsh and inconsistent parental disciplining emerged as significant partial mediators of changes in conduct problems, highlighting the importance of altering parenting practices to modify young children's conduct problems.

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

    PubMed

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

    2015-04-01

    Although there is substantial evidence that cognitive behavioural therapy alleviates symptoms in functional somatic syndromes, the mechanisms of change are less investigated. This study examined whether changes in illness perceptions mediated the effect of cognitive behavioural therapy. We analysed additional data from a randomised controlled trial comparing completers of cognitive behavioural group therapy (46 patients) to an enhanced usual care group (66 patients). Proposed mediators (illness perceptions) and primary (physical health) and secondary (somatic symptoms and illness worry) outcomes were assessed by means of questionnaires at referral, baseline, end of treatment, and 10 and 16 months after randomisation. Multiple mediation analysis determined whether (1) changes in specific illness perceptions during treatment mediated the effect of cognitive behavioural therapy (primary analysis), and (2) whether changes in illness perceptions during the whole trial period were associated with improved outcome (secondary analysis). Improvements in illness perceptions during treatment partially mediated the effect of cognitive behavioural therapy on physical health one year after treatment (sum of indirect effects 1.556, BCa 95% CI (0.006; 3.620)). Improving perceived control was particularly important. Changes in illness perceptions from baseline to 16 months after randomisation were associated with clinically meaningful improvements in physical health, somatic symptoms and illness worry during the same period. Our results suggest that changing patients' illness perceptions is an important process in cognitive behavioural therapy for functional somatic syndromes. Challenging patients' own understanding of their illness may hence be a key element of successful treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Population Distribution Analyses Reveal a Hierarchy of Molecular Players Underlying Parallel Endocytic Pathways

    PubMed Central

    Gupta, Gagan D.; Howes, Mark T.; Chandran, Ruma; Das, Anupam; Menon, Sindhu; Parton, Robert G.; Sowdhamini, R.; Thattai, Mukund; Mayor, Satyajit

    2014-01-01

    Single-cell-resolved measurements reveal heterogeneous distributions of clathrin-dependent (CD) and -independent (CLIC/GEEC: CG) endocytic activity in Drosophila cell populations. dsRNA-mediated knockdown of core versus peripheral endocytic machinery induces strong changes in the mean, or subtle changes in the shapes of these distributions, respectively. By quantifying these subtle shape changes for 27 single-cell features which report on endocytic activity and cell morphology, we organize 1072 Drosophila genes into a tree-like hierarchy. We find that tree nodes contain gene sets enriched in functional classes and protein complexes, providing a portrait of core and peripheral control of CD and CG endocytosis. For 470 genes we obtain additional features from separate assays and classify them into early- or late-acting genes of the endocytic pathways. Detailed analyses of specific genes at intermediate levels of the tree suggest that Vacuolar ATPase and lysosomal genes involved in vacuolar biogenesis play an evolutionarily conserved role in CG endocytosis. PMID:24971745

  7. An exponential decay model for mediation.

    PubMed

    Fritz, Matthew S

    2014-10-01

    Mediation analysis is often used to investigate mechanisms of change in prevention research. Results finding mediation are strengthened when longitudinal data are used because of the need for temporal precedence. Current longitudinal mediation models have focused mainly on linear change, but many variables in prevention change nonlinearly across time. The most common solution to nonlinearity is to add a quadratic term to the linear model, but this can lead to the use of the quadratic function to explain all nonlinearity, regardless of theory and the characteristics of the variables in the model. The current study describes the problems that arise when quadratic functions are used to describe all nonlinearity and how the use of nonlinear functions, such as exponential decay, address many of these problems. In addition, nonlinear models provide several advantages over polynomial models including usefulness of parameters, parsimony, and generalizability. The effects of using nonlinear functions for mediation analysis are then discussed and a nonlinear growth curve model for mediation is presented. An empirical example using data from a randomized intervention study is then provided to illustrate the estimation and interpretation of the model. Implications, limitations, and future directions are also discussed.

  8. An Exponential Decay Model for Mediation

    PubMed Central

    Fritz, Matthew S.

    2013-01-01

    Mediation analysis is often used to investigate mechanisms of change in prevention research. Results finding mediation are strengthened when longitudinal data are used because of the need for temporal precedence. Current longitudinal mediation models have focused mainly on linear change, but many variables in prevention change nonlinearly across time. The most common solution to nonlinearity is to add a quadratic term to the linear model, but this can lead to the use of the quadratic function to explain all nonlinearity, regardless of theory and the characteristics of the variables in the model. The current study describes the problems that arise when quadratic functions are used to describe all nonlinearity and how the use of nonlinear functions, such as exponential decay, addresses many of these problems. In addition, nonlinear models provide several advantages over polynomial models including usefulness of parameters, parsimony, and generalizability. The effects of using nonlinear functions for mediation analysis are then discussed and a nonlinear growth curve model for mediation is presented. An empirical example using data from a randomized intervention study is then provided to illustrate the estimation and interpretation of the model. Implications, limitations, and future directions are also discussed. PMID:23625557

  9. New aspects of grassland recovery in old-fields revealed by trait-based analyses of perennial-crop-mediated succession.

    PubMed

    Kelemen, András; Tóthmérész, Béla; Valkó, Orsolya; Miglécz, Tamás; Deák, Balázs; Török, Péter

    2017-04-01

    Classical old-field succession studies focused on vegetation changes after the abandonment of annual croplands or on succession after the elimination of cultivated crops. Perennial-crop-mediated succession, where fields are initially covered by perennial crops, reveals alternative aspects of old-field succession theories. We tested the validity of classical theories of old-field succession for perennial-crop-mediated succession. We formulated the following hypotheses: (1) functional diversity increases with increasing field age; (2) resource acquisition versus conservation trade-off shifts toward conservation at community level during the succession; (3) the importance of spatial and temporal seed dispersal decreases during the succession; and (4) competitiveness and stress-tolerance increases and ruderality decreases at community level during the succession. We studied functional diversity, trait distributions and plant strategies in differently aged old-fields using chronosequence method. We found increasing functional richness and functional divergence, but also unchanged or decreasing functional evenness. We detected a shift from resource acquisition to resource conservation strategy of communities during the succession. The role of spatial and temporal seed dispersal was found to be important not only at the initial but also at latter successional stages. We found an increasing stress-tolerance and a decreasing ruderality during succession, while the competitiveness remained unchanged at the community level. Despite the markedly different starting conditions, we found that classical and perennial-crop-mediated old-field successions have some similarities regarding the changes of functional diversity, resource acquisition versus conservation trade-off, and seed dispersal strategies. However, we revealed also the subsequent differences. The competitive character of communities remained stable during the succession; hence, the initial stages of perennial-crop-mediated

  10. A novel model for studies of blood-mediated long-term responses to cellular transplants

    PubMed Central

    Lindblom, Susanne; Hong, Jaan; Nilsson, Bo; Korsgren, Olle; Ronquist, Gunnar

    2015-01-01

    Aims Interaction between blood and bio-surfaces is important in many medical fields. With the aim of studying blood-mediated reactions to cellular transplants, we developed a whole-blood model for incubation of small volumes for up to 48 h. Methods Heparinized polyvinyl chloride tubing was cut in suitable lengths and sealed to create small bags. Multiple bags, with fresh venous blood, were incubated attached to a rotating wheel at 37°C. Physiological variables in blood were monitored: glucose, blood gases, mono- and divalent cations and chloride ions, osmolality, coagulation (platelet consumption, thrombin-antithrombin complexes (TAT)), and complement activation (C3a and SC5b-9), haemolysis, and leukocyte viability. Results Basic glucose consumption was high. Glucose depletion resulted in successive elevation of extracellular potassium, while sodium and calcium ions decreased due to inhibition of energy-requiring ion pumps. Addition of glucose improved ion balance but led to metabolic acidosis. To maintain a balanced physiological environment beyond 6 h, glucose and sodium hydrogen carbonate were added regularly based on analyses of glucose, pH, ions, and osmotic pressure. With these additives haemolysis was prevented for up to 72 h and leukocyte viability better preserved. Despite using non-heparinized blood, coagulation and complement activation were lower during long-term incubations compared with addition of thromboplastin and collagen. Conclusion A novel whole-blood model for studies of blood-mediated responses to a cellular transplant is presented allowing extended observations for up to 48 h and highlights the importance of stringent evaluations and adjustment of physiological conditions. PMID:25322825

  11. 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.

  12. Mechanisms of motivational interviewing in health promotion: a Bayesian mediation analysis

    PubMed Central

    2012-01-01

    Background Counselor behaviors that mediate the efficacy of motivational interviewing (MI) are not well understood, especially when applied to health behavior promotion. We hypothesized that client change talk mediates the relationship between counselor variables and subsequent client behavior change. Methods Purposeful sampling identified individuals from a prospective randomized worksite trial using an MI intervention to promote firefighters’ healthy diet and regular exercise that increased dietary intake of fruits and vegetables (n = 21) or did not increase intake of fruits and vegetables (n = 22). MI interactions were coded using the Motivational Interviewing Skill Code (MISC 2.1) to categorize counselor and firefighter verbal utterances. Both Bayesian and frequentist mediation analyses were used to investigate whether client change talk mediated the relationship between counselor skills and behavior change. Results Counselors’ global spirit, empathy, and direction and MI-consistent behavioral counts (e.g., reflections, open questions, affirmations, emphasize control) significantly correlated with firefighters’ total client change talk utterances (rs = 0.42, 0.40, 0.30, and 0.61, respectively), which correlated significantly with their fruit and vegetable intake increase (r = 0.33). Both Bayesian and frequentist mediation analyses demonstrated that findings were consistent with hypotheses, such that total client change talk mediated the relationship between counselor’s skills—MI-consistent behaviors [Bayesian mediated effect: αβ = .06 (.03), 95% CI = .02, .12] and MI spirit [Bayesian mediated effect: αβ = .06 (.03), 95% CI = .01, .13]—and increased fruit and vegetable consumption. Conclusion Motivational interviewing is a resource- and time-intensive intervention, and is currently being applied in many arenas. Previous research has identified the importance of counselor behaviors and client change talk in the

  13. 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).

  14. Using Additional Analyses to Clarify the Functions of Problem Behavior: An Analysis of Two Cases

    ERIC Educational Resources Information Center

    Payne, Steven W.; Dozier, Claudia L.; Neidert, Pamela L.; Jowett, Erica S.; Newquist, Matthew H.

    2014-01-01

    Functional analyses (FA) have proven useful for identifying contingencies that influence problem behavior. Research has shown that some problem behavior may only occur in specific contexts or be influenced by multiple or idiosyncratic variables. When these contexts or sources of influence are not assessed in an FA, further assessment may be…

  15. 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…

  16. 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

  17. 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.

  18. 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

  19. NUCLEAR FACTOR Y Transcription Factors Have Both Opposing and Additive Roles in ABA-Mediated Seed Germination

    PubMed Central

    Kumimoto, Roderick W.; Siriwardana, Chamindika L.; Gayler, Krystal K.; Risinger, Jan R.; Siefers, Nicholas; Holt, Ben F.

    2013-01-01

    In the model organism Arabidopsis thaliana the heterotrimeric transcription factor NUCLEAR FACTOR Y (NF-Y) has been shown to play multiple roles in facilitating plant growth and development. Although NF-Y itself represents a multi-protein transcriptional complex, recent studies have shown important interactions with other transcription factors, especially those in the bZIP family. Here we add to the growing evidence that NF-Y and bZIP form common complexes to affect many processes. We carried out transcriptional profiling on nf-yc mutants and through subsequent analyses found an enrichment of bZIP binding sites in the promoter elements of misregulated genes. Using NF-Y as bait, yeast two hybrid assays yielded interactions with bZIP proteins that are known to control ABA signaling. Accordingly, we find that plants mutant for several NF-Y subunits show characteristic phenotypes associated with the disruption of ABA signaling. While previous reports have shown additive roles for NF-YC family members in photoperiodic flowering, we found that they can have opposing roles in ABA signaling. Collectively, these results demonstrated the importance and complexity of NF-Y in the integration of environmental and hormone signals. PMID:23527203

  20. Application of Natural Mineral Additives in Construction

    NASA Astrophysics Data System (ADS)

    Linek, Malgorzata; Nita, Piotr; Wolka, Paweł; Zebrowski, Wojciech

    2017-12-01

    The article concerns the idea of using selected mineral additives in the pavement quality concrete composition. The basis of the research paper was the modification of cement concrete intended for airfield pavements. The application of the additives: metakaolonite and natural zeolite was suggested. Analyses included the assessment of basic physical properties of modifiers. Screening analysis, assessment of micro structure and chemical microanalysis were conducted in case of these materials. The influence of the applied additives on the change of concrete mix parameters was also presented. The impact of zeolite and metakaolinite on the mix density, oxygen content and consistency class was analysed. The influence of modifiers on physical and mechanical changes of the hardened cement concrete was discussed (concrete density, compressive strength and bending strength during fracturing) in diversified research periods. The impact of the applied additives on the changes of internal structure of cement concrete was discussed. Observation of concrete micro structure was conducted using the scanning electron microscope. According to the obtained lab test results, parameters of the applied modifiers and their influence on changes of internal structure of cement concrete are reflected in the increase of mechanical properties of pavement quality concrete. The increase of compressive and bending strength in case of all analysed research periods was proved.

  1. Workplace ostracism And workplace behaviors: A moderated mediation model of perceived stress and psychological empowerment.

    PubMed

    Chung, Yang Woon

    2018-05-01

    Workplace ostracism research has examined numerous underlying mechanisms to understand the link between workplace ostracism and behavioral outcomes. Ostracism has been suggested to be an interpersonal stressor; however, research has not investigated workplace ostracism from a stress perspective. Therefore, the study investigated the mediating effect of perceived stress for the relationships between workplace ostracism and helping behavior, voicing behavior, and task performance. The study also investigated the moderating effect of psychological empowerment for the relationships between perceived stress and behavioral outcomes. The study design was a three-wave self-reported questionnaire. The study sampled 225 full-time employees in South Korea and regression analyses with bootstrapping were conducted to test the moderated mediation models. The bootstrapped 95% CI around the indirect effects did not contain zero; therefore, perceived stress mediated the relationship between workplace ostracism and helping behavior (-.06), voicing behavior (-.07), and task performance (-.07). Further, the moderated mediation analyses found perceived stress mediated the relationships between workplace ostracism and behavioral outcomes only when individuals perceived low levels of psychological empowerment. The findings suggest that workplace ostracism is a stressor and psychological empowerment can mitigate the negative effects of ostracism on behavioral outcomes.

  2. Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions

    PubMed Central

    Leven, Matthias; Neudörfl, Jörg M

    2013-01-01

    Summary Four catalysts based on new amides of chiral 1,2-diamines and 2-sulfobenzoic acid have been developed. The alkali-metal salts of these betaine-like amides are able to form imines with enones, which are activated by Lewis acid interaction for nucleophilic attack by 4-hydroxycoumarin. The addition of 4-hydroxycoumarin to enones gives ee’s up to 83% and almost quantitative yields in many cases. This novel type of catalysis provides an effective alternative to conventional primary amino catalysis were strong acid additives are essential components. PMID:23400419

  3. Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

    PubMed

    Aguirre, Claudia G; Madrid, Jillian; Leventhal, Adam M

    2015-08-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction. (c) 2015 APA, all rights reserved).

  4. 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.

  5. The curvilinear relationship of early-life adversity and successful aging: the mediating role of mental health.

    PubMed

    Höltge, Jan; Mc Gee, Shauna L; Thoma, Myriam V

    2018-02-15

    The steeling effect suggests that early-life adversity can have a beneficial impact later in life. However, little is known about its underlying mechanisms and long-term outcomes . The study aimed to examine the role of early-life adversity (ELA) on successful aging, and whether this relationship can be explained by mental and physical health. Socio-demographics, early-life adversity (ELA), individual quality of life (iQoL), and mental and physical health of 270 individuals (M age = 66.82 years, 71.5% female) were assessed. Polynomial regressions and mediation analyses were conducted. Significant inverse U-shaped associations were found between ELA and iQoL (β = -.59, p = .005) and between ELA and mental health (β = -.64, p = .002), but not between ELA and physical health. Furthermore, mental health significantly mediated the relationship between ELA and iQoL (b = -.84, BCa CI [-1.66, -.27]). Highest level of individual quality of life (i.e. successful aging) was related to a moderate amount of ELA. Additionally, mental health significantly mediated this relationship. These findings suggest that some amount of ELA could be beneficial for successful aging. Resource-focused interventions are needed to improve health and promote successful aging for an underdetected, at-risk subgroup with low early-life adversity.

  6. Maternal socialization goals, parenting styles, and social-emotional adjustment among Chinese and European American young adults: testing a mediation model.

    PubMed

    Li, Yan; Costanzo, Philip R; Putallaz, Martha

    2010-01-01

    The authors compared the associations among perceived maternal socialization goals (self-development, filial piety, and collectivism), perceived maternal parenting styles (authoritative, authoritarian, and training), and the social-emotional adjustment (self-esteem, academic self-efficacy, and depression) between Chinese and European American young adults. The mediation processes in which socialization goals relate to young adults' adjustment outcomes through parenting styles were examined. Results showed that European American participants perceived higher maternal self-development socialization goals, whereas Chinese participants perceived higher maternal collectivism socialization goals as well as more authoritarian parenting. Cross-cultural similarities were found in the associations between perceived maternal authoritative parenting and socioemotional adjustment (e.g., higher self-esteem and higher academic self-efficacy) across the two cultural groups. However, perceived maternal authoritarian and training parenting styles were found only to be related to Chinese participants' adjustment (e.g., higher academic self-efficacy and lower depression). The mediation analyses showed that authoritative parenting significantly mediated the positive associations between the self-development and collectivism goal and socioemotional adjustment for both cultural groups. Additionally, training parenting significantly mediated the positive association between the filial piety goal and young adults' academic self-efficacy for the Chinese group only. Findings of this study highlight the importance of examining parental socialization goals in cross-cultural parenting research.

  7. Patient Expectancy as a Mediator of Placebo Effects in Antidepressant Clinical Trials.

    PubMed

    Rutherford, Bret R; Wall, Melanie M; Brown, Patrick J; Choo, Tse-Hwei; Wager, Tor D; Peterson, Bradley S; Chung, Sarah; Kirsch, Irving; Roose, Steven P

    2017-02-01

    Causes of placebo effects in antidepressant trials have been inferred from observational studies and meta-analyses, but their mechanisms have not been directly established. The goal of this study was to examine in a prospective, randomized controlled trial whether patient expectancy mediates placebo effects in antidepressant studies. Adult outpatients with major depressive disorder were randomly assigned to open or placebo-controlled citalopram treatment. Following measurement of pre- and postrandomization expectancy, participants were treated with citalopram or placebo for 8 weeks. Independent samples t tests determined whether patient expectancy differed between the open and placebo-controlled groups, and mixed-effects models assessed group effects on Hamilton Depression Rating Scale (HAM-D) scores over time while controlling for treatment assignment. Finally, mediation analyses tested whether between-group differences in patient expectancy mediated the group effect on HAM-D scores. Postrandomization expectancy scores were significantly higher in the open group (mean=12.1 [SD=2.1]) compared with the placebo-controlled group (mean=11.0 [SD=2.0]). Mixed-effects modeling revealed a significant week-by-group interaction, indicating that HAM-D scores for citalopram-treated participants declined at a faster rate in the open group compared with the placebo-controlled group. Patient expectations postrandomization partially mediated group effects on week 8 HAM-D. Patient expectancy is a significant mediator of placebo effects in antidepressant trials. Expectancy-related interventions should be investigated as a means of controlling placebo responses in antidepressant clinical trials and improving patient outcome in clinical treatment.

  8. Resource-mediated indirect effects of grassland management on arthropod diversity.

    PubMed

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

    2014-01-01

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

  9. Resource-Mediated Indirect Effects of Grassland Management on Arthropod Diversity

    PubMed Central

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

    2014-01-01

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

  10. 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.

  11. [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.

  12. Cravings as a mediator and moderator of drinking outcomes in the COMBINE study.

    PubMed

    Subbaraman, Meenakshi Sabina; Lendle, Samuel; van der Laan, Mark; Kaskutas, Lee Ann; Ahern, Jennifer

    2013-10-01

    Investigators of the COMBINE (Combining Medications and Behavioral Interventions for Alcoholism) study examined whether combining medications with a behavioral intervention would improve outcomes over monotherapies. Unexpectedly, the combination did not offer any advantage over either treatment alone. This study aimed to explain the lack of incremental benefit offered by the combination over either monotherapy by assessing the role of cravings as a treatment mediator and moderator. Secondary mediation and moderation analyses of COMBINE study data. Eleven United States academic sites. A total of 863 patients randomized to one of four treatment groups: naltrexone (100 mg/day; n = 209), the combined behavioral intervention (CBI, n = 236), naltrexone and CBI combined (n = 213) and placebo naltrexone (n = 205). Percentage of days abstinent (PDA) measured between 13 and 16 weeks post-baseline. Cravings, the potential mediator/moderator, were measured at baseline, weeks 4 and 12 using the Obsessive-Compulsive Drinking Scale. Compared with placebo, naltrexone, CBI and the combination all increased PDA by an additional 6-10 percentage points for those with high cravings (P < 0.05 for all three treatment groups). None had significant effects on PDA for those with low cravings. The effects of all three treatments were mediated at least partially by cravings; craving reduction explained 48-53% of treatment effects (P < 0.05 for all three treatment groups). Furthermore, naltrexone appeared to reduce cravings at 4 weeks, while CBI did not reduce cravings until 12 weeks. The Combining Medications and Behavioral Interventions for Alcoholism (COMBINE) naltrexone + CBI combination may not be more beneficial than either monotherapy because craving reduction is a common mechanism of both. © 2013 Society for the Study of Addiction.

  13. 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

  14. 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.

  15. 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.

  16. Inhibitory effects of low molecular weight heparin on mediator release by mast cells: preferential inhibition of cytokine production and mast cell-dependent cutaneous inflammation

    PubMed Central

    BARAM, D; RASHKOVSKY, M; HERSHKOVIZ, R; DRUCKER, I; RESHEF, T; BEN-SHITRIT, S; MEKORI, Y A

    1997-01-01

    There has been substantial evidence that suggests that heparin may modulate various aspects of immune function and inflammation in addition to its well known anticoagulant activity. In this regard heparin was found to suppress cell-mediated immune responses or asthmatic reactions to allergen challenge. In the present study we analyse the effects of low molecular weight heparin (LMWH) on mast cell degranulation and cytokine production in vitro and on the elicitation of IgE-mediated mast cell-dependent late cutaneous allergic inflammation in vivo. We have established that LMWH preferentially inhibited tumour necrosis factor-alpha (TNF-α) and IL-4 production without having any significant effect on mast cell degranulation. These effects have been observed in mast cells derived from three different origins that were activated by either immunological or non-immunological stimuli. We have shown that there is inhibition of TNF-α production (and not neutralization of activity), as elimination of the drug after a short preincubation and addition of LMWH to rTNF-α had no effect on TNF-α-mediated cytotoxic activity. These results were also confirmed by ELISA. In vivo, s.c. injection of the LMWH inhibited the leucocyte infiltration associated with the late cutaneous response which followed passive cutaneous anaphylaxis (PCA) reaction, without affecting mast cell numbers or degranulation. These data suggest that LMWH may have an inhibitory role in mast cell-mediated allergic inflammation, and thus might be considered as a possible therapeutic modality. PMID:9409655

  17. Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways

    PubMed Central

    Kawakami, Eiryo; Singh, Vivek K; Matsubara, Kazuko; Ishii, Takashi; Matsuoka, Yukiko; Hase, Takeshi; Kulkarni, Priya; Siddiqui, Kenaz; Kodilkar, Janhavi; Danve, Nitisha; Subramanian, Indhupriya; Katoh, Manami; Shimizu-Yoshida, Yuki; Ghosh, Samik; Jere, Abhay; Kitano, Hiroaki

    2016-01-01

    Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker’s or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow–tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow–tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. PMID:28725465

  18. Relationship authenticity partially mediates the effects of attachment on relationship satisfaction.

    PubMed

    Rasco, Danney; Warner, Rebecca M

    2017-01-01

    Individuals with anxious and avoidant attachment tend to experience less satisfaction in their relationships. Past research suggests the negative effects of attachment on relationship satisfaction may be partially mediated by self-disclosure and self-concealment; the present study evaluated relationship authenticity as a potential additional mediator. Confirmatory factor analysis indicated that relationship authenticity is distinct from self-disclosure and self-concealment. Relationship authenticity predicted additional variance in relationship satisfaction controlling for attachment, self-disclosure, and self-concealment. The results were consistent with relationship authenticity, along with self-disclosure and self-concealment, partially mediating the effects of attachment on relationship satisfaction. These findings suggest that relationship authenticity may play a unique role in understanding how attachment influences relationship satisfaction. Theoretical and clinical implications are discussed.

  19. 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.

  20. Women, Physical Activity, and Quality of Life: Self-concept as a Mediator.

    PubMed

    Gonzalo Silvestre, Tamara; Ubillos Landa, Silvia

    2016-02-22

    The objectives of this research are: (a) analyze the incremental validity of physical activity's (PA) influence on perceived quality of life (PQL); (b) determine if PA's predictive power is mediated by self-concept; and (c) study if results vary according to a unidimensional or multidimensional approach to self-concept measurement. The sample comprised 160 women from Burgos, Spain aged 18 to 45 years old. Non-probability sampling was used. Two three-step hierarchical regression analyses were applied to forecast PQL. The hedonic quality-of-life indicators, self-concept, self-esteem, and PA were included as independent variables. The first regression analysis included global self-concept as predictor variable, while the second included its five dimensions. Two mediation analyses were conducted to see if PA's ability to predict PQL was mediated by global and physical self-concept. Results from the first regression shows that self-concept, satisfaction with life, and PA were significant predictors. PA slightly but significantly increased explained variance in PQL (2.1%). In the second regression, substituting global self-concept with its five constituent factors, only the physical dimension and satisfaction with life predicted PQL, while PA ceased to be a significant predictor. Mediation analysis revealed that only physical self-concept mediates the relationship between PA and PQL (z = 1.97, p < .050), and not global self-concept. Physical self-concept was the strongest predictor and approximately 32.45 % of PA's effect on PQL was mediated by it. This study's findings support a multidimensional view of self-concept, and represent a more accurate image of the relationship between PQL, PA, and self-concept.

  1. Social Differentiation of Sun-Protection Behaviors: The Mediating Role of Cognitive Factors.

    PubMed

    Bocquier, Aurélie; Fressard, Lisa; Legleye, Stéphane; Verger, Pierre; Peretti-Watel, Patrick

    2016-03-01

    Adherence to sun-protection guidelines in developed countries is low, especially among people of low SES. Mechanisms underlying this social differentiation are poorly understood. This study aimed to examine the social differentiation of sun-protection behaviors and of two cognitive factors (knowledge about both sun health and behavioral risk factors for cancer) and to determine if these cognitive factors mediate the association between SES and sun-protection behaviors. Data came from the 2010 Baromètre Cancer survey (analyzed in 2014), a random cross-sectional telephone survey conducted among the French general population (n=3,359 individuals aged 15-75 years). First, bivariate associations between a composite individual SES indicator (based on education level, occupation, and income) and both sun-protection behaviors and cognitive factors were tested with chi-square tests and ANOVA. Then, confirmatory factor analysis and structural equation modeling were used to test the mediating role of cognitive factors with a multiple mediation model including four latent variables. In bivariate analyses, the individual SES indicator was positively associated with sun-protection behaviors and both cognitive factors. Multiple mediation analyses showed that both cognitive factors partially mediated the effect of individual SES on sun-protection behaviors. The overall proportion of mediated effects was 48%. The direct effect of SES remained significant. These results suggest that interventions aimed at modifying the knowledge and perceptions of people of low SES might help to reduce social differentiation of sun-protection behaviors. Further qualitative research is needed to better understand these cognitive factors and develop suitable prevention messages. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  2. How Teacher Emotional Support Motivates Students: The Mediating Roles of Perceived Peer Relatedness, Autonomy Support, and Competence

    ERIC Educational Resources Information Center

    Ruzek, Erik A.; Hafen, Christopher A.; Allen, Joseph P.; Gregory, Anne; Mikami, Amori Yee; Pianta, Robert C.

    2016-01-01

    Multilevel mediation analyses test whether students' mid-year reports of classroom experiences of autonomy, relatedness with peers, and competence mediate associations between early in the school year emotionally-supportive teacher-student interactions (independently observed) and student-reported academic year changes in mastery motivation and…

  3. Mediation Analysis in a Latent Growth Curve Modeling Framework

    ERIC Educational Resources Information Center

    von Soest, Tilmann; Hagtvet, Knut A.

    2011-01-01

    This article presents several longitudinal mediation models in the framework of latent growth curve modeling and provides a detailed account of how such models can be constructed. Logical and statistical challenges that might arise when such analyses are conducted are also discussed. Specifically, we discuss how the initial status (intercept) and…

  4. Constitutive Analyses of Nontraditional Stabilization Additives

    DTIC Science & Technology

    2004-11-01

    cm-I Figure 29. FTIRIATR spectrum of Ven-Set 950 soil stabilization agent Based on the information provided in the MSDS and the FTIR analysis above...emulsion. The MSDS states that it is composed of an acrylic polymer (52 percent) with zinc oxide (2 percent), activated carbon (8 to 9 percent), and...water. The polymer as yet is unidentified. However, it appears to be an acrylate/ methacrylate with some aromaticity (peak about 1,635 c-f’). The

  5. Parenting Behavior and Adolescent Conduct Problems: Reciprocal and Mediational Effects

    ERIC Educational Resources Information Center

    Simons-Morton, Bruce; Chen, Rusan; Hand, Laura Shaffer; Haynie, Denise L.

    2008-01-01

    This research examined the relationship between parenting practices and adolescent conduct problems and the mediation of these relationships by two parent-adolescent relationship variables, conflict and psychological autonomy. Autoregressive latent trajectory (ALT) analyses were used to assess relationships over time between parent practices and…

  6. Parasitic nematodes modulate PIN-mediated auxin transport to facilitate infection.

    PubMed

    Grunewald, Wim; Cannoot, Bernard; Friml, Jirí; Gheysen, Godelieve

    2009-01-01

    Plant-parasitic nematodes are destructive plant pathogens that cause significant yield losses. They induce highly specialized feeding sites (NFS) in infected plant roots from which they withdraw nutrients. In order to establish these NFS, it is thought that the nematodes manipulate the molecular and physiological pathways of their hosts. Evidence is accumulating that the plant signalling molecule auxin is involved in the initiation and development of the feeding sites of sedentary plant-parasitic nematodes. Intercellular transport of auxin is essential for various aspects of plant growth and development. Here, we analysed the spatial and temporal expression of PIN auxin transporters during the early events of NFS establishment using promoter-GUS/GFP fusion lines. Additionally, single and double pin mutants were used in infection studies to analyse the role of the different PIN proteins during cyst nematode infection. Based on our results, we postulate a model in which PIN1-mediated auxin transport is needed to deliver auxin to the initial syncytial cell, whereas PIN3 and PIN4 distribute the accumulated auxin laterally and are involved in the radial expansion of the NFS. Our data demonstrate that cyst nematodes are able to hijack the auxin distribution network in order to facilitate the infection process.

  7. Preliminary Evidence for Cognitive Mediation During Cognitive–Behavioral Therapy of Panic Disorder

    PubMed Central

    Hofmann, Stefan G.; Suvak, Michael K.; Barlow, David H.; Shear, M. Katherine; Meuret, Alicia E.; Rosenfield, David; Gorman, Jack M.; Woods, Scott W.

