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

PubMed

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

2016-10-01

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

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

PubMed

Agler, Robert; De Boeck, Paul

2017-01-01

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

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

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

PubMed Central

Agler, Robert; De Boeck, Paul

2017-01-01

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

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

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

PubMed

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

2018-04-02

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

A Bifactor Approach to Model Multifaceted Constructs in Statistical Mediation Analysis

ERIC Educational Resources Information Center

Gonzalez, Oscar; MacKinnon, David P.

2018-01-01

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

Childhood Maltreatment and PTSD: Spiritual Well-Being and Intimate Partner Violence as Mediators

PubMed Central

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-01

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

Dispositional optimism and sleep quality: a test of mediating pathways

PubMed Central

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

2016-01-01

Dispositional optimism has been related to beneficial influences on physical health outcomes. However, its links to global sleep quality and the psychological mediators responsible for such associations are less studied. This study thus examined if trait optimism predicted global sleep quality, and if measures of subjective well-being were statistical mediators of such links. A community sample of 175 participants (93 men, 82 women) completed measures of trait optimism, depression, and life satisfaction. Global sleep quality was assessed using the Pittsburgh Sleep Quality Index. Results indicated that trait optimism was a strong predictor of better PSQI global sleep quality. Moreover, this association was mediated by depression and life satisfaction in both single and multiple mediator models. These results highlight the importance of optimism for the restorative process of sleep, as well as the utility of multiple mediator models in testing distinct psychological pathways. PMID:27592128

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

PubMed

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

2017-04-01

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

Methods for Mediation Analysis with Missing Data

ERIC Educational Resources Information Center

Zhang, Zhiyong; Wang, Lijuan

2013-01-01

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

A multiple mediational test of the relationship between childhood maltreatment and non-suicidal self-injury.

PubMed

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

2010-04-01

Post-traumatic stress symptoms, depressive symptoms, and psychological dysregulation have been shown to mediate the relationship between child maltreatment and non-suicidal self-injury. However, these proposed mediators often co-occur and previous research has not tested mediation when all variables are assessed simultaneously. The current study sought to advance the literature on maltreatment and self-injury by estimating the mediational effects of post-traumatic stress symptoms, depressive symptoms, and psychological dysregulation in the same multiple mediator model. Both maltreated (n = 129) and non-maltreated (n = 82) adolescent females, consisting of Caucasian (55%), African-American (37%), and Bi-racial (8%) backgrounds, participated in the study. Results indicated that only post-traumatic stress symptoms mediated the relationship between maltreatment and self-injury when all variables were included in the model. Overall, post-traumatic symptoms represented a unique pathway from maltreatment to self-injury and warrant special attention when assessing and treating such behavior with adolescent females.

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 that engage bullied youth need to consider the multiple spheres of influence that may increase SI among male and female clients. To holistically and adequately assess SI among bullied youth, therapists must also consider how these mechanisms vary between gender groups.

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

PubMed

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

2018-01-01

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

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.

Multiple dimensions of spirituality in recovery: a lagged mediational analysis of Alcoholics Anonymous' principal theoretical mechanism of behavior change.

PubMed

Krentzman, Amy R; Cranford, James A; Robinson, Elizabeth A R

2013-01-01

Alcoholics Anonymous (AA) states that recovery is possible through spiritual experiences and spiritual awakenings. Research examining spirituality as a mediator of AA's effect on drinking has been mixed. It is unknown whether such findings are due to variations in the operationalization of key constructs, such as AA and spirituality. To answer these questions, the authors used a longitudinal model to test 2 dimensions of AA as focal predictors and 6 dimensions of spirituality as possible mediators of AA's association with drinking. Data from the first 18 months of a 3-year longitudinal study of 364 alcohol-dependent individuals were analyzed. Structural equation modeling was used to replicate the analyses of Kelly et al. (Alcohol Clin Exp Res. 2011;35:454-463) and to compare AA attendance and AA involvement as focal predictors. Multiple regression analyses were used to determine which spirituality dimensions changed as the result of AA participation. A trimmed, data-driven model was employed to test multiple mediation paths simultaneously. The findings of the Kelly et al. study were replicated. AA involvement was a stronger predictor of drinking outcomes than AA attendance. AA involvement predicted increases in private religious practices, daily spiritual experiences, and forgiveness of others. However, only private religious practices mediated the relationship between AA and drinking.

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

PubMed

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

2016-11-01

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

Relationship between pain and post-traumatic stress symptoms in palliative care.

PubMed

Roth, Maya L; St Cyr, Kate; Harle, Ingrid; Katz, Joel D

2013-08-01

Previous research suggests that patients receiving palliative care may simultaneously experience poorly managed pain and post-traumatic stress disorder (PTSD)-related symptoms as a result of their deteriorating health. To: 1) examine predictors of PTSD-related symptoms in patients requiring palliative care; 2) assess whether anxiety, depression, pain catastrophizing, and pain anxiety mediate the relationship between pain interference and PTSD-related symptoms; and 3) evaluate the impact of these variables on pain interference and PTSD-related symptoms. One hundred patients receiving palliative care at one of two palliative care sites in London, ON, Canada, completed the PTSD Checklist-Civilian version (PCL-C), the Hospital Anxiety and Depression Scale (HADS), the Pain Catastrophizing Scale (PCS), the Brief Pain Inventory-Short Form (BPI-SF), and the Pain Anxiety Symptoms Scale-20 (PASS-20). Hierarchical multiple regressions were used to examine HADS-Anxiety, HADS-Depression, PCS and PASS-20 scores as predictors of PCL-C scores; and mediation analyses were used to test the effect of HADS-Anxiety, HADS-Depression, PCS, and PASS-20 on the relationship between BPI-SF interference and PCL-C. Mediators that significantly affected this relationship in the individual mediator models were entered into a multiple mediator model. Only pain anxiety and pain catastrophizing emerged as significant mediators of the relationship between pain interference and PTSD-related symptoms. After being entered in a multiple mediator model, pain anxiety emerged as the strongest mediator. The findings of the present study reveal that pain and PTSD-related symptoms are important concerns in palliative care, and that pain must be addressed to best meet the needs of this population. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2013-12-01

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

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

PubMed

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

2014-01-01

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

Urban residential greenspace and mental health in youth: Different approaches to testing multiple pathways yield different conclusions.

PubMed

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

2018-01-01

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

The Presence of a Calling and Academic Satisfaction: Examining Potential Mediators

ERIC Educational Resources Information Center

Duffy, Ryan D.; Allan, Blake A.; Dik, Bryan J.

2011-01-01

The present study examined the relation of calling and academic satisfaction with a diverse sample of 312 undergraduate students. The presence of a calling was moderately correlated with academic satisfaction, and a multiple mediation model was utilized to test three potential mediators to this relation: career decision self-efficacy, work hope,…

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

PubMed

Lewis, Brian A

2010-01-15

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

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

PubMed

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

2016-01-01

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

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

PubMed

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

2017-12-01

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

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

PubMed Central

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

2017-01-01

Research teams face complex leadership and coordination challenges. We propose shared authentic leadership (SAL) as a timely approach to addressing these challenges. Drawing from authentic and functional leadership theories, we posit a multiple mediation model that suggests three mechanisms whereby SAL influences team effectiveness: shared mental models (SMM), team trust, and team coordination. To test our hypotheses, we collected survey data on leadership and teamwork within 142 research teams that recently published an article in a peer-reviewed management journal. The results indicate team coordination represents the primary mediating mechanism accounting for the relationship between SAL and research team effectiveness. While teams with high trust and SMM felt more successful and were more satisfied, they were less successful in publishing in high-impact journals. We also found the four SAL dimensions (i.e., self-awareness, relational transparency, balanced processing, and internalized moral perspective) to associate differently with team effectiveness. PMID:29187779

The Relationship of Core Self-Evaluations and Life Satisfaction in College Students with Disabilities: Evaluation of a Mediator Model

ERIC Educational Resources Information Center

Smedema, Susan Miller; Chan, Fong; Yaghmaian, Rana A.; Cardoso, Elizabeth DaSilva; Muller, Veronica; Keegan, John; Dutta, Alo; Ebener, Deborah J.

2015-01-01

This study examined the factorial structure of the construct core self-evaluations (CSE) and tested a mediational model of the relationship between CSE and life satisfaction in college students with disabilities. We conducted a quantitative descriptive design using exploratory and confirmatory factor analysis and multiple regression analysis.…

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

PubMed

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

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

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

PubMed

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

2010-12-01

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

A Bifactor Approach to Model Multifaceted Constructs in Statistical Mediation Analysis.

PubMed

Gonzalez, Oscar; MacKinnon, David P

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

Reconceptualizing decisional balance in an adolescent sun protection intervention: mediating effects and theoretical interpretations.

PubMed

Adams, Marc A; Norman, Gregory J; Hovell, Melbourne F; Sallis, James F; Patrick, Kevin

2009-03-01

The Transtheoretical model (TTM) integrates principles of operant learning, such as stimulus control and reinforcement, and psychological factors, such as decisional balance. Understanding interrelationships between decisions, behavior, and consequences from multiple-theoretical perspectives can advance theory and inform development of more effective interventions. This analysis examined the mediating effects of a special case of the decisional balance construct in which the pros of competing behaviors (i.e., sun protection vs. exposure) were measured rather than the pros and cons of the same behavior. Participants included 819 adolescents (10 to 16 years old, 53.5% girls, 58.4% White) randomized to a 24-month expert system intervention (SunSmart) or a physical activity and nutrition comparison group. Self-report measures included sun protection behaviors, pros for protection, and pros for exposure. Mediation analysis using latent growth curve models found both the treatment-to-mediator and mediator-to-behavior paths significant for decisional balance, producing an indirect effect of .323 (p < .01) and good model fit (CFI = .973, RMSEA = .055). Multiple strategies for conceptualizing and measuring decisional balance appear to be valid. Results are interpreted from the TTM and operant perspectives. (c) 2009 APA, all rights reserved

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.

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

An Index and Test of Linear Moderated Mediation.

PubMed

Hayes, Andrew F

2015-01-01

I describe a test of linear moderated mediation in path analysis based on an interval estimate of the parameter of a function linking the indirect effect to values of a moderator-a parameter that I call the index of moderated mediation. This test can be used for models that integrate moderation and mediation in which the relationship between the indirect effect and the moderator is estimated as linear, including many of the models described by Edwards and Lambert ( 2007 ) and Preacher, Rucker, and Hayes ( 2007 ) as well as extensions of these models to processes involving multiple mediators operating in parallel or in serial. Generalization of the method to latent variable models is straightforward. Three empirical examples describe the computation of the index and the test, and its implementation is illustrated using Mplus and the PROCESS macro for SPSS and SAS.

Working Memory and Cognitive Flexibility Mediates Visuoconstructional Abilities in Older Adults with Heterogeneous Cognitive Ability.

PubMed

Ávila, Rafaela T; de Paula, Jonas J; Bicalho, Maria A; Moraes, Edgar N; Nicolato, Rodrigo; Malloy-Diniz, Leandro F; Diniz, Breno S

2015-05-01

Previous studies suggest that executive functions influence the performance on visuoconstructional tasks. This study aims to investigate whether the relationship between planning ability and the copy of complex figures is mediated by distinct components of executive functions (i.e., working memory, inhibitory control and cognitive flexibility). We included a 129 older adults with Alzheimer's disease (n=36, AD), mild cognitive impairment (MCI, n=67), and with no evidence of cognitive impairment (controls, n=26). We evaluated the mediation effect of planning abilities, working memory, cognitive flexibility and inhibitory control on visuoconstructional tasks using a multiple mediation models. We found a significant direct effect of planning on visuoconstructional abilities and a partial mediation effect of working memory and cognitive flexibility on visuoconstructional abilities. The present results indicate that the performance on visuoconstructional task is mediated by multiple interrelated executive functions components, in particular working memory and cognitive flexibility.

Quality of Life as a Mediator between Behavioral Challenges and Autistic Traits for Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Garcia-Villamisar, Domingo; Dattilo, John; Matson, Johnny L.

2013-01-01

A multiple mediation model was proposed to integrate core concepts of challenging behaviors with autistic traits to increase understanding of their relationship to quality of life (QoL). It was hypothesized that QoL is a possible mediator between the severity of challenging behaviors and autistic traits in adults with intellectual disability.…

Evolved differences in larval social behavior mediated by novel pheromones

USDA-ARS?s Scientific Manuscript database

Pheromones, chemical signals that convey social information, mediate many insect social behaviors in both adult and immature stages. Multiple pheromones and neural pathways that underlie adult social behavior have been described in the genetic model organism, Drosophila melanogaster, but there is no...

Strategic Planning for Divorce Mediation.

ERIC Educational Resources Information Center

Weingarten, Helen R.

1986-01-01

Presents a theoretical model that focuses attention on the multiple arenas of life that are disrupted by divorce, the emotional stages of divorce, and the interpersonal dynamics of separating couples. Discusses the implications of these factors for strategically planning and carrying out the mediation process. (Author/ABB)

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

PubMed

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

2013-09-01

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

Mediators of the Association of Major Depressive Syndrome and Anxiety Syndrome with Postpartum Smoking Relapse

PubMed Central

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

2012-01-01

Objective Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Method Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a Bootstrapping procedure to test the indirect effects. Results Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally-based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. Conclusion The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse, and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, while affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse. PMID:22390410

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

PubMed

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

2012-08-01

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

Multiple Traumas, Maternal Depression, Mother-Child Relationship, Social Support, and Young Children's Behavioral Problems.

PubMed

Schiff, Miriam; Pat-Horenczyk, Ruth; Ziv, Yuval; Brom, Danny

2017-09-01

This study examined whether maternal depression, mother-child relationships, and maternal perceived social support mediate the associations between child's exposure to multiple traumatic events and behavioral problems. We recruited a representative sample of 904 Israeli (Jewish and Arab) mothers and their 2- to 6-year-old children. Data collection was conducted through structured face-to-face interviews with the mothers between July and November 2011. All measures were completed by the mothers. We used the child's and mother's exposure to political violence questionnaires, Child Behavior Checklist (CBCL), a short version of the Parental Acceptance-Rejection Questionnaire (PARQ), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Medical Outcomes Study (MOS) Social Support Survey. The research study model was tested using path analysis. The model showed a very good fit to the data, suggesting that maternal rejection, maternal depression, and social support play an important role in child's behavioral problems in the context of multiple traumatic events. Higher levels of maternal rejection were significantly associated with greater children behavior problems. Maternal rejection mediated the associations between maternal depressive symptoms and child's behavioral problems. Maternal perceived social support mediated the associations between child's exposure to multiple traumatic events and child's behavioral problems; child's exposure to multiple traumatic events was associated with lower levels of maternal perceived social support. In turn, lower levels of perceived social support were associated with higher levels of behavioral problems. In conclusion, in accordance with the "social stress framework," social support has a mediation role in the association between exposure to traumatic events and child's behavioral problems. Thus, enhancing social support to mothers to young children in the context of multiple traumatic events is essential for children resiliency.

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

PubMed Central

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

2016-01-01

We investigate a method to estimate the combined effect of multiple continuous/ordinal mediators on a binary outcome: 1) fit a structural equation model with probit link for the outcome and identity/probit link for continuous/ordinal mediators, 2) predict potential outcome probabilities, and 3) compute natural direct and indirect effects. Step 2 involves rescaling the latent continuous variable underlying the outcome to address residual mediator variance/covariance. We evaluate the estimation of risk-difference- and risk-ratio-based effects (RDs, RRs) using the ML, WLSMV and Bayes estimators in Mplus. Across most variations in path-coefficient and mediator-residual-correlation signs and strengths, and confounding situations investigated, the method performs well with all estimators, but favors ML/WLSMV for RDs with continuous mediators, and Bayes for RRs with ordinal mediators. Bayes outperforms WLSMV/ML regardless of mediator type when estimating RRs with small potential outcome probabilities and in two other special cases. An adolescent alcohol prevention study is used for illustration. PMID:27158217

Coping mediates the relationship between sense of coherence and mental quality of life in patients with chronic illness: a cross-sectional study.

PubMed

Kristofferzon, Marja-Leena; Engström, Maria; Nilsson, Annika

2018-07-01

The aim of the present study was to investigate relationships between sense of coherence, emotion-focused coping, problem-focused coping, coping efficiency, and mental quality of life (QoL) in patients with chronic illness. A model based on Lazarus' and Folkman's stress and coping theory tested the specific hypothesis: Sense of coherence has a direct and indirect effect on mental QoL mediated by emotion-focused coping, problem-focused coping, and coping efficiency in serial adjusted for age, gender, educational level, comorbidity, and economic status. The study used a cross-sectional and correlational design. Patients (n = 292) with chronic diseases (chronic heart failure, end-stage renal disease, multiple sclerosis, stroke, and Parkinson) completed three questionnaires and provided background data. Data were collected in 2012, and a serial multiple mediator model was tested using PROCESS macro for SPSS. The test of the conceptual model confirmed the hypothesis. There was a significant direct and indirect effect of sense of coherence on mental QoL through the three mediators. The model explained 39% of the variance in mental QoL. Self-perceived effective coping strategies are the most important mediating factors between sense of coherence and QoL in patients with chronic illness, which supports Lazarus' and Folkman's stress and coping theory.

Exposure to family violence and attachment styles as predictors of dating violence perpetration among men and women: a mediational model.

PubMed

Lee, Mary; Reese-Weber, Marla; Kahn, Jeffrey H

2014-01-01

This study examined a multiple mediator model explaining how sibling perpetration and one's attachment style mediate the relation between parent-to-child victimization and dating violence perpetration. A sample of undergraduate students (n = 392 women, n = 89 men) completed measures of the aforementioned variables on an Internet survey. For men, path analyses found no mediation; parent-to-child victimization had a direct association with dating violence perpetration, no association was found between sibling perpetration and dating violence perpetration, and attachment anxiety, but not attachment avoidance, was positively associated with dating violence perpetration for men. For women, the hypothesized mediation model was supported; parent-to-child victimization had a direct association with dating violence perpetration, and sibling perpetration and attachment anxiety served as mediating variables. Attachment avoidance was not associated with dating violence perpetration for women. Implications for future research and clinical practice are discussed.

Inhibiting poly(ADP-ribose) polymerase: a potential therapy against oligodendrocyte death

PubMed Central

Veto, Sara; Acs, Peter; Bauer, Jan; Lassmann, Hans; Berente, Zoltan; Setalo, Gyorgy; Borgulya, Gabor; Sumegi, Balazs; Komoly, Samuel; Gallyas, Ferenc; Illes, Zsolt

2010-01-01

Oligodendrocyte loss and demyelination are major pathological hallmarks of multiple sclerosis. In pattern III lesions, inflammation is minor in the early stages, and oligodendrocyte apoptosis prevails, which appears to be mediated at least in part through mitochondrial injury. Here, we demonstrate poly(ADP-ribose) polymerase activation and apoptosis inducing factor nuclear translocation within apoptotic oligodendrocytes in such multiple sclerosis lesions. The same morphological and molecular pathology was observed in an experimental model of primary demyelination, induced by the mitochondrial toxin cuprizone. Inhibition of poly(ADP-ribose) polymerase in this model attenuated oligodendrocyte depletion and decreased demyelination. Poly(ADP-ribose) polymerase inhibition suppressed c-Jun N-terminal kinase and p38 mitogen-activated protein kinase phosphorylation, increased the activation of the cytoprotective phosphatidylinositol-3 kinase-Akt pathway and prevented caspase-independent apoptosis inducing factor-mediated apoptosis. Our data indicate that poly(ADP-ribose) polymerase activation plays a crucial role in the pathogenesis of pattern III multiple sclerosis lesions. Since poly(ADP-ribose) polymerase inhibition was also effective in the inflammatory model of multiple sclerosis, it may target all subtypes of multiple sclerosis, either by preventing oligodendrocyte death or attenuating inflammation. PMID:20157013

Evaluation of a Multiple Mediator Model of the Relationship between Core Self-Evaluations and Job Satisfaction in Employed Individuals with Disabilities

ERIC Educational Resources Information Center

Smedema, Susan Miller; Kesselmayer, Rachel Friefeld; Peterson, Lauren

2018-01-01

Purpose: To test a meditation model of the relationship between core self-evaluations (CSE) and job satisfaction in employed individuals with disabilities. Method: A quantitative descriptive design using Hayes's (2012) PROCESS macro for SPSS and multiple regression analysis. Two-hundred fifty-nine employed persons with disabilities were recruited…

Quantitative pharmacokinetic-pharmacodynamic modelling of baclofen-mediated cardiovascular effects using BP and heart rate in rats.

PubMed

Kamendi, Harriet; Barthlow, Herbert; Lengel, David; Beaudoin, Marie-Eve; Snow, Debra; Mettetal, Jerome T; Bialecki, Russell A

2016-10-01

While the molecular pathways of baclofen toxicity are understood, the relationships between baclofen-mediated perturbation of individual target organs and systems involved in cardiovascular regulation are not clear. Our aim was to use an integrative approach to measure multiple cardiovascular-relevant parameters [CV: mean arterial pressure (MAP), systolic BP, diastolic BP, pulse pressure, heart rate (HR); CNS: EEG; renal: chemistries and biomarkers of injury] in tandem with the pharmacokinetic properties of baclofen to better elucidate the site(s) of baclofen activity. Han-Wistar rats were administered vehicle or ascending doses of baclofen (3, 10 and 30 mg·kg(-1) , p.o.) at 4 h intervals and baclofen-mediated changes in parameters recorded. A pharmacokinetic-pharmacodynamic model was then built by implementing an existing mathematical model of BP in rats. Final model fits resulted in reasonable parameter estimates and showed that the drug acts on multiple homeostatic processes. In addition, the models testing a single effect on HR, total peripheral resistance or stroke volume alone did not describe the data. A final population model was constructed describing the magnitude and direction of the changes in MAP and HR. The systems pharmacology model developed fits baclofen-mediated changes in MAP and HR well. The findings correlate with known mechanisms of baclofen pharmacology and suggest that similar models using limited parameter sets may be useful to predict the cardiovascular effects of other pharmacologically active substances. © 2016 The British Pharmacological Society.

Quantitative pharmacokinetic–pharmacodynamic modelling of baclofen‐mediated cardiovascular effects using BP and heart rate in rats

PubMed Central

Kamendi, Harriet; Barthlow, Herbert; Lengel, David; Beaudoin, Marie‐Eve; Snow, Debra

2016-01-01

Background and Purpose While the molecular pathways of baclofen toxicity are understood, the relationships between baclofen‐mediated perturbation of individual target organs and systems involved in cardiovascular regulation are not clear. Our aim was to use an integrative approach to measure multiple cardiovascular‐relevant parameters [CV: mean arterial pressure (MAP), systolic BP, diastolic BP, pulse pressure, heart rate (HR); CNS: EEG; renal: chemistries and biomarkers of injury] in tandem with the pharmacokinetic properties of baclofen to better elucidate the site(s) of baclofen activity. Experimental Approach Han‐Wistar rats were administered vehicle or ascending doses of baclofen (3, 10 and 30 mg·kg−1, p.o.) at 4 h intervals and baclofen‐mediated changes in parameters recorded. A pharmacokinetic–pharmacodynamic model was then built by implementing an existing mathematical model of BP in rats. Key Results Final model fits resulted in reasonable parameter estimates and showed that the drug acts on multiple homeostatic processes. In addition, the models testing a single effect on HR, total peripheral resistance or stroke volume alone did not describe the data. A final population model was constructed describing the magnitude and direction of the changes in MAP and HR. Conclusions and Implications The systems pharmacology model developed fits baclofen‐mediated changes in MAP and HR well. The findings correlate with known mechanisms of baclofen pharmacology and suggest that similar models using limited parameter sets may be useful to predict the cardiovascular effects of other pharmacologically active substances. PMID:27448216

Test of a Mediation Model of Perceived Organizational Support

ERIC Educational Resources Information Center

Chen, Zhen Xiong; Aryee, Samuel; Lee, Cynthia

2005-01-01

This study examined the mediating influence of trust in organization (TIO) and organization-based self-esteem (OBSE) on the relationship between perceived organization support (POS) and its work outcomes. Data were obtained from employee-supervisor dyads from multiple organizations located in a major city in southern China. Structural equation…

Editorial: Introduction to the Special Section on Causal Inference in Cross Sectional and Longitudinal Mediational Models

PubMed Central

West, Stephen G.

2016-01-01

Psychologists have long had interest in the processes through which antecedent variables produce their effects on the outcomes of ultimate interest (e.g., Wood-worth's Stimulus-Organism-Response model). Models involving such meditational processes have characterized many of the important psychological theories of the 20th century and continue to the present day. However, it was not until Judd and Kenny (1981) and Baron and Kenny (1986) combined ideas from experimental design and structural equation modeling that statistical methods for directly testing such models, now known as mediation analysis, began to be developed. Methodologists have improved these statistical methods, developing new, more efficient estimators for mediated effects. They have also extended mediation analysis to multilevel data structures, models involving multiple mediators, models in which interactions occur, and an array of noncontinuous outcome measures (see MacKinnon, 2008). This work nicely maps on to key questions of applied researchers and has led to an outpouring of research testing meditational models (As of August, 2011, Baron and Kenny's article has had over 24,000 citations according to Google Scholar). PMID:26736046

Experimental verification of nanofluid shear-wave reconversion in ultrasonic fields.

PubMed

Forrester, Derek Michael; Huang, Jinrui; Pinfield, Valerie J; Luppé, Francine

2016-03-14

Here we present the verification of shear-mediated contributions to multiple scattering of ultrasound in suspensions. Acoustic spectroscopy was carried out with suspensions of silica of differing particle sizes and concentrations in water to find the attenuation at a broad range of frequencies. As the particle sizes approach the nanoscale, commonly used multiple scattering models fail to match experimental results. We develop a new model, taking into account shear mediated contributions, and find excellent agreement with the attenuation spectra obtained using two types of spectrometer. The results determine that shear-wave phenomena must be considered in ultrasound characterisation of nanofluids at even relatively low concentrations of scatterers that are smaller than one micrometre in diameter.

Potential mediators between child abuse and both violence and victimization in juvenile offenders.

PubMed

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

2013-02-01

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

Minority stress and college persistence attitudes among African American, Asian American, and Latino students: perception of university environment as a mediator.

PubMed

Wei, Meifen; Ku, Tsun-Yao; Liao, Kelly Yu-Hsin

2011-04-01

We examined whether perception of university environment mediated the association between minority status stress and college persistence attitudes after controlling for perceived general stress. Participants were 160 Asian American, African American, and Latino students who attended a predominantly White university. Results of a path model analysis showed that university environment was a significant mediator for the association between minority status stress and college persistence attitudes. Additionally, minority status stress was distinct from perceived general stress. Finally, the results from a multiple-group comparison indicated that the magnitude of the mediation effect was invariant across Asian American, African American, and Latino college students, thus supporting the generalizability of the mediation model.

Childhood maltreatment, personality disorders and 3-year persistence of adult alcohol and nicotine dependence in a national sample.

PubMed

Elliott, Jennifer C; Stohl, Malka; Wall, Melanie M; Keyes, Katherine M; Skodol, Andrew E; Eaton, Nicholas R; Shmulewitz, Dvora; Goodwin, Renee D; Grant, Bridget F; Hasin, Deborah S

2016-05-01

Persistent cases of alcohol and nicotine dependence are associated with considerable morbidity and mortality, and are predicted by childhood maltreatment and personality disorders. Our aim was to test whether personality disorders (individually or conjointly) mediate the relationship between childhood maltreatment and the persistence of dependence. Personality disorders, modeled dimensionally, were tested as mediators of the relationship between childhood maltreatment and the 3-year persistence of alcohol and nicotine dependence in participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) who had current alcohol and nicotine dependence in their baseline interview. Individual personality disorders were assessed in separate models. Then, those that were significant were examined jointly in multiple mediator models to determine their total and unique effects. A large, nationally representative US survey. Participants ≥ 18 years who completed baseline and 3-year follow-up NESARC interviews who had baseline alcohol dependence (n = 1172; 68% male) or nicotine dependence (n = 4017; 52.9% male). Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS-IV) measures of childhood maltreatment, personality disorders and alcohol/nicotine dependence. Individual models indicated that many personality disorders mediated the relationship between childhood maltreatment and the 3-year persistence of alcohol and nicotine dependence (each explaining 6-46% of the total effect, Ps < 0.05). In multiple mediator models, borderline and antisocial symptoms remained significant mediators, each explaining 20-37% of the total effect (Ps < 0.01). Personality disorder symptoms (especially borderline and antisocial) help explain the association between childhood maltreatment and persistent alcohol and nicotine dependence. © 2016 Society for the Study of Addiction.

Childhood maltreatment, personality disorders, and 3-year persistence of adult alcohol and nicotine dependence in a national sample

PubMed Central

Elliott, Jennifer C.; Stohl, Malka; Wall, Melanie M.; Keyes, Katherine M.; Skodol, Andrew E.; Eaton, Nicholas R.; Shmulewitz, Dvora; Goodwin, Renee D.; Grant, Bridget F.; Hasin, Deborah S.

2015-01-01

Background and Aims Persistent cases of alcohol and nicotine dependence are associated with considerable morbidity and mortality, and are predicted by childhood maltreatment and personality disorders. Our aim was to test whether personality disorders (individually or conjointly) mediate the relationship between childhood maltreatment and the persistence of dependence. Design Personality disorders, modeled dimensionally, were tested as mediators of the relationship between childhood maltreatment and the 3-year persistence of alcohol and nicotine dependence in participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) who had current alcohol and nicotine dependence in their baseline interview. Individual personality disorders were assessed in separate models. Then, those that were significant were examined jointly in multiple mediator models to determine their total and unique effects. Setting A large, nationally representative United States survey. Participants Participants ≥18 years who completed baseline and 3-year follow-up NESARC interviews who had baseline alcohol dependence (n=1,172; 68% male) or nicotine dependence (n=4,017; 52.9% male). Measurements Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS-IV) measures of childhood maltreatment, personality disorders, and alcohol/nicotine dependence. Findings Individual models indicated that many personality disorders mediated the relationship between childhood maltreatment and the 3-year persistence of alcohol and nicotine dependence (each explaining 6%–46% of the total effect, ps<0.05). In multiple mediator models, borderline and antisocial symptoms remained significant mediators, each explaining 20%–37% of the total effect (ps<0.01). Conclusions Personality disorder symptoms (especially borderline and antisocial) help explain the association between childhood maltreatment and persistent alcohol and nicotine dependence. PMID:26714255

Humanizing Outgroups Through Multiple Categorization

PubMed Central

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

2016-01-01

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

Mediation analysis of alcohol consumption, DNA methylation, and epithelial ovarian cancer.

PubMed

Wu, Dongyan; Yang, Haitao; Winham, Stacey J; Natanzon, Yanina; Koestler, Devin C; Luo, Tiane; Fridley, Brooke L; Goode, Ellen L; Zhang, Yanbo; Cui, Yuehua

2018-03-01

Epigenetic factors and consumption of alcohol, which suppresses DNA methylation, may influence the development and progression of epithelial ovarian cancer (EOC). However, there is a lack of understanding whether these factors interact to affect the EOC risk. In this study, we aimed to gain insight into this relationship by identifying leukocyte-derived DNA methylation markers acting as potential mediators of alcohol-associated EOC. We implemented a causal inference test (CIT) and the VanderWeele and Vansteelandt multiple mediator model to examine CpG sites that mediate the association between alcohol consumption and EOC risk. We modified one step of the CIT by adopting a high-dimensional inference procedure. The data were based on 196 cases and 202 age-matched controls from the Mayo Clinic Ovarian Cancer Case-Control Study. Implementation of the CIT test revealed two CpG sites (cg09358725, cg11016563), which represent potential mediators of the relationship between alcohol consumption and EOC case-control status. Implementation of the VanderWeele and Vansteelandt multiple mediator model further revealed that these two CpGs were the key mediators. Decreased methylation at both CpGs was more common in cases who drank alcohol at the time of enrollment vs. those who did not. cg11016563 resides in TRPC6 which has been previously shown to be overexpressed in EOC. These findings suggest two CpGs may serve as novel biomarkers for EOC susceptibility.

Working memory and intraindividual variability as neurocognitive indicators in ADHD: examining competing model predictions.

PubMed

Kofler, Michael J; Alderson, R Matt; Raiker, Joseph S; Bolden, Jennifer; Sarver, Dustin E; Rapport, Mark D

2014-05-01

The current study examined competing predictions of the default mode, cognitive neuroenergetic, and functional working memory models of attention-deficit/hyperactivity disorder (ADHD) regarding the relation between neurocognitive impairments in working memory and intraindividual variability. Twenty-two children with ADHD and 15 typically developing children were assessed on multiple tasks measuring intraindividual reaction time (RT) variability (ex-Gaussian: tau, sigma) and central executive (CE) working memory. Latent factor scores based on multiple, counterbalanced tasks were created for each construct of interest (CE, tau, sigma) to reflect reliable variance associated with each construct and remove task-specific, test-retest, and random error. Bias-corrected, bootstrapped mediation analyses revealed that CE working memory accounted for 88% to 100% of ADHD-related RT variability across models, and between-group differences in RT variability were no longer detectable after accounting for the mediating role of CE working memory. In contrast, RT variability accounted for 10% to 29% of between-group differences in CE working memory, and large magnitude CE working memory deficits remained after accounting for this partial mediation. Statistical comparison of effect size estimates across models suggests directionality of effects, such that the mediation effects of CE working memory on RT variability were significantly greater than the mediation effects of RT variability on CE working memory. The current findings question the role of RT variability as a primary neurocognitive indicator in ADHD and suggest that ADHD-related RT variability may be secondary to underlying deficits in CE working memory.

Studies of transformational leadership in consumer service: market orientation behavior and alternative roles for the mediators and moderators of change commitment.

PubMed

Yang, Yi-Feng

2013-12-01

The present paper evaluates the relation between transformational leadership and market orientation along with the mediating and moderating effects of change commitment for employees in customer centers in Taiwan. 327 questionnaires were returned by personnel at several customer centers in four different insurance companies. Inter-rater agreement was acceptable based on the multiple raters (i.e., the consumer-related employees from the division groups) of one individual (i.e., a manager)--indicating the aggregated measures were acceptable. The multi-source sample comprised data taken from the four division centers: phone services, customer representatives, financial specialists, and front-line salespeople. The relations were assessed using a multiple mediation procedure incorporating bootstrap techniques and PRODCLIN2 with structural equation modeling analysis. The results reflect a mediating role for change commitment.

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

PubMed Central

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

2010-01-01

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

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

PubMed

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

2008-08-01

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

Determinants of lifestyle behavior change to prevent type 2 diabetes in high-risk individuals.

PubMed

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

2017-06-12

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

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.

A Knowledge-Modeling Approach to Integrate Multiple Clinical Practice Guidelines to Provide Evidence-Based Clinical Decision Support for Managing Comorbid Conditions.

PubMed

Abidi, Samina

2017-10-26

Clinical management of comorbidities is a challenge, especially in a clinical decision support setting, as it requires the safe and efficient reconciliation of multiple disease-specific clinical procedures to formulate a comorbid therapeutic plan that is both effective and safe for the patient. In this paper we pursue the integration of multiple disease-specific Clinical Practice Guidelines (CPG) in order to manage co-morbidities within a computerized Clinical Decision Support System (CDSS). We present a CPG integration framework-termed as COMET (Comorbidity Ontological Modeling & ExecuTion) that manifests a knowledge management approach to model, computerize and integrate multiple CPG to yield a comorbid CPG knowledge model that upon execution can provide evidence-based recommendations for handling comorbid patients. COMET exploits semantic web technologies to achieve (a) CPG knowledge synthesis to translate a paper-based CPG to disease-specific clinical pathways (CP) that include specialized co-morbidity management procedures based on input from domain experts; (b) CPG knowledge modeling to computerize the disease-specific CP using a Comorbidity CPG ontology; (c) CPG knowledge integration by aligning multiple ontologically-modeled CP to develop a unified comorbid CPG knowledge model; and (e) CPG knowledge execution using reasoning engines to derive CPG-mediated recommendations for managing patients with comorbidities. We present a web-accessible COMET CDSS that provides family physicians with CPG-mediated comorbidity decision support to manage Atrial Fibrillation and Chronic Heart Failure. We present our qualitative and quantitative analysis of the knowledge content and usability of COMET CDSS.

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

PubMed

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

2017-11-01

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

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

PubMed

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

2012-01-01

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

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.

A longitudinal examination of the interrelationship of multiple health behaviors.

PubMed

deRuiter, Wayne K; Cairney, John; Leatherdale, Scott T; Faulkner, Guy E J

2014-09-01

Evaluating the interrelationship of health behaviors could assist in the development of effective public health interventions. Furthermore, the ability to identify cognitive mediators that may influence multiple behavioral changes requires evaluation. To evaluate covariation among health behaviors, specifically alcohol consumption, leisure-time physical activity, and smoking, and examine whether mastery acts as a mediating social-cognitive mechanism that facilitates multiple health behavior change in a longitudinal analysis. In 2010, secondary data analysis was conducted on the first seven cycles of the Canadian National Population Health Survey. Data collection began in 1994-1995 and has continued biennially. At the time of this analysis, only seven cycles of data (2006-2007) were available. Parallel process growth curve models were used to analyze covariation between health behaviors and the potential mediating effects of perceived mastery. Increases in leisure-time physical activity were associated with reductions in tobacco use, whereas declines in alcohol consumption were associated with decreases in tobacco use. Covariation between alcohol consumption and leisure-time physical activity did not reach statistical significance. For the most part, mastery was unsuccessful in mediating the interrelationship of multiple behavioral changes. Health behaviors are not independent but rather interrelated. In order to optimize limited prevention resources, these results suggest that population-level intervention efforts targeting multiple modifiable behavioral risk factors may not need to occur simultaneously. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

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

PubMed

Bellavia, Andrea; Valeri, Linda

2018-06-01

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

Filipino Americans and Racism: A Multiple Mediation Model of Coping

ERIC Educational Resources Information Center

Alvarez, Alvin N.; Juang, Linda P.

2010-01-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

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

PubMed

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

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

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

PubMed Central

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

2015-01-01

Purpose When researchers find an association between two variables, it is useful to evaluate the role of other constructs in this association. While assessing these mediation effects, it is important to determine if results are equal for different groups. It is possible that the strength of a mediation effect may differ for males and females, for example – such an effect is known as moderated mediation. Design Participants were 2532 adolescents from diverse ethnic/racial backgrounds and equally distributed across gender. The goal of this study was to investigate parental respect as a potential mediator of the relationship between gender and delinquency and mental health, and to determine whether observed mediation is moderated by gender. Findings Parental respect mediated the association between gender and both delinquency and mental health. Specifically, parental respect was a protective factor against delinquency and mental health problems for both females and males. Practical implications Demonstrated the process of estimating models in Lavaan, using two approaches (i.e. single group regression and multiple group regression model), and including covariates in both models. PMID:26500722

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

PubMed

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

2010-01-01

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

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

PubMed

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

2013-11-01

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

Psychosocial Mechanisms Linking the Social Environment to Mental Health in African Americans.

PubMed

Mama, Scherezade K; Li, Yisheng; Basen-Engquist, Karen; Lee, Rebecca E; Thompson, Deborah; Wetter, David W; Nguyen, Nga T; Reitzel, Lorraine R; McNeill, Lorna H

2016-01-01

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination), and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p < .001) and U.S. (p < .001) and low social support (p < .001) were associated with poor mental health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans.

Evolving models of the immunopathogenesis of T-cell mediated drug allergy: the role of host, pathogens, and drug response

PubMed Central

White, Katie D.; Chung, Wen-Hung; Hung, Shuen-Iu; Mallal, Simon; Phillips, Elizabeth J.

2015-01-01

Immune-mediated adverse drug reactions (IM-ADRs) are an underrecognized source of preventable morbidity, mortality, and cost. Increasingly, genetic variation in the HLA loci is associated with risk of severe reactions, highlighting the importance of T-cell immune responses in the mechanisms of both B-cell mediated and primary T-cell mediated IM-ADRs. In this review, we summarize the role of host genetics, microbes and drugs in the development of IM-ADRs, expand upon the existing models of IM-ADR pathogenesis to address multiple unexplained observations, discuss the implications of this work in clinical practice today, and describe future applications for pre-clinical drug toxicity screening, drug design, and development. PMID:26254049

Strength and cardiometabolic risk in young adults: The mediator role of aerobic fitness and waist circumference.

PubMed

Díez-Fernández, A; Martínez-Vizcaíno, V; Torres-Costoso, A; Cañete García-Prieto, J; Franquelo-Morales, P; Sánchez-López, M

2018-07-01

The aim of this study was to analyze the mediation role of cardiorespiratory fitness and waist circumference in the association between muscular strength and cardiometabolic risk. A cross-sectional study involved first-year college students (n = 370) from a Spanish public university was performed. We measured weight, height, waist circumference, blood pressure, biochemical variables, maximum handgrip strength assessment, and cardiorespiratory fitness. We calculated handgrip dynamometry/weight and a previously validated cardiometabolic risk index. Analysis of covariance models was conducted to test differences in cardiometabolic risk values across muscular strength, cardiorespiratory fitness, and waist circumference categories, controlling for confounders. Hayes' PROCESS macro was used for the multiple mediation analysis. The relationship between muscular strength and cardiometabolic risk did not remain significant (c' = 1.76 [1.4]; P > .05) in a multiple serial bootstrapped mediation model including cardiorespiratory fitness and waist circumference as mediators when controlling for age and sex. According to the indirect effect, the significant paths in the model mediating this relationship between muscular strength and cardiometabolic risk index were as follows: muscular strength → waist circumference → cardiometabolic risk index (-4.899; 95% CI: -6.690; -3.450) and muscular strength → cardiorespiratory fitness → waist circumference → cardiometabolic risk index (-0.720; 95% CI: -1.316; -0.360). Both cardiorespiratory fitness and waist circumference mediate the association between muscular strength and cardiometabolic risk in young adults. Thus, our results place cardiorespiratory fitness and waist circumference as the main targets of physical activity programmes aimed at preventing cardiometabolic diseases. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association between injury pattern of patients with multiple injuries and circulating levels of soluble tumor necrosis factor receptors, interleukin-6 and interleukin-10, and polymorphonuclear neutrophil elastase.

PubMed

Hensler, Thorsten; Sauerland, Stefan; Bouillon, Bertil; Raum, Marcus; Rixen, Dieter; Helling, Hanns-J; Andermahr, Jonas; Neugebauer, Edmund A M

2002-05-01

Our knowledge about the bidirectional interactions between brain and whole organism after trauma is still limited. It was the purpose of this prospective clinical study to determine the influence of severe head trauma (SHT) as well as trauma in different anatomic injury regions on posttraumatic inflammatory mediator levels from patients with multiple injuries. Thirty-five healthy controls, 33 patients with an isolated SHT, 47 patients with multiple injuries without SHT, and 45 patients with both SHT and multiple injuries were studied. The posttraumatic plasma levels of soluble tumor necrosis factor receptors p55 and p75, interleukin (IL)-6, IL-10, and polymorphonuclear neutrophil (PMN) elastase were monitored using enzyme-linked immunosorbent assay technique. The influence of head injuries as well as thorax, abdomen, and extremity injuries on the mediator release from patients with multiple injuries was investigated by multivariate linear regression models. The soluble tumor necrosis factor receptor p55/p75 ratio was significantly elevated within 3 hours of trauma in all three injury groups and returned to reference ratios after 12 hours. The lowest increase was found in patients suffering from an isolated SHT. Lowest mediator levels in this patient population were also found for IL-6, IL-10, and PMN elastase during the first 36 hours after trauma. Additional injuries to the head, thorax, abdomen, and extremity modulated mediator levels to a different degree. No specific effect was found for SHT when compared with other injury groups. Thorax injuries caused the quickest rise in mediator levels, whereas abdominal injuries significantly increased PMN elastase levels 12 to 24 hours after trauma. Traumatic injuries cause the liberation of various mediators, without any specific association between anatomic injury pattern and the pattern of mediator release.

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.

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

PubMed

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

2017-06-01

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

Multiscale Modeling of Virus Entry via Receptor-Mediated Endocytosis

NASA Astrophysics Data System (ADS)

Liu, Jin

2012-11-01

Virus infections are ubiquitous and remain major threats to human health worldwide. Viruses are intracellular parasites and must enter host cells to initiate infection. Receptor-mediated endocytosis is the most common entry pathway taken by viruses, the whole process is highly complex and dictated by various events, such as virus motions, membrane deformations, receptor diffusion and ligand-receptor reactions, occurring at multiple length and time scales. We develop a multiscale model for virus entry through receptor-mediated endocytosis. The binding of virus to cell surface is based on a mesoscale three dimensional stochastic adhesion model, the internalization (endocytosis) of virus and cellular membrane deformation is based on the discretization of Helfrich Hamiltonian in a curvilinear space using Monte Carlo method. The multiscale model is based on the combination of these two models. We will implement this model to study the herpes simplex virus entry into B78 cells and compare the model predictions with experimental measurements.

Hierarchical Modeling of Sequential Behavioral Data: Examining Complex Association Patterns in Mediation Models

ERIC Educational Resources Information Center

Dagne, Getachew A.; Brown, C. Hendricks; Howe, George W.

2007-01-01

This article presents new methods for modeling the strength of association between multiple behaviors in a behavioral sequence, particularly those involving substantively important interaction patterns. Modeling and identifying such interaction patterns becomes more complex when behaviors are assigned to more than two categories, as is the case…

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

PubMed

Wang, Jian; Shete, Sanjay

2017-01-01

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

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

PubMed Central

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

2016-01-01

Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the “anchor away” (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. PMID:27185874

Emotional states as mediators between tinnitus loudness and tinnitus distress in daily life: Results from the “TrackYourTinnitus” application

PubMed Central

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

2016-01-01

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

A single-rate context-dependent learning process underlies rapid adaptation to familiar object dynamics.

PubMed

Ingram, James N; Howard, Ian S; Flanagan, J Randall; Wolpert, Daniel M

2011-09-01

Motor learning has been extensively studied using dynamic (force-field) perturbations. These induce movement errors that result in adaptive changes to the motor commands. Several state-space models have been developed to explain how trial-by-trial errors drive the progressive adaptation observed in such studies. These models have been applied to adaptation involving novel dynamics, which typically occurs over tens to hundreds of trials, and which appears to be mediated by a dual-rate adaptation process. In contrast, when manipulating objects with familiar dynamics, subjects adapt rapidly within a few trials. Here, we apply state-space models to familiar dynamics, asking whether adaptation is mediated by a single-rate or dual-rate process. Previously, we reported a task in which subjects rotate an object with known dynamics. By presenting the object at different visual orientations, adaptation was shown to be context-specific, with limited generalization to novel orientations. Here we show that a multiple-context state-space model, with a generalization function tuned to visual object orientation, can reproduce the time-course of adaptation and de-adaptation as well as the observed context-dependent behavior. In contrast to the dual-rate process associated with novel dynamics, we show that a single-rate process mediates adaptation to familiar object dynamics. The model predicts that during exposure to the object across multiple orientations, there will be a degree of independence for adaptation and de-adaptation within each context, and that the states associated with all contexts will slowly de-adapt during exposure in one particular context. We confirm these predictions in two new experiments. Results of the current study thus highlight similarities and differences in the processes engaged during exposure to novel versus familiar dynamics. In both cases, adaptation is mediated by multiple context-specific representations. In the case of familiar object dynamics, however, the representations can be engaged based on visual context, and are updated by a single-rate process.

The Long arm of Job Insecurity: Its Impact on Career-Specific Parenting Behaviors and Youths' Career Self-Efficacy

ERIC Educational Resources Information Center

Zhao, Xiuxi; Lim, Vivien K. G.; Teo, Thompson S. H.

2012-01-01

Applying a multiple-mediator model, we examine the mediating effect of three types of career-specific parenting behaviors: lack of engagement, support, and interference, on the relationship between paternal job insecurity and youths' career self-efficacy. Data were collected from a sample of undergraduate students and their fathers. Results of the…

Ethnic-Racial Socialization and Adjustment among Latino College Students: The Mediating Roles of Ethnic Centrality, Public Regard, and Perceived Barriers to Opportunity

ERIC Educational Resources Information Center

Rivas-Drake, Deborah

2011-01-01

Parents' efforts to socialize their children around issues of ethnicity and race have implications for well-being in several life domains, including academic and psychological adjustment. The present study tested a multiple mediator model in which parental ethnic-racial socialization was linked to psychological adjustment through two dimensions of…

Using Multiple Indicators of Cognitive State in Logistic Models that Predict Individual Performance in Machine-Mediated Learning Environments.

ERIC Educational Resources Information Center

Hancock, Thomas E.; And Others

1995-01-01

In machine-mediated learning environments, there is a need for more reliable methods of calculating the probability that a learner's response will be correct in future trials. A combination of domain-independent response-state measures of cognition along with two instructional variables for maximum predictive ability are demonstrated. (Author/LRW)

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

PubMed

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

2012-01-01

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

Mediation Analysis with Multiple Mediators

PubMed Central

VanderWeele, T.J.; Vansteelandt, S.

2014-01-01

Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators. PMID:25580377

Mediation Analysis with Multiple Mediators.

PubMed

VanderWeele, T J; Vansteelandt, S

2014-01-01

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

Do sophisticated epistemic beliefs predict meaningful learning? Findings from a structural equation model of undergraduate biology learning

NASA Astrophysics Data System (ADS)

Lee, Silvia Wen-Yu; Liang, Jyh-Chong; Tsai, Chin-Chung

2016-10-01

This study investigated the relationships among college students' epistemic beliefs in biology (EBB), conceptions of learning biology (COLB), and strategies of learning biology (SLB). EBB includes four dimensions, namely 'multiple-source,' 'uncertainty,' 'development,' and 'justification.' COLB is further divided into 'constructivist' and 'reproductive' conceptions, while SLB represents deep strategies and surface learning strategies. Questionnaire responses were gathered from 303 college students. The results of the confirmatory factor analysis and structural equation modelling showed acceptable model fits. Mediation testing further revealed two paths with complete mediation. In sum, students' epistemic beliefs of 'uncertainty' and 'justification' in biology were statistically significant in explaining the constructivist and reproductive COLB, respectively; and 'uncertainty' was statistically significant in explaining the deep SLB as well. The results of mediation testing further revealed that 'uncertainty' predicted surface strategies through the mediation of 'reproductive' conceptions; and the relationship between 'justification' and deep strategies was mediated by 'constructivist' COLB. This study provides evidence for the essential roles some epistemic beliefs play in predicting students' learning.

Collective-efficacy as a mediator of the relationship of leaders' personality traits and team performance: A cross-level analysis.

PubMed

Li, Xiaoshan; Zhou, Mingjie; Zhao, Na; Zhang, Shanshan; Zhang, Jianxin

2015-06-01

The relationship between a leader's personality and his team's performance has been established in organisational research, but the underlying process and mechanism responsible for this effect have not been fully explored. Both the traditional multiple linear regression and the multilevel structural equation model approaches were used in this study to test a proposed mediating model of subordinates' perception of collective efficacy between leader personality and team performance. The results show that the team leader's extraversion and conscientiousness personality traits were related positively to both the team-average (individual) perception of collective efficacy and team performance, and the collective efficacy mediated the relationship of the leader's personality traits and team performance. This study also discusses how Chinese cultural elements play a role in such a mediating model. © 2014 International Union of Psychological Science.

Mediating mechanisms of a military Web-based alcohol intervention.

PubMed

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

2009-03-01

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

Early Socioeconomic Adversity and Young Adult Physical Illness: The Role of Body Mass Index and Depressive Symptoms

PubMed Central

Wickrama, K. A. S.; Kwon, Josephine A.; Oshri, Assaf; Lee, Tae Kyoung

2014-01-01

Purpose The present study investigated the psycho-physiological inter and intra-individual processes that mediate the linkage between childhood/adolescent socioeconomic adversities and adult health outcomes. Specifically, the proposed model examined the roles of youth depressive symptoms and BMI trajectories as mediators that explain the link between early adversity and young adults’ general health and physical illnesses after controlling for gender, race/ethnicity, and earlier general health reports. Methods Using a nationally representative sample of 12,424 from National Longitudinal Study of Adolescent Health (Add Health), this study used growth curve modeling to consider both the severity (initial level) as well as the change over time (deterioration or elevation) as psycho-physiological mediators, thereby acknowledging multiple facets of depressive symptoms and BMI trajectories as psych-physiological mediators of early adversity to adult health. Results Results provide evidence for (a) the influence of early childhood and early adolescent cumulative socioeconomic adversity on both the initial levels and changes over time of depressive symptoms and BMI and (b) the independent influences depressive symptoms and BMI trajectories on the general health and the physical illnesses of young adults Conclusions These findings contribute valuable knowledge to existing research by elucidating how early adversity exerts an enduring long-term influence on physical health problems in young adulthood; further, this information suggests effective intervention and prevention programs should incorporate multiple facets (severity and change over time) of multiple mechanisms (psychological and physiological). PMID:24856408

Mediating the relation between workplace stressors and distress in ID support staff: comparison between the roles of psychological inflexibility and coping styles.

