Modeling the underlying biological processes in Alzheimer's disease using a multivariate competing risk joint model.

Many clinical trials repeatedly measure several longitudinal outcomes on patients. Patient follow-up can discontinue due to an outcome-dependent event, such as clinical diagnosis, death, or dropout. Joint modeling is a popular choice for the analysis of this type of data. Using example data from a prodromal Alzheimer's disease trial, we propose a new type of multivariate joint model in which longitudinal brain imaging outcomes and memory impairment ratings are allowed to be associated both with time to open-label medication and dropout, and where the brain imaging outcomes may also directly affect the memory impairment ratings. Existing joint models for multivariate longitudinal outcomes account for the correlation between the longitudinal outcomes through the random effects, often by assuming a multivariate normal distribution. However, for these models, it is difficult to interpret how the longitudinal outcomes affect each other. We model the dependence between the longitudinal outcomes differently so that a first longitudinal outcome affects a second one. Specifically, for each longitudinal outcome, we use a linear mixed-effects model to estimate its trajectory, where, for the second longitudinal outcome, we include the linear predictor of the first outcome as a time-varying covariate. This facilitates an easy and direct interpretation of the association between the longitudinal outcomes and provides a framework for latent mediation analysis to understand the underlying biological processes. For the trial considered here, we found that part of the intervention effect is mediated through hippocampal brain atrophy. The proposed joint models are fitted using a Bayesian framework via MCMC simulation.

A More Efficient Causal Mediator Model Without the No-Unmeasured-Confounder Assumption.

Mediator models have been developed primarily under the assumption of no-unmeasured-confounding. In many situations, this assumption is violated and may lead to the identification of mediator variables that actually are statistical artifacts. The rank preserving model (RPM) is an alternative approach to estimate controlled direct and mediator effects. It is based on the structural mean models framework and a no-effect-modifier assumption. The RPM assumes that unobserved confounders do not interact with treatment or mediators. This assumption is often more plausible to hold than the no-unmeasured-confounder assumption. So far, models using the no-effect-modifier assumption have been rarely used, which might be due to its low power and inefficiency in many scenarios. Here, a semi-parametric nonlinear extension, the nRPM, is proposed that overcomes this inefficiency using thin plate regression splines that both increase the predictive power of the model and decrease the misspecification present in many situations. In a simulation study, it is shown that the nRPM provides estimates that are robust against the violation of the no-effect-modifier assumption and that are substantively more efficient than those of the RPM. The model is illustrated using a data set on CD4 cell counts in a context of the human immunodeficiency virus (HIV).

Fine Motor Skill Mediates Visual Memory Ability with Microstructural Neuro-correlates in Cerebellar Peduncles in Prematurely Born Adolescents.

Adolescents born preterm (PT) with no evidence of neonatal brain injury are at risk of deficits in visual memory and fine motor skills that diminish academic performance. The association between these deficits and white matter microstructure is relatively unexplored. We studied 190 PTs with no brain injury and 92 term controls at age 16 years. The Rey-Osterrieth Complex Figure Test (ROCF), the Beery visual-motor integration (VMI), and the Grooved Pegboard Test (GPT) were collected for all participants, while a subset (40 PTs and 40 terms) underwent diffusion-weighted magnetic resonance imaging. PTs performed more poorly than terms on ROCF, VMI, and GPT (all P < 0.01). Mediation analysis showed fine motor skill (GPT score) significantly mediates group difference in ROCF and VMI (all P < 0.001). PTs showed a negative correlation (P < 0.05, corrected) between fractional anisotropy (FA) in the bilateral middle cerebellar peduncles and GPT score, with higher FA correlating to lower (faster task completion) GPT scores, and between FA in the right superior cerebellar peduncle and ROCF scores. PTs also had a positive correlation (P < 0.05, corrected) between VMI and left middle cerebellar peduncle FA. Novel strategies to target fine motor skills and the cerebellum may help PTs reach their full academic potential.

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

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 (ß = 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.

The Role of Two Factors of Negative Symptoms and Cognition on Social Functioning in Male Patients with Schizophrenia: A Mediator Model.