    2007-01-01

    Cognitive–behavioral therapy (CBT) and pharmacotherapy are similarly effective for treating panic disorder with mild or no agoraphobia, but little is known about the mechanism through which these treatments work. The present study examined some of the criteria for cognitive mediation of treatment change in CBT alone, imipramine alone, CBT plus imipramine, and CBT plus placebo. Ninety-one individuals who received 1 of these interventions were assessed before and after acute treatment, and after a 6-month maintenance period. Multilevel moderated mediation analyses provided preliminary support for the notion that changes in panic-related cognitions mediate changes in panic severity only in treatments that include CBT. PMID:17563154

  8. Anxiety Mediates Perceived Discrimination and Health in African-American Women.

    PubMed

    Carter, Sierra E; Walker, Rheeda L; Cutrona, Carolyn E; Simons, Ronald L; Beach, Steven R H

    2016-11-01

    We examined the mediational role of symptoms of anxiety in accounting for the association of discrimination and chronic health conditions among African-American women. Participants were 646 African-American women who completed self-report measures of perceived racial discrimination, symptoms of anxiety, and diagnosed chronic health problems. We examined the mediation hypothesis using a path analytic procedure. Mediational analyses indicated that, above and beyond symptoms of depression, age, and education status, anxiety symptoms were associated with both racial discrimination (β = .03, SE = .01, p < .001) and chronic health problems (β = .33, SE = .09, p < .001) and significantly mediated the discrimination-health association (β = -.01, SE = .01, p = .16). These findings highlight the potentially vital role of symptoms of anxiety in the process that occurs from an individual's perception of discrimination to reported chronic health outcomes. Future research expanding our understanding of the interconnection of psychosocial stressors, discrimination, and their biological sequelae is needed.

  9. [Immigrant women care in a health intercultural mediation program].

    PubMed

    Alcaraz Quevedo, Manuela; Paredes-Carbonell, Joan J; Sancho Mestre, Carla; López-Sánchez, Pilar; García Moreno, J Luis; Vivas Consuelo, David

    2014-01-01

    Intercultural Mediation is a strategy for quality health care aimed at reducing inequalities in immigrant population. The aim is to analyse main reasons consultation with the mediation service, women care profile and characteristics of intervention. Cross-sectional study of 339 episodes of care by two intercultural mediators (MI) from February 2008 to October 2011 in Valencia. Variables were analysed individual records of the consultations of the MI: reasons for referral to MI and professionals who refer, motives and problems identified by MI, kind of intervention, kind of derivation of MI and socio-economic variables. To evaluate the differences between countries, X2 test was used for qualitative variables and one-way ANOVA test for quantitative variables. 123 women (36,3%), were referred to the MI by the Sexual and Reproductive Health Centre and 98 (28,9%) by the midwife. 272 women (80,24%) were referred for information and demand for contraception. The MI conducted health education and detected social problems in 67 women (19,7%) and gender violence in 38 (11,21%). The women attending were Latin American immigrants (those of Bolivia showed more vulnerability) and were referred for contraception. The MI provided information, education and facilitated access to reproductive health services. Bolivian women showed more vulnerability factors: irregular situation, precarious work and low residence time.

  10. Organizational strategies mediate nonverbal memory impairment in obsessive-compulsive disorder.

    PubMed

    Savage, C R; Baer, L; Keuthen, N J; Brown, H D; Rauch, S L; Jenike, M A

    1999-04-01

    Previous neuropsychological studies of obsessive-compulsive disorder (OCD) have indicated impaired executive functioning and nonverbal memory. The extent to which impaired executive functioning impacts nonverbal memory has not been established. The current study investigated the mediating effects of organizational strategies used when copying a figure on subsequent nonverbal memory for that figure. We examined neuropsychological performance in 20 unmedicated subjects with OCD and 20 matched normal control subjects. Subjects were administered the Rey-Osterrieth Complex Figure Test (RCFT) and neuropsychological tests assessing various aspects of executive function. OCD subjects differed significantly from healthy control subjects in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in immediate percent recall were significantly mediated by copy organizational strategies. Further exploratory analyses indicated that organizational problems in OCD may be related to difficulties shifting mental and/or spatial set. Immediate nonverbal memory problems in OCD subjects were mediated by impaired organizational strategies used during the initial copy of the RCFT figure. Thus, the primary deficit was one affecting executive function, which then had a secondary effect on immediate memory. These findings are consistent with current theories proposing frontal-striatal system dysfunction in OCD.

  11. The role of proteosome-mediated proteolysis in modulating potentially harmful transcription factor activity in Saccharomyces cerevisiae

    PubMed Central

    Bonzanni, Nicola; Zhang, Nianshu; Oliver, Stephen G.; Fisher, Jasmin

    2011-01-01

    Motivation: The appropriate modulation of the stress response to variable environmental conditions is necessary to maintain sustained viability in Saccharomyces cerevisiae. Particularly, controlling the abundance of proteins that may have detrimental effects on cell growth is crucial for rapid recovery from stress-induced quiescence. Results: Prompted by qualitative modeling of the nutrient starvation response in yeast, we investigated in vivo the effect of proteolysis after nutrient starvation showing that, for the Gis1 transcription factor at least, proteasome-mediated control is crucial for a rapid return to growth. Additional bioinformatics analyses show that potentially toxic transcriptional regulators have a significantly lower protein half-life, a higher fraction of unstructured regions and more potential PEST motifs than the non-detrimental ones. Furthermore, inhibiting proteasome activity tends to increase the expression of genes induced during the Environmental Stress Response more than those in the rest of the genome. Our combined results suggest that proteasome-mediated proteolysis of potentially toxic transcription factors tightly modulates the stress response in yeast. Contact: jasmin.fisher@microsoft.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21685082

  12. 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.

  13. 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.

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

    ERIC Educational Resources Information Center

    Marsack, Christina N.; Samuel, Preethy S.

    2017-01-01

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

  15. Nostalgia-Evoked Inspiration: Mediating Mechanisms and Motivational Implications.

    PubMed

    Stephan, Elena; Sedikides, Constantine; Wildschut, Tim; Cheung, Wing-Yee; Routledge, Clay; Arndt, Jamie

    2015-10-01

    Six studies examined the nostalgia-inspiration link and its motivational implications. In Study 1, nostalgia proneness was positively associated with inspiration frequency and intensity. In Studies 2 and 3, the recollection of nostalgic (vs. ordinary) experiences increased both general inspiration and specific inspiration to engage in exploratory activities. In Study 4, serial mediational analyses supported a model in which nostalgia increases social connectedness, which subsequently fosters self-esteem, which then boosts inspiration. In Study 5, a rigorous evaluation of this serial mediational model (with a novel nostalgia induction controlling for positive affect) reinforced the idea that nostalgia-elicited social connectedness increases self-esteem, which then heightens inspiration. Study 6 extended the serial mediational model by demonstrating that nostalgia-evoked inspiration predicts goal pursuit (intentions to pursue an important goal). Nostalgia spawns inspiration via social connectedness and attendant self-esteem. In turn, nostalgia-evoked inspiration bolsters motivation. © 2015 by the Society for Personality and Social Psychology, Inc.

  16. Evaluating lipid mediator structural complexity using ion mobility spectrometry combined with mass spectrometry

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

    Kyle, Jennifer E.; Aly, Noor; Zheng, Xueyun

    Lipid mediators (LMs) are broadly defined as a class of bioactive lipophilic molecules that regulate cell-to-cell communication events with many having a strong correlation with various human diseases and conditions. LMs are usually analyzed with liquid chromatography and mass spectrometry (LC-MS), but their numerous isomers greatly complicate the measurements with essentially identical fragmentation spectra and LC separations not always sufficient for distinguishing the features. In this work, we characterized LMs having specific categories using ion mobility spectrometry coupled with mass spectrometry (IMS-MS). The IMS collision cross sections and MS m/z values displayed distinct trends for each LM category studied. LC-IMS-MSmore » analyses on flu infected mouse tissue samples also illustrated the presence of additional LM species not in our databases.« less

  17. 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.

  18. Treatment of Social Phobia: Potential Mediators and Moderators

    PubMed Central

    Hofmann, Stefan G.

    2006-01-01

    Although the efficacy of numerous psychosocial interventions for social phobia has been clearly demonstrated, little is known about the mediators and moderators of treatment change. Three potential mediators are discussed that are derived from prominent psychological theories: negative cognitive appraisal (estimated social costs), perceived self-efficacy (perceived social skills), and perceived emotional control. Furthermore, the generalized subtype of social phobia and the additional diagnosis of avoidant personality disorder are considered as potential treatment moderators. PMID:16799697

  19. Prospective Association of Childhood Receptive Vocabulary and Conduct Problems with Self-Reported Adolescent Delinquency: Tests of Mediation and Moderation in Sibling-Comparison Analyses

    PubMed Central

    Lahey, Benjamin B.; D'Onofrio, Brian M.; Van Hulle, Carol A.; Rathouz, Paul J.

    2014-01-01

    Associations among receptive vocabulary measured at 4–9 years, mother-reported childhood conduct problems at 4–9 years, and self-reported adolescent delinquency at 14–17 years were assessed using data from a prospective study of the offspring of a large U.S. nationally representative sample of women. A novel quasi-experimental strategy was used to rule out family-level confounding by estimating path-analytic associations within families in a sibling comparison design. This allowed simultaneous tests of the direct and indirect effects of receptive vocabulary and childhood conduct problems, and of their joint moderation, on adolescent delinquency without family-level environmental confounding. The significant association of receptive vocabulary with later adolescent delinquency was indirect, mediated by childhood conduct problems. Furthermore, a significant interaction between receptive vocabulary and childhood conduct problems reflected a steeper slope for the predictive association between childhood conduct problems and adolescent delinquency when receptive vocabulary scores were higher. These findings of significant indirect association were qualitatively identical in both population-level and within-family analyses, suggesting that they are not the result of family-level confounds. PMID:24736982

  20. Lysosomes as mediators of drug resistance in cancer.

    PubMed

    Zhitomirsky, Benny; Assaraf, Yehuda G

    2016-01-01

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

  1. [Relationship Between General Cognitive Abilities and School Achievement: The Mediation Role of Learning Behavior].

    PubMed

    Weber, H M; Rücker, S; Büttner, P; Petermann, F; Daseking, M

    2015-10-01

    General cognitive abilities are still considered as the most important predictor of school achievement and success. Whether the high correlation (r=0.50) can be explained by other variables has not yet been studied. Learning behavior can be discussed as one factor that influences the relationship between general cognitive abilities and school achievement. This study examined the relationship between intelligence, school achievement and learning behavior. Mediator analyses were conducted to check whether learning behavior would mediate the relationship between general cognitive abilities and school grades in mathematics and German. Statistical analyses confirmed that the relationship between general cognitive abilities and school achievement was fully mediated by learning behavior for German, whereas intelligence seemed to be the only predictor for achievement in mathematics. These results could be confirmed by non-parametric bootstrapping procedures. RESULTS indicate that special training of learning behavior may have a positive impact on school success, even for children and adolescents with low IQ. © Georg Thieme Verlag KG Stuttgart · New York.

  2. 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.

  3. 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

  4. Emotional intelligence and depressive symptoms in Spanish institutionalized elders: does emotional self-efficacy act as a mediator?

    PubMed Central

    2016-01-01

    Background. This work examines the relationship between emotional intelligence (EI) and depressive symptomatology in institutionalized older adults, delving into the mechanisms underlying this relationship. Considering that previous evidence of the variation of the EI-depression relationship depending on whether the emotional ability or the perception of that ability is evaluated, a model of multiple mediation was tested in which the dimensions of emotional self-efficacy (ESE) act as mediators in the relationship between ability EI and depressive symptomatology. Methods. The sample consisted of 115 institutionalized older adults (47.82% women; 80.3 ± 7.9 years of age) from the province of Jaén (Spain) who completed a test of ESE, a measure of ability EI, and a self-administered questionnaire of depressive symptoms. Results. The results showed a positive association between older adults’ emotional performance and depressive symptomatology, finding stronger associations with ESE than with EI abilities. In addition, multiple mediation analyses showed that two of the four dimensions of ESE fully mediated the relationship between ability EI and depressive symptoms. Discussion. These findings suggest that older adults’ high levels of emotional competence generate a feeling of ESE which can protect them against depressive symptoms. This work supports the predictive validity of emotional abilities and ESE for the mental health of a group that is particularly vulnerable to depression, institutionalized older adults. The limitations of the work are discussed, and future lines of research were considered. PMID:27547553

  5. TLR4 and RAGE conversely mediate pro-inflammatory S100A8/9-mediated inhibition of proliferation-linked signaling in myeloproliferative neoplasms.

    PubMed

    Kovačić, Marijana; Mitrović-Ajtić, Olivera; Beleslin-Čokić, Bojana; Djikić, Dragoslava; Subotički, Tijana; Diklić, Miloš; Leković, Danijela; Gotić, Mirjana; Mossuz, Pascal; Čokić, Vladan P

    2018-06-26

    Previously, the family of S100A proteins has been found to be associated with inflammation and myelopoiesis and to be able to induce or support myeloproliferation during chronic inflammation. Here, we studied the inflammatory myeloid-related proteins S100A4, S100A8, S100A9 and S100A12 in myeloproliferative neoplasms (MPNs) in order to assess the involvement of chronic inflammation in the pathogenesis of MPN. We analyzed the S100A4, S100A8, S100A9 and S100A12 mRNA and protein levels in the bone marrow and circulation of 140 patients with MPN and 15 healthy controls using Western blotting, microarray-based mRNA expression profiling and ELISA assays, respectively. In addition we performed functional studies on the proliferation-related AKT and ERK1/2 signaling pathways in MPN-derived granulocytes using Western blotting and proteomic analyses. We found that the S100A mRNA levels were increased in MPN patient-derived circulatory CD34 + cells, and that their protein expression levels were also augmented in their granulocytes and bone marrow stroma cells, depending on the JAK2V617F mutation allele burden. We also found that calreticulin (CALR) mutations were related to reduced S100A8 plasma levels in primary myelofibrosis (PMF). The S100A8 plasma levels were found to be increased in MPN, the S100A9 plasma levels in PMF and essential thrombocythemia (ET), and the S100A12 plasma levels in polycythemia vera (PV). These S100A plasma levels showed a positive correlation with the systemic inflammation marker IL-8, as well as with the numbers of leukocytes and thrombocytes, depending on the JAK2V617F mutation status. Additionally, we found that heterodimeric S100A8/9 can inhibit the AKT pathway in MPN-derived granulocytes mediated by the Toll-like receptor 4 (TLR4), depending on the CALR mutation status. Conversely, we found that blocking of the receptor for advanced glycation end products (RAGE) increased the S100A8/9-mediated inhibition of AKT signaling in the MPN

  6. 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

  7. The effect of computer-mediated administration on self-disclosure of problems on the addiction severity index.

    PubMed

    Butler, Stephen F; Villapiano, Albert; Malinow, Andrew

    2009-12-01

    People tend to disclose more personal information when communication is mediated through the use of a computer. This study was conducted to examine the impact of this phenomenon on the way respondents answer questions during computer-mediated, self-administration of the Addiction Severity Index (ASI) called the Addiction Severity Index-Multimedia Version((R)) (ASI-MV((R))). A sample of 142 clients in substance abuse treatment was administered the ASI via an interviewer and the computerized ASI-MV((R)), three to five days apart in a counterbalanced order. Seven composite scores were compared between the two test administrations using paired t-tests. Post hoc analyses examined interviewer effects. Comparisons of composite scores for each of the domains between the face-to-face administered and computer-mediated, self-administered ASI revealed that significantly greater problem severity was reported by clients in five of the seven domains during administration of the computer-mediated, self-administered version compared to the trained interviewer version. Item analyses identified certain items as responsible for significant differences, especially those asking clients to rate need for treatment. All items that were significantly different between the two modes of administration revealed greater problem severity reported on the ASI-MV((R)) as compared to the interview administered assessment. Post hoc analyses yielded significant interviewer effects on four of the five domains where differences were observed. These data support a growing literature documenting a tendency for respondents to be more self-disclosing in a computer-mediated format over a face-to-face interview. Differences in interviewer skill in establishing rapport may account for these observations.

  8. Sex differences in the mediators of functional disability in Major Depressive Disorder.

    PubMed

    Carmona, Nicole E; Subramaniapillai, Mehala; Mansur, Rodrigo B; Cha, Danielle S; Lee, Yena; Fus, Dominika; McIntyre, Roger S

    2018-01-01

    The aim of this study was to investigate sex differences in discrete domains of psychopathology as mediators of functional disability among individuals with Major Depressive Disorder (MDD). Adults (ages 18-65) with moderate-to-severe MDD (n = 100) and age-, sex-, and education-matched healthy controls (HC; n = 100) participated in a clinical trial validating the THINC-integrated tool, a newly developed cognitive assessment tool for patients with MDD. Variables assessed as possible mediators included depression symptom severity, anxiety symptoms, sleep disturbance, perceived cognitive deficits, and objective cognitive performance. Functional disability was assessed using the total score on the Sheehan Disability Scale. Separate mediation analyses were conducted for men and women. No significant differences were detected between men and women on the assessed domains of psychopathology or functional disability (ps > 0.05). However, the mediation analyses demonstrated different patterns with respect to determinants of functional disability in MDD between men and women. Functional disability was mediated by anxiety (95% CI: -3.17, -0.28) and sleep disturbance (95% CI: -0.69, -0.05) among men and by depressive symptom severity (95% CI: -7.82, -0.32) among women. These preliminary results instantiate the need to dimensionalize psychopathology in MDD. Our results at least in part support the hypothesis that, consistent with the sex differences in the prevalence and illness presentation of MDD, determinants of functional outcomes also differ between men and women, underscoring the need to consider sex differences in order to improve functional outcomes in the treatment of MDD. Copyright © 2017. Published by Elsevier Ltd.

  9. 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

  10. Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis

    PubMed Central

    Masterson, Joanne C; McNamee, Eóin N; Fillon, Sophie A; Hosford, Lindsay; Harris, Rachel; Fernando, Shahan D; Jedlicka, Paul; Iwamoto, Ryo; Jacobsen, Elizabeth; Protheroe, Cheryl; Eltzschig, Holger K; Colgan, Sean P; Arita, Makoto; Lee, James J; Furuta, Glenn T

    2015-01-01

    Objective Eosinophils reside in the colonic mucosa and increase significantly during disease. Although a number of studies have suggested that eosinophils contribute to the pathogenesis of GI inflammation, the expanding scope of eosinophil-mediated activities indicate that they also regulate local immune responses and modulate tissue inflammation. We sought to define the impact of eosinophils that respond to acute phases of colitis in mice. Design Acute colitis was induced in mice by administration of dextran sulfate sodium, 2,4,6-trinitrobenzenesulfonic acid or oxazolone to C57BL/6J (control) or eosinophil deficient (PHIL) mice. Eosinophils were also depleted from mice using antibodies against interleukin (IL)-5 or by grafting bone marrow from PHIL mice into control mice. Colon tissues were collected and analysed by immunohistochemistry, flow cytometry and reverse transcription PCR; lipids were analysed by mass spectroscopy. Results Eosinophil-deficient mice developed significantly more severe colitis, and their colon tissues contained a greater number of neutrophils, than controls. This compensatory increase in neutrophils was accompanied by increased levels of the chemokines CXCL1 and CXCL2, which attract neutrophils. Lipidomic analyses of colonic tissue from eosinophil-deficient mice identified a deficiency in the docosahexaenoic acid-derived anti-inflammatory mediator 10, 17- dihydroxydocosahexaenoic acid (diHDoHE), namely protectin D1 (PD1). Administration of an exogenous PD1-isomer (10S, 17S-DiHDoHE) reduced the severity of colitis in eosinophil-deficient mice. The PD1-isomer also attenuated neutrophil infiltration and reduced levels of tumour necrosis factor-α, IL-1β, IL-6 and inducible NO-synthase in colons of mice. Finally, in vitro assays identified a direct inhibitory effect of PD1-isomer on neutrophil transepithelial migration. Conclusions Eosinophils exert a protective effect in acute mouse colitis, via production of anti-inflammatory lipid

  11. Lifelong Learning in Artistic Context Mediated by Advanced Technologies

    ERIC Educational Resources Information Center

    Ferrari, Mirella

    2016-01-01

    This research starts by analysing the current state of artistic heritage in Italy and studying some examples in Europe: we try to investigate the scope of non-formal learning in artistic context, mediated by advanced technology. The framework within which we have placed our investigation is that of lifelong learning and lifedeep learning. The…

  12. Placental Abruption and Perinatal Mortality With Preterm Delivery as a Mediator: Disentangling Direct and Indirect Effects

    PubMed Central

    Ananth, Cande V.; VanderWeele, Tyler J.

    2011-01-01

    The authors use recent methodology in causal inference to disentangle the direct and indirect effects that operate through a mediator in an exposure-response association paradigm. They demonstrate how total effects can be partitioned into direct and indirect effects even when the exposure and mediator interact. The impact of bias due to unmeasured confounding on the exposure-response association is assessed through a series of sensitivity analyses. These methods are applied to a problem in perinatal epidemiology to examine the extent to which the effect of abruption on perinatal mortality is mediated through preterm delivery. Data on over 26 million US singleton births (1995–2002) were utilized. Risks of mortality among abruption and nonabruption births were 102.7 and 6.2 per 1,000 births, respectively. Risk ratios of the natural direct and indirect (preterm delivery-mediated) effects of abruption on mortality were 10.18 (95% confidence interval: 9.80, 10.58) and 1.35 (95% confidence interval: 1.33, 1.38), respectively. The proportion of increased mortality risk mediated through preterm delivery was 28.1%, with even higher proportions associated with deliveries at earlier gestational ages. Sensitivity analyses underscore that the qualitative conclusions of some mediated effects and substantial direct effects are reasonably robust to unmeasured confounding of a fairly considerable magnitude. PMID:21430195

  13. 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.

  14. Dyadic adjustment and parenting stress in internationally adoptive mothers and fathers: the mediating role of adult attachment dimensions

    PubMed Central

    Salcuni, Silvia; Miconi, Diana; Altoè, Gianmarco; Moscardino, Ughetta

    2015-01-01

    Previous research has shown that a positive marital functioning represents a resource in adoptive families, leading to a decrease in parenting stress, but little is known about the factors mediating such a relationship. This study aimed to explore whether adult attachment avoidance and anxiety mediate the effect of dyadic functioning on parenting stress in 90 internationally adoptive couples (mothers and fathers) who had adopted a child (aged 3–10 years) in the last 36 months. Participants completed self-report measures of dyadic adjustment, adult attachment, and parenting stress. A series of path analyses supported the mediation hypothesis, but differentially for mothers and fathers. Among mothers, there was a direct and negative relationship between dyadic adjustment and parenting stress. In addition, a better dyadic adjustment was related to lower levels of attachment anxiety, which in turn were associated with less parenting stress. Among fathers, increased dyadic adjustment was related to lower levels of attachment avoidance, which in turn were associated with reduced parenting stress. These findings suggest the importance of including both mothers and fathers in adoption research. Adoptive parents could benefit from specific interventions aimed at reducing attachment avoidance and anxiety by supporting parental sense of competence and involvement for mothers and fathers, respectively. PMID:26388799

  15. Cravings as a mediator and moderator of drinking outcomes in the COMBINE Study

    PubMed Central

    Lendle, Samuel; van der Laan, Mark; Kaskutas, Lee Ann; Ahern, Jennifer

    2014-01-01

    Aims Investigators of the COMBINE (Combining Medications and Behavioral Interventions for Alcoholism) Study examined whether combining medications with a behavioral intervention would improve outcomes over monotherapies. Unexpectedly, the combination did not offer any advantage over either treatment alone. This study aimed to explain the lack of incremental benefit offered by the combination over either monotherapy by assessing the role of cravings as a treatment mediator and moderator. Design Secondary mediation and moderation analyses of COMBINE study data. Setting Eleven United States academic sites. Participants 863 patients randomized to one of four treatment groups: naltrexone (100mg/d; n=209), the Combined Behavioral Intervention (CBI, n=236), naltrexone and CBI combined (n=213), and placebo naltrexone (n=205). Measurements Percent Days Abstinent (PDA) measured between 13 and 16 weeks post-baseline. Cravings, the potential mediator/moderator, was measured at baseline, week 4 and week 12 using the Obsessive-Compulsive Drinking Scale. Findings Compared to placebo, naltrexone, CBI, and the combination all increased PDA by an additional 6–10 percentage points for those with high cravings (p<0.05 for all three treatment groups). None had significant effects on PDA for those with low cravings. The effects of all three treatments were at least partially mediated by cravings; craving reduction explained 48–53% of treatment effects (p<0.05 for all three treatment groups). Furthermore, naltrexone appeared to reduce cravings at 4 weeks, while CBI did not reduce cravings until 12 weeks. Conclusions Naltrexone and the behavioral intervention both improved abstinence by reducing cravings and were no longer effective once cravings were low. Furthermore, naltrexone reduced cravings by 4 weeks, while the behavioral intervention took longer to affect cravings. The COMBINE naltrexone + CBI combination may not have been more beneficial than either monotherapy because

  16. Potential additional effect of omentectomy on metabolic syndrome, acute-phase reactants, and inflammatory mediators in grade III obese patients undergoing laparoscopic Roux-en-Y gastric bypass: a randomized trial.

    PubMed

    Herrera, Miguel F; Pantoja, Juan Pablo; Velázquez-Fernández, David; Cabiedes, Javier; Aguilar-Salinas, Carlos; García-García, Eduardo; Rivas, Alfredo; Villeda, Christian; Hernández-Ramírez, Diego F; Dávila, Andrea; Zaraín, Aarón

    2010-07-01

    To assess the additional effect of sudden visceral fat reduction by omentectomy on metabolic syndrome, acute-phase reactants, and inflammatory mediators in patients with grade III obesity (G-III O) undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB). Twenty-two patients were randomized into two groups, LRYGB alone or with omentectomy. Levels of interleukin-6, C-reactive protein, tumor necrosis factor-alpha, leptin, adiponectin, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, as well as clinical characteristics, were evaluated before surgery and at 1, 3, 6, and 12 months after surgery. Results were compared between groups. Baseline characteristics were comparable in both groups. Mean operative time was significantly higher in the group of patients who underwent omentectomy (P < 0.001). Median weight of the omentum was 795 +/- 341 g. In one patient, a duodenal perforation occurred at the time of omentectomy. BMI, blood pressure, glucose, total cholesterol, LDL, and triglycerides significantly improved in both groups at 1, 3, 6, and 12 months of follow-up when compared with basal values. However, there were no consistent statistically significant differences among the groups in terms of metabolic syndrome components, acute-phase reactants, and inflammatory mediators. Omentectomy does not have an ancillary short-term significant impact on the components of metabolic syndrome and does not induce important changes in the inflammatory mediators in patients undergoing LRYGB. Operative time is more prolonged when omentectomy is performed.

  17. Educators' Understanding of the Mediation Role in the Classroom

    ERIC Educational Resources Information Center

    Ngidi, D. P.

    2012-01-01

    This study investigated educators' understanding of the mediation role in the classroom. A quantitative research approach was used in a survey of a sample of 261 participants. To this end, a questionnaire was used for collecting data. The Chi-square test was used to analyse data and to test the hypotheses of the study. The findings indicated that…

  18. Negative thinking as a coping strategy mediator of pain and internalizing symptoms in adolescents with sickle cell disease.

    PubMed

    Barakat, Lamia P; Schwartz, Lisa A; Simon, Katherine; Radcliffe, Jerilynn

    2007-06-01

    The objective of this study was to examine the role of coping strategies, specifically negative thinking, in mediating the association of pain with symptoms of anxiety and depression in adolescents with sickle cell disease. Fifty-two 12-18-year-old adolescents with sickle cell disease completed a daily pain diary and paper-and-pencil measures of pain, pain coping, depression and anxiety. Symptoms of depression and anxiety were within the non-clinical range. Preliminary analyses indicated that lower family income was associated with higher reports of pain and negative thinking. Mediation regression analyses supported negative thinking as mediating the association of: (1) pain intensity with depression, and (2) pain interference with daily activities with anxiety. Findings highlight negative thinking as a factor compromising adolescents' adaptation to sickle cell pain; however, further investigation is required to determine the mediating influence of pain coping. Associations for lower income emphasize the multiple risk factors experienced by many of these adolescents.

  19. NMC stratospheric analyses during the 1987 Antarctic expedition

    NASA Technical Reports Server (NTRS)

    Gelman, Melvyn E.; Newman, Paul A.

    1988-01-01

    Stratospheric constant pressure analyses of geopotential height and temperature, produced as part of regular operations at the National Meteorological Center (NMC), were used by several participants of the Antarctic Ozone Expedition. A brief decription is given of the NMC stratospheric analyses and the data that are used to derive them. In addition, comparisons of the analysis values at the locations of radiosonde and aircraft data are presented to provide indications for assessing the representativeness of the NMC stratospheric analyses during the 1987 Antarctic winter-spring period.

  20. An examination of mediators of the transfer of cognitive speed of processing training to everyday functional performance.

    PubMed

    Edwards, Jerri D; Ruva, Christine L; O'Brien, Jennifer L; Haley, Christine B; Lister, Jennifer J

    2013-06-01

    The purpose of these analyses was to examine mediators of the transfer of cognitive speed of processing training to improved everyday functional performance (J. D. Edwards, V. G. Wadley,, D. E. Vance, D. L. Roenker, & K. K. Ball, 2005, The impact of speed of processing training on cognitive and everyday performance. Aging & Mental Health, 9, 262-271). Cognitive speed of processing and visual attention (as measured by the Useful Field of View Test; UFOV) were examined as mediators of training transfer. Secondary data analyses were conducted from the Staying Keen in Later Life (SKILL) study, a randomized cohort study including 126 community dwelling adults 63 to 87 years of age. In the SKILL study, participants were randomized to an active control group or cognitive speed of processing training (SOPT), a nonverbal, computerized intervention involving perceptual practice of visual tasks. Prior analyses found significant effects of training as measured by the UFOV and Timed Instrumental Activities of Daily Living (TIADL) Tests. Results from the present analyses indicate that speed of processing for a divided attention task significantly mediated the effect of SOPT on everyday performance (e.g., TIADL) in a multiple mediation model accounting for 91% of the variance. These findings suggest that everyday functional improvements found from SOPT are directly attributable to improved UFOV performance, speed of processing for divided attention in particular. Targeting divided attention in cognitive interventions may be important to positively affect everyday functioning among older adults. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  1. Does Competence Mediate the Associations between Puberty and Internalizing or Externalizing Problems in Adolescent Girls

    PubMed Central

    Negriff, Sonya; Hillman, Jennifer, B.; Dorn, Lorah D.