PubMed

Kurz, A Solomon; Bethay, J Scott; Ladner-Graham, Jennifer M

2014-10-01

The present study examined how different patterns of coping influence psychological distress for staff members in programs serving individuals with intellectual disabilities. With a series of path models, we examined the relative usefulness of constructs (i.e., wishful thinking and psychological inflexibility) from two distinct models of coping (i.e., the transactional model and the psychological flexibility models, respectively) as mediators to explain how workplace stressors lead to psychological distress in staff serving individuals with intellectual disabilities. Analyses involved self-report questionnaires from 128 staff members (84% female; 71% African American) from a large, state-funded residential program for individuals with intellectual and physical disabilities in the southern United States of America. Cross-sectional path models using bootstrapped standard errors and confidence intervals revealed both wishful thinking and psychological inflexibility mediated the relation between workplace stressors and psychological distress when they were included in separate models. However, when both variables were included in a multiple mediator model, only psychological inflexibility remained a significant mediator. The results suggest psychological inflexibility and the psychological flexibility model may be particularly useful for further investigation on the causes and amelioration of workplace-related stress in ID settings. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Impact of Transformational Leadership on Safety Climate and Individual Safety Behavior on Construction Sites.

PubMed

Shen, Yuzhong; Ju, Chuanjing; Koh, Tas Yong; Rowlinson, Steve; Bridge, Adrian J

2017-01-05

Unsafe acts contribute dominantly to construction accidents, and increasing safety behavior is essential to reduce accidents. Previous research conceptualized safety behavior as an interaction between proximal individual differences (safety knowledge and safety motivation) and distal contextual factors (leadership and safety climate). However, relatively little empirical research has examined this conceptualization in the construction sector. Given the cultural background of the sample, this study makes a slight modification to the conceptualization and views transformational leadership as an antecedent of safety climate. Accordingly, this study establishes a multiple mediator model showing the mechanisms through which transformational leadership translates into safety behavior. The multiple mediator model is estimated by the structural equation modeling (SEM) technique, using individual questionnaire responses from a random sample of construction personnel based in Hong Kong. As hypothesized, transformational leadership has a significant impact on safety climate which is mediated by safety-specific leader-member exchange (LMX), and safety climate in turn impacts safety behavior through safety knowledge. The results suggest that future safety climate interventions should be more effective if supervisors exhibit transformational leadership, encourage construction personnel to voice safety concerns without fear of retaliation, and repeatedly remind them about safety on the job.

The Impact of Transformational Leadership on Safety Climate and Individual Safety Behavior on Construction Sites

PubMed Central

Shen, Yuzhong; Ju, Chuanjing; Koh, Tas Yong; Rowlinson, Steve; Bridge, Adrian J.

2017-01-01

Unsafe acts contribute dominantly to construction accidents, and increasing safety behavior is essential to reduce accidents. Previous research conceptualized safety behavior as an interaction between proximal individual differences (safety knowledge and safety motivation) and distal contextual factors (leadership and safety climate). However, relatively little empirical research has examined this conceptualization in the construction sector. Given the cultural background of the sample, this study makes a slight modification to the conceptualization and views transformational leadership as an antecedent of safety climate. Accordingly, this study establishes a multiple mediator model showing the mechanisms through which transformational leadership translates into safety behavior. The multiple mediator model is estimated by the structural equation modeling (SEM) technique, using individual questionnaire responses from a random sample of construction personnel based in Hong Kong. As hypothesized, transformational leadership has a significant impact on safety climate which is mediated by safety-specific leader–member exchange (LMX), and safety climate in turn impacts safety behavior through safety knowledge. The results suggest that future safety climate interventions should be more effective if supervisors exhibit transformational leadership, encourage construction personnel to voice safety concerns without fear of retaliation, and repeatedly remind them about safety on the job. PMID:28067775

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

PubMed

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

2018-05-01

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

Psychosocial Mechanisms Linking the Social Environment to Mental Health in African Americans

PubMed Central

Basen-Engquist, Karen; Lee, Rebecca E.; Thompson, Deborah; Wetter, David W.; Reitzel, Lorraine R.

2016-01-01

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination), and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p < .001) and U.S. (p < .001) and low social support (p < .001) were associated with poor mental health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans. PMID:27119366

Stimulating Autonomous Learning Environments: Considering Group Efficacy as Mediating the Relationship between Perceived Autonomy Support and Self- Determinism in the Learning Environment

ERIC Educational Resources Information Center

Hogan, Shannon L.

2012-01-01

This study researched 120 college students and professors to test the mediation of group efficacy between perceived autonomy support and self-determinism. The study provided surveys to students in eight different classes. Studying multiple classes offered an opportunity to understand the model more effectively and in a broader scope. The classes…

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

PubMed

Hsu, Mei-Chi; Tu, Chun-Hsien

2014-09-01

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

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.

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

PubMed

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

2016-07-15

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

An In Silico Model of Endotoxic Shock Mediators (Briefing Charts)

DTIC Science & Technology

2012-03-12

complex probably because receptor activates multiple signaling pathways choline P O acetyl...calcium mobilization phospholipase C phospholipase D phospholipase A2 eicosanoids inositol metabolism protein kinase C COOH NH2 PAF

Attachment to parents and peers as a risk factor for adolescent depressive disorders: the mediating role of emotion regulation.

PubMed

Kullik, Angelika; Petermann, Franz

2013-08-01

This study examined emotion regulation as a mediator in the relationship of attachment and depression in adolescents. Participants (N girls = 127; M age = 14.50; N boys = 121; M age = 14.31) completed self-report questionnaires of attachment to parents and peers, emotion regulation and depression. Models with dysfunctional emotion regulation as a mediation variable were tested via hierarchical multiple regression analyses and bootstrapping procedure. Results revealed significant relations between attachment to parents and peers, dysfunctional emotion regulation and depression. For girls, internal-dysfunctional emotion regulation was a mediator in the relation of attachment to parents and depression and partly mediated the association of attachment to peers. For boys, internal- and external-dysfunctional emotion regulation acted as partly mediators in association of attachment to parents and depression. Results indicate important mechanisms that contribute to the refinement of conceptual models and provide indications for gender specific prevention and intervention for depressive disorders.

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

PubMed

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

2018-05-01

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

Parent involvement and student academic performance: A multiple mediational analysis

PubMed Central

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

2011-01-01

Parent involvement in a child's education is consistently found to be positively associated with a child's academic performance. However, there has been little investigation of the mechanisms that explain this association. The present study examines two potential mechanisms of this association: the child's perception of cognitive competence and the quality of the student-teacher relationship. This study used a sample of 158 seven-year old participants, their mothers, and their teachers. Results indicated a statistically significant association between parent involvement and a child's academic performance, over and above the impact of the child's intelligence. A multiple mediation model indicated that the child's perception of cognitive competence fully mediated the relation between parent involvement and the child's performance on a standardized achievement test. The quality of the student-teacher relationship fully mediated the relation between parent involvement and teacher ratings of the child's classroom academic performance. Limitations, future research directions, and implications for public policy initiatives were discussed. PMID:20603757

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

PubMed

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

2007-09-01

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

Wuling powder prevents the depression-like behavior in learned helplessness mice model through improving the TSPO mediated-mitophagy.

PubMed

Li, Dongmei; Zheng, Ji; Wang, Mingyang; Feng, Lu; Liu, Yanyong; Yang, Nan; Zuo, Pingping

2016-06-20

Wuling powder (trade name: Wuling capsule), a traditional Chinese medicine (TCM), was extracted from mycelia of precious Xylaria Nigripes (Kl.) Sacc by modern fermentation technology, and has been claimed to be fully potent in improving the signs of insomnia and cognitive deficits. Moreover, Wuling capsule was effective in treating post-stroke and orther co-cormbid depression both in clinical and in basic research. In order to clarify the molecular mechanisms of the antidepressant effect of Wuling powder, we established learned helplessness (LH) depression animal model and focused on 18kDa translocator protein (TSPO) mediated-mitophagy pathway. Mice were exposed to the inescapable e-shock (IS) once a day for three consecutive days to establish the LH model. Then mice were orally administered Wuling powder for 2 weeks. For the behavioral assessment, Shuttle box test, novelty suppressed feeding test (NSF) and forced swimming test (FST) were performed. Following the behavioral assessment, we assessed the protein expression level that were related to TSPO-mediated mitophagy signaling pathway by Western blotting analysis. Finally, immunohistochemistry method was used to assess the neuroprotective effects of Wuling powder. Compared with mice that were subjected to inescapable e-shock, Wuling powder exhibited antidepressant effect in the multiple behavioral tests. In addition, Wuling powder altered the expression level of multiple proteins related to TSPO-mediated mitophagy signaling pathway. Our results suggested that Wuling powder exhibited an obvious antidepressant effect, which could be due to the improvement of TSPO-mediated mitophagy signaling pathway. Copyright © 2016. Published by Elsevier Ireland Ltd.

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

ERIC Educational Resources Information Center

Rau, Martina A.; Scheines, Richard

2012-01-01

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

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

PubMed

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

2017-10-01

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

Examining Multiple Parenting Behaviors on Young Children's Dietary Fat Consumption

ERIC Educational Resources Information Center

Eisenberg, Christina M.; Ayala, Guadalupe X.; Crespo, Noe C.; Lopez, Nanette V.; Zive, Michelle Murphy; Corder, Kirsten; Wood, Christine; Elder, John P.

2012-01-01

Objective: To understand the association between parenting and children's dietary fat consumption, this study tested a comprehensive model of parenting that included parent household rules, parent modeling of rules, parent mediated behaviors, and parent support. Design: Cross-sectional. Setting: Baseline data from the "MOVE/me Muevo"…

Understanding catastrophizing from a misdirected problem-solving perspective.

PubMed

Flink, Ida K; Boersma, Katja; MacDonald, Shane; Linton, Steven J

2012-05-01

The aim is to explore pain catastrophizing from a problem-solving perspective. The links between catastrophizing, problem framing, and problem-solving behaviour are examined through two possible models of mediation as inferred by two contemporary and complementary theoretical models, the misdirected problem solving model (Eccleston & Crombez, 2007) and the fear-anxiety-avoidance model (Asmundson, Norton, & Vlaeyen, 2004). In this prospective study, a general population sample (n= 173) with perceived problems with spinal pain filled out questionnaires twice; catastrophizing and problem framing were assessed on the first occasion and health care seeking (as a proxy for medically oriented problem solving) was assessed 7 months later. Two different approaches were used to explore whether the data supported any of the proposed models of mediation. First, multiple regressions were used according to traditional recommendations for mediation analyses. Second, a bootstrapping method (n= 1000 bootstrap resamples) was used to explore the significance of the indirect effects in both possible models of mediation. The results verified the concepts included in the misdirected problem solving model. However, the direction of the relations was more in line with the fear-anxiety-avoidance model. More specifically, the mediation analyses provided support for viewing catastrophizing as a mediator of the relation between biomedical problem framing and medically oriented problem-solving behaviour. These findings provide support for viewing catastrophizing from a problem-solving perspective and imply a need to examine and address problem framing and catastrophizing in back pain patients. ©2011 The British Psychological Society.

Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model.

PubMed

Kim, Chulwon; Lee, Seok-Geun; Yang, Woong Mo; Arfuso, Frank; Um, Jae-Young; Kumar, Alan Prem; Bian, Jinsong; Sethi, Gautam; Ahn, Kwang Seok

2018-05-29

Aberrant reactions of signal transducer and transcriptional activator (STAT) are frequently detected in multiple myeloma (MM) cancers and can upregulate the expression of multiple genes related to cell proliferation, survival, metastasis, and angiogenesis. Therefore, agents capable of inhibiting STAT activation can form the basis of novel therapies for MM patients. In the present study, we investigated whether the potential anti-cancer effects of Formononetin (FT), a naturally occurring isoflavone derived from Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, against MM cell lines and human multiple myeloma xenograft tumors in athymic nu/nu mice model are mediated through the negative regulation of STAT3 and STAT5 pathways. Data from the in vitro studies indicated that FT could significantly inhibit cell viability, and induce apoptosis. Interestingly, FT also suppressed constitutive STAT3 (tyrosine residue 705 and serine residue 727) and STAT5 (tyrosine residue 694/699) activation, which correlated with the suppression of the upstream kinases (JAK1, JAK2, and c-Src) in MM cells, and this effect was found to be mediated via an increased production of reactive oxygen species (ROS) due to GSH/GSSG imbalance. Also, FT abrogated STAT3 and STAT5 DNA binding capacity and nuclear translocation. FT induced cell cycle arrest, downregulated the expression of STAT3-regulated anti-apoptotic, angiogenetic, and proliferative gene products; and this correlated with induction of caspase-3 activation and cleavage of PARP. Intraperitoneal administration of FT significantly suppressed the tumor growth in the multiple myeloma xenograft mouse model without exhibiting any significant adverse effects. Overall, our findings indicate that FT exhibits significant anti-cancer effects in MM that may be primarily mediated through the ROS-regulated inhibition of the STAT3 and STAT5 signaling cascade. Copyright © 2018 Elsevier B.V. All rights reserved.

Modeling the Relationship between Trauma and Psychological Distress among HIV-Positive and HIV-Negative Women.

PubMed

Brumsey, Ayesha Delany; Joseph, Nataria T; Myers, Hector F; Ullman, Jodie B; Wyatt, Gail E

2013-01-01

This study investigated the association between cumulative exposure to multiple traumatic events and psychological distress, as mediated by problematic substance use and impaired psychosocial resources. A sample of HIV-positive and HIV-negative women were assessed for a history of childhood and adult sexual abuse and non-sexual trauma as predictors of psychological distress (i.e., depression, non-specific anxiety, and posttraumatic stress), as mediated by problematic alcohol and drug use and psychosocial resources (i.e., social support, self-esteem and optimism). Structural equation modeling confirmed that cumulative trauma exposure is positively associated with greater psychological distress, and that this association is partially mediated through impaired psychosocial resources. However, although cumulative trauma was associated with greater problematic substance use, substance use did not mediate the relationship between trauma and psychological distress.

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.

Helplessness and loss as mediators between pain and depressive symptoms in fibromyalgia.

PubMed

Palomino, Rand A; Nicassio, Perry M; Greenberg, Melanie A; Medina, Ernesto P

2007-05-01

This study evaluated the contribution of condition-specific helplessness and loss to depression in fibromyalgia (FM). Two models were tested. The first model examined whether loss, measured by the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) Interference Scale, would mediate the relationship between disability and depression. The second model determined whether condition-specific helplessness and loss would mediate the relationship between pain and depression with disability controlled. Eighty patients with confirmed diagnoses of FM were recruited throughout Southern California from general medical clinics, newspaper advertisements, and rheumatology practices. The study design was cross-sectional, using self-report, observational, and interview measures. A composite measure of depression was adopted, consisting of the Center for Epidemiological Studies-Depression Scale and the Hamilton Rating Scale for Depression. Hierarchical multiple regression analyses were conducted using a path analytic framework to examine each model. In Model 1, loss fully mediated the relationship between disability and depression. In Model 2, condition-specific helplessness mediated the relationship between pain and depression, but the contribution of loss was not significant. The findings confirm the importance of helplessness and demonstrate that the cognitive meaning of having FM plays a more central role in predicting depressive symptomatology than illness-related stressors, such as pain or disability.

A mediator effect size in randomized clinical trials.

PubMed

Kraemer, Helena Chmura

2014-12-01

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

Causal mediation analysis for longitudinal data with exogenous exposure

PubMed Central

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

2016-01-01

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

Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis.

PubMed

McKenzie, Brienne A; Mamik, Manmeet K; Saito, Leina B; Boghozian, Roobina; Monaco, Maria Chiara; Major, Eugene O; Lu, Jian-Qiang; Branton, William G; Power, Christopher

2018-06-12

Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease of the CNS of unknown cause that remains incurable. Inflammasome-associated caspases mediate the maturation and release of the proinflammatory cytokines IL-1β and IL-18 and activate the pore-forming protein gasdermin D (GSDMD). Inflammatory programmed cell death, pyroptosis, was recently shown to be mediated by GSDMD. Here, we report molecular evidence for GSDMD-mediated inflammasome activation and pyroptosis in both myeloid cells (macrophages/microglia) and, unexpectedly, in myelin-forming oligodendrocytes (ODCs) in the CNS of patients with MS and in the MS animal model, experimental autoimmune encephalomyelitis (EAE). We observed inflammasome activation and pyroptosis in human microglia and ODCs in vitro after exposure to inflammatory stimuli and demonstrate caspase-1 inhibition by the small-molecule inhibitor VX-765 in both cell types. GSDMD inhibition by siRNA transduction suppressed pyroptosis in human microglia. VX-765 treatment of EAE animals reduced the expression of inflammasome- and pyroptosis-associated proteins in the CNS, prevented axonal injury, and improved neurobehavioral performance. Thus, GSDMD-mediated pyroptosis in select glia cells is a previously unrecognized mechanism of inflammatory demyelination and represents a unique therapeutic opportunity for mitigating the disease process in MS and other CNS inflammatory diseases.

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

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).

Investigating Transporter‐Mediated Drug‐Drug Interactions Using a Physiologically Based Pharmacokinetic Model of Rosuvastatin

PubMed Central

Wang, Q; Leil, T

2017-01-01

Rosuvastatin is a frequently used probe in transporter‐mediated drug‐drug interaction (DDI) studies. This report describes the development of a physiologically based pharmacokinetic (PBPK) model of rosuvastatin for prediction of pharmacokinetic (PK) DDIs. The rosuvastatin model predicted the observed single (i.v. and oral) and multiple dose PK profiles, as well as the impact of coadministration with transporter inhibitors. The predicted effects of rifampin and cyclosporine (6.58‐fold and 5.07‐fold increase in rosuvastatin area under the curve (AUC), respectively) were mediated primarily via inhibition of hepatic organic anion‐transporting polypeptide (OATP)1B1 (Inhibition constant (Ki) ∼1.1 and 0.014 µM, respectively) and OATP1B3 (Ki ∼0.3 and 0.007 µM, respectively), with cyclosporine also inhibiting intestinal breast cancer resistance protein (BCRP; Ki ∼0.07 µM). The predicted effects of gemfibrozil and its metabolite were moderate (1.88‐fold increase in rosuvastatin AUC) and mediated primarily via inhibition of hepatic OATP1B1 and renal organic cation transporter 3. This model of rosuvastatin will be useful in prospectively predicting transporter‐mediated DDIs with novel pharmaceutical agents in development. PMID:28296193

Precompetitive achievement goals, stress appraisals, emotions, and coping among athletes.

PubMed

Nicholls, Adam R; Perry, John L; Calmeiro, Luis

2014-10-01

Grounded in Lazarus's (1991, 1999, 2000) cognitive-motivational-relational theory of emotions, we tested a model of achievement goals, stress appraisals, emotions, and coping. We predicted that precompetitive achievement goals would be associated with appraisals, appraisals with emotions, and emotions with coping in our model. The mediating effects of emotions among the overall sample of 827 athletes and two stratified random subsamples were also explored. The results of this study support our proposed model in the overall sample and the stratified subsamples. Further, emotion mediated the relationship between appraisal and coping. Mediation analyses revealed that there were indirect effects of pleasant and unpleasant emotions, which indicates the importance of examining multiple emotions to reveal a more accurate representation of the overall stress process. Our findings indicate that both appraisals and emotions are just as important in shaping coping.

College drinking behaviors: mediational links between parenting styles, impulse control, and alcohol-related outcomes.

PubMed

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

2006-06-01

Mediational links between parenting styles (authoritative, authoritarian, permissive), impulsiveness (general control), drinking control (specific control), and alcohol use and abuse were tested. A pattern-mixture approach (for modeling non-ignorable missing data) with multiple-group structural equation models with 421 (206 female, 215 male) college students was used. Gender was examined as a potential moderator of parenting styles on control processes related to drinking. Specifically, the parent-child gender match was found to have implications for increased levels of impulsiveness (a significant mediator of parenting effects on drinking control). These findings suggest that a parent with a permissive parenting style who is the same gender as the respondent can directly influence control processes and indirectly influence alcohol use and abuse.

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.

Social Identity in People with Multiple Sclerosis: An Examination of Family Identity and Mood.

PubMed

Barker, Alex B; Lincoln, Nadina B; Hunt, Nigel; dasNair, Roshan

2018-01-01

Mood disorders are highly prevalent in people with multiple sclerosis (MS). MS causes changes to a person's sense of self. The Social Identity Model of Identity Change posits that group membership can have a positive effect on mood during identity change. The family is a social group implicated in adjustment to MS. The objectives of this study were to investigate whether family identity can predict mood in people with MS and to test whether this prediction was mediated by social support and connectedness to others. This cross-sectional survey of 195 participants comprised measures of family identity, family social support, connectedness to others, and mood. Family identity predicted mood both directly and indirectly through parallel mediators of family social support and connectedness to others. Family identity predicted mood as posited by the Social Identity Model of Identity Change. Involving the family in adjustment to MS could reduce low mood.

Mediators of the Relation between Childhood Sexual Abuse and Women’s Sexual Risk Behavior: A Comparison of Two Theoretical Frameworks

PubMed Central

Senn, Theresa E.; Carey, Michael P.; Coury-Doniger, Patricia

2012-01-01

Childhood sexual abuse (CSA) is associated with sexual risk behavior in adulthood, but little research has investigated processes that might mediate this relation. The purpose of this study was to investigate whether constructs suggested by the traumagenic dynamics (TD) model (a theory of the effects of CSA) or constructs suggested by the Information-Motivation-Behavioral skills (IMB) model (a theory of the antecedents of sexual risk behavior) better mediated the relation between CSA and sexual risk behavior in adulthood. Participants were 481 women attending an STI clinic (66% African American) who completed a computerized survey as well as behavioral simulations assessing condom application and sexual assertiveness skills. Forty-five percent of the sample met criteria for CSA and CSA was associated with sexual risk behavior in adulthood. In multiple mediator models, the TD constructs mediated the relation between CSA and the number of sexual partners whereas the IMB constructs mediated the relation between CSA and unprotected sex. In addition, the TD constructs better mediated the relation between CSA and the number of sexual partners; the TD and IMB constructs did not differ in their ability to mediate the relation between CSA and unprotected sex. Sexual risk reduction interventions for women who were sexually abused should target not only the constructs from health behavior models (e.g., motivation and skills to reduce sexual risk), but also constructs that are specific to sexual abuse (e.g., traumatic sexualization and guilt). PMID:22282323

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

Covariate Measurement Error Correction Methods in Mediation Analysis with Failure Time Data

PubMed Central

Zhao, Shanshan

2014-01-01

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

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

PubMed

Zhao, Shanshan; Prentice, Ross L

2014-12-01

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

Socio-Historical Factors Mediating Collaborative Teaching and Learning: A Design-Based Investigation and Intervention

ERIC Educational Resources Information Center

Hackett, Jacob

2016-01-01

Collaborative (Co-)teaching is a complex instructional delivery model used to improve teaching practice in inclusive settings. The model involves multiple certified teachers--representing both special and general education--sharing the same space and presenting material to classrooms with a wide variance in learning needs. Co-teaching has become…

Burnout and Engagement as Mediators in the Relationship between Work Characteristics and Turnover Intentions across Two Ibero-American Nations.

PubMed

Gabel Shemueli, Rachel; Dolan, Simon L; Suárez Ceretti, Adriana; Nuñez Del Prado, Pamela

2016-12-01

This study examines the mediating effects of burnout and engagement on the relationships between work characteristics (work overload and social support) and turnover intentions in the nursing community of two Ibero-American countries within the job demands-resources model. The sample consists of 316 registered nurses employed in Uruguay and 502 employed in Spain. We used multiple structural equation modelling analyses. The proposed model fit the data for both nursing samples. Burnout was found to fully mediate the relationship between work overload and turnover intention, whereas work engagement partially mediates the relationship between social support and turnover intention. The results contribute to our understanding of the potential applicability of two leading empirical models and of the dynamic relationship between work characteristics and turnover intentions through work engagement and burnout. Researchers should continue to focus on gaining a broader understanding of the effects of work characteristics in healthcare facilities and the associated organizational outcomes. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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

PubMed

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

2017-02-01

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

Multiscale regression modeling in mouse supraspinatus tendons reveals that dynamic processes act as mediators in structure-function relationships.

PubMed

Connizzo, Brianne K; Adams, Sheila M; Adams, Thomas H; Jawad, Abbas F; Birk, David E; Soslowsky, Louis J

2016-06-14

Recent advances in technology have allowed for the measurement of dynamic processes (re-alignment, crimp, deformation, sliding), but only a limited number of studies have investigated their relationship with mechanical properties. The overall objective of this study was to investigate the role of composition, structure, and the dynamic response to load in predicting tendon mechanical properties in a multi-level fashion mimicking native hierarchical collagen structure. Multiple linear regression models were investigated to determine the relationships between composition/structure, dynamic processes, and mechanical properties. Mediation was then used to determine if dynamic processes mediated structure-function relationships. Dynamic processes were strong predictors of mechanical properties. These predictions were location-dependent, with the insertion site utilizing all four dynamic responses and the midsubstance responding primarily with fibril deformation and sliding. In addition, dynamic processes were moderately predicted by composition and structure in a regionally-dependent manner. Finally, dynamic processes were partial mediators of the relationship between composition/structure and mechanical function, and results suggested that mediation is likely shared between multiple dynamic processes. In conclusion, the mechanical properties at the midsubstance of the tendon are controlled primarily by fibril structure and this region responds to load via fibril deformation and sliding. Conversely, the mechanical function at the insertion site is controlled by many other important parameters and the region responds to load via all four dynamic mechanisms. Overall, this study presents a strong foundation on which to design future experimental and modeling efforts in order to fully understand the complex structure-function relationships present in tendon. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-11-01

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

Are effort-reward imbalance and social isolation mediating the association between education and depressiveness? Baseline findings from the lidA(§)-study.

PubMed

du Prel, Jean-Baptist; Iskenius, Mario; Peter, Richard

2014-12-01

To investigate multiple mediations of the association between education and depressive symptoms (BDI-V) by work-related stress (ERI) and social isolation, the regional variation of the first mediation and a potential moderating effect of regional unemployment rate. 6339 employees born in 1959 and 1965 were randomly recruited from 222 sample points in a German cohort study on work, age, health and work participation. A multilevel model of moderated lower-level mediation was used to investigate the confirmatory research question. Multiple mediations were tested corresponding to Baron and Kenny. These analyses were stratified for age and adjusted for sex, negative affectivity and overcommitment. In the association between education and depressive symptoms, indirect effects of work-related stress and social isolation were significant in both age cohorts whereas a direct association was observable in the younger cohort, only. The significant regional variation in the association between work-related stress and depressive symptoms was not statistically explained by regional unemployment rate. Our findings point out that work-related stress and social isolation play an intermediary role between education and depressive symptoms in middle-aged employees.

Workplace support, discrimination, and person-organization fit: tests of the theory of work adjustment with LGB individuals.

PubMed

Velez, Brandon L; Moradi, Bonnie

2012-07-01

The present study explored the links of 2 workplace contextual variables--perceptions of workplace heterosexist discrimination and lesbian, gay, and bisexual (LGB)-supportive climates--with job satisfaction and turnover intentions in a sample of LGB employees. An extension of the theory of work adjustment (TWA) was used as the conceptual framework for the study; as such, perceived person-organization (P-O) fit was tested as a mediator of the relations between the workplace contextual variables and job outcomes. Data were analyzed from 326 LGB employees. Zero-order correlations indicated that perceptions of workplace heterosexist discrimination and LGB-supportive climates were correlated in expected directions with P-O fit, job satisfaction, and turnover intentions. Structural equation modeling (SEM) was used to compare multiple alternative measurement models evaluating the discriminant validity of the 2 workplace contextual variables relative to one another, and the 3 TWA job variables relative to one another; SEM was also used to test the hypothesized mediation model. Comparisons of multiple alternative measurement models supported the construct distinctiveness of the variables of interest. The test of the hypothesized structural model revealed that only LGB-supportive climates (and not workplace heterosexist discrimination) had a unique direct positive link with P-O fit and, through the mediating role of P-O fit, had significant indirect positive and negative relations with job satisfaction and turnover intentions, respectively. Moreover, P-O fit had a significant indirect negative link with turnover intentions through job satisfaction.

Causal mediation analysis for longitudinal data with exogenous exposure.

PubMed

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

2016-01-01

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

Verbal and Visual Memory Impairments in Bipolar I and II Disorder.

PubMed

Ha, Tae Hyon; Kim, Ji Sun; Chang, Jae Seung; Oh, Sung Hee; Her, Ju Young; Cho, Hyun Sang; Park, Tae Sung; Shin, Soon Young; Ha, Kyooseob

2012-12-01

To compare verbal and visual memory performances between patients with bipolar I disorder (BD I) and patients with bipolar II disorder (BD II) and to determine whether memory deficits were mediated by impaired organizational strategies. Performances on the Korean-California Verbal Learning Test (K-CVLT) and the Rey-Osterrieth Complex Figure Test (ROCF) in 37 patients with BD I, 46 patients with BD II and 42 healthy subjects were compared. Mediating effects of impaired organization strategies on poor delayed recall was tested by comparing direct and mediated models using multiple regression analysis. Both patients groups recalled fewer words and figure components and showed lower Semantic Clustering compared to controls. Verbal memory impairment was partly mediated by difficulties in Semantic Clustering in both subtypes, whereas the mediating effect of Organization deficit on the visual memory impairment was present only in BD I. In all mediated models, group differences in delayed recall remained significant. Our findings suggest that memory impairment may be one of the fundamental cognitive deficits in bipolar disorders and that executive dysfunctions can exert an additional influence on memory impairments.

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.

Mother-child relationship quality and effective discipline as mediators of the 6-year effects of the New Beginnings Program for children from divorced families.

PubMed

Zhou, Qing; Sandler, Irwin N; Millsap, Roger E; Wolchik, Sharlene A; Dawson-McClure, Spring R

2008-08-01

This study examines whether program effects on mother-child relationship quality and effective discipline mediated the 6-year longitudinal effects of the New Beginnings Program (NBP) to improve mental health and competence outcomes in 218 adolescents from divorced families in a randomized experimental trial. The NBP is a theory-based and parenting-focused preventive intervention to help children adjust to divorce, and it has previously shown significant main and/or Program x Baseline Risk interaction effects to reduce adolescents' mental health and social adaptation problems and to promote competence. Mediation analyses were conducted using single- and two-group (high and low baseline risk) structural equation modeling. A multiple-methods and multiple-informants approach was used to assess the putative mediators and adolescents' outcomes. Results indicated that program-induced improvement in maternal effective discipline at posttest mediated the intervention effect on adolescents' GPA at the 6-year follow-up. Moreover, program-induced improvement in mother-child relationship quality mediated the intervention effect on adolescents' mental health problems for those with high baseline risk for maladjustment. The discussion focuses on the implications of the mediation findings for advancing the developmental theories that informed the design of the NBP and the implications for implementation of the NBP in community settings. Copyright 2008 APA, all rights reserved.

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.

High fat diet exacerbates neuroinflammation in an animal model of multiple sclerosis by activation of the Renin Angiotensin system.

PubMed

Timmermans, Silke; Bogie, Jeroen F J; Vanmierlo, Tim; Lütjohann, Dieter; Stinissen, Piet; Hellings, Niels; Hendriks, Jerome J A

2014-03-01

Epidemiological studies suggest a positive correlation between the incidence and severity of multiple sclerosis (MS) and the intake of fatty acids. It remains to be clarified whether high fat diet (HFD) indeed can exacerbate the disease pathology associated with MS and what the underlying mechanisms are. In this study, we determined the influence of HFD on the severity and pathology of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Mice were fed either normal diet (ND) or HFD and subsequently induced with EAE. Immunohistochemical staining and real-time PCR were used to determine immune cell infiltration and inflammatory mediators in the central nervous system (CNS). Our data show that HFD increases immune cell infiltration and inflammatory mediator production in the CNS and thereby aggravates EAE. Moreover, our data demonstrate that activation of the renin angiotensin system (RAS) is associated with the HFD-mediated effects on EAE severity. These results show that HFD exacerbates an autoreactive immune response within the CNS. This indicates that diets containing excess fat have a significant influence on neuroinflammation in EAE, which may have important implications for the treatment and prevention of neuroinflammatory disorders.

Identity Confusion and Materialism Mediate the Relationship Between Excessive Social Network Site Usage and Online Compulsive Buying.

PubMed

Sharif, Saeed Pahlevan; Khanekharab, Jasmine

2017-08-01

This study investigates the mediating role of identity confusion and materialism in the relationship between social networking site (SNS) excessive usage and online compulsive buying among young adults. A total of 501 SNS users aged 17 to 23 years (M = 19.68, SD = 1.65) completed an online survey questionnaire. A serial multiple mediator model was developed and hypotheses were tested using structural equation modeling. The results showed that excessive young adult SNS users had a higher tendency toward compulsive buying online. This was partly because they experienced higher identity confusion and developed higher levels of materialism. Targeted psychological interventions seeking to gradually increase identity clarity to buffer the detrimental effects of SNS usage and identity confusion in young adults are suggested.

When the job is boring: the role of boredom in organizational contexts.

PubMed

Guglielmi, Dina; Simbula, Silvia; Mazzetti, Greta; Tabanelli, Maria Carla; Bonfiglioli, Roberta

2013-01-01

The present study investigates the role of boredom within the Job Demands-Resources model. Although empirical evidence suggests that the incidence of boredom at work is widespread, the study of job boredom remains neglected today. Data were collected from 269 mass-retail workers, by means of structured face-to-face interviews. Results of multiple mediation analyses partially supported our hypotheses. Boredom mediates the relationship between transformational leadership, low learning opportunities and general dysphoria, while work engagement mediates the relationship between transformational leadership, low learning opportunities and job satisfaction as well as general dysphoria. Taken together, our results confirm the suitability of conceptualizing boredom within the JD-R model and contribute to the ongoing conceptualization of both the boredom literature and the JD-R literature.

Probing the Dark Sector with Dark Matter Bound States

NASA Astrophysics Data System (ADS)

An, Haipeng; Echenard, Bertrand; Pospelov, Maxim; Zhang, Yue

2016-04-01

A model of the dark sector where O (few GeV ) mass dark matter particles χ couple to a lighter dark force mediator V , mV≪mχ, is motivated by the recently discovered mismatch between simulated and observed shapes of galactic halos. Such models, in general, provide a challenge for direct detection efforts and collider searches. We show that for a large range of coupling constants and masses, the production and decay of the bound states of χ , such as 0-+ and 1-- states, ηD and ϒD, is an important search channel. We show that e+e-→ηD+V or ϒD+γ production at B factories for αD>0.1 is sufficiently strong to result in multiple pairs of charged leptons and pions via ηD→2 V →2 (l+l-) and ϒD→3 V →3 (l+l-) (l =e ,μ ,π ). The absence of such final states in the existing searches performed at BABAR and Belle sets new constraints on the parameter space of the model. We also show that a search for multiple bremsstrahlung of dark force mediators, e+e-→χ χ ¯+n V , resulting in missing energy and multiple leptons, will further improve the sensitivity to self-interacting dark matter.

Probing the Dark Sector with Dark Matter Bound States.

PubMed

An, Haipeng; Echenard, Bertrand; Pospelov, Maxim; Zhang, Yue

2016-04-15

A model of the dark sector where O(few  GeV) mass dark matter particles χ couple to a lighter dark force mediator V, m_{V}≪m_{χ}, is motivated by the recently discovered mismatch between simulated and observed shapes of galactic halos. Such models, in general, provide a challenge for direct detection efforts and collider searches. We show that for a large range of coupling constants and masses, the production and decay of the bound states of χ, such as 0^{-+} and 1^{--} states, η_{D} and ϒ_{D}, is an important search channel. We show that e^{+}e^{-}→η_{D}+V or ϒ_{D}+γ production at B factories for α_{D}>0.1 is sufficiently strong to result in multiple pairs of charged leptons and pions via η_{D}→2V→2(l^{+}l^{-}) and ϒ_{D}→3V→3(l^{+}l^{-}) (l=e,μ,π). The absence of such final states in the existing searches performed at BABAR and Belle sets new constraints on the parameter space of the model. We also show that a search for multiple bremsstrahlung of dark force mediators, e^{+}e^{-}→χχ[over ¯]+nV, resulting in missing energy and multiple leptons, will further improve the sensitivity to self-interacting dark matter.

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).

Engineered three-dimensional multicellular culture model to recapitulate morphogenetic fusion using human cells

EPA Science Inventory

Tissue fusion during early mammalian development requires crosstalk between multiple cell types. For example, paracrine signaling between palatal epithelial cells and palatal mesenchyme mediates the fusion of opposing palatal shelves during embryonic development. Fusion events in...

Testing Self-Segregation: Multiple-Group Structural Modeling of College Students' Interracial Friendship by Race

ERIC Educational Resources Information Center

Kim, Young K.; Park, Julie J.; Koo, Katie K.

2015-01-01

Using structural equation modeling, this study examined the effects of peer environments on collegiate interracial friendship and how such effects vary by students' race. The results show that the peer environment of Greek life mediated the relationship between structural diversity and interracial friendship in college, in that students…

Work–Family Conflict and Mental Health Among Female Employees: A Sequential Mediation Model via Negative Affect and Perceived Stress

PubMed Central

Zhou, Shiyi; Da, Shu; Guo, Heng; Zhang, Xichao

2018-01-01

After the implementation of the universal two-child policy in 2016, more and more working women have found themselves caught in the dilemma of whether to raise a baby or be promoted, which exacerbates work–family conflicts among Chinese women. Few studies have examined the mediating effect of negative affect. The present study combined the conservation of resources model and affective events theory to examine the sequential mediating effect of negative affect and perceived stress in the relationship between work–family conflict and mental health. A valid sample of 351 full-time Chinese female employees was recruited in this study, and participants voluntarily answered online questionnaires. Pearson correlation analysis, structural equation modeling, and multiple mediation analysis were used to examine the relationships between work–family conflict, negative affect, perceived stress, and mental health in full-time female employees. We found that women’s perceptions of both work-to-family conflict and family-to-work conflict were significant negatively related to mental health. Additionally, the results showed that negative affect and perceived stress were negatively correlated with mental health. The 95% confidence intervals indicated the sequential mediating effect of negative affect and stress in the relationship between work–family conflict and mental health was significant, which supported the hypothesized sequential mediation model. The findings suggest that work–family conflicts affected the level of self-reported mental health, and this relationship functioned through the two sequential mediators of negative affect and perceived stress. PMID:29719522

Work-Family Conflict and Mental Health Among Female Employees: A Sequential Mediation Model via Negative Affect and Perceived Stress.

PubMed

Zhou, Shiyi; Da, Shu; Guo, Heng; Zhang, Xichao

2018-01-01

After the implementation of the universal two-child policy in 2016, more and more working women have found themselves caught in the dilemma of whether to raise a baby or be promoted, which exacerbates work-family conflicts among Chinese women. Few studies have examined the mediating effect of negative affect. The present study combined the conservation of resources model and affective events theory to examine the sequential mediating effect of negative affect and perceived stress in the relationship between work-family conflict and mental health. A valid sample of 351 full-time Chinese female employees was recruited in this study, and participants voluntarily answered online questionnaires. Pearson correlation analysis, structural equation modeling, and multiple mediation analysis were used to examine the relationships between work-family conflict, negative affect, perceived stress, and mental health in full-time female employees. We found that women's perceptions of both work-to-family conflict and family-to-work conflict were significant negatively related to mental health. Additionally, the results showed that negative affect and perceived stress were negatively correlated with mental health. The 95% confidence intervals indicated the sequential mediating effect of negative affect and stress in the relationship between work-family conflict and mental health was significant, which supported the hypothesized sequential mediation model. The findings suggest that work-family conflicts affected the level of self-reported mental health, and this relationship functioned through the two sequential mediators of negative affect and perceived stress.

Childhood adversity and social functioning in psychosis: Exploring clinical and cognitive mediators.

PubMed

Palmier-Claus, Jasper; Berry, Katherine; Darrell-Berry, Hannah; Emsley, Richard; Parker, Sophie; Drake, Richard; Bucci, Sandra

2016-04-30

Childhood adversity may increase risk of impaired social functioning across the continuum of psychosis. However, the pathways by which adversity dictates functional outcome remain underexplored. This study investigated the association between childhood adversity and social functioning, and the clinical and cognitive mediators of this relationship. Fifty-four clinical (20 chronic, 20 first episode, 14 at ultra-high risk) and 120 non-clinical participants completed standardised questionnaires, semi-structured interviews and tests of theory of mind ability. The authors used multiple group structural equation modelling to fit mediation models allowing for differential relationships between the clinical and non-clinical samples. When examining each pathway separately, depression, paranoia and anxious attachment mediated the effect of childhood adversity on social functioning. In a combined model, depression was the only significant mediating variable with greater adversity predicting lower mood across groups. Childhood adversity did not significantly predict theory of mind ability in any of the models. This is the first study to indicate that childhood adversity acts on social functioning by increasing levels of depression, suggesting a common mechanism across the spectrum of psychosis. Clinical interventions should target low mood in order to improve social functioning at all stages of psychotic disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Vascular risk factor burden, atherosclerosis, and functional dependence in old age: a population-based study.

PubMed

Welmer, Anna-Karin; Liang, Yajun; Angleman, Sara; Santoni, Giola; Yan, Zhongrui; Cai, Chuanzhu; Qiu, Chengxuan

2014-08-01

Vascular risk factors such as hypertension and obesity have been associated with physical limitations among older adults. The purpose of this study is to examine whether individual and aggregated vascular risk factors (VRFs) are associated with functional dependence and to what extent carotid atherosclerosis (CAS) or peripheral artery disease (PAD) may mediate the possible associations of aggregated VRFs with functional dependence. This cross-sectional study included 1,451 community-living participants aged ≥60 years in the Confucius Hometown Aging Project of China. Data on demographic features, hypertension, high total cholesterol, obesity, smoking, physical inactivity, diabetes, CAS, PAD, and cardiovascular diseases (CVDs) were collected through an interview, a clinical examination, and laboratory tests. Functional dependence was defined as being dependent in at least one activity in the personal or instrumental activities of daily living. Data were analyzed using multiple logistic models controlling for potential confounders. We used the mediation model to explore the potential mediating effect of CAS and PAD on the associations of aggregated VRFs with functional dependence. Of the 1,451 participants, 222 (15.3%) had functional dependence. The likelihood of functional dependence increased linearly with increasing number of VRFs (hypertension, high total cholesterol, abdominal obesity, and physical inactivity) (p for trend <0.002). Mediation analysis showed that controlling for demographics and CVDs up to 11% of the total association of functional dependence with clustering VRFs was mediated by CAS and PAD. Aggregation of multiple VRFs is associated with an increased likelihood of functional dependence among Chinese older adults; the association is partially mediated by carotid and peripheral artery atherosclerosis independently of CVDs.

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.

The Interplay among BMI z-Score, Peer Victmization, and Self-Concept in Outpatient Children and Adolescents with Overweight or Obesity.

PubMed

Bacchini, Dario; Licenziati, Maria Rosaria; Affuso, Gaetana; Garrasi, Alessandra; Corciulo, Nicola; Driul, Daniela; Tanas, Rita; Fiumani, Perla Maria; Di Pietro, Elena; Pesce, Sabino; Crinò, Antonino; Maltoni, Giulio; Iughetti, Lorenzo; Sartorio, Alessandro; Deiana, Manuela; Lombardi, Francesca; Valerio, Giuliana

2017-06-01

Research has provided evidence that obesity is associated with peer victimization and low levels of self-concept. No study has examined the relationship between BMI z-score, self-concept in multiple domains, and peer victimization. The aim of the research was to investigate the interplay between BMI z-score, self-concept in multiple domains (physical, athletic, social), and peer victimization, testing direct, mediated, and moderated associations. Eighty hundred fifteen outpatient children and adolescents were consecutively recruited in 14 hospitals distributed over the Italian country. The sample consisted of 419 males and 396 females; mean age 10.91 ± 1.97 years (range 6-14 years) and mean BMI z-score 1.85 ± 0.74 (range -0.97 ± 3.27). Peer victimization and self-concept were assessed with a revised Olweus Bully/Victim Questionnaire and with the Self-Perception Profile for Children. A structural equation model approach was used to determine the associations among variables, testing two competing models. In both models, path analysis revealed that BMI z-score was directly associated with peer victimization and self-concept in multiple domains. In the first model, peer victimization mediated the relationship between BMI-score and self-concept, whereas in the alternative model, self-concept mediated the relationship between BMI z-score and peer victimization. Interaction analyses revealed that social competence moderated the relationship between BMI z-score and peer victimization and that peer victimization moderated the relationship between BMI z-score and physical appearance. Higher levels of BMI z-score are a risk factor for peer victimization and poor self-concept. When high levels of BMI z-score are associated with a negative self-concept, the risk of victimization increases. Preventive and supportive interventions are needed to avoid negative consequences on quality of life in children and adolescents with obesity.

Mediation analysis with multiple versions of the mediator.

PubMed

Vanderweele, Tyler J

2012-05-01

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

Mediation analysis with multiple versions of the mediator

PubMed Central

VanderWeele, Tyler J.

2013-01-01

The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well defined hypothetical interventions on the mediator. In many settings there may be multiple ways to fix the mediator to a particular value and these different hypothetical interventions may have very different implications for the outcome of interest. In this paper we consider mediation analysis when multiple versions of the mediator are present. Specifically, we consider the problem of attempting to decompose a total effect of an exposure on an outcome into the portion through the intermediate and the portion through other pathways. We consider the setting in which there are multiple versions of the mediator but the investigator only has access to data on the particular measurement, not which version of the mediator may have brought that value about. We show that the quantity that is estimated as a natural indirect effect using only the available data does indeed have an interpretation as a particular type of mediated effect; however, the quantity estimated as a natural direct effect in fact captures both a true direct effect and an effect of the exposure on the outcome mediated through the effect of the version of the mediator that is not captured by the mediator measurement. The results are illustrated using two examples from the literature, one in which the versions of the mediator are unknown and another in which the mediator itself has been dichotomized. PMID:22475830

Studies of transformational leadership in the consumer service workgroup: cooperative conflict resolution and the mediating roles of job satisfaction and change commitment.

PubMed

Yang, Yi-Feng

2012-10-01

The present paper evaluates the effect of transformational leadership on job satisfaction and change commitment along with their interconnected effects (mediation) on cooperative conflict resolution (management) in customer service activities in Taiwan. The multi-source samples consist of data from personnel serving at customer centers (workgroups), such as phone service personnel, customer representatives, financial specialists, and front-line salespeople. An empirical study was carried out using a multiple mediation procedure incorporating boot-strapping techniques and PRODCLIN2 with structural equation modeling (SEM) analysis. The results indicate that the main effect of the leadership style on cooperative conflict resolution is mediated by change commitment and job satisfaction.

Helminthic therapy: using worms to treat immune-mediated disease.

PubMed

Elliott, David E; Weinstock, Joel V

2009-01-01

There is an epidemic of immune-mediated disease in highly-developed industrialized countries. Such diseases, like inflammatory bowel disease, multiple sclerosis and asthma increase in prevalence as populations adopt modern hygienic practices. These practices prevent exposure to parasitic worms (helminths). Epidemiologic studies suggest that people who carry helminths have less immune-mediated disease. Mice colonized with helminths are protected from disease in models of colitis, encephalitis, Type 1 diabetes and asthma. Clinical trials show that exposure to helminths reduce disease activity in patients with ulcerative colitis or Crohn's disease. This chapter reviews some of the work showing that colonization with helminths alters immune responses, against dysregulated inflammation. These helminth-host immune interactions have potentially important implications for the treatment of immune-mediated diseases.

Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs.

PubMed

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

2016-03-01

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

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

PubMed

Bortvedt, Sarah F; Lund, P Kay

2012-03-01

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

Mediational Links Among Parenting Styles, Perceptions of Parental Confidence, Self-Esteem, and Depression on Alcohol-Related Problems in Emerging Adulthood*

PubMed Central

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

2009-01-01

Objective: Depression is often found to be comorbid with alcohol-related problems. Parental overprotection, which may be of particular importance during emerging adulthood, has been linked to internalizing symptoms in offspring. This article evaluates the impact of parenting styles and parental confidence in their offspring on an internalizing pathway to alcohol-related problems through self-esteem and depression. Method: Mediational links were tested among parenting styles (authoritative, authoritarian, permissive), parental confidence (overprotection, autonomy), self-esteem, depression, and alcohol-related problems. A two-group, multiple indicator multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. Results: Overall, having a father who was confident in his child's ability to make autonomous decisions was protective against depression for both genders. Perceptions of paternal autonomy mediated the impact of the fathers' parenting styles (authoritative, permissive) on depression for both genders. For men, parental overprotection mediated the impact of an authoritarian father on self-esteem, and self-esteem mediated the impact of parental overprotection on depression. Moreover, among men, perceptions of maternal autonomy mediated the impact of the mothers' parenting styles (authoritative, permissive) on self-esteem, and self-esteem mediated the impact of maternal autonomy on depression. Conclusions: The current pattern of findings is distinct from pathways through behavioral undercontrol with influences from the same-sex parent for both genders. These findings indicate that parenting may have differential influences on internalizing pathways to alcohol-related problems. PMID:19261233

Mediational links among parenting styles, perceptions of parental confidence, self-esteem, and depression on alcohol-related problems in emerging adulthood.

PubMed

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

2009-03-01

Depression is often found to be comorbid with alcohol-related problems. Parental overprotection, which may be of particular importance during emerging adulthood, has been linked to internalizing symptoms in offspring. This article evaluates the impact of parenting styles and parental confidence in their offspring on an internalizing pathway to alcohol-related problems through self-esteem and depression. Mediational links were tested among parenting styles (authoritative, authoritarian, permissive), parental confidence (overprotection, autonomy), self-esteem, depression, and alcohol-related problems. A two-group, multiple indicator multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. Overall, having a father who was confident in his child's ability to make autonomous decisions was protective against depression for both genders. Perceptions of paternal autonomy mediated the impact of the fathers' parenting styles (authoritative, permissive) on depression for both genders. For men, parental overprotection mediated the impact of an authoritarian father on self-esteem, and self-esteem mediated the impact of parental overprotection on depression. Moreover, among men, perceptions of maternal autonomy mediated the impact of the mothers' parenting styles (authoritative, permissive) on self-esteem, and self-esteem mediated the impact of maternal autonomy on depression. The current pattern of findings is distinct from pathways through behavioral undercontrol with influences from the same-sex parent for both genders. These findings indicate that parenting may have differential influences on internalizing pathways to alcohol-related problems.

Proteomic analysis of lung tissue by DIGE

USDA-ARS?s Scientific Manuscript database

Lungs perform an essential physiological function, mediated by a complex series of events that involve the coordination of multiple cell types to support not only gaseous exchange, but homeostasis and protection from infection. Guinea pigs are an important animal disease model for a number of infect...

Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity.

PubMed

Feyerabend, Thorsten B; Weiser, Anne; Tietz, Annette; Stassen, Michael; Harris, Nicola; Kopf, Manfred; Radermacher, Peter; Möller, Peter; Benoist, Christophe; Mathis, Diane; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2011-11-23

Immunological functions of mast cells remain poorly understood. Studies in Kit mutant mice suggest key roles for mast cells in certain antibody- and T cell-mediated autoimmune diseases. However, Kit mutations affect multiple cell types of both immune and nonimmune origin. Here, we show that targeted insertion of Cre-recombinase into the mast cell carboxypeptidase A3 locus deleted mast cells in connective and mucosal tissues by a genotoxic Trp53-dependent mechanism. Cre-mediated mast cell eradication (Cre-Master) mice had, with the exception of a lack of mast cells and reduced basophils, a normal immune system. Cre-Master mice were refractory to IgE-mediated anaphylaxis, and this defect was rescued by mast cell reconstitution. This mast cell-deficient strain was fully susceptible to antibody-induced autoimmune arthritis and to experimental autoimmune encephalomyelitis. Differences comparing Kit mutant mast cell deficiency models to selectively mast cell-deficient mice call for a systematic re-evaluation of immunological functions of mast cells beyond allergy. Copyright © 2011 Elsevier Inc. All rights reserved.

The relation between perceived parental involvement and academic achievement: the roles of Taiwanese students' academic beliefs and filial piety.

PubMed

Chen, Wei-Wen; Ho, Hsiu-Zu

2012-01-01

The excellent academic performance among East-Asian students has drawn international attention from educators and psychologists. However, the process that underlies student academic achievement for this particular group has rarely been documented. The present study examines how the relation between perceived parental involvement and Taiwanese students' academic achievement is mediated by student academic beliefs (i.e., beliefs about effort, academic self-concept, and perceived control). The study further explores whether this mediating effect varies with types of filial piety. Participants were 468 first-year students from colleges and universities in Taiwan. Multiple-group mediating models were analyzed using structural equation modeling (SEM). Results indicated that, for the Taiwanese sample, students' academic beliefs mediated the relation between perceived parental involvement and academic achievement. Furthermore, the mediational effect was significant for the reciprocal filial type, but not for the authoritarian filial type. The importance of the quality of the parent-child relationship and the internalization process related to children's assumptions of their parents' educational values indicate the need for a contextual view when examining predictors of student academic achievement.