OBJECTIVE: This study aims to compare the cognitive function and social functioning in male patients with deficit syndrome (DS) and non-DS, and to explore whether cognitive function serves as a mediator in the relationship between the two factors of negative symptoms (motivation and pleasure (MAP) and expressivity (EXP) deficits, and social functioning in schizophrenia patients. METHODS: One hundred and fifty-six male patients with schizophrenia and 109 age- and education-matched normal controls were enrolled in the current study. The Chinese version of a Schedule for Deficit Syndrome (SDS) was used for DS and non-DS categorization. The Brief Psychiatric Rating Scale (BPRS) and the Brief Negative Symptoms Scale (BNSS) were used to assess psychotic and negative symptoms in patients. The Social-Adaptive Functioning Evaluation (SAFE) was adopted to evaluate patients' social functioning, and a battery of classical neurocognitive tests was used to assess cognition, including sustained vigilance/attention, cognitive flexibility, ideation fluency, and visuospatial memory. RESULTS: We found that male patients with DS performed worse in all four cognitive domains and social functioning compared to non-DS patients. Both total negative symptoms and its two factors were significantly associated with all four domains of cognition and social functioning in male patients. Interestingly, our results indicate that only cognitive flexibility mediates the relationship between negative symptoms and social functioning in schizophrenia patients, but there were no differences between EXP and MAP negative factors in this model. CONCLUSION: Our findings suggest that DS patients may represent a unique clinical subgroup of schizophrenia, and the integrated interventions targeting both negative symptoms and cognition, especially cognitive flexibility, may optimally improve functional outcomes in schizophrenia patients.

How does digital finance affect green technology innovation in the polluting industry? Based on the serial two-mediator model of financing constraints and research and development (R&D) investments.

This paper evaluates the importance of combining digital finance with conventional finance and information technology (IT) to bring new opportunities for green technology innovation and transformation within polluting industries. This study builds a theoretical framework "digital finance → financing constraints → R&D investment → green technology innovation" to demonstrate the causal mechanism between digital finance and firms' green innovation by using the serial two-mediator model. The study shows that digital finance could reduce financial constraints and increase R&D investments, thereby improving enterprises' green technology innovation in the long run. Moreover, based on the moderating effect model, we find that digital transformation in a polluting firm tends to strengthen the linkage between digital finance and green technology innovation through supervising the use of loans, reviewing green technology innovation projects, and reducing managers' short-sighted behaviors to avoid agency problems. Furthermore, the heterogeneity analysis shows that the effects of digital finance on green innovation are more apparent in state-owned enterprises and the regions with lower financial development and with higher financial supervision.

Conceptual Framework for Insomnia: A Cognitive Model in Practice.

Insomnia is a widespread neuropsychological sleep-related disorder known to result in various predicaments including cognitive impairments, emotional distress, negative thoughts, and perceived sleep insufficiency besides affecting the incidence and aggravation of other medical disorders. Despite the available insomnia-related theoretical cognitive models, clinical studies, and related guidelines, an evidence-based conceptual framework for a personalized approach to insomnia seems to be lacking. This study proposes a conceptual cognitive framework (CCF) providing insight into cognitive mechanisms involved in the predisposition, precipitation, and perpetuation of insomnia and consequent cognitive deficits. The current CCF for insomnia relies on evaluative conditional learning and appraisal which generates negative valence (emotional value) and arousal (cognitive value). Even with the limitations of this study, the suggested methodology is well-defined, reproducible, and accessible can help foster future high-quality clinical databases. During clinical insomnia but not the neutral one, negative mood (trait-anxiety) causes cognitive impairments only if mediating with a distorted perception of insomnia ( Ind-1 = 0.161, 95% CI 0.040-0.311). Further real-life testing of the CCF is intended to formulate a meticulous, decision-supporting platform for clinical interventions. Furthermore, the suggested methodology is expected to offer a reliable platform for CCF-development in other cognitive impairments and support the causal clinical data models. It may also improve our knowledge of psychological disturbances and complex comorbidities to help design rehabilitation interventions and comprehensive frameworks in line with the "preventive medicine" policies.