    2011-01-01

    Purpose To examine separate mediational models linking a) menarcheal status or b) pubertal timing to internalizing and externalizing problems through competence. Method Cross-sectional analyses of 262 adolescent girls (11–17 years; M=14.93, SD=2.17) enrolled in a longitudinal study examining the association of psychological functioning and smoking with reproductive and bone health. Measures of menarcheal status (pre/post), pubertal timing (early, on-time, or late), internalizing and externalizing behavior, and perceived competence (parent and adolescent report) were obtained. Structural Equation Modeling was used for analyses. Results Perceived competence was found to fully mediate the association between menarcheal status and parent report of internalizing and externalizing problems. For adolescent report, there was a full mediation effect for internalizing problems but a partial mediation effect for externalizing problems. Being menarcheal was related to lower competence which was related to higher internalizing and externalizing problems. Models including pubertal timing were not significant. Conclusions Perceived competence is important in understanding the associations between menarcheal status and internalizing and externalizing problems. Interventions targeting competence, particularly in post-menarcheal girls, may reduce or prevent problem behaviors. PMID:21939864

  2. Transforming growth factor beta induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis.

    PubMed

    Fantini, M C; Becker, C; Tubbe, I; Nikolaev, A; Lehr, H A; Galle, P; Neurath, M F

    2006-05-01

    The imbalance between effector and regulatory T cells plays a central role in the pathogenesis of inflammatory bowel diseases. In addition to the thymus, CD4+CD25+ regulatory T cells can be induced in the periphery from a population of CD25- T cells by treatment with transforming growth factor beta (TGF-beta). Here, we analysed the in vivo function of TGF-beta induced regulatory T (Ti-Treg) cells in experimental colitis. Ti-Treg cells were generated in cell culture in the presence or absence of TGF-beta and tested for their regulatory potential in experimental colitis using the CD4+CD62L+ T cell transfer model. Ti-Treg cells significantly suppressed Th1 mediated colitis on CD4+CD62L+ T cell transfer in vivo, as shown by high resolution endoscopy, histology, immunohistochemistry, and cytokine analysis. Further analysis of in vivo and in vitro expanded Ti-Treg cells showed that exogenous interleukin 2 (IL-2) was crucial for survival and expansion of these cells. Our data suggest that regulatory Ti-Treg cells expand by TGF-beta and exogenous IL-2 derived from effector T cells at the site of inflammation. In addition to Tr1 and thymic CD4+CD25+ T cells, peripheral Ti-Treg cells emerge as a class of regulatory T cells with therapeutic potential in T cell mediated chronic intestinal inflammation.

  3. The relationship between pain, disability, guilt and acceptance in low back pain: a mediation analysis.

    PubMed

    Serbic, Danijela; Pincus, Tamar

    2017-08-01

    Pain-related guilt is a common yet unexplored psychological factor in low back pain (LBP). It has recently been linked to greater depression, anxiety and disability in LBP, hence an understanding of how it can be managed in the presence of pain and disability is necessary. Since acceptance of pain has been shown to be associated with improved outcomes in chronic pain, we examined whether it might also help reduce guilt in people with LBP. To this end, a series of mediation analyses were conducted on data from 287 patients with chronic LBP, in which acceptance of pain was tested as a mediator of the relationship between pain/disability and guilt. Results showed that acceptance of pain reduced the impact of pain/disability on pain-related guilt in all mediation analyses. Pain-related guilt might be a potential target for acceptance based interventions, thus this relationship should be further tested using longitudinal designs.

  4. Socioeconomic status and executive function: developmental trajectories and mediation.

    PubMed

    Hackman, Daniel A; Gallop, Robert; Evans, Gary W; Farah, Martha J

    2015-09-01

    Childhood socioeconomic status (SES) predicts executive function (EF), but fundamental aspects of this relation remain unknown: the developmental course of the SES disparity, its continued sensitivity to SES changes during that course, and the features of childhood experience responsible for the SES-EF relation. Regarding course, early disparities would be expected to grow during development if caused by accumulating stressors at a given constant level of SES. Alternatively, they would narrow if schooling partly compensates for the effects of earlier deprivation, allowing lower-SES children to 'catch up'. The potential for later childhood SES change to affect EF is also unknown. Regarding mediating factors, previous analyses produced mixed answers, possibly due to correlation amongst candidate mediators. We address these issues with measures of SES, working memory and planning, along with multiple candidate mediators, from the NICHD Study of Early Childcare (n = 1009). Early family income-to-needs and maternal education predicted planning by first grade, and income-to-needs predicted working memory performance at 54 months. Effects of early SES remained consistent through middle childhood, indicating that the relation between early indicators of SES and EF emerges in childhood and persists without narrowing or widening across early and middle childhood. Changes in family income-to-needs were associated with significant changes in planning and trend-level changes in working memory. Mediation analyses supported the role of early childhood home characteristics in explaining the association between SES and EF, while early childhood maternal sensitivity was specifically implicated in the association between maternal education and planning. Early emerging and persistent SES-related differences in EF, partially explained by characteristics of the home and family environment, are thus a potential source of socioeconomic disparities in achievement and health across

  5. 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.

  6. Sexual Victimization and Somatic Complaints in Pregnancy: Examination of Depression as a Mediator.

    PubMed

    Littleton, Heather

    2015-01-01

    Research suggests that women with histories of sexual victimization are more likely to experience somatic complaints in pregnancy. However, prior studies have been limited by homogenous samples, have primarily only examined the relationship of childhood sexual abuse (CSA) to somatic complaints, and have not examined potential mechanisms explaining this association. Thus, the current study examined the relationship between lifetime sexual victimization history and somatic complaints in pregnancy in an ethnically diverse sample of pregnant women. Additionally, depressive symptoms were examined as a mediator of the sexual victimization-somatic complaints relationship. Women were recruited from the waiting room of a university-affiliated obstetrics-gynecology clinic to complete a study of psychological health and negative sexual experiences. The 407 currently pregnant participants who completed measures of their sexual victimization history, depressive symptoms, and somatic complaints were primarily African American (53.6%), low to middle income (75.4%), and reported an unplanned pregnancy (72%). A total of 27.7% of women had a history of CSA and/or adolescent/adult sexual assault. Mediation analyses using bootstrapping supported depression as a significant mediator of the relationship between sexual victimization and somatic complaints, with a medium-sized effect (κ(2) = .09). Having a history of sexual victimization is associated with risk for poor mental and physical health during pregnancy. There are likely multiple mechanisms explaining the association between sexual victimization and somatic complaints in pregnancy, which should be investigated in future research. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  7. Predicting fruit consumption: the role of habits, previous behavior and mediation effects

    PubMed Central

    2014-01-01

    Background This study assessed the role of habits and previous behavior in predicting fruit consumption as well as their additional predictive contribution besides socio-demographic and motivational factors. In the literature, habits are proposed as a stable construct that needs to be controlled for in longitudinal analyses that predict behavior. The aim of this study is to provide empirical evidence for the inclusion of either previous behavior or habits. Methods A random sample of 806 Dutch adults (>18 years) was invited by an online survey panel of a private research company to participate in an online study on fruit consumption. A longitudinal design (N = 574) was used with assessments at baseline and after one (T2) and two months (T3). Multivariate linear regression analysis was used to assess the differential value of habit and previous behavior in the prediction of fruit consumption. Results Eighty percent of habit strength could be explained by habit strength one month earlier, and 64% of fruit consumption could be explained by fruit consumption one month earlier. Regression analyses revealed that the model with motivational constructs explained 41% of the behavioral variance at T2 and 38% at T3. The addition of previous behavior and habit increased the explained variance up to 66% at T2 and to 59% at T3. Inclusion of these factors resulted in non-significant contributions of the motivational constructs. Furthermore, our findings showed that the effect of habit strength on future behavior was to a large extent mediated by previous behavior. Conclusions Both habit and previous behavior are important as predictors of future behavior, and as educational objectives for behavior change programs. Our results revealed less stability for the constructs over time than expected. Habit strength was to a large extent mediated by previous behavior and our results do not strongly suggest a need for the inclusion of both constructs. Future research needs to assess

  8. Force-Mediating Magnetic Nanoparticles to Engineer Neuronal Cell Function.

    PubMed

    Gahl, Trevor J; Kunze, Anja

    2018-01-01

    Cellular processes like membrane deformation, cell migration, and transport of organelles are sensitive to mechanical forces. Technically, these cellular processes can be manipulated through operating forces at a spatial precision in the range of nanometers up to a few micrometers through chaperoning force-mediating nanoparticles in electrical, magnetic, or optical field gradients. But which force-mediating tool is more suitable to manipulate cell migration, and which, to manipulate cell signaling? We review here the differences in forces sensation to control and engineer cellular processes inside and outside the cell, with a special focus on neuronal cells. In addition, we discuss technical details and limitations of different force-mediating approaches and highlight recent advancements of nanomagnetics in cell organization, communication, signaling, and intracellular trafficking. Finally, we give suggestions about how force-mediating nanoparticles can be used to our advantage in next-generation neurotherapeutic devices.

  9. Positive affect, negative affect, stress, and social support as mediators of the forgiveness-health relationship.

    PubMed

    Green, Michelle; Decourville, Nancy; Sadava, Stanley

    2012-01-01

    Structural equation modeling was used to test a model in which positive affect, negative affect, perceived stress, and social support were hypothesized to mediate the relationship between forgiveness and mental and physical health. Six hundred and twenty-three undergraduates completed a battery of self-report measures. Results of the analyses indicated that the forgiveness-health relation was mediated by positive affect, negative affect, stress, and the interrelationship between negative affect and stress. There was limited support for social support and the interrelationship between positive affect and social support as mediators. The results suggested that the relationship between forgiveness and health is mediated rather than direct. Implications and directions for future research are discussed.

  10. Shielding Analyses for VISION Beam Line at SNS

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

    Popova, Irina; Gallmeier, Franz X

    2014-01-01

    Full-scale neutron and gamma transport analyses were performed to design shielding around the VISION beam line, instrument shielding enclosure, beam stop, secondary shutter including a temporary beam stop for the still closed neighboring beam line to meet requirement is to achieve dose rates below 0.25 mrem/h at 30 cm from the shielding surface. The beam stop and the temporary beam stop analyses were performed with the discrete ordinate code DORT additionally to Monte Carlo analyses with the MCNPX code. Comparison of the results is presented.

  11. Bioavailable dietary phosphate, a mediator of cardiovascular disease, may be decreased with plant-based diets, phosphate binders, niacin, and avoidance of phosphate additives.

    PubMed

    McCarty, Mark F; DiNicolantonio, James J

    2014-01-01

    Increased fasting serum phosphate within the normal physiological range has been linked to increased cardiovascular risk in prospective epidemiology; increased production of fibroblast growth factor 23, and direct vascular effects of phosphate, may mediate this risk. Although dietary phosphate intake does not clearly influence fasting serum phosphate in individuals with normal renal function, increased phosphate intake can provoke a rise in fibroblast growth factor 23, and in diurnal phosphate levels, and hence may adversely influence vascular health. Dietary phosphate absorption can be moderated by emphasizing plant-based dietary choices (which provide phosphate in less bioavailable forms); avoidance of processed foods containing inorganic phosphate food additives; and by ingestion of phosphate-binder drugs, magnesium supplements, or niacin, which precipitate phosphate or suppress its gastrointestinal absorption. The propensity of dietary phosphate to promote vascular calcification may be opposed by optimal intakes of magnesium, vitamin K, and vitamin D; the latter should also counter the tendency of phosphate to elevate parathyroid hormone. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Metagenomic analyses of the late Pleistocene permafrost - additional tools for reconstruction of environmental conditions

    NASA Astrophysics Data System (ADS)

    Rivkina, Elizaveta; Petrovskaya, Lada; Vishnivetskaya, Tatiana; Krivushin, Kirill; Shmakova, Lyubov; Tutukina, Maria; Meyers, Arthur; Kondrashov, Fyodor

    2016-04-01

    A comparative analysis of the metagenomes from two 30 000-year-old permafrost samples, one of lake-alluvial origin and the other from late Pleistocene Ice Complex sediments, revealed significant differences within microbial communities. The late Pleistocene Ice Complex sediments (which have been characterized by the absence of methane with lower values of redox potential and Fe2+ content) showed a low abundance of methanogenic archaea and enzymes from both the carbon and nitrogen cycles, but a higher abundance of enzymes associated with the sulfur cycle. The metagenomic and geochemical analyses described in the paper provide evidence that the formation of the sampled late Pleistocene Ice Complex sediments likely took place under much more aerobic conditions than lake-alluvial sediments.

  13. 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).

  14. 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

  15. Structure and Sequence Analyses of Clustered Protocadherins Reveal Antiparallel Interactions that Mediate Homophilic Specificity.

    PubMed

    Nicoludis, John M; Lau, Sze-Yi; Schärfe, Charlotta P I; Marks, Debora S; Weihofen, Wilhelm A; Gaudet, Rachelle

    2015-11-03

    Clustered protocadherin (Pcdh) proteins mediate dendritic self-avoidance in neurons via specific homophilic interactions in their extracellular cadherin (EC) domains. We determined crystal structures of EC1-EC3, containing the homophilic specificity-determining region, of two mouse clustered Pcdh isoforms (PcdhγA1 and PcdhγC3) to investigate the nature of the homophilic interaction. Within the crystal lattices, we observe antiparallel interfaces consistent with a role in trans cell-cell contact. Antiparallel dimerization is supported by evolutionary correlations. Two interfaces, located primarily on EC2-EC3, involve distinctive clustered Pcdh structure and sequence motifs, lack predicted glycosylation sites, and contain residues highly conserved in orthologs but not paralogs, pointing toward their biological significance as homophilic interaction interfaces. These two interfaces are similar yet distinct, reflecting a possible difference in interaction architecture between clustered Pcdh subfamilies. These structures initiate a molecular understanding of clustered Pcdh assemblies that are required to produce functional neuronal networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Causal mediation analysis with multiple mediators.

    PubMed

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

    2015-03-01

    In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  17. Why childhood-onset type 1 diabetes impacts labour market outcomes: a mediation analysis.

    PubMed

    Persson, Sofie; Dahlquist, Gisela; Gerdtham, Ulf-G; Steen Carlsson, Katarina

    2018-02-01

    Previous studies show a negative effect of type 1 diabetes on labour market outcomes such as employment and earnings later in life. However, little is known about the mechanisms underlying these effects. This study aims to analyse the mediating role of adult health, education, occupation and family formation. A total of 4179 individuals from the Swedish Childhood Diabetes Register and 16,983 individuals forming a population control group born between 1962 and 1979 were followed between 30 and 50 years of age. The total effect of having type 1 diabetes was broken down into a direct effect and an indirect (mediating) effect using statistical mediation analysis. We also analysed whether type 1 diabetes has different effects on labour market outcome between the sexes and across socioeconomic status. Childhood-onset type 1 diabetes had a negative impact on employment (OR 0.68 [95% CI 0.62, 0.76] and OR 0.76 [95% CI 0.67, 0.86]) and earnings (-6%, p < 0.001 and -8%, p < 0.001) for women and men, respectively. Each of the mediators studied contributed to the total effect with adult health and occupational field accounting for the largest part. However, some of the effect could not be attributed to any of the mediators studied and was therefore likely related to other characteristics of the disease that hamper career opportunities. The effect of type 1 diabetes on employment and earnings did not vary significantly according to socioeconomic status of the family (parental education and earnings). A large part of the effect of type 1 diabetes on the labour market is attributed to adult health but there are other important mediating factors that need to be considered to reduce this negative effect.

  18. Job attitudes and well-being among public vs. private physicians: organizational justice and job control as mediators.

    PubMed

    Heponiemi, Tarja; Kuusio, Hannamaria; Sinervo, Timo; Elovainio, Marko

    2011-08-01

    The present study examined whether there are differences in job-related attitudes and well-being among physicians working in private sector and public sector. In addition, we examined whether psychosocial factors (organizational justice and job control) could mediate these possible differences in different sectors. Cross-sectional survey data from the Finnish Health Professional Study was used. A random sample of Finnish physicians included 1522 women and 1047 men aged 25-65 years. Outcome variables were job satisfaction, organizational commitment, psychological distress, work ability and sleeping problems. Job control and organizational justice were measured using established questionnaires. Series of regression analyses were performed and the mediational effects were tested following the procedures outlined by Baron and Kenny. Physicians working in private sector had higher levels of job satisfaction and organizational commitment and lower levels of psychological distress and sleeping problems when compared with physicians working in public sector. Private physicians also had higher levels of organizational justice, which acted as a mediator behind more positive attitudes and better well-being in private sector. Private physicians had higher levels of job control but it did not act as a mediator. Private physicians feel better than public physicians and this is partly due to higher organizational justice in private sector. Public health care organizations should invest effort to increase the fairness in their organizations and management and pay more attention in improving the well-being of their employees, which could possibly increase the attractiveness of public sector as a career option.

  19. Proteomic analysis of the signaling pathway mediated by the heterotrimeric Gα protein Pga1 of Penicillium chrysogenum.

    PubMed

    Carrasco-Navarro, Ulises; Vera-Estrella, Rosario; Barkla, Bronwyn J; Zúñiga-León, Eduardo; Reyes-Vivas, Horacio; Fernández, Francisco J; Fierro, Francisco

    2016-10-06

    The heterotrimeric Gα protein Pga1-mediated signaling pathway regulates the entire developmental program in Penicillium chrysogenum, from spore germination to the formation of conidia. In addition it participates in the regulation of penicillin biosynthesis. We aimed to advance the understanding of this key signaling pathway using a proteomics approach, a powerful tool to identify effectors participating in signal transduction pathways. Penicillium chrysogenum mutants with different levels of activity of the Pga1-mediated signaling pathway were used to perform comparative proteomic analyses by 2D-DIGE and LC-MS/MS. Thirty proteins were identified which showed differences in abundance dependent on Pga1 activity level. By modifying the intracellular levels of cAMP we could establish cAMP-dependent and cAMP-independent pathways in Pga1-mediated signaling. Pga1 was shown to regulate abundance of enzymes in primary metabolic pathways involved in ATP, NADPH and cysteine biosynthesis, compounds that are needed for high levels of penicillin production. An in vivo phosphorylated protein containing a pleckstrin homology domain was identified; this protein is a candidate for signal transduction activity. Proteins with possible roles in purine metabolism, protein folding, stress response and morphogenesis were also identified whose abundance was regulated by Pga1 signaling. Thirty proteins whose abundance was regulated by the Pga1-mediated signaling pathway were identified. These proteins are involved in primary metabolism, stress response, development and signal transduction. A model describing the pathways through which Pga1 signaling regulates different cellular processes is proposed.

  20. 'Not good enough:' Exploring self-criticism's role as a mediator between childhood emotional abuse & adult binge eating.

    PubMed

    Feinson, Marjorie C; Hornik-Lurie, Tzipi

    2016-12-01

    Empirical studies have identified emotional abuse in childhood (CEA) as a risk factor with long-term implications for psychological problems. Indeed, recent studies indicate it is more prevalent than behavioral forms of abuse, (i.e. childhood sexual and physical abuse) and the childhood trauma most clearly associated with subsequent eating pathology in adulthood. However, relatively little is understood about the mechanisms linking these distal experiences. This study explores three psychological mechanisms - self-criticism (SC), depression and anxiety symptoms - as plausible mediators that may account for the relationship between CEA and binge eating (BE) among adult women. Detailed telephone interviews conducted with a community-based sample of 498 adult women (mean age 44) assess BE, CEA and SC along with the most frequently researched psychological variables, anxiety and depression. Regression analyses reveal that BE is partially explained by CEA along with the three mediators. Bootstrapping analysis, which compares multiple mediators within a single model using thousands of repeated random sampling observations from the data set, reveals a striking finding: SC is the only psychological variable that makes a significant contribution to explaining BE severity. The unique role of punitive self-evaluations vis-à-vis binge eating warrants additional research and, in the interim, that clinicians consider broadening treatment interventions accordingly. Copyright © 2016. Published by Elsevier Ltd.

  1. Persistence of Animal and Human Glycopeptide-Resistant Enterococci on Two Norwegian Poultry Farms Formerly Exposed to Avoparcin Is Associated with a Widespread Plasmid-Mediated vanA Element within a Polyclonal Enterococcus faecium Population

    PubMed Central

    Johnsen, P. J.; Østerhus, J. I.; Sletvold, H.; Sørum, M.; Kruse, H.; Nielsen, K.; Simonsen, G. S.; Sundsfjord, A.

    2005-01-01

    The evolutionary processes responsible for the long-term persistence of glycopeptide-resistant Enterococcus faecium (GREF) in nonselective environments were addressed by genetic analyses of E. faecium populations in animals and humans on two Norwegian poultry farms that were previously exposed to avoparcin. A total of 222 fecal GREF (n = 136) and glycopeptide-susceptible (n = 86) E. faecium (GSEF) isolates were obtained from farmers and poultry on three separate occasions in 1998 and 1999. Pulsed-field gel electrophoresis (PFGE) and plasmid DNA analyses discerned 22 GREF and 32 GSEF PFGE types within shifting polyclonal animal and human E. faecium populations and indicated the presence of transferable plasmid-mediated vanA resistance, respectively. Examples of dominant, persistent GREF PFGE types supported the notion that environmentally well-adapted GREF types may counteract the reversal of resistance. PFGE analyses, sequencing of the purK housekeeping gene, and partial typing of vanA-containing Tn1546 suggested a common animal and human reservoir of glycopeptide resistance. Inverse PCR amplification and sequence analyses targeting the right end of the Tn1546-plasmid junction fragment strongly indicated the presence of a common single Tn1546-plasmid-mediated element in 20 of 22 GREF PFGE types. This observation was further strengthened by vanY-vanZ hybridization analyses of plasmid DNAs as well as the finding of a physical linkage between Tn1546 and a putative postsegregation killing system for seven GREF PFGE types. In conclusion, our observations suggest that the molecular unit of persistence of glycopeptide resistance is a common mobile plasmid-mediated vanA-containing element within a polyclonal GREF population that changes over time. In addition, we propose that “plasmid addiction systems” may contribute to the persistence of GREF in nonselective environments. PMID:15640183

  2. Recent meta-analyses neglect previous systematic reviews and meta-analyses about the same topic: a systematic examination.

    PubMed

    Helfer, Bartosz; Prosser, Aaron; Samara, Myrto T; Geddes, John R; Cipriani, Andrea; Davis, John M; Mavridis, Dimitris; Salanti, Georgia; Leucht, Stefan

    2015-04-14

    As the number of systematic reviews is growing rapidly, we systematically investigate whether meta-analyses published in leading medical journals present an outline of available evidence by referring to previous meta-analyses and systematic reviews. We searched PubMed for recent meta-analyses of pharmacological treatments published in high impact factor journals. Previous systematic reviews and meta-analyses were identified with electronic searches of keywords and by searching reference sections. We analyzed the number of meta-analyses and systematic reviews that were cited, described and discussed in each recent meta-analysis. Moreover, we investigated publication characteristics that potentially influence the referencing practices. We identified 52 recent meta-analyses and 242 previous meta-analyses on the same topics. Of these, 66% of identified previous meta-analyses were cited, 36% described, and only 20% discussed by recent meta-analyses. The probability of citing a previous meta-analysis was positively associated with its publication in a journal with a higher impact factor (odds ratio, 1.49; 95% confidence interval, 1.06 to 2.10) and more recent publication year (odds ratio, 1.19; 95% confidence interval 1.03 to 1.37). Additionally, the probability of a previous study being described by the recent meta-analysis was inversely associated with the concordance of results (odds ratio, 0.38; 95% confidence interval, 0.17 to 0.88), and the probability of being discussed was increased for previous studies that employed meta-analytic methods (odds ratio, 32.36; 95% confidence interval, 2.00 to 522.85). Meta-analyses on pharmacological treatments do not consistently refer to and discuss findings of previous meta-analyses on the same topic. Such neglect can lead to research waste and be confusing for readers. Journals should make the discussion of related meta-analyses mandatory.

  3. Romantic Relationship Length and its Perceived Quality: Mediating Role of Facebook-Related Conflict

    PubMed Central

    Rahaman, H. M. Saidur

    2015-01-01

    The purpose of this study was to investigate how Facebook use is leading to negative relationship outcomes such as cheating and breakup by assessing users’ perceived relationship qualities. It was hypothesized that Facebook-related conflict will be negatively related with users’ relationship length and will also be negatively related with their perceived relationship satisfaction, commitment, and love. Facebook-related conflict further mediates the relationship between relationship length and perceived relationship satisfaction, commitment, and love. Self-report data were gathered from participants (N = 101) in an online survey by employing standard questionnaires. A set of regression and mediation analyses confirmed all the hypotheses of the study. That is, Facebook-related conflict mediates the relationship between relationship length and perceived relationship satisfaction, commitment, and love. Moreover, the magnitude of mediation was highest for relationship satisfaction. Implications for future research and contributions are discussed. PMID:27247665

  4. Proteomic Interaction Patterns between Human Cyclins, the Cyclin-Dependent Kinase Ortholog pUL97 and Additional Cytomegalovirus Proteins

    PubMed Central

    Steingruber, Mirjam; Kraut, Alexandra; Socher, Eileen; Sticht, Heinrich; Reichel, Anna; Stamminger, Thomas; Amin, Bushra; Couté, Yohann; Hutterer, Corina; Marschall, Manfred

    2016-01-01

    The human cytomegalovirus (HCMV)-encoded cyclin-dependent kinase (CDK) ortholog pUL97 associates with human cyclin B1 and other types of cyclins. Here, the question was addressed whether cyclin interaction of pUL97 and additional viral proteins is detectable by mass spectrometry-based approaches. Proteomic data were validated by coimmunoprecipitation (CoIP), Western blot, in vitro kinase and bioinformatic analyses. Our findings suggest that: (i) pUL97 shows differential affinities to human cyclins; (ii) pUL97 inhibitor maribavir (MBV) disrupts the interaction with cyclin B1, but not with other cyclin types; (iii) cyclin H is identified as a new high-affinity interactor of pUL97 in HCMV-infected cells; (iv) even more viral phosphoproteins, including all known substrates of pUL97, are detectable in the cyclin-associated complexes; and (v) a first functional validation of pUL97-cyclin B1 interaction, analyzed by in vitro kinase assay, points to a cyclin-mediated modulation of pUL97 substrate preference. In addition, our bioinformatic analyses suggest individual, cyclin-specific binding interfaces for pUL97-cyclin interaction, which could explain the different strengths of interactions and the selective inhibitory effect of MBV on pUL97-cyclin B1 interaction. Combined, the detection of cyclin-associated proteins in HCMV-infected cells suggests a complex pattern of substrate phosphorylation and a role of cyclins in the fine-modulation of pUL97 activities. PMID:27548200

  5. Music-color associations are mediated by emotion.

    PubMed

    Palmer, Stephen E; Schloss, Karen B; Xu, Zoe; Prado-León, Lilia R

    2013-05-28

    Experimental evidence demonstrates robust cross-modal matches between music and colors that are mediated by emotional associations. US and Mexican participants chose colors that were most/least consistent with 18 selections of classical orchestral music by Bach, Mozart, and Brahms. In both cultures, faster music in the major mode produced color choices that were more saturated, lighter, and yellower whereas slower, minor music produced the opposite pattern (choices that were desaturated, darker, and bluer). There were strong correlations (0.89 < r < 0.99) between the emotional associations of the music and those of the colors chosen to go with the music, supporting an emotional mediation hypothesis in both cultures. Additional experiments showed similarly robust cross-modal matches from emotionally expressive faces to colors and from music to emotionally expressive faces. These results provide further support that music-to-color associations are mediated by common emotional associations.

  6. Music–color associations are mediated by emotion

    PubMed Central

    Palmer, Stephen E.; Schloss, Karen B.; Xu, Zoe; Prado-León, Lilia R.

    2013-01-01

    Experimental evidence demonstrates robust cross-modal matches between music and colors that are mediated by emotional associations. US and Mexican participants chose colors that were most/least consistent with 18 selections of classical orchestral music by Bach, Mozart, and Brahms. In both cultures, faster music in the major mode produced color choices that were more saturated, lighter, and yellower whereas slower, minor music produced the opposite pattern (choices that were desaturated, darker, and bluer). There were strong correlations (0.89 < r < 0.99) between the emotional associations of the music and those of the colors chosen to go with the music, supporting an emotional mediation hypothesis in both cultures. Additional experiments showed similarly robust cross-modal matches from emotionally expressive faces to colors and from music to emotionally expressive faces. These results provide further support that music-to-color associations are mediated by common emotional associations. PMID:23671106

  7. Negative Opinion of Company Environment Mediates Career Choice of Accountancy Students

    ERIC Educational Resources Information Center

    Tong, David Yoon Kin; Tong, Xue Fa

    2012-01-01

    Purpose: The purpose of this paper is to explore accountancy students' pre-employment decisions as regards pursuing a career after completing an internship. The paper aims to analyse the mediating effect of aspects of students' training experience in firms as direct/indirect factors which influence their career decisions.…

  8. Quantifying Special Generator Ridership in Transit Analyses

    DOT National Transportation Integrated Search

    1997-01-01

    In major investment analyses and transit corridor studies, the impact of conventions, sporting matches, and other special events on transit ridership is often of interest. In many locations, it is hypothesized that additional ridership to and from su...

  9. Attachment and alcohol use amongst athletes: the mediating role of conscientiousness and alexithymia.

    PubMed

    Andres, Fanny; Castanier, Carole; Le Scanff, Christine

    2014-02-01

    The present study aims to explore the mediating effects of conscientiousness and alexithymia in the relationship between parental attachment style and alcohol use in a large sample of athletic young people. Participants included 434 French sport sciences students. Alcohol use, parental attachment style, conscientiousness and alexithymia were assessed. The hypotheses were tested by using regression and bootstrapping mediation analyses. Maternal insecure attachment style is positively associated with alcohol use. The current study highlights a multiple pathway in this relationship. The results reveal the mediating effect of low conscientiousness and alexithymia between maternal insecure attachment and alcohol use. Athletes' alcohol use seems to be the result of a complex association of underlying psychological factors. © 2013.

  10. Mediators of change for multisystemic therapy with juvenile sexual offenders.

    PubMed

    Henggeler, Scott W; Letourneau, Elizabeth J; Chapman, Jason E; Borduin, Charles M; Schewe, Paul A; McCart, Michael R

    2009-06-01

    The mediators of favorable multisystemic therapy (MST) outcomes achieved at 12 months postrecruitment were examined within the context of a randomized effectiveness trial with 127 juvenile sexual offenders and their caregivers. Outcome measures assessed youth delinquency, substance use, externalizing symptoms, and deviant sexual interest/risk behaviors; hypothesized mediators included measures of parenting and peer relations. Data were collected at pretreatment, 6 months postrecruitment, and 12 months postrecruitment. Consistent with the MST theory of change and the small extant literature in this area of research, analyses showed that favorable MST effects on youth antisocial behavior and deviant sexual interest/risk behaviors were mediated by increased caregiver follow-through on discipline practices as well as decreased caregiver disapproval of and concern about the youth's bad friends during the follow-up. These findings have important implications for the community-based treatment of juvenile sexual offenders. Copyright 2009 APA

  11. Bioelectrochemical ethanol production through mediated acetate reduction by mixed cultures.

    PubMed

    Steinbusch, Kirsten J J; Hamelers, Hubertus V M; Schaap, Joris D; Kampman, Christel; Buisman, Cees J N

    2010-01-01

    Biological acetate reduction with hydrogen is a potential method to convert wet biomass waste into ethanol. Since the ethanol concentration and reaction rates are low, this research studies the feasibility of using an electrode, in stead of hydrogen, as an electron donor for biological acetate reduction in conjunction of an electron mediator. Initially, the effect of three selected mediators on metabolic flows during acetate reduction with hydrogen was explored; subsequently, the best performing mediator was used in a bioelectrochemical system to stimulate acetate reduction at the cathode with mixed cultures at an applied cathode potential of -550 mV. In the batch test, methyl viologen (MV) was found to accelerate ethanol production 6-fold and increased ethanol concentration 2-fold to 13.5 +/- 0.7 mM compared to the control. Additionally, MV inhibited n-butyrate and methane formation, resulting in high ethanol production efficiency (74.6 +/- 6%). In the bioelectrochemical system, MV addition to an inoculated cathode led directly to ethanol production (1.82 mM). Hydrogen was coproduced at the cathode (0.0035 Nm(3) hydrogen m(-2) d(-1)), so it remained unclear whether acetate was reduced to ethanol by electrons supplied by the mediator or by hydrogen. As MV reacted irreversibly at the cathode, ethanol production stopped after 5 days.