Workplace Bullying and Work Engagement: A Self-Determination Model.

PubMed

Goodboy, Alan K; Martin, Matthew M; Bolkan, San

2017-06-01

This study modeled motivational mechanisms that explain the negative effects of workplace bullying on work engagement. Guided by self-determination theory, workplace bullying was predicted to decrease worker engagement indirectly, due to the denial of employees' basic psychological needs and their intrinsic motivation to work. From a sample of 243 full-time employees, serial multiple mediation models revealed that the indirect relationships between workplace bullying and work engagement (i.e., vigor, dedication, absorption) were serially mediated by basic psychological needs and intrinsic motivation to work. In support of self-determination theory, this study revealed that workplace bullying indirectly disengages employees from their work by denying them of their autonomy and relatedness needs and thwarting their motivation to perform work in a fulfilling way.

Directly detecting isospin-violating dark matter

NASA Astrophysics Data System (ADS)

Kelso, Chris; Kumar, Jason; Marfatia, Danny; Sandick, Pearl

2018-03-01

We consider the prospects for multiple dark matter direct detection experiments to determine if the interactions of a dark matter candidate are isospin-violating. We focus on theoretically well-motivated examples of isospin-violating dark matter (IVDM), including models in which dark matter interactions with nuclei are mediated by a dark photon, a Z , or a squark. We determine that the best prospects for distinguishing IVDM from the isospin-invariant scenario arise in the cases of dark photon-or Z -mediated interactions, and that the ideal experimental scenario would consist of large exposure xenon- and neon-based detectors. If such models just evade current direct detection limits, then one could distinguish such models from the standard isospin-invariant case with two detectors with of order 100 ton-year exposure.

Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

PubMed

Khdair, Ayman; Chen, Di; Patil, Yogesh; Ma, Linan; Dou, Q Ping; Shekhar, Malathy P V; Panyam, Jayanth

2010-01-25

Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors. Copyright 2009 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-02-01

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

Socioeconomic Associations with ADHD: Findings from a Mediation Analysis.

PubMed

Russell, Abigail Emma; Ford, Tamsin; Russell, Ginny

2015-01-01

Children from disadvantaged socioeconomic backgrounds are at greater risk of a range of negative outcomes throughout their life course than their peers; however the specific mechanisms by which socioeconomic status relates to different health outcomes in childhood are as yet unclear. The current study investigates the relationship between socioeconomic disadvantage in childhood and attention deficit/hyperactivity disorder (ADHD), and investigates putative mediators of this association in a longitudinal population-based birth cohort in the UK. Data from the Avon Longitudinal Study of Parents and Children was used (n = 8,132) to explore the relationship between different measures of socioeconomic status at birth-3 years and their association with a diagnosis of ADHD at age 7. A multiple mediation model was utilised to examine factors occurring between these ages that may mediate the association. Financial difficulties, housing tenure, maternal age at birth of child and marital status were significantly associated with an outcome of ADHD, such that families either living in financial difficulty, living in council housing, with younger or single mothers' were more likely to have a child with a research diagnosis of ADHD at age 7. Financial difficulties was the strongest predictor of ADHD (OR 2.23 95% CI 1.57-3.16). In the multiple mediation model, involvement in parenting at age 6 and presence of adversity at age 2-4 mediated 27.8% of the association. Socioeconomic disadvantage, conceptualised as reported difficulty in affording basic necessities (e.g. heating, food) has both direct and indirect impacts on a child's risk of ADHD. Lower levels of parent involvement mediates this association, as does presence of adversity; with children exposed to adversity and those with less involved parents being at an increased risk of having ADHD. This study highlights the importance of home and environmental factors as small but important contributors toward the aetiology of ADHD.

Developmental Pathways from Childhood Aggression-Disruptiveness, Chronic Peer Rejection and Deviant Friendships to Early-Adolescent Rule Breaking

PubMed Central

Ettekal, Idean; Ladd, Gary W.

2015-01-01

Childhood aggression-disruptiveness, chronic peer rejection, and deviant friendships were examined as predictors of early-adolescent rule breaking behaviors. Using a sample of 383 children (193 girls and 190 boys) who were followed from ages 6 to 14, peer rejection trajectories were identified and incorporated into a series of alternative models to assess how chronic peer rejection and deviant friendships mediate the association between stable childhood aggression-disruptiveness and early-adolescent rule breaking. There were multiple mediated pathways to rule breaking that included both behavioral and relational risk factors and findings were consistent for boys and girls. Results have implications for better understanding the influence of multiple social processes in the continuity of antisocial behaviors from middle childhood to early adolescence. PMID:25403544

Emerging functions of multi-protein complex Mediator with special emphasis on plants.

PubMed

Malik, Naveen; Agarwal, Pinky; Tyagi, Akhilesh

2017-10-01

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

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

PubMed

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

2017-10-01

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

The association of adverse childhood experiences with mid-life depressive symptoms and quality of life among incarcerated males: exploring multiple mediation.

PubMed

Skarupski, Kimberly A; Parisi, Jeanine M; Thorpe, Roland; Tanner, Elizabeth; Gross, Deborah

2016-01-01

To explore the association of experiencing death, trauma, and abuse during childhood with depressive symptoms and quality of life at mid-life among incarcerated men and to understand how current social support and coping strategies mediate the impact of childhood trauma histories on mental health. Study participants were 192 male inmates in a maximum security prison. Participants completed measures of adverse childhood experiences related to death, trauma, and abuse, and depressive symptoms and quality of life. Data were analyzed using multiple mediation modeling. Men who reported having experienced adverse childhood experiences reported more depressive symptoms and lower quality of life than their counterparts. The results showed that in models both unadjusted and adjusted for age, race, education, number of years served, and whether the inmate had a life sentence, the association between adverse childhood experiences and quality of life were partially explained by the total of the indirect effects (point estimate = -.5052; CI.95 = -1.0364, -.0429 and point estimate = -.7792; CI.95 = -1.6369, -.0381), primarily via social support. However, the associations between adverse childhood experiences and depressive symptoms were not explained by social support and coping. Adverse childhood experiences are associated with deleterious mental health effects in later life. Social support and coping partially mediate the association between adverse childhood experiences and quality of life. The high prevalence of childhood trauma among aging prison inmates warrants attention to increasing social support mechanisms to improve mental health.

Effective connectivity during processing of facial affect: evidence for multiple parallel pathways.

PubMed

Dima, Danai; Stephan, Klaas E; Roiser, Jonathan P; Friston, Karl J; Frangou, Sophia

2011-10-05

The perception of facial affect engages a distributed cortical network. We used functional magnetic resonance imaging and dynamic causal modeling to characterize effective connectivity during explicit (conscious) categorization of affective stimuli in the human brain. Specifically, we examined the modulation of connectivity from posterior regions of the face-processing network to the lateral ventral prefrontal cortex (VPFC) during affective categorization and we tested for a potential role of the amygdala (AMG) in mediating this modulation. We found that explicit processing of facial affect led to prominent modulation (increase) in the effective connectivity from the inferior occipital gyrus (IOG) to the VPFC, while there was less evidence for modulation of the afferent connections from fusiform gyrus and AMG to VPFC. More specifically, the forward connection from IOG to the VPFC exhibited a selective increase under anger (as opposed to fear or sadness). Furthermore, Bayesian model comparison suggested that the modulation of afferent connections to the VPFC was mediated directly by facial affect, as opposed to an indirect modulation mediated by the AMG. Our results thus suggest that affective information is conveyed to the VPFC along multiple parallel pathways and that AMG activity is not sufficient to account for the gating of information transfer to the VPFC during explicit emotional processing.

Local adaptation in migrated interior Douglas-fir seedlings is mediated by ectomycorrhizas and other soil factors.

PubMed

Pickles, Brian J; Twieg, Brendan D; O'Neill, Gregory A; Mohn, William W; Simard, Suzanne W

2015-08-01

Separating edaphic impacts on tree distributions from those of climate and geography is notoriously difficult. Aboveground and belowground factors play important roles, and determining their relative contribution to tree success will greatly assist in refining predictive models and forestry strategies in a changing climate. In a common glasshouse, seedlings of interior Douglas-fir (Pseudotsuga menziesii var. glauca) from multiple populations were grown in multiple forest soils. Fungicide was applied to half of the seedlings to separate soil fungal and nonfungal impacts on seedling performance. Soils of varying geographic and climatic distance from seed origin were compared, using a transfer function approach. Seedling height and biomass were optimized following seed transfer into drier soils, whereas survival was optimized when elevation transfer was minimised. Fungicide application reduced ectomycorrhizal root colonization by c. 50%, with treated seedlings exhibiting greater survival but reduced biomass. Local adaptation of Douglas-fir populations to soils was mediated by soil fungi to some extent in 56% of soil origin by response variable combinations. Mediation by edaphic factors in general occurred in 81% of combinations. Soil biota, hitherto unaccounted for in climate models, interacts with biogeography to influence plant ranges in a changing climate. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

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

PubMed

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

2018-01-01

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

Inverse odds ratio-weighted estimation for causal mediation analysis.

PubMed

Tchetgen Tchetgen, Eric J

2013-11-20

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

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.

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…

Antisense oligonucleotide–mediated MDM4 exon 6 skipping impairs tumor growth

PubMed Central

Dewaele, Michael; Tabaglio, Tommaso; Willekens, Karen; Bezzi, Marco; Teo, Shun Xie; Low, Diana H.P.; Koh, Cheryl M.; Rambow, Florian; Fiers, Mark; Rogiers, Aljosja; Radaelli, Enrico; Al-Haddawi, Muthafar; Tan, Soo Yong; Hermans, Els; Amant, Frederic; Yan, Hualong; Lakshmanan, Manikandan; Koumar, Ratnacaram Chandrahas; Lim, Soon Thye; Derheimer, Frederick A.; Campbell, Robert M.; Bonday, Zahid; Tergaonkar, Vinay; Shackleton, Mark; Blattner, Christine; Marine, Jean-Christophe; Guccione, Ernesto

2015-01-01

MDM4 is a promising target for cancer therapy, as it is undetectable in most normal adult tissues but often upregulated in cancer cells to dampen p53 tumor-suppressor function. The mechanisms that underlie MDM4 upregulation in cancer cells are largely unknown. Here, we have shown that this key oncogenic event mainly depends on a specific alternative splicing switch. We determined that while a nonsense-mediated, decay-targeted isoform of MDM4 (MDM4-S) is produced in normal adult tissues as a result of exon 6 skipping, enhanced exon 6 inclusion leads to expression of full-length MDM4 in a large number of human cancers. Although this alternative splicing event is likely regulated by multiple splicing factors, we identified the SRSF3 oncoprotein as a key enhancer of exon 6 inclusion. In multiple human melanoma cell lines and in melanoma patient–derived xenograft (PDX) mouse models, antisense oligonucleotide–mediated (ASO-mediated) skipping of exon 6 decreased MDM4 abundance, inhibited melanoma growth, and enhanced sensitivity to MAPK-targeting therapeutics. Additionally, ASO-based MDM4 targeting reduced diffuse large B cell lymphoma PDX growth. As full-length MDM4 is enhanced in multiple human tumors, our data indicate that this strategy is applicable to a wide range of tumor types. We conclude that enhanced MDM4 exon 6 inclusion is a common oncogenic event and has potential as a clinically compatible therapeutic target. PMID:26595814

Husbands’ perceptions of their wives’ breast cancer coping efficacy: testing congruence models of adjustment

PubMed Central

Martinez Sanchez, MaryAnn

2018-01-01

Introduction Recent reviews have reinforced the notion that having a supportive spouse can help with the process of coping with and adjusting to cancer. Congruence between spouses’ perspectives has been proposed as one mechanism in that process, yet alternative models of congruence have not been examined closely. This study assessed alternative models of congruence in perceptions of coping and their mediating effects on adjustment to breast cancer. Methods Seventy-two women in treatment for breast cancer and their husbands completed measures of marital adjustment, self-efficacy for coping, and adjustment to cancer. Karnofsky Performance Status was obtained from medical records. Wives completed a measure of self-efficacy for coping (wives’ ratings of self-efficacy for coping [WSEC]) and husbands completed a measure of self-efficacy for coping (husbands’ ratings of wives’ self-efficacy for coping [HSEC]) based on their perceptions of their wives’ coping efficacy. Results Interestingly, the correlation between WSEC and HSEC was only 0.207; thus, they are relatively independent perspectives. The following three models were tested to determine the nature of the relationship between WSEC and HSEC: discrepancy model (WSEC − HSEC), additive model (WSEC + HSEC), and multiplicative model (WSEC × HSEC). The discrepancy model was not related to wives’ adjustment; however, the additive (B=0.205, P<0.001) and multiplicative (B=0.001, P<0.001) models were significantly related to wives’ adjustment. Also, the additive model mediated the relationship between performance status and adjustment. Discussion Husbands’ perception of their wives’ coping efficacy contributed marginally to their wives’ adjustment, and the combination of WSEC and HSEC mediated the relationship between functional status and wives’ adjustment, thus positively impacting wives’ adjustment to cancer. Future research is needed to determine the quality of the differences between HSEC and WSEC in order to develop interventions to optimize the impact of these two relatively independent perspectives on cancer outcomes. PMID:29491720

Husbands' perceptions of their wives' breast cancer coping efficacy: testing congruence models of adjustment.

PubMed

Merluzzi, Thomas V; Martinez Sanchez, MaryAnn

2018-01-01

Recent reviews have reinforced the notion that having a supportive spouse can help with the process of coping with and adjusting to cancer. Congruence between spouses' perspectives has been proposed as one mechanism in that process, yet alternative models of congruence have not been examined closely. This study assessed alternative models of congruence in perceptions of coping and their mediating effects on adjustment to breast cancer. Seventy-two women in treatment for breast cancer and their husbands completed measures of marital adjustment, self-efficacy for coping, and adjustment to cancer. Karnofsky Performance Status was obtained from medical records. Wives completed a measure of self-efficacy for coping (wives' ratings of self-efficacy for coping [WSEC]) and husbands completed a measure of self-efficacy for coping (husbands' ratings of wives' self-efficacy for coping [HSEC]) based on their perceptions of their wives' coping efficacy. Interestingly, the correlation between WSEC and HSEC was only 0.207; thus, they are relatively independent perspectives. The following three models were tested to determine the nature of the relationship between WSEC and HSEC: discrepancy model (WSEC - HSEC), additive model (WSEC + HSEC), and multiplicative model (WSEC × HSEC). The discrepancy model was not related to wives' adjustment; however, the additive ( B =0.205, P <0.001) and multiplicative ( B =0.001, P <0.001) models were significantly related to wives' adjustment. Also, the additive model mediated the relationship between performance status and adjustment. Husbands' perception of their wives' coping efficacy contributed marginally to their wives' adjustment, and the combination of WSEC and HSEC mediated the relationship between functional status and wives' adjustment, thus positively impacting wives' adjustment to cancer. Future research is needed to determine the quality of the differences between HSEC and WSEC in order to develop interventions to optimize the impact of these two relatively independent perspectives on cancer outcomes.

Understanding the Association Between Negative Life Events and Suicidal Risk in College Students: Examining Self-Compassion as a Potential Mediator.

PubMed

Chang, Edward C; Yu, Tina; Najarian, Alexandria S-M; Wright, Kaitlin M; Chen, Wenting; Chang, Olivia D; Du, Yifeng; Hirsch, Jameson K

2017-06-01

We tested a hypothesized model consistent with the notion that self-compassion mediates the association between negative life events and suicidal risk (viz., depressive symptoms and suicidal behaviors) in college students METHOD: The sample was comprised of 331 college students. Self-compassion facets (viz., self-kindness, self-judgment, common humanity, isolation, mindfulness, and overidentification) were used in testing for multiple mediation, controlling for sex. Common humanity, mindfulness, and overidentification were found to mediate the association between negative life events (NLE) and depressive symptoms. However, common humanity was found to be the only mediator of the association between NLE and suicidal behaviors. These findings suggest that there are specific facets of self-compassion that account for the association between NLE and suicidal risk in college students and that (loss of) common humanity plays a central role in this process. © 2016 Wiley Periodicals, Inc.

The mechanisms of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease

USDA-ARS?s Scientific Manuscript database

Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. Sirtuin 2 was previously shown to modulate proteotoxicity associated with age-associated neurodegenerative disorders such as Alzheimer and Parkinson disease (PD). However, the precise molecular mechanis...

Design, Development, and Validation of Learning Objects

ERIC Educational Resources Information Center

Nugent, Gwen; Soh, Leen-Kiat; Samal, Ashok

2006-01-01

A learning object is a small, stand-alone, mediated content resource that can be reused in multiple instructional contexts. In this article, we describe our approach to design, develop, and validate Shareable Content Object Reference Model (SCORM) compliant learning objects for undergraduate computer science education. We discuss the advantages of…

Communication: GAIMS—Generalized Ab Initio Multiple Spawning for both internal conversion and intersystem crossing processes

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

Curchod, Basile F. E.; Martínez, Todd J., E-mail: toddjmartinez@gmail.com; SLAC National Accelerator Laboratory, Menlo Park, California 94025

2016-03-14

Full multiple spawning is a formally exact method to describe the excited-state dynamics of molecular systems beyond the Born-Oppenheimer approximation. However, it has been limited until now to the description of radiationless transitions taking place between electronic states with the same spin multiplicity. This Communication presents a generalization of the full and ab initio multiple spawning methods to both internal conversion (mediated by nonadiabatic coupling terms) and intersystem crossing events (triggered by spin-orbit coupling matrix elements) based on a spin-diabatic representation. The results of two numerical applications, a model system and the deactivation of thioformaldehyde, validate the presented formalism andmore » its implementation.« less

Communication: GAIMS—generalized ab initio multiple spawning for both internal conversion and intersystem crossing processes

DOE PAGES

Curchod, Basile F. E.; Rauer, Clemens; Marquetand, Philipp; ...

2016-03-11

Full Multiple Spawning is a formally exact method to describe the excited-state dynamics of molecular systems beyond the Born-Oppenheimer approximation. However, it has been limited until now to the description of radiationless transitions taking place between electronic states with the same spin multiplicity. This Communication presents a generalization of the full and ab initio Multiple Spawning methods to both internal conversion (mediated by nonadiabatic coupling terms) and intersystem crossing events (triggered by spin-orbit coupling matrix elements) based on a spin-diabatic representation. Lastly, the results of two numerical applications, a model system and the deactivation of thioformaldehyde, validate the presented formalismmore » and its implementation.« less

Distinguishing Signatures of Multipathway Conformational Transitions

NASA Astrophysics Data System (ADS)

Pierse, Christopher A.; Dudko, Olga K.

2017-02-01

The folding and binding of biomolecules into functional conformations are thought to be commonly mediated by multiple pathways rather than a unique route. Yet even in experiments where one can "see" individual conformational transitions, their stochastic nature generally precludes one from determining whether the transitions occurred through one or multiple pathways. We establish model-free, observable signatures in the response of macromolecules to force that unambiguously identify multiple pathways—even when the pathways themselves cannot be resolved. The unified analytical description reveals that, through multiple pathways, the response of molecules to external forces can be shaped in diverse ways, resulting in a rich design space for a tailored biological function already at the single-molecule level.

Trauma exposure and cigarette smoking: the impact of negative affect and affect-regulatory smoking motives.

PubMed

Farris, Samantha G; Zvolensky, Michael J; Beckham, Jean C; Vujanovic, Anka A; Schmidt, Norman B

2014-01-01

Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association.

Trauma Exposure and Cigarette Smoking: The Impact of Negative Affect and Affect-Regulatory Smoking Motives

PubMed Central

Farris, Samantha G.; Zvolensky, Michael J.; Beckham, Jean C.; Vujanovic, Anka A.; Schmidt, Norman B.

2014-01-01

Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association. PMID:25299617

Restricted reproductive rights and risky sexual behaviour: How political disenfranchisement relates to women's sense of control, well-being and sexual health.

PubMed

Msetfi, Rachel; Jay, Sarah; O'Donnell, Aisling T; Kearns, Michelle; Kinsella, Elaine L; McMahon, Jennifer; Muldoon, Orla T; Naughton, Catherine; Creaven, Ann-Marie

2018-02-01

Few studies have investigated the role of disenfranchisement and denial of agency in women's sexual health. To address this, a cross-sectional study of disenfranchisement, control (general and reproductive control) and health was conducted in Ireland, where abortion is severely restricted. Multiple mediation models ( N = 513 women) indicated that general but not reproductive control mediates the association between disenfranchisement and psychological well-being. Additionally, serial mediation shows disenfranchisement is associated with lower sense of control, which is linked to poorer well-being and risky sexual behaviour. Disenfranchisement arising from socio-political contexts may have important implications for women's sexual health.

Suppression of immune-mediated liver injury after vaccination with attenuated pathogenic cells.

PubMed

Mei, Yunhua; Wang, Ying; Xu, Lingyun

2007-05-15

Cell vaccination via immunization with attenuated pathogenic cells is an effective preventive method that has been successfully applied in several animal models of inflammatory or autoimmune diseases. Concanavalin A (Con A)-induced hepatitis (CIH) is a commonly used experimental model to study immune-mediated liver injury. Multiple cell types including T lymphocytes, macrophages and neutrophils have been found to be involved in the pathogenesis of CIH. In this study, we used attenuated spleen lymphocytes or peripheral blood lymphocytes as vaccines to investigate whether they could induce protective immune responses to prevent mice from developing CIH. We found that mice receiving such vaccination before CIH induction developed much milder diseases, exhibited a lower level of alanine aminotransferase (ALT) released into their plasma and had less inflammatory lesions in their livers. Such CIH-suppression is dose- and frequency-dependent. The suppressive effect was associated with inhibition of several major inflammatory mediators, pro-inflammatory cytokines and chemokines.

Sequence determinants of improved CRISPR sgRNA design.

PubMed

Xu, Han; Xiao, Tengfei; Chen, Chen-Hao; Li, Wei; Meyer, Clifford A; Wu, Qiu; Wu, Di; Cong, Le; Zhang, Feng; Liu, Jun S; Brown, Myles; Liu, X Shirley

2015-08-01

The CRISPR/Cas9 system has revolutionized mammalian somatic cell genetics. Genome-wide functional screens using CRISPR/Cas9-mediated knockout or dCas9 fusion-mediated inhibition/activation (CRISPRi/a) are powerful techniques for discovering phenotype-associated gene function. We systematically assessed the DNA sequence features that contribute to single guide RNA (sgRNA) efficiency in CRISPR-based screens. Leveraging the information from multiple designs, we derived a new sequence model for predicting sgRNA efficiency in CRISPR/Cas9 knockout experiments. Our model confirmed known features and suggested new features including a preference for cytosine at the cleavage site. The model was experimentally validated for sgRNA-mediated mutation rate and protein knockout efficiency. Tested on independent data sets, the model achieved significant results in both positive and negative selection conditions and outperformed existing models. We also found that the sequence preference for CRISPRi/a is substantially different from that for CRISPR/Cas9 knockout and propose a new model for predicting sgRNA efficiency in CRISPRi/a experiments. These results facilitate the genome-wide design of improved sgRNA for both knockout and CRISPRi/a studies. © 2015 Xu et al.; Published by Cold Spring Harbor Laboratory Press.

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.

Direct evaluation of Pseudomonas aeruginosa biofilm mediators in a chronic infection model.

PubMed

Byrd, Matthew S; Pang, Bing; Hong, Wenzhou; Waligora, Elizabeth A; Juneau, Richard A; Armbruster, Chelsie E; Weimer, Kristen E D; Murrah, Kyle; Mann, Ethan E; Lu, Haiping; Sprinkle, April; Parsek, Matthew R; Kock, Nancy D; Wozniak, Daniel J; Swords, W Edward

2011-08-01

Biofilms contribute to Pseudomonas aeruginosa persistence in a variety of diseases, including cystic fibrosis, burn wounds, and chronic suppurative otitis media. However, few studies have directly addressed P. aeruginosa biofilms in vivo. We used a chinchilla model of otitis media, which has previously been used to study persistent Streptococcus pneumoniae and Haemophilus influenzae infections, to show that structures formed in vivo are biofilms of bacterial and host origin within a matrix that includes Psl, a P. aeruginosa biofilm polysaccharide. We evaluated three biofilm and/or virulence mediators of P. aeruginosa known to affect biofilm formation in vitro and pathogenesis in vivo--bis-(3',5')-cyclic dimeric GMP (c-di-GMP), flagella, and quorum sensing--in a chinchilla model. We show that c-di-GMP overproduction has a positive impact on bacterial persistence, while quorum sensing increases virulence. We found no difference in persistence attributed to flagella. We conclude from these studies that a chinchilla otitis media model provides a means to evaluate pathogenic mediators of P. aeruginosa and that in vitro phenotypes should be examined in multiple infection systems to fully understand their role in disease.

Multiple templates-based homology modeling enhances structure quality of AT1 receptor: validation by molecular dynamics and antagonist docking.

PubMed

Sokkar, Pandian; Mohandass, Shylajanaciyar; Ramachandran, Murugesan

2011-07-01

We present a comparative account on 3D-structures of human type-1 receptor (AT1) for angiotensin II (AngII), modeled using three different methodologies. AngII activates a wide spectrum of signaling responses via the AT1 receptor that mediates physiological control of blood pressure and diverse pathological actions in cardiovascular, renal, and other cell types. Availability of 3D-model of AT1 receptor would significantly enhance the development of new drugs for cardiovascular diseases. However, templates of AT1 receptor with low sequence similarity increase the complexity in straightforward homology modeling, and hence there is a need to evaluate different modeling methodologies in order to use the models for sensitive applications such as rational drug design. Three models were generated for AT1 receptor by, (1) homology modeling with bovine rhodopsin as template, (2) homology modeling with multiple templates and (3) threading using I-TASSER web server. Molecular dynamics (MD) simulation (15 ns) of models in explicit membrane-water system, Ramachandran plot analysis and molecular docking with antagonists led to the conclusion that multiple template-based homology modeling outweighs other methodologies for AT1 modeling.

A multi-process model of self-regulation: influences of mindfulness, integrative self-knowledge and self-control in Iran.

PubMed

Ghorbani, Nima; Watson, P J; Farhadi, Mehran; Chen, Zhuo

2014-04-01

Self-regulation presumably rests upon multiple processes that include an awareness of ongoing self-experience, enduring self-knowledge and self-control. The present investigation tested this multi-process model using the Five-Facet Mindfulness Questionnaire (FFMQ) and the Integrative Self-Knowledge and Brief Self-Control Scales. Using a sample of 1162 Iranian university students, we confirmed the five-factor structure of the FFMQ in Iran and documented its factorial invariance across males and females. Self-regulatory variables correlated negatively with Perceived Stress, Depression, and Anxiety and positively with Self-Esteem and Satisfaction with Life. Partial mediation effects confirmed that self-regulatory measures ameliorated the disturbing effects of Perceived Stress. Integrative Self-Knowledge and Self-Control interacted to partially mediate the association of Perceived Stress with lower levels of Satisfaction with Life. Integrative Self-Knowledge, alone or in interaction with Self-Control, was the only self-regulation variable to display the expected mediation of Perceived Stress associations with all other measures. Self-Control failed to be implicated in self-regulation only in the mediation of Anxiety. These data confirmed the need to further examine this multi-process model of self-regulation. © 2014 International Union of Psychological Science.

Parents' stressful life events and adolescent depressed mood.

PubMed

Ge, X; Conger, R D; Lorenz, F O; Simons, R L

1994-03-01

The present study of 451 families living in the rural Midwest examines a mediational model of the relationship between the stressful life events experienced by parents and adolescent depressed mood. This model is intended to overcome two limitations in previous research on the relationship between parents' stressful events and adolescent depressed mood by 1) examining a mediating process involving parental mood and parenting behavior, and 2) using multiple informants to assess the theoretical constructs. Findings from the present study indicate that stressful life events experienced by parents are first related to parents' depressed mood which operates to disrupt skillful parenting practices. The disrupted parenting practices in turn place adolescents at increased risk for developing depressive symptoms. The results show that inclusion of these mediating processes represents a significant improvement over the bivariate model and that the hypothesized mediational model generalizes to four parent-adolescent dyads: fathers and sons, fathers and daughters, mothers and sons, and mothers and daughters. Moreover, parents' stressful life events are related directly to adolescent boys' depressed mood only when parents' reports are included in both theoretical constructs. When parents' reports are removed as an indicator for the adolescent depressed mood construct, the effects of parental stress on adolescent depressed mood are largely accounted for by stress-related parental depressed mood and harsh/inconsistent parenting.

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

PubMed Central

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

2017-01-01

Post-traumatic stress disorder (PTSD) symptoms can develop after person experiences one or more traumatic events. Little research, however, has been done on PTSD symptoms of patients with ovarian cancer. The present study aimed to estimate the prevalence of PTSD symptoms in patients with ovarian cancer in China; the effects of demographic and clinical variables on PTSD symptoms; multiple mediation roles in the association between social support and PTSD symptoms in patients with ovarian cancer in China. We collected demographic and clinical information of patients with ovarian cancer in the first and second hospitals of China Medical University between January 1, 2014 and December 31, 2015. Qualified patients were asked to complete the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Duke-UNC Functional Social Support Questionnaire, Herth Hope Index (HHI), and Resilience Scale-14 (RS-14). 201 patients provided responses. We performed hierarchical linear regression to assess the correlation between social support and PTSD symptoms and bootstrapping to test the mediating role of hope and resilience as potential mediators. After controlling demographic and clinical characteristics, social support negatively correlated with PTSD symptoms (β = -0.406, P < 0.01). Social support explained 14.7% of the variance in PTSD symptoms. Hope and resilience explained 17.0% of the variance in PTSD symptoms. The proportion of the hope mediating effect was 43.37% for social support and the proportion of the resilience mediating effect was 10.64% for social support. Hope and resilience partly mediated the correlation between social support and PTSD symptoms despite accounting for different proportions of the mediating effect. Future intervention plans should pay more attention to social support as well as hope and resilience to prevent, relieve and treat PTSD symptoms. PMID:28475593

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

PubMed

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

2017-01-01

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

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

PubMed

Park, Soojin; Kürüm, Esra

2018-05-20

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

Circuit QED with qutrits: Coupling three or more atoms via virtual-photon exchange

NASA Astrophysics Data System (ADS)

Zhao, Peng; Tan, Xinsheng; Yu, Haifeng; Zhu, Shi-Liang; Yu, Yang

2017-10-01

We present a model to describe a generic circuit QED system which consists of multiple artificial three-level atoms, namely, qutrits, strongly coupled to a cavity mode. When the state transition of the atoms disobeys the selection rules the process that does not conserve the number of excitations can happen determinatively. Therefore, we can realize coherent exchange interaction among three or more atoms mediated by the exchange of virtual photons. In addition, we generalize the one-cavity-mode mediated interactions to the multicavity situation, providing a method to entangle atoms located in different cavities. Using experimentally feasible parameters, we investigate the dynamics of the model including three cyclic-transition three-level atoms, for which the two lowest energy levels can be treated as qubits. Hence, we have found that two qubits can jointly exchange excitation with one qubit in a coherent and reversible way. In the whole process, the population in the third level of atoms is negligible and the cavity photon number is far smaller than 1. Our model provides a feasible scheme to couple multiple distant atoms together, which may find applications in quantum information processing.

Peer Victimization and Dating Violence Victimization: The Mediating Role of Loneliness, Depressed Mood, and Life Satisfaction.

PubMed

Cava, María-Jesús; Buelga, Sofía; Tomás, Inés

2018-03-01

Peer victimization and dating violence victimization have serious negative effects on adolescents' health, and they seem to be related. However, the mediating processes in this relationship have not been sufficiently analyzed. The purpose of this study was to analyze the direct and indirect relationships between peer victimization and dating violence victimization, considering the possible mediator role of loneliness, depressed mood, and life satisfaction. These relationships are analyzed in boys and girls, and in early and middle adolescence. From an initial sample of 1,038 Spanish adolescents, those who had or had had in the past 12 months a dating relationship (647 adolescents; 49.1% boys, M = 14.38, SD = 1.43) were included in this study. Multigroup structural equation modeling was used to test a double mediation model simultaneously for boys and girls, testing the invariance of the relationships among variables across genders. The same technique was used to test the model simultaneously for early and middle adolescence, testing the invariance of the relationships among variables across age groups. Results revealed a positive direct relationship between peer victimization and dating violence victimization, as well as the partial mediating role of loneliness and life satisfaction in this relationship. The mediator role of depressed mood was not supported. The same mediational model was confirmed in boys and girls, and in early and middle adolescence. These results highlight the important role of loneliness and life satisfaction to explain the link between peer victimization and dating violence victimization in adolescence. These findings may be useful for developing intervention programs aimed at preventing situations of multiple victimization during adolescence.

The relationship between childhood trauma and the severity of adulthood depression and anxiety symptoms in a clinical sample: The mediating role of cognitive emotion regulation strategies.

PubMed

Huh, Hyu Jung; Kim, Kyung Hee; Lee, Hee-Kyung; Chae, Jeong-Ho

2017-04-15

Childhood trauma is an important factor in adverse mental health outcomes, including depression and anxiety. The purpose of the present study was to evaluate a hypothesized model describing a pathway of childhood trauma and its influence on psychiatric symptoms in patients with depressive disorder. In this model, childhood trauma was positively associated with current depression and anxiety symptoms, which were mediated by a cognitive emotional regulation strategy. Patients with depressive disorder (n=585, 266 men, 316 women) completed the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Childhood Trauma Questionnaire (CTQ), and Cognitive Emotion Regulation Questionnaire (CERQ). We divided the cognitive emotion regulation strategies into adaptive and maladaptive strategies using a CERQ subscore. We employed structural equation modeling (SEM) and simple/multiple mediation analyses. The indirect effect of maladaptive strategies was significant in the relationship between overall childhood trauma and depression/anxiety severity, whereas the mediation effect of adaptive strategies was limited to depressive symptoms. With respect to specific types of trauma, maladaptive strategies mediated the association between emotional abuse and current depression/anxiety, while the mediation effect of adaptive strategies was limited to emotional neglect. This study's cross-sectional design does not allow establishment of causal relationships. Childhood trauma recall bias may be possible. These findings support the hypothesized model in which childhood trauma is associated with adulthood depression/anxiety symptoms in clinical samples, and mediated by emotion regulation strategies. These results suggest that cognitive emotion dysregulation is an important factor affecting depression/anxiety symptoms in patients with childhood trauma. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiple functions of the S-phase checkpoint mediator.

PubMed

Tanaka, Katsunori

2010-01-01

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

Parent-Reported Behavioral and Psychiatric Problems Mediate the Relationship between Sleep-Disordered Breathing and Cognitive Deficits in School-Aged Children.

PubMed

Smith, Dale L; Gozal, David; Hunter, Scott J; Kheirandish-Gozal, Leila

2017-01-01

Numerous studies over the past several decades have illustrated that children who suffer from sleep-disordered breathing (SDB) are at greater risk for cognitive, behavioral, and psychiatric problems. Although behavioral problems have been proposed as a potential mediator between SDB and cognitive functioning, these relationships have not been critically examined. This analysis is based on a community-based cohort of 1,115 children who underwent overnight polysomnography, and cognitive and behavioral phenotyping. Structural model of the relationships between SDB, behavior, and cognition, and two recently developed mediation approaches based on propensity score weighting and resampling were used to assess the mediational role of parent-reported behavior and psychiatric problems in the relationship between SDB and cognitive functioning. Multiple models utilizing two different SDB definitions further explored direct effects of SDB on cognition as well as indirect effects through behavioral pathology. All models were adjusted for age, sex, race, BMI z -score, and asthma status. Indirect effects of SDB through behavior problems were significant in all mediation models, while direct effects of SDB on cognition were not. The findings were consistent across different mediation procedures and remained essentially unaltered when different criteria for SDB, behavior, and cognition were used. Potential effects of SDB on cognitive functioning appear to occur through behavioral problems that are detectable in this pediatric population. Thus, early attentional or behavioral pathology may be implicated in the cognitive functioning deficits associated with SDB, and may present an early morbidity-related susceptibility biomarker.

Explaining socio-economic differences in intention to smoke among primary school children

PubMed Central

2014-01-01

Background Smoking prevalence is higher among low socio-economic status (LSES) groups, and this difference may originate from a higher intention to smoke in childhood. This study aims to identify factors that explain differences in intention to smoke between children living in high socio-economic status (HSES) and LSES neighbourhoods. Methods Cross-sectional data were derived from the baseline assessment of a smoking prevention intervention study. Dutch primary school children, aged 10 – 11 years (N = 2,612), completed a web-based questionnaire about their attitude, subjective norm, self-efficacy expectations, modelling and intention to smoke. Linear and logistic regression analyses were performed to assess potential individual cognitive (attitude, subjective norm and self-efficacy) and social environmental (modelling) mediators between SES and intention to smoke. Results Multiple mediation models indicated that modelling mediated the association between SES (B = -0.09 (p < 0.01)) and intention to smoke (B = 1.06 (p < 0.01)). Mainly the father, mother and other family members mediated this association. Gender did not moderate the association between SES and intention to smoke and the potential mediators indicating that there are no differences in mediating factors between boys and girls. Conclusions This study indicates that future smoking prevention studies may focus on the social environment to prevent smoking onset. However, replication of this study is warranted. Trial registration This study was approved by the Medical Ethics Committee of the Atrium-Orbis-Zuyd Hospital (NL32093.096.11 / MEC 11-T-25) and registered in the Dutch Trial Register (NTR3116). PMID:24555819

Fibrinogen signal transduction as a mediator and therapeutic target in inflammation: lessons from multiple sclerosis.

PubMed

Adams, R A; Schachtrup, C; Davalos, D; Tsigelny, I; Akassoglou, K

2007-01-01

The blood protein fibrinogen as a ligand for integrin and non-integrin receptors functions as the molecular nexus of coagulation, inflammation and immunity. Studies in animal models and in human disease have demonstrated that extravascular fibrinogen that is deposited in tissues upon vascular rupture is not merely a marker, but a mediator of diseases with an inflammatory component, such as rheumatoid arthritis, multiple sclerosis, sepsis, myocardial infarction and bacterial infection. The present article focuses on the recent discoveries of specific cellular targets and receptors for fibrinogen within tissues that have extended the role of fibrinogen from a coagulation factor to a regulator of inflammation and immunity. Fibrinogen has the potential for selective drug targeting that would target its proinflammatory properties without affecting its beneficial effects in hemostasis, since it interacts with different receptors to mediate blood coagulation and inflammation. Strategies to target receptors for fibrinogen and fibrin within the tissue microenvironment could reveal selective and disease-specific agents for therapeutic intervention in a variety of human diseases associated with fibrin deposition.

Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus.

PubMed

Sonoda, Mika; Shoji, Tetsuo; Kuwamura, Yukinobu; Okute, Yujiro; Naganuma, Toshihide; Shima, Hideaki; Motoyama, Koka; Morioka, Tomoaki; Mori, Katsuhito; Fukumoto, Shinya; Shioi, Atsushi; Shimono, Taro; Fujii, Hisako; Kabata, Daijiro; Shintani, Ayumi; Emoto, Masanori; Inaba, Masaaki

2017-06-29

Cognitive impairment is more prevalent in those with decreased kidney function. We tested a hypothesis that an increased homocysteine and/or cerebral small vessel diseases (SVDs) mediate the link between kidney and cognitive functions in a cross-sectional study in 143 type 2 diabetes patients without diagnosis of dementia or prior stroke. The exposure and outcome variables were estimated glomerular filtration rate (eGFR) and cognitive performance evaluated with Modified Mini-Mental State (3 MS) examination, respectively. The candidate mediators were plasma homocysteine concentration, and SVDs including silent cerebral infarction, cerebral microbleed, periventricular hyperintensity, and deep and subcortical white matter hyperintensity by magnetic resonance imaging. In multiple regression models adjusted for 12 potential confounders, eGFR was positively associated with 3 MS score, inversely with homocysteine, but not significantly with the presence of any type of SVD. The association of eGFR with 3 MS remained significant when each of the SVDs was added to the model, whereas it disappeared when homocysteine was included in place of SVD. Mediation analysis indicated nearly significant mediation of homocysteine (P = 0.062) but no meaningful mediations of SVDs (P = 0.842-0.930). Thus, homocysteine, not SVDs, was shown to be the possible mediator between kidney and cognitive functions in patients with type 2 diabetes mellitus.

Disentangling Sense of Coherence and Resilience in case of multiple traumas.

PubMed

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

2014-05-01

Depressive and anxiety disorders (DAD) are a major public health problem. Trauma endured during childhood is known to increase the risk of DAD in adulthood. We investigate the hypothesis that Sense of Coherence (SOC) is a mediator between childhood trauma and depressive and anxious symptoms (DAD) in adulthood. We also explore the nature (personality trait or aptitude) of SOC and attempt to disentangle the concepts of resilience and SOC. Former hidden children (FHC), the Jewish youths who spent World War II in various hideaway shelters across Nazi-occupied Europe, were compared with a control group. In each group we measured the presence of multiple traumas, the resilience with the Resilience Scale for Adults, the DAD with the Hopkins Symptoms Checklist and the SOC with the SOC-13 self-report questionnaire. We tested a mediated moderation model with childhood Trauma as the predictor; Adulthood trauma as the moderator; SOC as the mediator; and DAD as the outcome variable. Results were consistent with a sensitization model of DAD partially mediated by SOC. A first component of SOC was similar to an aptitude and another part of SOC was more similar to a personality trait. We are unable to differentiate if the sensitization process is a consequence of the nature of the trauma endured by FHC (long-standing exposure to extreme external events) or a consequence of the fact that this first trauma occurred during childhood. Our results could account for the controversial debate regarding the life time stability of SOC. Copyright © 2014 Elsevier B.V. All rights reserved.

Five-Factor Model of Personality and Organizational Commitment: The Mediating Role of Positive and Negative Affective States

ERIC Educational Resources Information Center

Panaccio, Alexandra; Vandenberghe, Christian

2012-01-01

Using a one-year longitudinal study of four components of organizational commitment (affective, normative, continuance-sacrifices, and continuance-alternatives) on a sample of employees from multiple organizations (N=220), we examined the relationships of employee Big-Five personality traits to employee commitment components, and the mediating…

Multiple ß-defensin genes are upregulated by the vitamin D pathway in cattle

USDA-ARS?s Scientific Manuscript database

Experimental models of bacterial and viral infections in cattle have suggested vitamin D has a role in innate immunity of cattle. The intracrine vitamin D pathway of bovine macrophages, however, has only been shown to activate a nitric oxide-mediated defense mechanism, as opposed to cathelicidin and...

A Community-Based Early Intervention Program for Toddlers with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Rollins, Pamela Rosenthal; Campbell, Michelle; Hoffman, Renee Thibodeau; Self, Kayli

2016-01-01

This study examined Pathways Early Autism Intervention, a community-based, parent-mediated, intensive behavioral and developmental intervention program for children with autism spectrum disorders that could be used as a model for state-funded early intervention programs. A single-subject, multiple-baseline, across-participants design was used.…

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

PubMed

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

2015-01-01

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

The relationship of social support with treatment adherence and weight loss in Latinos with type 2 diabetes.

PubMed

Marquez, Becky; Anderson, Andrea; Wing, Rena R; West, Delia S; Newton, Robert L; Meacham, Maria; Hazuda, Helen P; Peters, Anne; Montez, Maria G; Broyles, Stephanie T; Walker, Martha; Evans-Hudsnall, Gina

2016-03-01

Little is known about the effects of social support on weight loss in Latinos. This study determined whether sex moderated and treatment adherence mediated the association between social support and weight loss. Data from 278 Latino males and females with type 2 diabetes in the Intensive Lifestyle Intervention of the Look AHEAD trial were analyzed. Multivariable modeling tested for moderation and parallel multiple mediator modeling simultaneously tested the mediating effects of adherence to physical activity, diet, and session attendance on the relationship between baseline social support and percent weight loss at 1 year. Social support for physical activity (having family and friends join in physical activity) was related to weight loss. Adherence to physical activity was related to both social support for physical activity and weight loss. Sex did not moderate these relationships. Adherence to physical activity completely mediated the relationship between social support for physical activity and weight loss. Increasing companionship for physical activity may be an effective intervention strategy to promote behaviors important for weight loss among Latinos. © 2016 The Obesity Society.

The relationship of social support with treatment adherence and weight loss in Latinos with type 2 diabetes

PubMed Central

Marquez, Becky; Anderson, Andrea; Wing, Rena R.; West, Delia S.; Newton, Robert L.; Meacham, Maria; Hazuda, Helen P.; Peters, Anne; Montez, Maria G.; Broyles, Stephanie T.; Walker, Martha; Evans-Hudsnall, Gina

2016-01-01

Objective Little is known about the effects of social support on weight loss in Latinos. This study determined whether sex moderated and treatment adherence mediated the association between social support and weight loss. Methods Data from 278 Latino males and females with type 2 diabetes in the Intensive Lifestyle Intervention of the Look AHEAD trial were analyzed. Multivariable modeling tested for moderation and parallel multiple mediator modeling simultaneously tested the mediating effects of adherence to physical activity, diet, and session attendance on the relationship between baseline social support and percent weight loss at 1 year. Results Social support for physical activity (having family and friends join in physical activity) was related to weight loss. Adherence to physical activity was related to both social support for physical activity and weight loss. Sex did not moderate these relationships. Adherence to physical activity completely mediated the relationship between social support for physical activity and weight loss. Conclusion Increasing companionship for physical activity may be an effective intervention strategy to promote behaviors important for weight loss among Latinos. PMID:26833676

Multiple hypotheses testing of fish incidence patterns in an urbanized ecosystem

USGS Publications Warehouse

Chizinski, C.J.; Higgins, C.L.; Shavlik, C.E.; Pope, K.L.

2006-01-01

Ecological and evolutionary theories have focused traditionally on natural processes with little attempt to incorporate anthropogenic influences despite the fact that humans are such an integral part of virtually all ecosystems. A series of alternate models that incorporated anthropogenic factors and traditional ecological mechanisms of invasion to account for fish incidence patterns in urban lakes was tested. The models were based on fish biology, human intervention, and habitat characteristics. However, the only models to account for empirical patterns were those that included fish invasiveness, which incorporated species-specific information about overall tolerance and fecundity. This suggests that species-specific characteristics are more important in general distributional patterns than human-mediated dispersal. Better information of illegal stocking activities is needed to improve human-mediated models, and more insight into basic life history of ubiquitous species is needed to truly understand underlying mechanisms of biotic homogenization. ?? Springer 2005.

Early Adolescent Alcohol Use in Context: How Neighborhoods, Parents and Peers Impact Youth

PubMed Central

Trucco, Elisa M.; Colder, Craig R.; Wieczorek, William F.; Lengua, Liliana J.; Hawk, Larry W.

2014-01-01

Developmental-ecological models are useful for integrating risk factors across multiple contexts and conceptualizing mediational pathways for adolescent alcohol use; yet, these comprehensive models are rarely tested. This study used a developmental-ecological framework to investigate the influence of neighborhood, family, and peer contexts on alcohol use in early adolescence (N = 387). Results from a multi-informant longitudinal cross-lagged mediation path model suggested that high levels of neighborhood disadvantage were associated with high levels of alcohol use two years later via an indirect pathway that included exposure to delinquent peers and adolescent delinquency. Results also indicated that adolescent involvement with delinquent peers and alcohol use led to decrements in parenting, rather than being consequences of poor parenting. Overall, the study supported hypothesized relationships among key microsystems thought to influence adolescent alcohol use, and thus findings underscore the utility of developmental-ecological models of alcohol use. PMID:24621660

Perceived social support, hopefulness, and emotional regulations as mediators of the relationship between enacted stigma and post-traumatic growth among children affected by parental HIV/AIDS in rural China.

PubMed

Wei, Wei; Li, Xiaoming; Tu, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang

2016-01-01

Some previous studies have revealed a negative impact of enacted stigma on post-traumatic growth (PTG) of children affected by HIV/AIDS, but little is known about protective psychological factors that can mitigate the effect of enacted stigma on children's PTG. This study aims to examine the mediating effects of perceived social support, hopefulness, and emotional regulation on the relationship between enacted stigma and PTG among HIV-affected children. Cross-sectional data were collected from 790 children affected by parental HIV (382 girls, 408 boys) aged 6-17 years in 2012 in rural central China. Multiple regression was conducted to test the mediation model. The study found that the experience of enacted stigma had a negative effect on PTG among children affected by HIV/AIDS. Emotional regulation together with hopefulness and perceived social support mediated the impact of enacted stigma on PTG. Perceived social support, hopefulness, and emotional regulation offer multiple levels of protection that can mitigate the impact of enacted stigma on PTG. Results suggest that future psychological intervention programs should seek strategies to reduce the stigmatizing experience of these children and promote children's level of PTG, and health professionals should also emphasize the development of these protective psychological factors.

Assessing natural direct and indirect effects through multiple pathways.

PubMed

Lange, Theis; Rasmussen, Mette; Thygesen, Lau Caspar

2014-02-15

Within the fields of epidemiology, interventions research and social sciences researchers are often faced with the challenge of decomposing the effect of an exposure into different causal pathways working through defined mediator variables. The goal of such analyses is often to understand the mechanisms of the system or to suggest possible interventions. The case of a single mediator, thus implying only 2 causal pathways (direct and indirect) from exposure to outcome, has been extensively studied. By using the framework of counterfactual variables, researchers have established theoretical properties and developed powerful tools. However, in practical problems, it is not uncommon to have several distinct causal pathways from exposure to outcome operating through different mediators. In this article, we suggest a widely applicable approach to quantifying and ranking different causal pathways. The approach is an extension of the natural effect models proposed by Lange et al. (Am J Epidemiol. 2012;176(3):190-195). By allowing the analysis of distinct multiple pathways, the suggested approach adds to the capabilities of modern mediation techniques. Furthermore, the approach can be implemented using standard software, and we have included with this article implementation examples using R (R Foundation for Statistical Computing, Vienna, Austria) and Stata software (StataCorp LP, College Station, Texas).

What have we learned about GPER function in physiology and disease from knockout mice?

PubMed Central

Prossnitz, Eric R.; Hathaway, Helen J.

2015-01-01

Estrogens, predominantly 17β-estradiol, exert diverse effects throughout the body in both normal and patho-physiology, during development and in reproductive, metabolic, endocrine, cardiovascular, nervous, musculoskeletal and immune systems. Estrogen and its receptors also play important roles in carcinogenesis and therapy, particularly for breast cancer. In addition to the classical nuclear estrogen receptors (ERα and ERβ) that traditionally mediate predominantly genomic signaling, the G protein-coupled estrogen receptor GPER has become recognized as a critical mediator of rapid signaling in response to estrogen. Mouse models, and in particular knockout (KO) mice, represent an important approach to understand the functions of receptors in normal physiology and disease. Whereas ERα KO mice display multiple significant defects in reproduction and mammary gland development, ERβ KO phenotypes are more limited, and GPER KO exhibit no reproductive deficits. However, the study of GPER KO mice over the last six years has revealed that GPER deficiency results in multiple physiological alterations including obesity, cardiovascular dysfunction, insulin resistance and glucose intolerance. In addition, the lack of estrogen-mediated effects in numerous tissues of GPER KO mice, studied in vivo or ex vivo, including those of the cardiovascular, endocrine, nervous and immune systems, reveals GPER as a genuine mediator of estrogen action. Importantly, GPER KO mice have also revealed roles for GPER in breast carcinogenesis and metastasis. In combination with the supporting effects of GPER-selective ligands and GPER knockdown approaches, GPER KO mice demonstrate the therapeutic potential of targeting GPER activity in diseases as diverse as obesity, diabetes, multiple sclerosis, hypertension, atherosclerosis, myocardial infarction, stroke and cancer. PMID:26189910

Adolescent impulsivity and soft drink consumption: The role of parental regulation.

PubMed

Melbye, Elisabeth L; Bergh, Ingunn H; Hausken, Solveig E S; Sleddens, Ester F C; Glavin, Kari; Lien, Nanna; Bjelland, Mona

2016-01-01

The present study aimed to explore the process in which impulsivity might influence soft drink consumption in adolescents, addressing potential mediating effects of perceived parental regulation regarding unhealthy eating. A cross-sectional survey was performed among 440 13-15-year-olds in Eastern Norway. The survey questionnaire included measures of impulsivity, six types of maternal and paternal regulation (as perceived by the adolescents), and consumption of sugar-sweetened beverages (SSB). Parallel multiple-mediator analyses were performed to reveal potential mediating effects of perceived parental regulatory behaviors on the association between adolescent impulsivity and SSB consumption. Separate models were run for maternal and paternal regulation. Results from our model analyses (both maternal and paternal models) indicated that all the six measured parental regulatory behaviors jointly acted as mediators on the association between adolescent impulsivity and SSB consumption. However, only perceived maternal and paternal legitimacy of regulation showed a unique contribution to the mediated effect. This finding suggests that adolescents' perception of parental legitimate authority is of particular importance in explaining the relationship between impulsivity and unhealthy eating behaviors in adolescents. Future nutrition interventions targeting adolescents and their parents should take personal factors such as adolescents' level of impulsivity into account. Ultimately; what may be an appropriate approach to impulsive individuals and their parents may diverge from what may be an appropriate approach to less impulsive individuals and their parents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early Childhood Adversity and Pregnancy Outcomes

PubMed Central

Smith, Megan V.; Gotman, Nathan; Yonkers, Kimberly A.

