Search

A prior randomized trial found a school social intervention yielded significantly better outcomes (social and autism features) immediately following intervention compared to typical school programming (services-as-usual [SAU]) for children on the autism spectrum. In that study, children in the SAU condition subsequently completed a summer social intervention. This study tested longer-term maintenance of effects for children who completed both interventions. A total of 103 children (ages 6-12 years) on the autism spectrum enrolled and 102 completed the initial RCT. Following the summer social intervention, 90 children from the original RCT completed the longer-term follow-up study. In addition to baseline and posttest in the initial RCT, children from both groups were tested at three follow-up points (five total testing points). At the time of first longitudinal follow-up testing, the children were 1.25-4.25 years post-intervention (ages 8-15 years). Longitudinal multilevel model analyses (and follow-up contrasts) revealed significant improvements for both groups post-intervention on measures of emotion recognition, autism features, and social skills, indicating maintenance of post-intervention improvements over the three follow-up testing points. No between-group differences were found for autism features or social skills over time; however, the school social intervention may have yielded somewhat better emotion recognition skills. Exploratory tests found that child IQ, language level, and length of time since completing the intervention did not moderate outcomes. Both social interventions yielded positive and durable longer-term improvements for children on the autism spectrum. [ClinicalTrials.gov, NCT03338530; November 8, 2017; original retrospectively registered trial]., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Campylobacter spp. are a leading cause of bacterial foodborne zoonosis worldwide, with poultry meat and products recognised as a significant source of human infection. In Vietnam there are few data regarding the occurrence, antimicrobial resistance, and genomic diversity of Campylobacter in poultry and poultry meat. The aim of this study was to estimate the prevalence of Campylobacter in chicken meat at retail in Hanoi, determine antimicrobial sensitivities of the Campylobacter isolated, and assess their genetic diversity. A total of 120 chicken meat samples were collected from eight traditional retail markets ( n =80) and four supermarkets ( n =40). Campylobacter was isolated following ISO 10272-1 : 2017 and identification verified by PCR. The prevalence of Campylobacter was 38.3 % (46/120) and C. coli was the most prevalent species in both retail markets (74 %) and supermarkets (88 %). The minimum inhibitory concentrations for ciprofloxacin, erythromycin, gentamicin, nalidixic acid, streptomycin, and tetracycline were determined by broth microdilution for 32 isolates. All characterised Campylobacter were resistant to ciprofloxacin, nalidixic acid, and tetracycline, with corresponding resistance determinants detected in the sequenced genomes. Most C. coli were multidrug resistant (24/28) and two harboured the erythromycin resistance gene ermB on a multiple drug-resistance genomic island, a potential mechanism for dissemination of resistance. The 32 isolates belonged to clonal complexes associated with both poultry and people, such as CC828 for C. coli . These results contribute to the One Health approach for addressing Campylobacter in Vietnam by providing detailed new insights into a main source of human infection and can inform the design of future surveillance approaches.

Children with ASD are more likely to be involved in bullying compared to typically developing peers; however, studies rarely examine bullying perpetration and the contributing factors among this population. The primary aim of this study was to examine the extent to which parent-reported ASD symptoms, social skills, and comorbid externalizing and internalizing symptoms predicted bullying perpetration in a sample of 390 children with ASD without intellectual disability. Findings from hierarchical regression analyses indicated that social skill deficits, externalizing symptoms (i.e., hyperactivity, aggression, and conduct problems), and depressive symptoms were associated with higher likelihood of bullying perpetration, while severity of ASD symptoms and anxiety were not significant predictors. Further research is needed to better understand bullying perpetration among children with ASD., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