  12. Anti-Vascular Endothelial Growth Factor Comparative Effectiveness Trial for Diabetic Macular Edema: Additional Efficacy Post Hoc Analyses of a Randomized Clinical Trial.

    PubMed

    Jampol, Lee M; Glassman, Adam R; Bressler, Neil M; Wells, John A; Ayala, Allison R

    2016-12-01

    Post hoc analyses from the Diabetic Retinopathy Clinical Research Network randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME) might influence interpretation of study results. To provide additional outcomes comparing 3 anti-vascular endothelial growth factor (VEGF) agents for DME. Post hoc analyses performed from May 3, 2016, to June 21, 2016, of a randomized clinical trial performed from August 22, 2012, to September 23, 2015, of 660 participants comparing 3 anti-VEGF treatments in eyes with center-involved DME causing vision impairment. Randomization to intravitreous aflibercept (2.0 mg), bevacizumab (1.25 mg), or ranibizumab (0.3 mg) administered up to monthly based on a structured retreatment regimen. Focal/grid laser treatment was added after 6 months for the treatment of persistent DME. Change in visual acuity (VA) area under the curve and change in central subfield thickness (CST) within subgroups based on whether an eye received laser treatment for DME during the study. Post hoc analyses were performed for 660 participants (mean [SD] age, 61 [10] years; 47% female, 65% white, 16% black or African American, 16% Hispanic, and 3% other). For eyes with an initial VA of 20/50 or worse, VA improvement was greater with aflibercept than the other agents at 1 year but superior only to bevacizumab at 2 years. Mean (SD) letter change in VA over 2 years (area under curve) was greater with aflibercept (+17.1 [9.7]) than with bevacizumab (+12.1 [9.4]; 95% CI, +1.6 to +7.3; P < .001) or ranibizumab (+13.6 [8.5]; 95% CI, +0.7 to +6.0; P = .009). When VA was 20/50 or worse at baseline, bevacizumab reduced CST less than the other agents at 1 year, but at 2 years the differences had diminished. In subgroups stratified by baseline VA, anti-VEGF agent, and whether focal/grid laser treatment was performed for DME, the only participants to have a substantial reduction in mean CST between 1 and 2 years were those

  13. Cognitive mediators of treatment outcomes in pediatric functional abdominal pain.

    PubMed

    Levy, Rona L; Langer, Shelby L; Romano, Joan M; Labus, Jennifer; Walker, Lynn S; Murphy, Tasha B; Tilburg, Miranda A L van; Feld, Lauren D; Christie, Dennis L; Whitehead, William E

    2014-12-01

    Cognitive-behavioral (CB) interventions improve outcomes for many pediatric health conditions, but little is known about which mechanisms mediate these outcomes. The goal of this study was to identify whether changes in targeted process variables from baseline to 1 week posttreatment mediate improvement in outcomes in a randomized controlled trial of a brief CB intervention for idiopathic childhood abdominal pain. Two hundred children with persistent functional abdominal pain and their parents were randomly assigned to 1 of 2 conditions: a 3-session social learning and CB treatment (N=100), or a 3-session educational intervention controlling for time and attention (N=100). Outcomes were assessed at 3-, 6-, and 12-month follow-ups. The intervention focused on altering parental responses to pain and on increasing adaptive cognitions and coping strategies related to pain in both parents and children. Multiple mediation analyses were applied to examine the extent to which the effects of the social learning and CB treatment condition on child gastrointestinal (GI) symptom severity and pain as reported by children and their parents were mediated by changes in targeted cognitive process variables and parents' solicitous responses to their child's pain symptoms. Reductions in parents' perceived threat regarding their child's pain mediated reductions in both parent-reported and child-reported GI symptom severity and pain. Reductions in children's catastrophic cognitions mediated reductions in child-reported GI symptom severity but no other outcomes. Reductions in parental solicitousness did not mediate outcomes. Results suggest that reductions in reports of children's pain and GI symptoms after a social learning and CB intervention were mediated at least in part by decreasing maladaptive parent and child cognitions.

  14. Self-reported peer victimization and suicidal ideation in adolescent psychiatric inpatients: the mediating role of negative self-esteem.

    PubMed

    Jones, Heather A; Bilge-Johnson, Sumru; Rabinovitch, Annie E; Fishel, Hazel

    2014-10-01

    The current study investigated relationships among self-reported peer victimization, suicidality, and depression in adolescent psychiatric inpatients. Sixty-seven adolescent psychiatric inpatients at a Midwestern children's hospital completed measures of bullying and peer victimization, suicidal ideation, and depression during their inpatient stay. Analyses indicated significant moderate correlations among victimization, suicidal ideation, and depression in adolescents. Results from mediational analyses found that negative self-esteem mediated the relationship between peer victimization and suicidal ideation. To date, this study is the first to directly examine the mechanisms underlying the relationship between peer victimization and suicidal ideation in adolescent psychiatric inpatients. © The Author(s) 2013.

  15. A Single Peroxisomal Targeting Signal Mediates Matrix Protein Import in Diatoms

    PubMed Central

    Gonzalez, Nicola H.; Felsner, Gregor; Schramm, Frederic D.; Klingl, Andreas; Maier, Uwe-G.; Bolte, Kathrin

    2011-01-01

    Peroxisomes are single membrane bound compartments. They are thought to be present in almost all eukaryotic cells, although the bulk of our knowledge about peroxisomes has been generated from only a handful of model organisms. Peroxisomal matrix proteins are synthesized cytosolically and posttranslationally imported into the peroxisomal matrix. The import is generally thought to be mediated by two different targeting signals. These are respectively recognized by the two import receptor proteins Pex5 and Pex7, which facilitate transport across the peroxisomal membrane. Here, we show the first in vivo localization studies of peroxisomes in a representative organism of the ecologically relevant group of diatoms using fluorescence and transmission electron microscopy. By expression of various homologous and heterologous fusion proteins we demonstrate that targeting of Phaeodactylum tricornutum peroxisomal matrix proteins is mediated only by PTS1 targeting signals, also for proteins that are in other systems imported via a PTS2 mode of action. Additional in silico analyses suggest this surprising finding may also apply to further diatoms. Our data suggest that loss of the PTS2 peroxisomal import signal is not reserved to Caenorhabditis elegans as a single exception, but has also occurred in evolutionary divergent organisms. Obviously, targeting switching from PTS2 to PTS1 across different major eukaryotic groups might have occurred for different reasons. Thus, our findings question the widespread assumption that import of peroxisomal matrix proteins is generally mediated by two different targeting signals. Our results implicate that there apparently must have been an event causing the loss of one targeting signal even in the group of diatoms. Different possibilities are discussed that indicate multiple reasons for the detected targeting switching from PTS2 to PTS1. PMID:21966495

  16. Force-Mediating Magnetic Nanoparticles to Engineer Neuronal Cell Function

    PubMed Central

    Gahl, Trevor J.; Kunze, Anja

    2018-01-01

    Cellular processes like membrane deformation, cell migration, and transport of organelles are sensitive to mechanical forces. Technically, these cellular processes can be manipulated through operating forces at a spatial precision in the range of nanometers up to a few micrometers through chaperoning force-mediating nanoparticles in electrical, magnetic, or optical field gradients. But which force-mediating tool is more suitable to manipulate cell migration, and which, to manipulate cell signaling? We review here the differences in forces sensation to control and engineer cellular processes inside and outside the cell, with a special focus on neuronal cells. In addition, we discuss technical details and limitations of different force-mediating approaches and highlight recent advancements of nanomagnetics in cell organization, communication, signaling, and intracellular trafficking. Finally, we give suggestions about how force-mediating nanoparticles can be used to our advantage in next-generation neurotherapeutic devices. PMID:29867315

  17. Victimization Mediates the Longitudinal Association Between Depressive Symptoms and Violent Behaviors in Adolescence.

    PubMed

    Yu, Rongqin; Branje, Susan; Meeus, Wim; Koot, Hans M; van Lier, Pol; Fazel, Seena

    2018-05-01

    Despite evidence of a positive link between depressive symptoms and violent behaviors, the pathways underlying this longitudinal association remain unknown. Depressive symptoms might drive and reinforce victimization which in turn could increase risk of individuals becoming violent towards others. Thus, we tested whether victimization mediated the link between depressive symptoms and violent behaviors using a 6-year longitudinal study of a community sample of adolescents. The sample included 682 Dutch adolescents (54% boys) from an ongoing longitudinal study RADAR (Research on Adolescent Development and Relationships). From ages 13 to 18 years, depressive symptoms, victimization experiences, and violent behaviors were annually assessed. We conducted longitudinal mediation analyses to test pathways to violence in adolescents with depressive symptoms. Longitudinal analyses revealed that victimization mediated the association between depressive symptoms and violent behaviors from early to late adolescence. As part of this, we found that adolescents' depressive symptoms predicted victimization, and this victimization increased risk of subsequent violent behaviors. In conclusion, links between depressive symptoms and violent behaviors are potentially important to understand adolescent development. Decreasing the occurence of victimization is likely to be an important target for the prevention of violent behaviors in adolescents with depressive symptoms.

  18. Consumer-mediated recycling and cascading trophic interactions.

    PubMed

    Leroux, Shawn J; Loreau, Michel

    2010-07-01

    Cascading trophic interactions mediated by consumers are complex phenomena, which encompass many direct and indirect effects. Nonetheless, most experiments and theory on the topic focus uniquely on the indirect, positive effects of predators on producers via regulation of herbivores. Empirical research in aquatic ecosystems, however, demonstrate that the indirect, positive effects of consumer-mediated recycling on primary producer stocks may be larger than the effects of herbivore regulation, particularly when predators have access to alternative prey. We derive an ecosystem model with both recipient- and donor-controlled trophic relationships to test the conditions of four hypotheses generated from recent empirical work on the role of consumer-mediated recycling in cascading trophic interactions. Our model predicts that predator regulation of herbivores will have larger, positive effects on producers than consumer-mediated recycling in most cases but that consumer-mediated recycling does generally have a positive effect on producer stocks. We demonstrate that herbivore recycling will have larger effects on producer biomass than predator recycling when turnover rates and recycling efficiencies are high and predators prefer local prey. In addition, predictions suggest that consumer-mediated recycling has the largest effects on primary producers when predators prefer allochthonous prey and predator attack rates are high. Finally, our model predicts that consumer-mediated recycling effects may not be largest when external nutrient loading is low. Our model predictions highlight predator and prey feeding relationships, turnover rates, and external nutrient loading rates as key determinants of the strength of cascading trophic interactions. We show that existing hypotheses from specific empirical systems do not occur under all conditions, which further exacerbates the need to consider a broad suite of mechanisms when investigating trophic cascades.

  19. Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer.

    PubMed

    Liang, Haihai; Zhao, Xiaoguang; Wang, Chengyu; Sun, Jian; Chen, Yingzhun; Wang, Guoyuan; Fang, Lei; Yang, Rui; Yu, Mengxue; Gu, Yunyan; Shan, Hongli

    2018-06-21

    A deeper mechanistic understanding of epithelial-to-mesenchymal transition (EMT) regulation is needed to improve current anti-metastasis strategies in ovarian cancer (OvCa). This study was designed to investigate the role of lncRNAs in EMT regulation during process of invasion-metastasis in serous OvCa to improve current anti-metastasis strategies for OvCa. We systematically analyzes high-throughput gene expression profiles of both lncRNAs and protein-coding genes in OvCa samples with integrated epithelial (iE) subtype and integrated mesenchymal (iM) subtype labels. Mouse models, cytobiology, molecular biology assays and clinical samples were performed to elucidate the function and underlying mechanisms of lncRNA PTAF-mediated promotion of EMT and invasion-metastasis in serous OvCa. We constructed a lncRNA-mediated competing endogenous RNA (ceRNA) regulatory network that affects the expression of many EMT-related protein-coding genes in mesenchymal OvCa. Using a combination of in vitro and in vivo studies, we provided evidence that the lncRNA PTAF-miR-25-SNAI2 axis controlled EMT in OvCa. Our results revealed that up-regulated PTAF induced elevated SNAI2 expression by competitively binding to miR-25, which in turn promoted OvCa cell EMT and invasion. Moreover, we found that silencing of PTAF inhibited tumor progression and metastasis in an orthotopic mouse model of OvCa. We then observed a significant correlation between PTAF expression and EMT markers in OvCa patients. The lncRNA PTAF, a mediator of TGF-β signaling, can predispose OvCa patients to metastases and may serve as a potential target for anti-metastatic therapies for mesenchymal OvCa patients.

  20. Astrocytes Regulate GLP-1 Receptor-Mediated Effects on Energy Balance

    PubMed Central

    Reiner, David J.; Mietlicki-Baase, Elizabeth G.; McGrath, Lauren E.; Zimmer, Derek J.; Bence, Kendra K.; Sousa, Gregory L.; Konanur, Vaibhav R.; Krawczyk, Joanna; Burk, David H.; Kanoski, Scott E.; Hermann, Gerlinda E.; Rogers, Richard C.

    2016-01-01

    Astrocytes are well established modulators of extracellular glutamate, but their direct influence on energy balance-relevant behaviors is largely understudied. As the anorectic effects of glucagon-like peptide-1 receptor (GLP-1R) agonists are partly mediated by central modulation of glutamatergic signaling, we tested the hypothesis that astrocytic GLP-1R signaling regulates energy balance in rats. Central or peripheral administration of a fluorophore-labeled GLP-1R agonist, exendin-4, localizes within astrocytes and neurons in the nucleus tractus solitarius (NTS), a hindbrain nucleus critical for energy balance control. This effect is mediated by GLP-1R, as the uptake of systemically administered fluorophore-tagged exendin-4 was blocked by central pretreatment with the competitive GLP-1R antagonist exendin-(9–39). Ex vivo analyses show prolonged exendin-4-induced activation (live cell calcium signaling) of NTS astrocytes and neurons; these effects are also attenuated by exendin-(9–39), indicating mediation by the GLP-1R. In vitro analyses show that the application of GLP-1R agonists increases cAMP levels in astrocytes. Immunohistochemical analyses reveal that endogenous GLP-1 axons form close synaptic apposition with NTS astrocytes. Finally, pharmacological inhibition of NTS astrocytes attenuates the anorectic and body weight-suppressive effects of intra-NTS GLP-1R activation. Collectively, data demonstrate a role for NTS astrocytic GLP-1R signaling in energy balance control. SIGNIFICANCE STATEMENT Glucagon-like peptide-1 receptor (GLP-1R) agonists reduce food intake and are approved by the Food and Drug Administration for the treatment of obesity, but the cellular mechanisms underlying the anorectic effects of GLP-1 require further investigation. Astrocytes represent a major cellular population in the CNS that regulates neurotransmission, yet the role of astrocytes in mediating energy balance is largely unstudied. The current data provide novel evidence that

  1. Childhood abuse and late-life depression: Mediating effects of psychosocial factors for early- and late-onset depression.

    PubMed

    Wielaard, Ilse; Hoyer, Mathijs; Rhebergen, Didi; Stek, Max L; Comijs, Hannie C

    2018-03-01

    Childhood abuse makes people vulnerable to developing depression, even in late life. Psychosocial factors that are common in late life, such as loneliness or lack of a partner, may explain this association. Our aim was to investigate whether the association between childhood abuse and depression in older adults can be explained by psychosocial factors. Cross-sectional data were derived from the Netherlands Study of Depression in Older Persons (aged 60-93), including 132 without lifetime depression, 242 persons with an early-onset depression (<60 years), and 125 with a late-onset (≥60 years) depression. Childhood abuse (yes/no) and a frequency-based childhood abuse index were included. Multinomial regression and multivariable mediation analyses were used to examine the association between childhood abuse and the onset of depression, and the influence of loneliness, social network, and partner status. Multinomial regression analyses showed a significant association between childhood abuse and the childhood abuse index with early- and late-onset depression. Multivariable mediation analyses showed that the association between childhood abuse and early-onset depression was partly mediated by social network size and loneliness. This was particularly present for emotional neglect and psychological abuse, but not for physical and sexual abuse. No psychosocial mediators were found for the association between childhood abuse and late-onset depression. A smaller social network and feelings of loneliness mediate the association between childhood abuse and early-onset depression in older adults. Our findings show the importance of detecting childhood abuse as well as the age at depression onset and mapping of relevant psychosocial factors in the treatment of late-life depression. Copyright © 2018 John Wiley & Sons, Ltd.

  2. Development of Brassica oleracea-nigra monosomic alien addition lines: genotypic, cytological and morphological analyses.

    PubMed

    Tan, Chen; Cui, Cheng; Xiang, Yi; Ge, Xianhong; Li, Zaiyun

    2017-12-01

    We report the development and characterization of Brassica oleracea - nigra monosomic alien addition lines (MAALs) to dissect the Brassica B genome. Brassica nigra (2n = 16, BB) represents the diploid Brassica B genome which carries many useful genes and traits for breeding but received limited studies. To dissect the B genome from B. nigra, the triploid F 1 hybrid (2n = 26, CCB) obtained previously from the cross B. oleracea var. alboglabra (2n = 18, CC) × B. nigra was used as the maternal parent and backcrossed successively to parental B. oleracea. The progenies in BC 1 to BC 3 generations were analyzed by the methods of FISH and SSR markers to screen the monosomic alien addition lines (MAALs) with each of eight different B-genome chromosomes added to C genome (2n = 19, CC + 1B 1-8 ), and seven different MAALs were established, except for the one with chromosome B2 which existed in one triple addition. Most of these MAALs were distinguishable morphologically from each other, as they expressed the characters from B. nigra differently and at variable extents. The alien chromosome remained unpaired as a univalent in 86.24% pollen mother cells at diakinesis or metaphase I, and formed a trivalent with two C-genome chromosomes in 13.76% cells. Transmission frequency of all the added chromosomes was far higher through the ovules (averagely 14.40%) than the pollen (2.64%). The B1, B4 and B5 chromosomes were transmitted by female at much higher rates (22.38-30.00%) than the other four (B3, B6, B7, B8) (5.04-8.42%). The MAALs should be valuable for exploiting the genome structure and evolution of B. nigra.

  3. Friends' Alcohol-Related Social Networking Site Activity Predicts Escalations in Adolescent Drinking: Mediation by Peer Norms.

    PubMed

    Nesi, Jacqueline; Rothenberg, W Andrew; Hussong, Andrea M; Jackson, Kristina M

    2017-06-01

    Adolescents' increased use of social networking sites (SNS) coincides with a developmental period of heightened risk for alcohol use initiation. However, little is known regarding associations between adolescents' SNS use and drinking initiation nor the mechanisms of this association. This study examined longitudinal associations among adolescents' exposure to friends' alcohol-related SNS postings, alcohol-favorable peer injunctive norms, and initiation of drinking behaviors. Participants were 658 high-school students who reported on posting of alcohol-related SNS content by self and friends, alcohol-related injunctive norms, and other developmental risk factors for alcohol use at two time points, 1 year apart. Participants also reported on initiation of three drinking behaviors: consuming a full drink, becoming drunk, and heavy episodic drinking (three or more drinks per occasion). Probit regression analyses were used to predict initiation of drinking behaviors from exposure to alcohol-related SNS content. Path analyses examined mediation of this association by peer injunctive norms. Exposure to friends' alcohol-related SNS content predicted adolescents' initiation of drinking and heavy episodic drinking 1 year later, controlling for demographic and known developmental risk factors for alcohol use (i.e., parental monitoring and peer orientation). In addition, alcohol-favorable peer injunctive norms statistically mediated the relationship between alcohol-related SNS exposure and each drinking milestone. Results suggest that social media plays a unique role in contributing to peer influence processes surrounding alcohol use and highlight the need for future investigative and preventive efforts to account for adolescents' changing social environments. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  4. Mentalizing mediates the relationship between psychopathy and type of aggression in schizophrenia.

    PubMed

    Bo, Sune; Abu-Akel, Ahmad; Kongerslev, Mickey; Haahr, Ulrik Helt; Bateman, Anthony

    2014-01-01

    Convincing evidence demonstrates that psychopathy is associated with premeditated aggression. However, studies have failed to explain why this association exists and whether socio-cognitive functions, such as mentalizing, could explain the relation. This cross-sectional study investigates, in 108 patients with schizophrenia, the association of psychopathy and mentalizing abilities with premeditated and impulsive aggression and probes the nature of their influence on these specific aggression patterns. Patients' engagement in premeditated aggression was associated with diminishing mentalizing and increasing psychopathic tendencies. Moreover, mediation analyses reveal that the ability to attribute mental states to others mediates the relation between psychopathy and type of aggression. This mediation is facilitated by a specific mentalizing profile characterized by the presence of intact cognitive and deficient emotional mentalizing capacities. This study is the first to report a mediating effect of mentalizing on the relationship between psychopathy and type of aggression in schizophrenia. Implications of these results are discussed.

  5. Does competence mediate the associations between puberty and internalizing or externalizing problems in adolescent girls?

    PubMed

    Negriff, Sonya; Hillman, Jennifer B; Dorn, Lorah D

    2011-10-01

    To examine separate mediational models linking (a) menarcheal status or (b) pubertal timing to internalizing and externalizing problems through competence. This study involved cross-sectional analyses of 262 adolescent girls (age: 11-17 years; mean = 14.93, standard deviation = 2.17) enrolled in a longitudinal study examining the association of psychological functioning and smoking with reproductive and bone health. Measures of menarcheal status (pre/post), pubertal timing (early, on-time, or late), internalizing and externalizing behavior, and perceived competence (parent and adolescent report) were obtained. Structural equation modeling was used for analyses. Perceived competence was found to fully mediate the association between menarcheal status and parent report of internalizing and externalizing problems. For adolescent report, there was a full mediation effect for internalizing problems but a partial mediation effect for externalizing problems. Being menarcheal was related to lower competence, which was in turn related to higher internalizing and externalizing problems. Models including pubertal timing were not significant. Perceived competence is important in understanding the associations between menarcheal status and internalizing and externalizing problems. Interventions targeting competence, particularly in postmenarcheal girls, may reduce or prevent problem behaviors. Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  6. Oncologist burnout and compassion fatigue: investigating time pressure at work as a predictor and the mediating role of work-family conflict.

    PubMed

    Kleiner, Sibyl; Wallace, Jean E

    2017-09-11

    Oncologists are at high risk of poor mental health. Prior research has focused on burnout, and has identified heavy workload as a key predictor. Compassion fatigue among physicians has generally received less attention, although medical specialties such as oncology may be especially at risk of compassion fatigue. We contribute to research by identifying predictors of both burnout and compassion fatigue among oncologists. In doing so, we distinguish between quantitative workload (e.g., work hours) and subjective work pressure, and test whether work-family conflict mediates the relationships between work pressure and burnout or compassion fatigue. In a cross-sectional study, oncologists from across Canada (n = 312) completed questionnaires assessing burnout, compassion fatigue, workload, time pressure at work, work-family conflict, and other personal, family, and occupational characteristics. Analyses use Ordinary Least Squares regression. Subjective time pressure at work is a key predictor of both burnout and compassion fatigue. Our results also show that work-family conflict fully mediates these relationships. Overall, the models explain more of the variation in burnout as compared to compassion fatigue. Our study highlights the need to consider oncologists' subjective time pressure, in addition to quantitative workload, in interventions to improve mental health. The findings also highlight a need to better understand additional predictors of compassion fatigue.

  7. The Mediational Role of Coping Strategies in the Relationship Between Self-Esteem and Risk of Internet Addiction

    PubMed Central

    Servidio, Rocco; Gentile, Ambra; Boca, Stefano

    2018-01-01

    The aim of the present study is to explore, through a mediation model, the relationship among self-esteem, coping strategies, and the risk of Internet addiction in a sample of 300 Italian university students. We submitted the data to a descriptive, mediational comparison between variables (t-test), and correlational statistical analyses. The results confirmed the effect of self-esteem on the risk of Internet addiction. However, we found that the introduction of coping strategies as a mediator gives rise to partial mediation. A low level of self-esteem is a predictor of avoidance-oriented coping that, in turn, affects the risk of Internet addiction.

  8. Evidence for the indirect effects of perceived public stigma on psychosocial outcomes: The mediating role of self-stigma.

    PubMed

    Kao, Yu-Chen; Lien, Yin-Ju; Chang, Hsin-An; Wang, Sheng-Chiang; Tzeng, Nian-Sheng; Loh, Ching-Hui

    2016-06-30

    This study examined the possible mediating role of self-stigma in the relationship between perceived public stigma and psychosocial outcomes and how this mechanism may be contingent on illness severity in a non-Western (Chinese) sample. A total of 251 participants, namely 151 psychiatric outpatients with psychotic disorders and 100 psychiatric outpatients without psychotic disorders, completed a questionnaire on stigma and psychosocial outcomes that covered topics such as self-esteem, depressive symptoms, and subjective quality of life (QoL). Using a cross-sectional design, ordinary least squares regression and bootstrapping mediation analyses were used to test whether self-stigma mediated the relationship between perceived public stigma and psychosocial outcomes and whether this mediating process was moderated by diagnostic status. The results indicated that self-stigma mediated the effect of perceived public stigma on psychosocial outcomes such as self-esteem, depressive symptoms, and subjective QoL among both patients with psychotic disorders and those without psychotic disorders after controlling for demographic and clinical characteristics. Further, moderated mediation analyses revealed that the indirect effect of perceived public stigma on psychosocial outcomes were not moderated by the status of psychotic diagnoses. Self-stigma might be an essential and tractable target for interventions aimed at breaking the vicious cycle of discrimination and stigmatization toward people with mental illness regardless of their diagnoses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. 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.

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

    PubMed

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

    2014-05-01

    Using mediation analysis, a causal relationship between the AHSG gene and bone mineral density (BMD) through fetuin-A and body mass index (BMI) mediators was suggested. Fetuin-A, a multifunctional protein of hepatic origin, is associated with bone mineral density. It is unclear if this association is causal. This study aimed at clarification of this issue. A cross-sectional study was conducted among 1,741 healthy workers from the Electricity Generating Authority of Thailand (EGAT) cohort. The alpha-2-Heremans-Schmid glycoprotein (AHSG) rs2248690 gene was genotyped. Three mediation models were constructed using seemingly unrelated regression analysis. First, the ln[fetuin-A] group was regressed on the AHSG gene. Second, the BMI group was regressed on the AHSG gene and the ln[fetuin-A] group. Finally, the BMD model was constructed by fitting BMD on two mediators (ln[fetuin-A] and BMI) and the independent AHSG variable. All three analyses were adjusted for confounders. The prevalence of the minor T allele for the AHSG locus was 15.2%. The AHSG locus was highly related to serum fetuin-A levels (P < 0.001). Multiple mediation analyses showed that AHSG was significantly associated with BMD through the ln[fetuin-A] and BMI pathway, with beta coefficients of 0.0060 (95% CI 0.0038, 0.0083) and 0.0030 (95% CI 0.0020, 0.0045) at the total hip and lumbar spine, respectively. About 27.3 and 26.0% of total genetic effects on hip and spine BMD, respectively, were explained by the mediation effects of fetuin-A and BMI. Our study suggested evidence of a causal relationship between the AHSG gene and BMD through fetuin-A and BMI mediators.

  11. Baclofen, a GABABR Agonist, Ameliorates Immune-Complex Mediated Acute Lung Injury by Modulating Pro-Inflammatory Mediators

    PubMed Central

    Jin, Shunying; Merchant, Michael L.; Ritzenthaler, Jeffrey D.; McLeish, Kenneth R.; Lederer, Eleanor D.; Torres-Gonzalez, Edilson; Fraig, Mostafa; Barati, Michelle T.; Lentsch, Alex B.; Roman, Jesse; Klein, Jon B.; Rane, Madhavi J.

    2015-01-01

    Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP), in the bronchoalveolar lavage fluid (BALF). Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting a

  12. Mediation analysis of decisional balance, sun avoidance and sunscreen use in the precontemplation and preparation stages for sun protection.

    PubMed

    Santiago-Rivas, Marimer; Velicer, Wayne F; Redding, Colleen

    2015-01-01

    Mediation analyses of sun protection were conducted testing structural equation models using longitudinal data with three waves. An effect was said to be mediated if the standardised path between processes of change, decisional balance and sun protection outcomes was significant. Longitudinal models of sun protection using data from individuals in the precontemplation (N = 964) and preparation (N = 463) stages who participated of an expert system intervention. Nine processes of change for sun protection, decisional balance constructs of sun protection (pros and cons), sun avoidance behaviour and sunscreen use. With the exception of two processes in the preparation stage, processes of change predicted the pros (r = .126-.614), and the pros predicted the outcomes (r = .181-.272). Three models with the cons as mediator in the preparation stage, and none in the precontemplation stage, showed a mediated relationship between processes and outcomes. In general, mediation analyses found both the process of change-to-pros and pros-to-behaviour paths significant for both precontemplation and preparation stages, and for both sun avoidance and sunscreen use outcomes. Findings provide support for the importance of assessing the role of underlying risk cognitions in improving sun protection adherence.

  13. Computational Analyses of an Evolutionary Arms Race between Mammalian Immunity Mediated by Immunoglobulin A and Its Subversion by Bacterial Pathogens

    PubMed Central

    Pinheiro, Ana; Woof, Jenny M.; Abi-Rached, Laurent; Parham, Peter; Esteves, Pedro J.

    2013-01-01

    IgA is the predominant immunoglobulin isotype in mucosal tissues and external secretions, playing important roles both in defense against pathogens and in maintenance of commensal microbiota. Considering the complexity of its interactions with the surrounding environment, IgA is a likely target for diversifying or positive selection. To investigate this possibility, the action of natural selection on IgA was examined in depth with six different methods: CODEML from the PAML package and the SLAC, FEL, REL, MEME and FUBAR methods implemented in the Datamonkey webserver. In considering just primate IgA, these analyses show that diversifying selection targeted five positions of the Cα1 and Cα2 domains of IgA. Extending the analysis to include other mammals identified 18 positively selected sites: ten in Cα1, five in Cα2 and three in Cα3. All but one of these positions display variation in polarity and charge. Their structural locations suggest they indirectly influence the conformation of sites on IgA that are critical for interaction with host IgA receptors and also with proteins produced by mucosal pathogens that prevent their elimination by IgA-mediated effector mechanisms. Demonstrating the plasticity of IgA in the evolution of different groups of mammals, only two of the eighteen selected positions in all mammals are included in the five selected positions in primates. That IgA residues subject to positive selection impact sites targeted both by host receptors and subversive pathogen ligands highlights the evolutionary arms race playing out between mammals and pathogens, and further emphasizes the importance of IgA in protection against mucosal pathogens. PMID:24019941

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

    PubMed

    Otsuka, Ayano; Takaesu, Yoshikazu; Sato, Mitsuhiko; Masuya, Jiro; Ichiki, Masahiko; Kusumi, Ichiro; Inoue, Takeshi

    2017-01-01

    Recent studies have suggested that multiple factors interact with the onset and prognosis of major depressive disorders. In this study, we investigated how child abuse, affective temperaments, and interpersonal sensitivity are interrelated, and how they affect depressive symptoms in the general adult population. A total of 415 volunteers from the general adult population completed the Patient Health Questionnaire-9, the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire version, the Child Abuse and Trauma Scale, and the Interpersonal Sensitivity Measure, which are all self-administered questionnaires. Data were subjected to structural equation modeling (Mplus), and single and multiple regression analyses. The effect of child abuse on depressive symptoms was mediated by interpersonal sensitivity and 4 affective temperaments, including depressive, cyclothymic, anxious, and irritable temperaments. In addition, the effect of these temperaments on depressive symptoms was mediated by interpersonal sensitivity, indicating the indirect enhancement of depressive symptoms. In contrast to these 4 temperaments, the hyperthymic temperament did not mediate the effect of child abuse on depressive symptoms; its effect was not mediated by interpersonal sensitivity. However, a greater hyperthymic temperament predicted decreased depressive symptoms and interpersonal sensitivity, independent of any mediation effect. Because this is a cross-sectional study, long-term prospective studies are necessary to confirm its findings. Therefore, recall bias should be considered when interpreting the results. As the subjects were adults from the general population, the results may not be generalizable towards all patients with major depression. This study suggests that child abuse and affective temperaments affect depressive symptoms partly through interpersonal sensitivity. Interpersonal sensitivity may have a major role in forming the link between abuse, affective

  15. Potential mediating pathways through which sports participation relates to reduced risk of suicidal ideation.

    PubMed

    Taliaferro, Lindsay A; Rienzo, Barbara A; Miller, M David; Pigg, R Morgan; Dodd, Virginia J

    2010-09-01

    Suicide ranks as the third leading cause of death for American youth. Researchers examining sport participation and suicidal behavior have regularly found inverse relationships. This study represents the first effort to test a model depicting potential mechanisms through which sport participation relates to reduced risk of suicidal ideation. The participants were 450 undergraduate students. Measures assessed participants' involvement in university-run sports and other activities; frequency of physical activity; and perceived social support, self-esteem, depression, hopelessness, loneliness, and suicidal ideation. Regression analyses confirmed a path model and tested for mediation effects. Vigorous activity mediated relationships between sport participation and self-esteem and depression; and self-esteem and depression mediated the relationship between vigorous activity and suicidal ideation. Social support mediated relationships between sport participation and depression, hopelessness, and loneliness; and each of these risk factors partially mediated the relationship between social support and suicidal ideation. However no variable fully mediated the relationship between sport participation and suicidal ideation. This study provides a foundation for research designed to examine pathways through which sport participation relates to reduced risk of suicidal behavior.