2016-01-01

Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

Software Framework for Advanced Power Plant Simulations

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

John Widmann; Sorin Munteanu; Aseem Jain

2010-08-01

This report summarizes the work accomplished during the Phase II development effort of the Advanced Process Engineering Co-Simulator (APECS). The objective of the project is to develop the tools to efficiently combine high-fidelity computational fluid dynamics (CFD) models with process modeling software. During the course of the project, a robust integration controller was developed that can be used in any CAPE-OPEN compliant process modeling environment. The controller mediates the exchange of information between the process modeling software and the CFD software. Several approaches to reducing the time disparity between CFD simulations and process modeling have been investigated and implemented. Thesemore » include enabling the CFD models to be run on a remote cluster and enabling multiple CFD models to be run simultaneously. Furthermore, computationally fast reduced-order models (ROMs) have been developed that can be 'trained' using the results from CFD simulations and then used directly within flowsheets. Unit operation models (both CFD and ROMs) can be uploaded to a model database and shared between multiple users.« less

Model of early self-replication based on covalent complementarity for a copolymer of glycerate-3-phosphate and glycerol-3-phosphate

NASA Technical Reports Server (NTRS)

Weber, Arthur L.

1989-01-01

Glyceraldehyde-3-phosphate acts as the substrate in a model of early self-replication of a phosphodiester copolymer of glycerate-3-phosphate and glycerol-3-phosphate. This model of self-replication is based on covalent complementarity in which information transfer is mediated by a single covalent bond, in contrast to multiple weak interactions that establish complementarity in nucleic acid replication. This replication model is connected to contemporary biochemistry through its use of glyceraldehyde-3-phosphate, a central metabolite of glycolysis and photosynthesis.

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 resistance as well as novel modalities to overcome this chemoresistance. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-07-01

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

Explaining academic-track boys' underachievement in language grades: Not a lack of aptitude but students' motivational beliefs and parents' perceptions?

PubMed

Heyder, Anke; Kessels, Ursula; Steinmayr, Ricarda

2017-06-01

Boys earn lower grades in languages than girls. The expectancy-value model by Eccles et al. (, A series of books in psychology. Achievement and achievement motives. Psychological and sociological approaches, W.H. Freeman, San Francisco, CA, 76) is a comprehensive theoretical model for explaining gender differences in educational outcomes. In the past, most studies have focused on girls' disadvantage in math and science and on the role of the students' motivational beliefs. We aimed to explain boys' lower language grades by applying the expectancy-value model while taking into account students' motivational beliefs as well as their aptitude, prior achievement, and socializers' beliefs. In addition, we aimed at exploring the incremental contribution of each potential mediator. Five hundred and twenty German students (age M = 17 years; 58% female) and 374 parents (age M = 47 years). Student-reported ability self-concept (ASC) and task values, parents' perceptions of students' ability, students' prior achievement as reported by schools, and students' verbal intelligence test scores were all tested as mediators of the effect of gender on grades in German while controlling for parents' socioeconomic status. Single-mediator models and a multiple-mediator model were estimated using structural equation modelling. All variables proved to be relevant for explaining boys' underachievement in language grades. Whereas students' ASC, task values, prior achievement, and parents' perceptions mediated the gender effect, verbal intelligence was identified as a suppressor variable increasing the gender effect. Our results challenge the stereotypic belief that boys' lower grades are due to lower verbal aptitude. Rather, students' motivational beliefs and parents' perceptions seem critical factors. Implications for both future research and practice are discussed. © 2017 The British Psychological Society.

The mediating role of the home environment in relation to parental educational level and preschool children's screen time: a cross-sectional study.

PubMed

Määttä, Suvi; Kaukonen, Riikka; Vepsäläinen, Henna; Lehto, Elviira; Ylönen, Anna; Ray, Carola; Erkkola, Maijaliisa; Roos, Eva

2017-09-02

Previous studies suggest that preschoolers from low socioeconomic backgrounds engage in more screen time. Still, the factors in the social and physical home environment driving these differences in preschool children's screen time are poorly understood. This study examines potential home environment mediators in the associations between parental educational level and preschoolers' screen time. A total of 864 children aged 3-6 years and their parents participated in a cross-sectional DAGIS study in 2015-2016. Parents recorded their children's screen time in a diary (N = 823). For the analyses, the daily average screen time at home was calculated. Parental questionnaires (N = 808) assessed educational level and eight social and physical environment factors in the home (i.e., descriptive norm for children's screen time, parental screen use in front of children, parental importance for limiting children's screen time, parental attitude toward societal pressures for children's screen time, access to screens at home, parental self-efficacy for limiting children's screen time, satisfaction of children's screen time, and rules for limiting children's screen time). Parental education was grouped into low, middle, and high education. The associations were tested by conducting mediation analyses adjusted by season and children's sex and age. The significant mediators in the single-mediator models were included in the final multiple-mediator models. Of the potential eight mediators, the following four had a significant indirect association: descriptive norm for children's screen time, parental screen use in front of children, parental importance for limiting children's screen time, and parental attitude toward societal pressures for children's screen time. Parents with high education had lower descriptive norm and used fewer screens in front of children compared to parents with middle or low education, and in turn, these factors were associated with less screen time among children from parents with a higher education level. Parents with high education placed greater importance on limiting children's screen time and felt less societal pressures about children's screen time compared to parents with low education, and in turn, these factors were associated with less screen time among children from parents with a higher education level. Our study recognized multiple modifiable mediators in the associations between parental education and preschool children's screen time. When aiming to diminish socioeconomic status differences in preschool children's screen time, the focus should be on parental role models, attitudes, and norm related to children's screen time.

T Lymphocytes Do Not Directly Mediate the Protective Effect of Estrogen on Experimental Autoimmune Encephalomyelitis

PubMed Central

Polanczyk, Magdalena J.; Jones, Richard E.; Subramanian, Sandhya; Afentoulis, Michael; Rich, Cathleen; Zakroczymski, Melissa; Cooke, Paul; Vandenbark, Arthur A.; Offner, Halina

2004-01-01

Gender influences mediated by 17β-estradiol (E2) have been associated with susceptibility to and severity of autoimmune diseases such as diabetes, arthritis, and multiple sclerosis. In this regard, we have shown that estrogen receptor-α (Esr1) is crucial for the protective effect of 17β-estradiol (E2) in murine experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis. The expression of estrogen receptors among various immune cells (eg, T and B lymphocytes, antigen-presenting cells) suggests that the therapeutic effect of E2 is likely mediated directly through specific receptor binding. However, the target immune cell populations responsive to E2 treatment have not been identified. In the current study, we induced EAE in T-cell-deficient, severe combined immunodeficient mice or in immunocompetent mice with encephalitogenic T cells from wild-type Esr1+/+ or Esr1 knockout (Esr1−/−) donors and compared the protective E2 responses. The results showed that E2-responsive, Esr1+/+ disease-inducing encephalitogenic T cells were neither necessary nor sufficient for E2-mediated protection from EAE. Instead, the therapeutic response appeared to be mediated through direct effects on nonlymphocytic, E2-responsive cells and down-regulation of the inflammatory response in the central nervous system. These results provide the first demonstration that the protective effect of E2 on EAE is not mediated directly through E2-responsive T cells and raise the alternative possibility that nonlymphocytic cells such as macrophages, dendritic cells, or other nonlymphocytic cells are primarily responsive to E2 treatment in EAE. PMID:15579449

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.

A mediational model of racial discrimination and alcohol-related problems among african american college students.

PubMed

Boynton, Marcella H; O'Hara, Ross E; Covault, Jonathan; Scott, Denise; Tennen, Howard

2014-03-01

Racial discrimination has been identified as an important predictor of alcohol-related outcomes for African Americans. The goal of the current study was to extend previously found links between lifetime discrimination, alcohol use, and alcohol problems as well as to elucidate the affective mechanisms underlying these associations, as moderated by gender. A multiple-groups structural equation model was computed using survey data collected from 619 students from a historically Black college/university. The final model provided excellent fit to the data, explaining 6% of the variance in alcohol consumption and 37% of the variance in alcohol problems. Discrimination was a significant predictor of alcohol-related problems but not, by and large, level of use. For men, anger-but not discrimination-specific anger-was a significant partial mediator of the link between discrimination and both alcohol use and alcohol problems. Depression partially mediated the link between discrimination and alcohol problems for both men and women. The results suggest that, for African Americans whose drinking leads to drinking-related problems, discrimination and poor affective self-regulation are highly relevant and predictive factors, especially for men.

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.

Understanding nanoparticle-mediated nucleation pathways of anisotropic nanoparticles

NASA Astrophysics Data System (ADS)

Laramy, Christine R.; Fong, Lam-Kiu; Jones, Matthew R.; O'Brien, Matthew N.; Schatz, George C.; Mirkin, Chad A.

2017-09-01

Several seed-mediated syntheses of low symmetry anisotropic nanoparticles yield broad product distributions with multiple defect structures. This observation challenges the role of the nanoparticle precursor as a seed for certain syntheses and suggests the possibility of alternate nucleation pathways. Herein, we report a method to probe the role of the nanoparticle precursor in anisotropic nanoparticle nucleation with compositional and structural 'labels' to track their fate. We use the synthesis of gold triangular nanoprisms (Au TPs) as a model system. We propose a mechanism in which, rather than acting as a template, the nanoparticle precursor catalyzes homogenous nucleation of Au TPs.

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

PubMed Central

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

2016-01-01

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

The relationship of sociodemographic and psychological variables with chronic pain variables in a low-income population.

PubMed

Newman, Andrea K; Van Dyke, Benjamin P; Torres, Calia A; Baxter, Jacob W; Eyer, Joshua C; Kapoor, Shweta; Thorn, Beverly E

2017-09-01

Chronic pain is a pervasive condition that is complicated by economic, educational, and racial disparities. This study analyzes key factors associated with chronic pain within an understudied and underserved population. The sample is characterized by a triple disparity with respect to income, education/literacy, and racial barriers that substantially increase the vulnerability to the negative consequences of chronic pain. The study examined the pretreatment data of 290 participants enrolled in the Learning About My Pain trial, a randomized controlled comparative effectiveness trial of psychosocial interventions (B.E.T., Principal Investigator, Patient-Centered Outcomes Research Institute Contract No. 941; clinicaltrials.gov identifier NCT01967342) for chronic pain. Hierarchical multiple regression analyses evaluated the relationships among sociodemographic (sex, age, race, poverty status, literacy, and education level) and psychological (depressive symptoms and pain catastrophizing) variables and pain interference, pain severity, and disability. The indirect effects of depressive symptoms and pain catastrophizing on the sociodemographic and pain variables were investigated using bootstrap resampling. Reversed mediation models were also examined. Results suggested that the experience of chronic pain within this low-income sample is better accounted for by psychological factors than sex, age, race, poverty status, literacy, and education level. Depressive symptoms and pain catastrophizing mediated the relationships between age and pain variables, whereas pain catastrophizing mediated the effects of primary literacy and poverty status. Some reversed models were equivalent to the hypothesized models, suggesting the possibility of bidirectionality. Although cross-sectional findings cannot establish causality, our results highlight the critical role psychological factors play in individuals with chronic pain and multiple health disparities.

Mechanisms and mediation in survival analysis: towards an integrated analytical framework.

PubMed

Pratschke, Jonathan; Haase, Trutz; Comber, Harry; Sharp, Linda; de Camargo Cancela, Marianna; Johnson, Howard

2016-02-29

A wide-ranging debate has taken place in recent years on mediation analysis and causal modelling, raising profound theoretical, philosophical and methodological questions. The authors build on the results of these discussions to work towards an integrated approach to the analysis of research questions that situate survival outcomes in relation to complex causal pathways with multiple mediators. The background to this contribution is the increasingly urgent need for policy-relevant research on the nature of inequalities in health and healthcare. The authors begin by summarising debates on causal inference, mediated effects and statistical models, showing that these three strands of research have powerful synergies. They review a range of approaches which seek to extend existing survival models to obtain valid estimates of mediation effects. They then argue for an alternative strategy, which involves integrating survival outcomes within Structural Equation Models via the discrete-time survival model. This approach can provide an integrated framework for studying mediation effects in relation to survival outcomes, an issue of great relevance in applied health research. The authors provide an example of how these techniques can be used to explore whether the social class position of patients has a significant indirect effect on the hazard of death from colon cancer. The results suggest that the indirect effects of social class on survival are substantial and negative (-0.23 overall). In addition to the substantial direct effect of this variable (-0.60), its indirect effects account for more than one quarter of the total effect. The two main pathways for this indirect effect, via emergency admission (-0.12), on the one hand, and hospital caseload, on the other, (-0.10) are of similar size. The discrete-time survival model provides an attractive way of integrating time-to-event data within the field of Structural Equation Modelling. The authors demonstrate the efficacy of this approach in identifying complex causal pathways that mediate the effects of a socio-economic baseline covariate on the hazard of death from colon cancer. The results show that this approach has the potential to shed light on a class of research questions which is of particular relevance in health research.

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

PubMed

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

2009-11-01

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

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.

Mediation and moderation of the association between cynical hostility and systolic blood pressure in low-income women.

PubMed

Versey, H Shellae; Kaplan, George A

2012-04-01

Hostility may be related to risk factors for cardiovascular disease (CVD), such as blood pressure. However, the process by which hostility affects blood pressure is not fully understood. The current study sought to evaluate abdominal obesity (waist-to-hip ratio [WHR]) as a potential mediator and modifier of the relationship between cynical hostility and systolic blood pressure (SBP) in a group of disadvantaged women. Path analysis and multiple regression models were used to identify mediating and moderating pathways in the relationship between cynical hostility and SBP. Results indicate a significant interaction between WHR and cynical hostility. WHR was a partial mediator and significant moderator of the association between hostility and blood pressure. These findings highlight the potential importance of examining abdominal obesity and psychosocial factors as conjunctive determinants of CVD and risk factors for related metabolic conditions.

Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells.

PubMed

Hernandez, Amanda L; Kitz, Alexandra; Wu, Chuan; Lowther, Daniel E; Rodriguez, Donald M; Vudattu, Nalini; Deng, Songyan; Herold, Kevan C; Kuchroo, Vijay K; Kleinewietfeld, Markus; Hafler, David A

2015-11-02

FOXP3+ Tregs are central for the maintenance of self-tolerance and can be defective in autoimmunity. In multiple sclerosis and type-1 diabetes, dysfunctional self-tolerance is partially mediated by a population of IFNγ-secreting Tregs. It was previously reported that increased NaCl concentrations promote the induction of proinflammatory Th17 cells and that high-salt diets exacerbate experimental models of autoimmunity. Here, we have shown that increasing NaCl, either in vitro or in murine models via diet, markedly impairs Treg function. NaCl increased IFNγ secretion in Tregs, and reducing IFNγ - either by neutralization with anti-IFNγ antibodies or shRNA-mediated knockdown - restored suppressive activity in Tregs. The heightened IFNγ secretion and loss of Treg function were mediated by the serum/glucocorticoid-regulated kinase (SGK1). A high-salt diet also impaired human Treg function and was associated with the induction of IFNγ-secreting Tregs in a xenogeneic graft-versus-host disease model and in adoptive transfer models of experimental colitis. Our results demonstrate a putative role for an environmental factor that promotes autoimmunity by inducing proinflammatory responses in CD4 effector cells and Treg pathways.

Explaining the justice-performance relationship: trust as exchange deepener or trust as uncertainty reducer?

PubMed

Colquitt, Jason A; Lepine, Jeffery A; Piccolo, Ronald F; Zapata, Cindy P; Rich, Bruce L

2012-01-01

Past research has revealed significant relationships between organizational justice dimensions and job performance, and trust is thought to be one mediator of those relationships. However, trust has been positioned in justice theorizing in 2 different ways, either as an indicator of the depth of an exchange relationship or as a variable that reflects levels of work-related uncertainty. Moreover, trust scholars distinguish between multiple forms of trust, including affect- and cognition-based trust, and it remains unclear which form is most relevant to justice effects. To explore these issues, we built and tested a more comprehensive model of trust mediation in which procedural, interpersonal, and distributive justice predicted affect- and cognition-based trust, with those trust forms predicting both exchange- and uncertainty-based mechanisms. The results of a field study in a hospital system revealed that the trust variables did indeed mediate the relationships between the organizational justice dimensions and job performance, with affect-based trust driving exchange-based mediation and cognition-based trust driving uncertainty-based mediation.

Short sleep mediates the association between long work hours and increased body mass index.

PubMed

Magee, Christopher A; Caputi, Peter; Iverson, Don C

2011-04-01

This study examined whether short sleep duration, physical activity and time spent sitting each day mediated the association between long work hours and body mass index (BMI). Participants included 16,951 middle aged Australian adults who were employed in full time work (i.e. ≥35 h a week). Data on BMI, sleep duration, work hours and other health and demographic variables were obtained through a self-report questionnaire. A multiple mediation model was tested whereby sleep duration, physical activity and amount of time spent sitting were entered as potential mediators between work hours and BMI. The results demonstrated that short sleep partially mediated the association between long work hours and increased BMI in males. In females, long work hours were indirectly related to higher BMI through short sleep. The results provide some support for the hypothesis that long work hours could contribute to obesity via a reduction in sleep duration; this warrants further investigation in prospective studies.

Children's appraisals as mediators of the relationship between domestic violence and child adjustment.

PubMed

Fortin, Andrée; Doucet, Martin; Damant, Dominique

2011-01-01

This study examines the relationships among variables that were likely to mediate the effects of exposure to domestic violence on children's internalizing problems (i.e., children's appraisals of domestic violence and their perceptions of family relationships). The study was conducted with 79 children exposed to domestic violence, including 41 boys and 38 girls, aged between 9 and 12 years old. Indicators used for children's appraisals of violence were attribution of blame and perceived threat. Children's perceptions of family relationships were based on their levels of parentification and the degree of their loyalty conflicts. A path analysis was used to verify the predictive model's pathways and to test the multiple mediator effects. Findings confirm the contribution of mediating variables and also reflect the association between self-blame and children's parentification. The results stress the relevance of evaluating the combined role of different potential mediators to provide a better understanding of the impact of domestic violence on children.

An Exploration of the Mediators Between Childhood Maltreatment and Intimate Partner Violence.

PubMed

Smyth, Elizabeth J; Gardner, Frank L; Marks, Donald R; Moore, Zella E

2017-08-01

Intimate partner violence (IPV) is associated with numerous long-term consequences and warrants significant clinical attention. Recent theoretical models and empirical research have suggested that several factors play a role in the development of IPV perpetration, including childhood maltreatment, early maladaptive schemas, anger, and difficulties in emotion regulation. This study investigated the relationship between childhood maltreatment and IPV, specifically examining the mediation of this relationship by several variables thought to be related to this pernicious problem, including early maladaptive schemas, the experience of anger, and emotion regulation difficulties. In a young adult collegiate sample of 110 women in relationships, results of a bootstrapped multiple mediation analysis supported the hypothesis that childhood maltreatment predicted physical aggression within intimate partner relationships and found that the total indirect effect of childhood maltreatment on physical aggression through the 3 proposed mediators was significant. However, consistent with recent empirical findings, only difficulties in emotion regulation significantly mediated the relationship between childhood maltreatment and physical aggression within the sample.

Protective factors associated with fewer multiple problem behaviors among homeless/runaway youth.

PubMed

Lightfoot, Marguerita; Stein, Judith A; Tevendale, Heather; Preston, Kathleen

2011-01-01

Although homeless youth exhibit numerous problem behaviors, protective factors that can be targeted and modified by prevention programs to decrease the likelihood of involvement in risky behaviors are less apparent. The current study tested a model of protective factors for multiple problem behavior in a sample of 474 homeless youth (42% girls; 83% minority) ages 12 to 24 years. Higher levels of problem solving and planning skills were strongly related to lower levels of multiple problem behaviors in homeless youth, suggesting both the positive impact of preexisting personal assets of these youth and important programmatic targets for further building their resilience and decreasing problem behaviors. Indirect relationships between the background factors of self-esteem and social support and multiple problem behaviors were significantly mediated through protective skills. The model suggests that helping youth enhance their skills in goal setting, decision making, and self-reliant coping could lessen a variety of problem behaviors commonly found among homeless youth.

Protective Factors Associated with Fewer Multiple Problem Behaviors Among Homeless/Runaway Youth

PubMed Central

Lightfoot, Marguerita; Stein, Judith A.; Tevendale, Heather; Preston, Kathleen

2015-01-01

Although homeless youth exhibit numerous problem behaviors, protective factors that can be targeted and modified by prevention programs to decrease the likelihood of involvement in risky behaviors are less apparent. The current study tested a model of protective factors for multiple problem behavior in a sample of 474 homeless youth (42% girls; 83% minority) ages 12 to 24 years. Higher levels of problem solving and planning skills were strongly related to lower levels of multiple problem behaviors in homeless youth, suggesting both the positive impact of preexisting personal assets of these youth and important programmatic targets for further building their resilience and decreasing problem behaviors. Indirect relationships between the background factors of self-esteem and social support and multiple problem behaviors were significantly mediated through protective skills. The model suggests that helping youth enhance their skills in goal setting, decision making, and self-reliant coping could lessen a variety of problem behaviors commonly found among homeless youth. PMID:22023279

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

Self-Verification and Depressive Symptoms in Marriage and Courtship: A Multiple Pathway Model.

ERIC Educational Resources Information Center

Katz, Jennifer; Beach, Steven R. H.

1997-01-01

Examines whether self-verifying feedback may lead to decreased depressive symptoms. Results, based on 138 married women and 258 dating women, showed full mediational effects in the married sample and partial effects in the dating sample. Findings suggest that partner self-verifying feedback may intensify the effect of self-esteem on depression.…

Perceiving a Calling, Living a Calling, and Job Satisfaction: Testing a Moderated, Multiple Mediator Model

ERIC Educational Resources Information Center

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

2012-01-01

The current study examined the relation between perceiving a calling, living a calling, and job satisfaction among a diverse group of employed adults who completed an online survey (N = 201). Perceiving a calling and living a calling were positively correlated with career commitment, work meaning, and job satisfaction. Living a calling moderated…

Design, Fabrication, Characterization and Modeling of Integrated Functional Materials

DTIC Science & Technology

2011-10-01

the integration of multiple functionalities with desirable properties (thermal, electrical, magnetic, mechanical , optical, etc.), the connection to...mediated magnetic interactions in the nanocomposites. Our systematic studies on the underlying mechanism of magnetic interactions between graphene...or 3- nanocrystalline phases have been seen simultaneously within an amorphous matrix. The mechanism for induced magnetic anisotropy in these alloys

Optimism, Social Support, and Well-Being in Mothers of Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Ekas, Naomi V.; Lickenbrock, Diane M.; Whitman, Thomas L.

2010-01-01

This study used structural equation modeling to examine the relationship between multiple sources of social support (e.g., partner, family, and friends), optimism, and well-being among mothers of children with ASD. Social support was examined as a mediator and moderator of the optimism-maternal well-being relationship. Moreover, the role of…

Competitive testing of health behavior theories: how do benefits, barriers, subjective norm, and intention influence mammography behavior?

PubMed Central

Murphy, Caitlin C.; Vernon, Sally W.; Diamond, Pamela M.; Tiro, Jasmin A.

2013-01-01

Background Competitive hypothesis testing may explain differences in predictive power across multiple health behavior theories. Purpose We tested competing hypotheses of the Health Belief Model (HBM) and Theory of Reasoned Action (TRA) to quantify pathways linking subjective norm, benefits, barriers, intention, and mammography behavior. Methods We analyzed longitudinal surveys of women veterans randomized to the control group of a mammography intervention trial (n=704). We compared direct, partial mediation, and full mediation models with Satorra-Bentler χ2 difference testing. Results Barriers had a direct and indirect negative effect on mammography behavior; intention only partially mediated barriers. Benefits had little to no effect on behavior and intention; however, it was negatively correlated with barriers. Subjective norm directly affected behavior and indirectly affected intention through barriers. Conclusions Our results provide empiric support for different assertions of HBM and TRA. Future interventions should test whether building subjective norm and reducing negative attitudes increases regular mammography. PMID:23868613

Can community consciousness be a bad thing? A moderated mediation analysis of heterosexism, mental health, and body appreciation in sexual minority men

PubMed Central

Simpson, Courtney C.; Sutter, Megan; Perrin, Paul B.

2016-01-01

This study examined the connections among heterosexism, mental health, body appreciation, and community consciousness in sexual minority men. Participants (N = 89) completed a national online survey. Simultaneous multiple regression found that heterosexism explained 9.4% of the variance in body appreciation and 25.8% of the variance in mental health; mental health accounted for 28.0% of the variance in body appreciation. Within these models, harassment/rejection heterosexism was a unique positive predictor of mental health and a unique negative predictor of body appreciation; depression was a unique negative predictor of body appreciation. A moderated mediational model found that depression mediated the relationship between harassment/rejection heterosexism and body appreciation, but only in men who endorsed high community consciousness. Intervention research might benefit from helping sexual minority men explore the ways in which body image is affected by heterosexism and mental health, as well as the ways that contemporary Western gay communities might contribute to these connections. PMID:27210047

Neutrophils Are Central to Antibody-Mediated Protection against Genital Chlamydia.

PubMed

Naglak, Elizabeth K; Morrison, Sandra G; Morrison, Richard P

2017-10-01

Determining the effector populations involved in humoral protection against genital chlamydia infection is crucial to development of an effective chlamydial vaccine. Antibody has been implicated in protection studies in multiple animal models, and we previously showed that the passive transfer of immune serum alone does not confer immunity in the mouse. Using the Chlamydia muridarum model of genital infection, we demonstrate a protective role for both Chlamydia -specific immunoglobulin G (IgG) and polymorphonuclear neutrophils and show the importance of an antibody/effector cell interaction in mediating humoral immunity. While neutrophils were found to contribute significantly to antibody-mediated protection in vivo , natural killer (NK) cells were dispensable for protective immunity. Furthermore, gamma interferon (IFN-γ)-stimulated primary peritoneal neutrophils (PPNs) killed chlamydiae in vitro in an antibody-dependent manner. The results from this study support the view that an IFN-γ-activated effector cell population cooperates with antibody to protect against genital chlamydia and establish neutrophils as a key effector cell in this response. Copyright © 2017 Naglak et al.

Can community consciousness be a bad thing? A moderated mediation analysis of heterosexism, mental health and body appreciation in sexual minority men.

PubMed

Simpson, Courtney C; Sutter, Megan; Perrin, Paul B

2016-11-01

This study examined the connections between heterosexism, mental health, body appreciation and community consciousness in sexual minority men (SMM). Participants (n = 89) completed a national online survey. Simultaneous multiple regressions found that heterosexism explained 9.4% of the variance in body appreciation and 25.8% of the variance in mental health; mental health accounted for 28.0% of the variance in body appreciation. Within these models, harassment/rejection heterosexism was a unique positive predictor of mental health problems and a unique negative predictor of body appreciation; depression was a unique negative predictor of body appreciation. A moderated mediational model found that depression mediated the relationship between harassment/rejection heterosexism and body appreciation, but only in men who endorsed high community consciousness. Intervention research might benefit from helping SMM explore the ways in which body image is affected by heterosexism and mental health, as well as the ways that contemporary Western gay communities might contribute to these connections.

The role of anger and ongoing stressors in mental health following a natural disaster.

PubMed

Forbes, David; Alkemade, Nathan; Waters, Elizabeth; Gibbs, Lisa; Gallagher, Colin; Pattison, Phillipa; Lusher, Dean; MacDougall, Colin; Harms, Louise; Block, Karen; Snowdon, Elyse; Kellet, Connie; Sinnott, Vikki; Ireton, Greg; Richardson, John; Bryant, Richard A

2015-08-01

Research has established the mental health sequelae following disaster, with studies now focused on understanding factors that mediate these outcomes. This study focused on anger, alcohol, subsequent life stressors and traumatic events as mediators in the development of mental health disorders following the 2009 Black Saturday Bushfires, Australia's worst natural disaster in over 100 years. This study examined data from 1017 (M = 404, F = 613) adult residents across 25 communities differentially affected by the fires and participating in the Beyond Bushfires research study. Data included measures of fire exposure, posttraumatic stress disorder, depression, alcohol abuse, anger and subsequent major life stressors and traumatic events. Structural equation modeling assessed the influence of factors mediating the effects of fire exposure on mental health outcomes. Three mediation models were tested. The final model recorded excellent fit and observed a direct relationship between disaster exposure and mental health outcomes (b = .192, p < .001) and mediating relationships via Anger (b = .102, p < .001) and Major Life Stressors (b = .128, p < .001). Each gender was compared with multiple group analyses and while the mediation relationships were still significant for both genders, the direct relationship between exposure and outcome was no longer significant for men (p = .069), but remained significant (b = .234, p < .001) for women. Importantly, anger and major life stressors mediate the relationship between disaster exposure and development of mental health problems. The findings have significant implications for the assessment of anger post disaster, the provision of targeted anger-focused interventions and delivery of government and community assistance and support in addressing ongoing stressors in the post-disaster context to minimize subsequent mental health consequences. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Prediction of Drug-Drug Interactions with Crizotinib as the CYP3A Substrate Using a Physiologically Based Pharmacokinetic Model.

PubMed

Yamazaki, Shinji; Johnson, Theodore R; Smith, Bill J

2015-10-01

An orally available multiple tyrosine kinase inhibitor, crizotinib (Xalkori), is a CYP3A substrate, moderate time-dependent inhibitor, and weak inducer. The main objectives of the present study were to: 1) develop and refine a physiologically based pharmacokinetic (PBPK) model of crizotinib on the basis of clinical single- and multiple-dose results, 2) verify the crizotinib PBPK model from crizotinib single-dose drug-drug interaction (DDI) results with multiple-dose coadministration of ketoconazole or rifampin, and 3) apply the crizotinib PBPK model to predict crizotinib multiple-dose DDI outcomes. We also focused on gaining insights into the underlying mechanisms mediating crizotinib DDIs using a dynamic PBPK model, the Simcyp population-based simulator. First, PBPK model-predicted crizotinib exposures adequately matched clinically observed results in the single- and multiple-dose studies. Second, the model-predicted crizotinib exposures sufficiently matched clinically observed results in the crizotinib single-dose DDI studies with ketoconazole or rifampin, resulting in the reasonably predicted fold-increases in crizotinib exposures. Finally, the predicted fold-increases in crizotinib exposures in the multiple-dose DDI studies were roughly comparable to those in the single-dose DDI studies, suggesting that the effects of crizotinib CYP3A time-dependent inhibition (net inhibition) on the multiple-dose DDI outcomes would be negligible. Therefore, crizotinib dose-adjustment in the multiple-dose DDI studies could be made on the basis of currently available single-dose results. Overall, we believe that the crizotinib PBPK model developed, refined, and verified in the present study would adequately predict crizotinib oral exposures in other clinical studies, such as DDIs with weak/moderate CYP3A inhibitors/inducers and drug-disease interactions in patients with hepatic or renal impairment. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Emergency room nurses' pathway to turnover intention: a moderated serial mediation analysis.

PubMed

Bruyneel, Luk; Thoelen, Tom; Adriaenssens, Jef; Sermeus, Walter

2017-04-01

The aim of this study was to explore the association between the quality of the work environment, job characteristics, demographic characteristics and a pathway of job satisfaction, emotional exhaustion and turnover intention among nurses in emergency departments and perform subgroup analyses. Turnover intention among nurses is high. Multiple causes have been described, mostly in large studies of nurses working on general wards, often without considering complementarity of conceptual models and showing scant interest in the consistency of associations across subgroups of nurses. Cross-sectional multicentre survey. Convenience sample of 294 nurses in 11 Belgian emergency departments during 2014-2015. Indirect effects in the form of mediation and serial mediation were estimated to assess the association between work environment (Magnet model), job characteristics (Job Demand Control Support model) and turnover intention via job satisfaction and emotional exhaustion. Consistency of these indirect effects across subgroups of nurses was examined using moderated mediation analysis (conditional indirect effects). Several Magnet and Job Demand Control Support dimensions were related to turnover intention, either via job dissatisfaction (mediation) or via job satisfaction and emotional exhaustion (serial mediation). In the case of social support from supervisor, these indirect effects were only significant for female nurses, among whom turnover intention was higher. Last, nurses with more years of experience were less likely to indicate turnover intention. To maximize prevention of turnover intention at emergency departments, interventions could target early career nurses, work environment and job characteristics. Female nurses in particular may also benefit from improved social support from their supervisor. © 2016 John Wiley & Sons Ltd.

Associations between neighbourhood and household environmental variables and fruit consumption: exploration of mediation by individual cognitions and habit strength in the GLOBE study.

PubMed

Tak, Nannah I; te Velde, Saskia J; Kamphuis, Carlijn Bm; Ball, Kylie; Crawford, David; Brug, Johannes; van Lenthe, Frank J

2013-03-01

The present study examined associations of several home and neighbourhood environmental variables with fruit consumption and explored whether these associations were mediated by variables derived from the Theory of Planned Behaviour (TPB) and by habit strength. Data of the Dutch GLOBE study on household and neighbourhood environment, fruit intake and related factors were used, obtained by self-administered questionnaires (cross-sectional), face-to-face interviews and audits. The city of Eindhoven in the Netherlands Adults (n 333; mean age 58 years, 54% female). Multiple mediation analyses were conducted using regression analyses to assess the association between environmental variables and fruit consumption, as well as mediation of these associations by TPB variables and by habit strength. Intention, perceived behaviour control, subjective norm and habit strength were associated with fruit intake. None of the neighbourhood environmental variables was directly or indirectly associated with fruit intake. The home environmental variable 'modelling behaviour by family members' was indirectly, but not directly, associated with fruit intake. Habit strength and perceived behaviour control explained most of the mediated effect (71.9%). Modelling behaviour by family members was indirectly associated with fruit intake through habit strength and perceived behaviour control. None of the neighbourhood variables was directly or indirectly, through any of the proposed mediators, associated with adult fruit intake. These findings suggest that future interventions promoting fruit intake should address a combination of the home environment (especially modelling behaviour by family members), TPB variables and habit strength for fruit intake.

Can Job Control Ameliorate Work-family Conflict and Enhance Job Satisfaction among Chinese Registered Nurses? A Mediation Model.

PubMed

Ding, Xiaotong; Yang, Yajuan; Su, Dan; Zhang, Ting; Li, Lunlan; Li, Huiping

2018-04-01

Low job satisfaction is the most common cause of nurses' turnover and influences the quality of nursing service. Moreover, we have no idea regarding whether job control, as an individual factor, can play a role in the relationship. To explore the relationship between work-family conflict and job satisfaction among Chinese registered nurses and the mediating role of job control in this relationship. From August 2015 to November 2016, 487 Chinese registered nurses completed a survey. The study used work-family conflict scale, job control scale, job satisfaction scale, as well as general information. Multiple regression analysis was used to explore the independent factors of job satisfaction. Structural equation model was used to explore the mediating role of job control. Work-family conflict was negatively correlated with job satisfaction (r ‑0.432, p<0.01). In addition, job control was positively related to job satisfaction (r 0.567, p<0.01). Work-family conflict and job control had significant predictive effects on job satisfaction. Job control partially mediated the relationship between work-family conflict and job satisfaction. Work-family conflict affected job satisfaction and job control was a mediator in this relationship among Chinese registered nurses. Job control could potentially improve nurses' job satisfaction.

Optimism on quality of life in Portuguese chronic patients: moderator/mediator?

PubMed

Vilhena, Estela; Pais-Ribeiro, José; Silva, Isabel; Pedro, Luísa; Meneses, Rute F; Cardoso, Helena; Silva, António Martins da; Mendonça, Denisa

2014-07-01

optimism is an important variable that has consistently been shown to affect adjustment to quality of life in chronic diseases. This study aims to clarify if dispositional optimism exerts a moderating or a mediating influence on the personality traits-quality of life association, in Portuguese chronic patients. multiple regression models were used to test the moderation and mediation effects of dispositional optimism in quality of life. A sample of 729 patients was recruited in Portugal's main hospitals and completed self-reported questionnaires assessing socio-demographic and clinical variables, personality, dispositional optimism, quality of life (QoL) and subjective well-being (SWB). the results of the regression models showed that dispositional optimism did not moderate the relationships between personality traits and quality of life. After controlling for gender, age, education level and severity of disease perception, the effects of personality traits on QoL and in SWB were mediated by dispositional optimism (partially and completely), except for the links between neuroticism/openness to experience and physical health. dispositional optimism is more likely to play a mediating, rather than a moderating role in personality traits-quality of life pathway in Portuguese chronic patients, suggesting that "the expectation that good things will happen" contributes to a better quality of life and subjective well-being.

Examining the Links between Challenging Behaviors in Youth with ASD and Parental Stress, Mental Health, and Involvement: Applying an Adaptation of the Family Stress Model to Families of Youth with ASD

ERIC Educational Resources Information Center

Schiltz, Hillary K.; McVey, Alana J.; Magnus, Brooke; Dolan, Bridget K.; Willar, Kirsten S.; Pleiss, Sheryl; Karst, Jeffrey; Carson, Audrey M.; Caiozzo, Christina; Vogt, Elisabeth; Van Hecke, Amy Vaughan

2018-01-01

Raising a child with autism spectrum disorder (ASD) poses unique challenges that may impact parents' mental health and parenting experiences. The current study analyzed self-report data from 77 parents of youth with ASD. A serial multiple mediation model revealed that parenting stress (SIPA) and parental mental health (BAI and BDI-II) appears to…

Search for supersymmetry in the multijet and missing transverse momentum channel in pp collisions at 13 TeV: Z + jets background

NASA Astrophysics Data System (ADS)

Mulholland, Troy; CMS Collaboration

2016-03-01

We present a search for supersymmetry (SUSY) with data collected from the Compact Muon Solenoid (CMS) detector. The sample corresponds to 2 . 3fb-1 of proton-proton collisions with √{ s} = 13 TeV delivered by the Large Hadron Collider (LHC). The search looks at events with large hadronic activity, missing transverse energy, and without any identified leptons. The data are analyzed in bins of jet multiplicity, bottom-quark tagged jet (b-jet) multiplicity, scalar sum of jet transverse momentum, and vector sum of jet transverse momentum. A standard model (SM) background to this search includes the SM production of multiple jets and a Z boson that decays to two undetectable neutrinos. This talk focuses on the measurement of this particular background and its context in the wider search. Observations are consistent with SM backgrounds and limits are set on gluino mediated simplified SUSY models.

Relationships among depressive symptoms, benefit-finding, optimism, and positive affect in multiple sclerosis patients after psychotherapy for depression.

PubMed

Hart, Stacey L; Vella, Lea; Mohr, David C

2008-03-01

While many patients with multiple sclerosis (MS) experience psychological problems, such as depression, benefit-finding is commonly reported. Using the Broaden-and-Build Model of positive emotions (Fredrickson, 2001) and the Expectancy-Value Model of optimism (Carver & Scheier, 1998) as two related, yet, distinct conceptual frameworks, this study examined positive affect and optimism as mediators of the relationship between improved depression and enhanced benefit-finding. MS patients (N=127), who participated in a larger, randomized clinical trial comparing two types of telephone psychotherapy for depression, were assessed at baseline, midtherapy (8 weeks), end of therapy (16 weeks), and 6- and 12-month posttherapy. Depression was measured with a telephone administered version of the Hamilton Rating Scale for Depression; Positive Affect was measured with the Positive Affect Subscale from the Positive and Negative Affect Scale; Optimism was measured with the Life Orientation Test-Revised; Benefit-Finding was measured with the revised version of the Stress-Related Growth Scale. Data were analyzed with multilevel random-effects models, controlling for time since MS diagnosis and type of treatment. Improved depression was associated with increased benefit-finding over time. The relationship between improved depression and benefit-finding was significantly mediated by both increased optimism and increased positive affect. Findings provide support to both theoretical models. Positivity appears to promote benefit-finding in MS. Copyright (c) 2008 APA, all rights reserved.

Neurocognitive Predictors of Mathematical Processing in School-Aged Children with Spina Bifida and Their Typically Developing Peers: Attention, Working Memory, and Fine Motor Skills

PubMed Central

Raghubar, Kimberly P.; Barnes, Marcia A.; Dennis, Maureen; Cirino, Paul T.; Taylor, Heather; Landry, Susan

2015-01-01

Objective Math and attention are related in neurobiological and behavioral models of mathematical cognition. This study employed model-driven assessments of attention and math in children with spina bifida myelomeningocele (SBM), who have known math difficulties and specific attentional deficits, to more directly examine putative relations between attention and mathematical processing. The relation of other domain general abilities and math was also investigated. Method Participants were 9.5-year-old children with SBM (N = 44) and typically developing children (N = 50). Participants were administered experimental exact and approximate arithmetic tasks, and standardized measures of math fluency and calculation. Cognitive measures included the Attention Network Test (ANT), and standardized measures of fine motor skills, verbal working memory (WM), and visual-spatial WM. Results Children with SBM performed similarly to peers on exact arithmetic but more poorly on approximate and standardized arithmetic measures. On the ANT, children with SBM differed from controls on orienting attention but not alerting and executive attention. Multiple mediation models showed that: fine motor skills and verbal WM mediated the relation of group to approximate arithmetic; fine motor skills and visual-spatial WM mediated the relation of group to math fluency; and verbal and visual-spatial WM mediated the relation of group to math calculation. Attention was not a significant mediator of the effects of group for any aspect of math in this study. Conclusions Results are discussed with reference to models of attention, WM, and mathematical cognition. PMID:26011113

Neurocognitive predictors of mathematical processing in school-aged children with spina bifida and their typically developing peers: Attention, working memory, and fine motor skills.

PubMed

Raghubar, Kimberly P; Barnes, Marcia A; Dennis, Maureen; Cirino, Paul T; Taylor, Heather; Landry, Susan

2015-11-01

Math and attention are related in neurobiological and behavioral models of mathematical cognition. This study employed model-driven assessments of attention and math in children with spina bifida myelomeningocele (SBM), who have known math difficulties and specific attentional deficits, to more directly examine putative relations between attention and mathematical processing. The relation of other domain general abilities and math was also investigated. Participants were 9.5-year-old children with SBM (n = 44) and typically developing children (n = 50). Participants were administered experimental exact and approximate arithmetic tasks, and standardized measures of math fluency and calculation. Cognitive measures included the Attention Network Test (ANT), and standardized measures of fine motor skills, verbal working memory (WM), and visual-spatial WM. Children with SBM performed similarly to peers on exact arithmetic, but more poorly on approximate and standardized arithmetic measures. On the ANT, children with SBM differed from controls on orienting attention, but not on alerting and executive attention. Multiple mediation models showed that fine motor skills and verbal WM mediated the relation of group to approximate arithmetic; fine motor skills and visual-spatial WM mediated the relation of group to math fluency; and verbal and visual-spatial WM mediated the relation of group to math calculation. Attention was not a significant mediator of the effects of group for any aspect of math in this study. Results are discussed with reference to models of attention, WM, and mathematical cognition. (c) 2015 APA, all rights reserved).

An Extract of Artemisia dracunculus L. Promotes Psychological Resilience in a Mouse Model of Depression

PubMed Central

Wang, Jun; Fernández, Adelaida Esteban; Tiano, Simoni; Huang, Jing; Floyd, Elizabeth; Poulev, Alexander

2018-01-01

Stress-induced peripheral inflammation contributes to depression-like behaviors in both human and experimental models. PMI 5011, a botanical extract of Artemisia dracunculus L., was previously shown to have multiple bioactivities, including anti-inflammatory activity. In this work, using a repeated social defeat stress (RSDS) model of depression, we demonstrate that oral administration of the botanical extract PMI 5011 promotes resilience to RSDS-mediated depression-like phenotypes. We also show that the behavioral improvements are associated with attenuation of stress-mediated induction of inflammatory cytokines in the periphery and alteration of synaptic plasticity in the nucleus accumbens (NAc). Our studies provide experimental evidence that botanical extracts such as PMI 5011, which target pathological mechanisms (i.e., peripheral inflammation) not addressed by currently available antidepressants, could be further developed as novel therapeutics for the treatment of stress disorders and anxiety in humans. PMID:29861834

Bayesian Cue Integration as a Developmental Outcome of Reward Mediated Learning

PubMed Central

Weisswange, Thomas H.; Rothkopf, Constantin A.; Rodemann, Tobias; Triesch, Jochen

2011-01-01

Average human behavior in cue combination tasks is well predicted by Bayesian inference models. As this capability is acquired over developmental timescales, the question arises, how it is learned. Here we investigated whether reward dependent learning, that is well established at the computational, behavioral, and neuronal levels, could contribute to this development. It is shown that a model free reinforcement learning algorithm can indeed learn to do cue integration, i.e. weight uncertain cues according to their respective reliabilities and even do so if reliabilities are changing. We also consider the case of causal inference where multimodal signals can originate from one or multiple separate objects and should not always be integrated. In this case, the learner is shown to develop a behavior that is closest to Bayesian model averaging. We conclude that reward mediated learning could be a driving force for the development of cue integration and causal inference. PMID:21750717

Proposal for a telehealth concept in the translational research model.

PubMed

Silva, Angélica Baptista; Morel, Carlos Médicis; Moraes, Ilara Hämmerli Sozzi de

2014-04-01

To review the conceptual relationship between telehealth and translational research. Bibliographical search on telehealth was conducted in the Scopus, Cochrane BVS, LILACS and MEDLINE databases to find experiences of telehealth in conjunction with discussion of translational research in health. The search retrieved eight studies based on analysis of models of the five stages of translational research and the multiple strands of public health policy in the context of telehealth in Brazil. The models were applied to telehealth activities concerning the Network of Human Milk Banks, in the Telemedicine University Network. The translational research cycle of human milk collected, stored and distributed presents several integrated telehealth initiatives, such as video conferencing, and software and portals for synthesizing knowledge, composing elements of an information ecosystem, mediated by information and communication technologies in the health system. Telehealth should be composed of a set of activities in a computer mediated network promoting the translation of knowledge between research and health services.

Motivation towards extracurricular activities and motivation at school: A test of the generalization effect hypothesis.

PubMed

Denault, Anne-Sophie; Guay, Frédéric

2017-01-01

Participation in extracurricular activities is a promising avenue for enhancing students' school motivation. Using self-determination theory (Deci & Ryan, 2000), the goal of this study was to test a serial multiple mediator model. In this model, students' perceptions of autonomy support from their extracurricular activity leader predicted their activity-based intrinsic and identified regulations. In turn, these regulations predicted their school-based intrinsic and identified regulations during the same school year. Finally, these regulations predicted their school-based intrinsic and identified regulations one year later. A total of 276 youths (54% girls) from disadvantaged neighborhoods were surveyed over two waves of data collection. The proposed mediation model was supported for both types of regulation. These results highlight the generalization effects of motivation from the extracurricular activity context to the school context. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2012-10-01

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

The cerebellum in action: a simulation and robotics study.

PubMed

Hofstötter, Constanze; Mintz, Matti; Verschure, Paul F M J

2002-10-01

The control or prediction of the precise timing of events are central aspects of the many tasks assigned to the cerebellum. Despite much detailed knowledge of its physiology and anatomy, it remains unclear how the cerebellar circuitry can achieve such an adaptive timing function. We present a computational model pursuing this question for one extensively studied type of cerebellar-mediated learning: the classical conditioning of discrete motor responses. This model combines multiple current assumptions on the function of the cerebellar circuitry and was used to investigate whether plasticity in the cerebellar cortex alone can mediate adaptive conditioned response timing. In particular, we studied the effect of changes in the strength of the synapses formed between parallel fibres and Purkinje cells under the control of a negative feedback loop formed between inferior olive, cerebellar cortex and cerebellar deep nuclei. The learning performance of the model was evaluated at the circuit level in simulated conditioning experiments as well as at the behavioural level using a mobile robot. We demonstrate that the model supports adaptively timed responses under real-world conditions. Thus, in contrast to many other models that have focused on cerebellar-mediated conditioning, we investigated whether and how the suggested underlying mechanisms could give rise to behavioural phenomena.

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

PubMed

Comello, Maria Leonora G; Farman, Lisa

2016-10-02

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

Father Involvement and Young, Rural African American Men's Engagement in Substance Misuse and Multiple Sexual Partnerships.

PubMed

Barton, Allen W; Kogan, Steven M; Cho, Junhan; Brown, Geoffrey L

2015-12-01

This study was designed to examine the associations of biological father and social father involvement during childhood with African American young men's development and engagement in risk behaviors. With a sample of 505 young men living in the rural South of the United States, a dual mediation model was tested in which retrospective reports of involvement from biological fathers and social fathers were linked to young men's substance misuse and multiple sexual partnerships through men's relational schemas and future expectations. Results from structural equation modeling indicated that levels of involvement from biological fathers and social fathers predicted young men's relational schemas; only biological fathers' involvement predicted future expectations. In turn, future expectations predicted levels of substance misuse, and negative relational schemas predicted multiple sexual partnerships. Biological fathers' involvement evinced significant indirect associations with young men's substance misuse and multiple sexual partnerships through both schemas and expectations; social fathers' involvement exhibited an indirect association with multiple sexual partnerships through relational schemas. Findings highlight the unique influences of biological fathers and social fathers on multiple domains of African American young men's psychosocial development that subsequently render young men more or less likely to engage in risk behaviors.

What have we learned about GPER function in physiology and disease from knockout mice?

PubMed

Prossnitz, Eric R; Hathaway, Helen J

2015-09-01

Estrogens, predominantly 17β-estradiol, exert diverse effects throughout the body in both normal and pathophysiology, during development and in reproductive, metabolic, endocrine, cardiovascular, nervous, musculoskeletal and immune systems. Estrogen and its receptors also play important roles in carcinogenesis and therapy, particularly for breast cancer. In addition to the classical nuclear estrogen receptors (ERα and ERβ) that traditionally mediate predominantly genomic signaling, the G protein-coupled estrogen receptor GPER has become recognized as a critical mediator of rapid signaling in response to estrogen. Mouse models, and in particular knockout (KO) mice, represent an important approach to understand the functions of receptors in normal physiology and disease. Whereas ERα KO mice display multiple significant defects in reproduction and mammary gland development, ERβ KO phenotypes are more limited, and GPER KO exhibit no reproductive deficits. However, the study of GPER KO mice over the last six years has revealed that GPER deficiency results in multiple physiological alterations including obesity, cardiovascular dysfunction, insulin resistance and glucose intolerance. In addition, the lack of estrogen-mediated effects in numerous tissues of GPER KO mice, studied in vivo or ex vivo, including those of the cardiovascular, endocrine, nervous and immune systems, reveals GPER as a genuine mediator of estrogen action. Importantly, GPER KO mice have also demonstrated roles for GPER in breast carcinogenesis and metastasis. In combination with the supporting effects of GPER-selective ligands and GPER knockdown approaches, GPER KO mice demonstrate the therapeutic potential of targeting GPER activity in diseases as diverse as obesity, diabetes, multiple sclerosis, hypertension, atherosclerosis, myocardial infarction, stroke and cancer. Copyright © 2015. Published by Elsevier Ltd.

Mood instability as a precursor to depressive illness: A prospective and mediational analysis.

PubMed

Marwaha, Steven; Balbuena, Lloyd; Winsper, Catherine; Bowen, Rudy

2015-06-01

Mood instability levels are high in depression, but temporal precedence and potential mechanisms are unknown. Hypotheses tested were as follows: (1) mood instability is associated with depression cross-sectionally, (2) mood instability predicts new onset and maintenance of depression prospectively and (3) the mood instability and depression link are mediated by sleep problems, alcohol abuse and life events. Data from the National Psychiatric Morbidity Survey 2000 at baseline (N = 8580) and 18-month follow-up (N = 2413) were used. Regression modeling controlling for socio-demographic factors, anxiety and hypomanic mood was conducted. Multiple mediational analyses were used to test our conceptual path model. Mood instability was associated with depression cross-sectionally (odds ratio: 5.28; 95% confidence interval: [3.67, 7.59]; p < 0.001) and predicted depression inception (odds ratio: 2.43; 95% confidence interval: [1.03-5.76]; p = 0.042) after controlling for important confounders. Mood instability did not predict maintenance of depression. Sleep difficulties and severe problems with close friends and family significantly mediated the link between mood instability and new onset depression (23.05% and 6.19% of the link, respectively). Alcohol abuse and divorce were not important mediators in the model. Mood instability is a precursor of a depressive episode, predicting its onset. Difficulties in sleep are a significant part of the pathway. Interventions targeting mood instability and sleep problems have the potential to reduce the risk of depression. © The Royal Australian and New Zealand College of Psychiatrists 2015.

