Using Self-Management and Visual Cues to Improve Responses to Nonverbal Social Cues in Adults With Autism Spectrum Disorder.

Many individuals with Autism Spectrum Disorder (ASD) experience challenges with social communication, including recognizing and responding to non-verbal cues. The purpose of this study was to assess the efficacy of self-management combined with textual cues to teach adults with ASD to recognize and respond to nonverbal expressions of boredom and confusion during social conversation. A multiple baseline across participants design was used to assess the efficacy of this intervention for three participants. Results showed substantial gains across all participants in their recognition and responsiveness to the targeted nonverbal cues. Moreover, this skill maintained after the completion of intervention and generalized to novel conversation partners and settings with large effect sizes. The findings add to the literature base on interventions for adults with ASD, and further support the use of self-management and textual cues as effective intervention strategies for improving nonverbal communication.

Using a Question Bank Intervention to Improve Socially Initiated Questions in Adolescents and Adults With Autism.

Purpose Individuals with autism spectrum disorder (ASD) often have difficulty asking questions during social conversation, which can negatively impact their interactions with peers. The purpose of this study was to assess whether a question bank intervention would be effective in improving question asking during social conversation. Method In the context of a multiple-baseline experimental design, we implemented an intervention using prepractice with question banks designed to increase the number and diversity of questions asked by adolescents and adults with ASD during social conversations with their peers. Results Following intervention, all participants improved their use of questions in natural settings with their neurotypical peers. Generalization to novel questions occurred, and gains were maintained at follow-up. Finally, supplemental measures of social validity showed that similarly aged neurotypical peers who were naïve to the experimental hypothesis rated two of the three participants with higher social desirability following intervention. Conclusion Individuals with ASD can improve their appropriate question asking during social conversation using a brief question bank intervention with generalization to their peers in natural settings.

Imaging assisted evaluation of antitumor efficacy of a new histone deacetylase inhibitor in the castration-resistant prostate cancer.

PURPOSE: Castration-resistant prostate cancer (CRPC) is the most common cause of death in men. The effectiveness of HDAC inhibitors has been demonstrated by preclinical models, but not in clinical studies, probably due to the ineffectively accumulation of HDACI in prostate cancer cells. The purpose of this work was to evaluate effects of a novel HDACI (CN133) on CRPC xenograft model and 22Rv1 cells, and develops methods, PET/CT imaging, to detect the therapeutic effects of CN133 on this cancer. METHODS: We designed and performed study to compare the effects of CN133 with SAHA on the 22Rv1 xenograft model and 22Rv1 cells. Using PET/CT imaging with [11C] Martinostat and [18F] FDG, we imaged mice bearing 22Rv1 xenografts before and after 21-day treatment with placebo and CN133 (1 mg/kg), and uptake on pre-treatment and post-treatment imaging was measured. The anti-tumor mechanisms of CN133 were investigated by qPCR, western blot, and ChIP-qPCR. RESULTS: Our data showed that the CN133 treatment led to a 50% reduction of tumor volume compared to the placebo that was more efficacious than SAHA treatment in this preclinical model. [11C] Martinostat PET imaging could identify early lesions of prostate cancer and can also be used to monitor the therapeutic effect of CN133 in CRPC. Using pharmacological approaches, we demonstrated that effects of CN133 showed almost 100-fold efficacy than SAHA treatment in the experiment of cell proliferation, invasion, and migration. The anti-tumor mechanisms of CN133 were due to the inhibition of AR signaling pathway activity by decreased HDAC 2 and 3 protein expressions. CONCLUSION: Taken together, these studies provide not only a novel epigenetic approach for prostate cancer therapy but also offering a potential tool, [11C] Martinostat PET/CT imaging, to detect the early phase of prostate cancer and monitor therapeutic effect of CN133. These results will likely lead to human trials in the future.

Molecular imaging of Alzheimer's disease-related gamma-secretase in mice and nonhuman primates.