Follower Dependence, Independence, or Interdependence: A Multi-Foci Framework to Unpack the Mystery of Transformational Leadership Effects.

We develop a multi-foci framework-"follower dependence," "follower independence," and "leader-follower interdependence"-to explain how transformational leadership influences follower performance. Follower's personal identification with the leader, psychological empowerment, and leader-member exchange are employed as proxies for each of the three foci. Two separate studies consistently show that personal identification (denoting a "follower dependence" focus) is a more salient mechanism than the other two in explaining the transformational leadership-organizational citizenship behavior relationship. These results suggest transformational leadership is perhaps a theory of follower dependence rather than independence or interdependence. Theoretical implications, limitations, and future directions are discussed.

Trait Emotional Intelligence and Relationship Satisfaction: The Mediating Role of Dyadic Coping.

Trait emotional intelligence (TEI) is an important individual difference variable that is related to the quality of romantic relationships. The present study investigated the associations between TEI, dyadic coping, and relationship satisfaction. A convenience sample of N = 136 heterosexual couples was recruited online. When the actor-partner interdependence model was applied to the data, TEI showed a positive actor effect and a positive partner effect on relationship satisfaction. The actor effect and partner effect of TEI on relationship satisfaction were partially mediated through positive dyadic coping and common dyadic coping, respectively. A small total indirect actor effect was also found for negative dyadic coping. Controlling for potential content overlap between TEI and relationship satisfaction did not alter the results. However, removing variance from the TEI score that was shared with the Big Five trait factors attenuated TEI's actor and partner effects on relationship satisfaction and rendered all but one actor effect for TEI on dyadic coping and all but one indirect effect nonsignificant. The results underline the importance of TEI for the quality of romantic relationships and they shed light on underlying mechanisms. Implications for theory, research, and applications in counseling contexts will be discussed.

A longitudinal model of executive function development from birth through adolescence in children born very or extremely preterm.

Executive function deficits are often reported as a specific weakness in preterm children. Yet, executive function development is still not fully understood. In a prospective longitudinal study, 115 preterm born children, ≤31 weeks of gestation, were recruited at birth and subject to neuropsychological assessments at ages 5.5 and 18 years. By applying Miyake and colleagues' integrative framework of executive function to our data, two core components of executive function, working memory and cognitive flexibility, were identified through confirmatory factor analysis. Developmental stability was investigated in a serial multiple mediator structural equation model. Biological, medical, and social factors as well as mental development at 10 months were entered as predictors. Both components of executive function were highly stable from 5.5 to 18 years. Gestational age, intrauterine growth, lack of perinatal medical complications, and female sex were positively related to mental development at 10 months, which together with parental education influenced both core executive functions at 5.5 years. Working memory at 5.5 years mediated outcome in working memory at 18 years. In addition to the mediation of cognitive flexibility at 5.5 years, perinatal medical complications and restricted intrauterine growth had a continued direct negative impact on cognitive flexibility at 18 years. The application of a theoretical framework added to our understanding of executive function development in preterm born children. The study supports early identification of executive deficits among children born preterm, as deficits are unlikely to diminish with maturation.

Inter-relations among negative social control, self-efficacy, and physical activity in healthy couples.