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

PubMed

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

2010-06-01

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

Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota

PubMed Central

van den Hoogen, Ward J.; Laman, Jon D.; ’t Hart, Bert A.

2017-01-01

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research. PMID:28928747

Cellular sources and targets of IFN-gamma-mediated protection against viral demyelination and neurological deficits.

PubMed

Murray, Paul D; McGavern, Dorian B; Pease, Larry R; Rodriguez, Moses

2002-03-01

IFN-gamma is an anti-viral and immunomodulatory cytokine critical for resistance to multiple pathogens. Using mice with targeted disruption of the gene for IFN-gamma, we previously demonstrated that this cytokine is critical for resistance to viral persistence and demyelination in the Theiler's virus model of multiple sclerosis. During viral infections, IFN-gamma is produced by natural killer (NK) cells, CD4(+) and CD8(+) T cells; however, the proportions of lymphocyte subsets responding to virus infection influences the contributions to IFN-gamma-mediated protection. To determine the lymphocyte subsets that produce IFN-gamma to maintain resistance, we used adoptive transfer strategies to generate mice with lymphocyte-specific deficiencies in IFN-gamma-production. We demonstrate that IFN-gamma production by both CD4(+) and CD8(+) T cell subsets is critical for resistance to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination and neurological disease, and that CD4(+) T cells make a greater contribution to IFN-gamma-mediated protection. To determine the cellular targets of IFN-gamma-mediated responses, we used adoptive transfer studies and bone marrow chimerism to generate mice in which either hematopoietic or somatic cells lacked the ability to express IFN-gamma receptor. We demonstrate that IFN-gamma receptor must be present on central nervous system glia, but not bone marrow-derived lymphocytes, in order to maintain resistance to TMEV-induced demyelination.

Cellular sources and targets of IFN-γ-mediated protection against viral demyelination and neurological deficits

PubMed Central

Murray, Paul D.; McGavern, Dorian B.; Pease, Larry R.; Rodriguez, Moses

2017-01-01

IFN-γ is an anti-viral and immunomodulatory cytokine critical for resistance to multiple pathogens. Using mice with targeted disruption of the gene for IFN-γ, we previously demonstrated that this cytokine is critical for resistance to viral persistence and demyelination in the Theiler’s virus model of multiple sclerosis. During viral infections, IFN-γ is produced by natural killer (NK) cells, CD4+ and CD8+ T cells; however, the proportions of lymphocyte subsets responding to virus infection influences the contributions to IFN-γ-mediated protection. To determine the lymphocyte subsets that produce IFN-γ to maintain resistance, we used adoptive transfer strategies to generate mice with lymphocyte-specific deficiencies in IFN-γ-production. We demonstrate that IFN-γ production by both CD4+ and CD8+ T cell subsets is critical for resistance to Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelination and neurological disease, and that CD4+ T cells make a greater contribution to IFN-γ-mediated protection. To determine the cellular targets of IFN-γ-mediated responses, we used adoptive transfer studies and bone marrow chimerism to generate mice in which either hematopoietic or somatic cells lacked the ability to express IFN-γ receptor. We demonstrate that IFN-γ receptor must be present on central nervous system glia, but not bone marrow-derived lymphocytes, in order to maintain resistance to TMEV-induced demyelination. PMID:11857334

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 temperament, and depression.

DOES ALCOHOLICS ANONYMOUS WORK DIFFERENTLY FOR MEN AND WOMEN? A MODERATED MULTIPLE-MEDIATION ANALYSIS IN A LARGE CLINICAL SAMPLE

PubMed Central

Kelly, John F.; Hoeppner, Bettina B.

2012-01-01

Background Alcoholics Anonymous (AA) began as a male organization, but about one third is now female. Studies have found that women participate at least as much as men and benefit equally from AA, but it is unclear whether women benefit from AA in the same or different ways as men. This study tested whether gender moderated the mechanisms through which AA aids recovery. Methods A cohort study of alcohol dependent adults (N=1,726; 24% female; Project MATCH) was assessed on AA attendance during treatment; with mediators at 9 months; outcomes (Percent Days Abstinent [PDA] and Drinks per Drinking Day [DDD]) at 15 months. Multiple mediator models tested whether purported mechanisms (i.e., self-efficacy, depression, social networks, spirituality/religiosity) explained AA's effects differently for men and women controlling for baseline values, mediators, treatment, and other confounders. Results For PDA, the proportion of AA's effect accounted for by the mediators was similar for men (53%) and women (49%). Both men and women were found to benefit from changes in social factors but these mechanisms were more important among men. For DDD, the mediators accounted for 70% of the effect of AA for men and 41% for women. Again, men benefitted mostly from social changes. Independent of AA's effects, negative affect self-efficacy was shown to have a strong relationship to outcome for women but not men. Conclusions The recovery benefits derived from AA differ in nature and magnitude between men and women and may reflect differing needs based on recovery challenges related to gender-based social roles and drinking contexts. PMID:23206376

Life stressors as mediators of the relation between socioeconomic position and mental health problems in early adolescence: the TRAILS study.

PubMed

Amone-P'Olak, Kennedy; Ormel, Johan; Huisman, Martijn; Verhulst, Frank C; Oldehinkel, Albertine J; Burger, Huibert

2009-10-01

Life stressors and family socioeconomic position have often been associated with mental health status. The aim of the present study is to contribute to the understanding of the pathways from low socioeconomic position and life stressors to mental problems. In a cross-sectional analysis using data from a longitudinal study of early adolescents (N = 2,149, 51% girls; mean age 13.6 years, SD 0.53, range 12-15), we assessed the extent of mediation of the association between family socioeconomic position and mental health problems by different types of life stressors in multiple regression models. Stressors were rated as environment related or person related. Information on socioeconomic position was obtained directly from parents, and internalizing and externalizing problem behaviors were assessed by reports from multiple informants (parents, self, and teachers). Low socioeconomic position was associated with more mental health problems and more life stressors. Both environment-related and person-related stressors predicted mental health problems independently of socioeconomic position. The associations between socioeconomic position and all mental health outcomes were partly mediated by environment-related life stressors. Mediation by environment-related and person-related stressors as assessed by linear regression amounted to 56% (95% confidence interval [CI] 35%-78%) and 7% (95% CI -25% to 38%) for internalizing problems and 13% (95% CI 7%-19%) and 5% (95% CI -2% to 13%) for externalizing problems, respectively. Environment-related, but not person-related, stressors partly mediated the association between socio economic position and adolescent mental problems. The extent of mediation was larger for internalizing than for externalizing problems. Because the effect sizes of the associations were relatively small, targeted interventions to prevent impaired mental health may have only modest benefits to adolescents from low socioeconomic background.

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

PubMed

Kelly, John F; Hoeppner, Bettina B

2013-06-01

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

Allostatic load: A theoretical model for understanding the relationship between maternal posttraumatic stress disorder and adverse birth outcomes.

PubMed

Li, Yang; Rosemberg, Marie-Anne Sanon; Seng, Julia S

2018-07-01

Adverse birth outcomes such as preterm birth and low birth weight are significant public health concerns and contribute to neonatal morbidity and mortality. Studies have increasingly been exploring the predictive effects of maternal posttraumatic stress disorder (PTSD) on adverse birth outcomes. However, the biological mechanisms by which maternal PTSD affects birth outcomes are not well understood. Allostatic load refers to the cumulative dysregulations of the multiple physiological systems as a response to multiple social-ecological levels of chronic stress. Allostatic load has been well documented in relation to both chronic stress and adverse health outcomes in non-pregnant populations. However, the mediating role of allostatic load is less understood when it comes to maternal PTSD and adverse birth outcomes. To propose a theoretical model that depicts how allostatic load could mediate the impact of maternal PTSD on birth outcomes. We followed the procedures for theory synthesis approach described by Walker and Avant (2011), including specifying focal concepts, identifying related factors and relationships, and constructing an integrated representation. We first present a theoretical overview of the allostatic load theory and the other 4 relevant theoretical models. Then we provide a brief narrative review of literature that empirically supports the propositions of the integrated model. Finally, we describe our theoretical model. The theoretical model synthesized has the potential to advance perinatal research by delineating multiple biomarkers to be used in future. After it is well validated, it could be utilized as the theoretical basis for health care professionals to identify high-risk women by evaluating their experiences of psychosocial and traumatic stress and to develop and evaluate service delivery and clinical interventions that might modify maternal perceptions or experiences of stress and eliminate their impacts on adverse birth outcomes. Copyright © 2018. Published by Elsevier Ltd.

Severity of Children's ADHD Symptoms and Parenting Stress: A Multiple Mediation Model of Self-Regulation

ERIC Educational Resources Information Center

Graziano, Paulo A.; McNamara, Joseph P.; Geffken, Gary R.; Reid, Adam

2011-01-01

The goal of the current study was to determine the extent to which the perceived self-regulation deficits across behavioral, cognitive, and emotional domains seen in children with ADHD explain the association between the severity of ADHD symptoms and parenting stress. Participants for this study included 80 children (mean age = 10 years, 9 months)…

Understanding the Relationships between Gender Inequitable Behaviours, Childhood Trauma and Socio-Economic Status in Single and Multiple Perpetrator Rape in Rural South Africa: Structural Equation Modelling.

PubMed

Jewkes, Rachel; Nduna, Mzikazi; Jama-Shai, Nwabisa; Chirwa, Esnat; Dunkle, Kristin

2016-01-01

Interventions to prevent rape perpetration must be designed to address its drivers. This paper seeks to extend understanding of drivers of single and multiple perpetrator rape (referred to here as SPR and MPR respectively) and the relationships between socio-economic status, childhood trauma, peer pressure, other masculine behaviours and rape. 1370 young men aged 15 to 26 were interviewed as part of the randomised controlled trial evaluation of Stepping Stones in the rural Eastern Cape. We used multinomial to compare the characteristics of men who reported rape perpetration at baseline. We used structural equation modelling (SEM) to examine pathways to rape perpetration. 76.1% of young men had never raped, 10.0% had perpetrated SPR and 13.9% MPR. The factors associated with both MPR and SPR (compared to never having raped) were indicators of socio-economic status (SES), childhood trauma, sexual coercion by a woman, drug and alcohol use, peer pressure susceptibility, having had transactional sex, multiple sexual partners and being physically violent towards a partner. The SEM showed the relationship between SES and rape perpetration to be mediated by gender inequitable masculinity. It was complex as there was a direct path indicating that SES correlated with the masculinity variable directly such that men of higher SES had more gender inequitable masculinities, and indirect path mediated by peer pressure resistance indicated that the former pertained so long as men lacked peer pressure resistance. Having a higher SES conveyed greater resistance for some men. There was also a path mediated through childhood trauma, such that men of lower SES were more likely to have a higher childhood trauma exposure and this correlated with a higher likelihood of having the gender inequitable masculinity (with or without the mediating effect of peer pressure resistance). Both higher and lower socio-economic status were associated with raping. Prevention of rape perpetration must focus on changing men's gender ideals, entitlements and inequitable practices. Reducing poverty and adverse childhood experiences should also be of benefit.

Understanding the Relationships between Gender Inequitable Behaviours, Childhood Trauma and Socio-Economic Status in Single and Multiple Perpetrator Rape in Rural South Africa: Structural Equation Modelling

PubMed Central

Jewkes, Rachel; Nduna, Mzikazi; Jama-Shai, Nwabisa; Chirwa, Esnat; Dunkle, Kristin

2016-01-01

Background Interventions to prevent rape perpetration must be designed to address its drivers. This paper seeks to extend understanding of drivers of single and multiple perpetrator rape (referred to here as SPR and MPR respectively) and the relationships between socio-economic status, childhood trauma, peer pressure, other masculine behaviours and rape. Method 1370 young men aged 15 to 26 were interviewed as part of the randomised controlled trial evaluation of Stepping Stones in the rural Eastern Cape. We used multinomial to compare the characteristics of men who reported rape perpetration at baseline. We used structural equation modelling (SEM) to examine pathways to rape perpetration. Results 76.1% of young men had never raped, 10.0% had perpetrated SPR and 13.9% MPR. The factors associated with both MPR and SPR (compared to never having raped) were indicators of socio-economic status (SES), childhood trauma, sexual coercion by a woman, drug and alcohol use, peer pressure susceptibility, having had transactional sex, multiple sexual partners and being physically violent towards a partner. The SEM showed the relationship between SES and rape perpetration to be mediated by gender inequitable masculinity. It was complex as there was a direct path indicating that SES correlated with the masculinity variable directly such that men of higher SES had more gender inequitable masculinities, and indirect path mediated by peer pressure resistance indicated that the former pertained so long as men lacked peer pressure resistance. Having a higher SES conveyed greater resistance for some men. There was also a path mediated through childhood trauma, such that men of lower SES were more likely to have a higher childhood trauma exposure and this correlated with a higher likelihood of having the gender inequitable masculinity (with or without the mediating effect of peer pressure resistance). Discussion Both higher and lower socio-economic status were associated with raping. Prevention of rape perpetration must focus on changing men’s gender ideals, entitlements and inequitable practices. Reducing poverty and adverse childhood experiences should also be of benefit. PMID:27182972

The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation.

PubMed

Malik, Sohail; Roeder, Robert G

2010-11-01

The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action of numerous other co-activators and co-repressors, including those acting at the level of chromatin. These interactions ultimately allow the Mediator to deliver outputs that range from maximal activation of genes to modulation of basal transcription to long-term epigenetic silencing.

Test of a mediated performance-turnover relationship highlighting the moderating roles of visibility and reward contingency.

PubMed

Allen, D G; Griffeth, R W

2001-10-01

Despite the importance of understanding the conditions under which high performing employees are more likely or less likely to voluntarily leave an organization, the nature of the relationship between job performance and voluntary turnover has proven to be elusive. A model of the performance-turnover relationship that highlights important moderators and mediators is proposed and tested. Data consisted of organizational performance and turnover records and survey responses for 130 employees of a medical services organization. Results indicate that visibility and reward contingencies moderate performance relationships with alternatives and job satisfaction, respectively, and that performance may influence turnover through multiple mechanisms.

Multiple transport systems mediate virus-induced acquired resistance to oxidative stress

USDA-ARS?s Scientific Manuscript database

In this paper, we report the phenomenon of acquired cross-tolerance to oxidative (UV-C and H2O2) stress in Nicotiana benthamiana plants infected with Potato virus X (PVX) and investigate the functional expression of transport systems in mediating this phenomenon. By combining multiple approaches, we...

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.

Cross-sectional evidence for a stress-negative affect pathway to substance use among sexual minority girls.

PubMed

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

2013-08-01

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

Mechanistic kinetic modeling generates system-independent P-glycoprotein mediated transport elementary rate constants for inhibition and, in combination with 3D SIM microscopy, elucidates the importance of microvilli morphology on P-glycoprotein mediated efflux activity.

PubMed

Ellens, Harma; Meng, Zhou; Le Marchand, Sylvain J; Bentz, Joe

2018-06-01

In vitro transporter kinetics are typically analyzed by steady-state Michaelis-Menten approximations. However, no clear evidence exists that these approximations, applied to multiple transporters in biological membranes, yield system-independent mechanistic parameters needed for reliable in vivo hypothesis generation and testing. Areas covered: The classical mass action model has been developed for P-glycoprotein (P-gp) mediated transport across confluent polarized cell monolayers. Numerical integration of the mass action equations for transport using a stable global optimization program yields fitted elementary rate constants that are system-independent. The efflux active P-gp was defined by the rate at which P-gp delivers drugs to the apical chamber, since as much as 90% of drugs effluxed by P-gp partition back into nearby microvilli prior to reaching the apical chamber. The efflux active P-gp concentration was 10-fold smaller than the total expressed P-gp for Caco-2 cells, due to their microvilli membrane morphology. The mechanistic insights from this analysis are readily extrapolated to P-gp mediated transport in vivo. Expert opinion: In vitro system-independent elementary rate constants for transporters are essential for the generation and validation of robust mechanistic PBPK models. Our modeling approach and programs have broad application potential. They can be used for any drug transporter with minor adaptations.

Association Between Internalized HIV-Related Stigma and HIV Care Visit Adherence.

PubMed

Rice, Whitney S; Crockett, Kaylee B; Mugavero, Michael J; Raper, James L; Atkins, Ghislaine C; Turan, Bulent

2017-12-15

Internalized HIV-related stigma acts as a barrier to antiretroviral therapy (ART) adherence, but its effects on other HIV care continuum outcomes are unclear. Among 196 HIV clinic patients in Birmingham, AL, we assessed internalized HIV-related stigma and depressive symptom severity using validated multi-item scales and assessed ART adherence using a validated single-item measure. HIV visit adherence (attended out of total scheduled visits) was calculated using data from clinic records. Using covariate-adjusted regression analysis, we investigated the association between internalized stigma and visit adherence. Using path analytic methods with bootstrapping, we tested the mediating role of depressive symptoms in the association between internalized stigma and visit adherence and the mediating role of visit adherence in the association between internalized stigma and ART adherence. Higher internalized stigma was associated with lower visit adherence (B = -0.04, P = 0.04). Black (versus white) race and depressive symptoms were other significant predictors within this model. Mediation analysis yielded no indirect effect through depression in the association between internalized stigma and visit adherence (B = -0.18, SE = 0.11, 95% confidence interval: -0.44 to -0.02) in the whole sample. Supplemental mediated moderation analyses revealed gender-specific effects. Additionally, the effect of internalized stigma on suboptimal ART adherence was mediated by lower visit adherence (B = -0.18, SE = 0.11, 95% confidence interval: -0.44 to -0.02). Results highlight the importance of internalized HIV stigma to multiple and sequential HIV care continuum outcomes. Also, findings suggest multiple intervention targets, including addressing internalized stigma directly, reducing depressive symptoms, and promoting consistent engagement in care.

A Single Multiplex crRNA Array for FnCpf1-Mediated Human Genome Editing.

PubMed

Sun, Huihui; Li, Fanfan; Liu, Jie; Yang, Fayu; Zeng, Zhenhai; Lv, Xiujuan; Tu, Mengjun; Liu, Yeqing; Ge, Xianglian; Liu, Changbao; Zhao, Junzhao; Zhang, Zongduan; Qu, Jia; Song, Zongming; Gu, Feng

2018-06-15

Cpf1 has been harnessed as a tool for genome manipulation in various species because of its simplicity and high efficiency. Our recent study demonstrated that FnCpf1 could be utilized for human genome editing with notable advantages for target sequence selection due to the flexibility of the protospacer adjacent motif (PAM) sequence. Multiplex genome editing provides a powerful tool for targeting members of multigene families, dissecting gene networks, modeling multigenic disorders in vivo, and applying gene therapy. However, there are no reports at present that show FnCpf1-mediated multiplex genome editing via a single customized CRISPR RNA (crRNA) array. In the present study, we utilize a single customized crRNA array to simultaneously target multiple genes in human cells. In addition, we also demonstrate that a single customized crRNA array to target multiple sites in one gene could be achieved. Collectively, FnCpf1, a powerful genome-editing tool for multiple genomic targets, can be harnessed for effective manipulation of the human genome. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

cit: hypothesis testing software for mediation analysis in genomic applications.

PubMed

Millstein, Joshua; Chen, Gary K; Breton, Carrie V

2016-08-01

The challenges of successfully applying causal inference methods include: (i) satisfying underlying assumptions, (ii) limitations in data/models accommodated by the software and (iii) low power of common multiple testing approaches. The causal inference test (CIT) is based on hypothesis testing rather than estimation, allowing the testable assumptions to be evaluated in the determination of statistical significance. A user-friendly software package provides P-values and optionally permutation-based FDR estimates (q-values) for potential mediators. It can handle single and multiple binary and continuous instrumental variables, binary or continuous outcome variables and adjustment covariates. Also, the permutation-based FDR option provides a non-parametric implementation. Simulation studies demonstrate the validity of the cit package and show a substantial advantage of permutation-based FDR over other common multiple testing strategies. The cit open-source R package is freely available from the CRAN website (https://cran.r-project.org/web/packages/cit/index.html) with embedded C ++ code that utilizes the GNU Scientific Library, also freely available (http://www.gnu.org/software/gsl/). joshua.millstein@usc.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

An integrated 3-Dimensional Genome Modeling Engine for data-driven simulation of spatial genome organization.

PubMed

Szałaj, Przemysław; Tang, Zhonghui; Michalski, Paul; Pietal, Michal J; Luo, Oscar J; Sadowski, Michał; Li, Xingwang; Radew, Kamen; Ruan, Yijun; Plewczynski, Dariusz

2016-12-01

ChIA-PET is a high-throughput mapping technology that reveals long-range chromatin interactions and provides insights into the basic principles of spatial genome organization and gene regulation mediated by specific protein factors. Recently, we showed that a single ChIA-PET experiment provides information at all genomic scales of interest, from the high-resolution locations of binding sites and enriched chromatin interactions mediated by specific protein factors, to the low resolution of nonenriched interactions that reflect topological neighborhoods of higher-order chromosome folding. This multilevel nature of ChIA-PET data offers an opportunity to use multiscale 3D models to study structural-functional relationships at multiple length scales, but doing so requires a structural modeling platform. Here, we report the development of 3D-GNOME (3-Dimensional Genome Modeling Engine), a complete computational pipeline for 3D simulation using ChIA-PET data. 3D-GNOME consists of three integrated components: a graph-distance-based heat map normalization tool, a 3D modeling platform, and an interactive 3D visualization tool. Using ChIA-PET and Hi-C data derived from human B-lymphocytes, we demonstrate the effectiveness of 3D-GNOME in building 3D genome models at multiple levels, including the entire genome, individual chromosomes, and specific segments at megabase (Mb) and kilobase (kb) resolutions of single average and ensemble structures. Further incorporation of CTCF-motif orientation and high-resolution looping patterns in 3D simulation provided additional reliability of potential biologically plausible topological structures. © 2016 Szałaj et al.; Published by Cold Spring Harbor Laboratory Press.

Attachment, hope, and participation: Testing an expanded model of Snyder's hope theory for prediction of participation for individuals with spinal cord injury.

PubMed

Blake, John; Yaghmaian, Rana; Brooks, Jessica; Fais, Connor; Chan, Fong

2018-05-01

The aim of the study was to test an expanded model of Snyder's hope theory for prediction of participation for individuals with spinal cord injury (SCI). Statistical model testing focused on evaluation of hope theory constructs (i.e., agency thoughts and pathways thoughts) as serial mediators of relationships between attachment and community participation. Quantitative, cross-sectional, descriptive design using multiple regression and correlational techniques. The sample comprised 108 persons with SCI recruited from spinal cord injury advocacy organizations in the United States, the United Kingdom, and Canada. Secure attachment, avoidant attachment, anxious attachment, and the hope constructs were significantly related to participation. Significant mediational effects were observed when agency thoughts and pathways thoughts were specified as mediators in series between attachment and community participation for people with SCI (i.e., agency specified as M1 and pathways specified as M2). Results provide support for Snyder's theoretical conceptualization and the use of hope-based interventions by rehabilitation practitioners for improving global participation outcomes for people with SCI who experience attachment-related difficulties. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Linking childhood abuse and hypertension: sleep disturbance and inflammation as mediators.

PubMed

Petrov, Megan E; Davis, Mary C; Belyea, Michael J; Zautra, Alex J

2016-08-01

The indirect association of childhood abuse with prevalent hypertension in adulthood through sleep disturbance and pro-inflammatory biomarkers was investigated in 589 community-dwelling, middle-aged adults. Participants completed the Childhood Trauma Questionnaire and self-reported current sleep disturbance and medical diagnoses including hypertension. Blood pressure was taken and blood samples were analyzed for C-reactive protein, interleukin-6, and fibrinogen. Hypertension was present in 41.3 % of the sample. In the full multiple mediation model, tested using structural equation modeling, all hypothesized pathways were significant (p's < 0.05). Childhood abuse was significantly related to both body mass index and sleep disturbance, which, both in turn, were significantly associated with inflammation, which was subsequently associated with hypertension status. The model demonstrated good fit [χ(2) (122) = 352.0, p < 0.001, CFI = 0.918, RMSEA = 0.057] and the indirect effect of all mediators was significant (indirect effect: 0.02, 95 % CI 0.005-0.03, p = 0.001). Sleep disturbance, body mass, and inflammation may be independent, intermediate steps between childhood abuse and subsequent hypertension that may be amenable to biobehavioral interventions.

Immunopharmacological role of the leukotriene receptor antagonists and inhibitors of leukotrienes generating enzymes in multiple sclerosis.

PubMed

Mirshafiey, Abbas; Jadidi-Niaragh, Farhad

2010-06-01

Multiple sclerosis (MS) is a chronic inflammatory disease that involves central nervous system, and is generally associated with demyelination and axonal lesion. The effective factors for initiation of the inflammatory responses have not been known precisely so far. Leukotrienes (LTs) are inflammatory mediators with increased levels in the cerebrospinal fluid of MS patients and in experimental models of multiple sclerosis. Inhibition of LT receptors with specific antagonists can decrease inflammatory responses. In this review article we try to clarify the role of LT receptor antagonists and also inhibitors of enzymes which are involved in LTs generating pathway for treating multiple sclerosis as new targets for MS therapy. Moreover, we suggest that blockage of LT receptors by potent specific antagonists and/or agonists can be as a novel useful method in treatment of MS.

[Socioeconomical level and behavior in school-age children: the mediating role of parents].

PubMed

Ulloa Vidal, Natalia; Cova Solar, Félix; Bustos N, Claudio

2017-06-01

A determinant of particular relevance in human development is the socioeconomic status (SES) and, specifically, low SES and poverty. Likewise, family environment is essential in the development of children and a potential mediator or moderator of the effect of broader social conditions. To analyze the role of parenting stress as a mediating variable of the relationship between SES and both externalized and internalized behaviors in preschool children. Descriptive secondary base study based on the Longitudinal Survey of Chilean First Infancy that selected a stratified sample, representative by clusters, of 9.996 children from 3 to 5 years old and their caregivers, that completed a battery of instruments for measuring SES variables, parenting stress and externalized and internalized behaviors. The analysis used a linear model with least square estimate. As hypothesis testing, the Dm (an adaptation of the F-test for multiple imputation method) was used. The mediation model of parenting stress in the relationship between SES and both externalized and internalized behaviors was confirmed for the latter; regarding externalized behaviors a model of moderation was observed, being the stress influence lower on the low SES. Parental stress showed a clear relationship with the presence of externalized and internalized behaviors, stronger than the SES. The relationship between SES and parenting stress is very important to understand the processes that affect children’s development.

Adult attachment, hostile conflict, and relationship adjustment among couples facing multiple sclerosis.

PubMed

Crangle, Cassandra J; Hart, Tae L

2017-11-01

Couples facing multiple sclerosis (MS) report significantly elevated rates of relationship distress, yet the effects of attachment have never been examined in this population. We examined whether hostile conflict mediated the dyadic effects of attachment on relationship adjustment in couples facing MS and whether these associations were moderated by gender or role. We also explored whether dyadic adjustment mediated the relationship between attachment and hostile conflict. The study was cross-sectional and included 103 couples in which one partner had been diagnosed with MS. Participants completed the Experiences in Close Relationships-Revised, Dyadic Adjustment Scale, and Aversive Interactions Scale, as well as demographic variables. We used the actor-partner interdependence model for data analysis. There were significant actor and partner effects of greater anxious attachment and worse dyadic adjustment. Actor and partner effects of anxious attachment were significantly mediated by greater hostile conflict. Gender significantly moderated the effects between avoidant attachment and dyadic adjustment. The actor effect was significant for males and females; the partner effect was only significant for females. The actor effect for females but not males was significantly mediated by greater hostile conflict. Role was not a significant moderator. Exploratory analyses also showed that dyadic adjustment mediated the relationship between anxious and avoidant attachment and hostile conflict. Findings highlight the important effects of attachment on relationship adjustment in MS couples. Both hostile conflict and dyadic adjustment appear to be mechanisms through which insecure attachment has a detrimental effect. Statement of contribution What is already known on this subject? Despite higher-than-normal rates of marital distress and separation/divorce, the effects of attachment on relationship adjustment among couples facing multiple sclerosis have never been examined. Prior studies within healthy populations have supported within-person and cross-dyadic associations between attachment and relationship adjustment; however, they have failed to use dyadic analyses. Hostile conflict has been associated with both insecure attachment and relationship adjustment and therefore may be an important mediator to help understand these relationships. What does this study add? Women were more negatively affected by their partner's avoidant attachment then men. Hostile conflict mediated the effects of anxious attachment on dyadic adjustment for individuals and across dyads. Hostile conflict accounted for the individual effect of avoidant attachment on dyadic adjustment for women. © 2017 The British Psychological Society.

Psychiatric disability as mediator of the neurocognition-functioning link in schizophrenia spectrum disorders: SEM analysis using the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale.

PubMed

Roux, Paul; Urbach, Mathieu; Fonteneau, Sandrine; Berna, Fabrice; Brunel, Lore; Capdevielle, Delphine; Chereau, Isabelle; Dubreucq, Julien; Faget-Agius, Catherine; Fond, Guillaume; Leignier, Sylvain; Perier, Claire-Cécile; Richieri, Raphaëlle; Schneider, Priscille; Schürhoff, Franck; Tronche, Anne-Marie; Yazbek, Hanan; Zinetti-Bertschy, Anna; Passerieux, Christine; Brunet-Gouet, Eric

2018-06-22

The functional outcome in schizophrenia spectrum disorders is affected by multiple factors such as cognitive performance and clinical symptoms. Psychiatric disability may be another important determinant of functional outcome. The purpose of this study was to test whether schizophrenia symptoms and psychiatric disability mediated the association between cognition and functioning. Between April 2013 and July 2017, we included 108 community-dwelling adults with stable schizophrenia spectrum disorder in a multicenter study. Psychiatric disability was assessed with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale by relatives of patients. ECPDS focused on the broad array of motivational, neurocognitive, sociocognitive, and metacognitive impairments that result in activity restrictions. We used a battery of tests to assess seven cognition domains (processing speed, attention/vigilance, working, verbal and visual memory, reasoning and problem solving, and executive functioning) and cross-sectional structural equation modeling (SEM) for the mediation analyses. We estimated the one-year temporal stability of ECPDS scores in 45 participants. The model provided showed good fit and explained 43.9% of the variance in functioning. The effect of neurocognition on functioning was fully mediated by symptoms (proportion mediated: 36.5%) and psychiatric disability (proportion mediated: 31.3%). The ECPDS score had acceptable one-year temporal stability. The ECPDS scale has satisfactory psychometric properties, and shows significant convergence with neurocognition and functioning, suggesting a role for this tool in the routine evaluation of cognitive remediation needs. Our model validates psychiatric disability as a crucial step from cognitive impairment to restricted participation in life situations. Copyright © 2018 Elsevier B.V. All rights reserved.

Impulsivity-related traits, college alcohol beliefs, and alcohol outcomes: Examination of a prospective multiple mediation model among college students in Spain, Argentina, and USA.

PubMed

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

2018-06-01

The present study examined (both cross-sectionally and prospectively) the mediational role of college alcohol beliefs in the relationship between impulsivity-related traits and alcohol outcomes (i.e., alcohol use and negative consequences) among college student drinkers from the United States (U.S.), Spain, and Argentina. A sample of 1429 (U.S. = 733, Spain = 292, Argentina = 404) drinkers (at least one drinking episode within the previous month) completed the baseline survey, and 242 drinkers completed the follow-up. To test study aims, a cross-sectional model was first employed to examine whether the proposed double-mediated paths (i.e., each dimension of impulsivity → college alcohol beliefs → alcohol use → negative alcohol-related consequences) extends across samples with different cultural backgrounds (i.e., structural invariance testing). A longitudinal model was then conducted to assess if college alcohol beliefs prospectively mediate the associations between trait impulsivity and alcohol outcomes. College alcohol beliefs were concurrently and prospectively associated with both greater alcohol use and increased number of negative alcohol-related consequences. These internalized beliefs about college student drinking culture significantly mediated the effects of several distinct impulsivity-related traits on alcohol-related outcomes including urgency (positive and negative), sensation seeking, and perseverance. These findings were invariant across gender and across three countries (Argentina, Spain, and the U.S.). Our findings highlight the modulatory role of cognitive factors on problematic alcohol use among college students with different cultural backgrounds. Our results suggest that, despite the cultural differences exhibited by these three countries, the unique and mediational effects of college alcohol beliefs appear relatively universal. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transcriptome-Wide Analysis of Hepatitis B Virus-Mediated Changes to Normal Hepatocyte Gene Expression.

PubMed

Lamontagne, Jason; Mell, Joshua C; Bouchard, Michael J

2016-02-01

Globally, a chronic hepatitis B virus (HBV) infection remains the leading cause of primary liver cancer. The mechanisms leading to the development of HBV-associated liver cancer remain incompletely understood. In part, this is because studies have been limited by the lack of effective model systems that are both readily available and mimic the cellular environment of a normal hepatocyte. Additionally, many studies have focused on single, specific factors or pathways that may be affected by HBV, without addressing cell physiology as a whole. Here, we apply RNA-seq technology to investigate transcriptome-wide, HBV-mediated changes in gene expression to identify single factors and pathways as well as networks of genes and pathways that are affected in the context of HBV replication. Importantly, these studies were conducted in an ex vivo model of cultured primary hepatocytes, allowing for the transcriptomic characterization of this model system and an investigation of early HBV-mediated effects in a biologically relevant context. We analyzed differential gene expression within the context of time-mediated gene-expression changes and show that in the context of HBV replication a number of genes and cellular pathways are altered, including those associated with metabolism, cell cycle regulation, and lipid biosynthesis. Multiple analysis pipelines, as well as qRT-PCR and an independent, replicate RNA-seq analysis, were used to identify and confirm differentially expressed genes. HBV-mediated alterations to the transcriptome that we identified likely represent early changes to hepatocytes following an HBV infection, suggesting potential targets for early therapeutic intervention. Overall, these studies have produced a valuable resource that can be used to expand our understanding of the complex network of host-virus interactions and the impact of HBV-mediated changes to normal hepatocyte physiology on viral replication.

Short-term mediating factors of a school-based intervention to prevent youth substance use in Europe.

PubMed

Giannotta, Fabrizia; Vigna-Taglianti, Federica; Rosaria Galanti, Maria; Scatigna, Maria; Faggiano, Fabrizio

2014-05-01

To investigate factors mediating the effects of a European school-based intervention (Unplugged) based on a social influence approach to youths' substance use. Schools in seven European countries (n = 143, including 7,079 pupils) were randomly assigned to an experimental condition (Unplugged curriculum) or a control condition (usual health education). Data were collected before (pretest) and 3 months after the end of the program (posttest). Multilevel multiple mediation models were applied to the study of effect mediation separately for tobacco, alcohol, and cannabis use. Analyses were conducted on the whole sample, and separately on baseline users and nonusers of each substance. Compared with the control group, participants in the program endorsed less positive attitudes toward drugs; positive beliefs about cigarettes, alcohol, and cannabis; and the normative perception of peers using tobacco and cannabis. They also increased in knowledge about all substances and refusal skills toward tobacco. Decreased positive attitudes toward drugs, increase in refusal skills, and reappraisal of norms about peer using tobacco and cannabis appeared to mediate the effects of the program on the use of substances. However, mediating effects were generally weak and some of them were only marginally significant. This study lends some support to the notion that school-based programs based on a social influence model may prevent juvenile substance use through the modification of attitudes, refusal skills, and normative perceptions. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Linking Family Economic Hardship to Early Childhood Health: An Investigation of Mediating Pathways.

PubMed

Hsu, Hui-Chin; Wickrama, Kandauda A S

2015-12-01

The underlying mechanisms through which family economic adversity influences child health are less understood. Taking a process-oriented approach, this study examined maternal mental health and investment in children, child health insurance, and child healthcare as mediators linking family economic hardship (FEH) to child health. A structural equation modeling was applied to test the hypothesized mediating model. After adjustment for sociodemographic risk factors, results revealed: (1) a significant direct path linking FEH to poor child health (effect size = .372), and (2) six significant mediating pathways (total effect size = .089). In two mediating pathways, exposures to FEH undermined mothers' mental health: in the first pathway poor maternal mental health led to decreased parental investment, which, in turn, contributed to poor child health, whereas in the second pathway the adverse effect of poor maternal mental health was cascaded through child unmet healthcare need, which resulted in poor child health. One pathway involved child insurance status, where the effect of FEH increased the likelihood to be uninsured, which led to unmet healthcare need, and, in turn, to poor health. Three pathways involved preventive care: in one pathway FEH contributed to poor preventive care, which led to unmet healthcare need and then to poor health; in the other two pathways where poor preventive care respectively gave rise to decreased investment in children or poor maternal mental health, which further contributed to poor child health. Results suggest that the association between FEH and children's health is mediated by multiple pathways.

Shame versus trauma-related guilt as mediators of the relationship between PTSD symptoms and aggression among returning veterans.

PubMed

Crocker, Laura D; Haller, Moira; Norman, Sonya B; Angkaw, Abigail C

2016-07-01

It is well established that posttraumatic stress disorder (PTSD) is associated with various forms of aggression, though the mechanisms by which PTSD is related to aggression are not fully understood. Some research suggests that the tendency to experience shame, but not guilt, contributes to aggression in individuals with a history of interpersonal trauma. This study tested the hypothesis that trait shame but not trauma-related guilt would mediate the relationship between PTSD symptoms and verbal and physical aggression in veterans with combat/military-related trauma seeking PTSD treatment. In a sample of 127 returning veterans (95% male, mean age = 32.93), negative binomial path analyses tested multiple mediational models in which shame versus trauma-related guilt (separate models entered the effects of global guilt, guilt cognitions, and guilt distress) were examined as mediators of PTSD symptoms on verbal and physical aggression separately. Results indicated that shame partially mediated the association of PTSD symptoms with verbal aggression but not physical aggression when accounting for trauma-related guilt. Although PTSD symptoms were associated with higher scores on all aspects of trauma-related guilt, guilt did not significantly mediate relations between PTSD symptoms and verbal or physical aggression when accounting for shame. These results indicate that it is worthwhile to examine whether addressing shame in PTSD treatment may also reduce verbal aggression in returning veterans. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

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

PubMed

Chu, Li-Chuan

2015-03-01

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

Quiet Ego, Self-Regulatory Skills, and Perceived Stress in College Students.

PubMed

Wayment, Heidi A; Cavolo, Keragan

2018-04-13

Examine the unique contributions of self-control and grit subscales (perseverance, interest consistency) as potential mediators of the relationship between quiet ego characteristics and less perceived stress in college students. Data from 1117 college students were collected between October, 2015 and May, 2016. The sample was split randomly into exploratory and confirmatory samples. Multiple mediator models were tested with PROCESS module (SPSS v. 24) in both samples. Hypotheses were largely confirmed with self-control fully mediating the link between quiet ego and perceived stress in both samples. Although many self-regulatory constructs may argue for their positive impact on college student outcomes, interventions that strengthen self-control, and not grit, may be most promising to reduce perceived stress. Further, interventions to strengthen quiet ego characteristics may be beneficial for strengthening self-control in college students.

Forgiveness and relationship satisfaction: mediating mechanisms.

PubMed

Braithwaite, Scott R; Selby, Edward A; Fincham, Frank D

2011-08-01

Although the ability to forgive transgressions has been linked to overall relationship satisfaction, the mechanisms that mediate this association have not been established. We propose that the tendency to forgive a romantic partner increases relationship satisfaction via increased relational effort and decreased negative conflict. In two studies, we used structural equations modeling to examine these variables as potential mechanisms that drive this association. In Study 1 (N = 523) and Study 2 (N = 446) we found that these variables significantly mediated the association between forgiveness and relationship satisfaction. The findings were robust when examined concurrently and longitudinally, across multiple measures of forgiveness, and when accounting for baseline relationship satisfaction and interpersonal commitment. These two mechanisms parallel theorized positive and negative dimensions of forgiveness and the motivational transformation that is said to underlie forgiveness. Theoretical implications and implications for intervention are discussed.

Ghrelin-mediated sympathoinhibition and suppression of inflammation in sepsis

PubMed Central

Cheyuo, Cletus; Jacob, Asha

2012-01-01

Sepsis, a systemic inflammatory response to infection, continues to carry a high mortality despite advances in critical care medicine. Elevated sympathetic nerve activity in sepsis has been shown to contribute to early hepatocellular dysfunction and subsequently multiple organ failure, resulting in a poor prognosis, especially in the elderly. Thus, suppression of sympathetic nerve activity represents a novel therapeutic option for sepsis. Ghrelin is a 28-amino acid peptide shown to inhibit sympathetic nerve activity and inflammation in animal models of tissue injury. Age-related ghrelin hyporesponsiveness has also been shown to exacerbate sepsis. However, the mechanistic relationship between ghrelin-mediated sympathoinhibition and suppression of inflammation remains poorly understood. This review assesses the therapeutic potential of ghrelin in sepsis in the context of the neuroanatomical and molecular basis of ghrelin-mediated suppression of inflammation through inhibition of central sympathetic outflow. PMID:22068604

G protein-coupled receptors as therapeutic targets for multiple sclerosis

PubMed Central

Du, Changsheng; Xie, Xin

2012-01-01

G protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants. They are considered as the most successful therapeutic targets for a broad spectrum of diseases. Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system (CNS). It is the leading cause of non-traumatic disability in young adults. Great progress has been made over the past few decades in understanding the pathogenesis of MS. Numerous data from animal and clinical studies indicate that many GPCRs are critically involved in various aspects of MS pathogenesis, including antigen presentation, cytokine production, T-cell differentiation, T-cell proliferation, T-cell invasion, etc. In this review, we summarize the recent findings regarding the expression or functional changes of GPCRs in MS patients or animal models, and the influences of GPCRs on disease severity upon genetic or pharmacological manipulations. Hopefully some of these findings will lead to the development of novel therapies for MS in the near future. PMID:22664908

The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: a systems biology approach.

PubMed

Calçada, Dulce; Vianello, Dario; Giampieri, Enrico; Sala, Claudia; Castellani, Gastone; de Graaf, Albert; Kremer, Bas; van Ommen, Ben; Feskens, Edith; Santoro, Aurelia; Franceschi, Claudio; Bouwman, Jildau

2014-01-01

Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic function. Systems biology has helped in identifying the mediators and pathways involved in these phenomena, mainly through the application of high-throughput screening methods, valued for their molecular comprehensiveness. Nevertheless, inflammation and metabolic regulation are dynamical processes whose behavior must be understood at multiple levels of biological organization (molecular, cellular, organ, and system levels) and on multiple time scales. Mathematical modeling of such behavior, with incorporation of mechanistic knowledge on interactions between inflammatory and metabolic mediators, may help in devising nutritional interventions capable of preventing, or ameliorating, the age-associated functional decline of the corresponding systems. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade

PubMed Central

Nakamura, Takao; Ohbayashi, Masaharu; Kuo, Chuan Hui; Komatsu, Naoki; Yakura, Keiko; Tominaga, Takeshi; Inoue, Yoshitsugu; Higashi, Hidemitsu; Murata, Meguru; Takeda, Shuzo; Fukushima, Atsuki; Liu, Fu-Tong; Rothenberg, Marc E.; Ono, Santa Jeremy

2009-01-01

The immune response is regulated, in part, by effector cells whose activation requires multiple signals. For example, T cells require signals emanating from the T cell antigen receptor and co-stimulatory molecules for full activation. Here, we present evidence indicating that IgE-mediated hypersensitivity reactions in vivo also require cognate signals to activate mast cells. Immediate hypersensitivity reactions in the conjunctiva are ablated in mice deficient in eotaxin-1, despite normal numbers of tissue mast cells and levels of IgE. To further define the co-stimulatory signals mediated by chemokine receptor 3 (CCR3), an eotaxin-1 receptor, effects of CCR3 blockade were tested with an allergic conjunctivitis model and in ex vivo isolated connective tissue-type mast cells. Our results show that CCR3 blockade significantly suppresses allergen-mediated hypersensitivity reactions as well as IgE-mediated mast cell degranulation. We propose that a co-stimulatory axis by CCR3, mainly stimulated by eotaxin-1, is pivotal in mast cell-mediated hypersensitivity reactions. PMID:19147836

Pathways to fraction learning: Numerical abilities mediate the relation between early cognitive competencies and later fraction knowledge.

PubMed

Ye, Ai; Resnick, Ilyse; Hansen, Nicole; Rodrigues, Jessica; Rinne, Luke; Jordan, Nancy C

2016-12-01

The current study investigated the mediating role of number-related skills in the developmental relationship between early cognitive competencies and later fraction knowledge using structural equation modeling. Fifth-grade numerical skills (i.e., whole number line estimation, non-symbolic proportional reasoning, multiplication, and long division skills) mapped onto two distinct factors: magnitude reasoning and calculation. Controlling for participants' (N=536) demographic characteristics, these two factors fully mediated relationships between third-grade general cognitive competencies (attentive behavior, verbal and nonverbal intellectual abilities, and working memory) and sixth-grade fraction knowledge (concepts and procedures combined). However, specific developmental pathways differed by type of fraction knowledge. Magnitude reasoning ability fully mediated paths from all four cognitive competencies to knowledge of fraction concepts, whereas calculation ability fully mediated paths from attentive behavior and verbal ability to knowledge of fraction procedures (all with medium to large effect sizes). These findings suggest that there are partly overlapping, yet distinct, developmental pathways from cognitive competencies to general fraction knowledge, fraction concepts, and fraction procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

Behavioral and Nondirective Guided Self-Help for Parents of Children with Externalizing Behavior: Mediating Mechanisms in a Head-To-Head Comparison.

PubMed

Katzmann, Josepha; Hautmann, Christopher; Greimel, Lisa; Imort, Stephanie; Pinior, Julia; Scholz, Kristin; Döpfner, Manfred

2017-05-01

Parent training (PT) delivered as a guided self-help intervention may be a cost- and time-effective intervention in the treatment of children with externalizing disorders. In face-to-face PT, parenting strategies have repeatedly been identified as mediating mechanisms for the decrease of children's problem behavior. Few studies have examined possible mediating effects in guided self-help interventions for parents. The present study aimed to investigate possible mediating variables of a behaviorally oriented guided self-help program for parents of children with externalizing problems compared to a nondirective intervention in a clinical sample. A sample of 110 parents of children with externalizing disorders (80 % boys) were randomized to either a behaviorally oriented or a nondirective guided self-help program. Four putative mediating variables were examined simultaneously in a multiple mediation model using structural equation modelling. The outcomes were child symptoms of ADHD and ODD as well as child externalizing problems, assessed at posttreatment. Analyses showed a significant indirect effect for dysfunctional parental attributions in favor of the group receiving the behavioral program, and significant effects of the behavioral program on positive and negative parenting and parental self-efficacy, compared to the nondirective intervention. Our results indicate that a decrease of dysfunctional parental attributions leads to a decrease of child externalizing problems when parents take part in a behaviorally oriented guided self-help program. However, none of the putative mediating variables could explain the decrease in child externalizing behavior problems in the nondirective group. A change in dysfunctional parental attributions should be considered as a possible mediator in the context of PT.

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

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2013-01-01

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

Perceived Control and Psychological Contract Breach as Explanations of the Relationships Between Job Insecurity, Job Strain and Coping Reactions: Towards a Theoretical Integration.

PubMed

Vander Elst, Tinne; De Cuyper, Nele; Baillien, Elfi; Niesen, Wendy; De Witte, Hans

2016-04-01

This study aims to further knowledge on the mechanisms through which job insecurity is related to negative outcomes. Based on appraisal theory, two explanations-perceived control and psychological contract breach-were theoretically integrated in a comprehensive model and simultaneously examined as mediators of the job insecurity-outcome relationship. Different categories of outcomes were considered, namely work-related (i.e. vigour and need for recovery) and general strain (i.e. mental and physical health complaints), as well as psychological (i.e. job satisfaction and organizational commitment) and behavioural coping reactions (i.e. self-rated performance and innovative work behaviour). The hypotheses were tested using data of a heterogeneous sample of 2413 Flemish employees by means of both single and multiple mediator structural equation modelling analyses (bootstrapping method). Particularly, psychological contract breach accounted for the relationship between job insecurity and strain. Both perceived control and psychological contract breach mediated the relationships between job insecurity and psychological coping reactions, although the indirect effects were larger for psychological contract breach. Finally, perceived control was more important than psychological contract breach in mediating the relationships between job insecurity and behavioural coping reactions. This study meets previous calls for a theoretical integration regarding mediators of the job insecurity-outcome relationship. Copyright © 2014 John Wiley & Sons, Ltd.

[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.

Behavioral Self-Regulation and Weight-Related Behaviors in Inner-City Adolescents: A Model of Direct and Indirect Effects

PubMed Central

Isasi, Carmen R.; Wills, Thomas A.

2012-01-01

Background This study examined the association of two distinct self-regulation constructs, effortful control and dysregulation, with weight-related behaviors in adolescents and tested whether these effects were mediated by self-efficacy variables. Methods A school-based survey was conducted with 1771 adolescents from 11 public schools in the Bronx, New York. Self-regulation was assessed by multiple indicators and defined as two latent constructs. Dependent variables included fruit/vegetable intake, intake of snack/junk food, frequency of physical activity, and time spent in sedentary behaviors. Structural equation modeling examined the relation of effortful control and dysregulation to lifestyle behaviors, with self-efficacy variables as possible mediators. Results Study results showed that effortful control had a positive indirect effect on fruit and vegetable intake, mediated by self-efficacy, as well as a direct effect. Effortful control also had a positive indirect effect on physical activity, mediated by self-efficacy. Dysregulation had direct effects on intake of junk food/snacks and time spent in sedentary behaviors. Conclusions These findings indicate that self-regulation characteristics are related to diet and physical activity and that some of these effects are mediated by self-efficacy. Different effects were noted for the two domains of self-regulation. Prevention researchers should consider including self-regulation processes in programs to improve health behaviors in adolescents. PMID:23243551

Natural killer cell lines preferentially kill clonogenic multiple myeloma cells and decrease myeloma engraftment in a bioluminescent xenograft mouse model.

PubMed

Swift, Brenna E; Williams, Brent A; Kosaka, Yoko; Wang, Xing-Hua; Medin, Jeffrey A; Viswanathan, Sowmya; Martinez-Lopez, Joaquin; Keating, Armand

2012-07-01

Novel therapies capable of targeting drug resistant clonogenic MM cells are required for more effective treatment of multiple myeloma. This study investigates the cytotoxicity of natural killer cell lines against bulk and clonogenic multiple myeloma and evaluates the tumor burden after NK cell therapy in a bioluminescent xenograft mouse model. The cytotoxicity of natural killer cell lines was evaluated against bulk multiple myeloma cell lines using chromium release and flow cytometry cytotoxicity assays. Selected activating receptors on natural killer cells were blocked to determine their role in multiple myeloma recognition. Growth inhibition of clonogenic multiple myeloma cells was assessed in a methylcellulose clonogenic assay in combination with secondary replating to evaluate the self-renewal of residual progenitors after natural killer cell treatment. A bioluminescent mouse model was developed using the human U266 cell line transduced to express green fluorescent protein and luciferase (U266eGFPluc) to monitor disease progression in vivo and assess bone marrow engraftment after intravenous NK-92 cell therapy. Three multiple myeloma cell lines were sensitive to NK-92 and KHYG-1 cytotoxicity mediated by NKp30, NKp46, NKG2D and DNAM-1 activating receptors. NK-92 and KHYG-1 demonstrated 2- to 3-fold greater inhibition of clonogenic multiple myeloma growth, compared with killing of the bulk tumor population. In addition, the residual colonies after treatment formed significantly fewer colonies compared to the control in a secondary replating for a cumulative clonogenic inhibition of 89-99% at the 20:1 effector to target ratio. Multiple myeloma tumor burden was reduced by NK-92 in a xenograft mouse model as measured by bioluminescence imaging and reduction in bone marrow engraftment of U266eGFPluc cells by flow cytometry. This study demonstrates that NK-92 and KHYG-1 are capable of killing clonogenic and bulk multiple myeloma cells. In addition, multiple myeloma tumor burden in a xenograft mouse model was reduced by intravenous NK-92 cell therapy. Since multiple myeloma colony frequency correlates with survival, our observations have important clinical implications and suggest that clinical studies of NK cell lines to treat MM are warranted.

The mechanisms mediating the effects of poverty on children's intellectual development.

PubMed

Guo, G; Harris, K M

2000-11-01

Although adverse consequences of poverty for children are documented widely, little is understood about the mechanisms through which the effects of poverty disadvantage young children. In this analysis we investigate multiple mechanisms through which poverty affects a child's intellectual development. Using data from the NLSY and structural equation models, we have constructed five latent factors (cognitive stimulation, parenting style, physical environment, child's ill health at birth, and ill health in childhood) and have allowed these factors, along with child care, to mediate the effects of poverty and other exogenous variables. We produce two main findings. First, the influence of family poverty on children's intellectual development is mediated completely by the intervening mechanisms measured by our latent factors. Second, our analysis points to cognitive stimulation in the home, and (to a lesser extent) to parenting style, physical environment of the home, and poor child health at birth, as mediating factors that are affected by lack of income and that influence children's intellectual development.