The pathogenesis of Alzheimer's disease (AD) is primarily driven by brain accumulation of the amyloid-ß-42 (Aß42) peptide generated from the amyloid-ß precursor protein (APP) via cleavages by ß- and γ-secretase. γ-Secretase is a prime drug target for AD; however, its brain regional expression and distribution remain largely unknown. Here, we are aimed at developing molecular imaging tools for visualizing γ-secretase. We used our recently developed γ-secretase modulators (GSMs) and synthesized our GSM-based imaging agent, [11C]SGSM-15606. We subsequently performed molecular imaging in rodents, including AD transgenic animals, and macaques, which revealed that our probe displayed good brain uptake and selectivity, stable metabolism, and appropriate kinetics and distribution for imaging γ-secretase in the brain. Interestingly, rodents and macaques shared certain brain areas with high γ-secretase expression, suggesting a functional conservation of γ-secretase. Collectively, we have provided the first molecular brain imaging of γ-secretase, which may not only accelerate our drug discovery for AD but also advance our understanding of AD.

Targeting IEP Social Goals for Children with Autism in an Inclusive Summer Camp.

Children with autism spectrum disorder demonstrate challenges in socialization that can interfere with their participation in common childhood activities and can persist or worsen if not addressed. The purpose of this study was to assess whether individualized education program (IEP) social goals could be targeted by a supervised paraprofessional during a short-term inclusive summer camp program. Data were collected using a concurrent multiple baseline design across four children. Results showed that following a 2-week summer camp program all participants made social improvements, reaching their year-long IEP goals, that maintained at follow-up in natural environments. Further, the paraprofessionals reached fidelity of implementation. Findings are discussed in terms of the value and feasibility of providing social interventions in inclusive summer camps.

Treatment for Higher-Order Restricted Repetitive Behaviors (H-RRB) in Children with Autism Spectrum Disorder.

Restricted repetitive behaviors (RRB) are one of the core symptoms of autism spectrum disorder (ASD). Evidence suggests that higher-order RRB (H-RRB) are particularly challenging and can negatively impact family functioning (e.g., insistence on sameness, following idiosyncratic routines). The study examined the effects of a parent-implemented behavior intervention using a multiple baseline single case experimental design in three young children with ASD. The intervention involved self-management procedures and included principles of pivotal response treatment during which parents provided bids for children to vary from H-RRB and children obtained points for engaging in these other interests and activities. Results showed improvements in child behavior, parent and child affect and interactions, children's engagement in family activities, and overall parent ratings of RRB.

The Impact of Prior Activity History on the Influence of Restricted Repetitive Behaviors on Socialization for Children With High-Functioning Autism.

Research has demonstrated that incorporating restricted interests of an individual with autism into recess activities is effective at increasing socialization with typically developing peers. However, certain activity contexts may alter the reinforcing influence of the restricted repetitive behaviors (RRBs) depending on an individual's history in that activity. Using an alternating treatment design, this study examined whether an individual's history with an activity affected socialization. RRBs were embedded into activities with a reported positive history (i.e., prior history of positive experiences) and activities with a reported negative history (i.e., prior history of aversive experiences) for participants. Data indicated that socialization increased and remained above baseline levels when RRBs were introduced during activities with a positive history, whereas socialization was minimal when RRBs were introduced in activities with a negative history. Social significance and implications for designing activities that incorporate a child's RRBs are discussed.

Increasing Social Integration for College Students with Autism Spectrum Disorder.

Increasing numbers of individuals with Autism Spectrum Disorder (ASD) are entering postsecondary education; however, many report feeling lonely and isolated. These difficulties with socialization have been found to impact students' academic success, involvement within the university, and overall well being. Therefore, the purpose of this study was to assess, within the context of a multiple-baseline across participants design, whether a structured social planning intervention would increase social integration for college students with ASD. The intervention consisted of weekly meetings to plan social activities around the student with ASD's interests, improve organizational skills, and target specific social skills. Additionally, each participant had a peer mentor for support during the social activities. The results showed that following intervention all participants increased their number of community-based social events, extracurricular activities, and peer interactions. Furthermore, participants improved in their academic performance and satisfaction with their college experience. Results are discussed in regards to developing specialized programs to assist college students with ASD.

Improving Functional Language and Social Motivation with a Parent-Mediated Intervention for Toddlers with Autism Spectrum Disorder.

Recent research suggests that children with autism spectrum disorder (ASD) may now be reliably identified in later infancy, highlighting the need for empirically-validated interventions for infants and toddlers with early symptoms of ASD. Using a multiple baseline design across 15- to 21-month-old toddlers, this study implemented a brief, parent-mediated, Pivotal Response Treatment program, focusing on improving expressive communication. The results indicated that verbal communication improved as a consequence of the intervention, with concomitant improvements in untreated areas for all participants. Following the intervention, symptoms of autism decreased and parents reported satisfaction with the program's ease of implementation and observed child gains. The results are discussed in terms of developing very early interventions to improve developmental trajectories for infants and toddlers.

