Internalizing Psychiatric Symptoms in People with Mosaicism for Trisomy 21.

People with mosaicism for trisomy 21 have been shown to exhibit the many of same phenotypic traits present in people with non-mosaic Down syndrome, but with varying symptom severity. However, the behavioral phenotype of people with mosaic Down syndrome (mDS) has not been well characterized. This study aimed to examine the prevalence of self-report and caregiver-report symptoms of depression and anxiety among a sample of 62 participants with mDS aged 12 - 46, and assess their association with the percentage of trisomy 21 in blood and/or buccal mucosa cells. The results showed that 53% of the participants reported clinically significant depression symptoms and 76% reported clinically significant anxiety symptoms. No clear associations were observed between the percentage of trisomic cells and total anxiety or depression, but a significant positive association between the proband-reported specific fears subscale and the percentage of trisomic cells in buccal specimens was detected (r = .43, p = .007). This study highlights the high occurrence of depression and anxiety symptoms in individuals with mDS and the need for routine assessment to optimize their care. It also demonstrates the ability of people with mDS to complete these evaluations, thereby supporting their inclusion in research studies/clinical trials.

Self-Replicating RNAs Drive Protective Anti-tumor T Cell Responses to Neoantigen Vaccine Targets in a Combinatorial Approach.

Historically poor clinical results of tumor vaccines have been attributed to weakly immunogenic antigen targets, limited specificity, and vaccine platforms that fail to induce high-quality polyfunctional T cells, central to mediating cellular immunity. We show here that the combination of antigen selection, construct design, and a robust vaccine platform based on the Synthetically Modified Alpha Replicon RNA Technology (SMARRT), a self-replicating RNA, leads to control of tumor growth in mice. Therapeutic immunization with SMARRT replicon-based vaccines expressing tumor-specific neoantigens or tumor-associated antigen were able to generate polyfunctional CD4+ and CD8+ T cell responses in mice. Additionally, checkpoint inhibitors, or co-administration of cytokine also expressed from the SMARRT platform, synergized to enhance responses further. Lastly, SMARRT-based immunization of non-human primates was able to elicit high-quality T cell responses, demonstrating translatability and clinical feasibility of synthetic replicon technology for therapeutic oncology vaccines.

CD8+ T cells mediate protection against Zika virus induced by an NS3-based vaccine.

Zika virus (ZIKV) is associated with congenital malformations in infants born to infected mothers, and with Guillain-Barré syndrome in infected adults. Development of ZIKV vaccines has focused predominantly on the induction of neutralizing antibodies, although a suboptimal antibody response may theoretically enhance disease severity through antibody-dependent enhancement (ADE). Here, we report induction of a protective anti-ZIKV CD8+ T cell response in the HLA-B*0702 Ifnar1-/- transgenic mice using an alphavirus-based replicon RNA vaccine expressing ZIKV nonstructural protein NS3, a potent T cell antigen. The NS3 vaccine did not induce a neutralizing antibody response but elicited polyfunctional CD8+ T cells that were necessary and sufficient for preventing death in lethally infected adult mice and fetal growth restriction in infected pregnant mice. These data identify CD8+ T cells as the major mediators of ZIKV NS3 vaccine-induced protection and suggest a new strategy to develop safe and effective anti-flavivirus vaccines.

Using video vignettes in research and program evaluation for people with intellectual and developmental disabilities: A case study of the Leadership for Empowerment and Abuse Prevention (LEAP) project.

People with intellectual and developmental disabilities (IDD) are often excluded from meaningful participation in research and program evaluation for various reasons, including protocols and measures that are inaccessible for people with varying cognitive and communication abilities. Emancipatory research models emphasize the importance of inclusive research practices. Video vignettes are a promising tool for research and program evaluation with people with IDD because they are standardized, they use visual imagery rather than relying on written or verbal communication, and they allow for distance from sensitive topics. The Leadership for Empowerment and Abuse Prevention (LEAP) project used video vignettes to evaluate a healthy relationship program for people with IDD. The authors discuss the process of piloting various protocols and measures, which then ultimately led to the use of video vignettes in the evaluation.

Implementing a UDL Framework: A Study of Current Personnel Preparation Practices.

Young adults with intellectual disability (ID) continue to experience the least successful postschool outcomes among transition-aged youth ( Sanford et al., 2011 ). Experts disagree on the most effective approach to improve outcomes such as employment, postsecondary education, and community living. In 2015, the National Goals Conference brought together educational researchers to set an agenda to guide the field in terms of research, practice, and policy ( Thoma, Cain, & Walther-Thomas, 2015 ). One of their recommendations, based on promising research and practices, urged the field to identify effective personnel preparation and professional development practices that ensure general and special educators can implement a UDL framework ( Thoma, Cain, et al., 2015 ). This study surveyed program coordinators at accredited universities to determine what is currently being done to prepare educators to implement a Universal Design for Learning (UDL) framework, the extent to which a UDL framework is being incorporated into preservice courses in higher education, and how a UDL framework is being used to improve postschool outcomes for youth with ID.