  16. Identification of Mediator Kinase Substrates in Human Cells using Cortistatin A and Quantitative Phosphoproteomics.

    PubMed

    Poss, Zachary C; Ebmeier, Christopher C; Odell, Aaron T; Tangpeerachaikul, Anupong; Lee, Thomas; Pelish, Henry E; Shair, Matthew D; Dowell, Robin D; Old, William M; Taatjes, Dylan J

    2016-04-12

    Cortistatin A (CA) is a highly selective inhibitor of the Mediator kinases CDK8 and CDK19. Using CA, we now report a large-scale identification of Mediator kinase substrates in human cells (HCT116). We identified over 16,000 quantified phosphosites including 78 high-confidence Mediator kinase targets within 64 proteins, including DNA-binding transcription factors and proteins associated with chromatin, DNA repair, and RNA polymerase II. Although RNA-seq data correlated with Mediator kinase targets, the effects of CA on gene expression were limited and distinct from CDK8 or CDK19 knockdown. Quantitative proteome analyses, tracking around 7,000 proteins across six time points (0-24 hr), revealed that CA selectively affected pathways implicated in inflammation, growth, and metabolic regulation. Contrary to expectations, increased turnover of Mediator kinase targets was not generally observed. Collectively, these data support Mediator kinases as regulators of chromatin and RNA polymerase II activity and suggest their roles extend beyond transcription to metabolism and DNA repair. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  17. The Mediating Role of Partner Communication Frequency on Condom Use Among African-American Adolescent Females Participating in an HIV Prevention Intervention

    PubMed Central

    Sales, Jessica M.; Lang, Delia L.; DiClemente, Ralph J.; Latham, Teaniese P; Wingood, Gina M.; Hardin, James W.; Rose, Eve S.

    2011-01-01

    Objective Although effective HIV prevention interventions have been developed for adolescents, few interventions have explored whether components of the intervention are responsible for the observed changes in behaviors post-intervention. This study examined the mediating role of partner communication frequency on African-American adolescent females’ condom use post-participation in a demonstrated efficacious HIV risk-reduction intervention. Main Outcome Measures Percent condom use in the past 60 days and consistent condom use in the past 6o days across the 12-month follow-up period. Design As part of a randomized controlled trial of African-American adolescent females (N=715), 15-21 years, seeking sexual health services, completed a computerized interview at baseline (prior to intervention) and again 6- and 12-month follow-up post-intervention participation. The interview assessed adolescents’ sexual behavior and partner communication skills, among other variables, at each time point. Using generalized estimating equation (GEE) techniques, both logistic and linear regression models were employed to test mediation over the 12-month follow-up period. Additional tests were conducted to assess the significance of the mediated models. Results Mediation analyses observed that partner communication frequency was a significant partial mediator of both proportion condom-protected sex acts (p =.001) and consistent condom use (p = .001). Conclusion Partner communication frequency, an integral component of this HIV intervention, significantly increased as a function of participating in the intervention partially explaining the change in condom use observed 12-months post-intervention. Understanding what intervention components are associated with behavior change is important for future intervention development. PMID:21843001

  18. Filipino Americans and racism: A multiple mediation model of coping.

    PubMed

    Alvarez, Alvin N; Juang, Linda P

    2010-04-01

    Although the literature on Asian Americans and racism has been emerging, few studies have examined how coping influences one's encounters with racism. To advance the literature, the present study focused on the psychological impact of Filipino Americans' experiences with racism and the role of coping as a mediator using a community-based sample of adults (N = 199). Two multiple mediation models were used to examine the mediating effects of active, avoidance, support-seeking, and forbearance coping on the relationship between perceived racism and psychological distress and self-esteem, respectively. Separate analyses were also conducted for men and women given differences in coping utilization. For men, a bootstrap procedure indicated that active, support-seeking, and avoidance coping were mediators of the relationship between perceived racism and psychological distress. Active coping was negatively associated with psychological distress, whereas both support seeking and avoidance were positively associated with psychological distress. A second bootstrap procedure for men indicated that active and avoidance coping mediated the relationship between perceived racism and self-esteem such that active coping was positively associated with self-esteem, and avoidance was negatively associated with self-esteem. For women, only avoidance coping had a significant mediating effect that was associated with elevations in psychological distress and decreases in self-esteem. The results highlight the importance of examining the efficacy of specific coping responses to racism and the need to differentiate between the experiences of men and women. PsycINFO Database Record (c) 2010 APA, all rights reserved.

  19. Cardiorespiratory Fitness as a Mediator of the Influence of Diet on Obesity in Children.

    PubMed

    Lahoz-García, Noelia; García-Hermoso, Antonio; Milla-Tobarra, Marta; Díez-Fernández, Ana; Soriano-Cano, Alba; Martínez-Vizcaíno, Vicente

    2018-03-16

    The association between diet and obesity has been widely studied and it continues to be controversial; however, the extent to which cardiorespiratory fitness (CRF) acts as a confounder or mediator in this relation has not been analyzed. The aim of this study is to examine if the relation between diet and obesity is mediated by CRF. In this cross-sectional study, fat mass (by electronic bioimpedance) was measured in 320 schoolchildren, aged 9-11 years. Diet was measured through two computerised 24-h dietary recalls and CRF was assessed by the 20-m shuttle run test. Simple mediation analyses were fitted. CRF acts as a partial mediator in the negative relationship between dietary factors (energy intake/weight, carbohydrate intake/weight, protein intake/weight, and fat intake/weight) and fat mass. The percentage of mediation ranged from 24.3 to 33.2%. Thus, Spanish schoolchildren with higher levels of energy and macronutrients intake had lower adiposity levels, especially when they had good levels of CRF.

  20. Cardiorespiratory Fitness as a Mediator of the Influence of Diet on Obesity in Children

    PubMed Central

    Lahoz-García, Noelia; Milla-Tobarra, Marta; Soriano-Cano, Alba

    2018-01-01

    The association between diet and obesity has been widely studied and it continues to be controversial; however, the extent to which cardiorespiratory fitness (CRF) acts as a confounder or mediator in this relation has not been analyzed. The aim of this study is to examine if the relation between diet and obesity is mediated by CRF. In this cross-sectional study, fat mass (by electronic bioimpedance) was measured in 320 schoolchildren, aged 9–11 years. Diet was measured through two computerised 24-h dietary recalls and CRF was assessed by the 20-m shuttle run test. Simple mediation analyses were fitted. CRF acts as a partial mediator in the negative relationship between dietary factors (energy intake/weight, carbohydrate intake/weight, protein intake/weight, and fat intake/weight) and fat mass. The percentage of mediation ranged from 24.3 to 33.2%. Thus, Spanish schoolchildren with higher levels of energy and macronutrients intake had lower adiposity levels, especially when they had good levels of CRF. PMID:29547513

  1. Adult attachment, perceived social support, cultural orientation, and depressive symptoms: A moderated mediation model.

    PubMed

    Zhu, Wenzhen; Wang, Chiachih Dc; Chong, Chu Chian

    2016-11-01

    In the current study, we tested a moderated mediation model in which cultural orientation moderated the mediation model of adult attachment-perceived social support-depressive symptoms, using 2 comparable cross-cultural samples of college students recruited from China and the U.S. (n = 363 for each group). Results indicated that perceived social support mediated the effect of attachment anxiety on depressive symptoms as well as the link between attachment avoidance and depression in both samples. Moderated mediation analyses using PROCESS revealed that interdependent self-construal significantly buffered the indirect effect of attachment avoidance (via perceived social support) on depressive symptoms. The findings indicated significant differences in the mediation models between the U.S. and China groups and interdependent self-construal accounted for the between-country differences. Limitations, implications of the findings, and future research directions are discussed from the perspectives of cross-cultural variation of adult attachment functioning. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  2. Morningness-eveningness and daytime functioning in university students: the mediating role of sleep characteristics.

    PubMed

    Bakotic, Marija; Radosevic-Vidacek, Biserka; Koscec Bjelajac, Adrijana

    2017-04-01

    The aim of this study was to explore the mediating role of sleep characteristics in the relationship between morningness-eveningness and three different aspects of daytime functioning: daytime sleepiness, depressive mood and substance use in university students. A multiple mediator model was proposed with sleep debt, poor sleep quality and bedtime delay at weekends as parallel mediators in these relationships. We analysed the data of 1052 university students aged 18-25 years who completed a modified version of the School Sleep Habits Survey, which included questions on sleep and the Composite Scale of Morningness, Sleepiness Scale, Depressive Mood Scale and Substance Use Scale. Students with more pronounced eveningness reported greater daytime sleepiness, greater depressive mood and more frequent substance use, as well as greater sleep debt, poorer sleep quality and greater bedtime delay at weekends. Mediation analyses indicated that morningness-eveningness affected daytime sleepiness and substance use both directly and indirectly through all proposed sleep-related mediators. However, the effect of morningness-eveningness on depressive mood was entirely indirect and was accounted for more by poor sleep than by sleep debt or bedtime irregularity. In conclusion, there are multiple possible mechanisms through which morningness-eveningness affects daytime functioning in university students, and sleep characteristics are a significant mechanism. Sleep debt, poor sleep quality and bedtime irregularity can, to a significant extent, explain the feeling of daytime sleepiness and greater substance use in students with eveningness preferences. However, more depressed mood in the evening-orientated students is primarily a consequence of their poor sleep quality. © 2016 European Sleep Research Society.

  3. The Mediating Role of Emotion Dysregulation in the Relations Between Childhood Trauma History and Adult Attachment and Borderline Personality Disorder Features: A Study of Italian Nonclinical Participants.

    PubMed

    Fossati, Andrea; Gratz, Kim L; Somma, Antonella; Maffei, Cesare; Borroni, Serena

    2016-10-01

    In order to evaluate if emotion dysregulation significantly mediates the relationships between childhood abuse and adult attachment and borderline personality disorder features, 354 community Italian adults were administered the Borderline Personality Inventory (Leichsenring, 1999a), the Difficulties in Emotion Regulation Scale (Gratz & Roemer, 2004), the Child Abuse and Trauma Scale (Sanders & Becker-Lausen, 1995), and the Attachment Style Questionnaire (Feeney, Noller, & Hanrahan, 1994). Hierarchical regression analyses showed that both childhood abuse and adult attachment were positively associated with emotion dysregulation and borderline personality features; however, only emotional abuse and the attachment dimension of need for approval were common predictors of both dependent variables. No significant interaction effects were detected in regression analyses. Mediation analyses provided support for partial mediation, revealing a significant mediating role of emotion dysregulation in the relationships between both emotional abuse and need for approval and borderline personality features in this community sample.

  4. Cognitive and family therapies for adolescent depression: treatment specificity, mediation, and moderation.

    PubMed

    Kolko, D J; Brent, D A; Baugher, M; Bridge, J; Birmaher, B

    2000-08-01

    The specificity of cognitive and family therapies, and potential treatment mediators and moderators, was examined in a randomized clinical trial for adolescent depression. After acute treatment, cognitive-behavioral therapy (CBT) exerted specific effects on cognitive distortions relative to either systemic-behavioral family therapy (SBFT) or nondirective supportive therapy (NST). At 2-year follow-up, SBFT was found to impact family conflict and parent-child relationship problems more than CBT; NST and CBT tended to show a greater reduction in anxiety symptoms than SBFT. Nonspecific therapist variables qualified few outcome analyses. No measures of cognitive distortion or family dysfunction mediated or moderated treatment outcome. As in adult studies, relatively few areas of treatment specificity or mediation were identified. The implications of these findings for clinical treatment and research in adolescent depression are discussed.

  5. Perceived Social Support Mediating the Relationship between Perceived Stress and Job Satisfaction

    ERIC Educational Resources Information Center

    Sultan, Sarwat; Rashid, Safia

    2015-01-01

    This research was conducted to examine the mediating effect of perceived social support between perceived stress and job satisfaction among employees. A conveniently selected sample of 280 employees provided the information on Perceived Social Support Scale, Perceived Stress Scale, and Job Satisfaction Survey. Employing Regression analyses,…

  6. Mediation of Changes in Anxiety and Depression During Treatment of Social Phobia

    ERIC Educational Resources Information Center

    Moscovitch, David A.; Stefan G. Hofmann, Michael K.; Suvak, Michael K.; In-Albon, Tina

    2005-01-01

    To investigate the interactive process of changes in social anxiety and depression during treatment, the authors assessed weekly symptoms in 66 adult outpatients with social phobia (social anxiety disorder) who participated in cognitive- behavioral group therapy. Multilevel mediational analyses revealed that improvements in social anxiety mediated…

  7. Functional metabolomics as a tool to analyze Mediator function and structure in plants.

    PubMed

    Davoine, Celine; Abreu, Ilka N; Khajeh, Khalil; Blomberg, Jeanette; Kidd, Brendan N; Kazan, Kemal; Schenk, Peer M; Gerber, Lorenz; Nilsson, Ove; Moritz, Thomas; Björklund, Stefan

    2017-01-01

    Mediator is a multiprotein transcriptional co-regulator complex composed of four modules; Head, Middle, Tail, and Kinase. It conveys signals from promoter-bound transcriptional regulators to RNA polymerase II and thus plays an essential role in eukaryotic gene regulation. We describe subunit localization and activities of Mediator in Arabidopsis through metabolome and transcriptome analyses from a set of Mediator mutants. Functional metabolomic analysis based on the metabolite profiles of Mediator mutants using multivariate statistical analysis and heat-map visualization shows that different subunit mutants display distinct metabolite profiles, which cluster according to the reported localization of the corresponding subunits in yeast. Based on these results, we suggest localization of previously unassigned plant Mediator subunits to specific modules. We also describe novel roles for individual subunits in development, and demonstrate changes in gene expression patterns and specific metabolite levels in med18 and med25, which can explain their phenotypes. We find that med18 displays levels of phytoalexins normally found in wild type plants only after exposure to pathogens. Our results indicate that different Mediator subunits are involved in specific signaling pathways that control developmental processes and tolerance to pathogen infections.

  8. White matter microstructural variability mediates the relation between obesity and cognition in healthy adults.

    PubMed

    Zhang, Rui; Beyer, Frauke; Lampe, Leonie; Luck, Tobias; Riedel-Heller, Steffi G; Loeffler, Markus; Schroeter, Matthias L; Stumvoll, Michael; Villringer, Arno; Witte, A Veronica

    2018-05-15

    Obesity has been linked with structural and functional brain changes. However, the impact of obesity on brain and cognition in aging remains debatable, especially for white matter. We therefore aimed to determine the effects of obesity on white matter microstructure and potential implications for cognition in a well-characterized large cohort of healthy adults. In total, 1255 participants (50% females, 19-80 years, BMI 16.8-50.2 kg/m 2 ) with diffusion-weighted magnetic resonance imaging at 3T were analysed. Tract-based spatial statistics (TBSS) probed whether body mass index (BMI) and waist-to-hip ratio (WHR) were related to fractional anisotropy (FA). We conducted partial correlations and mediation analyses to explore whether obesity or regional FA were related to cognitive performance. Analyses were adjusted for demographic, genetic, and obesity-associated confounders. Results showed that higher BMI and higher WHR were associated with lower FA in multiple white matter tracts (p < 0.05, FWE-corrected). Mediation analyses provided evidence for indirect negative effects of higher BMI and higher WHR on executive functions and processing speed through lower FA in fiber tracts connecting (pre)frontal, visual, and associative areas (indirect paths, |ß| ≥ 0.01; 99% |CI| > 0). This large cross-sectional study showed that obesity is correlated with lower FA in multiple white matter tracts in otherwise healthy adults, independent of confounders. Moreover, although effect sizes were small, mediation results indicated that visceral obesity was linked to poorer executive functions and lower processing speed through lower FA in callosal and associative fiber tracts. Longitudinal studies are needed to support this hypothesis. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Self-centeredness and selflessness: happiness correlates and mediating psychological processes.

    PubMed

    Dambrun, Michael

    2017-01-01

    The main objective of this research was to test central assumptions from the Self-centeredness/Selflessness Happiness Model. According to this model, while self-centered psychological functioning induces fluctuating happiness, authentic-durable happiness results from selflessness. Distinct mediating processes are supposed to account for these relationships: afflictive affects (e.g., anger, fear, jealousy, frustration) in the case of the former, and both emotional stability and feelings of harmony in the case of the latter. We tested these hypotheses in two studies based on heterogeneous samples of citizens ( n  = 547). Factor analyses revealed that self-centeredness (assessed through egocentrism and materialism) and selflessness (assessed through self-transcendence and connectedness to other) were two distinct psychological constructs. Second, while self-centeredness was positively and significantly related to fluctuating happiness, selflessness was positively and significantly related to authentic-durable happiness. Finally, distinct psychological processes mediated these relationships (study 2). On one hand, the relationship between self-centeredness and fluctuating happiness was fully mediated by afflictive affects. On the other hand, emotional stability and the feeling of being in harmony partially mediated the relation between selflessness and authentic-durable happiness.

  10. Self-centeredness and selflessness: happiness correlates and mediating psychological processes

    PubMed Central

    2017-01-01

    The main objective of this research was to test central assumptions from the Self-centeredness/Selflessness Happiness Model. According to this model, while self-centered psychological functioning induces fluctuating happiness, authentic–durable happiness results from selflessness. Distinct mediating processes are supposed to account for these relationships: afflictive affects (e.g., anger, fear, jealousy, frustration) in the case of the former, and both emotional stability and feelings of harmony in the case of the latter. We tested these hypotheses in two studies based on heterogeneous samples of citizens (n = 547). Factor analyses revealed that self-centeredness (assessed through egocentrism and materialism) and selflessness (assessed through self-transcendence and connectedness to other) were two distinct psychological constructs. Second, while self-centeredness was positively and significantly related to fluctuating happiness, selflessness was positively and significantly related to authentic–durable happiness. Finally, distinct psychological processes mediated these relationships (study 2). On one hand, the relationship between self-centeredness and fluctuating happiness was fully mediated by afflictive affects. On the other hand, emotional stability and the feeling of being in harmony partially mediated the relation between selflessness and authentic–durable happiness. PMID:28507820

  11. MEK-Dependent Negative Feedback Underlies BCR-ABL-Mediated Oncogene Addiction

    PubMed Central

    Asmussen, Jennifer; Lasater, Elisabeth A.; Tajon, Cheryl; Oses-Prieto, Juan; Jun, Young-wook; Taylor, Barry S.; Burlingame, Alma; Craik, Charles S.; Shah, Neil P.

    2014-01-01

    The clinical experience with BCR-ABL tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML) provides compelling evidence for oncogene addiction. Yet, the molecular basis of oncogene addiction remains elusive. Through unbiased quantitative phosphoproteomic analyses of CML cells transiently exposed to BCR-ABL TKI, we identified persistent downregulation of growth factor receptor (GF-R) signaling pathways. We then established and validated a tissue-relevant isogenic model of BCR-ABL-mediated addiction, and found evidence for myeloid GF-R signaling pathway rewiring that profoundly and persistently dampens physiologic pathway activation. We demonstrate that eventual restoration of ligand-mediated GF-R pathway activation is insufficient to fully rescue cells from a competing apoptotic fate. In contrast to previous work with BRAFV600E in melanoma cells, feedback inhibition following BCR-ABL TKI treatment is markedly prolonged, extending beyond the time required to initiate apoptosis. Mechanistically, BCR-ABL-mediated oncogene addiction is facilitated by persistent high levels of MEK-dependent negative feedback. PMID:24362263

  12. Mediators of sexual revictimization risk in adult sexual assault victims.

    PubMed

    Ullman, Sarah E; Vasquez, Amanda L

    2015-01-01

    This study examined sexual risk behaviors and sexual refusal assertiveness in relationship to child sexual abuse, emotion dysregulation, and adult sexual revictimization. Path analyses of 1,094 survivors who had sex in the past year were done to examine sexual risk behavior and sexual refusal assertiveness mediational pathways by which child sexual abuse severity and emotion dysregulation may affect revictimization over one year in adult female sexual assault survivors. Exchanging sex for money and sexual refusal assertiveness were significantly associated with emotion dysregulation, whereas exchanging sex for money, and not sexual refusal assertiveness, was only significantly related to child sexual abuse severity. Both exchanging sex for money and sex refusal assertiveness mediated the relationship between emotion dysregulation and adult sexual revictimization. Exchanging sex for money mediated the child sexual abuse severity-revictimization relationship. These findings demonstrate the importance of considering both risky and protective sexual behaviors in research and prevention programming that address sexual revictimization in women.

  13. Mediators of Sexual Revictimization Risk in Adult Sexual Assault Victims

    PubMed Central

    Ullman, Sarah E.; Vasquez, Amanda L.

    2015-01-01

    This study examined sexual risk behaviors and sexual refusal assertiveness in relationship to child sexual abuse (CSA), emotion dysregulation, and adult sexual revictimization. Path analyses of 1,094 survivors who had sex in the past year were done to examine sexual risk behavior, and sexual refusal assertiveness mediational pathways by which CSA severity and emotion dysregulation may affect revictimization over one year in adult female sexual assault survivors. Exchanging sex for money and sexual refusal assertiveness were significantly associated with emotion dysregulation, whereas exchanging sex for money, and not sexual refusal assertiveness, was only significantly related to CSA severity. Both exchanging sex for money and sex refusal assertiveness mediated the relationship between emotion dysregulation and adult sexual revictimization. Exchanging sex for money mediated the CSA severity-revictimization relationship. These findings demonstrate the importance of considering both risky and protective sexual behaviors in research and prevention programming that address sexual revictimization in women. PMID:25942287

  14. 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.

  15. Non-additive interactions involving two distinct elements mediate sloppy-paired regulation by pair-rule transcription factors

    PubMed Central

    Prazak, Lisa; Fujioka, Miki; Gergen, J. Peter

    2010-01-01

    The relatively simple combinatorial rules responsible for establishing the initial metameric expression of sloppy-paired-1 (slp1) in the Drosophila blastoderm embryo make this system an attractive model for investigating the mechanism of regulation by pair rule transcription factors. This investigation of slp1 cis-regulatory architecture identifies two distinct elements, a proximal early stripe element (PESE) and a distal early stripe element (DESE) located from −3.1 kb to −2.5 kb and from −8.1 kb to −7.1 kb upstream of the slp1 promoter, respectively, that mediate this early regulation. The proximal element expresses only even-numbered stripes and mediates repression by Even-skipped (Eve) as well as by the combination of Runt and Fushi-tarazu (Ftz). A 272 basepair sub-element of PESE retains Eve-dependent repression, but is expressed throughout the even-numbered parasegments due to the loss of repression by Runt and Ftz. In contrast, the distal element expresses both odd and even-numbered stripes and also drives inappropriate expression in the anterior half of the odd-numbered parasegments due to an inability to respond to repression by Eve. Importantly, a composite reporter gene containing both early stripe elements recapitulates pair-rule gene-dependent regulation in a manner beyond what is expected from combining their individual patterns. These results indicate interactions involving distinct cis-elements contribute to the proper integration of pair-rule regulatory information. A model fully accounting for these results proposes that metameric slp1 expression is achieved through the Runt-dependent regulation of interactions between these two pair-rule response elements and the slp1 promoter. PMID:20435028

  16. Evaluating mediation and moderation effects in school psychology: a presentation of methods and review of current practice.

    PubMed

    Fairchild, Amanda J; McQuillin, Samuel D

    2010-02-01

    Third variable effects elucidate the relation between two other variables, and can describe why they are related or under what conditions they are related. This article demonstrates methods to analyze two third-variable effects: moderation and mediation. The utility of examining moderation and mediation effects in school psychology is described and current use of the analyses in applied school psychology research is reviewed and evaluated. Proper statistical methods to test the effects are presented, and different effect size measures for the models are provided. Extensions of the basic moderator and mediator models are also described.

  17. Mediators of effects of a selective family-focused violence prevention approach for middle school students.

    PubMed

    2012-02-01

    This study examined how parenting and family characteristics targeted in a selective prevention program mediated effects on key youth proximal outcomes related to violence perpetration. The selective intervention was evaluated within the context of a multi-site trial involving random assignment of 37 schools to four conditions: a universal intervention composed of a student social-cognitive curriculum and teacher training, a selective family-focused intervention with a subset of high-risk students, a condition combining these two interventions, and a no-intervention control condition. Two cohorts of sixth-grade students (total N = 1,062) exhibiting high levels of aggression and social influence were the sample for this study. Analyses of pre-post change compared to controls using intent-to-treat analyses found no significant effects. However, estimates incorporating participation of those assigned to the intervention and predicted participation among those not assigned revealed significant positive effects on student aggression, use of aggressive strategies for conflict management, and parental estimation of student's valuing of achievement. Findings also indicated intervention effects on two targeted family processes: discipline practices and family cohesion. Mediation analyses found evidence that change in these processes mediated effects on some outcomes, notably aggressive behavior and valuing of school achievement. Results support the notion that changing parenting practices and the quality of family relationships can prevent the escalation in aggression and maintain positive school engagement for high-risk youth.

  18. 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.

  19. Gender differences in eating behavior and eating pathology: The mediating role of rumination.

    PubMed

    Opwis, Mareile; Schmidt, Jennifer; Martin, Alexandra; Salewski, Christel

    2017-03-01

    Rumination is a maladaptive emotion regulation strategy which contributes to psychopathology and is more frequently used by women than men. It has been found to mediate the relationship between gender and the occurrence of anxiety disorders or depression. Since gender differences also appear in dysfunctional eating, the aim of the study is to test, whether rumination mediates the association between gender and several facets of eating pathology. A total of 295 participants (205 women) completed an online-questionnaire including the assessment of different facets of dysfunctional eating and rumination. Mediation analyses were conducted with PROCESS. Women reported significantly higher levels in both, rumination and eating pathology. Moreover, rumination mediated the relationship between gender and all assessed aspects of dysfunctional eating. The present study extends findings on the mediating role of rumination accounting for gender differences in psychopathology to eating pathology in a community sample. Results suggest that cognitive factors play a substantial role in explaining gender differences in eating pathology which tend to be reduced to biologicals factors and beauty ideals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. 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).

  1. 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.

  2. Suicidal ideation among suburban adolescents: The influence of school bullying and other mediating risk factors.

    PubMed

    Lardier, David T; Barrios, Veronica R; Garcia-Reid, Pauline; Reid, Robert J

    2016-10-01

    Prior research has identified multiple factors that influence suicidal ideation (SI) among bullied youth. The effects of school bullying on SI cannot be considered in isolation. In this study, we examined the influence of school bullying on SI, through a constellation of risks, which include depressive and anxiety symptoms, family conflict, and alcohol, tobacco, and other drug (ATOD) use. We also provide recommendations for therapists working with bullied youth. Our sample consisted of 488 adolescents (ages 10-18 years) from a northern New Jersey, United States suburban community. Students were recruited through the district's physical education and health classes. Students responded to multiple measures, which included family cohesion/conflict, ATOD use, mental health indicators, SI, and school bullying experiences. Following preliminary analyses, several logistic regression models were used to assess the direct influence of bullying on SI, as well as the unique effects of family conflict, depressive and anxiety symptoms, and substance use. In addition, a parallel multiple mediating model with the PROCESS macro in SPSS was used to further assess mediating effects. Logistic regression results indicated that school bullying increased the odds of SI among males and females and that when mediating variables were added to the model, bullying no longer had a significant influence on SI. Overall, these results display that for both males and females, school bullying was a significant contributor to SI. Results from the parallel multiple mediating model further illustrated the mediating effects that family conflict, depression, and ATOD use had between bullying and SI. Some variation was noted based on gender. This study draws attention to the multiple experiences associated with school bullying on SI, and how these results may differ by gender. The results of this study are particularly important for those working directly and indirectly with bullied youth. Therapists

  3. How teacher emotional support motivates students: The mediating roles of perceived peer relatedness, autonomy support, and competence.

    PubMed

    Ruzek, Erik A; Hafen, Christopher A; Allen, Joseph P; Gregory, Anne; Mikami, Amori Yee; Pianta, Robert C

    2016-04-01

    Multilevel mediation analyses test whether students' mid-year reports of classroom experiences of autonomy, relatedness with peers, and competence mediate associations between early in the school year emotionally-supportive teacher-student interactions (independently observed) and student-reported academic year changes in mastery motivation and behavioral engagement. When teachers were observed to be more emotionally-supportive in the beginning of the school year, adolescents reported academic year increases in their behavioral engagement and mastery motivation. Mid-year student reports indicated that in emotionally-supportive classrooms, adolescents experienced more developmentally-appropriate opportunities to exercise autonomy in their day-to-day activities and had more positive relationships with their peers. Analyses of the indirect effects of teacher emotional support on students' engagement and motivation indicated significant mediating effects of autonomy and peer relatedness experiences, but not competence beliefs, in this sample of 960 students (ages 11-17) in the classrooms of 68 middle and high school teachers in 12 U.S. schools.

  4. How teacher emotional support motivates students: The mediating roles of perceived peer relatedness, autonomy support, and competence

    PubMed Central

    Ruzek, Erik A.; Hafen, Christopher A.; Allen, Joseph P.; Gregory, Anne; Mikami, Amori Yee; Pianta, Robert C.

    2017-01-01

    Multilevel mediation analyses test whether students' mid-year reports of classroom experiences of autonomy, relatedness with peers, and competence mediate associations between early in the school year emotionally-supportive teacher-student interactions (independently observed) and student-reported academic year changes in mastery motivation and behavioral engagement. When teachers were observed to be more emotionally-supportive in the beginning of the school year, adolescents reported academic year increases in their behavioral engagement and mastery motivation. Mid-year student reports indicated that in emotionally-supportive classrooms, adolescents experienced more developmentally-appropriate opportunities to exercise autonomy in their day-to-day activities and had more positive relationships with their peers. Analyses of the indirect effects of teacher emotional support on students' engagement and motivation indicated significant mediating effects of autonomy and peer relatedness experiences, but not competence beliefs, in this sample of 960 students (ages 11–17) in the classrooms of 68 middle and high school teachers in 12 U.S. schools. PMID:28190936

  5. Degradation mechanisms of DDX induced by the addition of toluene and glycerol as cosubstrates in a zero-valent iron pretreated soil.