OBJECTIVES: In romantic relationships, partners can influence each other's health-relevant behaviour by exerting negative social control (e.g., pressuring), however, with mixed success. To elucidate this phenomenon, we examined couples motivated to increase their physical activity and investigated the degree to which both partners exerted negative control on each other, their self-efficacy, reciprocal associations among the two behaviour-specific constructs, and their relationship with moderate-to-vigorous physical activity (MVPA). DESIGN: This was a longitudinal study with three assessment periods (T0, T2, T3) spanning 7 weeks. METHODS: We performed secondary analyses with data from the control condition (N = 113 heterosexual couples) of a published randomized controlled trial. Dyadic mediator models specified either both partners' self-efficacy as predictors and provided negative partner control to each other as mediators or vice versa. The outcomes comprised both partners' accelerometer-assessed MVPA. Mediators and outcomes were controlled for their T0 values. RESULTS: The first model showed that women's and men's provided negative partner control (T0) was positively related to the other partners' self-efficacy (T2). Testing the alternative predictive direction, the second model showed that only women's self-efficacy (T0) was associated with more provided negative partner control (T2) by men. Women and men showed less MVPA (T3) when their partners had provided them with more negative control at T2. CONCLUSIONS: As negative control provided to partners may be detrimental to their behaviour change, interventionists should advise couples to avoid it. However, active ingredients of negative control that may benefit recipients' self-efficacy beliefs should be investigated in future work. Statement of contribution What is already known on this subject? Couples often try to change each other's health behaviour not just using supportive tactics, but also controlling ones. Negative partner control (e.g., rebuking and nagging) was found to have adverse or no effects on control recipients' health behaviour change. To understand underlying mechanisms of this relationship, reactance and negative affect of recipients have been investigated, but only rarely their self-efficacy, a consistent individual predictor of behaviour change that is likely to share reciprocal relations with social exchange processes, including negative social control. What does this study add? Although harmful for behaviour change, negative partner control may increase control recipients' self-efficacy. Higher self-efficacy of one partner may also increase provided negative partner control by the other.

Understanding the Links Between Self-Report Emotional Intelligence and Suicide Risk: Does Psychological Distress Mediate This Relationship Across Time and Samples?

Objective: In the last decades, increasing attention has been paid to examining psychological resources that might contribute to our understanding of suicide risk. Although Emotional Intelligence (EI) is one dimension that has been linked with decreased suicidal ideation and behaviors, we detected several gaps in the literature in this area regarding the research designs and samples involved. In this research, we aimed to test a mediator model considering self-report EI, psychological distress and suicide risk across samples adopting both cross-sectional and prospective designs in two independent studies. Method: In Study 1, our purpose was to examine the potential role of psychological distress as a mediator in the relationship between self-report EI and suicide risk in a community sample comprised of 438 adults (270 women; mean age: 33.21 years). In Study 2, we sought to examine the proposed mediator model considering a 2-month prospective design in a sample of college students (n = 330 in T1; n = 311 in T2; 264 women; mean age: 22.22 years). Results: In Study 1, we found that psychological distress partially mediated the effect of self-report EI on suicide risk. More interestingly, findings from Study 2 showed that psychological distress fully mediated the relationship between self-report EI and suicide risk at Time 2. Conclusion: These results point out the role of psychological distress as a mediator in the association between self-report EI and suicide risk. These findings suggest an underlying process by which self-report EI may act as a protective factor against suicidal ideation and behaviors. In line with the limitations of our work, plausible avenues for future research and interventions are discussed.

Power in Bayesian Mediation Analysis for Small Sample Research.

It was suggested that Bayesian methods have potential for increasing power in mediation analysis (Koopman, Howe, Hollenbeck, & Sin, 2015; Yuan & MacKinnon, 2009). This paper compares the power of Bayesian credibility intervals for the mediated effect to the power of normal theory, distribution of the product, percentile, and bias-corrected bootstrap confidence intervals at N≤ 200. Bayesian methods with diffuse priors have power comparable to the distribution of the product and bootstrap methods, and Bayesian methods with informative priors had the most power. Varying degrees of precision of prior distributions were also examined. Increased precision led to greater power only when N≥ 100 and the effects were small, N < 60 and the effects were large, and N < 200 and the effects were medium. An empirical example from psychology illustrated a Bayesian analysis of the single mediator model from prior selection to interpreting results.

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.

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

Suicidality, depression, major and minor negative life events: a mediator model.

BACKGROUND: Major negative life events are associated with higher suicidality. In this association, two mediating paths were hypothesized: (a) via minor negative life events and (b) via depression. METHODS: Ninety-six adolescent primary care patients were recruited in clinics, a physician's office, and school nurses' offices. RESULTS: (1) Minor negative life events were associated with depressive symptoms and suicidality. (2) Depressive symptoms were associated with suicidality. (3) Depressive symptoms mediated the association of minor negative life events with suicidality. CONCLUSIONS: Findings suggest that minor negative life events may be associated with suicidal ideation among adolescent primary care patients, and that depressive symptoms may mediate the association of minor negative life events with suicidality.