HELPING YOUTH WITH AUTISM SPECTRUM DISORDER DEVELOP SOCIAL COMPETENCE IN COMMUNITY-BASED SETTINGS

The purpose of the current dissertation is to identify the features of effective interventions by exploring the experiences of youth with ASD who participate in such interventions, through two intervention studies (Studies 1 and 2) and one interview study (Study 3). Studies 1 and 2 were designed to support the development of social competence of youth with ASD through Structured Play with LEGO TM (Study 1, 12 youths with ASD, ages 7–12) and Minecraft TM (Study 2, 4 youths with ASD, ages 11–13). Over the course of the sessions, the play of the youth developed from parallel play (children playing alone, without interacting) to co-operative play (playing together with shared objectives). The results of Study 2 showed that rates of initiations and levels of engagement increased from the first session to the final session. In Study 3, 12 youths with ASD (ages 10–14) and at least one of their parents were interviewed to explore what children and their parents want from programs designed to improve social competence, which activities and practices were perceived to promote social competence by the participants, and which factors affected their decisions regarding these programs. The adolescents and parents looked for programs that supported social development and emotional wellbeing, but did not always have access to the programs they would have preferred, with factors such as cost and location reducing their options. Three overarching themes emerged through analysis of the three studies: (a) interests of the youth; (b) structure, both through interactions and instruction; and (c) naturalistic settings. Adolescents generally engage more willingly in interventions that incorporate their interests, such as play with Minecraft TM in Study 2. Additionally, Structured Play and structured instruction were crucial components of providing safe and supportive contexts for the development of social competence. Finally, skills learned in naturalistic settings tend to be applied more successfully in everyday situations. The themes are analysed through the lens of Vygotsky’s (1978) perspectives on learning, play, and development. Implications of the results for practitioners and researchers are discussed.

LINEUP SIZE AND NUMBER OF CUES: WHEN BIGGER ISN’T BETTER

Larger lineups could protect innocent suspects from being misidentified; however, they can also decrease correct identifications. Bertrand (2006) investigated whether the decrease in correct identifications could be prevented by adding more cues, in the form of additional views of lineup members’ faces, to the lineup. Adding these cues was successful to an extent. The current series of studies attempted to replicate Bertrand’s (2006) findings while addressing some methodological issues—namely, the inconsistency in image size as lineup size increased. First, I investigated whether image size could affect face recognition (Chapter 2) and found it could, but that it also affected previously-seen (“old”) versus previously-unseen (“new”) faces differently. Specifically, smaller image sizes at exposure lowered accuracy for old faces, while these same image sizes at recognition lowered accuracy for new faces. Although these results indicate that target recognition would be unaffected by image size at recognition (i.e., during a lineup), lineups are also comprised of previously-unseen faces, in the form of fillers and innocent suspects. Because image size could affect lineup decisions, as it could become more difficult to realize fillers are previously-unseen, I decided to replicate Bertrand (2006) while keeping image size constant in Chapters 3 (simultaneous lineups) and 4 (simultaneous-presentation, sequential decisions). In both Chapters, the integral findings were the same: correct identification rates decreased as lineup size increased from 6- to 24-person lineups, but adding cues had no effect. The inability to replicate Bertrand (2006) could mean that the original finding was due to chance, but alternate explanations also exist, such as the overall size of the array, the degree to which additional cues overlap, and the length of the target exposure. These alternate explanations, along with directions for future research, are discussed in the following Chapters.

Characterization of ALDH1A1 as a novel tumorigenic target mediating TAZ-induced lung tumorigenesis and stem cell phenotypes

Recent studies suggest that lung cancer stem cells (CSCs) may play major roles in lung cancer development, metastasis and drug resistance. Therefore, identification of lung CSC drivers may provide promising targets for lung cancer. TAZ (transcriptional co-activator with PDZ-binding motif) is a transcriptional co-activator and key downstream effector of the Hippo pathway, which plays critical roles in various biological processes. TAZ has been shown to be overexpressed in non-small cell lung cancer (NSCLC) and involved in tumorigenicity of lung epithelial cells. However, whether TAZ is a driver for lung CSCs and tumor formation in vivo is unknown. In addition, the molecular mechanism underlying TAZ-induced lung tumorigenesis remains to be determined. In this study, we provided evidence that constitutively active TAZ (TAZ-S89A) is a driver for lung tumorigenesis in vivo in mice and formation of lung CSC. Oncogenes upregulated in TAZ-overexpressing cells were identified with further validation. The most dramatically activated gene, Aldh1a1 (Aldehyde dehydrogenase 1 family member a1), a well-established CSC marker, showed that TAZ induces Aldh1a1 transcription by activating its promoter activity through interaction with the transcription factor TEA domain (TEAD) family member. Most significantly, inhibition of ALDH1A1 with its inhibitor A37 or CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) gene knockout in lung cancer cells suppressed lung tumorigenic and CSC phenotypes in vitro, and tumor formation in mice in vivo. In conclusion, this study identified TAZ as a novel inducer of lung CSCs and the first transcriptional activator of the stem cell marker ALDH1A1. Most significantly, we identified ALDH1A1 as a critical meditator of TAZ-induced tumorigenic and CSC phenotypes in lung cancer. Our studies provided preclinical data for targeting of TAZ-TEAD-ALDH1A1 signaling to inhibit CSC-induced lung tumorigenesis and drug resistance in the future.