Somatic TARDBP variants as a cause of semantic dementia

The aetiology of late-onset neurodegenerative diseases is largely unknown. Here we investigated whether de novo somatic variants for semantic dementia can be detected, thereby arguing for a more general role of somatic variants in neurodegenerative disease. Semantic dementia is characterized by a non-familial occurrence, early onset (<65 years), focal temporal atrophy and TDP-43 pathology. To test whether somatic variants in neural progenitor cells during brain development might lead to semantic dementia, we compared deep exome sequencing data of DNA derived from brain and blood of 16 semantic dementia cases. Somatic variants observed in brain tissue and absent in blood were validated using amplicon sequencing and digital PCR. We identified two variants in exon one of the TARDBP gene (L41F and R42H) at low level (1-3%) in cortical regions and in dentate gyrus in two semantic dementia brains, respectively. The pathogenicity of both variants is supported by demonstrating impaired splicing regulation of TDP-43 and by altered subcellular localization of the mutant TDP-43 protein. These findings indicate that somatic variants may cause semantic dementia as a non-hereditary neurodegenerative disease, which might be exemplary for other late-onset neurodegenerative disorders

A generalized invariant imbedding equation II

Research into fetal development and medicin

Game-Based Social Learning for Socially Sustainable Water Management

An important aspect of the social sustainability of a proposed solution is acceptance by societal stakeholders. Acceptance is determined by the extent to which the solution matches with stakeholder perspectives on the problem and preferred ways to deal with it. Social learning can contribute to the social sustainability of water management strategies by achieving a convergence in perspectives among societal stakeholders. Serious games have proven to be effective in generating this type of social learning outcomes, but the underlying mechanisms are still unclear. This article aims to clarify how a multi-player serious game on river management (Sustainable Delta) supports social learning among participants with initially diverging perspectives. Based on a conceptual framework for game-based social learning, hypotheses and expectations were formulated and tested with quantitative and qualitative analyses of game sessions. Convergence of perspectives was observed in 10 out of 12 gaming sessions, but could not, or could only to a limited extent, be explained by the presumed learning support mechanisms in the game’s design. This underlines the importance of opening up the black box of serious games to determine how and why they work. If this is neglected, there is a clear risk that the design of games will be based on wrong, untested assumptions and will be less effective in supporting social learning and social sustainability

Reframing the future : the role of reflexivity in governance networks in sustainability transitions

Regional sustainability networks in the Netherlands are rooted in regional culture and have an emphasis on social learning and effective collaboration between multiple actors. The national ‘Duurzaam Door’ (Moving Forward Sustainably) Policy Programme regards these networks as generative governance arrangements where new knowledge, actions and relations can co-evolve together with new insights in governance and learning within sustainability transitions. In order to understand the dynamics of the learning in these networks we have monitored emergent properties of social learning between 2014 and 2016. Our focus is particularly on the interrelated role of trust, commitment, reframing and reflexivity. Our aim is to better understand the role and the dynamics of these emergent properties and to see which actors and roles can foster the effectiveness of social learning in regional transitions towards more sustainable ways of living. We used a retrospective analysis with Reflexive Monitoring in Action (RMA), which we combined with the Most Significant Change approach. We found that reflexivity in particular is a critical property at moments that can make or break the process

Reframing the future : the role of reflexivity in governance networks in sustainability transitions

Regional sustainability networks in the Netherlands are rooted in regional culture and have an emphasis on social learning and effective collaboration between multiple actors. The national ‘Duurzaam Door’ (Moving Forward Sustainably) Policy Programme regards these networks as generative governance arrangements where new knowledge, actions and relations can co-evolve together with new insights in governance and learning within sustainability transitions. In order to understand the dynamics of the learning in these networks we have monitored emergent properties of social learning between 2014 and 2016. Our focus is particularly on the interrelated role of trust, commitment, reframing and reflexivity. Our aim is to better understand the role and the dynamics of these emergent properties and to see which actors and roles can foster the effectiveness of social learning in regional transitions towards more sustainable ways of living. We used a retrospective analysis with Reflexive Monitoring in Action (RMA), which we combined with the Most Significant Change approach. We found that reflexivity in particular is a critical property at moments that can make or break the process