This study assessed the potential short-term effects of COVID-19 stay-at-home restrictions on ratings of ASD and comorbid symptoms severity and adaptive functioning of 69 youth, ages 8-16 years with ASD without intellectual disability. Parent/caregiver ratings were being collected in fall and spring over approximately two years when the restrictions were imposed four months prior to the final data collection point. Results indicated no significant changes in parent/caregiver ratings of ASD symptom severity, comorbid symptoms severity, social skills, or adaptive behaviors following the stay-at-home restrictions and little variability across the four data collection points. Although findings suggested minimal short-term effects on these symptoms and adaptive skills, ongoing monitoring is needed to assess longer-term impacts., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Objective: This study tested the efficacy of an intensive outpatient psychosocial treatment for children with autism spectrum disorder (ASD) without intellectual disability (ID). Method: Eighty-eight children (ages 7-12 years) were randomly assigned to the treatment or control (waitlist) condition. The 18-week cognitive-behavioral treatment (two 90-min sessions per week) included small-group instruction and therapeutic activities targeting social/social-communication skills, face-emotion recognition, nonliteral language skills, and interest expansion. A behavioral system was used to increase skills development and reduce ASD symptoms. Efficacy was tested immediately following treatment (posttest), with maintenance assessed 4-6 weeks later (follow-up). Measures included parent ratings of the children's social/social-communication skills, ASD symptoms, broad social skills, and behavior symptoms, child tests of social-cognitive skills (emotion recognition and nonliteral language), and behavioral observations. Results: Significant effects favoring the treatment group were found at posttest on the primary measures of ASD symptoms (Social Responsiveness Scale, Second Edition; Constantino & Gruber, 2012) and social/social-communication skills (Adapted Skillstreaming Checklist; Lopata, Thomeer, Volker, Nida & Lee, 2008), and secondary measures of nonliteral language skills, broad social skills, and behavior symptoms (measures of emotion-recognition skills and social behaviors during structured game sessions were non-significant). The significant treatment effects found at posttest were all maintained at follow-up. Conclusions: The outpatient treatment improved several core areas of functioning for children with ASD without ID. Additional elements may be needed to expand the efficacy of the treatment so that the observed skills/symptom improvements generalize to social interactions during gameplay.

Objectives: The present research used a continuous measurement approach to extend the evidence that autism is associated with significant struggles in physical health as well as mental health and psychological well-being., Methods: The relationship of autism characteristics to physical health and psychological well-being was examined in 294 individuals (M age = 70.51, SD age = 8.17, age range = 53-96). The sample is 57.4% female (n = 166) and primarily White (n = 270, 96.8%). The majority of the participants did not identify as having an autism diagnosis (n = 284, 96.6%). Participants completed the Autism-Spectrum Quotient Scale alongside self-report measures of physical health, mental health, and psychological well-being., Results: Autism characteristics correlated strongly with challenges in social engagement due to poor health (r = 0.46), depression (r = 0.39) and anxiety (r = 0.47), limitations due to poor mental health (r = 0.41), satisfaction with life (r = -0.47), and psychological well-being (r = -0.62)., Discussion: These findings help shed light on the challenges experienced by individuals aging with elevated autism characteristics. The limitations of this study and prior work on this topic help identify important avenues for future research in this area., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study examined the psychometric characteristics of the Cambridge-Mindreading Face-Voice Battery for Children (CAM-C) for a sample of 333 children, ages 6-12 years with ASD (with no intellectual disability). Internal consistency was very good for the Total score (0.81 for both Faces and Voices) and respectable for the Complex emotions score (0.72 for Faces and 0.74 for Voices); however, internal consistency was lower for Simple emotions (0.65 for Faces and 0.61 for Voices). Test-retest reliability at 18 and 36 weeks was very good for the faces and voices total (0.76-0.81) and good for simple and complex faces and voices (0.53-0.75). Significant correlations were found between CAM-C Faces and scores on another measure of face-emotion recognition (Diagnostic Analysis of Nonverbal Accuracy-Second Edition), and between Faces and Voices scores and child age, IQ (except perceptual IQ and Simple Voice emotions), and language ability. Parent-reported ASD symptom severity and the Emotion Recognition scale on the SRS-2 were not related to CAM-C scores. Suggestions for future studies and further development of the CAM-C are provided. LAY SUMMARY: Facial and vocal emotion recognition are important for social interaction and have been identified as a challenge for individuals with autism spectrum disorder. Emotion recognition is an area frequently targeted by interventions. This study evaluated a measure of emotion recognition (the CAM-C) for its consistency and validity in a large sample of children with autism. The study found the CAM-C showed many strengths needed to accurately measure the change in emotion recognition during intervention., (© 2021 International Society for Autism Research and Wiley Periodicals LLC.)

Purpose : Children with autism spectrum disorder (ASD) without intellectual disability (ID) exhibit social and motor impairments and circumscribed interests/behaviors that contribute to lower physical activity (PA) levels. Despite the need for exercise interventions for these children, there is a dearth of evidence-based treatments. This study tested the feasibility of a high-intensity exercise program for children with ASD without ID, and associated changes in physical performance. Method : Fifty-eight children, ages 7-12 with ASD without ID participated. The intervention (5 weeks, 19 sessions, 60 mins ea.) was conducted during the summer. Each session was manualized (operationalized instructional procedure and curriculum) and targeted components of fitness and motor performance using skill development exercises, workouts, and game-related activities. Feasibility was assessed via fidelity (implementation accuracy), satisfaction surveys, attrition, and injuries. Physical performance was tested at baseline and posttest using measures of work production (completed rounds of an exercise circuit) and within-session activity levels (time in moderate-to-vigorous PA), and six exercise tests (sit and reach, push-ups, sit-ups, air squats, long jump, and PACER). Results : Results indicated high levels of fidelity (93.7%) and child and staff satisfaction, and no attrition or injuries, supporting the feasibility, tolerability, and safety of the protocol. Significant increases were found in work production and activity levels ( d s 0.83 and 1.05, respectively) and on three exercise tests (sit ups, air squats, and long jump; d s 0.29-0.37). Conclusion : The exercise program was feasible and safe, and completion was associated with significant improvements in multiple areas of performance; a randomized controlled trial appears warranted.