    PubMed

    Velasco, Antonio; Aburto-Medina, Arturo; Shahsavari, Esmaeil; Revah, Sergio; Ortiz, Irmene

    2017-01-05

    Abiotic and biotic processes can be used to remediate DDX (DDT, DDD, DDE, and DDNS) contaminated soils; these processes can be fostered using specific carbon-amendments to stimulate particular soil indigenous microbial communities to improve rates or extent of degradation. In this study, toluene and glycerol were evaluated as cosubstrates under aerobic and anoxic conditions to determine the degradation efficiencies of DDX and to elucidate possible degradation mechanisms. Slurry microcosms experiments were performed during 60 days using pretreated soil with zero-valent iron (ZVI). Toluene addition enhanced the percentage of degradation of DDX. DDNS was the main compound degraded (around 86%) under aerobic conditions, suggesting cometabolic degradation of DDX by toluene-degrading soil bacteria. Glycerol addition under anoxic conditions favored the abiotic degradation of DDX mediated by sulfate-reducing bacteria activity, where DDT was the main compound degraded (around 90%). The 16S rDNA metagenomic analyses revealed Rhodococcus ruber and Desulfosporosinus auripigmenti as the predominant bacterial species after 40 days of treatment with toluene and glycerol additions, respectively. This study provides evidence of biotic and abiotic DDX degradation by the addition of toluene and glycerol as cosubstrates in ZVI pretreated DDX-contaminated soil. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Nitric oxide mediates local activity-dependent excitatory synapse development.

    PubMed

    Nikonenko, Irina; Nikonenko, Alexander; Mendez, Pablo; Michurina, Tatyana V; Enikolopov, Grigori; Muller, Dominique

    2013-10-29

    Learning related paradigms play an important role in shaping the development and specificity of synaptic networks, notably by regulating mechanisms of spine growth and pruning. The molecular events underlying these synaptic rearrangements remain poorly understood. Here we identify NO signaling as a key mediator of activity-dependent excitatory synapse development. We find that chronic blockade of NO production in vitro and in vivo interferes with the development of hippocampal and cortical excitatory spine synapses. The effect results from a selective loss of activity-mediated spine growth mechanisms and is associated with morphological and functional alterations of remaining synapses. These effects of NO are mediated by a cGMP cascade and can be reproduced or prevented by postsynaptic expression of vasodilator-stimulated phosphoprotein phospho-mimetic or phospho-resistant mutants. In vivo analyses show that absence of NO prevents the increase in excitatory synapse density induced by environmental enrichment and interferes with the formation of local clusters of excitatory synapses. We conclude that NO plays an important role in regulating the development of excitatory synapses by promoting local activity-dependent spine-growth mechanisms.

  7. Service climate as a mediator of organizational empowerment in customer-service employees.

    PubMed

    Mendoza-Sierra, Maria Isabel; Orgambídez-Ramos, Alejandro; Carrasco-González, Ana María; León-Jariego, José Carlos

    2014-01-01

    The aim of this study is to examine the mediating role of the service climate between organizational empowerment (i.e., dynamic structural framework, control of workplace decisions, fluidity in information sharing) and service quality (functional and relational). 428 contact employees from 46 hotels participated in the survey. Correlations demonstrated that dynamic structural framework, control decisions, and fluidity in information sharing are related to both functional and relational service quality. Regression analyses and Sobel tests revealed that service climate totally mediated the relationship between all three dimensions of organizational empowerment and relational service quality. Implications for practice and future research are discussed.

  8. Integrated omics analyses of retrograde signaling mutant delineate interrelated stress-response strata.

    PubMed

    Bjornson, Marta; Balcke, Gerd Ulrich; Xiao, Yanmei; de Souza, Amancio; Wang, Jin-Zheng; Zhabinskaya, Dina; Tagkopoulos, Ilias; Tissier, Alain; Dehesh, Katayoon

    2017-07-01

    To maintain homeostasis in the face of intrinsic and extrinsic insults, cells have evolved elaborate quality control networks to resolve damage at multiple levels. Interorganellar communication is a key requirement for this maintenance, however the underlying mechanisms of this communication have remained an enigma. Here we integrate the outcome of transcriptomic, proteomic, and metabolomics analyses of genotypes including ceh1, a mutant with constitutively elevated levels of both the stress-specific plastidial retrograde signaling metabolite methyl-erythritol cyclodiphosphate (MEcPP) and the defense hormone salicylic acid (SA), as well as the high MEcPP but SA deficient genotype ceh1/eds16, along with corresponding controls. Integration of multi-omic analyses enabled us to delineate the function of MEcPP from SA, and expose the compartmentalized role of this retrograde signaling metabolite in induction of distinct but interdependent signaling cascades instrumental in adaptive responses. Specifically, here we identify strata of MEcPP-sensitive stress-response cascades, among which we focus on selected pathways including organelle-specific regulation of jasmonate biosynthesis; simultaneous induction of synthesis and breakdown of SA; and MEcPP-mediated alteration of cellular redox status in particular glutathione redox balance. Collectively, these integrated multi-omic analyses provided a vehicle to gain an in-depth knowledge of genome-metabolism interactions, and to further probe the extent of these interactions and delineate their functional contributions. Through this approach we were able to pinpoint stress-mediated transcriptional and metabolic signatures and identify the downstream processes modulated by the independent or overlapping functions of MEcPP and SA in adaptive responses. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  9. The Big Five Personality Traits and French Firefighter Burnout: The Mediating Role of Achievement Goals.

    PubMed

    Vaulerin, Jérôme; Colson, Serge S; Emile, Mélanie; Scoffier-Mériaux, Stéphanie; d'Arripe-Longueville, Fabienne

    2016-04-01

    We investigated the associations between the Big Five personality traits and occupational burnout in firefighters and the mediating role of achievement goals in this relationship. Two hundred twenty male firefighters from 20 to 62 years old participated and mediation analyses were performed. The results showed that neuroticism was positively related to the three dimensions of burnout, both directly and through mastery avoidance goals. Mastery approach goals mediated the relationships between conscientiousness and physical fatigue and between openness to experience and physical fatigue. Three of the Big Five personality traits, neuroticism, conscientiousness and openness to experience, and achievement goals, may be important factors in understanding and preventing firefighter burnout.

  10. Interventions based on self-management of well-being theory: pooling data to demonstrate mediation and ceiling effects, and to compare formats.

    PubMed

    Goedendorp, M M; Steverink, N

    2017-09-01

    Interventions based on self-management of well-being (SMW) theory have shown positive effects, but additional questions remain: (1) Are improvements in well-being, as induced by the interventions, mediated by improved self-management ability (SMA)? (2) Do the interventions show ceiling effects? (3) Is a particular format of SMW intervention (individual, group, or self-help) more effective? Data of three randomized controlled trials were pooled. The greater part of the sample (N = 445) consisted of single older females. A bootstrap analysis was performed to test for mediation. Regression analyses with interaction effects were performed to test for ceiling effects. Controlled and transformed effect sizes (proportion of maximum change) were calculated to compare formats. There was a full significant mediation of well-being by SMA. A significant interaction (ceiling) effect was found on well-being, but not on SMA. The controlled effect sizes of the raw scores were small to medium (.04-.49), and were small to large after transformation (.41-.73). None of the intervention formats was more effective. Support for SMW theory was found, i.e. increasing self-management ability lead to improved well-being. Some ceiling effect was found. We conclude that various SMW interventions formats can improve self-management abilities and well-being with medium effects.

  11. Self-regulatory processes mediate the intention-behavior relation for adherence and exercise behaviors.

    PubMed

    de Bruin, Marijn; Sheeran, Paschal; Kok, Gerjo; Hiemstra, Anneke; Prins, Jan M; Hospers, Harm J; van Breukelen, Gerard J P

    2012-11-01

    Understanding the gap between people's intentions and actual health behavior is an important issue in health psychology. Our aim in this study was to investigate whether self-regulatory processes (monitoring goal progress and responding to discrepancies) mediate the intention-behavior relation in relation to HIV medication adherence (Study 1) and intensive exercise behavior (Study 2). In Study 1, questionnaire and electronically monitored adherence data were collected at baseline and 3 months later from patients in the control arm of an HIV-adherence intervention study. In Study 2, questionnaire data was collected at 3 time points 6-weeks apart in a cohort study of physical activity. Complete data at all time points were obtained from 51 HIV-infected patients and 499 intensive exercise participants. Intentions were good predictors of behavior and explained 25 to 30% of the variance. Self-regulatory processes explained an additional 11% (Study 1) and 6% (Study 2) of variance in behavior on top of intentions. Regression and bootstrap analyses revealed at least partial, and possibly full, mediation of the intention-behavior relation by self-regulatory processes. The present studies indicate that self-regulatory processes may explain how intentions drive behavior. Future tests, using different health behaviors and experimental designs, could firmly establish whether self-regulatory processes complement current health behavior theories and should become routine targets for intervention. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  12. Exploring peers as a mediator of the association between depression and smoking in young adolescents.

    PubMed

    Ritt-Olson, Anamara; Unger, Jennifer; Valente, Tom; Nezami, Elahe; Chou, Chih-ping; Trinidad, Dennis; Milam, Joel; Earleywine, Mitchell; Tan, Sylvia; Johnson, C Anderson

    2005-01-01

    Recent research has suggested that depression causes teens to begin smoking to elevate their mood. Other studies, however, have suggested the reverse causal direction: smoking causes depression. To gain a more complete understanding of the relationship between smoking and depression, potential mediators should be explored. This study explored how peer influences could mediate the relationship between depression and smoking. The methodology of Baron and Kenney was followed to test for mediation and moderation. Peers mediated the relationship between depression and smoking. Separate analyses by gender showed that depression remained significantly associated with smoking when peers were included in the model for girls only. Peer influence was related to depressed affect for both genders. These results provide evidence that peer influences are an important variable to take into consideration when addressing a depression smoking relationship.

  13. Mediation Analysis of the Efficacy of the Eban HIV/STD Risk-Reduction Intervention for African American HIV Serodiscordant Couples.

    PubMed

    El-Bassel, Nabila; Jemmott, John B; Bellamy, Scarlett L; Pequegnat, Willo; Wingood, Gina M; Wyatt, Gail E; Landis, J Richard; Remien, Robert H

    2016-06-01

    Targeting couples is a promising behavioral HIV risk-reduction strategy, but the mechanisms underlying the effects of such interventions are unknown. We report secondary analyses testing whether Social-Cognitive-Theory variables mediated the Eban HIV-risk-reduction intervention's effects on condom-use outcomes. In a multisite randomized controlled trial conducted in four US cities, 535 African American HIV-serodiscordant couples were randomized to the Eban HIV risk-reduction intervention or attention-matched control intervention. Outcomes were proportion condom-protected sex, consistent condom use, and frequency of unprotected sex measured pre-, immediately post-, and 6 and 12 months post-intervention. Potential mediators included Social-Cognitive-Theory variables: outcome expectancies and self-efficacy. Mediation analyses using the product-of-coefficients approach in a generalized-estimating-equations framework revealed that condom-use outcome expectancy, partner-reaction outcome expectancy, intention, self-efficacy, and safer-sex communication improved post-intervention and mediated intervention-induced improvements in condom-use outcomes. These findings underscore the importance of targeting outcome expectancies, self-efficacy, and safer-sex communication in couples-level HIV risk-reduction interventions.

  14. Anger and depression: evidence of a possible mediating role for rumination.

    PubMed

    Balsamo, Michela

    2010-02-01

    Tendency to ruminate may mediate the relationship between anger and depression. In this preliminary study, 353 Italian community participants completed the State-Trait Anger Expression Inventory-2, the Padua Inventory's Tendency to Doubt and to Ruminate subscale, and the Beck Depression Inventory-II. Trait anger and depression were expected to have a positive relationship, and separate relationships with the tendency to ruminate. Theoretically, a new hypothesis was that the tendency to ruminate would mediate the relationship between depression and anger. Zero-order and partial correlations and a path analysis based on Baron and Kenny's method for calculating multiple regression analyses were calculated. Consistent with the hypotheses, anger and depression were strongly associated; the tendency to ruminate was significantly associated with both anger and depression; and the mediation model fit the data. Behaviors related to the tendency to ruminate could help to explain how depression is related to anger.

  15. 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.

  16. Harm mediates the disgust-immorality link.

    PubMed

    Schein, Chelsea; Ritter, Ryan S; Gray, Kurt

    2016-09-01

    Many acts are disgusting, but only some of these acts are immoral. Dyadic morality predicts that disgusting acts should be judged as immoral to the extent that they seem harmful. Consistent with this prediction, 3 studies reveal that perceived harm mediates the link between feelings of disgust and moral condemnation-even for ostensibly harmless "purity" violations. In many cases, accounting for perceived harm completely eliminates the link between disgust and moral condemnation. Analyses also reveal the predictive power of anger and typicality/weirdness in moral judgments of disgusting acts. The mediation of disgust by harm holds across diverse acts including gay marriage, sex acts, and religious blasphemy. Revealing the endogenous presence and moral relevance of harm within disgusting-but-ostensibly harmless acts argues against modular accounts of moral cognition such as moral foundations theory. Instead, these data support pluralistic conceptions of harm and constructionist accounts of morality and emotion. Implications for moral cognition and the concept of "purity" are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  17. Pheromonally mediated sexual isolation among denning populations of red-sided garter snakes, Thamnophis sirtalis parietalis.

    PubMed

    Lemaster, Michael P; Mason, Robert T

    2003-04-01

    Utilizing behavioral experiments and chemical analyses, we examined whether pheromonally mediated sexual isolation exists between denning populations of red-sided garter snakes (Thamtnophis sirtalis parietalis) in Manitoba, Canada. Simultaneous choice tests conducted during the breeding season revealed that adult males from a hibernaculum in central Manitoba displayed a strong courtship preference for females from their own population over females from a hibernaculum in western Manitoba, whereas males from the western Manitoba hibernaculum showed no such preference. In addition. trailing experiments testing the response of males from the two hibernacula to familiar and unfamiliar female trails showed similar results, demonstrating that the observed male preference is mediated through chemical cues. Subsequent chemical analysis of the female sexual attractiveness pheromone. a homologous series of long-chain saturated and (omega-9 cis-unsaturated methyl ketones responsible for eliciting male courtship behavior and trailing behavior in garter snakes, showed significant variation in the composition of the pheromone between the two populations. Specifically, the two populations varied in the relative concentrations of individual unsaturated methyl ketones expressed by females. These results suggest that sexual isolation exists to a degree among denning populations of red-sided garter snakes due to variation in the expression of the female sexual attractiveness pheromone.

  18. 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.

  19. Identification of miRNAs and Their Targets in the Liverwort Marchantia polymorpha by Integrating RNA-Seq and Degradome Analyses

    PubMed Central

    Lin, Pin-Chun; Lu, Chia-Wei; Shen, Bing-Nan; Lee, Guan-Zong; Bowman, John L.; Arteaga-Vazquez, Mario A.; Liu, Li-Yu Daisy; Hong, Syuan-Fei; Lo, Chu-Fang; Su, Gong-Min; Kohchi, Takayuki; Ishizaki, Kimitsune; Zachgo, Sabine; Althoff, Felix; Takenaka, Mizuki; Yamato, Katsuyuki T.; Lin, Shih-Shun

    2016-01-01

    Bryophytes (liverworts, hornworts and mosses) comprise the three earliest diverging lineages of land plants (embryophytes). Marchantia polymorpha, a complex thalloid Marchantiopsida liverwort that has been developed into a model genetic system, occupies a key phylogenetic position. Therefore, M. polymorpha is useful in studies aiming to elucidate the evolution of gene regulation mechanisms in plants. In this study, we used computational, transcriptomic, small RNA and degradome analyses to characterize microRNA (miRNA)-mediated pathways of gene regulation in M. polymorpha. The data have been integrated into the open access ContigViews-miRNA platform for further reference. In addition to core components of the miRNA pathway, 129 unique miRNA sequences, 11 of which could be classified into seven miRNA families that are conserved in embryophytes (miR166a, miR390, miR529c, miR171-3p, miR408a, miR160 and miR319a), were identified. A combination of computational and degradome analyses allowed us to identify and experimentally validate 249 targets. In some cases, the target genes are orthologous to those of other embryophytes, but in other cases, the conserved miRNAs target either paralogs or members of different gene families. In addition, the newly discovered Mpo-miR11707.1 and Mpo-miR11707.2 are generated from a common precursor and target MpARGONAUTE1 (LW1759). Two other newly discovered miRNAs, Mpo-miR11687.1 and Mpo-miR11681.1, target the MADS-box transcription factors MpMADS1 and MpMADS2, respectively. Interestingly, one of the pentatricopeptide repeat (PPR) gene family members, MpPPR_66 (LW9825), the protein products of which are generally involved in various steps of RNA metabolism, has a long stem–loop transcript that can generate Mpo-miR11692.1 to autoregulate MpPPR_66 (LW9825) mRNA. This study provides a foundation for further investigations of the RNA-mediated silencing mechanism in M. polymorpha as well as of the evolution of this gene silencing pathway in

  20. Recall of threat and submissiveness in childhood and psychopathology: the mediator effect of self-criticism.

    PubMed

    Castilho, Paula; Pinto-Gouveia, José; Amaral, Vânia; Duarte, Joana

    2014-01-01

    Research has robustly shown that early negative parenting experiences are associated with psychopathology and self-criticism in adulthood. This study investigates recall of personal feelings of perceived threat and subordination in childhood and its relation to psychopathology. In addition, we explore the mediator role of self-criticism in this association. A sample of 193 subjects from the general population completed self-report questionnaires measuring the study variables. The mediator analyses suggested that the impact of submissiveness experiences in childhood on depression and anxiety is mediated by self-criticism. Our findings highlight the route through which the recall of personal feelings of perceived involuntary subordination to parents contributes to depression and anxiety in adulthood. Although the relation between early experiences of abuse and later psychological problems is now well established, there has been less study on subtler forms of threat and subordinate behaviour in childhood. Given ours and previous findings, therapists should be aware of, and prone to explore, these early experiences. Most studies exploring early negative experiences mainly refer to attachment theory-related constructs (e.g., attachment style). We also highlight the importance of noting rank structure and rank style in the family. Self-criticism seems to be a key process in the relation between early aversive experiences of subordination and psychopathology. Given the idea that self-reassuring operates through a different affect system, helping people develop inner warmth and compassion for the self may be important to counteract feelings of self-hatred and self-attack. Copyright © 2012 John Wiley & Sons, Ltd.

  1. No mediating effects of glycemic control and inflammation on the association between vitamin D and lung function in the general population.

    PubMed

    Kaul, Anne; Gläser, Sven; Hannemann, Anke; Stubbe, Beate; Felix, Stefan B; Nauck, Matthias; Ewert, Ralf; Friedrich, Nele

    2017-04-01

    Vitamin D deficiency is discussed to be associated with lung health. While former studies focused on subjects suffering from pulmonary diseases, we aimed to investigate the association of 25-hydroxy vitamin D [25(OH)D] with lung function in the general population and examined whether mediating effects of inflammation, glycemic control or renal function exist. 1404 participants from the Study of Health in Pomerania with pulmonary function testing assessed by expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), total lung capacity and Krogh index were used. Adjusted analysis of variance, linear regression models and mediation analyses were performed. Significant positive associations between 25(OH)D levels and FEV 1 , FVC and Krogh index were found. Mediator analyses revealed no mediating effect of inflammation (fibrinogen), glycemic control (HbA1c) or renal function (eGFR) on associations with FEV 1 or FVC. With respect to Krogh-Index, the association to 25(OH)D was slightly mediated by fibrinogen with a proportion mediated of 9.7%. Significant positive associations of 25(OH)D with lung function were revealed in a general population. The proposed mediating effects of inflammation, glycemic control and renal function on these relations were not confirmed. Further studies examining the causality of the association between 25(OH)D and lung function are necessary. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Work characteristics, socioeconomic position and health: a systematic review of mediation and moderation effects in prospective studies

    PubMed Central

    Hoven, Hanno; Siegrist, Johannes

    2013-01-01

    Social inequalities in health persist in modern societies. The contribution of adverse work and employment conditions towards their explanation is analysed by two approaches, mediation and moderation. Yet the relative significance of each approach remains unclear in respective research. We set out to study this question by conducting a systematic literature review. We included all original papers based on prospective observational studies of employed cohorts that were published between January 1980 and October 2012 meeting our search criteria, by using major databases and by observing established quality criteria. 26 reports were included after quality assessment. 17 studies examined the mediation hypothesis and nine studies tested the moderation hypothesis. Moderate support was found for the mediation hypothesis where OR or HR of health according to socioeconomic position (SEP) were reduced in a majority of analyses after introducing work characteristics in multivariate models. Evidence in favour of the moderation hypothesis was found in some studies, demonstrating stronger effects of adverse work on health among people with low SEP. Despite some support in favour of the two hypotheses future research should aim at reducing the heterogeneity in defining and measuring core variables and at applying advanced statistical analyses. Policy recommendations would benefit from a higher degree of consistency of respective research evidence. PMID:23739492

  3. Work characteristics, socioeconomic position and health: a systematic review of mediation and moderation effects in prospective studies.

    PubMed

    Hoven, Hanno; Siegrist, Johannes

    2013-09-01

    Social inequalities in health persist in modern societies. The contribution of adverse work and employment conditions towards their explanation is analysed by two approaches, mediation and moderation. Yet the relative significance of each approach remains unclear in respective research. We set out to study this question by conducting a systematic literature review. We included all original papers based on prospective observational studies of employed cohorts that were published between January 1980 and October 2012 meeting our search criteria, by using major databases and by observing established quality criteria. 26 reports were included after quality assessment. 17 studies examined the mediation hypothesis and nine studies tested the moderation hypothesis. Moderate support was found for the mediation hypothesis where OR or HR of health according to socioeconomic position (SEP) were reduced in a majority of analyses after introducing work characteristics in multivariate models. Evidence in favour of the moderation hypothesis was found in some studies, demonstrating stronger effects of adverse work on health among people with low SEP. Despite some support in favour of the two hypotheses future research should aim at reducing the heterogeneity in defining and measuring core variables and at applying advanced statistical analyses. Policy recommendations would benefit from a higher degree of consistency of respective research evidence.

  4. Reducing Agent-Assisted Excessive Galvanic Replacement Mediated Seed-Mediated Synthesis of Porous Gold Nanoplates and Highly Efficient Gene-Thermo Cancer Therapy.

    PubMed

    Kang, Seounghun; Kang, Kyunglee; Huh, Hyun; Kim, Hyungjun; Chang, Sung-Jin; Park, Tae Jung; Chang, Ki Soo; Min, Dal-Hee; Jang, Hongje

    2017-10-11

    Porous Au nanoplates (pAuNPs) were manufactured by a reducing agent-assisted galvanic replacement reaction on Ag nanoplates using a seed-mediated synthetic approach. Two core additives, poly(vinylpyrrolidone) and l-ascorbic acid, prevented fragmentation and proceeded secondary growth. By controlling the concentration of the additives and the amount of replacing ion AuCl 4 - , various nanostructures including nanoplates with holes, nanoframes, porous nanoplates, and bumpy nanoparticles with unity and homogeneity were synthesized. The present synthetic method is advantageous, because it can be used to manufacture pAuNPs with ease, robustness, and convenience. The prepared pAuNPs exhibited a highly efficient photothermal conversion effect and cargo loading capacity on exposed surfaces by Au-thiol linkage. By using dual cargo mixed loading of the hepatitis C virus (HCV) targeting gene drug DNAzyme and cell-penetrating peptide TAT onto the surface of the pAuNPs and photothermal conversion-mediated hyperthermic treatment, successful gene-thermo therapy against HCV genomic human hepatocarcinoma cells were demonstrated.

  5. Intramolecular addition of benzylic radicals onto ketenimines. Synthesis of 2-alkylindoles.

    PubMed

    Alajarín, Mateo; Vidal, Angel; Ortín, María-Mar

    2003-12-07

    The inter- and intramolecular addition of free radicals onto ketenimines is studied. All the attempts to add intermolecularly several silicon, oxygen or carbon centered radicals to N-(4-methylphenyl)-C,C-diphenyl ketenimine were unsuccessful. In contrast, the intramolecular addition of benzylic radicals, generated from xanthates, onto the central carbon of a ketenimine function with its N atom linked to the ortho position of the aromatic ring occurred under a variety of reaction conditions. These intramolecular cyclizations provide a novel radical-mediated synthesis of 2-alkylindoles.

  6. 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. "Small Talk Is Not Cheap": Phatic Computer-Mediated Communication in Intercultural Classes

    ERIC Educational Resources Information Center

    Maíz-Arévalo, Carmen

    2017-01-01

    The present study aims to analyse the phatic exchanges performed by a class of nine intercultural Master's students during a collaborative assignment which demanded online discussion using English as a lingua franca (ELF). Prior studies on the use of phatic communication in computer-mediated communication have concentrated on social networking…

  8. When Mothers Have Serious Mental Health Problems: Parenting as a Proximal Mediator

    ERIC Educational Resources Information Center

    Oyserman, D.; Bybee, D.; Mowbray, C.; Hart-Johnson, T.

    2005-01-01

    Maternal mental health (MMH) problems are associated with lack of confidence in one's parenting, overly lax or too harsh discipline, and child academic underperformance. We asked if parenting mediates the effect of MMH problems on academic outcomes even among mothers with serious mental illness (n=164). Structural equation analyses show a…

  9. Substrate-Mediated Laser Ablation under Ambient Conditions for Spatially-Resolved Tissue Proteomics

    PubMed Central

    Fatou, Benoit; Wisztorski, Maxence; Focsa, Cristian; Salzet, Michel; Ziskind, Michael; Fournier, Isabelle

    2015-01-01

    Numerous applications of ambient Mass Spectrometry (MS) have been demonstrated over the past decade. They promoted the emergence of various micro-sampling techniques such as Laser Ablation/Droplet Capture (LADC). LADC consists in the ablation of analytes from a surface and their subsequent capture in a solvent droplet which can then be analyzed by MS. LADC is thus generally performed in the UV or IR range, using a wavelength at which analytes or the matrix absorb. In this work, we explore the potential of visible range LADC (532 nm) as a micro-sampling technology for large-scale proteomics analyses. We demonstrate that biomolecule analyses using 532 nm LADC are possible, despite the low absorbance of biomolecules at this wavelength. This is due to the preponderance of an indirect substrate-mediated ablation mechanism at low laser energy which contrasts with the conventional direct ablation driven by sample absorption. Using our custom LADC system and taking advantage of this substrate-mediated ablation mechanism, we were able to perform large-scale proteomic analyses of micro-sampled tissue sections and demonstrated the possible identification of proteins with relevant biological functions. Consequently, the 532 nm LADC technique offers a new tool for biological and clinical applications. PMID:26674367

  10. Emotional eating as a mediator between depression and weight gain.

    PubMed

    van Strien, Tatjana; Konttinen, Hanna; Homberg, Judith R; Engels, Rutger C M E; Winkens, Laura H H

    2016-05-01

    Depression is often associated with weight gain but underlying mechanisms are unclear. This study assessed whether three psychological eating styles (emotional eating, external eating and restrained eating) act as mediators between depression and weight gain. We used structural equation modelling to test the hypothesized mediation models in a sample of 298 fathers and 294 mothers by assessing self-reported eating styles (Dutch Eating Behavior Questionnaire), depressive feelings (Depressive Mood List) and body mass index (BMI) at baseline and BMI after five years. In the model with emotional eating we also assessed the moderation effect of 5-HTTLPR genotype in a sub-sample of 520 Caucasians. All analyses were performed separately for the two sexes. Although the overall effect of depression on weight gain was statistically non-significant in both sexes, there was a causal chain between depression, emotional eating and weight gain in the mothers. Depressive symptoms were related to higher emotional eating and emotional eating predicted greater increases in BMI independently of depression. Moreover, the indirect effect (via emotional eating) of depression on BMI change was significant (Beta = 0.18, P = 0.026). This mediation effect was found to be independent of 5-HTTLPR genotype. No such mediation effect was found for the fathers. Further, external eating and restrained eating did not act as mediators between depression and weight gain in either sex. The finding that emotional eating acted as mediator between depression and weight gain in the mothers suggests that obesity interventions should take emotional eating into account. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Adolescents' physical activities and peer norms: the mediating role of self-efficacy.

    PubMed

    Lu, Frank J H; Lin, Ju-Han; Hsu, Ya-Wen; Chou, Chien-Chih; Wang, Erica T W; Yeh, Li-Chin

    2014-04-01

    The purpose of the present study was to examine the relations among adolescents' self-efficacy and social norms, and physical activity and whether self-efficacy mediated the relationship between social norms and physical activity. 400 junior high school students (202 boys, 198 girls, 2 not identified; M age = 15.3yr., SD = 0.6) completed a demographic questionnaire, the International Physical Activity Questionnaire (IPAQ), the Perceived Self-Efficacy in Physical Activity Scale, and the Physical Activity Social Norms Scale. Regression analyses indicated that both self-efficacy and social norms predicted physical activity. Self-efficacy fully mediated the relationship between peer norms and physical activity for boys but partially mediated the relationship for girls. An application of the results may be to foster self-efficacy and peer norms as a motivational strategy for supporting increased physical activity.

  12. Receptor-mediated cell mechanosensing

    PubMed Central

    Chen, Yunfeng; Ju, Lining; Rushdi, Muaz; Ge, Chenghao; Zhu, Cheng

    2017-01-01

    Mechanosensing describes the ability of a cell to sense mechanical cues of its microenvironment, including not only all components of force, stress, and strain but also substrate rigidity, topology, and adhesiveness. This ability is crucial for the cell to respond to the surrounding mechanical cues and adapt to the changing environment. Examples of responses and adaptation include (de)activation, proliferation/apoptosis, and (de)differentiation. Receptor-mediated cell mechanosensing is a multistep process that is initiated by binding of cell surface receptors to their ligands on the extracellular matrix or the surface of adjacent cells. Mechanical cues are presented by the ligand and received by the receptor at the binding interface; but their transmission over space and time and their conversion into biochemical signals may involve other domains and additional molecules. In this review, a four-step model is described for the receptor-mediated cell mechanosensing process. Platelet glycoprotein Ib, T-cell receptor, and integrins are used as examples to illustrate the key concepts and players in this process. PMID:28954860

  13. Mediation Analysis of Decisional Balance, Sun Avoidance, and Sunscreen Use in the Precontemplation and Preparation Stages for Sun Protection

    PubMed Central

    Velicer, Wayne F.; Redding, Colleen

    2015-01-01

    Objective Mediation analyses of sun protection were conducted testing structural equation models using longitudinal data with three waves. An effect was said to be mediated if the standardized path between processes of change, decisional balance, and sun protection outcomes were significant. Design Longitudinal models of sun protection using data from individuals in the precontemplation (N=964) and preparation (N =463) stages who participated of an expert system intervention. Main Outcome Measures Nine processes of change for sun protection, decisional balance constructs of sun protection (pros and cons), sun avoidance behavior, and sunscreen use. Results With the exception of two processes in the preparation stage, processes of change predicted the pros (r= .126 to .614), and the pros predicted the outcomes (r= .181 to .272). Three models with the cons as mediator in the preparation stage, and none in the precontemplation stage, showed a mediated relationship between processes and outcomes. Conclusion In general, mediation analyses found both the process of change-to-pros and pros-to-behavior paths significant for both precontemplation and preparation stages, and for both sun avoidance and sunscreen use outcomes. Findings provide support for the importance of assessing the role of underlying risk cognitions in improving sun protection adherence. PMID:26040293

  14. 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

  15. Mediation of an efficacious HIV risk reduction intervention for South African men.

    PubMed

    O'Leary, Ann; Jemmott, John B; Jemmott, Loretta S; Bellamy, Scarlett; Icard, Larry D; Ngwane, Zolani

    2015-10-01

    "Men, Together Making a Difference!" is an HIV/STD risk-reduction intervention that significantly increased self-reported consistent condom use during vaginal intercourse compared with a health-promotion attention-control intervention among men (N = 1181) in Eastern Cape Province, South Africa. The present analyses were designed to identify mediators of the intervention's efficacy. The potential mediators were Social Cognitive Theory (SCT) constructs that the intervention targeted, including several aspects of condom-use self-efficacy, outcome expectancies, and knowledge. Mediation was assessed using a product-of-coefficients approach where an α path (the intervention's effect on the potential mediator) and a β path (the potential mediator's effect on the outcome of interest, adjusting for intervention) were estimated independently in a generalized estimating equations framework. Condom-use negotiation self-efficacy, technical-skill self-efficacy, and impulse-control self-efficacy were significant mediators. Although not mediators, descriptive norm and expected friends' approval of condom use predicted subsequent self-reported condom use, whereas the expected approval of sexual partner did not. The present results suggest that HIV/STD risk-reduction interventions that draw upon SCT and that address self-efficacy to negotiate condom use, to apply condoms correctly, and to exercise sufficient control when sexually aroused to use condoms may contribute to efforts to reduce sexual risk behavior among South African men. Future research must examine whether approaches that build normative support for condom use among men's friends are also efficacious.

