Promoting Positive Youth Development: Relational Data Analysis (RDA)

This article provides an overview of the origins and use of relational data analysis (RDA). RDA is a multidimensional, multiphasic framework for unifying data analytic strategies across dimensions (quantitative/qualitative, causal/structural, observation/interpretation, etc.) and phases of analyses (conceptual, theoretical, and research analyses). RDA was developed within a relational metatheoretical methodological framework for overcoming the splits that have historically characterized methodological metatheory. The aim was to formulate a practical, ready-at-hand framework that the developmental scientist could use to unify the analysis of developmental change in real life “applied” settings as well as clinic and laboratory settings

Promoting Positive Identity Development in Troubled Youth: A Developmental Intervention Science Outreach Research Approach

This article illustrates how developmental intervention science outreach research contributes to knowledge development on the promotion of positive identity development by describing results from the Miami Youth Development Project. The project is committed to the use of descriptive and explanatory knowledge about evidence-based individual and institutional intervention strategies for promoting developmental change in self and identity. Our efforts, described here, include a method for measuring theoretically and personally meaningful identity change, a procedure for integrating key aspects of qualitative and quantitative data through relational data analysis, and an evidence-based positive youth development intervention that fosters measurable and meaningful identity change

A Developmental Intervention Science (DIS) outreach research approach to promoting youth development: Theoretical, methodological, and meta-theoretical challenges.

This paper describes work directed toward creating community-supported positive youth development interventions that draw on a developmental intervention science outreach research approach. With respect to developmental interventions, this approach focuses on creating evidence-based longitudinal change intervention strategies for promoting long-term developmental change. The paper describes three broad challenges (theoretical, methodological, and meta-theoretical) that the authors faced in their efforts to develop and implement community-supported intervention programs built on this approach. The authors describe first the theoretical challenges they addressed in developing the conceptual framework for their community-supported intervention; second, the challenge of developing and refining a methodological framework for evaluating positive youth development interventions in “real-world” settings; and third, the meta-theoretical challenges that arose in the context of implementing community-supported positive development programs

A Developmental Intervention Approach to Promoting Positive Development: Pathways of Intervention Change

This paper describes work directed toward creating community-supported positive youth development interventions that draw on a developmental intervention science outreach research approach. With respect to developmental interventions, this approach focuses on creating evidence-based longitudinal change intervention strategies for promoting long-term developmental change. The paper describes three broad challenges (theoretical, methodological, and meta-theoretical) that the authors faced in their efforts to develop and implement community-supported intervention programs built on this approach. The authors describe first the theoretical challenges they addressed in developing the conceptual framework for their community-supported intervention; second, the challenge of developing and refining a methodological framework for evaluating positive youth development interventions in “real-world” settings; and third, the meta-theoretical challenges that arose in the context of implementing community-supported positive development programs

Modulation of the tumour promoting functions of cancer associated fibroblasts by phosphodiesterase type 5 inhibition increases the efficacy of chemotherapy in human preclinical models of esophageal adenocarcinoma

Background and aims: Esophageal adenocarcinoma (EAC) is chemoresistant in the majority of cases. The tumor-promoting biology of cancer associated fibroblasts (CAF) make them a target for novel therapies. Phosphodiesterase type 5 inhibitors (PDE5i) have been shown to regulate the activated fibroblast phenotype in benign disease. We investigated the potential for CAF modulation in EAC using PDE5i to enhance the efficacy of chemotherapy. Methods: EAC fibroblasts were treated with PDE5i and phenotypic effects examined using immunoblotting, immunohistochemistry, gel contraction, transwell invasion, organotypics, single cell RNAseq and shotgun proteomics. The combination of PDE5i with standard-of-care chemotherapy (Epirubicin, 5-Fluorouracil and Cisplatin) was tested for safety and efficacy in validated near-patient model systems (3D tumor growth assays (3D-TGAs) and patient derived xenograft (PDX) mouse models). Results: PDE5i treatment reduced alpha-SMA expression in CAFs by 50% (p<0.05), associated with a significant reduction in the ability of CAFs to contract collagen-1 gels and induce cancer cell invasion, (p<0.05). RNAseq and proteomic analysis of CAF and EAC cell lines revealed PDE5i specific regulation of pathways related to fibroblast activation and tumor promotion. 3D-TGA assays confirmed the importance of stromal cells to chemoresistance in EAC, which could be attenuated by PDE5i. Chemotherapy+PDE5i in PDX-bearing mice was safe and significantly reduced PDX tumor volume (p<0.05). Conclusion: PDE5 is a candidate for clinical trials to alter the fibroblast phenotype in esophageal cancer. We demonstrate the specificity of PDE5i for fibroblasts to prevent transdifferentiation and revert the CAF phenotype. Finally, we confirm the efficacy of PDE5i in combination with chemotherapy in close-to-patient in vitro and in vivo PDX-based model systems

A Modeling Study on Child Occupant Safety With Unconventional Seating Configurations

DTNH2215D00017/693JJ920F000158This study uses computer models to study how unconventional seating positions and orientations such as those conceptualized to be offered in vehicles with Automated Driving Systems may affect occupant response metrics of children restrained by child restraint systems (CRS) equipped with internal harnesses (CRS harness-restrained) or the vehicle lap-shoulder belt, with and without belt-positioning boosters. A total of 550 simulations were conducted with the CRABI 12MO in rear-facing CRS, the H33YO in both rear-facing and forward-facing CRS, the H36YO in a backless booster, and the H310YO with and without a booster across a range of conventional and unconventional seating locations and orientations under five impact directions and various CRS installation methods. This is the first study using different child ATDs and CRSs to investigate child occupant responses in a wide range of impact directions and seating orientations