Synaptic Vesicle Endocytosis Occurs on Multiple Timescales and Is Mediated by Formin-Dependent Actin Assembly.

PubMed

Soykan, Tolga; Kaempf, Natalie; Sakaba, Takeshi; Vollweiter, Dennis; Goerdeler, Felix; Puchkov, Dmytro; Kononenko, Natalia L; Haucke, Volker

2017-02-22

Neurotransmission is based on the exocytic fusion of synaptic vesicles (SVs) followed by endocytic membrane retrieval and the reformation of SVs. Recent data suggest that at physiological temperature SVs are internalized via clathrin-independent ultrafast endocytosis (UFE) within hundreds of milliseconds, while other studies have postulated a key role for clathrin-mediated endocytosis (CME) of SV proteins on a timescale of seconds to tens of seconds. Here we demonstrate using cultured hippocampal neurons as a model that at physiological temperature SV endocytosis occurs on several timescales from less than a second to several seconds, yet, is largely independent of clathrin. Clathrin-independent endocytosis (CIE) of SV membranes is mediated by actin-nucleating formins such as mDia1, which are required for the formation of presynaptic endosome-like vacuoles from which SVs reform. Our results resolve previous discrepancies in the field and suggest that SV membranes are predominantly retrieved via CIE mediated by formin-dependent actin assembly. Copyright © 2017 Elsevier Inc. All rights reserved.

Deliberate Rumination and Positive Reappraisal as Serial Mediators Between Life Impact and Posttraumatic Growth in Victims of State Terrorism in Chile (1973-1990).

PubMed

Cárdenas Castro, Manuel; Arnoso Martínez, Maitane; Faúndez Abarca, Ximena

2016-04-06

This study examines the role of coping strategies related to positive reappraisal versus other cognitive strategies (deliberate rumination) as mediators between life impact and posttraumatic growth in survivors of the military dictatorship in Chile between 1973 and 1990 (tortured political prisoners and family members of political prisoners executed and missing). Survey data from 251 political violence survivors were analyzed using the SPSS PROCESS macro for bootstrapping indirect effects (Hayes, 2013). Results indicated that positive reappraisal (or reframing) coping mediated the relationship between life impact and posttraumatic growth. A serial multiple mediation model indicates that in the life impact to growth moderation process, rumination must be followed by positive reappraisal to drive this growth. These findings suggest that positive reappraisal of the traumatic experience is essential to achieve growth reports. Implications of these more complex relations are discussed for both counseling interventions and further research. © The Author(s) 2016.

A Dog Is a Doctor's Best Friend: The Use of a Service Dog as a Perioperative Assistant.

PubMed

Tew, Shannon; Taicher, Brad M

2016-01-01

Service dogs are beneficial in providing assistance to people with multiple types of disabilities and medical disorders including visual impairment, physical disabilities, seizure disorders, diabetes, and mental illness. Some service animals have been trained as a screening tool for cancer. We review a case involving a 6-year-old female with a history of mast cell mediator release and immediate hypersensitivity due to the urticaria pigmentosa variant of cutaneous mastocytosis who underwent a cystourethroscopy. Her service dog, JJ, who would alert to mast cell mediator release, was used throughout the perioperative course as a means of anxiolysis and comfort and to monitor for mast cell mediator release. This case presents an example of a service dog used in a family-care model in the field of anesthesiology and provides a unique example of using a service dog as an additional monitor to alert the care team for impending mast cell mediator release.

A Dog Is a Doctor's Best Friend: The Use of a Service Dog as a Perioperative Assistant

PubMed Central

Tew, Shannon

2016-01-01

Service dogs are beneficial in providing assistance to people with multiple types of disabilities and medical disorders including visual impairment, physical disabilities, seizure disorders, diabetes, and mental illness. Some service animals have been trained as a screening tool for cancer. We review a case involving a 6-year-old female with a history of mast cell mediator release and immediate hypersensitivity due to the urticaria pigmentosa variant of cutaneous mastocytosis who underwent a cystourethroscopy. Her service dog, JJ, who would alert to mast cell mediator release, was used throughout the perioperative course as a means of anxiolysis and comfort and to monitor for mast cell mediator release. This case presents an example of a service dog used in a family-care model in the field of anesthesiology and provides a unique example of using a service dog as an additional monitor to alert the care team for impending mast cell mediator release. PMID:27843665

Health-Related Behavior Mediates the Association Between Personality and Memory Performance in Older Adults.

PubMed

Allen, Mark S; Laborde, Sylvain; Walter, Emma E

2017-03-01

This prospective study explored the potential mediating role of health-related behavior (alcohol involvement, diet, television viewing, and physical activity) in the association between personality and change in memory performance over 2 years. A nationally representative sample of 8,376 U.K. participants aged 55 years and older (4,572 women, 3,804 men) completed self-report measures of personality and health-related behavior in 2010, and completed a memory performance task in 2010 and 2012. After removing variance associated with potential confounding variables, neuroticism and agreeableness had negative associations, and openness and conscientiousness positive associations with change in memory performance. There were no moderation effects by age, sex, education level, or ethnicity. Multiple mediator models demonstrated that physical activity, television viewing, and alcohol intake mediated associations between personality and change in memory performance. These findings provide evidence that the association between personality and memory performance in older adults can be explained, in part, through health-related behavior.

The mediational role of helplessness in psychological outcomes in systemic lupus erythematosus.

PubMed

Mills, S D; Azizoddin, D; Gholizadeh, S; Racaza, G Z; Nicassio, P M

2018-06-01

Objective Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can result in disability and psychological distress. Although pain has been associated with depressive symptomatology and stress in SLE, a paucity of theoretical models have been used to explain the relationship between pain and psychological distress in this population. Thus, the present study examined helplessness as a mediator of the relationship between pain and psychological distress among patients with SLE. Methods Multiple mediation analysis was used to examine the hypothesis that learned helplessness mediates the relationship between pain and symptoms of anxiety, depression, and stress in a sample of patients with SLE ( N = 136) receiving medical care at Cedars Sinai Medical Center. Results The mean score on the Helplessness subscale was 14.5 ( SD = 5.4). Helplessness fully mediated the relationship between pain vitality and symptoms of anxiety (BCa 95% CI (-0.073, -0.015)), depression (BCa 95% CI (-0.502, -0.212)), and stress (BCa 95% CI (-0.063, -0.027)). Conclusion Participants reported a high level of perceived inability to control one's disease. Helplessness fully mediated the relationship between pain and measures of anxiety, depression, and perceived stress among patients with SLE.

CAREGIVER-CHILD INTERACTION, CAREGIVER TRANSITIONS, AND GROUP SIZE AS MEDIATORS BETWEEN INTERVENTION CONDITION AND ATTACHMENT AND PHYSICAL GROWTH OUTCOMES IN INSTITUTIONALIZED CHILDREN.

PubMed

Warner, Hilary A; McCall, Robert B; Groark, Christina J; Kim, Kevin H; Muhamedrahimov, Rifkat J; Palmov, Oleg I; Nikiforova, Natalia V

2017-09-01

This report describes a secondary analysis of data from a comprehensive intervention project which included training and structural changes in three Baby Homes in St. Petersburg, Russian Federation. Multiple mediator models were tested according to the R.M. Baron and D.A. Kenny () causal-steps approach to examine whether caregiver-child interaction quality, number of caregiver transitions, and group size mediated the effects of the intervention on children's attachment behaviors and physical growth. The study utilized a subsample of 163 children from the original Russian Baby Home project, who were between 11 and 19 months at the time of assessment. Results from comparisons of the training and structural changes versus no intervention conditions are presented. Caregiver-child interaction quality and number of caregiver transitions fully mediated the association between intervention condition and attachment behavior. No other mediation was found. Results suggest that the quality of interaction between caregivers and children in institutional care is of primary importance to children's development, but relationship context may play a less direct mediational role, supporting caregiver-child interactions. © 2017 Michigan Association for Infant Mental Health.

Why do boys eat less fruit and vegetables than girls?

PubMed

Bere, Elling; Brug, Johannes; Klepp, Knut-Inge

2008-03-01

To explore why boys eat less fruit and vegetables (F&V) than girls, using longitudinal data following pupils from the age of 12.5 to 15.5 years, including perceived accessibility, modelling, intention, preferences, self-efficacy and knowledge of recommendations as potential mediators. A longitudinal study, based on data collected among the control schools within the intervention project 'Fruits and Vegetables Make the Marks'. This sample contains 896 6th and 7th graders from 20 randomly selected elementary schools within two Norwegian counties. Questionnaires were administered in May 2002 and May 2005 (when the participants were in 9th and 10th grade in 18 secondary elementary schools). In single mediation analyses all determinants mediated parts of the gender difference, but only preferences decreased the gender difference to a level below statistical significance. Preferences alone explained 81% of the gender difference. In the multiple mediation analyses, the six mediators together explained 91% of the gender difference, but only preferences and perceived accessibility contributed uniquely to the explanation, with 25% and 10% respectively. Preference appears as the strongest mediator of the difference in F&V intakes between boys and girls. Further research should explore why girls like F&V more than boys.

The Cascading Effects of Multiple Dimensions of Implementation on Program Outcomes: a Test of a Theoretical Model.

PubMed

Berkel, Cady; Mauricio, Anne M; Sandler, Irwin N; Wolchik, Sharlene A; Gallo, Carlos G; Brown, C Hendricks

2017-12-14

This study tests a theoretical cascade model in which multiple dimensions of facilitator delivery predict indicators of participant responsiveness, which in turn lead to improvements in targeted program outcomes. An effectiveness trial of the 10-session New Beginnings Program for divorcing families was implemented in partnership with four county-level family courts. This study included 366 families assigned to the intervention condition who attended at least one session. Independent observers provided ratings of program delivery (i.e., fidelity to the curriculum and process quality). Facilitators reported on parent attendance and parents' competence in home practice of program skills. At pretest and posttest, children reported on parenting and parents reported child mental health. We hypothesized effects of quality on attendance, fidelity and attendance on home practice, and home practice on improvements in parenting and child mental health. Structural Equation Modeling with mediation and moderation analyses were used to test these associations. Results indicated quality was significantly associated with attendance, and attendance moderated the effect of fidelity on home practice. Home practice was a significant mediator of the links between fidelity and improvements in parent-child relationship quality and child externalizing and internalizing problems. Findings provide support for fidelity to the curriculum, process quality, attendance, and home practice as valid predictors of program outcomes for mothers and fathers. Future directions for assessing implementation in community settings are discussed.

Distributed cerebellar plasticity implements generalized multiple-scale memory components in real-robot sensorimotor tasks.

PubMed

Casellato, Claudia; Antonietti, Alberto; Garrido, Jesus A; Ferrigno, Giancarlo; D'Angelo, Egidio; Pedrocchi, Alessandra

2015-01-01

The cerebellum plays a crucial role in motor learning and it acts as a predictive controller. Modeling it and embedding it into sensorimotor tasks allows us to create functional links between plasticity mechanisms, neural circuits and behavioral learning. Moreover, if applied to real-time control of a neurorobot, the cerebellar model has to deal with a real noisy and changing environment, thus showing its robustness and effectiveness in learning. A biologically inspired cerebellar model with distributed plasticity, both at cortical and nuclear sites, has been used. Two cerebellum-mediated paradigms have been designed: an associative Pavlovian task and a vestibulo-ocular reflex, with multiple sessions of acquisition and extinction and with different stimuli and perturbation patterns. The cerebellar controller succeeded to generate conditioned responses and finely tuned eye movement compensation, thus reproducing human-like behaviors. Through a productive plasticity transfer from cortical to nuclear sites, the distributed cerebellar controller showed in both tasks the capability to optimize learning on multiple time-scales, to store motor memory and to effectively adapt to dynamic ranges of stimuli.

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 of autonomous motivation on intentions and behavior across multiple health-related behaviors with little evidence of moderation by individual differences. Findings have implications for the generalizability of proposed effects in self-determination theory and intentions as a mediator of distal motivational factors on health-related behavior. PMID:25750803

'I remember therefore I am, and I am therefore I remember': exploring the contributions of episodic and semantic self-knowledge to strength of identity.

PubMed

Haslam, Catherine; Jetten, Jolanda; Haslam, S Alexander; Pugliese, Cara; Tonks, James

2011-05-01

The present research explores the relationship between the two components of autobiographical memory--episodic and semantic self-knowledge--and identity strength in older adults living in the community and residential care. Participants (N= 32) completed the autobiographical memory interview and measures of personal identity strength and multiple group memberships. Contrary to previous research, autobiographical memory for all time periods (childhood, early adulthood, and recent life) in the semantic domain was associated with greater strength in personal identity. Further, we obtained support for the hypothesis that the relationship between episodic self-knowledge and identity strength would be mediated by knowledge of personal semantic facts. However, there was also support for a reverse mediation model indicating that a strong sense of identity is associated with semantic self-knowledge and through this may enhance self-relevant recollection. The discussion elaborates on these findings and we propose a self-knowledge and identity model (SKIM) whereby semantic self-knowledge mediates a bidirectional relationship between episodic self-knowledge and identity. ©2010 The British Psychological Society.

Vulnerability to depression: A moderated mediation model of the roles of child maltreatment, peer victimization, and 5-HTTLPR genetic variation among children from low-SES backgrounds

PubMed Central

Banny, Adrienne M.; Cicchetti, Dante; Rogosch, Fred A.; Oshri, Assaf; Crick, Nicki R.

2014-01-01

Child maltreatment, peer victimization, and a polymorphism of the serotonin transporter gene (5-HTTLPR) were examined as predictors of depressive symptomatology. Children (M age = 11.26, SD = 1.65), including 156 maltreated and 145 nonmaltreated children from comparable low socioeconomic backgrounds, provided DNA samples and self-reports of relational peer victimization, overt peer victimization, and depressive symptoms. Path analysis showed that relational and overt victimization mediated the association between child maltreatment and depressive symptoms. Bootstrapping procedures were used to test moderated mediation and demonstrated that genotype moderated the indirect effects of relational and overt victimization on child depressive symptoms, such that victimized children with the l/l variation were at an increased risk for depressive symptoms compared to victimized children carrying an s allele. Results highlight the utility of examining process models that incorporate biological and psychological factors contributing to the development of depressive symptomatology, and provide direction toward understanding and promoting resilience among high risk youth from a multiple levels of analysis approach. PMID:23880379

Helminth–host immunological interactions: prevention and control of immune-mediated diseases

PubMed Central

Elliott, David E.; Weinstock, Joel V.

2013-01-01

Exposure to commensal and pathogenic organisms strongly influences our immune system. Exposure to helminths was frequent before humans constructed their current highly hygienic environment. Today, in highly industrialized countries, contact between humans and helminths is rare. Congruent with the decline in helminth infections is an increase in the prevalence of autoimmune and inflammatory disease. It is possible that exclusion of helminths from the environment has permitted the emergence of immune-mediated disease. We review the protective effects of helminths on expression of inflammatory bowel disease, multiple sclerosis, and animal models of these and other inflammatory diseases. We also review the immune pathways altered by helminths that may afford protection from these illnesses. Helminth exposure tends to inhibit IFN-γ and IL-17 production, promote IL-4, IL-10, and TGF-β release, induce CD4+ T cell Foxp3 expression, and generate regulatory macrophages, dendritic cells, and B cells. Helminths enable protective pathways that may vary by specific species and disease model. Helminths or their products likely have therapeutic potential to control or prevent immune-mediated illness. PMID:22239614

Functional Pathways of Social Support for Mental Health in Work and Family Domains Among Chinese Scientific and Technological Professionals.

PubMed

Gan, Yiqun; Gan, Tingting; Chen, Zhiyan; Miao, Miao; Zhang, Kan

2015-10-01

This study investigated the role of social support in the complex pattern of associations among stressors, work-family interferences and depression in the domains of work and family. A questionnaire was administered to a nationwide sample of 11,419 Chinese science and technology professionals. Several structural equation models were specified to determine whether social support functioned as a predictor or a mediator. Using Mplus 5.0, we compared the moderation model, the independence model, the antecedent model and the mediation model. The results revealed that the relationship between work-family interference and social support was domain specific. The independence model fit the data best in the work domain. Both the moderation model and the antecedent model fit the family domain data equally well. The current study was conducted to answer the need for comprehensive investigations of cultural uniqueness in the antecedents of work-family interference. The domain specificity, i.e. the multiple channels of the functions of support in the family domain and not in the work domain, ensures that this study is unique and culturally specific. Copyright © 2014 John Wiley & Sons, Ltd.

Longitudinal Mediators of Achievement in Mathematics and Reading in Typical and Atypical Development

PubMed Central

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

2014-01-01

Longitudinal studies of neurodevelopmental disorders that are diagnosed at or before birth and which are associated with specific learning difficulties at school-age provide one method for investigating developmental precursors of later-emerging academic disabilities. Spina bifida myelomeningocele (SBM) is a neurodevelopmental disorder associated with particular problems in mathematics, in contrast to well-developed word reading. Children with SBM (n = 30) and typically developing children (n = 35) were used to determine whether cognitive abilities measured at 36 and 60 months of age mediated the effect of group on mathematical and reading achievement outcomes at 8.5 and 9.5 years of age. A series of multiple mediator models showed that: visual-spatial working memory at 36 months and phonological awareness at 60 months partially mediated the effect of group on math calculations; phonological awareness partially mediated the effect of group on small addition and subtraction problems on a test of math fluency; and visual-spatial working memory mediated the effect of group on a test of math problem solving. Groups did not differ on word reading, and phonological awareness was the only mediator for reading fluency and reading comprehension. The findings are discussed with reference to theories of mathematical development and disability and with respect to both common and differing cognitive correlates of math and reading. PMID:24269579

Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb.

PubMed

Wang, Wei; Yao, Xiao; Huang, Yan; Hu, Xiangming; Liu, Runzhong; Hou, Dongming; Chen, Ruichuan; Wang, Gang

2013-01-01

The Mediator is a multi-subunit complex that transduces regulatory information from transcription regulators to the RNA polymerase II apparatus. Growing evidence suggests that Mediator plays roles in multiple stages of eukaryotic transcription, including elongation. However, the detailed mechanism by which Mediator regulates elongation remains elusive. In this study, we demonstrate that Mediator MED23 subunit controls a basal level of transcription by recruiting elongation factor P-TEFb, via an interaction with its CDK9 subunit. The mRNA level of Egr1, a MED23-controlled model gene, is reduced 4-5 fold in Med23 (-/-) ES cells under an unstimulated condition, but Med23-deficiency does not alter the occupancies of RNAP II, GTFs, Mediator complex, or activator ELK1 at the Egr1 promoter. Instead, Med23 depletion results in a significant decrease in P-TEFb and RNAP II (Ser2P) binding at the coding region, but no changes for several other elongation regulators, such as DSIF and NELF. ChIP-seq revealed that Med23-deficiency partially reduced the P-TEFb occupancy at a set of MED23-regulated gene promoters. Further, we demonstrate that MED23 interacts with CDK9 in vivo and in vitro. Collectively, these results provide the mechanistic insight into how Mediator promotes RNAP II into transcription elongation.

Moderators of the mediated effect of intentions, planning, and saturated-fat intake in obese individuals.

PubMed

Soureti, Anastasia; Hurling, Robert; van Mechelen, Willem; Cobain, Mark; ChinAPaw, Mai

2012-05-01

The present study aimed to advance our understanding of health-related theory, that is, the alleged intention-behavior gap in an obese population. It examined the mediating effects of planning on the intention-behavior relationship and the moderated mediation effects of age, self-efficacy and intentions within this relationship. The study was conducted over a five-week period. Complete data from 571 obese participants were analyzed. The moderated mediation hypothesis was conducted using multiple-regression analysis. To test our theoretical model, intentions (Week 2), action self-efficacy (Week 2), maintenance self-efficacy (Week 5), planning (Week 5), and saturated-fat intake (Weeks 1 and 5) were measured by self-report. As hypothesized, planning mediated the intention-behavior relationship for perceived (two-item scale) and percentage-saturated-fat intake (measured by a food frequency questionnaire). Age, self-efficacy, and intention acted as moderators in the above mediation analysis. In specific, younger individuals, those with stronger intention, and people with higher levels of maintenance self-efficacy at higher levels of planning showed greater reductions in their perceived saturated-fat intake. For successful behavior change, knowledge of its mediators and moderators is needed. Future interventions targeting planning to change saturated-fat intake should be guided by people's intentions, age, and self-efficacy levels.

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

PubMed Central

Lidster, Katie; Jackson, Samuel J.; Ahmed, Zubair; Munro, Peter; Coffey, Pete; Giovannoni, Gavin; Baker, Mark D.; Baker, David

2013-01-01

Multiple sclerosis is an immune-mediated, demyelinating and neurodegenerative disease that currently lacks any neuroprotective treatments. Innovative neuroprotective trial designs are required to hasten the translational process of drug development. An ideal target to monitor the efficacy of strategies aimed at treating multiple sclerosis is the visual system, which is the most accessible part of the human central nervous system. A novel C57BL/6 mouse line was generated that expressed transgenes for a myelin oligodendrocyte glycoprotein-specific T cell receptor and a retinal ganglion cell restricted-Thy1 promoter-controlled cyan fluorescent protein. This model develops spontaneous or induced optic neuritis, in the absence of paralytic disease normally associated with most rodent autoimmune models of multiple sclerosis. Demyelination and neurodegeneration could be monitored longitudinally in the living animal using electrophysiology, visual sensitivity, confocal scanning laser ophthalmoscopy and optical coherence tomography all of which are relevant to human trials. This model offers many advantages, from a 3Rs, economic and scientific perspective, over classical experimental autoimmune encephalomyelitis models that are associated with substantial suffering of animals. Optic neuritis in this model led to inflammatory damage of axons in the optic nerve and subsequent loss of retinal ganglion cells in the retina. This was inhibited by the systemic administration of a sodium channel blocker (oxcarbazepine) or intraocular treatment with siRNA targeting caspase-2. These novel approaches have relevance to the future treatment of neurodegeneration of MS, which has so far evaded treatment. PMID:24223903

Pre- and Perinatal Risk for Attention-Deficit Hyperactivity Disorder: Does Neuropsychological Weakness Explain the Link?

PubMed

Wiggs, Kelsey; Elmore, Alexis L; Nigg, Joel T; Nikolas, Molly A

2016-11-01

Etiological investigations of attention-deficit hyperactivity disorder (ADHD) and disruptive behavior problems support multiple causal pathways, including involvement of pre- and perinatal risk factors. Because these risks occur early in life, well before observable ADHD and externalizing symptoms emerge, the relation between risk and symptoms may be mediated by neurodevelopmental effects that manifest later in neuropsychological functioning. However, potential dissociable effects of pre/perinatal risk elements on ADHD and familial confounds must also be considered to test alternative hypotheses. 498 youth aged 6-17 years (55.0 % male) completed a multi-stage, multi-informant assessment including parent and teacher symptom reports of symptoms and parent ratings of pre/perinatal health risk indicators. Youth completed a neuropsychological testing battery. Multiple mediation models examined direct effects of pre- and perinatal health risk on ADHD and other disruptive behavior disorder symptoms and indirect effects via neuropsychological functioning. Parental ADHD symptoms and externalizing status was covaried to control for potential familial effects. Effects of prenatal substance exposure on inattention were mediated by memory span and temporal processing deficits. Further, effects of perinatal health risk on inattention, hyperactivity-impulsivity, and ODD were mediated by deficits in response variability and temporal processing. Further, maternal health risks during pregnancy appeared to exert direct rather than indirect effects on outcomes. Results suggest that after controlling for familial relatedness of ADHD between parent and child, early developmental health risks may influence ADHD via effects on neuropsychological processes underpinning the disorder.

Seemingly irrational driving behavior model: The effect of habit strength and anticipated affective reactions.

PubMed

Chung, Yi-Shih

2015-09-01

An increasing amount of evidence suggests that aberrant driving behaviors are not entirely rational. On the basis of the dual-process theory, this study postulates that drivers may learn to perform irrational aberrant driving behaviors, and these behaviors could be derived either from a deliberate or an intuitive decision-making approach. Accordingly, a seemingly irrational driving behavior model is proposed; in this model, the theory of planned behavior (TPB) was adopted to represent the deliberate decision-making mechanism, and habit strength was incorporated to reflect the intuitive decision process. A multiple trivariate mediation structure was designed to reflect the process through which driving behaviors are learned. Anticipated affective reactions (AARs) were further included to examine the effect of affect on aberrant driving behaviors. Considering the example of speeding behaviors, this study developed scales and conducted a two-wave survey of students in two departments at a university in Northern Taiwan. The analysis results show that habit strength consists of multiple aspects, and frequency of past behavior cannot be a complete repository for accumulating habit strength. Habit strength appeared to be a crucial mediator between intention antecedents (e.g., attitude) and the intention itself. Including habit strength in the TPB model enhanced the explained variance of speeding intention by 26.7%. In addition, AARs were different from attitudes; particularly, young drivers tended to perform speeding behaviors to reduce negative feelings such as regret. The proposed model provides an effective alternative approach for investigating aberrant driving behaviors; corresponding countermeasures are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

ERIC Educational Resources Information Center

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

2013-01-01

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

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

ERIC Educational Resources Information Center

Mohanty, Jayashree

2013-01-01

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

Multiscale Modelling of Cancer Progression and Treatment Control: The Role of Intracellular Heterogeneities in Chemotherapy Treatment

NASA Astrophysics Data System (ADS)

Chaplain, Mark A. J.; Powathil, Gibin G.

Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.

Multiscale Modelling of Cancer Progression and Treatment Control: The Role of Intracellular Heterogeneities in Chemotherapy Treatment

NASA Astrophysics Data System (ADS)

Chaplain, Mark A. J.; Powathil, Gibin G.

2015-04-01

Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.

Parent’s Socioeconomic Status, Adolescents’ Disposable Income, and Adolescents’ Smoking Status in Massachusetts

PubMed Central

Soteriades, Elpidoforos S.; DiFranza, Joseph R.

2003-01-01

Objectives. This study examined the association between parental socioeconomic status (SES) and adolescent smoking. Methods. We conducted telephone interviews with a probability sample of 1308 Massachusetts adolescents aged 12 to 17 years. We used multiple-variable-adjusted logistic regression models. Results. The risk of adolescent smoking increased by 28% with each step down in parental education and increased by 30% for each step down in parental household income. These associations persisted after adjustment for age, sex, race/ethnicity, and adolescent disposable income. Parental smoking status was a mediator of these associations. Conclusions. Parental SES is inversely associated with adolescent smoking. Parental smoking is a mediator but does not fully explain the association. PMID:12835202

Stress and Quality of Life in Breast Cancer Recurrence: Moderation or Mediation of Coping?

PubMed Central

Yang, Hae-Chung; Brothers, Brittany M.; Andersen, Barbara L.

2008-01-01

Background/Purpose Diagnosis with breast cancer recurrence often brings high levels of stress. Successful coping to alleviate stress could improve patients' quality of life (QoL). The intervening role coping plays between stress and QoL may depend on the types of stress encountered and the types of coping strategies used. The present study investigates the longitudinal relationships between stress, coping, and mental health QoL. Methods Breast cancer patients recently diagnosed with recurrence (N=65) were assessed shortly after the diagnosis and 4 months later. Four moderation and four mediation models were tested using hierarchical multiple regressions and path analyses. In the models, either traumatic stress or symptom-related stress at recurrence diagnosis was a predictor of mental health QoL at follow-up. Both engagement and disengagement coping strategies were tested as moderators or mediators between stress and QoL. Results Engagement coping moderated the effect of symptom stress on mental health QoL, whereas disengagement coping mediated the effects of both traumatic stress and symptom stress on mental health QoL. Conclusion The findings imply that interventions teaching engagement coping strategies would be important for patients experiencing high symptom stress, while discouraging the use of disengagement coping strategies would be important for all patients. PMID:18347897

Race-Based Medical Mistrust, Medication Beliefs and HIV Treatment Adherence: Test of a Mediation Model in People Living with HIV/AIDS

PubMed Central

Kalichman, Seth C.; Eaton, Lisa; Kalichman, Moira O.; Grebler, Tama; Merely, Cynthia; Welles, Brandi

2016-01-01

Race-based medical mistrust significantly predicts non-adherence to antiretroviral therapy (ART) in people living with HIV. The current study builds on previous research that shows beliefs about medication necessity (i.e., “My medicines protect me from becoming worse”) and concerns (i.e., Having to take my medicines worries me) mediate the association between race-based medical mistrust and medication adherence. Racial and ethnic minority men and women living with HIV and receiving ART (N=178) in a southern US city completed computerized measures of demographic and health characteristics, telephone interviews of race-based medical mistrust and medication beliefs, and unannounced phone-based pill counts for ART adherence. Multiple mediation modeling showed that medical mistrust is related to medication necessity and concerns beliefs and ART adherence. Furthermore, medication necessity beliefs predicted ART adherence. The indirect effect of medical mistrust on adherence through medication necessity beliefs was also significant. Results confirm that medication necessity beliefs, although not concerns beliefs, mediate the association between medical mistrust and ART adherence. Medication necessity beliefs offer a viable target for interventions to improve ART adherence in the context of mistrust that patients may have for medical providers and health care systems. PMID:27392477

Racial Disparities in Cleanliness Attitudes Mediate Purchasing Attitudes Toward Cleaning Products: a Serial Mediation Model.

PubMed

Litman, Leib; Williams, Monnica T; Rosen, Zohn; Weinberger-Litman, Sarah L; Robinson, Jonathan

2017-09-22

The present study has three objectives (1) to examine whether there are differences in cleanliness concerns between African Americans and European Americans toward kitchen items that are known to be vectors of disease, (2) to examine whether disparities in cleanliness attitudes have an impact on purchasing attitudes toward kitchen cleaning products, and (3) to explore the mechanisms that may account for these differences utilizing a serial mediation model. Five hundred participants, 50% African American and 50% European American were shown a picture of a sponge cleaning product and filled out multiple survey instruments relating to cleanliness attitudes. We found greater concern with cleanliness of kitchen items (d = .46) and a greater willingness to purchase cleaning products among African Americans compared to European Americans (17 vs 10%). A serial mediation analysis revealed that general cleanliness concerns account for the increased willingness to spend money on cleaning products among African Americans. These results suggest that African Americans are more sensitive to issues of cleanliness compared to European Americans and, in particular, are more sensitive to cleanliness of kitchen items such as sponges, which can be vectors of food-borne pathogens. Potential reasons for the observed racial disparities in cleanliness attitudes and the implications of these results for public health are discussed.

Socioeconomic position, health behaviors, and C-reactive protein: A moderated-mediation analysis

PubMed Central

Kershaw, Kiarri N.; Mezuk, Briana; Abdou, Cleopatra M.; Rafferty, Jane A.; Jackson, James S.

2010-01-01

Objective We sought to understand the link between low SEP and cardiovascular disease (CVD) by examining the association between SEP, health-related coping behaviors, and C-reactive protein (CRP), an inflammatory marker and independent risk factor for CVD in a US sample of adults. Design We used a multiple mediation model to evaluate how these behaviors work in concert to influence CRP levels and whether these relationships were moderated by gender and race/ethnicity. Main outcome measures CRP levels were divided into two categories: elevated CRP (3.1–10.0 mg/L) and normal CRP (≤ 3.0 mg/L). Results Both poverty and low educational attainment were associated with elevated CRP, and these associations were primarily explained through higher levels of smoking and lower levels of exercise. In the education model, poor diet also emerged as a significant mediator. These behaviors accounted for 87.9% of the total effect of education on CRP and 55.8% the total effect of poverty on CRP. We also found significant moderation of these mediated effects by gender and race/ethnicity. Conclusion These findings demonstrate the influence of socioeconomically-patterned environmental constraints on individual-level health behaviors. Specifically, reducing socioeconomic inequalities may have positive effects on CVD disparities through reducing cigarette smoking and increasing vigorous exercise. PMID:20496985

Testing the 4Rs and 2Ss Multiple Family Group intervention: study protocol for a randomized controlled trial.

PubMed

Acri, Mary; Hamovitch, Emily; Mini, Maria; Garay, Elene; Connolly, Claire; McKay, Mary

2017-12-04

Oppositional defiant disorder (ODD) is a major mental health concern and highly prevalent among children living in poverty-impacted communities. Despite that treatments for ODD are among the most effective, few children living in poverty receive these services due to substantial barriers to access, as well as difficulties in the uptake and sustained adoption of evidence-based practices (EBPs) in community settings. The purpose of this study is to examine implementation processes that impact uptake of an evidence-based practice for childhood ODD, and the impact of a Clinic Implementation Team (CIT)-driven structured adaptation to enhance its fit within the public mental health clinic setting. This study, a Hybrid Type II effectiveness-implementation research trial, blends clinical effectiveness and implementation research methods to examine the impact of the 4Rs and 2Ss Multiple Family Group (MFG) intervention, family level mediators of child outcomes, clinic/provider-level mediators of implementation, and the impact of CITs on uptake and long-term utilization of this model. All New York City public outpatient mental health clinics have been invited to participate. A sampling procedure that included randomization at the agency level and a sub-study to examine the impact of clinic choice upon outcomes yielded a distribution of clinics across three study conditions. Quantitative data measuring child outcomes, organizational factors and implementation fidelity will be collected from caregivers and providers at baseline, 8, and 16 weeks from baseline, and 6 months from treatment completion. The expected participation is 134 clinics, 268 providers, and 2688 caregiver/child dyads. We will use mediation analysis with a multi-level Structural Equation Modeling (SEM) (MSEM including family level variables, provider variables, and clinic variables), as well as mediation tests to examine study hypotheses. The aim of the study is to generate knowledge about effectiveness and mediating factors in the treatment of ODDs in children in the context of family functioning, and to propose an innovative approach to the adaptation and implementation of new treatment interventions within clinic settings. The proposed CIT adaptation and implementation model has the potential to enhance implementation and sustainability, and ultimately increase the extent to which effective interventions are available and can impact children and families in need of services for serious behavior problems. ClinicalTrials.gov, ID: NCT02715414 . Registered on 3 March 2016.

Accounting for sex differences in PTSD: A multi-variable mediation model.

PubMed

Christiansen, Dorte M; Hansen, Maj

2015-01-01

Approximately twice as many females as males are diagnosed with posttraumatic stress disorder (PTSD). However, little is known about why females report more PTSD symptoms than males. Prior studies have generally focused on few potential mediators at a time and have often used methods that were not ideally suited to test for mediation effects. Prior research has identified a number of individual risk factors that may contribute to sex differences in PTSD severity, although these cannot fully account for the increased symptom levels in females when examined individually. The present study is the first to systematically test the hypothesis that a combination of pre-, peri-, and posttraumatic risk factors more prevalent in females can account for sex differences in PTSD severity. The study was a quasi-prospective questionnaire survey assessing PTSD and related variables in 73.3% of all Danish bank employees exposed to bank robbery during the period from April 2010 to April 2011. Participants filled out questionnaires 1 week (T1, N=450) and 6 months after the robbery (T2, N=368; 61.1% females). Mediation was examined using an analysis designed specifically to test a multiple mediator model. Females reported more PTSD symptoms than males and higher levels of neuroticism, depression, physical anxiety sensitivity, peritraumatic fear, horror, and helplessness (the A2 criterion), tonic immobility, panic, dissociation, negative posttraumatic cognitions about self and the world, and feeling let down. These variables were included in the model as potential mediators. The combination of risk factors significantly mediated the association between sex and PTSD severity, accounting for 83% of the association. The findings suggest that females report more PTSD symptoms because they experience higher levels of associated risk factors. The results are relevant to other trauma populations and to other trauma-related psychiatric disorders more prevalent in females, such as depression and anxiety.

Accounting for sex differences in PTSD: A multi-variable mediation model

PubMed Central

Christiansen, Dorte M.; Hansen, Maj

2015-01-01

Background Approximately twice as many females as males are diagnosed with posttraumatic stress disorder (PTSD). However, little is known about why females report more PTSD symptoms than males. Prior studies have generally focused on few potential mediators at a time and have often used methods that were not ideally suited to test for mediation effects. Prior research has identified a number of individual risk factors that may contribute to sex differences in PTSD severity, although these cannot fully account for the increased symptom levels in females when examined individually. Objective The present study is the first to systematically test the hypothesis that a combination of pre-, peri-, and posttraumatic risk factors more prevalent in females can account for sex differences in PTSD severity. Method The study was a quasi-prospective questionnaire survey assessing PTSD and related variables in 73.3% of all Danish bank employees exposed to bank robbery during the period from April 2010 to April 2011. Participants filled out questionnaires 1 week (T1, N=450) and 6 months after the robbery (T2, N=368; 61.1% females). Mediation was examined using an analysis designed specifically to test a multiple mediator model. Results Females reported more PTSD symptoms than males and higher levels of neuroticism, depression, physical anxiety sensitivity, peritraumatic fear, horror, and helplessness (the A2 criterion), tonic immobility, panic, dissociation, negative posttraumatic cognitions about self and the world, and feeling let down. These variables were included in the model as potential mediators. The combination of risk factors significantly mediated the association between sex and PTSD severity, accounting for 83% of the association. Conclusions The findings suggest that females report more PTSD symptoms because they experience higher levels of associated risk factors. The results are relevant to other trauma populations and to other trauma-related psychiatric disorders more prevalent in females, such as depression and anxiety. PMID:25604705

Multiple sclerosis pathogenesis: missing pieces of an old puzzle.

PubMed

Rahmanzadeh, Reza; Brück, Wolfgang; Minagar, Alireza; Sahraian, Mohammad Ali

2018-06-08

Traditionally, multiple sclerosis (MS) was considered to be a CD4 T cell-mediated CNS autoimmunity, compatible with experimental autoimmune encephalitis model, which can be characterized by focal lesions in the white matter. However, studies of recent decades revealed several missing pieces of MS puzzle and showed that MS pathogenesis is more complex than the traditional view and may include the following: a primary degenerative process (e.g. oligodendroglial pathology), generalized abnormality of normal-appearing brain tissue, pronounced gray matter pathology, involvement of innate immunity, and CD8 T cells and B cells. Here, we review these findings and discuss their implications in MS pathogenesis.

Predicting the Influence of Situational and Immigration Stress on Latino Day Laborers' Workplace Injuries: An Exploratory Structural Equation Model.

PubMed

Fernández-Esquer, Maria Eugenia; Gallardo, Kathryn R; Diamond, Pamela M

2018-05-16

Latino day laborers are a socially and economically marginalized immigrant population with a high risk of occupational injury. These workers confront multiple social, psychological, and environmental hardships that increase their risk for adverse health outcomes. How these stressors interact and influence work-related injuries in this population remains unclear. We conducted an exploratory study with 327 Latino day laborers who completed a community survey. We developed a structural equation model, using cross-sectional data to explore the relationships among socioeconomic status, situational and immigration stress, depression, work risk exposure, and occupational injury. The model revealed a statistically significant mediated effect from situational stress to injury through work risk exposure as well as a significant mediated effect from immigration stress through depression to injury. These initial findings suggest that situational and immigration-related stress have a detrimental impact on Latino day laborers' mental health and workplace safety and, ultimately, increase their risk of occupational injury.

A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis

PubMed Central

Fransén-Pettersson, Nina; Duarte, Nadia; Nilsson, Julia; Lundholm, Marie; Mayans, Sofia; Larefalk, Åsa; Hannibal, Tine D.; Hansen, Lisbeth; Schmidt-Christensen, Anja; Ivars, Fredrik; Cardell, Susanna; Palmqvist, Richard; Rozell, Björn

2016-01-01

Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders. PMID:27441847

Two ways related to performance in elite sport: the path of self-confidence and competitive anxiety and the path of group cohesion and group goal-clarity.

PubMed

Kjørmo, Odd; Halvari, Hallgeir

2002-06-01

A model tested among 136 Norwegian Olympic-level athletes yielded two paths related to performance. The first path indicated that self-confidence, modeled as an antecedent of competitive anxiety, is negatively correlated with anxiety. Competitive anxiety in turn is negatively correlated with performance. The second path indicated that group cohesion is positively correlated with group goal-clarity, which in turn is positively correlated with performance. Competitive anxiety mediates the relation between self-confidence and performance, whereas group goal-clarity mediates the relation between group cohesion and performance. Results from multiple regression analyses supported the model in the total sample and among individual sport athletes organized in training groups (n = 100). Among team sport athletes (n = 36), personality and group measures are more strongly intercorrelated than among individual sport athletes, and the relation with performance is more complex for the former group. The interaction of self-confidence and competitive anxiety is related to performance among team sport athletes.

Proposal for a telehealth concept in the translational research model

PubMed Central

Silva, Angélica Baptista; Morel, Carlos Médicis; de Moraes, Ilara Hämmerli Sozzi

2014-01-01

OBJECTIVE To review the conceptual relationship between telehealth and translational research. METHODS Bibliographical search on telehealth was conducted in the Scopus, Cochrane BVS, LILACS and MEDLINE databases to find experiences of telehealth in conjunction with discussion of translational research in health. The search retrieved eight studies based on analysis of models of the five stages of translational research and the multiple strands of public health policy in the context of telehealth in Brazil. The models were applied to telehealth activities concerning the Network of Human Milk Banks, in the Telemedicine University Network. RESULTS The translational research cycle of human milk collected, stored and distributed presents several integrated telehealth initiatives, such as video conferencing, and software and portals for synthesizing knowledge, composing elements of an information ecosystem, mediated by information and communication technologies in the health system. CONCLUSIONS Telehealth should be composed of a set of activities in a computer mediated network promoting the translation of knowledge between research and health services. PMID:24897057

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

PubMed

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

2018-01-01

Ecological stressors (i.e., environmental factors outside their normal range of variation) can mediate each other through their interactions, leading to unexpected combined effects on communities. Determining whether the net effect of stressors is ecologically surprising requires comparing their cumulative impact to a null model that represents the linear combination of their individual effects (i.e., an additive expectation). However, we show that standard additive and multiplicative null models that base their predictions on the effects of single stressors on community properties (e.g., species richness or biomass) do not provide this linear expectation, leading to incorrect interpretations of antagonistic and synergistic responses by communities. We present an alternative, the compositional null model, which instead bases its predictions on the effects of stressors on individual species, and then aggregates them to the community level. Simulations demonstrate the improved ability of the compositional null model to accurately provide a linear expectation of the net effect of stressors. We simulate the response of communities to paired stressors that affect species in a purely additive fashion and compare the relative abilities of the compositional null model and two standard community property null models (additive and multiplicative) to predict these linear changes in species richness and community biomass across different combinations (both positive, negative, or opposite) and intensities of stressors. The compositional model predicts the linear effects of multiple stressors under almost all scenarios, allowing for proper classification of net effects, whereas the standard null models do not. Our findings suggest that current estimates of the prevalence of ecological surprises on communities based on community property null models are unreliable, and should be improved by integrating the responses of individual species to the community level as does our compositional null model. © 2017 John Wiley & Sons Ltd.

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

The pharmacokinetics and hepatic disposition of repaglinide in pigs: mechanistic modeling of metabolism and transport.

PubMed

Sjögren, Erik; Bredberg, Ulf; Lennernäs, Hans

2012-04-02

The predictive power of using in vitro systems in combination with physiologically based pharmacokinetic (PBPK) modeling to elucidate the relative importance of metabolism and carrier-mediated transport for the pharmacokinetics was evaluated using repaglinide as a model compound and pig as the test system. Repaglinide was chosen as model drug as previous studies in humans have shown that repaglinide is subject to both carrier-mediated influx to the liver cells and extensive hepatic metabolism. A multiple sampling site model in pig was chosen since it provides detailed in vivo information about the liver disposition. The underlying assumption was that both metabolism and carrier-mediated transport are also important for the hepatic disposition of repaglinide in pigs. Microsomes and primary hepatocytes were used for in vitro evaluation of enzyme kinetics and cellular disposition, respectively. In vitro data were generated both with and without metabolism inhibitors (ketoconazole, bezafibrate and trimethoprim) and transport inhibitors (diclofenac and quinine) providing input into a semi-PBPK model. In vivo data were also generated with and without the same enzyme and transporter inhibitors, alone and in combination. The pigs were given repaglinide as intravenous infusions with and without inhibitors in a sequential manner, i.e., a control phase and a test phase. Parameters describing the passive and carrier-mediated flux as well as metabolism were estimated in the control phase. The result from test phase was used to gain further knowledge of the findings from the control phase. The in vivo pig model enabled simultaneous sampling from plasma (pre- and postliver and peripheral) as well as from bile and urine. A semi-PBPK model consisting of 11 compartments (6 tissues + 5 sampling sites) was constructed for the mechanistic elucidation of the liver disposition, in vitro based in vivo predictions, sensitivity analyses and estimations of individual pharmacokinetic parameters. Both in vitro and in vivo results showed that carrier-mediated influx was important for the liver disposition. The in vivo findings were supported by the result from the test phase where hepatic clearance (4.3 mL min⁻¹ kg⁻¹) was decreased by 29% (metabolism inhibition), 43% (transport inhibition) and 57% (metabolism + transport inhibition). These effects were in good agreement with predicted levels. This study suggests that both metabolism and carrier-mediated uptake are of significant importance for the liver disposition of repaglinide in pigs.

Mothers, Fathers, Peers, and Mexican-Origin Adolescents’ Sexual Intentions

PubMed Central

Killoren, Sarah E.; Updegraff, Kimberly A.; Christopher, F. Scott; Umaña-Taylor, Adriana J.

2011-01-01

Drawing on a symbolic-interaction perspective and a compensation model, the processes linking mother-and father-adolescent relationship qualities, deviant peer affiliations, and adolescents’ sexual intentions were investigated for 246 Mexican-origin youths born in the United States and in Mexico using multiple-group structural equation models. Deviant peer affiliations significantly mediated the relations between paternal acceptance and sexual intentions and between disclosure to mothers and sexual intentions for U.S.-born youths but not for Mexico-born youths. Findings highlight the importance of examining variability as a function of youth nativity. PMID:21278903

The mediating role of avoidance coping between intimate partner violence (IPV) victimization, mental health, and substance abuse among women experiencing bidirectional IPV.

PubMed

Flanagan, Julianne C; Jaquier, Véronique; Overstreet, Nicole; Swan, Suzanne C; Sullivan, Tami P

2014-12-15

Avoidance coping is consistently linked with negative mental health outcomes among women experiencing intimate partner violence (IPV). This study extended the literature examining the potentially mediating role of avoidance coping strategies on both mental health and substance use problems to a highly generalizable, yet previously unexamined population (i.e., women experiencing bidirectional IPV) and examined multiple forms of IPV (i.e., psychological, physical, and sexual) simultaneously. Among a sample of 362 women experiencing bidirectional IPV, four separate path models were examined, one for each outcome variable. Avoidance coping mediated the relationships between psychological and sexual IPV victimization and the outcomes of PTSD symptom severity, depression severity, and drug use problems. Findings indicate nuanced associations among IPV victimization, avoidance coping, and mental health and substance use outcomes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Beyond group engagement: Multiple pathways from encounters with the police to cooperation and compliance in Northern Ireland

PubMed Central

Devaney, Lee; Bryan, Dominic; Blaylock, Danielle L.

2017-01-01

In a sample of young people in Northern Ireland (N = 819), we examine the relationships between the quality of experience with police officers and police legitimacy. We examine potential pathways through which experiences may either support or undermine the legitimacy of the police, and thus cooperation and compliance with them. We find evidence that perceptions of the police as having goals that align with those of wider society, and as being fair in general, mediate relations between the quality of encounters and legitimacy, which in turn mediates the relation with cooperation and compliance. Identification with wider society was not a reliable mediator, contrary to our predictions based on the Group Engagement Model. Moreover, our analysis of the structure of police fairness perceptions finds no support for the distinction between procedural and distributive police fairness as usually conceived. Implications for the social psychological understanding of legitimate authority are discussed. PMID:28880946

Beyond group engagement: Multiple pathways from encounters with the police to cooperation and compliance in Northern Ireland.

PubMed

Pehrson, Samuel; Devaney, Lee; Bryan, Dominic; Blaylock, Danielle L

2017-01-01

In a sample of young people in Northern Ireland (N = 819), we examine the relationships between the quality of experience with police officers and police legitimacy. We examine potential pathways through which experiences may either support or undermine the legitimacy of the police, and thus cooperation and compliance with them. We find evidence that perceptions of the police as having goals that align with those of wider society, and as being fair in general, mediate relations between the quality of encounters and legitimacy, which in turn mediates the relation with cooperation and compliance. Identification with wider society was not a reliable mediator, contrary to our predictions based on the Group Engagement Model. Moreover, our analysis of the structure of police fairness perceptions finds no support for the distinction between procedural and distributive police fairness as usually conceived. Implications for the social psychological understanding of legitimate authority are discussed.

Occupational turnover intentions among substance abuse counselors

PubMed Central

Rothrauff, Tanja C.; Abraham, Amanda J.; Bride, Brian E.; Roman, Paul M.

2010-01-01

This study examined predictor, moderator, and mediator variables of occupational turnover intention (OcTI) among substance abuse counselors. Data were obtained via questionnaires from 929 counselors working in 225 private substance abuse treatment (SAT) programs across the U.S. Hierarchical multiple regression models were conducted to assess predictor, moderator, and mediator variables of OcTI. OcTI scores were relatively low on a 7-point scale, indicating that very few counselors definitely intended to leave the SAT field. Age, certification, positive perceptions of procedural and distributive justice, and hospital-based status negatively predicted OcTI. Counselors’ substance use disorder impacted history moderated the association between organizational commitment and OcTI. Organizational turnover intention partially mediated the link between organizational commitment and OcTI. Workforce stability might be achieved by promoting perceptions of advantages to working in a particular treatment program, organizational commitment, showing appreciation for counselors’ work, and valuing employees from diverse backgrounds. PMID:20947285

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.

Pricing strategies, the strength of bidding intentions, and online auction performance: a cross-cultural study.

PubMed

Peng, Yu-Shu; Jan, Lih-Tsyr

2009-10-01

Over the past decade, electronic markets based on the Internet, particularly online auctions, have become popular venues for conducting business. Previous studies often focused on the construction of the best bidding model, while few studies have tried to integrate multiple pricing strategies to predict the probability of closing an auction and the price premium. This study constructs a mediated model to examine the relationship among pricing strategies, the strength of bidding intentions, and online auction performance. The sample consists of 1,055 auctions of iPod MP3 players from eBay Web sites in Hong Kong, Singapore, Belgium, and France. Empirical results show that the pricing strategies directly influence both the probability of closing an auction and the level of price premium. The pricing strategies also indirectly influence the price premium through the mediating effect of the strength of bidding intentions.

Youth violence in South Africa: exposure, attitudes, and resilience in Zulu adolescents.

PubMed

Choe, Daniel Ewon; Zimmerman, Marc A; Devnarain, Bashi

2012-01-01

Exposure to violence is common in South Africa. Yet, few studies examine how violence exposure contributes to South African adolescents' participation in youth violence. The aims of this study were to examine effects of different violence exposures on violent attitudes and behavior, to test whether attitudes mediated effects of violence exposures on violent behavior, and to test whether adult involvement had protective or promotive effects. Questionnaires were administered to 424 Zulu adolescents in township high schools around Durban, South Africa. Structural equation modeling (SEM) was used to test associations among violence exposures and both violent attitudes and behavior. Victimization, witnessing violence, and friends' violent behavior contributed directly to violent behavior. Only family conflict and friends' violence influenced violent attitudes. Attitudes mediated effects of friends' violence on violent behavior. Multiple-group SEM indicated that adult involvement fit a protective model of resilience. These findings are discussed regarding their implications for prevention.

Investigation of the Structural Relationships Between Social Support, Self-Compassion, and Subjective Well-Being in Korean Elite Student Athletes.

PubMed

Jeon, Hyunsoo; Lee, Keunchul; Kwon, Sungho

2016-08-01

The study examined whether self-compassion mediates the relationship between social support and subjective well-being, as perceived by athletes. It also investigated the structural relationships between these variables. Participants were 333 athletes attending high school or university. Structural equation analysis showed that self-compassion partially mediated the relationship between social support and subjective well-being. To test the stability of the model, a multiple group analysis was performed according to sex of participant and school level, and this demonstrated that the model had similar fit to the data regardless of group. The confirmation that self-compassion plays an intermediary role in the relationship between social support and subjective well-being demonstrates that self-compassionate attitudes can be fostered by social support, and that, in turn, has a positive effect on an individual's subjective well-being. © The Author(s) 2016.