  16. Parental education associations with children's body composition: mediation effects of energy balance-related behaviors within the ENERGY-project.

    PubMed

    Fernández-Alvira, Juan M; te Velde, Saskia J; De Bourdeaudhuij, Ilse; Bere, Elling; Manios, Yannis; Kovacs, Eva; Jan, Natasa; Brug, Johannes; Moreno, Luis A

    2013-06-21

    It is well known that the prevalence of overweight and obesity is considerably higher among youth from lower socio-economic families, but there is little information about the role of some energy balance-related behaviors in the association between socio-economic status and childhood overweight and obesity. The objective of this paper was to assess the possible mediation role of energy balance-related behaviors in the association between parental education and children's body composition. Data were obtained from the cross sectional study of the "EuropeaN Energy balance Research to prevent excessive weight Gain among Youth" (ENERGY) project. 2121 boys and 2516 girls aged 10 to 12 from Belgium, Greece, Hungary, the Netherlands, Norway, Slovenia and Spain were included in the analyses. Data were obtained via questionnaires assessing obesity related dietary, physical activity and sedentary behaviors and basic anthropometric objectively measured indicators (weight, height, waist circumference). The possible mediating effect of sugared drinks intake, breakfast consumption, active transportation to school, sports participation, TV viewing, computer use and sleep duration in the association between parental education and children's body composition was explored via MacKinnon's product-of-coefficients test in single and multiple mediation models. Two different body composition indicators were included in the models, namely Body Mass Index and waist circumference. The association between parental education and children's body composition was partially mediated by breakfast consumption, sports participation, TV viewing and computer use. Additionally, a suppression effect was found for sugared drinks intake. No mediation effect was found for active transportation and sleep duration. The significant mediators explained a higher proportion of the association between parental education and waist circumference compared to the association between parental education and BMI

  17. Mediating role of borderline personality disorder traits in the effects of childhood maltreatment on suicidal behaviour among mood disorder patients.

    PubMed

    Aaltonen, K I; Rosenström, T; Baryshnikov, I; Karpov, B; Melartin, T; Suominen, K; Heikkinen, M; Näätänen, P; Koivisto, M; Joffe, G; Isometsä, E

    2017-07-01

    Substantial evidence supports an association between childhood maltreatment and suicidal behaviour. However, few studies have examined factors mediating this relationship among patients with unipolar or bipolar mood disorders. Depressive disorder and bipolar disorder (ICD-10-DCR) patients (n=287) from the Helsinki University Psychiatric Consortium (HUPC) Study were surveyed on self-reported childhood experiences, current depressive symptoms, borderline personality disorder traits, and lifetime suicidal behaviour. Psychiatric records served to complement the information on suicide attempts. We examined by formal mediation analyses whether (1) the effect of childhood maltreatment on suicidal behaviour is mediated through borderline personality disorder traits and (2) the mediation effect differs between lifetime suicidal ideation and lifetime suicide attempts. The impact of childhood maltreatment in multivariate models on either lifetime suicidal ideation or lifetime suicide attempts showed comparable total effects. In formal mediation analyses, borderline personality disorder traits mediated all of the total effect of childhood maltreatment on lifetime suicide attempts, but only one fifth of the total effect on lifetime suicidal ideation. The mediation effect was stronger for lifetime suicide attempts than for lifetime suicidal ideation (P=0.002) and independent of current depressive symptoms. The mechanisms of the effect of childhood maltreatment on suicidal ideation versus suicide attempts may diverge among psychiatric patients with mood disorders. Borderline personality disorder traits may contribute to these mechanisms, although the influence appears considerably stronger for suicide attempts than for suicidal ideation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. 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.

  19. 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.

  20. Why is discrimination stressful? The mediating role of cognitive appraisal.

    PubMed

    King, Kimberly R

    2005-08-01

    This study attempts to shed light on past findings that experiences of racial and gender discrimination are associated with poor psychological and physical health outcomes by investigating the role of cognitive appraisal as a mediator of the relationship between experiences of discrimination and affective stress reactions. African American female college students (N = 115) imagined themselves in an audiotaped scenario in which they overheard 2 European American male classmates make negative evaluations of them. Participants then completed measures of causal attributions, cognitive appraisal, and affective stress reactions. Multiple regression analyses supported the hypotheses that attributions to racism and to discrimination that combines racism and sexism were associated with increased stress reactions. This relationship was mediated by cognitive appraisals of centrality. (c) 2005 APA

  1. An experiment in software reliability: Additional analyses using data from automated replications

    NASA Technical Reports Server (NTRS)

    Dunham, Janet R.; Lauterbach, Linda A.

    1988-01-01

    A study undertaken to collect software error data of laboratory quality for use in the development of credible methods for predicting the reliability of software used in life-critical applications is summarized. The software error data reported were acquired through automated repetitive run testing of three independent implementations of a launch interceptor condition module of a radar tracking problem. The results are based on 100 test applications to accumulate a sufficient sample size for error rate estimation. The data collected is used to confirm the results of two Boeing studies reported in NASA-CR-165836 Software Reliability: Repetitive Run Experimentation and Modeling, and NASA-CR-172378 Software Reliability: Additional Investigations into Modeling With Replicated Experiments, respectively. That is, the results confirm the log-linear pattern of software error rates and reject the hypothesis of equal error rates per individual fault. This rejection casts doubt on the assumption that the program's failure rate is a constant multiple of the number of residual bugs; an assumption which underlies some of the current models of software reliability. data raises new questions concerning the phenomenon of interacting faults.

  2. The Mediating and Moderating Effects of Workplace Social Capital on the Associations between Adverse Work Characteristics and Psychological Distress among Japanese Workers

    PubMed Central

    OSHIO, Takashi; INOUE, Akiomi; TSUTSUMI, Akizumi

    2014-01-01

    Our current study investigated how workplace social capital (WSC) mediates and moderates the associations between adverse work characteristics and psychological distress among Japanese workers. We collected cross-sectional data (N=9,350) from a baseline survey of an occupational Japanese cohort study. We focused on individual WSC and considered job demands/control, effort/reward, and two types (i.e., procedural and interactional) of organizational justice as work-characteristic variables. We defined psychological distress as a score of ≥5 on the Kessler Psychological Distress Scale (K6 scale). Multivariate logistic regression analyses predicted a binary variable of psychological distress by individual WSC and adverse work characteristics, adjusting for individual-level covariates. Individual WSC mediated the associations between adverse work characteristics and psychological distress in almost all model specifications. Additionally, individual WSC moderated the associations of psychological distress with high job demands, high effort, and low interactional justice when we used a high WSC cutoff point. In contrast, individual WSC did not moderate such interactions with low job control, reward, or procedural justice. We concluded that individual WSC mediated the associations between adverse work characteristics and psychological distress among Japanese workers while selectively moderating their associations at high levels of WSC. PMID:24705803

  3. Increases in soil aggregation following phosphorus additions in a tropical premontane forest are not driven by root and arbuscular mycorrhizal fungal abundances

    NASA Astrophysics Data System (ADS)

    Camenzind, Tessa; Papathanasiou, Helena; Foerster, Antje; Dietrich, Karla; Hertel, Dietrich; Homeier, Juergen; Oelmann, Yvonne; Olsson, Pål Axel; Suárez, Juan; Rillig, Matthias

    2015-12-01

    Tropical ecosystems have an important role in global change scenarios, in part because they serve as a large terrestrial carbon pool. Carbon protection is mediated by soil aggregation processes, whereby biotic and abiotic factors influence the formation and stability of aggregates. Nutrient additions may affect soil structure indirectly by simultaneous shifts in biotic factors, mainly roots and fungal hyphae, but also via impacts on abiotic soil properties. Here, we tested the hypothesis that soil aggregation will be affected by nutrient additions primarily via changes in arbuscular mycorrhizal fungal (AMF) hyphae and root length in a pristine tropical forest system. Therefore, the percentage of water-stable macroaggregates (> 250µm) (WSA) and the soil mean weight diameter (MWD) was analyzed, as well as nutrient contents, pH, root length and AMF abundance. Phosphorus additions significantly increased the amount of WSA, which was consistent across two different sampling times. Despite a positive effect of phosphorus additions on extraradical AMF biomass, no relationship between WSA and extra-radical AMF nor roots was revealed by regression analyses, contrary to the proposed hypothesis. These findings emphasize the importance of analyzing soil structure in understudied tropical systems, since it might be affected by increasing nutrient deposition expected in the future.

  4. Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit.

    PubMed

    Cevher, Murat A; Shi, Yi; Li, Dan; Chait, Brian T; Malik, Sohail; Roeder, Robert G

    2014-12-01

    The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas the reconstituted head and middle modules can stably associate, basal and coactivator functions are acquired only after incorporation of MED14 into the bimodular complex. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematic dissection of the multiple layers of functionality associated with the Mediator complex.

  5. Twins' risk of childhood asthma mediated by gestational age and birthweight.

    PubMed

    Ullemar, V; Lundholm, C; Almqvist, C

    2015-08-01

    Children born with low gestational age (GA) or low birthweight (BW) are at increased risk of asthma. Twins as compared to singletons are on average more likely to be born with lower GA and BW and have been hypothesized to comprise a high-risk population for asthma. Many previous studies have not accounted for potential confounders or mediators. To investigate the association between twinship and childhood asthma or early life wheeze and identify potential mediators, such as GA/BW. The study population consisted of two cohorts including all children born in Sweden from 1 January 1993 to 1 June 2001 (n = 756,363 singletons, n = 22,478 twins) and 1 July 2005 to 31 December 2009 (n = 456,239 singletons, n = 12,872 twins). Asthma was defined using validated register-based outcomes of diagnosis or medication. The data were analysed using logistic (older cohort) and Cox regression (younger cohort). Adjusted models incorporated potential confounding or mediating factors including gestational age and birthweight. In the younger cohort, the crude hazard ratio (HR) of asthma medication after 1.5 years of age was 1.12 (95% CI 1.01-1.23), and fully adjusted HR was 0.80, 95% CI 0.72-0.89. Crude HR of asthma diagnosis in the same age group was 1.14 (95% CI 0.99-1.30), fully adjusted 0.78 (0.68-0.98). Adjusted analyses in the older group yielded similar results. Twins were at significantly higher unadjusted risk of asthma or early life wheeze compared to singletons in the younger, but not in the older cohort. Associations attenuated following adjustment for GA/BW, suggesting that GA/BW mediates the effect of twinship on asthma risk. After adjustments, twins were at lower risk of asthma outcomes, possibly due to unmeasured confounding. © 2015 John Wiley & Sons Ltd.

  6. Sexual Attraction and Psychological Adjustment in Dutch Adolescents: Coping Style as a Mediator

    PubMed Central

    Bos, Henny; van Beusekom, Gabriël; Sandfort, Theo

    2018-01-01

    This study examined whether feelings of same-sex attraction (SSA) in 12- to 15-year-old Dutch adolescents were related to psychological health (self-esteem and psychological distress) and whether this relation was mediated by coping styles and moderated by biological sex. Data were collected from 1,546 high school students (802 boys and 744 girls; M age = 13.57 years) by means of standardized measurements. SSA was found to predict lower levels of self-esteem and higher levels of psychological distress. Further analyses showed that passive coping style partly mediated these associations. This mediation was not moderated by biological sex. The findings suggest that in understanding and addressing mental health disparities between sexual minorities and heterosexual youth attention should be paid to intrapersonal psychological factors such as coping styles. PMID:24938587

  7. 10 CFR 52.158 - Contents of application; additional technical information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Contents of application; additional technical information... APPROVALS FOR NUCLEAR POWER PLANTS Manufacturing Licenses § 52.158 Contents of application; additional technical information. The application must contain: (a)(1) Inspections, tests, analyses, and acceptance...

  8. Evaluating mediation and moderation effects in school psychology: A presentation of methods and review of current practice

    PubMed Central

    Fairchild, Amanda J.; McQuillin, Samuel D.

    2017-01-01

    Third variable effects elucidate the relation between two other variables, and can describe why they are related or under what conditions they are related. This article demonstrates methods to analyze two third-variable effects: moderation and mediation. The utility of examining moderation and mediation effects in school psychology is described and current use of the analyses in applied school psychology research is reviewed and evaluated. Proper statistical methods to test the effects are presented, and different effect size measures for the models are provided. Extensions of the basic moderator and mediator models are also described. PMID:20006988

  9. Flexible Mediation Analysis With Multiple Mediators.

    PubMed

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

    2017-07-15

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

  10. Brief Intervention for Drug Abusing Adolescents in a School Setting: Outcomes and Mediating Factors

    PubMed Central

    Winters, Ken C.; Fahnhorst, Tamara; Botzet, Andria; Lee, Susanne; Lalone, Britani

    2011-01-01

    This randomized controlled trial evaluated the use of two brief intervention conditions for adolescents (aged 12–18 years) who have been identified in a school setting as abusing alcohol and other drugs. Adolescents and their parent (N = 315) were randomly assigned to receive either a 2-session adolescent only (BI-A), 2-session adolescent and additional parent session (BI-AP), or assessment only control condition (CON). Interventions were manually guided and delivered in a school setting by trained counselors. Adolescents and parents were assessed at intake and at 6 months following the completion of the intervention. Analyses of relative (change from intake to 6-months) and absolute (status at 6-months) outcome variables indicated that for the most part, adolescents in the BI-A and BI-AP conditions showed significantly more reductions in drug use behaviors compared to the CON group. Also, youth receiving the BI-AP condition showed significantly better outcomes compared to the BI-A group on several variables. Problem-solving skills and utilization of additional counseling services mediated outcome. The value of a school-based brief intervention for students is discussed. PMID:22000326

  11. Internalized weight bias mediates the relationship between depressive symptoms and disordered eating behavior among women who think they are overweight.

    PubMed

    Sienko, Rachel M; Saules, Karen K; Carr, Meagan M

    2016-08-01

    This study tested the potential mediating role of Internalized Weight Bias (IWB) in the relationship between depressive symptoms (DEP-SX) and disordered eating behavior. In particular, we hypothesized that IWB may be an intervening variable in the well documented association between depression and disordered eating. College women (N=172) who were taking undergraduate psychology courses and who endorsed thinking they were overweight completed the Patient Health Questionnaire depression screener (PHQ-9), the Weight Bias Internalization Scale (WBIS), and the Eating Disorder Examination Questionnaire (EDE-Q). Bootstrapping mediation analyses were conducted to explore the relationships between these variables. IWB was significantly correlated with eating disorder symptoms and DEP-SX, but not Body Mass Index. Mediation analyses supported a model in which IWB mediated the relationship between DEP-SX and disordered eating behavior. Results indicate that individuals with elevated DEP-SX may be likely to internalize weight bias, which may in turn lead to maladaptive approaches to eating and weight control, regardless of one's actual weight status. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Rumination and depression in Chinese university students: The mediating role of overgeneral autobiographical memory.

    PubMed

    Kong, Tianzhu; He, Yini; Auerbach, Randy P; McWhinnie, Chad M; Xiao, Jing

    2015-04-01

    In this study, we examined the mediator effects of overgeneral autobiographical memory (OGM) on the relationship between rumination and depression in 323 Chinese university students. 323 undergraduates completed the questionnaires measuring OGM (Autobiographical Memory Test), rumination (Ruminative Response Scale) and depression (Center for Epidemiologic Studies Depression Scale). Results using structural equation modeling showed that OGM partially-mediated the relationship between rumination and depression (χ 2 = 88.61, p < .01; RMSEA = .051; SRMR = .040; and CFI = .91). Bootstrap methods were used to assess the magnitude of the indirect effects. The results of the bootstrap estimation procedure and subsequent analyses indicated that the indirect effects of OGM on the relationship between rumination and depressive symptoms were significant. The results indicated that rumination and depression were partially mediated by OGM.

  13. Pollinator-mediated interactions in experimental arrays vary with neighbor identity.

    PubMed

    Ha, Melissa K; Ivey, Christopher T

    2017-02-01

    Local ecological conditions influence the impact of species interactions on evolution and community structure. We investigated whether pollinator-mediated interactions between coflowering plants vary with plant density, coflowering neighbor identity, and flowering season. We conducted a field experiment in which flowering time and floral neighborhood were manipulated in a factorial design. Early- and late-flowering Clarkia unguiculata plants were placed into arrays with C. biloba neighbors, noncongeneric neighbors, additional conspecific plants, or no additional plants as a density control. We compared whole-plant pollen limitation of seed set, pollinator behavior, and pollen deposition among treatments. Interactions mediated by shared pollinators depended on the identity of the neighbor and possibly changed through time, although flowering-season comparisons were compromised by low early-season plant survival. Interactions with conspecific neighbors were likely competitive late in the season. Interactions with C. biloba appeared to involve facilitation or neutral interactions. Interactions with noncongeners were more consistently competitive. The community composition of pollinators varied among treatment combinations. Pollinator-mediated interactions involved competition and likely facilitation, depending on coflowering neighbor. Experimental manipulation helped to reveal context-dependent variation in indirect biotic interactions. © 2017 Botanical Society of America.

  14. Rumination mediates the association between cyber-victimization and depressive symptoms.

    PubMed

    Feinstein, Brian A; Bhatia, Vickie; Davila, Joanne

    2014-06-01

    The current study examined the 3-week prospective associations between cyber-victimization and both depressive symptoms and rumination. In addition, a mediation model was tested, wherein rumination mediated the association between cyber-victimization and depressive symptoms. Participants (N = 565 college-age young adults) completed online surveys at two time points 3 weeks apart. Results indicated that cyber-victimization was associated with increases in both depressive symptoms and rumination over time. Furthermore, results of the path analysis indicated that cyber-victimization was associated with increases in rumination over time, which were then associated with greater depressive symptoms, providing support for the proposed mediation effect for women, but not men. Findings extend previous correlational findings by demonstrating that cyber-victimization is associated with increases in symptomatology over time. Findings also suggest that the negative consequences of cyber-victimization extend beyond mental health problems to maladaptive emotion regulation. In fact, rumination may be a mechanism through which cyber-victimization influences mental health problems, at least for women. Mental health professionals are encouraged to assess cyber-victimization as part of standard victimization assessments and to consider targeting maladaptive emotion regulation in addition to mental health problems in clients who have experienced cyber-victimization.

  15. Coexposure to phytoestrogens and bisphenol a mimics estrogenic effects in an additive manner.

    PubMed

    Katchy, Anne; Pinto, Caroline; Jonsson, Philip; Nguyen-Vu, Trang; Pandelova, Marchela; Riu, Anne; Schramm, Karl-Werner; Samarov, Daniel; Gustafsson, Jan-Åke; Bondesson, Maria; Williams, Cecilia

    2014-03-01

    Endocrine-disrupting chemicals (EDC) are abundant in our environment. A number of EDCs, including bisphenol A (BPA) can bind to the estrogen receptors (ER), ERα and ERβ, and may contribute to estrogen-linked diseases such as breast cancer. Early exposure is of particular concern; many EDCs cross the placenta and infants have measurable levels of, eg, BPA. In addition, infants are frequently fed soy-based formula (SF) that contains phytoestrogens. Effects of combined exposure to xeno- and phytoestrogens are poorly studied. Here, we extensively compared to what extent BPA, genistein, and an extract of infant SF mimic estrogen-induced gene transcription and cell proliferation. We investigated ligand-specific effects on ER activation in HeLa-ERα and ERβ reporter cells; on proliferation, genome-wide gene regulation and non-ER-mediated effects in MCF7 breast cancer cells; and how coexposure influenced these effects. The biological relevance was explored using enrichment analyses of differentially regulated genes and clustering with clinical breast cancer profiles. We demonstrate that coexposure to BPA and genistein, or SF, results in increased functional and transcriptional estrogenic effects. Using statistical modeling, we determine that BPA and phytoestrogens act in an additive manner. The proliferative and transcriptional effects of the tested compounds mimic those of 17β-estradiol, and are abolished by cotreatment with an ER antagonist. Gene expression profiles induced by each compound clustered with poor prognosis breast cancer, indicating that exposure may adversely affect breast cancer prognosis. This study accentuates that coexposure to BPA and soy-based phytoestrogens results in additive estrogenic effects, and may contribute to estrogen-linked diseases, including breast cancer.

  16. Coexposure to Phytoestrogens and Bisphenol A Mimics Estrogenic Effects in an Additive Manner

    PubMed Central

    Katchy, Anne; Pinto, Caroline; Williams, Cecilia

    2014-01-01

    Endocrine-disrupting chemicals (EDC) are abundant in our environment. A number of EDCs, including bisphenol A (BPA) can bind to the estrogen receptors (ER), ERα and ERβ, and may contribute to estrogen-linked diseases such as breast cancer. Early exposure is of particular concern; many EDCs cross the placenta and infants have measurable levels of, eg, BPA. In addition, infants are frequently fed soy-based formula (SF) that contains phytoestrogens. Effects of combined exposure to xeno- and phytoestrogens are poorly studied. Here, we extensively compared to what extent BPA, genistein, and an extract of infant SF mimic estrogen-induced gene transcription and cell proliferation. We investigated ligand-specific effects on ER activation in HeLa-ERα and ERβ reporter cells; on proliferation, genome-wide gene regulation and non-ER–mediated effects in MCF7 breast cancer cells; and how coexposure influenced these effects. The biological relevance was explored using enrichment analyses of differentially regulated genes and clustering with clinical breast cancer profiles. We demonstrate that coexposure to BPA and genistein, or SF, results in increased functional and transcriptional estrogenic effects. Using statistical modeling, we determine that BPA and phytoestrogens act in an additive manner. The proliferative and transcriptional effects of the tested compounds mimic those of 17β-estradiol, and are abolished by cotreatment with an ER antagonist. Gene expression profiles induced by each compound clustered with poor prognosis breast cancer, indicating that exposure may adversely affect breast cancer prognosis. This study accentuates that coexposure to BPA and soy-based phytoestrogens results in additive estrogenic effects, and may contribute to estrogen-linked diseases, including breast cancer. PMID:24284790

  17. Age mediation of frontoparietal activation during visual feature search.

    PubMed

    Madden, David J; Parks, Emily L; Davis, Simon W; Diaz, Michele T; Potter, Guy G; Chou, Ying-hui; Chen, Nan-kuei; Cabeza, Roberto

    2014-11-15

    Activation of frontal and parietal brain regions is associated with attentional control during visual search. We used fMRI to characterize age-related differences in frontoparietal activation in a highly efficient feature search task, detection of a shape singleton. On half of the trials, a salient distractor (a color singleton) was present in the display. The hypothesis was that frontoparietal activation mediated the relation between age and attentional capture by the salient distractor. Participants were healthy, community-dwelling individuals, 21 younger adults (19-29 years of age) and 21 older adults (60-87 years of age). Top-down attention, in the form of target predictability, was associated with an improvement in search performance that was comparable for younger and older adults. The increase in search reaction time (RT) associated with the salient distractor (attentional capture), standardized to correct for generalized age-related slowing, was greater for older adults than for younger adults. On trials with a color singleton distractor, search RT increased as a function of increasing activation in frontal regions, for both age groups combined, suggesting increased task difficulty. Mediational analyses disconfirmed the hypothesized model, in which frontal activation mediated the age-related increase in attentional capture, but supported an alternative model in which age was a mediator of the relation between frontal activation and capture. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Age Mediation of Frontoparietal Activation during Visual Feature Search

    PubMed Central

    Madden, David J.; Parks, Emily L.; Davis, Simon W.; Diaz, Michele T.; Potter, Guy G.; Chou, Ying-hui; Chen, Nan-kuei; Cabeza, Roberto

    2014-01-01

    Activation of frontal and parietal brain regions is associated with attentional control during visual search. We used fMRI to characterize age-related differences in frontoparietal activation in a highly efficient feature search task, detection of a shape singleton. On half of the trials, a salient distractor (a color singleton) was present in the display. The hypothesis was that frontoparietal activation mediated the relation between age and attentional capture by the salient distractor. Participants were healthy, community-dwelling individuals, 21 younger adults (19 – 29 years of age) and 21 older adults (60 – 87 years of age). Top-down attention, in the form of target predictability, was associated with an improvement in search performance that was comparable for younger and older adults. The increase in search reaction time (RT) associated with the salient distractor (attentional capture), standardized to correct for generalized age-related slowing, was greater for older adults than for younger adults. On trials with a color singleton distractor, search RT increased as a function of increasing activation in frontal regions, for both age groups combined, suggesting increased task difficulty. Mediational analyses disconfirmed the hypothesized model, in which frontal activation mediated the age-related increase in attentional capture, but supported an alternative model in which age was a mediator of the relation between frontal activation and capture. PMID:25102420

  19. Additive effects of nicotine and high-fat diet on hepatocellular apoptosis in mice: involvement of caspase 2 and inducible nitric oxide synthase-mediated intrinsic pathway signaling.

    PubMed

    Ivey, R; Desai, M; Green, K; Sinha-Hikim, I; Friedman, T C; Sinha-Hikim, A P

    2014-07-01

    Smoking is a major risk factor for diabetes and cardiovascular disease and may contribute to nonalcoholic fatty liver disease (NAFLD). The health risk associated with smoking is exaggerated by obesity and is the leading causes of morbidity and mortality worldwide. We recently demonstrated that combined treatment with nicotine and a high-fat diet (HFD) triggers greater oxidative stress, activates hepatocellular apoptosis, and exacerbates HFD-induced hepatic steatosis. Given that hepatocellular apoptosis plays a pivotal role in the pathogenesis of NAFLD, using this model of exacerbated hepatic steatosis, we elucidated the signal transduction pathways involved in HFD plus nicotine-induced liver cell death. Adult C57BL6 male mice were fed a normal chow diet or HFD with 60% of calories derived from fat and received twice daily IP injections of 0.75 mg/kg BW of nicotine or saline for 10 weeks. High-resolution light microscopy revealed markedly higher lipid accumulation in hepatocytes from mice received HFD plus nicotine, compared to mice on HFD alone. Addition of nicotine to HFD further resulted in an increase in the incidence of hepatocellular apoptosis and was associated with activation of caspase 2, induction of inducible nitric oxide synthase (iNOS), and perturbation of the BAX/BCL-2 ratio. Together, our data indicate the involvement of caspase 2 and iNOS-mediated apoptotic signaling in nicotine plus HFD-induced hepatocellular apoptosis. Targeting the caspase 2-mediated death pathway may have a protective role in development and progression of NAFLD. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Authentic leadership and thriving among nurses: the mediating role of empathy.

    PubMed

    Mortier, Anneleen Viona; Vlerick, Peter; Clays, Els

    2016-04-01

    To examine the relationship between perceived authentic leadership and two dimensions of thriving (learning and vitality) among nurses, and to study the mediating role of empathy in this relationship. Nurses' thriving is a key asset for health care organisations, and its significant role warrants the need to identify the underlying key determinants and psychological mechanisms. A cross-sectional design was carried out in a large hospital in September 2013. Self-administered questionnaires were distributed to 360 nurses. The main hypotheses were tested through hierarchical regression analyses. The significant positive relationship between perceived authentic leadership and vitality was mediated by perceived empathy. This mediation, however, was not confirmed in relation to learning. Nurse managers' authentic leadership enhances nurses' thriving at work. Furthermore, empathic nurse managers seem to increase the vitality of their nurses. Training nurse managers in authentic leadership skills is important for the nursing field, as those skills help nurse managers to better express empathy and consequently foster thriving in nursing. © 2015 John Wiley & Sons Ltd.

  1. Mediators of Effects of a Selective Family-Focused Violence Prevention Approach for Middle School Students

    PubMed Central

    2013-01-01

    This study examined how parenting and family characteristics targeted in a selective prevention program mediated effects on key youth proximal outcomes related to violence perpetration. The selective intervention was evaluated within the context of a multi-site trial involving random assignment of 37 schools to four conditions: a universal intervention composed of a student social-cognitive curriculum and teacher training, a selective family-focused intervention with a subset of high-risk students, a condition combining these two interventions, and a no-intervention control condition. Two cohorts of sixth-grade students (total N=1,062) exhibiting high levels of aggression and social influence were the sample for this study. Analyses of pre-post change compared to controls using intent-to-treat analyses found no significant effects. However, estimates incorporating participation of those assigned to the intervention and predicted participation among those not assigned revealed significant positive effects on student aggression, use of aggressive strategies for conflict management, and parental estimation of student’s valuing of achievement. Findings also indicated intervention effects on two targeted family processes: discipline practices and family cohesion. Mediation analyses found evidence that change in these processes mediated effects on some outcomes, notably aggressive behavior and valuing of school achievement. Results support the notion that changing parenting practices and the quality of family relationships can prevent the escalation in aggression and maintain positive school engagement for high-risk youth. PMID:21932067

  2. STAT6: its role in interleukin 4-mediated biological functions.

    PubMed

    Takeda, K; Kishimoto, T; Akira, S

    1997-05-01

    Interleukin (IL) 4 is known to be a cytokine which plays a central role in the regulation of immune response. Studies on cytokine signal transduction have clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic proteins, signal transducer and activator of transcription (STAT) 6 and IL4-induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are activated in IL4 signal transduction. Recent studies from STAT6-deficient mice have revealed the essential role of STAT6 in IL4-mediated biological actions. In addition, STAT6 has also been demonstrated to be important for the functions mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to induce the production of IgE, which is a major mediator in an allergic response. These findings indicate that STAT6 activation is involved in IL4- and IL13-mediated disorders such as allergy.

  3. Work climate and the mediating role of workplace bullying related to job performance, job satisfaction, and work ability: A study among hospital nurses.