A dyadic perspective on parent-child dyadic coping in children with a chronic condition

Objective In this study, we examined the extent to which parents and their children with a chronic condition communicate their stress to one another and whether stress communication is associated with different forms of dyadic coping. Methods In a sample of 239 parent-child dyads, self-reported stress communication and different forms of perceived dyadic coping (i.e., emotion-oriented, problem-oriented, and negative dyadic coping) were assessed using a cross-sectional design. Results We first found that children's stress communication was positively associated with more positive (r = 0.28, p < .001) and less negative dyadic coping responses by children (r = −0.22, p < .001). Children's stress communication was also associated with more positive (r = 0.52, r = 0.45, p's < 0.001), and less negative dyadic coping responses by parents (r = −0.19, p < .001). Using dyadic data of children with a chronic condition and their parents, we found that more stress communication of children was associated with healthier coping responses of both children (perceived emotion-oriented dyadic coping: β = 0.23, p < .001) and parents (perceived emotion-oriented dyadic coping: β = 0.33, p < .001; perceived problem-oriented dyadic coping: β = 0.22, p < .001). Conclusion This underscores the importance of communication and adaptive coping strategies of parents and children in the context of a child's chronic condition. These findings may help us find ways to support children and their parents to optimally communicate about and deal with their stress

Reframing the future: the role of reflexivity in governance networks in sustainability transitions

Regional sustainability networks in the Netherlands are rooted in regional culture and have an emphasis on social learning and effective collaboration between multiple actors. The national ‘Duurzaam Door’ (Moving Forward Sustainably) Policy Programme regards these networks as generative governance arrangements where new knowledge, actions and relations can co-evolve together with new insights in governance and learning within sustainability transitions. In order to understand the dynamics of the learning in these networks we have monitored emergent properties of social learning between 2014 and 2016. Our focus is particularly on the interrelated role of trust, commitment, reframing and reflexivity. Our

Can computer models be used for social learning? A serious game in water management

Computer simulation models are increasingly used to support solving complex problems in natural resource management, with social learning as subsidiary goal of the solution process. In this research, a serious game on water management is used where participants receive feedback on consequences of their choices from an Integrated Assessment Meta Model. This study aims to determine if and how social learning takes place and explores the role of the model in social learning. Group discussions were qualitatively analysed to uncover and understand the mechanisms in this process. Results show that social learning took place in 10 of the 12 game sessions. Though model feedback was an important driver for social learning, social learning was driven most by the team's reflection on their perspective. We conclude that using a model can facilitate social learning in a serious-game setting, in particular in combination with reflection on teams' perspectives.</p

Parent-Child Dyadic Coping and Quality of Life in Chronically Diseased Children

Different forms of dyadic coping are associated with positive outcomes in partner relationships, yet little is known about dyadic coping in parent-child relationships. The current research explored the association between parent-child dyadic coping and children's quality of life in 12-18-year old children with a chronic disease (i.e., cystic fibrosis, autoimmune diseases, and children post-cancer treatment). In a sample of 105 parent-child dyads, self-reported forms of dyadic coping (i.e., stress communication, problem-oriented, emotion-oriented, and negative dyadic coping) and children's quality of life were assessed. Children reported more stress communication and negative dyadic coping than their parents, while parents reported more problem-oriented dyadic coping and emotion-oriented dyadic coping than their children. More stress communication of the child was associated with more emotion-oriented dyadic coping and less negative dyadic coping of the parent. More negative dyadic coping of the child was associated with less stress communication, problem-oriented dyadic coping and emotion-oriented dyadic coping of the parent. Additionally, both children's and parents' negative dyadic coping were associated with lower self-reported pediatric quality of life and parents' emotion-oriented dyadic coping was associated with higher pediatric quality of life. These findings emphasize that children and their parents mutually influence each other and that dyadic coping is associated with children's quality of life. Theoretical and practical implications are discussed