Social Influence and Individual Risk Factors of HIV Unsafe Sex among Female Entertainment Workers in China

PubMed Central

Yang, Xiushi; Xia, Guomei; Li, Xiaoming; Latkin, Carl; Celentano, David

2010-01-01

Female entertainment workers in China are at increased sexual risk of HIV, but causes of their unprotected sex remain poorly understood. We develop a model that integrates information-motivation-behavioral skills (IMB) with social influences and test the model in a venue-based sample of 732 female entertainment workers in Shanghai. Most IMB and social influence measures are statistically significant in bivariate relationships to condom use; only HIV prevention motivation and behavioral self-efficacy remain significant in the multiple regressions. Self-efficacy in condom use is the most proximate correlate, mediating the relationship between information and motivation and condom use. Both peer and venue supports are important, but their influences over condom use are indirect and mediated through prevention motivation and/or self-efficacy. Behavioral intervention is urgently needed and should take a multi-level approach, emphasizing behavioral skills training and promoting a supportive social/working environment. PMID:20166789

Searching for Physics Beyond the Standard Model and Beyond

NASA Astrophysics Data System (ADS)

Abdullah, Mohammad

The hierarchy problem, convolved with the various known puzzles in particle physics, grants us a great outlook of new physics soon to be discovered. We present multiple approaches to searching for physics beyond the standard model. First, two models with a minimal amount of theoretical guidance are analyzed using existing or simulated LHC data. Then, an extension of the Minimal Supersymmetric Standard Model (MSSM) is studied with an emphasis on the cosmological implications as well as the current and future sensitivity of colliders, direct detection and indirect detection experiments. Finally, a more complete model of the MSSM is presented through which we attempt to resolve tension with observations within the context of gauge mediated supersymmetry breaking.

Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis.

PubMed

Jurynczyk, Maciej; Geraldes, Ruth; Probert, Fay; Woodhall, Mark R; Waters, Patrick; Tackley, George; DeLuca, Gabriele; Chandratre, Saleel; Leite, Maria I; Vincent, Angela; Palace, Jacqueline

2017-03-01

Brain imaging characteristics of MOG antibody disease are largely unknown and it is unclear whether they differ from those of multiple sclerosis and AQP4 antibody disease. The aim of this study was to identify brain imaging discriminators between those three inflammatory central nervous system diseases in adults and children to support diagnostic decisions, drive antibody testing and generate disease mechanism hypotheses. Clinical brain scans of 83 patients with brain lesions (67 in the training and 16 in the validation cohort, 65 adults and 18 children) with MOG antibody (n = 26), AQP4 antibody disease (n = 26) and multiple sclerosis (n = 31) recruited from Oxford neuromyelitis optica and multiple sclerosis clinical services were retrospectively and anonymously scored on a set of 29 predefined magnetic resonance imaging features by two independent raters. Principal component analysis was used to perform an overview of patients without a priori knowledge of the diagnosis. Orthogonal partial least squares discriminant analysis was used to build models separating diagnostic groups and identify best classifiers, which were then tested on an independent cohort set. Adults and children with MOG antibody disease frequently had fluffy brainstem lesions, often located in pons and/or adjacent to fourth ventricle. Children across all conditions showed more frequent bilateral, large, brainstem and deep grey matter lesions. MOG antibody disease spontaneously separated from multiple sclerosis but overlapped with AQP4 antibody disease. Multiple sclerosis was discriminated from MOG antibody disease and from AQP4 antibody disease with high predictive values, while MOG antibody disease could not be accurately discriminated from AQP4 antibody disease. Best classifiers between MOG antibody disease and multiple sclerosis were similar in adults and children, and included ovoid lesions adjacent to the body of lateral ventricles, Dawson's fingers, T1 hypointense lesions (multiple sclerosis), fluffy lesions and three lesions or less (MOG antibody). In the validation cohort patients with antibody-mediated conditions were differentiated from multiple sclerosis with high accuracy. Both antibody-mediated conditions can be clearly separated from multiple sclerosis on conventional brain imaging, both in adults and children. The overlap between MOG antibody oligodendrocytopathy and AQP4 antibody astrocytopathy suggests that the primary immune target is not the main substrate for brain lesion characteristics. This is also supported by the clear distinction between multiple sclerosis and MOG antibody disease both considered primary demyelinating conditions. We identify discriminatory features, which may be useful in classifying atypical multiple sclerosis, seronegative neuromyelitis optica spectrum disorders and relapsing acute disseminated encephalomyelitis, and characterizing cohorts for antibody discovery. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lactoferricin mediates Anti-Inflammatory and Anti-Catabolic Effects via Inhibition of IL-1 and LPS Activity in the Intervertebral Disc†

PubMed Central

Kim, Jae-Sung; Ellman, Michael B.; Yan, Dongyao; An, Howard S.; Kc, Ranjan; Li, Xin; Chen, Di; Xiao, Guozhi; Cs-Zabo, Gabriella; Hoskin, David W.; Buechter, D.D.; Van Wijnen, Andre J.; Im, Hee-Jeong

2013-01-01

The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. PMID:23460134

Lactoferricin mediates anti-inflammatory and anti-catabolic effects via inhibition of IL-1 and LPS activity in the intervertebral disc.

PubMed

Kim, Jae-Sung; Ellman, Michael B; Yan, Dongyao; An, Howard S; Kc, Ranjan; Li, Xin; Chen, Di; Xiao, Guozhi; Cs-Szabo, Gabriella; Hoskin, David W; Buechter, Doug D; Van Wijnen, Andre J; Im, Hee-Jeong

2013-09-01

The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production, and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. Copyright © 2013 Wiley Periodicals, Inc.

An assessment of the social cognitive predictors of exclusive breastfeeding behavior using the Health Action Process Approach.

PubMed

Martinez-Brockman, J L; Shebl, F M; Harari, N; Pérez-Escamilla, R

2017-06-01

In the United States rates of exclusive breastfeeding duration remain exceedingly low. Exclusive breastfeeding is a complex learned behavior that is influenced by social cognitive, interpersonal, and structural factors. Interventions are needed that address factors at multiple levels of the social-ecological model. This study was designed to examine the social cognitive predictors of exclusive breastfeeding behavior in a sample of low-income women attending the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) breastfeeding peer counseling program and enrolled in the Lactation Advice Through Texting Can Help (LATCH) study. The objectives were to examine whether: (1) the theoretical model, the Health Action Process Approach (HAPA), fit the data well; (2) planning mediated the effect of intentions and maintenance self-efficacy on exclusive breastfeeding; and (3) recovery self-efficacy mediated the association between maintenance self-efficacy and exclusive breastfeeding behavior. Outcome expectancies, action self-efficacy and intentions were assessed prenatally at baseline in N = 119 participants. Maintenance self-efficacy, planning, recovery self-efficacy and breastfeeding behavior were measured at two weeks post partum. Structural equation modeling with mean and variance adjusted Weighted Least Squares estimation was used to examine the applicability of the HAPA model to the data. Phase specific self-efficacy and planning significantly predicted exclusive breastfeeding status. Planning and recovery self-efficacy mediated the association between maintenance self-efficacy and exclusive breastfeeding. Planning did not emerge as a mediator between intentions and behavior. These results demonstrate the utility of the HAPA model in predicting exclusive breastfeeding behavior among low-income women attending WIC. LATCH is a theoretically sound text messaging intervention that can be used to augment and reinforce the WIC breastfeeding peer counseling process. Copyright © 2017 Elsevier Ltd. All rights reserved.

Serial Multiple Mediation of General Belongingness and Life Satisfaction in the Relationship between Attachment and Loneliness in Adolescents

ERIC Educational Resources Information Center

Yildiz, Mehmet Ali

2016-01-01

The current research aims to investigate the serial-multiple mediation of general belongingness and life satisfaction in the relationship between loneliness and attachment to parents and peers in adolescents. The participants of the research consisted of 218 high school students (F = 126, 57.8%; M = 92, 42.2%). Age of the participants' ranged…

Having a Lot of a Good Thing: Multiple Important Group Memberships as a Source of Self-Esteem

PubMed Central

Jetten, Jolanda; Branscombe, Nyla R.; Haslam, S. Alexander; Haslam, Catherine; Cruwys, Tegan; Jones, Janelle M.; Cui, Lijuan; Dingle, Genevieve; Liu, James; Murphy, Sean; Thai, Anh; Walter, Zoe; Zhang, Airong

2015-01-01

Membership in important social groups can promote a positive identity. We propose and test an identity resource model in which personal self-esteem is boosted by membership in additional important social groups. Belonging to multiple important group memberships predicts personal self-esteem in children (Study 1a), older adults (Study 1b), and former residents of a homeless shelter (Study 1c). Study 2 shows that the effects of multiple important group memberships on personal self-esteem are not reducible to number of interpersonal ties. Studies 3a and 3b provide longitudinal evidence that multiple important group memberships predict personal self-esteem over time. Studies 4 and 5 show that collective self-esteem mediates this effect, suggesting that membership in multiple important groups boosts personal self-esteem because people take pride in, and derive meaning from, important group memberships. Discussion focuses on when and why important group memberships act as a social resource that fuels personal self-esteem. PMID:26017554

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

ERIC Educational Resources Information Center

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

2010-01-01

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

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

PubMed

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

2015-07-01

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

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

PubMed Central

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

2015-01-01

Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science), Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms “stress*” AND “multiple sclerosis.” Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset (n = 9) were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression (n = 14) were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis. PMID:28070374

An Analytical Model for Determining Two-Dimensional Receptor-Ligand Kinetics

PubMed Central

Cheung, Luthur Siu-Lun; Konstantopoulos, Konstantinos

2011-01-01

Cell-cell adhesive interactions play a pivotal role in major pathophysiological vascular processes, such as inflammation, infection, thrombosis, and cancer metastasis, and are regulated by hemodynamic forces generated by blood flow. Cell adhesion is mediated by the binding of receptors to ligands, which are both anchored on two-dimensional (2-D) membranes of apposing cells. Biophysical assays have been developed to determine the unstressed (no-force) 2-D affinity but fail to disclose its dependence on force. Here we develop an analytical model to estimate the 2-D kinetics of diverse receptor-ligand pairs as a function of force, including antibody-antigen, vascular selectin-ligand, and bacterial adhesin-ligand interactions. The model can account for multiple bond interactions necessary to mediate adhesion and resist detachment amid high hemodynamic forces. Using this model, we provide a generalized biophysical interpretation of the counterintuitive force-induced stabilization of cell rolling observed by a select subset of receptor-ligand pairs with specific intrinsic kinetic properties. This study enables us to understand how single-molecule and multibond biophysics modulate the macroscopic cell behavior in diverse pathophysiological processes. PMID:21575567

Indirect detection constraints on s- and t-channel simplified models of dark matter

NASA Astrophysics Data System (ADS)

Carpenter, Linda M.; Colburn, Russell; Goodman, Jessica; Linden, Tim

2016-09-01

Recent Fermi-LAT observations of dwarf spheroidal galaxies in the Milky Way have placed strong limits on the gamma-ray flux from dark matter annihilation. In order to produce the strongest limit on the dark matter annihilation cross section, the observations of each dwarf galaxy have typically been "stacked" in a joint-likelihood analysis, utilizing optical observations to constrain the dark matter density profile in each dwarf. These limits have typically been computed only for singular annihilation final states, such as b b ¯ or τ+τ- . In this paper, we generalize this approach by producing an independent joint-likelihood analysis to set constraints on models where the dark matter particle annihilates to multiple final-state fermions. We interpret these results in the context of the most popular simplified models, including those with s- and t-channel dark matter annihilation through scalar and vector mediators. We present our results as constraints on the minimum dark matter mass and the mediator sector parameters. Additionally, we compare our simplified model results to those of effective field theory contact interactions in the high-mass limit.

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

PubMed

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

2007-11-09

Although it is important to investigate how interventions work, no formal mediation analyses have been conducted to explain behavioral outcomes in school-based fat intake interventions in adolescents. The aim of the present study was to examine mediation effects of changes in psychosocial determinants of dietary fat intake (attitude, social support, self-efficacy, perceived benefits and barriers) on changes in fat intake in adolescent girls. Data from a 1-year prospective intervention study were used. A random sample of 804 adolescent girls was included in the study. Girls in the intervention group (n = 415) were exposed to a multi-component school-based intervention program, combining environmental changes with a computer tailored fat intake intervention and parental support. Fat intake and psychosocial determinants of fat intake were measured with validated self-administered questionnaires. To assess mediating effects, a product-of-coefficient test, appropriate for cluster randomized controlled trials, was used. None of the examined psychosocial factors showed a reliable mediating effect on changes in fat intake. The single-mediator model revealed a statistically significant suppression effect of perceived barriers on changes in fat intake (p = 0.011). In the multiple-mediator model, this effect was no longer significant, which was most likely due to changes in perceived barriers being moderately related to changes in self-efficacy (-0.30) and attitude (-0.25). The overall mediated-suppressed effect of the examined psychosocial factors was virtually zero (total mediated effect = 0.001; SE = 7.22; p = 0.992). Given the lack of intervention effects on attitudes, social support, self-efficacy and perceived benefits and barriers, it is suggested that future interventions should focus on the identification of effective strategies for changing these theoretical mediators in the desired direction. Alternatively, it could be argued that these constructs need not be targeted in interventions aimed at adolescents, as they may not be responsible for the intervention effects on fat intake. To draw any conclusions regarding mediators of fat-intake change in adolescent' girls and regarding optimal future intervention strategies, more systematic research on the mediating properties of psychosocial variables is needed.

Terminology development towards harmonizing multiple clinical neuroimaging research repositories.

PubMed

Turner, Jessica A; Pasquerello, Danielle; Turner, Matthew D; Keator, David B; Alpert, Kathryn; King, Margaret; Landis, Drew; Calhoun, Vince D; Potkin, Steven G; Tallis, Marcelo; Ambite, Jose Luis; Wang, Lei

2015-07-01

Data sharing and mediation across disparate neuroimaging repositories requires extensive effort to ensure that the different domains of data types are referred to by commonly agreed upon terms. Within the SchizConnect project, which enables querying across decentralized databases of neuroimaging, clinical, and cognitive data from various studies of schizophrenia, we developed a model for each data domain, identified common usable terms that could be agreed upon across the repositories, and linked them to standard ontological terms where possible. We had the goal of facilitating both the current user experience in querying and future automated computations and reasoning regarding the data. We found that existing terminologies are incomplete for these purposes, even with the history of neuroimaging data sharing in the field; and we provide a model for efforts focused on querying multiple clinical neuroimaging repositories.

Terminology development towards harmonizing multiple clinical neuroimaging research repositories

PubMed Central

Turner, Jessica A.; Pasquerello, Danielle; Turner, Matthew D.; Keator, David B.; Alpert, Kathryn; King, Margaret; Landis, Drew; Calhoun, Vince D.; Potkin, Steven G.; Tallis, Marcelo; Ambite, Jose Luis; Wang, Lei

2015-01-01

Data sharing and mediation across disparate neuroimaging repositories requires extensive effort to ensure that the different domains of data types are referred to by commonly agreed upon terms. Within the SchizConnect project, which enables querying across decentralized databases of neuroimaging, clinical, and cognitive data from various studies of schizophrenia, we developed a model for each data domain, identified common usable terms that could be agreed upon across the repositories, and linked them to standard ontological terms where possible. We had the goal of facilitating both the current user experience in querying and future automated computations and reasoning regarding the data. We found that existing terminologies are incomplete for these purposes, even with the history of neuroimaging data sharing in the field; and we provide a model for efforts focused on querying multiple clinical neuroimaging repositories. PMID:26688838

Cognitive Impairment as a Mediator in the Developmental Pathway from Infant Malnutrition to Adolescent Depressive Symptoms in Barbadian Youth

PubMed Central

Waber, Deborah P.; Eaglesfield, David; Fitzmaurice, Garrett M.; Bryce, Cyralene; Harrison, Robert H.; Galler, Janina R.

2011-01-01

Background Depressive symptoms are elevated in adolescents who experienced significant malnutrition early in life. Early malnutrition can also have a significant impact on cognitive functioning, presumably due to the adverse impact of the malnutrition on the very young brain. In the context of a developmental cascade model, we tested the hypothesis that the association between early malnutrition and adolescent depressive symptoms is mediated by the cognitive impairment that ensues from the malnutrition. Method We evaluated Barbadian youth (N=57) hospitalized for moderate to severe protein-energy malnutrition in the first year of life and healthy controls (N=60) longitudinally. The primary hypothesis was tested by multiple regression models. Results After adjusting for covariates, early malnutrition predicted both cognitive functioning in childhood (IQ, p<0.001; attention problems, p<.01; Common Entrance Examination, p<0.01) and adolescent depressive symptoms (p<0.05). Childhood cognitive functioning mediated the association between early malnutrition and depressive symptoms in adolescence (p<0.001). Maternal depressive symptoms were a significant but independent predictor of adolescent depressive symptoms (p<0.05). Conclusions Cognitive compromise in childhood accounts indirectly for elevated depressive symptoms in previously malnourished adolescents, consistent with a developmental cascade model. The direct link between malnutrition and depressive symptoms in adolescence is small. PMID:21285893

Distress Tolerance as a Mediator of the Association Between Borderline Personality Symptoms and Obsessive Relational Intrusion: An Exploratory Analysis.

PubMed

Reilly, Meghan E; Hines, Denise A

2017-06-01

Obsessive relational intrusion (ORI) is the process by which a pursuer makes multiple attempts at establishing an unwanted, intimate relationship with an individual. It encompasses the more widely known behavior, stalking, which is a widespread problem, particularly among college-aged young adults. However, research on the underlying psychological processes involved in ORI and stalking perpetration is still in its infancy. Using relational goal pursuit theory and the emotional cascade model as guides to explore these processes, we investigated whether distress tolerance mediated the association between borderline personality disorder (BPD) symptoms and ORI, among a college student sample. Participants ( N = 224; 62.5% female; M age = 19.6 years) were recruited from an online survey panel and through the psychology research pool at a small, Northeastern university. Consistent with our hypotheses, path modeling showed that distress tolerance was a significant partial mediator between BPD symptoms and frequency of ORI perpetration. These results seem to provide new insight into the established link between BPD symptoms and ORI, and thus may contribute to our understanding of the underlying psychology of people who engage in unwanted pursuit. Future research should look toward replicating the current findings, testing potential gender differences in the model, and exploring other predictors of both the frequency and initiation of ORI behaviors.

Borrelia burgdorferi infection induces lipid mediator production during Lyme arthritis.

PubMed

Brown, Charles R; Dennis, Edward A

2017-10-01

Experimental Lyme arthritis provides a mouse model for exploring the development of pathology following infection of C3H mice with Borrelia burgdorferi. Infected mice develop a reliable inflammatory arthritis of the ankle joint with severity that typically peaks around two to three weeks post-infection and then undergoes spontaneous resolution. This makes experimental Lyme arthritis an excellent model for investigating the mechanisms that drive both the development and resolution phases of inflammatory disease. Eicosanoids are powerful lipid mediators of inflammation and are known to regulate multiple aspects of inflammatory processes. While much is known about the role of eicosanoids in regulating immune responses during autoimmune disease and cancer, relatively little is known about their role during bacterial infection. In this review, we discuss the role of eicosanoid biosynthetic pathways in mediating inflammatory responses during bacterial infection using experimental Lyme arthritis as a model system. We point out the critical role eicosanoids play in disease development and highlight surprising differences between sterile autoimmune responses and those occurring in response to bacterial infection. These differences should be kept in mind when designing therapies and treatments for inflammatory diseases. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

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

PubMed

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

2011-06-01

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

Perceived discrimination and mental health among older African Americans: the role of psychological well-being.

PubMed

Yoon, Eunkyung; Coburn, Corvell; Spence, Susie A

2018-01-15

Examine the effect of perceived discrimination (both racial and non-racial) on the mental health of older African Americans and explore the buffering role of psychological well-being (purpose in life and self-acceptance). Using an older African American subsample from the National Health Measurement Study (n = 397), multiple regression model by gender was used to estimate the effects of two types of discrimination (every day and lifetime) on SF-36 mental component and mediating role of two concepts of psychological well-being. With no gender difference on the everyday discrimination, older men experienced more lifetime discrimination than older women. The older men's model found that the depressive symptomology was significantly explained by only everyday discrimination and mediated by self-acceptance. The older women's model was significant, with everyday discrimination and both self-acceptance and purpose in life emerging as mediating variables. The prevalence of institutional lifetime discrimination for older African American men is consistent with previous research. Inconsistency with past research indicated that only everyday discrimination is statistically associated with depressive symptoms. Considering the buffering role of psychological well-being served for mental health problems, practitioners need to emphasize these factors when providing services to older African Americans. Equally important, they must address racial discrimination in mental health care settings.

Molecular study on some antibiotic resistant genes in Salmonella spp. isolates

NASA Astrophysics Data System (ADS)

Nabi, Ari Q.

2017-09-01

Studying the genes related with antimicrobial resistance in Salmonella spp. is a crucial step toward a correct and faster treatment of infections caused by the pathogen. In this work Integron mediated antibiotic resistant gene IntI1 (Class I Integrase IntI1) and some plasmid mediated antibiotic resistance genes (Qnr) were scanned among the isolated non-Typhoid Salmonellae strains with known resistance to some important antimicrobial drugs using Sybr Green real time PCR. The aim of the study was to correlate the multiple antibiotics and antimicrobial resistance of Salmonella spp. with the presence of integrase (IntI1) gene and plasmid mediated quinolone resistant genes. Results revealed the presence of Class I Integrase gene in 76% of the isolates with confirmed multiple antibiotic resistances. Moreover, about 32% of the multiple antibiotic resistant serotypes showed a positive R-PCR for plasmid mediated qnrA gene encoding for nalidixic acid and ciprofloxacin resistance. No positive results could be revealed form R-PCRs targeting qnrB or qnrS. In light of these results we can conclude that the presence of at least one of the qnr genes and/or the presence of Integrase Class I gene were responsible for the multiple antibiotic resistance to for nalidixic acid and ciprofloxacin from the studied Salmonella spp. and further studies required to identify the genes related with multiple antibiotic resistance of the pathogen.

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

PubMed Central

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

2015-01-01

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

In vitro transfer of multiple resistance observed in vivo during a Salmonella london epidemic.

PubMed

Lantos, J; Marjai, E

1980-01-01

Between 1976 and 1978, waves of Salmonella london infections conveyed by raw meat and meat products were observed. The strains isolated during the epidemic were first susceptible then developed multiple antibiotic resistance. The identical antibiotic resistance patterns of the strain and their more frequent occurrence in hospital environments indicated plasmid-mediated resistance. R-plasmid transfer, minimum inhibition concentration and resistance elimination were studied in representative strains. The resistant S. london strain and transconjugants of Escherichia coli rendered resistant were compared. The results proved that multiple resistance was plasmid-mediated.

Mathematical modeling of alignment dynamics in active motor-filament systems

NASA Astrophysics Data System (ADS)

Swaminathan, Sumanth

The formation of the cytoskeleton, via motor-mediated microtubule self-organization, is an important subject of study in the biological sciences as well as in nonequilibrium, soft matter physics. Accurate modeling of the dynamics is a formidable task as it involves intrinsic nonlinearities, structural anisotropies, nonequilibrium processes, and a broad window of time scales, length scales, and densities. In this thesis, we study the ordering dynamics and pattern formations arising from motor-mediated microtubule self-organization in dilute and semi-dilute filament solutions. In the dilute case, we use a probabilistic model in which microtubules interact through motor induced, inelastic binary collisions. This model shows that initially disordered filament solutions exhibit an ordering transition resulting in the emergence of well aligned rod bundles. We study the existence and dynamic interaction of microtubule bundles analytically and numerically. Our results show a long term attraction and coalescing of bundles indicating a clear coarsening in the system; microtubule bundles concentrate into fewer orientations on a slow logarithmic time scale. In the semi-dilute case, multiple motors can bind a filament to several others and, for a critical motor density, induce a transition to an ordered state with a nonzero mean orientation. We develop a spatially homogeneous, mean-field theory that explicitly accounts for motor forcing and thermal fluctuations which enter into the model as multiplicative and additive noises respectively. Our model further incorporates a force-dependent detachment rate of motors, which in turn affects the mean and the fluctuations of the net force acting on a filament. We demonstrate that the transition to the oriented state changes from second order to first order when the force-dependent detachment becomes important. In our final analysis, we add complex spatial inhomogeneities to our mean field theory. The revised model consists of a system of stochastic differential equations governing the time evolution of the orientation and center of mass of each filament; microtubules translate and rotate under the influence of motor forces and intrinsic thermal fluctuations. We show through a molecular dynamics type stochastic simulation that initially disordered systems of microtubules exhibit an ordering transition resulting in the formation of bundles and vortices. This finding is compared with previous binary interaction and hydrodynamic models and shown to be consistent with in vitro experiments on motor-mediated self-organization of microtubules and actin filaments.

Mediating and/or moderating roles of psychological empowerment.

PubMed

Meng, Lina; Jin, Yi; Guo, Jiajia

2016-05-01

The purpose of this study was to explore the mediating and/or moderating effects of psychological empowerment in the relationship between structural empowerment and burnout among nurses in China. Burnout is prevalent among nurses. Previous studies have found that empowering organizational structures contribute to reduce nurses' burnout. However, little is known about the mediating or moderating role of psychological empowerment in the relationship between structural empowerment and burnout among nurses in China. A cross-sectional design was conducted. A total of 244 nurses participated in this study. The data were collected in March 2013. Multiple regressions were used to test the hypothesized models. Psychological empowerment was found to be a significant mediator of the relationship between structural empowerment and burnout (standardized β=-0.553, Sobel test: z=7.79, p<0.001). The moderating effect of psychological empowerment in that relationship was not verified. Both structural and psychological empowerment negatively correlated with burnout. The psychological empowerment had a mediating effect on burnout. It is important for nurse managers to develop strategies to ensure that empowering structures are in place and to facilitate nurses' perception of psychological empowerment. Copyright © 2015 Elsevier Inc. All rights reserved.

Do interoceptive awareness and interoceptive responsiveness mediate the relationship between body appreciation and intuitive eating in young women?

PubMed

Oswald, Alana; Chapman, Janine; Wilson, Carlene

2017-02-01

The extent to which an individual appreciates their own body is recognised as a proximal predictor of intuitive eating, but the mechanisms underlying this relationship are less clearly understood. This study tested whether two partially independent, self-reported facets of interoceptive ability: 'interoceptive awareness' (defined as the ability to detect internal bodily cues) and 'interoceptive responsiveness' (the way in which individuals value and respond to these cues) mediated the relationship between body appreciation and three subscales of intuitive eating: 'unconditional permission to eat'; 'reliance on internal hunger and satiety cues', and 'eating for physical rather than emotional reasons'. Multiple mediation analyses of data from an online survey of Australian college women (n = 200) showed that: (1) interoceptive awareness partially mediated the relationship between body appreciation and 'reliance on internal hunger and satiety cues', and (2) interoceptive responsiveness partially mediated the relationship between all three subscales of intuitive eating. Although preliminary, this work lends support to the theoretical framework of the acceptance model of intuitive eating and extends it by suggesting that the different facets of intuitive eating may have distinct underlying mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mediating relationship of differential products in understanding integration in introductory physics

NASA Astrophysics Data System (ADS)

Amos, Nathaniel; Heckler, Andrew F.

2018-01-01

In the context of introductory physics, we study student conceptual understanding of differentials, differential products, and integrals and possible pathways to understanding these quantities. We developed a multiple choice conceptual assessment employing a variety of physical contexts probing physical understanding of these three quantities and administered the instrument to over 1000 students in first and second semester introductory physics courses. Using a regression-based mediation analysis with conceptual understanding of integration as the dependent variable, we found evidence consistent with a simple mediation model: the relationship between differentials scores and integral scores may be mediated by the understanding of differential products. The indirect effect (a quantifiable metric of mediation) was estimated as a b =0.29 , 95% CI [0.25, 0.33] for N =1102 Physics 1 students, and a b =0.27 , 95% CI [0.14, 0.48] for N =65 Physics 2 students. We also find evidence that the physical context of the questions can be an important factor. These results imply that for introductory physics courses, instructional emphasis first on differentials then on differential products in a variety of contexts may in turn promote better integral understanding.

Auditory Verbal Hallucinations: can Beliefs about Voices Mediate the Relationship Patients establish with them and Negative Affect?

PubMed

León-Palacios, María de Gracia; Úbeda-Gómez, Juan; Escudero-Pérez, Silvia; Barros-Albarán, María Dolores; López-Jiménez, Ana María; Perona-Garcelán, Salvador

2015-10-13

This study was designed to find out whether a person's relationship with his voices and the negative affect he suffers from are mediated by beliefs about the voices. Research done to date shows contradictory results (Sorrell, Hayward, & Meddings, 2010, Vaughan & Fowler, 2004). A cross-sectional study was done to study the associations among variables, and a multiple mediation model (Preacher & Hayes, 2008) in which the beliefs about voices were the mediating variables was tested. Sixty subjects who heard voices participated. The VAY (Hayward, Denney, Vaughan, & Fowler, 2008), BAVQ (Chadwick & Birchwood, 1995), BAI (Beck & Steer, 1993) and BDI-II (Beck, Steer & Brown, 1996) were given. We found a significant positive correlation between perception of voices as dominant and intrusive and maintaining a position of distance from them on one hand, and negative affect [anxiety (r = .57, p < .001; r = .40, p < .001; r = .34, p < .01 respectively) and depression (r = .58, p < .001; r = .37, p < .01; r = .38, p < .001 respectively)] on the other. We also found that beliefs of malevolence and omnipotence mediated between relating style and negative affect (anxiety and depression). The theoretical implications of the results and clinical implications of the mediating relationships found are discussed.

Exploring revictimization process among Turkish women: The role of early maladaptive schemas on the link between child abuse and partner violence.

PubMed

Atmaca, Sinem; Gençöz, Tülin

2016-02-01

The purpose of the current study is to explore the revictimization process between child abuse and neglect (CAN), and intimate partner violence (IPV) based on the schema theory perspective. For this aim, 222 married women recruited in four central cities of Turkey participated in the study. Results indicated that early negative CAN experiences increased the risk of being exposed to later IPV. Specifically, emotional abuse and sexual abuse in the childhood predicted the four subtypes of IPV, which are physical, psychological, and sexual violence, and injury, while physical abuse only associated with physical violence. To explore the mediational role of early maladaptive schemas (EMSs) on this association, first, five schema domains were tested via Parallel Multiple Mediation Model. Results indicated that only Disconnection/Rejection (D/R) schema domains mediated the association between CAN and IPV. Second, to determine the particular mediational roles of each schema, eighteen EMS were tested as mediators, and results showed that Emotional Deprivation Schema and Vulnerability to Harm or Illness Schema mediated the association between CAN and IPV. These findings provided an empirical support for the crucial roles of EMSs on the effect of revictimization process. Clinical implications were discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Does Mindfulness Enhance Critical Thinking? Evidence for the Mediating Effects of Executive Functioning in the Relationship between Mindfulness and Critical Thinking.

PubMed

Noone, Chris; Bunting, Brendan; Hogan, Michael J

2015-01-01

Mindfulness originated in the Buddhist tradition as a way of cultivating clarity of thought. Despite the fact that this behavior is best captured using critical thinking (CT) assessments, no studies have examined the effects of mindfulness on CT or the mechanisms underlying any such possible relationship. Even so, mindfulness has been suggested as being beneficial for CT in higher education. CT is recognized as an important higher-order cognitive process which involves the ability to analyze and evaluate evidence and arguments. Such non-automatic, reflective responses generally require the engagement of executive functioning (EF) which includes updating, inhibition, and shifting of representations in working memory. Based on research showing that mindfulness enhances aspects of EF and certain higher-order cognitive processes, we hypothesized that individuals higher in facets of dispositional mindfulness would demonstrate greater CT performance, and that this relationship would be mediated by EF. Cross-sectional assessment of these constructs in a sample of 178 university students was achieved using the observing and non-reactivity sub-scales of the Five Factor Mindfulness Questionnaire, a battery of EF tasks and the Halpern Critical Thinking Assessment. Our hypotheses were tested by constructing a multiple meditation model which was analyzed using Structural Equation Modeling. Evidence was found for inhibition mediating the relationships between both observing and non-reactivity and CT in different ways. Indirect-only (or full) mediation was demonstrated for the relationship between observing, inhibition, and CT. Competitive mediation was demonstrated for the relationship between non-reactivity, inhibition, and CT. This suggests additional mediators of the relationship between non-reactivity and CT which are not accounted for in this model and have a negative effect on CT in addition to the positive effect mediated by inhibition. These findings are discussed in the context of the Default Interventionist Dual Process Theory of Higher-order Cognition and previous studies on mindfulness, self-regulation, EF, and higher-order cognition. In summary, dispositional mindfulness appears to facilitate CT performance and this effect is mediated by the inhibition component of EF. However, this relationship is not straightforward which suggests many possibilities for future research.

Does Mindfulness Enhance Critical Thinking? Evidence for the Mediating Effects of Executive Functioning in the Relationship between Mindfulness and Critical Thinking

PubMed Central

Noone, Chris; Bunting, Brendan; Hogan, Michael J.

2016-01-01

Mindfulness originated in the Buddhist tradition as a way of cultivating clarity of thought. Despite the fact that this behavior is best captured using critical thinking (CT) assessments, no studies have examined the effects of mindfulness on CT or the mechanisms underlying any such possible relationship. Even so, mindfulness has been suggested as being beneficial for CT in higher education. CT is recognized as an important higher-order cognitive process which involves the ability to analyze and evaluate evidence and arguments. Such non-automatic, reflective responses generally require the engagement of executive functioning (EF) which includes updating, inhibition, and shifting of representations in working memory. Based on research showing that mindfulness enhances aspects of EF and certain higher-order cognitive processes, we hypothesized that individuals higher in facets of dispositional mindfulness would demonstrate greater CT performance, and that this relationship would be mediated by EF. Cross-sectional assessment of these constructs in a sample of 178 university students was achieved using the observing and non-reactivity sub-scales of the Five Factor Mindfulness Questionnaire, a battery of EF tasks and the Halpern Critical Thinking Assessment. Our hypotheses were tested by constructing a multiple meditation model which was analyzed using Structural Equation Modeling. Evidence was found for inhibition mediating the relationships between both observing and non-reactivity and CT in different ways. Indirect-only (or full) mediation was demonstrated for the relationship between observing, inhibition, and CT. Competitive mediation was demonstrated for the relationship between non-reactivity, inhibition, and CT. This suggests additional mediators of the relationship between non-reactivity and CT which are not accounted for in this model and have a negative effect on CT in addition to the positive effect mediated by inhibition. These findings are discussed in the context of the Default Interventionist Dual Process Theory of Higher-order Cognition and previous studies on mindfulness, self-regulation, EF, and higher-order cognition. In summary, dispositional mindfulness appears to facilitate CT performance and this effect is mediated by the inhibition component of EF. However, this relationship is not straightforward which suggests many possibilities for future research. PMID:26834669

Can differences in physical activity by socio-economic status in European adolescents be explained by differences in psychosocial correlates? A mediation analysis within the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study.

PubMed

De Cocker, Katrien; Artero, Enrique G; De Henauw, Stefaan; Dietrich, Sabine; Gottrand, Frédéric; Béghin, Laurent; Hagströmer, Maria; Sjöström, Michael; Plada, Maria; Manios, Yannis; Mauro, Beatrice; Molnár, Dénes; Moreno, Luis A; Ottevaere, Charlene; Valtueña, Jara; Maes, Lea; De Bourdeaudhuij, Ilse

2012-11-01

Socio-economic status (SES) has been positively associated with physical activity (PA) levels in adolescents. In order to tackle these social inequalities, information is needed about the underlying mechanisms of this association. The present study aimed to investigate the potential mediating role of psychosocial correlates of PA on the relationship between SES and PA in European adolescents. Cross-sectional study testing the mediating role of psychosocial correlates in the SES-PA association using the product-of-coefficients test of MacKinnon. Ten European cities in nine different countries, the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Adolescents (n 2780) aged 12·5-17·49 years self-reported on PA (moderate-to-vigorous intensity PA and total PA), SES indicators (education of the mother and Family Affluence Scale) and psychosocial correlates of PA (stage of change, attitudes, awareness, modelling, social support, self-efficacy, benefits, barriers and environmental correlates). SES (Family Affluence Scale) was significantly associated with moderate-to-vigorous intensity PA. According to single-mediator models, this association was significantly mediated by stage of change (t = 3·6, P ≤ 0·001), awareness (t = 2·7, 0·001 < P ≤ 0·01), modelling (t = 4·8, P ≤ 0·001), self-efficacy (t = 2·5, 0·01

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

ERIC Educational Resources Information Center

Yildiz, Mehmet Ali

2017-01-01

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

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.

A single dose of a neuron-binding human monoclonal antibody improves brainstem NAA concentrations, a biomarker for density of spinal cord axons, in a model of progressive multiple sclerosis.

PubMed

Wootla, Bharath; Denic, Aleksandar; Watzlawik, Jens O; Warrington, Arthur E; Rodriguez, Moses

2015-04-29

Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis (MS). We previously showed that as the disease progresses, a marked decrease in brainstem N-acetyl aspartate (NAA; metabolite associated with neuronal integrity) concentrations, reflecting axon health, is measured. We also demonstrated stimulation of neurite outgrowth by a neuron-binding natural human antibody, IgM12. Treatment with either the serum-derived or recombinant human immunoglobulin M 12 (HIgM12) preserved functional motor activity in the TMEV model. In this study, we examined IgM-mediated changes in brainstem NAA concentrations and central nervous system (CNS) pathology. (1)H-magnetic resonance spectroscopy (MRS) showed that treatment with HIgM12 significantly increased brainstem NAA concentrations compared to controls in TMEV-infected mice. Pathologic analysis demonstrated a significant preservation of axons in the spinal cord of animals treated with HIgM12. This study links drug efficacy of slowing deficits with axon preservation and NAA concentrations in the brainstem in a model of progressive MS. HIgM12-mediated changes of NAA concentrations in the brainstem are a surrogate marker of axon injury/preservation throughout the spinal cord. This study provides proof-of-concept that a neuron-reactive human IgM can be therapeutic and provides a biomarker for clinical trials.

An integrative model links multiple inputs and signaling pathways to the onset of DNA synthesis in hepatocytes

PubMed Central

Huard, Jérémy; Mueller, Stephanie; Gilles, Ernst D; Klingmüller, Ursula; Klamt, Steffen

2012-01-01

During liver regeneration, quiescent hepatocytes re-enter the cell cycle to proliferate and compensate for lost tissue. Multiple signals including hepatocyte growth factor, epidermal growth factor, tumor necrosis factor α, interleukin-6, insulin and transforming growth factor β orchestrate these responses and are integrated during the G1 phase of the cell cycle. To investigate how these inputs influence DNA synthesis as a measure for proliferation, we established a large-scale integrated logical model connecting multiple signaling pathways and the cell cycle. We constructed our model based upon established literature knowledge, and successively improved and validated its structure using hepatocyte-specific literature as well as experimental DNA synthesis data. Model analyses showed that activation of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways was sufficient and necessary for triggering DNA synthesis. In addition, we identified key species in these pathways that mediate DNA replication. Our model predicted oncogenic mutations that were compared with the COSMIC database, and proposed intervention targets to block hepatocyte growth factor-induced DNA synthesis, which we validated experimentally. Our integrative approach demonstrates that, despite the complexity and size of the underlying interlaced network, logical modeling enables an integrative understanding of signaling-controlled proliferation at the cellular level, and thus can provide intervention strategies for distinct perturbation scenarios at various regulatory levels. PMID:22443451

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

PubMed

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

2013-01-01

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

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

PubMed

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

2014-03-01

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

Examining mediators of child sexual abuse and sexually transmitted infections.

PubMed

Sutherland, Melissa A

2011-01-01

Interpersonal violence has increasingly been identified as a risk factor for sexually transmitted infections. Understanding the pathways between violence and sexually transmitted infections is essential to designing effective interventions. The aim of this study was to examine dissociative symptoms, alcohol use, and intimate partner physical violence and sexual coercion as mediators of child sexual abuse and lifetime sexually transmitted infection diagnosis among a sample of women. A convenience sample of 202 women was recruited from healthcare settings, with 189 complete cases for analysis. A multiple mediation model tested the proposed mediators of child sexual abuse and lifetime sexually transmitted infection diagnosis. Bootstrapping, a resampling method, was used to test for mediation. Key variables included child sexual abuse, dissociative symptoms, alcohol use, and intimate partner violence. Child sexual abuse was reported by 46% of the study participants (n = 93). Child sexual abuse was found to have an indirect effect on lifetime sexually transmitted infection diagnosis, with the effect occurring through dissociative symptoms (95% confidence interval = 0.0033-0.4714) and sexual coercion (95% confidence interval = 0.0359-0.7694). Alcohol use and physical violence were not found to be significant mediators. This study suggests that dissociation and intimate partner sexual coercion are important mediators of child sexual abuse and sexually transmitted infection diagnosis. Therefore, interventions that consider the roles of dissociative symptoms and interpersonal violence may be effective in preventing sexually transmitted infections among women.

Natural killer cell lines preferentially kill clonogenic multiple myeloma cells and decrease myeloma engraftment in a bioluminescent xenograft mouse model

PubMed Central

Swift, Brenna E.; Williams, Brent A.; Kosaka, Yoko; Wang, Xing-Hua; Medin, Jeffrey A.; Viswanathan, Sowmya; Martinez-Lopez, Joaquin; Keating, Armand

2012-01-01

Background Novel therapies capable of targeting drug resistant clonogenic MM cells are required for more effective treatment of multiple myeloma. This study investigates the cytotoxicity of natural killer cell lines against bulk and clonogenic multiple myeloma and evaluates the tumor burden after NK cell therapy in a bioluminescent xenograft mouse model. Design and Methods The cytotoxicity of natural killer cell lines was evaluated against bulk multiple myeloma cell lines using chromium release and flow cytometry cytotoxicity assays. Selected activating receptors on natural killer cells were blocked to determine their role in multiple myeloma recognition. Growth inhibition of clonogenic multiple myeloma cells was assessed in a methylcellulose clonogenic assay in combination with secondary replating to evaluate the self-renewal of residual progenitors after natural killer cell treatment. A bioluminescent mouse model was developed using the human U266 cell line transduced to express green fluorescent protein and luciferase (U266eGFPluc) to monitor disease progression in vivo and assess bone marrow engraftment after intravenous NK-92 cell therapy. Results Three multiple myeloma cell lines were sensitive to NK-92 and KHYG-1 cytotoxicity mediated by NKp30, NKp46, NKG2D and DNAM-1 activating receptors. NK-92 and KHYG-1 demonstrated 2- to 3-fold greater inhibition of clonogenic multiple myeloma growth, compared with killing of the bulk tumor population. In addition, the residual colonies after treatment formed significantly fewer colonies compared to the control in a secondary replating for a cumulative clonogenic inhibition of 89–99% at the 20:1 effector to target ratio. Multiple myeloma tumor burden was reduced by NK-92 in a xenograft mouse model as measured by bioluminescence imaging and reduction in bone marrow engraftment of U266eGFPluc cells by flow cytometry. Conclusions This study demonstrates that NK-92 and KHYG-1 are capable of killing clonogenic and bulk multiple myeloma cells. In addition, multiple myeloma tumor burden in a xenograft mouse model was reduced by intravenous NK-92 cell therapy. Since multiple myeloma colony frequency correlates with survival, our observations have important clinical implications and suggest that clinical studies of NK cell lines to treat MM are warranted. PMID:22271890

Methylene blue induces macroautophagy through 5′ adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation

PubMed Central

Xie, Luokun; Li, Wenjun; Winters, Ali; Yuan, Fang; Jin, Kunlin; Yang, Shaohua

2013-01-01

Methylene blue has been shown to be neuroprotective in multiple experimental neurodegenerative disease models. However, the mechanisms underlying the neuroprotective effects have not been fully elucidated. Previous studies have shown that macroautophagy has multiple beneficial roles for maintaining normal cellular homeostasis and that induction of macroautophagy after myocardial ischemia is protective. In the present study we demonstrated that methylene blue could protect HT22 hippocampal cell death induced by serum deprivation, companied by induction of macroautophagy. We also found that methylene blue-mediated neuroprotection was abolished by macroautophagy inhibition. Interestingly, 5′ adenosine monophosphate-activated protein kinase (AMPK) signaling, but not inhibition of mammalian target of rapamycin signaling, was activated at 12 and 24 h after methylene blue treatment in a dose-dependent manner. Methylene blue-induced macroautophagy was blocked by AMPK inhibitor. Consistent with in vitro data, macroautophagy was induced in the cortex and hippocampus of mouse brains treated with methylene blue. Our findings suggest that methylene blue-induced neuroprotection is mediated, at least in part, by macroautophagy though activation of AMPK signaling. PMID:23653592

Methylene blue induces macroautophagy through 5' adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation.

PubMed

Xie, Luokun; Li, Wenjun; Winters, Ali; Yuan, Fang; Jin, Kunlin; Yang, Shaohua

2013-01-01

Methylene blue has been shown to be neuroprotective in multiple experimental neurodegenerative disease models. However, the mechanisms underlying the neuroprotective effects have not been fully elucidated. Previous studies have shown that macroautophagy has multiple beneficial roles for maintaining normal cellular homeostasis and that induction of macroautophagy after myocardial ischemia is protective. In the present study we demonstrated that methylene blue could protect HT22 hippocampal cell death induced by serum deprivation, companied by induction of macroautophagy. We also found that methylene blue-mediated neuroprotection was abolished by macroautophagy inhibition. Interestingly, 5' adenosine monophosphate-activated protein kinase (AMPK) signaling, but not inhibition of mammalian target of rapamycin signaling, was activated at 12 and 24 h after methylene blue treatment in a dose-dependent manner. Methylene blue-induced macroautophagy was blocked by AMPK inhibitor. Consistent with in vitro data, macroautophagy was induced in the cortex and hippocampus of mouse brains treated with methylene blue. Our findings suggest that methylene blue-induced neuroprotection is mediated, at least in part, by macroautophagy though activation of AMPK signaling.

The CD8 T cell in multiple sclerosis: suppressor cell or mediator of neuropathology?

PubMed

Johnson, Aaron J; Suidan, Georgette L; McDole, Jeremiah; Pirko, Istvan

2007-01-01

Multiple sclerosis (MS) is the most common human demyelinating disease of the central nervous system. It is universally accepted that the immune system plays a major role in the pathogenesis of MS. For decades, CD4 T cells have been considered the predominant mediator of neuropathology in MS. This perception was largely due to the similarity between MS and CD4 T-cell-driven experimental allergic encephalomyelitis, the most commonly studied murine model of MS. Over the last decade, several new observations in MS research imply an emerging role for CD8 T cells in neuropathogenesis. In certain experimental autoimmune encephalomyelitis (EAE) models, CD8 T cells are considered suppressors of pathology, whereas in other EAE models, neuropathology can be exacerbated by adoptive transfer of CD8 T cells. Studies using the Theiler's murine encephalomyelitis virus (TMEV) model have demonstrated preservation of motor function and axonal integrity in animals deficient in CD8 T cells or their effector molecules. CD8 T cells have also been demonstrated to be important regulators of blood-brain barrier permeability. There is also an emerging role for CD8 T cells in human MS. Human genetic studies reveal an important role for HLA class I molecules in MS susceptibility. In addition, neuropathologic studies demonstrate that CD8 T cells are the most numerous inflammatory infiltrate in MS lesions at all stages of lesion development. CD8 T cells are also capable of damaging neurons and axons in vitro. In this chapter, we discuss the neuropathologic, genetic, and experimental evidence for a critical role of CD8 T cells in the pathogenesis of MS and its most frequently studied animal models. We also highlight important new avenues for future research.

Social pathways to health: On the mediating role of the social network in the relation between socio-economic position and health.

PubMed

Aartsen, Marja; Veenstra, Marijke; Hansen, Thomas

2017-12-01

Good health is one of the key qualities of life, but opportunities to be and remain healthy are unequally distributed across socio-economic groups. The beneficial health effects of the social network are well known. However, research on the social network as potential mediator in the pathway from socio-economic position (SEP) to health is scarce, while there are good reasons to expect a socio-economical patterning of networks. We aim to contribute to our understanding of socio-economic inequalities in health by examining the mediating role of structural and functional characteristics of the social network in the SEP-health relationship. Data were from the second wave of the Norwegian study on the life course, aging and generation study (NorLAG) and comprised 4534 men and 4690 women aged between 40 and 81. We applied multiple mediation models to evaluate the relative importance of each network characteristic, and multiple group analysis to examine differences between middle-aged and older men and women. Our results indicated a clear socio-economical patterning of the social network for men and women. People with higher SEP had social networks that better protect against loneliness, which in turn lead to better health outcomes. The explained variance in health in older people by the social network and SEP was only half of the explained variance observed in middle-aged people, suggesting that other factors than SEP were more important for health when people age. We conclude that it is the function of the network, rather than the structure, that counts for health.

ADHD and risky sexual behavior in adolescents: Conduct problems and substance use as mediators of risk

PubMed Central

Sarver, Dustin E.; McCart, Michael R.; Sheidow, Ashli J.; Letourneau, Elizabeth J.

2015-01-01

Background Recent studies have linked attention-deficit/hyperactivity disorder (ADHD) to elevated rates of risky sexual behavior (RSB) in adult samples. The current study tested whether ADHD symptoms were associated with RSB among adolescents, and examined comorbid conduct problems and problematic substance use as joint mediators of this association. Methods ADHD symptoms, conduct problems (oppositional defiant disorder/conduct disorder symptoms), problematic alcohol use (alcohol use disorder symptoms, alcohol use frequency), problematic marijuana use (marijuana use disorder symptoms, marijuana use frequency), and RSB were assessed among an ethnically diverse cross-sectional sample of adolescents (N=115; mean age=14.9 years) involved in the juvenile justice system. Results Bootstrapped mediation models revealed an initial association between ADHD symptoms and RSB that was accounted for fully by the influence of problematic alcohol and marijuana use, but not conduct problems. A follow-up multiple groups mediation analysis demonstrated that the relationship between ADHD symptoms and RSB emerged only among youth with clinically elevated conduct problems, and that problematic marijuana use fully accounted for this relationship. Hyperactive/impulsive but not inattentive symptoms were related to RSB, although the pattern of indirect effects was consistent with the multiple groups analysis. Conclusions The association between ADHD and adolescent RSB is restricted to youth with elevated comorbid conduct problems and reflects the contributions of comorbid marijuana use problems, and to a lesser extent alcohol use problems. Early identification and treatment of these comorbid conditions may be important for the prevention of negative sexual health outcomes among youth with ADHD. PMID:24813803

Associations Between Multiple Forms of Discrimination and Tobacco Use Among People Living With HIV: The Mediating Role of Avoidance Coping.

PubMed

Crockett, Kaylee B; Rice, Whitney S; Turan, Bulent

2018-05-01

People living with HIV (PLWH) have higher levels of tobacco use compared with the general population, increasing their risk of morbidity and mortality. PLWH also face potential chronic stressors related to the stigma and discrimination associated with HIV and other characteristics (eg, race and sexual orientation). These experiences may be associated with harmful health behaviors, such as tobacco use. The purpose of the current study is to explore the psychosocial context of tobacco use in PLWH, examining avoidance coping as a mediator in the relationship between multiple forms of discrimination and tobacco use. Participants included 202 PLWH recruited from an HIV primary care clinic in Birmingham, AL, between 2013 and 2015. Participants responded to parallel items assessing experiences of discrimination related to HIV status, race, and sexual orientation, as well as items assessing avoidance coping. Data on current tobacco use were obtained from participants' clinic records. Mediation models for each form of discrimination (HIV, race and sexual orientation) adjusting for demographic variables and the other forms of discrimination were evaluated. The indirect effect of HIV-related discrimination on likelihood of tobacco use through avoidance coping was significant, suggesting that avoidance coping mediates the association between HIV-related discrimination and tobacco use. However, the indirect effects of the other forms of discrimination were not significant. Given the disparity in tobacco use in PLWH, behavioral scientists and interventionists should consider including content specific to coping with experiences of discrimination in tobacco prevention and cessation programs for PLWH.

SchizConnect: Mediating neuroimaging databases on schizophrenia and related disorders for large-scale integration.

PubMed

Wang, Lei; Alpert, Kathryn I; Calhoun, Vince D; Cobia, Derin J; Keator, David B; King, Margaret D; Kogan, Alexandr; Landis, Drew; Tallis, Marcelo; Turner, Matthew D; Potkin, Steven G; Turner, Jessica A; Ambite, Jose Luis

2016-01-01

SchizConnect (www.schizconnect.org) is built to address the issues of multiple data repositories in schizophrenia neuroimaging studies. It includes a level of mediation--translating across data sources--so that the user can place one query, e.g. for diffusion images from male individuals with schizophrenia, and find out from across participating data sources how many datasets there are, as well as downloading the imaging and related data. The current version handles the Data Usage Agreements across different studies, as well as interpreting database-specific terminologies into a common framework. New data repositories can also be mediated to bring immediate access to existing datasets. Compared with centralized, upload data sharing models, SchizConnect is a unique, virtual database with a focus on schizophrenia and related disorders that can mediate live data as information is being updated at each data source. It is our hope that SchizConnect can facilitate testing new hypotheses through aggregated datasets, promoting discovery related to the mechanisms underlying schizophrenic dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Investing in the ideal: does objectified body consciousness mediate the association between appearance contingent self-worth and appearance self-esteem in women?