    PubMed

    Olsen, Espen; Bjaalid, Gunhild; Mikkelsen, Aslaug

    2017-11-01

    To increase understanding of workplace bullying and its relation to work climate and different outcomes among nurses. Examine a proposed bullying model including both job resource and job demands, as well as nurse outcomes reflected in job performance, job satisfaction, and work ability. Workplace bullying has been identified as some of the most damaging mechanisms in workplace settings. It is important to increase understanding of workplace bullying in relation to work climate and different outcomes among nurses. This study adopted a cross-sectional web based survey design. A sample of 2946 Registered Nurses from four public Norwegian hospitals were collected during October 2014. We analysed data using descriptive statistics, correlations, Cronbach's alpa, confirmatory factor analyses, and structural equation modelling. The majority of work climate characteristics confirmed to influence workplace bullying, and additionally had direct influence on nurse outcomes; job performance, job satisfaction, and work ability. Bullying had a mediational role between most of the work climate dimensions and nurse outcomes. This study increases our understanding of organizational antecedent of bullying among nurses. Workplace bullying among nurses functions as a mediator between the majority of work climate dimensions and outcomes related to job satisfaction and work ability. Strategies to reduce bullying should look at the study finding and specifically job resources and job demands that influence bullying and nurse outcomes. © 2017 John Wiley & Sons Ltd.

  4. Procrastination and suicide proneness: A moderated-mediation model for cognitive schemas and gender.

    PubMed

    Klibert, Jeffrey; LeLeux-LaBarge, Kayla; Tarantino, Nicholas; Yancey, Thresa; Lamis, Dorian A

    2016-07-01

    This study examined the direct and indirect paths between procrastination and suicide proneness while considering gender differences. Participants included 547 undergraduates from a southeastern university. Procrastination was positively related to suicide proneness for both genders, although this relation was stronger for women. Moderated-mediation analyses with bootstrapping highlighted insufficient self-control schemas as a mediator in the relation between procrastination and suicide proneness. However, indirect pathways did not vary by gender. Results represent an extension of the Procrastination-Health Model by highlighting the contribution of cognitive factors in explaining the relation between procrastination and suicide proneness.

  5. 10 CFR 52.80 - Contents of applications; additional technical information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Contents of applications; additional technical information... APPROVALS FOR NUCLEAR POWER PLANTS Combined Licenses § 52.80 Contents of applications; additional technical information. The application must contain: (a) The proposed inspections, tests, and analyses, including those...

  6. 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.

  7. Linking organizational resources and work engagement to employee performance and customer loyalty: the mediation of service climate.

    PubMed

    Salanova, Marisa; Agut, Sonia; Peiró, José María

    2005-11-01

    This study examined the mediating role of service climate in the prediction of employee performance and customer loyalty. Contact employees (N=342) from 114 service units (58 hotel front desks and 56 restaurants) provided information about organizational resources, engagement, and service climate. Furthermore, customers (N=1,140) from these units provided information on employee performance and customer loyalty. Structural equation modeling analyses were consistent with a full mediation model in which organizational resources and work engagement predict service climate, which in turn predicts employee performance and then customer loyalty. Further analyses revealed a potential reciprocal effect between service climate and customer loyalty. Implications of the study are discussed, together with limitations and suggestions for future research. ((c) 2005 APA, all rights reserved).

  8. Arg354 in the catalytic centre of bovine liver catalase is protected from methylglyoxal-mediated glycation.

    PubMed

    Scheckhuber, Christian Q

    2015-12-30

    In addition to controlled post-translational modifications proteins can be modified with highly reactive compounds. Usually this leads to a compromised functionality of the protein. Methylglyoxal is one of the most common agents that attack arginine residues. Methylglyoxal is also regarded as a pro-oxidant that affects cellular redox homeostasis by contributing to the formation of reactive oxygen species. Antioxidant enzymes like catalase are required to protect the cell from oxidative damage. These enzymes are also targets for methylglyoxal-mediated modification which could severely affect their catalytic activity in breaking down reactive oxygen species to less reactive or inert compounds. Here, bovine liver catalase was incubated with high levels of methylglyoxal to induce its glycation. This treatment did not lead to a pronounced reduction of enzymatic activity. Subsequently methylglyoxal-mediated arginine modifications (hydroimidazolone and dihydroxyimidazolidine) were quantitatively analysed by sensitive nano high performance liquid chromatography/electron spray ionisation/tandem mass spectrometry. Whereas several arginine residues displayed low to moderate levels of glycation (e.g., Arg93, Arg365, Arg444) Arg354 in the active centre of catalase was never found to be modified. Bovine liver catalase is able to tolerate very high levels of the modifying α-oxoaldehyde methylglyoxal so that its essential enzymatic function is not impaired.

  9. High Fidelity Additive Manufacturing of Optically Transparent Glass Structures

    NASA Astrophysics Data System (ADS)

    Inamura, Chikara

    Glass has been an integral part of human civilization with expressions across scales and disciplines: from the microscope to the telescope, from fiber optics to mobile interface, and from the petri dish to a building envelope. Such a diverse range of applications is enabled by the inherent material properties including mechanical strength, optical transparency and chemical inertness. Additive manufacturing provides opportunities for integrating the unique properties of glass to engineer novel structures that are functionary graded through precise spatiotemporal deposition of molten glass. This talk presents the Mediated Matter Group's latest development of a novel additive manufacturing platform, and related processes, for 3D Printing optically transparent glass for architectural scale applications.

  10. 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.

  11. The association between home environmental variables and soft drink consumption among adolescents. Exploration of mediation by individual cognitions and habit strength.

    PubMed

    Tak, N I; Te Velde, S J; Oenema, A; Van der Horst, K; Timperio, A; Crawford, D; Brug, J

    2011-04-01

    Soft-drink consumption is one of the important target behaviours for the prevention of excessive weight gain among adolescents. To be able to modify these behaviours in obesity prevention interventions, further understanding of the underlying factors and mediational pathways is required. The present study aimed to explore associations between home environment variables and adolescent soft drink consumption and potential mediation of these associations by individual cognitions derived from the Theory of Planned Behaviour and habit strength. The ENDORSE study (N=1005) provided data on soft drink consumption and on home environment variables related to soft drink consumption (availability, accessibility, parental modelling, and parental rules), cognitive variables (intention, attitude, perceived behaviour control, and parental norm) and habit strength. Multiple mediation analyses were conducted using regression analyses according to the steps described by MacKinnon to assess the association between home environment variables and soft drink consumption and mediation of these associations by cognitive variables and habit strength. The bootstrapping method was used to calculate the confidence intervals. There were significant associations between the home environment variables and soft drink consumption. After inclusion of the mediators the strength of these associations was reduced. In the multiple mediator models, habit strength (39.4-62.6%) and intention (19.1-36.6%) were the strongest mediators. Intention and habit strength partly mediate the associations between home environment factors and soft drink consumption, suggesting that home environment variables influence soft drink consumption both indirectly and directly. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Effects of tylosin, tilmicosin and tulathromycin on inflammatory mediators in bronchoalveolar lavage fluid of lipopolysaccharide-induced lung injury.

    PubMed

    Er, Ayse; Yazar, Enver

    2012-12-01

    The aim of this study was to determine the anti-inflammatory effects of macrolides through kinetic parameters in bronchoalveolar lavage fluid (BALF) of lipopolysaccharide-induced lung injury. Rats were divided into four groups: lipopolysaccharide (LPS), LPS + tylosin, LPS + tilmicosin and LPS + tulathromycin. BALF samples were collected at sampling times. TNF, IL-1β, IL-6, IL-10 and 13,14-dihydro-15-keto-prostaglandin F2α (PGM) and C-reactive protein (CRP) were analysed. Area under the curve (AUC) and maximum plasma concentration (Cmax) values of inflammatory mediators were determined by a pharmacokinetic computer programme. When inflammatory mediator concentrations were compared between the LPS group and other groups for each sampling time, the three macrolides had no pronounced depressor effect on cytokine levels, but they depressed PGM and CRP levels. In addition, tylosin and tilmicosin decreased the AUC0-24 level of TNF, while tilmicosin decreased the AUC0-24 level of IL-10. Tylosin and tulathromycin decreased the AUC0-24 of PGM, and all three macrolides decreased the AUC0-24 of CRP. Especially tylosin and tulathromycin may have more expressed anti-inflammatory effects than tilmicosin, via depressing the production of inflammatory mediators in the lung. The AUC may be used for determining the effects of drugs on inflammation. In this study, the antiinflammatory effects of these antibiotics were evaluated with kinetic parameters as a new and different approach.

  13. Does multitasking mediate the relationships between episodic memory, attention, executive functions and apathetic manifestations in traumatic brain injury?

    PubMed

    Arnould, Annabelle; Rochat, Lucien; Dromer, Emilie; Azouvi, Philippe; Van der Linden, Martial

    2018-03-01

    Apathy is frequently described in patients with traumatic brain injury (TBI); its negative consequences particularly affect functional independence. Among apathetic manifestations, lack of initiative and lack of interest have mainly been associated with cognitive impairments. However, few studies have been conducted to precisely identify the underlying cognitive processes. Our aims were (1) to determine the best predictor of apathy from among several cognitive processes, including episodic memory and attention/executive mechanisms and multitasking, and (2) to examine to what extent multitasking could mediate the relationships between specific cognitive processes and lack of initiative/interest. Seventy participants (34 patients with TBI matched with 36 control participants) were given a questionnaire to assess anxio-depressive symptoms, four tasks to assess specific cognitive processes, and one task to assess real-life multitasking. Participants' relatives completed an apathy questionnaire. Multitasking, as assessed by the number of goals not achieved, was the only significant predictor of apathetic manifestations. In addition, the mediation analyses revealed that multitasking performance mediated the relationships between verbal episodic memory and lack of initiative/interest, whereas executive and attentional functions were only indirectly related to lack of initiative/interest due to their significant impacts on multitasking. These results shed new light on the aetiology of apathetic manifestations in patients with TBI, indicating how specific cognitive deficits are expressed in real-life multitasking, and consequently, how they may lead to the development and/or maintenance of apathetic manifestations. © 2016 The British Psychological Society.

  14. Cancer survivors in the workplace: sleep disturbance mediates the impact of cancer on healthcare expenditures and work absenteeism.

    PubMed

    Gonzalez, Brian D; Grandner, Michael A; Caminiti, Courtney B; Hui, Siu-Kuen Azor

    2018-06-05

    History of cancer is significantly associated with increases in healthcare costs, worse work performance, and higher absenteeism in the workplace. This is particularly important as most cancer survivors return to employment. Sleep disturbance is a largely overlooked potential contributor to these changes. Data from 9488 state employees participating in the Kansas State employee wellness program were used to assess cancer history, sleep disturbance, healthcare expenditures, work performance ratings, and absenteeism. Participants were categorized as having had no history of breast or prostate cancer, a past history only with no current cancer treatment, or current treatment for breast or prostate cancer. Indirect mediation analyses determined whether sleep disturbance mediated the influence of cancer status on outcomes. Employees receiving treatment for breast or prostate cancer had significantly greater healthcare expenditures and absenteeism than those with a past history or no history of cancer (ps < .0001). Sleep disturbance significantly mediated the impact of cancer on healthcare expenditures and absenteeism (ps < .05), accounting for 2 and 8% of the impact of cancer on healthcare expenditure and missed full days of work, respectively. The worse outcomes observed among employees receiving treatment for breast and prostate cancer, the most common forms of cancer among women and men, were partially explained by the impacts of cancer and treatment for cancer on sleep disturbance. These findings suggest that preventing or addressing sleep disturbance may result in economic benefits in addition to improvements in health and quality of life.

  15. Autonomous and controlled motivational regulations for multiple health-related behaviors: between- and within-participants analyses

    PubMed Central

    Hagger, M.S.; Hardcastle, S.J.; Chater, A.; Mallett, C.; Pal, S.; Chatzisarantis, N.L.D.

    2014-01-01

    Self-determination theory has been applied to the prediction of a number of health-related behaviors with self-determined or autonomous forms of motivation generally more effective in predicting health behavior than non-self-determined or controlled forms. Research has been confined to examining the motivational predictors in single health behaviors rather than comparing effects across multiple behaviors. The present study addressed this gap in the literature by testing the relative contribution of autonomous and controlling motivation to the prediction of a large number of health-related behaviors, and examining individual differences in self-determined motivation as a moderator of the effects of autonomous and controlling motivation on health behavior. Participants were undergraduate students (N = 140) who completed measures of autonomous and controlled motivational regulations and behavioral intention for 20 health-related behaviors at an initial occasion with follow-up behavioral measures taken four weeks later. Path analysis was used to test a process model for each behavior in which motivational regulations predicted behavior mediated by intentions. Some minor idiosyncratic findings aside, between-participants analyses revealed significant effects for autonomous motivational regulations on intentions and behavior across the 20 behaviors. Effects for controlled motivation on intentions and behavior were relatively modest by comparison. Intentions mediated the effect of autonomous motivation on behavior. Within-participants analyses were used to segregate the sample into individuals who based their intentions on autonomous motivation (autonomy-oriented) and controlled motivation (control-oriented). Replicating the between-participants path analyses for the process model in the autonomy- and control-oriented samples did not alter the relative effects of the motivational orientations on intention and behavior. Results provide evidence for consistent effects

  16. Interparental hostility and children's externalizing symptoms: Attention to anger as a mediator.

    PubMed

    Davies, Patrick T; Coe, Jesse L; Hentges, Rochelle F; Sturge-Apple, Melissa L; Ripple, Michael T

    2018-07-01

    This study examined children's attention biases to negative emotional stimuli as mediators of associations between interparental hostility and children's externalizing symptoms. Participants included 243 children (Mage = 4.60 years) and their parents and teachers across three annual measurement occasions. Cross-lagged latent change analyses revealed that the association between interparental hostility and children's externalizing symptoms was mediated by children's attention to angry, but not sad or fearful, adult faces. Consistent with defensive exclusion models, the multimethod, multi-informant assessment of interparental hostility at Wave 1 specifically predicted decreases in children's attention to angry faces from Waves 1 to 2 in a visual search task. Declines in children's attention to anger, in turn, predicted increases in teacher reports of their externalizing problems across the three waves. Follow-up analyses further indicated that children's decreasing levels of emotional security in the interparental relationship were associated with the decreases in children's attention to angry stimuli. Results are discussed in relation to how they inform and advance information processing and social threat models in developmental psychopathology. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  17. 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

  18. 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

  19. Mediation of early maladaptive schemas between perceptions of parental rearing style and personality disorder symptoms.

    PubMed

    Thimm, Jens C

    2010-03-01

    In schema therapy (ST), early maladaptive schemas (EMS) are proposed to be the defining core of personality disorders. Adverse relational experiences in childhood are assumed to be the main cause for the development of EMS. The present study explored the links between perceived parental rearing behaviours, EMS, and personality disorder symptoms in a clinical sample (N=108). Results from mediation analyses suggest that EMS mediate the relationships between recalled parenting rearing behaviours and personality disorder symptoms. Findings give support to the theoretical model ST is based on.

  20. 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.

  1. Antigen-mediated regulation in monoclonal gammopathies and myeloma.

    PubMed

    Nair, Shiny; Sng, Joel; Boddupalli, Chandra Sekhar; Seckinger, Anja; Chesi, Marta; Fulciniti, Mariateresa; Zhang, Lin; Rauniyar, Navin; Lopez, Michael; Neparidze, Natalia; Parker, Terri; Munshi, Nikhil C; Sexton, Rachael; Barlogie, Bart; Orlowski, Robert; Bergsagel, Leif; Hose, Dirk; Flavell, Richard A; Mistry, Pramod K; Meffre, Eric; Dhodapkar, Madhav V

    2018-04-19

    A role for antigen-driven stimulation has been proposed in the pathogenesis of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) based largely on the binding properties of monoclonal Ig. However, insights into antigen binding to clonal B cell receptors and in vivo responsiveness of the malignant clone to antigen-mediated stimulation are needed to understand the role of antigenic stimulation in tumor growth. Lysolipid-reactive clonal Ig were detected in Gaucher disease (GD) and some sporadic gammopathies. Here, we show that recombinant Ig (rIg) cloned from sort-purified single tumor cells from lipid-reactive sporadic and GD-associated gammopathy specifically bound lysolipids. Liposome sedimentation and binding assays confirmed specific interaction of lipid-reactive monoclonal Ig with lysolipids. The clonal nature of lysolipid-binding Ig was validated by protein sequencing. Gene expression profiling and cytogenetic analyses from 2 patient cohorts showed enrichment of nonhyperdiploid tumors in lipid-reactive patients. In vivo antigen-mediated stimulation led to an increase in clonal Ig and plasma cells (PCs) in GD gammopathy and also reactivated previously suppressed antigenically related nonclonal PCs. These data support a model wherein antigenic stimulation mediates an initial polyclonal phase, followed by evolution of monoclonal tumors enriched in nonhyperdiploid genomes, responsive to underlying antigen. Targeting underlying antigens may therefore prevent clinical MM.

  2. Reconstitution of active human core Mediator complex reveals a pivotal role of the MED14 subunit

    PubMed Central

    Cevher, Murat A.; Shi, Yi; Li, Dan; Chait, Brian T.; Malik, Sohail; Roeder, Robert G.

    2014-01-01

    The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here, we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to mass spectrometry (CX-MS). Whereas the reconstituted head and middle modules can stably associate, only with incorporation of MED14 into the bi-modular complex does it acquire basal and coactivator functions. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematically dissecting the multiple layers of functionalities associated with the Mediator complex. PMID:25383669

  3. Mediation of symptom changes during inpatient treatment for eating disorders: the role of obsessive-compulsive features.

    PubMed

    Olatunji, Bunmi O; Tart, Candyce D; Shewmaker, Shona; Wall, David; Smits, Jasper A J

    2010-10-01

    The present study examined the relative contributions of changes in obsessive-compulsive symptoms among eating-disorder patients with (n = 254) and without (n = 254) obsessive-compulsive disorder (OCD) to eating-disorder symptom improvement observed with inpatient treatment. Consistent with hypothesis, multilevel mediation analyses revealed that improvements in OCD symptoms over time accounted for significant variance in the improvements in eating-disorder symptoms over time, with stronger mediation evident among eating-disorder patients with comorbid OCD (percent mediated; P(M) = 22.5%) compared to those without OCD (P(M) = 12.2%). However, decreases in eating-disorder symptoms over time fully mediated improvements in OCD symptoms over time, and this mediated pathway did not vary substantially as a function of comorbid OCD status. The theoretical and treatment implications of these findings for conceptualizing the relationship between eating disorders and OCD are discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Hypnotherapy to Reduce Hot Flashes: Examination of Response Expectancies as a Mediator of Outcomes

    PubMed Central

    Sliwinski, Jim R.; Elkins, Gary R.

    2017-01-01

    The mechanism of action responsible for hypnotherapy’s effect in reducing hot flashes is not yet known. The purpose of this study was to examine the role of response expectancies as a potential mediator. Hypnotizability was also tested as an effect moderator. Data were collected from a sample of 172 postmenopausal women, who had been randomized to receive either a 5-week hypnosis intervention or structured attention counseling. Measures of response expectancies were analyzed to determine if the relationship between group assignment and hot flashes frequency was mediated by expectancies for treatment efficacy. A series of simple mediation and conditional process analyses did not support mediation of the relationship between treatment condition and hot flash frequency through response expectancy. The effect of hypnotherapy in reducing hot flashes does not appear to be due to placebo effects as determined by response expectancies. Implications for clinical practice and future research are discussed. PMID:28528570

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

    PubMed

    Kleiman, Evan M; Riskind, John H

    2013-01-01

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

  6. Attention Deficit/Hyperactivity Disorder Symptoms and Depression Symptoms as Mediators in the Intergenerational Transmission of Smoking

    PubMed Central

    Zoloto, Alex; Nagoshi, Craig T.; Presson, Clark; Chassin, Laurie

    2012-01-01

    Background Attention deficit/hyperactivity disorder and depression have been found to be comorbid with smoking behaviors, and all three behavioral syndromes have been shown to be familially transmitted. The present paper reports on the results of analyses testing whether child attention deficit/hyperactivity disorder and depression symptoms were mediators in the intergenerational transmission of cigarette smoking. Method Path analyses using bootstrapped mediation procedures were conducted on data from a community sample of 764 families (one or both parents and one adolescent offspring) from the Indiana University Smoking Survey. Parents reported on their smoking behaviors, ADHD, and depression and their child’s ADHD, while offspring reported on their smoking behaviors and depression. Results Although fathers’ and mothers’ smoking status, depression, and ADHD were not significantly correlated with boys’ smoking initiation, there was a significant mediated (indirect) pathway from mothers’ depression to boys’ smoking initiation through boys’ depression. Several parental variables were significantly correlated with smoking initiation in girls, and the pathways from mothers’ smoking status, mothers’ ADHD, and fathers’ smoking status to girls’ smoking initiation were significantly mediated by girls’ ADHD. Conclusions For adolescent girls, the intergenerational transmission of ADHD appears to be important in understanding the intergenerational transmission of cigarette smoking. Sex differences in the intergenerational transmission of psychopathology as it leads to smoking initiation were also discussed. PMID:22682659

  7. Does alcohol craving mediate the impulsivity-aggression relationship in recently detoxified alcohol-dependent patients?

    PubMed

    Roozen, H G; Wetering, B J M van de; Franken, I H A

    2013-01-01

    The relationship between the use of alcohol and aggression is complex and represents major public health issues. Delving into the nature of this association is vital, since various underlying factors may contribute to the expression of aggression. This study examined trait aggression by assessing correlates and, subsequently, the unique contribution of alcohol craving, and dysfunctional impulsivity, by means of correlational and mediational analyses. Forty inpatient detoxified alcohol-dependent patients were recruited. These participants completed the Desire for Alcohol Questionnaire (DAQ), Dickman Impulsivity Inventory (DII), and the Aggression Questionnaire (AQ). The findings indicated that aggression, dysfunctional impulsivity, and alcohol craving were all positively intercorrelated. The association between dysfunctional impulsivity and aggression was robust. The mediational analyses yielded that craving partially mediated this relationship, although not very substantial. It was shown that impulsivity, as a personality characteristic, is strongly associated with aggressive behaviors, whereby the impact of craving on the relationship between impulsivity and trait aggression in alcohol-dependent inpatients was weak. Since it has been posited that factors such as impulsivity and craving may contribute to the lucid association between substance use and aggression, these findings mirror previous research on stimulant users and, subsequently, substantiates that craving exerts only a minor weight on the strong impulsivity-aggression relationship.

  8. 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…

  9. 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…

  10. Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration.

    PubMed

    Kempuraj, Duraisamy; Thangavel, Ramasamy; Selvakumar, Govindhasamy P; Zaheer, Smita; Ahmed, Mohammad E; Raikwar, Sudhanshu P; Zahoor, Haris; Saeed, Daniyal; Natteru, Prashant A; Iyer, Shankar; Zaheer, Asgar

    2017-01-01

    Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions. In addition, inflammatory mediators released from activated glial cells induce neurodegeneration in the brain. Systemic inflammation-derived proinflammatory cytokines/chemokines and other factors cause a breach in the blood brain-barrier (BBB) thereby allowing for the entry of immune/inflammatory cells including mast cell progenitors, mast cells and proinflammatory cytokines and chemokines into the brain. These peripheral-derived factors and intrinsically generated cytokines/chemokines, α-synuclein, corticotropin-releasing hormone (CRH), substance P (SP), beta amyloid 1-42 (Aβ1-42) peptide and amyloid precursor proteins can activate glial cells, T-cells and mast cells in the brain can induce additional release of inflammatory and neurotoxic molecules contributing to chronic neuroinflammation and neuronal death. The glia maturation factor (GMF), a proinflammatory protein discovered in our laboratory released from glia, activates mast cells to release inflammatory cytokines and chemokines. Chronic increase in the proinflammatory mediators induces neurotoxic Aβ and plaque formation in AD brains and neurodegeneration in PD brains. Glial cells, mast cells and T-cells can reactivate each other in neuroinflammatory conditions in the brain and augment neuroinflammation. Further, inflammatory mediators from the brain can

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

    PubMed

    Landau, Sabine; Emsley, Richard; Dunn, Graham

    2018-06-01

    Random allocation avoids confounding bias when estimating the average treatment effect. For continuous outcomes measured at post-treatment as well as prior to randomisation (baseline), analyses based on (A) post-treatment outcome alone, (B) change scores over the treatment phase or (C) conditioning on baseline values (analysis of covariance) provide unbiased estimators of the average treatment effect. The decision to include baseline values of the clinical outcome in the analysis is based on precision arguments, with analysis of covariance known to be most precise. Investigators increasingly carry out explanatory analyses to decompose total treatment effects into components that are mediated by an intermediate continuous outcome and a non-mediated part. Traditional mediation analysis might be performed based on (A) post-treatment values of the intermediate and clinical outcomes alone, (B) respective change scores or (C) conditioning on baseline measures of both intermediate and clinical outcomes. Using causal diagrams and Monte Carlo simulation, we investigated the performance of the three competing mediation approaches. We considered a data generating model that included three possible confounding processes involving baseline variables: The first two processes modelled baseline measures of the clinical variable or the intermediate variable as common causes of post-treatment measures of these two variables. The third process allowed the two baseline variables themselves to be correlated due to past common causes. We compared the analysis models implied by the competing mediation approaches with this data generating model to hypothesise likely biases in estimators, and tested these in a simulation study. We applied the methods to a randomised trial of pragmatic rehabilitation in patients with chronic fatigue syndrome, which examined the role of limiting activities as a mediator. Estimates of causal mediation effects derived by approach (A) will be biased if one of

  12. Intervention and Revision: Expertise and Interaction in Text Mediation

    ERIC Educational Resources Information Center

    Luo, Na; Hyland, Ken

    2017-01-01

    Many EAL (English as an Additional Language) scholars enlist text mediators' support when faced with the challenges of writing for international publication. However, the contributions these individuals are able to make in improving scientific manuscripts remains unclear, especially when language professionals such as English teachers do this…

  13. Comparative proteomic analyses reveal that FlbA down-regulates gliT expression and SOD activity in Aspergillus fumigatus.

    PubMed

    Shin, Kwang-Soo; Park, Hee-Soo; Kim, Young-Hwan; Yu, Jae-Hyuk

    2013-07-11

    FlbA is a regulator of G-protein signaling protein that plays a central role in attenuating heterotrimeric G-protein mediated vegetative growth signaling in Aspergillus. The deletion of flbA (∆flbA) in the opportunistic human pathogen Aspergillus fumigatus results in accelerated cell death and autolysis in submerged culture. To further investigate the effects of ∆flbA on intracellular protein levels we carried out 2-D proteome analyses of 2-day old submerged cultures of ∆flbA and wild type (WT) strains and observed 160 differentially expressed proteins. Via nano-LC-ESI-MS/MS analyses, we revealed the identity of 10 and 2 proteins exhibiting high and low level accumulation, respectively, in ∆flbA strain. Notably, the GliT protein is accumulated at about 1800-fold higher levels in ∆flbA than WT. Moreover, GliT is secreted at high levels from ∆flbA strain, whereas Sod1 (superoxide dismutase) is secreted at a higher level in WT. Northern blot analyses reveal that ∆flbA results in elevated accumulation of gliT mRNA. Consequently, ∆flbA strain exhibits enhanced tolerance to gliotoxin toxicity. Finally, ∆flbA strain displayed enhanced SOD activity and elevated resistance to menadione and paraquat. In summary, FlbA-mediated signaling control negatively affects cellular responses associated with detoxification of reactive oxygen species and of exogenous gliotoxin in A. fumigatus. Regulator of G protein Signaling (RGS) proteins play crucial roles in fundamental biological processes in filamentous fungi. FlbA is the first studied filamentous fungal RGS protein, yet much remains to be understood about its roles in the opportunistic human pathogen Aspergillus fumigatus. In the present study, we examined the effects of the deletion of flbA using comprehensive analyses of the intra- and extracellular proteomes of A. fumigatus wild type and the flbA deletion mutant. Via MS analyses, we identified 10 proteins exhibiting high level accumulation in the flbA deletion

  14. Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM)

    PubMed Central

    2014-01-01

    Background Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, An individual patient data meta-analysis oF low-molecular-weight heparin For prevention of placenta-medIated pRegnancy coMplications. Methods/Design We conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy. Discussion The goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and

  15. Speaking to Read: Meta-Analysis of Peer-Mediated Learning for English Language Learners

    ERIC Educational Resources Information Center

    Cole, Mikel W.

    2014-01-01

    This meta-analysis examines the effectiveness of a group of instructional approaches (i.e., cooperative, collaborative, and peer tutoring) at improving literacy outcomes for English language learners. Main effects analyses of a sample of 28 experimental and quasi-experimental studies reveal that peer-mediation is more effective for ELLs than…

  16. Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.

    PubMed

    Varbo, Anette; Benn, Marianne; Smith, George Davey; Timpson, Nicholas J; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G

    2015-02-13

    Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressure, glucose, and C-reactive protein. Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. The increased IHD risk because of obesity was partly mediated through elevated levels of nonfasting remnant and low-density lipoprotein cholesterol and through elevated blood pressure. Our results suggest that there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss. © 2014 American Heart Association, Inc.

  17. 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.

  18. The mediation effect of experiential avoidance between coping and psychopathology in chronic pain.

    PubMed

    Costa, Joana; Pinto-Gouveia, José

    2011-01-01

    This study explores experiential avoidance as a mediator in the relationship between coping (rational coping, avoidant coping and detached/ emotional coping) and psychopathology (depression, anxiety and stress). A battery of self-report questionnaires was used to assess coping, experiential avoidance and depression, anxiety and stress in 70 participants with a chronic pain from Portuguese primary health care units. Regression analyses were performed and showed preliminary evidence supporting the mediation role of experiential avoidance in a Portuguese sample with chronic pain. Results show that experiential avoidance partially or fully mediate the effects of rational coping and detached/emotional coping on depression and stress. Implications for clinical practice were discussed and suggest that psychopathology is not necessary direct product of coping and other processes, such as experiential avoidance, are likely involved. Copyright © 2010 John Wiley & Sons, Ltd.

  19. Perceived Work Conditions and Turnover Intentions: The Mediating Role of Meaning of Work

    PubMed Central

    Arnoux-Nicolas, Caroline; Sovet, Laurent; Lhotellier, Lin; Di Fabio, Annamaria; Bernaud, Jean-Luc

    2016-01-01

    Perceived working conditions lead to various negative outcomes for employee behaviors, including turnover intentions. Although potential mediators for these relationships were previously identified, the importance of meaning of work has not yet been investigated. This study examines the role of this psychological resource as a mediator for the relationships between perceived working conditions and turnover intentions in a sample of 336 French workers from different job contexts. Results show that adverse working conditions were positively and significantly associated with turnover intentions. Meaning of work is negatively related to both perceived working conditions and turnover intentions. Mediation analyses for meaning of work demonstrated indirect effects of several adverse working conditions on turnover intentions. The role of meaning of work as a psychological resource for employees facing adverse working conditions is discussed, especially regarding its implications for research and practice within organizational contexts. PMID:27242616

  20. Perceived Work Conditions and Turnover Intentions: The Mediating Role of Meaning of Work.

    PubMed

    Arnoux-Nicolas, Caroline; Sovet, Laurent; Lhotellier, Lin; Di Fabio, Annamaria; Bernaud, Jean-Luc

    2016-01-01

    Perceived working conditions lead to various negative outcomes for employee behaviors, including turnover intentions. Although potential mediators for these relationships were previously identified, the importance of meaning of work has not yet been investigated. This study examines the role of this psychological resource as a mediator for the relationships between perceived working conditions and turnover intentions in a sample of 336 French workers from different job contexts. Results show that adverse working conditions were positively and significantly associated with turnover intentions. Meaning of work is negatively related to both perceived working conditions and turnover intentions. Mediation analyses for meaning of work demonstrated indirect effects of several adverse working conditions on turnover intentions. The role of meaning of work as a psychological resource for employees facing adverse working conditions is discussed, especially regarding its implications for research and practice within organizational contexts.