Improving Empathic Communication Skills in Adults with Autism Spectrum Disorder.

The literature suggests that many individuals diagnosed with Autism Spectrum Disorder (ASD) experience challenges with recognizing and describing emotions in others, which may result in difficulties with the verbal expression of empathy during communication. Thus, there is a need for intervention techniques targeting this area. Using a multiple baseline across participants design, this study examined the effectiveness of a video-feedback intervention with a visual framework component to improve verbal empathetic statements and questions during conversation for adults with ASD. Following intervention, all participants improved in verbal expression of empathetic statements and empathetic questions during conversation with generalization and maintenance of gains. Furthermore, supplemental assessments indicated that each participant improved in their general level of empathy and confidence in communication skills.

Assessing and Improving Early Social Engagement in Infants.

Empirical studies have documented a variety of social abnormalities in infancy that indicate risk for later social and behavioral difficulties. There is very little research illustrating the presence of such behavioral vulnerabilities with frequent repeated measures, and the feasibility of designing interventions for improving social engagement in infants under one year of age. In the context of a multiple baseline research design, three young infants, ages 4, 7, and 9 months referred for concerns about social engagement were assessed for affect, social interest, eye contact avoidance, and response to name. Additionally, the feasibility of implementing an intervention to target social behaviors was examined. Results demonstrated that: (1) consistently low or erratic levels of social behavior were evident throughout the baseline assessment period; (2) these patterns could be improved with a brief intervention (a modified Pivotal Response Treatment) showing an immediate increase and stability of social engagement; and (3) social engagement remained at a stable and high level at follow-up. The results are discussed in terms of implications of early assessment and intervention for clinical populations, including infants with Autism Spectrum Disorder.

Training paraprofessionals to improve socialization in students with ASD.

An important line of research relates to whether school personnel, such as paraprofessionals, who are present during unstructured social periods, such as lunch-recess, could successfully implement interventions to improve socialization between students with ASD and their typical peers in a group setting. Therefore, within the context of a multiple baseline across participants design, we assessed whether training paraprofessionals to provide social interventions would enhance social development in students with ASD in a group setting. Results showed that paraprofessionals who were not providing any social opportunities during baseline were able to meet fidelity of implementation following a brief training. Consequently, the children with ASD increased their levels of engagement and rates of initiation with typically developing peers following intervention. Implications for training paraprofessionals to implement effective social interventions for students with ASD are discussed.

Improving question-asking initiations in young children with autism using pivotal response treatment.

Social initiations make up a core deficit for children with autism spectrum disorder (ASD). In particular, initiated questions during social interactions are often minimal or absent in this population. In the context of a multiple baseline design, the efficacy of using the motivational procedures of Pivotal Response Treatment to increase social question-asking for three young children with autism was assessed. Results indicated that participants initiated a greater number of targeted questions following intervention. Additionally, all children exhibited increases in initiation of untargeted questions during social interaction in novel settings. Furthermore, post intervention data revealed collateral gains in communication and adaptive behavior. Theoretical implications of incorporating motivational strategies into intervention to improve social initiations in young children with ASD are discussed.

The importance of early identification and intervention for children with or at risk for autism spectrum disorders.

There has been a dramatic rise in the number of children being diagnosed with autism spectrum disorders (ASD), which has led to increased attention paid to assessment and intervention issues. This manuscript agrees with Camarata (2014) that the evidence base for early assessment and intervention should be expanded. However, it disagrees with Warren et al.'s (2011) assumption that there are not empirically validated early interventions. Reliable diagnosis has been documented during infancy and toddlerhood, and evidence suggests that the earlier the onset of intervention, the greater likelihood of an improved developmental trajectory. It is argued that early intervention is more cost and time efficient than a "wait and see" approach. With regard to published studies, the large amount of heterogeneity in the ASD population supports the use of rigorous single case experimental design research. It is an error to limit empirical evidence for treatments to only randomized clinical trials, which have the weakness of masking individual differences. Single case experimental designs examine the effects of intervention beyond typical maturation by allowing for clear estimations of developmental trajectories prior to the onset of intervention, followed by evaluation of the impact of the intervention. This commentary discusses the short- and long-term benefits of early diagnosis and intervention.