PubMed

Noser, Amy; Zeigler-Hill, Virgil

2014-03-01

Appearance contingent self-worth has been shown to be associated with low appearance self-esteem but little is known about the role that objectified body consciousness may play in this relationship. The purpose of the present study with 465 female undergraduates was to examine whether objectified body consciousness mediates the association between appearance contingent self-worth and low levels of appearance self-esteem. This was accomplished using a multiple mediation model to examine whether components of objectified body consciousness (i.e., body surveillance, body shame, and control beliefs) play unique roles in the connection between appearance contingent self-worth and appearance self-esteem. Results showed that body surveillance and body shame were significant mediators of the connection between appearance contingent self-worth and low levels of appearance self-esteem. Discussion focuses on the implications of these results for the ways in which appearance contingent self-worth may promote heightened body consciousness and possibly contribute to low levels of appearance self-esteem. Copyright © 2013 Elsevier Ltd. All rights reserved.

School Engagement Mediates Long Term Prevention Effects for Mexican American Adolescents

PubMed Central

Gonzales, Nancy A.; Wong, Jessie J.; Toomey, Russell B.; Millsap, Roger; Dumka, Larry E.; Mauricio, Anne M.

2014-01-01

This five year follow-up of a randomized clinical trial evaluated the efficacy of a family-focused intervention delivered in middle school to increase school engagement following transition to high school (2 years posttest), and also evaluated mediated effects through school engagement on multiple problem outcomes in late adolescence (5 years posttest). The study sample included 516 Mexican American adolescents who participated in a randomized trial of the Bridges to High School Program (Bridges/ Puentes). Path models representing the direct and indirect effects of the program on four outcome variables were evaluated using school engagement measured in the 9th grade as a mediator. The program significantly increased school engagement, with school engagement mediating intervention effects on internalizing symptoms, adolescent substance use, and school dropout in late adolescence when most adolescents were in the 12th grade. Effects on substance use were stronger for youth at higher risk based on pretest report of substance use initiation. There were no direct or indirect intervention effects on externalizing symptoms. Findings support that school engagement is an important prevention target for Mexican American adolescents. PMID:24398825

Mental well-being mediates the relationship between perceived stress and perceived health.

PubMed

Teh, Hui Chian; Archer, Josephine A; Chang, Weining; Chen, S H Annabel

2015-02-01

The association between stress and health has been well researched in the past; however, comparatively few mediators have been tested to understand the underlying mechanism. With increasing awareness on mental well-being, this study evaluated the relationship between perceived stress and perceived health and examined mental well-being as a mediator. Two-hundred undergraduates aged 21 to 26 years completed the English Perceived Stress Scale, Health Status Questionnaire and Asian Mental Well-Being Scale that assess perceived stress, perceived health and mental well-being, respectively. Factor analysis and structural equation modelling on the Perceived Stress Scale replicated the reported two-factor structure after excluding an insignificant item. Linear multiple regression analyses indicated that perceived stress was negatively associated with perceived health. Results showed that mental well-being partially mediated the relationship between perceived stress and perceived health, although it is acknowledged that this association could be bidirectional. Findings from the present study suggest that future research could focus on reducing stress and improving mental well-being to alleviate the effect of stress on health. © 2013 John Wiley & Sons, Ltd.

Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons

PubMed Central

Kim, Yujin; Hsu, Ching-Lung; Cembrowski, Mark S; Mensh, Brett D; Spruston, Nelson

2015-01-01

Dendritic integration of synaptic inputs mediates rapid neural computation as well as longer-lasting plasticity. Several channel types can mediate dendritically initiated spikes (dSpikes), which may impact information processing and storage across multiple timescales; however, the roles of different channels in the rapid vs long-term effects of dSpikes are unknown. We show here that dSpikes mediated by Nav channels (blocked by a low concentration of TTX) are required for long-term potentiation (LTP) in the distal apical dendrites of hippocampal pyramidal neurons. Furthermore, imaging, simulations, and buffering experiments all support a model whereby fast Nav channel-mediated dSpikes (Na-dSpikes) contribute to LTP induction by promoting large, transient, localized increases in intracellular calcium concentration near the calcium-conducting pores of NMDAR and L-type Cav channels. Thus, in addition to contributing to rapid neural processing, Na-dSpikes are likely to contribute to memory formation via their role in long-lasting synaptic plasticity. DOI: http://dx.doi.org/10.7554/eLife.06414.001 PMID:26247712

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.

Estradiol Membrane-Initiated Signaling in the Brain Mediates Reproduction.

PubMed

Micevych, Paul E; Mermelstein, Paul G; Sinchak, Kevin

2017-11-01

Over the past few years our understanding of estrogen signaling in the brain has expanded rapidly. Estrogens are synthesized in the periphery and in the brain, acting on multiple receptors to regulate gene transcription, neural function, and behavior. Various estrogen-sensitive signaling pathways often operate in concert within the same cell, increasing the complexity of the system. In females, estrogen concentrations fluctuate over the estrous/menstrual cycle, dynamically modulating estrogen receptor (ER) expression, activity, and trafficking. These dynamic changes influence multiple behaviors but are particularly important for reproduction. Using the female rodent model, we review our current understanding of estradiol signaling in the regulation of sexual receptivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Selective Tie2 Inhibitor Rebastinib Blocks Recruitment and Function of Tie2Hi Macrophages in Breast Cancer and Pancreatic Neuroendocrine Tumors.

PubMed

Harney, Allison S; Karagiannis, George S; Pignatelli, Jeanine; Smith, Bryan D; Kadioglu, Ece; Wise, Scott C; Hood, Molly M; Kaufman, Michael D; Leary, Cynthia B; Lu, Wei-Ping; Al-Ani, Gada; Chen, Xiaoming; Entenberg, David; Oktay, Maja H; Wang, Yarong; Chun, Lawrence; De Palma, Michele; Jones, Joan G; Flynn, Daniel L; Condeelis, John S

2017-11-01

Tumor-infiltrating myeloid cells promote tumor progression by mediating angiogenesis, tumor cell intravasation, and metastasis, which can offset the effects of chemotherapy, radiation, and antiangiogenic therapy. Here, we show that the kinase switch control inhibitor rebastinib inhibits Tie2, a tyrosine kinase receptor expressed on endothelial cells and protumoral Tie2-expressing macrophages in mouse models of metastatic cancer. Rebastinib reduces tumor growth and metastasis in an orthotopic mouse model of metastatic mammary carcinoma through reduction of Tie2 + myeloid cell infiltration, antiangiogenic effects, and blockade of tumor cell intravasation mediated by perivascular Tie2 Hi /Vegf-A Hi macrophages in the tumor microenvironment of metastasis (TMEM). The antitumor effects of rebastinib enhance the efficacy of microtubule inhibiting chemotherapeutic agents, either eribulin or paclitaxel, by reducing tumor volume, metastasis, and improving overall survival. Rebastinib inhibition of angiopoietin/Tie2 signaling impairs multiple pathways in tumor progression mediated by protumoral Tie2 + macrophages, including TMEM-dependent dissemination and angiopoietin/Tie2-dependent angiogenesis. Rebastinib is a promising therapy for achieving Tie2 inhibition in cancer patients. Mol Cancer Ther; 16(11); 2486-501. ©2017 AACR . ©2017 American Association for Cancer Research.

Cumulative Risk Exposure and Waist Circumference in Preschool-Aged Children: the Mediating Role of Television and Moderating Role of Sex.

PubMed

Grummon, Anna H; Vaughn, Amber; Jones, Deborah J; Ward, Dianne S

2017-08-01

Children exposed to multiple stressors are more likely to be overweight, but little is known about the mechanisms explaining this association. This cross-sectional study examined whether children exposed to multiple stressors had higher waist circumference, and whether this association was mediated through children's television time. Participants were 319 parent-child dyads. Children were 2-5 years old and had at least one overweight parent (BMI ≥ 25 kg/m 2 ). Data were collected at baseline of a larger childhood obesity prevention study and included information on psychosocial stressors (e.g., parenting stress), demographic stressors (e.g., low income), children's television time, and children's waist circumference. Two cumulative risk scores were created by summing stressors in each domain (demographic and psychosocial). Mediation and moderated mediation analyses were conducted. Indirect effects of both cumulative risk scores on waist circumference through television time were not significant; however, moderated mediation analyses found significant moderation by gender. The indirect effects of both risk scores on waist circumference through television time were significant and positive for girls, but near-zero for boys. Reducing television time should be explored as a strategy for buffering against the negative health effects of exposure to multiple stressors among girls. Longitudinal and intervention research is needed to confirm these results and to identify mediating factors between cumulative risk and body weight among boys.

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

PubMed

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

2012-01-25

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

From Training to Organizational Behavior: A Mediation Model through Absorptive and Innovative Capacities

PubMed Central

Yáñez-Araque, Benito; Hernández-Perlines, Felipe; Moreno-Garcia, Juan

2017-01-01

The training of human resources improves business performance: myth or reality? While the literature has extensively addressed this issue, the transfer that occurs from training to performance still remains unresolved. The present study suggests an empirical solution to this gap, through a multiple mediation model of dynamic capabilities. Accordingly, the study makes a major contribution to the effectiveness of an organizational-level training: the “true” relationship between training and performance is mediated by absorptive and innovative capacities. It is difficult from training to directly affect the results: it must be done through a chain of intermediate variables. Training can be argued to be indirectly related to performance, through absorptive capacity in the first place, and innovative capacity in the second, sequentially in this order (three-path mediated effect). Of all immediate relationships received by performance, its explained variance is achieved partly via absorptive capacity and partly via innovation. The direct relationship through training is not significant and only explains a small percentage of the variance in performance. These results have been corroborated by combining two methods of analysis: PLS-SEM and fsQCA, using data from an online survey. This dual methodology in the study of the same phenomenon allows overcoming the limitations of each method, which would not have been possible with a single methodological approach, and confirming the findings obtained by any of them. PMID:28966599

From Training to Organizational Behavior: A Mediation Model through Absorptive and Innovative Capacities.

PubMed

Yáñez-Araque, Benito; Hernández-Perlines, Felipe; Moreno-Garcia, Juan

2017-01-01

The training of human resources improves business performance: myth or reality? While the literature has extensively addressed this issue, the transfer that occurs from training to performance still remains unresolved. The present study suggests an empirical solution to this gap, through a multiple mediation model of dynamic capabilities. Accordingly, the study makes a major contribution to the effectiveness of an organizational-level training: the "true" relationship between training and performance is mediated by absorptive and innovative capacities. It is difficult from training to directly affect the results: it must be done through a chain of intermediate variables. Training can be argued to be indirectly related to performance, through absorptive capacity in the first place, and innovative capacity in the second, sequentially in this order (three-path mediated effect). Of all immediate relationships received by performance, its explained variance is achieved partly via absorptive capacity and partly via innovation. The direct relationship through training is not significant and only explains a small percentage of the variance in performance. These results have been corroborated by combining two methods of analysis: PLS-SEM and fsQCA, using data from an online survey. This dual methodology in the study of the same phenomenon allows overcoming the limitations of each method, which would not have been possible with a single methodological approach, and confirming the findings obtained by any of them.

Generation and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered mouse models of sarcoma

PubMed Central

Huang, Jianguo; Chen, Mark; Whitley, Melodi Javid; Kuo, Hsuan-Cheng; Xu, Eric S.; Walens, Andrea; Mowery, Yvonne M.; Van Mater, David; Eward, William C.; Cardona, Diana M.; Luo, Lixia; Ma, Yan; Lopez, Omar M.; Nelson, Christopher E.; Robinson-Hamm, Jacqueline N.; Reddy, Anupama; Dave, Sandeep S.; Gersbach, Charles A.; Dodd, Rebecca D.; Kirsch, David G.

2017-01-01

Genetically engineered mouse models that employ site-specific recombinase technology are important tools for cancer research but can be costly and time-consuming. The CRISPR-Cas9 system has been adapted to generate autochthonous tumours in mice, but how these tumours compare to tumours generated by conventional recombinase technology remains to be fully explored. Here we use CRISPR-Cas9 to generate multiple subtypes of primary sarcomas efficiently in wild type and genetically engineered mice. These data demonstrate that CRISPR-Cas9 can be used to generate multiple subtypes of soft tissue sarcomas in mice. Primary sarcomas generated with CRISPR-Cas9 and Cre recombinase technology had similar histology, growth kinetics, copy number variation and mutational load as assessed by whole exome sequencing. These results show that sarcomas generated with CRISPR-Cas9 technology are similar to sarcomas generated with conventional modelling techniques and suggest that CRISPR-Cas9 can be used to more rapidly generate genotypically and phenotypically similar cancers. PMID:28691711

Weight-teasing and emotional well-being in adolescents: longitudinal findings from Project EAT.

PubMed

Eisenberg, Marla E; Neumark-Sztainer, Dianne; Haines, Jess; Wall, Melanie

2006-06-01

To determine if weight-teasing predicts subsequent low self-esteem, poor body image, and depressive symptoms; and to examine two mechanisms through which early teasing may influence later emotional health. A racially and socio-economically diverse sample of 2516 adolescents completed surveys for both Wave 1 (1998-99) and Wave 2 (2003-04) of the Project EAT study. Approximately one third of these were early adolescents who transitioned into middle adolescence, and two thirds were middle adolescents who transitioned into young adulthood. Multiple linear regression analysis was conducted in three stages to test Model A: the total effect of Time 1 teasing on Time 2 emotional health; Model B: Model A, mediated by Time 2 teasing and body mass index (BMI); and Model C: Model B, also mediated by Time 1 emotional health. Approximately one third of males and slightly under half of females reported that they had been teased about their weight at Time 1. Time 1 teasing predicted lower self-esteem, lower body image, and higher depressive symptoms at Time 2 for males and females in the older and younger age groups. This relationship was fully mediated, however, by Time 2 teasing and BMI, and by Time 1 emotional health. Adjusted R2 statistics for the final models ranged from .11 to .36. Weight-teasing in adolescence affects emotional well-being at 5-year follow-up, and appears to function through two mechanisms. Reducing early teasing and its concurrent damages to emotional health may prevent longer-term emotional health consequences.

Direct and indirect associations between the family physical activity environment and sports participation among 10-12 year-old European children: testing the EnRG framework in the ENERGY project.

PubMed

Timperio, Anna F; van Stralen, Maartje M; Brug, Johannes; Bere, Elling; Chinapaw, Mai J M; De Bourdeaudhuij, Ilse; Jan, Nataša; Maes, Lea; Manios, Yannis; Moreno, Luis A; Salmon, Jo; Te Velde, Saskia J

2013-02-03

Sport participation makes an important contribution to children's overall physical activity. Understanding influences on sports participation is important and the family environment is considered key, however few studies have explored the mechanisms by which the family environment influences children's sport participation. The purpose of this study was to examine whether attitude, perceived behavioural control, health belief and enjoyment mediate associations between the family environment and 10-12 year-old children's sports participation. Children aged 10-12 years ( = 7,234) and one of their parents (n = 6,002) were recruited from 175 schools in seven European countries in 2010. Children self-reported their weekly duration of sports participation, physical activity equipment items at home and the four potential mediator variables. Parents responded to items on financial, logistic and emotional support, reinforcement, modelling and co-participation in physical activity. Cross-sectional single and multiple mediation analyses were performed for 4952 children with complete data using multi-level regression analyses. Availability of equipment (OR = 1.16), financial (OR = 1.53), logistic (OR = 1.47) and emotional (OR = 1.51) support, and parental modelling (OR = 1.07) were positively associated with participation in ≥  30 mins/wk of sport. Attitude, beliefs, perceived behavioural control and enjoyment mediated and explained between 21-34% of these associations. Perceived behavioural control contributed the most to the mediated effect for each aspect of the family environment. Both direct (unmediated) and indirect (mediated) associations were found between most family environment variables and children's sports participation. Thus, family-based physical activity interventions that focus on enhancing the family environment to support children's sport participation are warranted.

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

PubMed

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

2018-06-01

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

Five-Factor Personality Traits and Subjective Health Among Caregivers: The Role of Caregiver Strain and Self-Efficacy

PubMed Central

Löckenhoff, Corinna E.; Duberstein, Paul R.; Friedman, Bruce; Costa, Paul T.

2011-01-01

This study examined the association among caregivers’ five-factor personality traits and subjective health with particular emphasis on the role of two theoretically implicated mediators: multi-domain self-efficacy and caregiver strain. The sample comprised 536 informal caregivers (mean age = 62.9 years, SD = 19.9, 72% female, 98% White) of community-dwelling older adults with multiple functional impairments. Both physical health and mental health were negatively associated with neuroticism and positively associated with extraversion and conscientiousness. Agreeableness and openness were associated with better subjective mental health and physical health, respectively. Multiple mediation analyses indicated that self-efficacy mediated all observed associations between personality and subjective health, whereas caregiver strain selectively mediated the associations of neuroticism and agreeableness with mental health. PMID:21417534

Predicting homophobic behavior among heterosexual youth: domain general and sexual orientation-specific factors at the individual and contextual level.

PubMed

Poteat, V Paul; DiGiovanni, Craig D; Scheer, Jillian R

2013-03-01

As a form of bias-based harassment, homophobic behavior remains prominent in schools. Yet, little attention has been given to factors that underlie it, aside from bullying and sexual prejudice. Thus, we examined multiple domain general (empathy, perspective-taking, classroom respect norms) and sexual orientation-specific factors (sexual orientation identity importance, number of sexual minority friends, parents' sexual minority attitudes, media messages). We documented support for a model in which these sets of factors converged to predict homophobic behavior, mediated through bullying and prejudice, among 581 students in grades 9-12 (55 % female). The structural equation model indicated that, with the exception of media messages, these additional factors predicted levels of prejudice and bullying, which in turn predicted the likelihood of students to engage in homophobic behavior. These findings highlight the importance of addressing multiple interrelated factors in efforts to reduce bullying, prejudice, and discrimination among youth.

Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis.

PubMed

Migliore, Marco; Pontis, Silvia; Fuentes de Arriba, Angel Luis; Realini, Natalia; Torrente, Esther; Armirotti, Andrea; Romeo, Elisa; Di Martino, Simona; Russo, Debora; Pizzirani, Daniela; Summa, Maria; Lanfranco, Massimiliano; Ottonello, Giuliana; Busquet, Perrine; Jung, Kwang-Mook; Garcia-Guzman, Miguel; Heim, Roger; Scarpelli, Rita; Piomelli, Daniele

2016-09-05

Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are endogenous lipid mediators that suppress inflammation. Their actions are terminated by the intracellular cysteine amidase, N-acylethanolamine acid amidase (NAAA). Even though NAAA may offer a new target for anti-inflammatory therapy, the lipid-like structures and reactive warheads of current NAAA inhibitors limit the use of these agents as oral drugs. A series of novel benzothiazole-piperazine derivatives that inhibit NAAA in a potent and selective manner by a non-covalent mechanism are described. A prototype member of this class (8) displays high oral bioavailability, access to the central nervous system (CNS), and strong activity in a mouse model of multiple sclerosis (MS). This compound exemplifies a second generation of non-covalent NAAA inhibitors that may be useful in the treatment of MS and other chronic CNS disorders. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo

PubMed Central

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

2015-01-01

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. PMID:26240385

Social oppression, psychological vulnerability, and unprotected intercourse among young Black men who have sex with men.

PubMed

Huebner, David M; Kegeles, Susan M; Rebchook, Gregory M; Peterson, John L; Neilands, Torsten B; Johnson, Wayne D; Eke, Agatha N

2014-12-01

Young Black men who have sex with men (YBMSM) are at extraordinarily high risk for HIV infection. Given their dual minority identity, they experience multiple forms of social oppression-racism, homophobia, and poverty. This study tested a model for how these forces contribute to their sexual risk behavior. YBMSM (n = 1,289) from 2 Texas cities completed a 1-time assessment of sexual behaviors and psychosocial variables. Structural equation modeling was used to characterize relationships among variables. Experiences of racism, homophobia, and socioeconomic distress were all associated with unprotected anal intercourse (UAI) either directly or indirectly in a manner largely consistent with Díaz's (1997, 1998) model of the effects of social oppression. Racism, homophobia, and socioeconomic distress were each associated with specific psychological vulnerabilities, which were in turn associated with participation in difficult sexual situations (e.g., in a public setting), and then UAI. The effects of racism were largely mediated by depressive symptoms and participation in difficult sexual situations. Homophobia was mediated by depressive symptoms, social support, and internalized homophobia. The effects of socioeconomic distress were partially mediated by decreased social support and greater participation in difficult sexual situations. Socioeconomic distress also had a significant direct effect on UAI not explained by the proposed mediators. Social oppression contributes to YBMSM's psychological vulnerabilities, participation in difficult sexual situations, and their UAI. Interventions to reduce sexual risk in YBMSM should address socioeconomic disadvantage, homophobia, and racism, as well as the psychological challenges that social oppression creates for them.

The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease.

PubMed

Finkelstein, David I; Billings, Jessica L; Adlard, Paul A; Ayton, Scott; Sedjahtera, Amelia; Masters, Colin L; Wilkins, Simon; Shackleford, David M; Charman, Susan A; Bal, Wojciech; Zawisza, Izabela A; Kurowska, Ewa; Gundlach, Andrew L; Ma, Sheri; Bush, Ashley I; Hare, Dominic J; Doble, Philip A; Crawford, Simon; Gautier, Elisabeth Cl; Parsons, Jack; Huggins, Penny; Barnham, Kevin J; Cherny, Robert A

2017-06-28

Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions. In vitro, PBT434 was far less potent than deferiprone or deferoxamine at lowering cellular iron levels, yet was found to inhibit iron-mediated redox activity and iron-mediated aggregation of α-synuclein, a protein that aggregates in the neuropathology. In vivo, PBT434 did not deplete tissue iron stores in normal rodents, yet prevented loss of substantia nigra pars compacta neurons (SNpc), lowered nigral α-synuclein accumulation, and rescued motor performance in mice exposed to the Parkinsonian toxins 6-OHDA and MPTP, and in a transgenic animal model (hA53T α-synuclein) of PD. These improvements were associated with reduced markers of oxidative damage, and increased levels of ferroportin (an iron exporter) and DJ-1. We conclude that compounds designed to target a pool of pathological iron that is not held in high-affinity complexes in the tissue can maintain the survival of SNpc neurons and could be disease-modifying in PD.

Parental drinking as a risk factor for children's maladjustment: the mediating role of family environment.

PubMed

Bijttebier, Patricia; Goethals, Eveline

2006-06-01

In the present study, the relationships among parental drinking, family environment, and child adjustment is investigated in a community sample of 207 10-14-year-olds. Multiple aspects of perceived family environment (e.g., cohesion, organization, conflict) as well as multiple indicators of adjustment (e.g., negative affect, feelings of competence, self-esteem) are taken into consideration. Parental alcohol problems are found to be associated with low family cohesion, poor family organization, and low global self-worth of the child. A mediational analysis reveals that the relation between parental drinking and low global self-worth is mediated by family cohesion.

Helminths as governors of immune-mediated inflammation.

PubMed

Elliott, David E; Summers, Robert W; Weinstock, Joel V

2007-04-01

Immune-mediated diseases (e.g. inflammatory bowel disease, asthma, multiple sclerosis and autoimmune diabetes) are increasing in prevalence and emerge as populations adopt meticulously hygienic lifestyles. This change in lifestyles precludes exposure to helminths (parasitic worms). Loss of natural helminth exposure removes a previously universal Th2 and regulatory immune biasing imparted by these organisms. Helminths protect animals from developing immune-mediated diseases (colitis, reactive airway disease, encephalitis and diabetes). Clinical trials show that exposure to helminths can reduce disease activity in patients with ulcerative colitis or Crohn's disease. This paper summarises work by multiple groups demonstrating that colonization with helminths alters immune reactivity and protects against disease from dysregulated inflammation.

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

PubMed

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

2015-01-01

Concern about falling can have devastating physical and psychological consequences in people with multiple sclerosis (MS). However, little is known about physical and cognitive determinants for increased concern about falling inthis group. To investigate direct and indirect relationships between MS severity and concern about falling using structural equation modelling (SEM). Two hundred and ten community-dwelling people (21-73 years) with MS Disease Steps 0-5 completed several physical, cognitive and psychological assessments. Concern about falling was assessed using the Falls Efficacy Scale-International. Concern about falling was significantly associated with MS Disease Step and also balance, muscle strength, disability, previous falls, and executive functioning. SEM revealed a strong direct path between MS Disease Step and concern about falling (r = 0.31, p <  0.01), as well as indirect paths explained by impaired physical ability (r = 0.25, p <  0.01) and reduced cognitive function (r = 0.13, p <  0.01). The final model explained 51% of the variance of concern about falling in people with MS and had an excellent goodness-of-fit. The relationship between MS severity and increased concern about falling was primarily mediated by reduced physical ability (especially if this resulted in disability and falls) and less so by executive functioning. This suggests people with MS have a realistic appraisal of their concern about falling.

Linking Family Characteristics with Poor Peer Relations: The Mediating Role of Conduct Problems

PubMed Central

Bierman, Karen Linn; Smoot, David L.

2012-01-01

Parent, teacher, and peer ratings were collected for 75 grade school boys to test the hypothesis that certain family interaction patterns would be associated with poor peer relations. Path analyses provided support for a mediational model, in which punitive and ineffective discipline was related to child conduct problems in home and school settings which, in turn, predicted poor peer relations. Further analyses suggested that distinct subgroups of boys could be identified who exhibited conduct problems at home only, at school only, in both settings, or in neither setting. Boys who exhibited cross-situational conduct problems were more likely to experience multiple concurrent problems (e.g., in both home and school settings) and were more likely than any other group to experience poor peer relations. However, only about one-third of the boys with poor peer relations in this sample exhibited problem profiles consistent with the proposed model (e.g., experienced high rates of punitive/ineffective home discipline and exhibited conduct problems in home and school settings), suggesting that the proposed model reflects one common (but not exclusive) pathway to poor peer relations. PMID:1865049

Mouse and Guinea Pig Models of Tuberculosis.

PubMed

Orme, Ian M; Ordway, Diane J

2016-08-01

This article describes the nature of the host response to Mycobacterium tuberculosis in the mouse and guinea pig models of infection. It describes the great wealth of information obtained from the mouse model, reflecting the general availability of immunological reagents, as well as genetic manipulations of the mouse strains themselves. This has led to a good understanding of the nature of the T-cell response to the infection, as well as an appreciation of the complexity of the response involving multiple cytokine- and chemokine-mediated systems. As described here and elsewhere, we have a growing understanding of how multiple CD4-positive T-cell subsets are involved, including regulatory T cells, TH17 cells, as well as the subsequent emergence of effector and central memory T-cell subsets. While, in contrast, our understanding of the host response in the guinea pig model is less advanced, considerable strides have been made in the past decade in terms of defining the basis of the immune response, as well as a better understanding of the immunopathologic process. This model has long been the gold standard for vaccine testing, and more recently is being revisited as a model for testing new drug regimens (bedaquiline being the latest example).

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

PubMed Central

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

2018-01-01

Introduction Empirical work has documented a robust and consistent relation between panic attacks and smoking behavior. Theoretical models posit smokers with panic attacks may rely on smoking to help them manage chronically elevated negative affect due to uncomfortable bodily states, which may explain higher levels of nicotine dependence and quit problems. Methods The current study examined the effects of panic attack history on nicotine dependence, perceived barriers for quitting, smoking inflexibility when emotionally distressed, and expired carbon monoxide among 461 treatment-seeking smokers. A multiple mediator path model was evaluated to examine the indirect effects of negative affect and negative affect reduction motives as mediators of the panic attack-smoking relations. Results Panic attack history was indirectly related to greater levels of nicotine dependence (b=0.039, CI95%=0.008, 0.097), perceived barriers to smoking cessation (b=0.195, CI95%=0.043, 0.479), smoking inflexibility/avoidance when emotionally distressed (b=0.188, CI95%=0.041, 0.445), and higher levels of expired carbon monoxide (b=0.071, CI95%=0.010, 0.230) through the sequential effects of negative affect and negative affect smoking motives. Conclusions The present results provide empirical support for the sequential mediating role of negative affect and smoking motives for negative affect reduction in the relation between panic attacks and a variety of smoking variables in treatment-seeking smokers. These mediating variables are likely important processes to address in smoking cessation treatment, especially in panic-vulnerable smokers. PMID:24720260

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

PubMed

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

2014-05-01

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

A biomaterial screening approach reveals microenvironmental mechanisms of drug resistance.

PubMed

Schwartz, Alyssa D; Barney, Lauren E; Jansen, Lauren E; Nguyen, Thuy V; Hall, Christopher L; Meyer, Aaron S; Peyton, Shelly R

2017-12-11

Traditional drug screening methods lack features of the tumor microenvironment that contribute to resistance. Most studies examine cell response in a single biomaterial platform in depth, leaving a gap in understanding how extracellular signals such as stiffness, dimensionality, and cell-cell contacts act independently or are integrated within a cell to affect either drug sensitivity or resistance. This is critically important, as adaptive resistance is mediated, at least in part, by the extracellular matrix (ECM) of the tumor microenvironment. We developed an approach to screen drug responses in cells cultured on 2D and in 3D biomaterial environments to explore how key features of ECM mediate drug response. This approach uncovered that cells on 2D hydrogels and spheroids encapsulated in 3D hydrogels were less responsive to receptor tyrosine kinase (RTK)-targeting drugs sorafenib and lapatinib, but not cytotoxic drugs, compared to single cells in hydrogels and cells on plastic. We found that transcriptomic differences between these in vitro models and tumor xenografts did not reveal mechanisms of ECM-mediated resistance to sorafenib. However, a systems biology analysis of phospho-kinome data uncovered that variation in MEK phosphorylation was associated with RTK-targeted drug resistance. Using sorafenib as a model drug, we found that co-administration with a MEK inhibitor decreased ECM-mediated resistance in vitro and reduced in vivo tumor burden compared to sorafenib alone. In sum, we provide a novel strategy for identifying and overcoming ECM-mediated resistance mechanisms by performing drug screening, phospho-kinome analysis, and systems biology across multiple biomaterial environments.

Exemplary Care as a Mediator of the Effects of Caregiver Subjective Appraisal and Emotional Outcomes

PubMed Central

Harris, Grant M.; Durkin, Daniel W.; Allen, Rebecca S.; DeCoster, Jamie; Burgio, Louis D.

2011-01-01

Purpose: Exemplary care (EC) is a new construct encompassing care behaviors that warrants further study within stress process models of dementia caregiving. Previous research has examined EC within the context of cognitively intact older adult care recipients (CRs) and their caregivers (CGs). This study sought to expand our knowledge of quality of care by investigating EC within a diverse sample of dementia CGs. Design and Methods: We examined the relation between CG subjective appraisal (daily care bother, burden, and behavioral bother), EC, and CG emotional outcomes (depression and positive aspects of caregiving [PAC]). Specifically, EC was examined as a possible mediator of the effects of CG subjective appraisals on emotional outcomes. Using a bootstrapping method and an SPSS macro developed by Preacher and Hayes (2008 Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models), we tested the indirect effect of EC on the relation between CG subjective appraisals and CG emotional outcomes. Results: Overall, EC partially mediates the relation between the subjective appraisal variables (daily care bother, burden, and behavioral bother) and PAC. Results for depression were similar except that EC did not mediate the relation between burden and depression. This pattern of results varied by race/ethnicity. Implications: Overall, CGs’ perception of providing EC to individuals with dementia partially explains the relation between subjective appraisal and symptoms of depression and PAC. Results of this study suggest that interventions may benefit from training CGs to engage in EC to improve their emotional outcomes and quality of care. PMID:21350038

Patient Health Communication Mediating Effects Between Gastrointestinal Symptoms and Gastrointestinal Worry in Pediatric Inflammatory Bowel Disease.

PubMed

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

2017-05-01

To investigate the effects of patient health communication regarding their inflammatory bowel disease (IBD) to their health care providers and significant others in their daily life as a mediator in the relationship between gastrointestinal symptoms and gastrointestinal worry in pediatric patients. The Pediatric Quality of Life Inventory Gastrointestinal Symptoms, Gastrointestinal Worry, and Communication Scales, and Pediatric Quality of Life Inventory 4.0 Generic Core Scales were completed in a 9-site study by 252 pediatric patients with IBD. Gastrointestinal Symptoms Scales measuring stomach pain, constipation, or diarrhea and patient communication were tested for bivariate and multivariate linear associations with Gastrointestinal Worry Scales specific to patient worry about stomach pain or bowel movements. Mediational analyses were conducted to test the hypothesized mediating effects of patient health communication as an intervening variable in the relationship between gastrointestinal symptoms and gastrointestinal worry. The predictive effects of gastrointestinal symptoms on gastrointestinal worry were mediated in part by patient health communication with health care providers/significant others in their daily life. In predictive models using multiple regression analyses, the full conceptual model of demographic variables, gastrointestinal symptoms (stomach pain, constipation, or diarrhea), and patient communication significantly accounted for 46, 43, and 54 percent of the variance in gastrointestinal worry (all Ps < 0.001), respectively, reflecting large effect sizes. Patient health communication explains in part the effects of gastrointestinal symptoms on gastrointestinal worry in pediatric patients with IBD. Supporting patient disease-specific communication to their health care providers and significant others may improve health-related quality of life for pediatric patients with IBD.

The association between school bullying victimization and substance use among adolescents in Malawi: the mediating effect of loneliness.

PubMed

Kim, Youn Kyoung; Okumu, Moses; Small, Eusebius; Nikolova, Silviya Pavlova; Mengo, Cecilia

2018-06-12

Background and objectives Research has shown an increased prevalence of substance use among adolescents in countries in Sub-Saharan Africa. Peer affiliation, bullying, and psychological stress are significantly associated with substance use. This study empirically tested theoretical frameworks linking peer affiliation, bullying victimization, loneliness and substance use (specifically tobacco or alcohol use) among adolescents. Materials and methods Data were obtained from the 2009 Malawi Global School-based Health Survey (GSHS) with a representative sample of 2359 students aged 13-17 years in Malawi, Sub-Saharan Africa. Missing data were handled using multiple imputation. The study conducted path analyses using Mplus to test the conceptual models of tobacco use and alcohol use. Results The results showed that loneliness partially mediated the association between bullying victimization and tobacco use in the first model, as well as the relationship between bullying victimization and alcohol use in the second model. Results indicated statistically significant indirect paths from bullying victimization to tobacco use and alcohol use through the mediation of loneliness. However, peer affiliation did not directly predict bullying victimization in the two path models; it directly predicted tobacco use only. Conclusions These findings have important implications in early intervention for health practitioners in school and mental health settings to prevent feelings of loneliness and substance use among adolescents who have experience with bullying victimization but no experience with depression, alcohol use or tobacco use.

Vaccination for treatment and prevention of cancer in animal models.

PubMed

Cavallo, Federica; Offringa, Rienk; van der Burg, Sjoerd H; Forni, Guido; Melief, Cornelis J M

2006-01-01

Two approaches to immunological intervention in tumor-host interactions in mouse models are discussed in this review. The first is described with reference to experiments in which CD8(+) T lymphocytes are used to kill established transplantable tumors. Peptides and their optimal presentation by dendritic cells and intervention in immune regulatory mechanisms are the key issues for efficient induction of T-killer cell-mediated tumor eradication. The time frame of tumor therapy and the threat imposed by tumor growth in transplantable models and cancer patients require the induction of a robust T-cell reaction. Prevention of the progression of small preneoplastic lesions, on the other hand, requires the significant and prolonged immune protection sought in the second approach. This is based on antibody production and the coordinated activation of multiple low-avidity cell-mediated mechanisms elicited by DNA vaccination in genetically modified cancer-prone mice, transgenic for a mutant Her-2/neu growth factor receptor expressed at the plasma membrane surface of preneoplastic mammary gland epithelial cells. Vaccination with appropriate DNA formulations results in prolonged immune inhibition of the progression of preneoplastic mammary lesions but is ineffective against established tumors. The use of molecularly defined adjuvants and intervention in immune regulatory mechanisms are critical in both the elicitation of an effective T-cell mediated reaction required for tumor debulking in the first set of models and the induction by vaccination of a sustained immune memory able to prevent the expansion of preneoplastic lesions in genetically cancer-prone mice.

Identification of Mom12 and Mom13, two novel modifier loci of Apc (Min) -mediated intestinal tumorigenesis.

PubMed

Crist, Richard C; Roth, Jacquelyn J; Lisanti, Michael P; Siracusa, Linda D; Buchberg, Arthur M

2011-04-01

Colorectal cancer is a heterogeneous disease resulting from a combination of genetic and environmental factors. The C57BL/6J (B6) Apc (Min/+) mouse develops polyps throughout the gastrointestinal tract and has been a valuable model for understanding the genetic basis of intestinal tumorigenesis. Apc (Min/+) mice have been used to study known oncogenes and tumor suppressor genes on a controlled genetic background. These studies often utilize congenic knockout alleles, which can carry an unknown amount of residual donor DNA. The Apc (Min) model has also been used to identify modifer loci, known as Modifier of Min (Mom) loci, which alter Apc (Min) -mediated intestinal tumorigenesis. B6 mice carrying a knockout allele generated in WW6 embryonic stem cells were crossed to B6 Apc (Min/+) mice to determine the effect on polyp multiplicity. The newly generated colony developed significantly more intestinal polyps than Apc (Min/+) controls. Polyp multiplicity did not correlate with inheritance of the knockout allele, suggesting the presence of one or more modifier loci segregating in the colony. Genotyping of simple sequence length polymorphism (SSLP) markers revealed residual 129X1/SvJ genomic DNA within the congenic region of the parental knockout line. An analysis of polyp multiplicity data and SSLP genotyping indicated the presence of two Mom loci in the colony: 1) Mom12, a dominant modifier linked to the congenic region on chromosome 6, and 2) Mom13, which is unlinked to the congenic region and whose effect is masked by Mom12. The identification of Mom12 and Mom13 demonstrates the potential problems resulting from residual heterozygosity present in congenic lines.

Multiple Translocation of the AVR-Pita Effector Gene among Chromosomes of the Rice Blast Fungus Magnaporthe oryzae and Related Species

PubMed Central

Chuma, Izumi; Isobe, Chihiro; Hotta, Yuma; Ibaragi, Kana; Futamata, Natsuru; Kusaba, Motoaki; Yoshida, Kentaro; Terauchi, Ryohei; Fujita, Yoshikatsu; Nakayashiki, Hitoshi; Valent, Barbara; Tosa, Yukio

2011-01-01

Magnaporthe oryzae is the causal agent of rice blast disease, a devastating problem worldwide. This fungus has caused breakdown of resistance conferred by newly developed commercial cultivars. To address how the rice blast fungus adapts itself to new resistance genes so quickly, we examined chromosomal locations of AVR-Pita, a subtelomeric gene family corresponding to the Pita resistance gene, in various isolates of M. oryzae (including wheat and millet pathogens) and its related species. We found that AVR-Pita (AVR-Pita1 and AVR-Pita2) is highly variable in its genome location, occurring in chromosomes 1, 3, 4, 5, 6, 7, and supernumerary chromosomes, particularly in rice-infecting isolates. When expressed in M. oryzae, most of the AVR-Pita homologs could elicit Pita-mediated resistance, even those from non-rice isolates. AVR-Pita was flanked by a retrotransposon, which presumably contributed to its multiple translocation across the genome. On the other hand, family member AVR-Pita3, which lacks avirulence activity, was stably located on chromosome 7 in a vast majority of isolates. These results suggest that the diversification in genome location of AVR-Pita in the rice isolates is a consequence of recognition by Pita in rice. We propose a model that the multiple translocation of AVR-Pita may be associated with its frequent loss and recovery mediated by its transfer among individuals in asexual populations. This model implies that the high mobility of AVR-Pita is a key mechanism accounting for the rapid adaptation toward Pita. Dynamic adaptation of some fungal plant pathogens may be achieved by deletion and recovery of avirulence genes using a population as a unit of adaptation. PMID:21829350

Metastable neural dynamics mediates expectation

NASA Astrophysics Data System (ADS)

Mazzucato, Luca; La Camera, Giancarlo; Fontanini, Alfredo

Sensory stimuli are processed faster when their presentation is expected compared to when they come as a surprise. We previously showed that, in multiple single-unit recordings from alert rat gustatory cortex, taste stimuli can be decoded faster from neural activity if preceded by a stimulus-predicting cue. However, the specific computational process mediating this anticipatory neural activity is unknown. Here, we propose a biologically plausible model based on a recurrent network of spiking neurons with clustered architecture. In the absence of stimulation, the model neural activity unfolds through sequences of metastable states, each state being a population vector of firing rates. We modeled taste stimuli and cue (the same for all stimuli) as two inputs targeting subsets of excitatory neurons. As observed in experiment, stimuli evoked specific state sequences, characterized in terms of `coding states', i.e., states occurring significantly more often for a particular stimulus. When stimulus presentation is preceded by a cue, coding states show a faster and more reliable onset, and expected stimuli can be decoded more quickly than unexpected ones. This anticipatory effect is unrelated to changes of firing rates in stimulus-selective neurons and is absent in homogeneous balanced networks, suggesting that a clustered organization is necessary to mediate the expectation of relevant events. Our results demonstrate a novel mechanism for speeding up sensory coding in cortical circuits. NIDCD K25-DC013557 (LM); NIDCD R01-DC010389 (AF); NSF IIS-1161852 (GL).

Gene expression profiles of immune mediators and histopathological findings in animal models of leptospirosis: comparison between susceptible hamsters and resistant mice.

PubMed

Matsui, Mariko; Rouleau, Vincent; Bruyère-Ostells, Lilian; Goarant, Cyrille

2011-11-01

Leptospirosis is a widespread zoonosis characterized by multiple organ failure and variable host susceptibility toward pathogenic Leptospira strains. In this study, we put the role of inflammatory mediators in parallel with bacterial burdens and organ lesions by comparing a susceptible animal model, the hamster, and a resistant one, the Oncins France 1 (OF1) mouse, both infected with virulent Leptospira interrogans serovar Icterohaemorrhagiae strain Verdun. Histological observations evidenced edema, congestion, hemorrhage, and inflammatory infiltration in the organs of hamsters, in contrast to limited changes in mice. Using reverse transcription-quantitative PCR techniques, we showed that the relative Leptospira burden progressively increased in hamster tissues, while a rapid clearance was observed in mouse tissues. The early regulation of the proinflammatory mediators interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, and cyclo-oxygenase-2 and the chemokines gamma interferon-inducible protein 10 kDa/CXCL10 and macrophage inflammatory protein-1α/CCL3 in mouse tissues contrasted with their delayed and massive overexpression in hamster tissues. Conversely, the induction of the anti-inflammatory cytokine IL-10 was faster in the resistant than in the susceptible animal model. The role of these cytokines in the pathophysiology of leptospirosis and the implications of their differential regulation in the development of this disease are discussed.

Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells

PubMed Central

Novobrantseva, Tatiana I; Borodovsky, Anna; Wong, Jamie; Klebanov, Boris; Zafari, Mohammad; Yucius, Kristina; Querbes, William; Ge, Pei; Ruda, Vera M; Milstein, Stuart; Speciner, Lauren; Duncan, Rick; Barros, Scott; Basha, Genc; Cullis, Pieter; Akinc, Akin; Donahoe, Jessica S; Narayanannair Jayaprakash, K; Jayaraman, Muthusamy; Bogorad, Roman L; Love, Kevin; Whitehead, Katie; Levins, Chris; Manoharan, Muthiah; Swirski, Filip K; Weissleder, Ralph; Langer, Robert; Anderson, Daniel G; de Fougerolles, Antonin; Nahrendorf, Matthias; Koteliansky, Victor

2012-01-01

Leukocytes are central regulators of inflammation and the target cells of therapies for key diseases, including autoimmune, cardiovascular, and malignant disorders. Efficient in vivo delivery of small interfering RNA (siRNA) to immune cells could thus enable novel treatment strategies with broad applicability. In this report, we develop systemic delivery methods of siRNA encapsulated in lipid nanoparticles (LNP) for durable and potent in vivo RNA interference (RNAi)-mediated silencing in myeloid cells. This work provides the first demonstration of siRNA-mediated silencing in myeloid cell types of nonhuman primates (NHPs) and establishes the feasibility of targeting multiple gene targets in rodent myeloid cells. The therapeutic potential of these formulations was demonstrated using siRNA targeting tumor necrosis factor-α (TNFα) which induced substantial attenuation of disease progression comparable to a potent antibody treatment in a mouse model of rheumatoid arthritis (RA). In summary, we demonstrate a broadly applicable and therapeutically relevant platform for silencing disease genes in immune cells. PMID:23344621

SchizConnect: Mediating Neuroimaging Databases on Schizophrenia and Related Disorders for Large-Scale Integration

PubMed Central

Wang, Lei; Alpert, Kathryn I.; Calhoun, Vince D.; Cobia, Derin J.; Keator, David B.; King, Margaret D.; Kogan, Alexandr; Landis, Drew; Tallis, Marcelo; Turner, Matthew D.; Potkin, Steven G.; Turner, Jessica A.; Ambite, Jose Luis

2015-01-01

SchizConnect (www.schizconnect.org) is built to address the issues of multiple data repositories in schizophrenia neuroimaging studies. It includes a level of mediation—translating across data sources—so that the user can place one query, e.g. for diffusion images from male individuals with schizophrenia, and find out from across participating data sources how many datasets there are, as well as downloading the imaging and related data. The current version handles the Data Usage Agreements across different studies, as well as interpreting database-specific terminologies into a common framework. New data repositories can also be mediated to bring immediate access to existing datasets. Compared with centralized, upload data sharing models, SchizConnect is a unique, virtual database with a focus on schizophrenia and related disorders that can mediate live data as information are being updated at each data source. It is our hope that SchizConnect can facilitate testing new hypotheses through aggregated datasets, promoting discovery related to the mechanisms underlying schizophrenic dysfunction. PMID:26142271

Investigating the Effects of Mass Media Exposure on the Uptake of Preventive Measures by Hong Kong Residents during the 2015 MERS Outbreak: The Mediating Role of Interpersonal Communication and the Perception of Concern.

PubMed

Ludolph, Ramona; Schulz, Peter J; Chen, Ling

2018-01-01

In 2015, South Korea experienced the largest outbreak to date of the Middle East Respiratory Syndrome (MERS-CoV) outside the Middle East. Fears related to a potential spread of the disease led to an increased alert level as well as heightened media coverage in the neighboring Hong Kong. A cross-sectional survey (N = 533) among residents of Hong Kong was conducted to assess the relationships between the effects of outbreak-related mass media coverage, interpersonal communication, the perceived level of concern in one's close environment, and the uptake of preventive measures. A serial multiple mediator model finds that interpersonal communication and higher perceived concern indirectly influence the effects of media coverage on the engagement in preventive actions. These results expand previous research on the mediating role of interpersonal communication and support assumptions about a modified two-step flow of communication in the context of a public health emergency.

Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells

PubMed Central

Göbel, Kerstin; Pankratz, Susann; Asaridou, Chloi-Magdalini; Herrmann, Alexander M.; Bittner, Stefan; Merker, Monika; Ruck, Tobias; Glumm, Sarah; Langhauser, Friederike; Kraft, Peter; Krug, Thorsten F.; Breuer, Johanna; Herold, Martin; Gross, Catharina C.; Beckmann, Denise; Korb-Pap, Adelheid; Schuhmann, Michael K.; Kuerten, Stefanie; Mitroulis, Ioannis; Ruppert, Clemens; Nolte, Marc W.; Panousis, Con; Klotz, Luisa; Kehrel, Beate; Korn, Thomas; Langer, Harald F.; Pap, Thomas; Nieswandt, Bernhard; Wiendl, Heinz; Chavakis, Triantafyllos; Kleinschnitz, Christoph; Meuth, Sven G.

2016-01-01

Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. PMID:27188843

Complementary shifts in photoreceptor spectral tuning unlock the full adaptive potential of ultraviolet vision in birds.

PubMed

Toomey, Matthew B; Lind, Olle; Frederiksen, Rikard; Curley, Robert W; Riedl, Ken M; Wilby, David; Schwartz, Steven J; Witt, Christopher C; Harrison, Earl H; Roberts, Nicholas W; Vorobyev, Misha; McGraw, Kevin J; Cornwall, M Carter; Kelber, Almut; Corbo, Joseph C

2016-07-12

Color vision in birds is mediated by four types of cone photoreceptors whose maximal sensitivities (λmax) are evenly spaced across the light spectrum. In the course of avian evolution, the λmax of the most shortwave-sensitive cone, SWS1, has switched between violet (λmax > 400 nm) and ultraviolet (λmax < 380 nm) multiple times. This shift of the SWS1 opsin is accompanied by a corresponding short-wavelength shift in the spectrally adjacent SWS2 cone. Here, we show that SWS2 cone spectral tuning is mediated by modulating the ratio of two apocarotenoids, galloxanthin and 11’,12’-dihydrogalloxanthin, which act as intracellular spectral filters in this cell type. We propose an enzymatic pathway that mediates the differential production of these apocarotenoids in the avian retina, and we use color vision modeling to demonstrate how correlated evolution of spectral tuning is necessary to achieve even sampling of the light spectrum and thereby maintain near-optimal color discrimination.

Spotlight on elotuzumab in the treatment of multiple myeloma: the evidence to date

PubMed Central

Weisel, Katja

2016-01-01

Despite advances in the treatment of multiple myeloma, it remains an incurable disease, with relapses and resistances frequently observed. Recently, immunotherapies, in particular, monoclonal antibodies, have become important treatment options in anticancer therapies. Elotuzumab is a humanized monoclonal antibody to signaling lymphocytic activation molecule F7, which is highly expressed on myeloma cells and, to a lower extent, on selected leukocyte subsets such as natural killer cells. By directly activating natural killer cells and by antibody-dependent cell-mediated cytotoxicity, elotuzumab exhibits a dual mechanism of action leading to myeloma cell death with minimal effects on normal tissue. In several nonclinical models of multiple myeloma, elotuzumab was effective as a single agent and in combination with standard myeloma treatments, supporting the use of elotuzumab in patients. In combination with lenalidomide and dexamethasone, elotuzumab showed a significant increase in tumor response rates and progression-free survival in patients with relapsed and/or refractory multiple myeloma. This review summarizes the nonclinical and clinical development of elotuzumab as a single agent and in combination with established therapies for the treatment of multiple myeloma. PMID:27785050

Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex.

PubMed

Tuttle, Lisa M; Pacheco, Derek; Warfield, Linda; Luo, Jie; Ranish, Jeff; Hahn, Steven; Klevit, Rachel E

2018-03-20

Transcription activation domains (ADs) are inherently disordered proteins that often target multiple coactivator complexes, but the specificity of these interactions is not understood. Efficient transcription activation by yeast Gcn4 requires its tandem ADs and four activator-binding domains (ABDs) on its target, the Mediator subunit Med15. Multiple ABDs are a common feature of coactivator complexes. We find that the large Gcn4-Med15 complex is heterogeneous and contains nearly all possible AD-ABD interactions. Gcn4-Med15 forms via a dynamic fuzzy protein-protein interface, where ADs bind the ABDs in multiple orientations via hydrophobic regions that gain helicity. This combinatorial mechanism allows individual low-affinity and specificity interactions to generate a biologically functional, specific, and higher affinity complex despite lacking a defined protein-protein interface. This binding strategy is likely representative of many activators that target multiple coactivators, as it allows great flexibility in combinations of activators that can cooperate to regulate genes with variable coactivator requirements. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis.

PubMed

Colbert, James F; Ford, Joshay A; Haeger, Sarah M; Yang, Yimu; Dailey, Kyrie L; Allison, Kristen C; Neudecker, Viola; Evans, Christopher M; Richardson, Vanessa L; Brodsky, Kelley S; Faubel, Sarah; Eltzschig, Holger K; Schmidt, Eric P; Ginde, Adit A

2017-08-01

Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used. In the absence of miR-223, mice demonstrated exaggerated AKI in sterile models of sepsis (LPS injection) and attenuated AKI in a live-infection model of sepsis (cecal ligation and puncture). We demonstrated that miR-223 expression is induced in kidney homogenate after cecal ligation and puncture, but not after LPS or fecal slurry injection. We investigated additional potential mechanistic explanations including differences in peritoneal bacterial clearance and host stool virulence. Our findings highlight the complex role of miR-223 in the pathogenesis of septic kidney injury, as well as the importance of differences in experimental sepsis models and their consequent translational applicability. Copyright © 2017 the American Physiological Society.

On the biophysics and kinetics of toehold-mediated DNA strand displacement

PubMed Central

Srinivas, Niranjan; Ouldridge, Thomas E.; Šulc, Petr; Schaeffer, Joseph M.; Yurke, Bernard; Louis, Ard A.; Doye, Jonathan P. K.; Winfree, Erik

2013-01-01

Dynamic DNA nanotechnology often uses toehold-mediated strand displacement for controlling reaction kinetics. Although the dependence of strand displacement kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding has remained elusive. Here, we study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Two factors explain the dependence of strand displacement kinetics on toehold length: (i) the physical process by which a single step of branch migration occurs is significantly slower than the fraying of a single base pair and (ii) initiating branch migration incurs a thermodynamic penalty, not captured by state-of-the-art nearest neighbor models of DNA, due to the additional overhang it engenders at the junction. Our findings are consistent with previously measured or inferred rates for hybridization, fraying and branch migration, and they provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems. PMID:24019238