Evaluation of a Role-Playing Game to Improve Social Skills for Individuals with ASD

Autism spectrum disorder (ASD) affects one in 59 children (Centers for Disease Control and Prevention, 2018). Impairments in social communication and restricted and repetitive behaviorsare often associated with debilitating outcomes for individuals with ASD. Therefore, it is critical to identify successful treatments to address the social deficits characteristic of ASD. This study investigated the effects of a role-playing game (RPG) on social skill acquisition for individuals with ASD. The primary dependent variable was skill acquisition within the context of the RPG setting. Generalization of skill acquisition outside of the game-context and social functioning was also evaluated. Results indicated that the role-playing game improved social skill acquisition across all participants and was rated as a socially valid intervention by both parents and participants. Furthermore, there were mixed results for participants generalized skill acquisition. Future research should incorporate a specific strategy within the role-playing game to promote generalization of skill acquisition

Effects of a Function-Based Peer Management Intervention with Middle-School Students with ADHD

Attention Deficit/Hyperactivity Disorder (ADHD) is characterized by impairment in functioning due to inattention, hyperactivity, or impulsivity, as well as difficulties in school with social rejection and academic underachievement (American Psychiatric Association, 2013). The purpose of this study was to investigate the effectiveness of a peer-mediated non-contingent reinforcement (NCR) intervention informed by functional assessment data to decrease disruptive behavior for students with a special education classification of OHI-ADHD. Participants included three student dyads in a middle school setting located in the Southeastern United States. An A/B/A/B withdrawal design was used to evaluate the effectiveness of this intervention. The primary dependent variables were target student disruptive and on-task behavior. Student interventionist integrity was also evaluated. Results indicated this intervention was effective in decreasing percentages of disruptive behavior as well as increasing percentages of on-task behavior during academic instruction across all participants. Additionally, each student interventionist was able to implement the NCR intervention with high integrity

An Evaluation of a Teaching Interaction Procedure Implemented in a Recess Setting

The teaching interaction procedure (TIP) is a strategy that has been demonstrated as effective in promoting social skill acquisition in school settings for young students with social communication deficits (Leaf et al., 2009; Leaf et al., 2010). However, a frequently cited criticism of social skills training is the lack of generalizability of target skills to novel contexts (Bellini et al., 2007). The purpose of the study was to evaluate a TIP-based social skills intervention conducted on the playground, intended to promote generalizability through training in naturalistic settings and to evaluate generalizability of skill acquisition to the classroom. Eight students 5-8 years old with an educational classification of autism or developmental delay participated in the study. The primary dependent variable was skill acquisition in the playground setting, and a secondary measure was generalized skill acquisition to the classroom setting. Target skills included appropriate body language, participation, and responding to initiations. A multi-probe design embedded within a multiple baseline design across target skills with concurrent replication across participants was used to evaluate the primary and secondary measures. Overall, results suggest that increases in skill acquisition were observed during implementation of the TIP across most participants and skills in both training and generalization phases. However, substantial variability was noted across participants related to maintaining skill acquisition during maintenance and follow-up phases in both the training and generalization settings. Limitations of these results are discussed as well as implications for school practitioners

Community oncologists\u27 perceptions and utilization of large-panel genomic tumor testing.

PURPOSE: Large-panel genomic tumor testing (GTT) is an emerging technology with great promise but uncertain clinical value. Previous research has documented variability in academic oncologists\u27 perceptions and use of GTT, but little is known about community oncologists\u27 perceptions of GTT and how perceptions relate to clinicians\u27 intentions to use GTT. METHODS: Community oncology physicians (N = 58) participating in a statewide initiative aimed at improving access to large-panel GTT completed surveys assessing their confidence in using GTT, attitudes regarding the value of GTT, perceptions of barriers to GTT implementation, and future intentions to use GTTs. Descriptive and multivariable regression analyses were conducted to characterize these perceptions and to explore the relationships between them. RESULTS: There was substantial variability in clinicians\u27 perceptions of GTT. Clinicians generally had moderate confidence in their ability to use GTT, but lower confidence in patients\u27 ability to understand test results and access targeted treatment. Clinicians had positive attitudes regarding the value of GTT. Clinicians\u27 future intentions to use GTT were associated with greater confidence in using GTT and greater perceived barriers to implementing GTT, but not with attitudes about the value of GTT. CONCLUSIONS: Community oncologists\u27 perceptions of large-panel genomic tumor testing are variable, and their future intentions to use GTT are associated with both their confidence in and perceived barriers to its use, but not with their attitudes towards GTT. More research is needed to understand other factors that determine how oncologists perceive and use GTT in clinical practice

Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as path

Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32

Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, Pmeta = 2.5 × 10−9, OR[T] = 0.81) and 17q21.32 (rs72823592, Pmeta = 9.3 × 10−9, OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, Pmeta = 9.1 × 10−9, OR[T] = 0.68) and at 1q43 for JME (rs12059546, Pmeta = 4.1 × 10−8, OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, Pmeta = 4.0 × 10−6) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndrome

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Use of Superheroes Social Skills With Middle School-Age Students With Autism Spectrum Disorder

The current study evaluated use of the Superheroes Social Skills program as a means of increasing social skill accuracy in adolescents with autism spectrum disorder. Participants included four Caucasian male students that were eligible for special education services within the autism category. Social skills training was presented twice weekly for 9 weeks. The results demonstrated that implementation of the intervention improved social skill accuracy within the training setting as indicated by visual analysis and nonoverlap of all pairs. Additionally, improvements in social skill accuracy during probes conducted within the classroom with typically developing peers was observed. Despite improvements in social skill accuracy in both settings, sociometric status of participants demonstrated little change from baseline to postintervention

The Effects of a Modified PEERS Curriculum on Accurate and Novel Responding of Children with Autism Spectrum Disorder

Lag schedules of reinforcement have been found to be useful in addressing invariant behavior of individuals with autism spectrum disorder (ASD). The purpose of this study was to conduct an additive analysis of lag schedules and rules. Three participants with ASD were exposed to a Lag 2 schedule of reinforcement in isolation. Following, participants were introduced to an incomplete rule and then a complete rule regarding reinforcement in conjunction with the lag schedule. Results indicated that lag schedules in isolation were generally sufficient for increasing novel responding. The addition of incomplete and complete rules often resulted in increases, albeit small, in novel responding. Results are discussed in terms of applied use of lag schedules of reinforcement and addressing nonresponse