Using self-management to improve the reciprocal social conversation of children with autism spectrum disorder.

Individuals with autism spectrum disorders often exhibit difficulties with reciprocal social conversation, engaging in limited verbal exchanges, even when language structures are intact. This study employed a multiple baseline design to examine the effectiveness of a self-management intervention targeting (1) on-topic responsiveness to a conversational partner; (2) expansion of the conversational topic; and (3) on-topic question asking. Results demonstrated improved reciprocal social conversation through elaborated responses and on-topic question asking, which generalized and maintained. Social validity measures by naïve observers indicated that the intervention led to meaningful improvements during conversation, including interest, naturalness, and desirability as a conversational partner.

Is Medication Information for Children with Autism Spectrum Disorder Monitored and Coordinated Across Professionals? Findings from a Teacher Survey.

Prescription medications are commonly used for children with autism spectrum disorder (ASD), however, there is little research regarding how the effect of medication is monitored across settings once prescribed. The present study addressed this issue for children with ASD in school by administering a questionnaire to teachers of students with ASD who were and were not being given medication. Specifically, the questionnaire assessed the teachers' knowledge about whether the child was being given medication, and whether behavior changes or side effects were being communicated in any way to the child's family and prescribing physician. The results showed that for children who were being given medication, fewer than half of the teachers reported knowing the child was being given medication. For those children who were not being given medication, only 53% of the teachers reported correct information for their students. Of the teachers who knew their students were being given medication, all reported that they were not conferring with the child's prescribing physician regarding behavioral observations or side effects. Whether teachers are blind to the medication types and dosage the students are being given or not, some type of communication to physicians about the children's behavior at school is important. Given the importance of monitoring medication for children with ASD, implications for system change, for professionals and for funding agencies are discussed.

Improving socialization for high school students with ASD by using their preferred interests.

There has been a paucity of research on effective social interventions for adolescents with autism spectrum disorders (ASD) in inclusive high school settings. The literature, however, suggests that incorporating the student with ASD's special interests into activities may help improve their socialization with typical peers. Within the context of a multiple baseline across participants design, we implemented lunchtime activities incorporating the adolescent with ASD's preferred interests that were similar to ongoing activities already available at the schools. Results showed this increased both level of engagement and their rate of initiations made to typical peers. Social validation measures suggest that both adolescents with ASD and typical peers enjoyed participating in these activities and that the results generalized to other similar activities.

Acquisition of multiple questions in the context of social conversation in children with autism.

Verbal initiations, such as questions, are essential components of social conversation often lacking in children with autism. Building on research showing that single questions can be taught in isolation, this study used a multiple baseline design to investigate whether a self-management intervention was effective for teaching concurrent acquisition and discrimination of three social questions in the context of conversation. Following intervention, participants rapidly increased their appropriate use of all three questions in a conversational context and maintained these gains over time. The participants also used questions appropriately with partners uninvolved in treatment. Additionally, the occasional presence of appropriate questions during baseline coupled with rapid improvement during intervention support theories that a lack of question-asking may be motivation-based rather than ability-based.

Improving generalization of peer socialization gains in inclusive school settings using initiations training.

Social engagement by children with autism spectrum disorder (ASD) in unstructured school settings generally occurs at very low levels, if at all. Although many interventions improve peer socialization, generalization and maintenance of such gains when interventions are faded are typically low. The present study employed a multiple baseline design across participants to target generalization in the absence of interventionists in elementary school children with ASD at recess. Teaching initiations has been suggested as one method to increase generalization. The results of the present study showed that when initiations were targeted during intervention for social play, the participants demonstrated generalized peer social engagement, increases in unprompted peer-directed initiations, and more positive affect during peer interactions. Results are discussed in terms of theoretical and applied implications of incorporating initiations training into social interventions.

An early social engagement intervention for young children with autism and their parents.

The social vulnerabilities associated with young children with autism are recognized as important intervention targets due to their influence on subsequent development. Current research suggests that interventions that combine motivational and social components can create meaningful changes in social functioning. Simultaneously, it is hypothesized that parent delivery of such strategies can invoke increases in these core social behaviors and parent engagement. This study examined the effects of teaching parents to implement a social engagement intervention with their children. The results indicated that the use of this parent-delivered social intervention led to (a) increases in their children's use of eye contact, directed positive affect, and verbal initiations, (b) increases in parent positive affect and synchronous engagement, and (c) generalized increases in parent and child behaviors.