Background: The historical focus on autism as a childhood disorder means that evidence regarding autism in adulthood lags significantly behind research in other age groups. Emerging studies on the relationship of age with autism characteristics do not target older adult samples, which presents a barrier to studying the important variability that exists in life span developmental research. This study aims to further our understanding of the relationship between the Autism-Spectrum Quotient Scale and age in a large adult sample. Methods: The present study examines the relationship of Autism-Spectrum Quotient Scale (AQ) scores with age in 1139 adults, ages 18-97 years. Participants came from three distinct samples-a sample of primarily students, a sample of MTurk participants, and a sample of primarily community dwelling older adults. The majority of the participants did not self-report an autism diagnosis (91%), were female (67%), and identified as White (81%). Participants completed the AQ primarily via online surveys. Researchers scored the AQ following six common scoring practices. Results: Results of preregistered analyses indicate that autism characteristics measured by the AQ are not strongly associated with age ( r values from -0.01 to -0.11). Further findings indicate that the measurement of autism characteristics is consistent across age into late life using both multiple groups and local structural equation modeling approaches to measurement invariance (comparative fit indices = 0.82-0.83, root mean square error = 0.06) as well as reliability analysis. Finally, demographic and autism-related variables (sex, race, self-identified autism spectrum disorder diagnosis, and degree of autism characteristics) did not moderate the relationship between age and autism characteristics. Conclusion: These results suggest that self-reports of autism characteristics using the AQ do not vary strongly by age in this large age-representative sample. Findings suggest that the AQ can potentially serve as a useful tool for future research on autism across the life span. Important limitations on what we can learn from these findings point toward critical avenues for future research in this area., Lay Summary: Why was this study done?: Self-report questionnaires of autism characteristics are a potentially important resource for studying autism in adulthood. This study sought to provide additional information about one of the most commonly used self-report questionnaires, the Autism-Spectrum Quotient Scale (AQ), across adulthood. What was the purpose of this study?: This study intended to determine if there is a relationship between scores on the AQ and age. Researchers also worked to identify which of the multiple different ways of scoring the AQ worked best across adulthood. What did the researchers do?: Researchers collected data from over a thousand participants aged 18-97 years. Participants from three different age groups completed online surveys to self-report their levels of autism characteristics on the AQ. Researchers tested the relationship between AQ scores and age with six different commonly used ways to calculate AQ scores. Researchers used multiple statistical techniques to evaluate various measurement properties of the AQ. What were the results of the study?: The results indicate that autism characteristics measured by the AQ are not strongly associated with age. Along with that, there is evidence that certain approaches to measuring of autism characteristics are consistent across age into late life and do not vary with demographic and autism-related factors. What do these findings add to what was already known?: These results add to the growing evidence that self-reports of autism characteristics using the AQ in general samples are not strongly associated with age across adulthood. These findings also provide guidance about ways of scoring the AQ that work well through late life. What are potential weaknesses in the study?: While the AQ has a degree of relationship with autism diagnoses, this is far from perfect and has not been evaluated in the context of aging research. Therefore, findings from the present research must be carefully interpreted to be about autism characteristics not diagnoses. The sample was also limited in a number of other ways. As in any studies including a broad age range of individuals, the oldest participants are likely quite healthy, engaged individuals. This may particularly be the case given the higher mortality rates and health challenges seen with autism. Similarly, as with any self-report research, this research is limited to those individuals who could answer questions about their autism characteristics. The sample was also predominantly White and nonautistic. Finally, the research was limited to one point in time and so cannot tell us about how autism characteristics may change across adulthood. How will these findings help autistic adults now or in the future?: These findings support the potential for the AQ to be a useful tool for future research on autism in adulthood. For example, researchers can use measures such as the AQ to study how autism characteristics change over time or are associated with aging-related issues such as changes in physical health and memory. Such research may be able to provide a better understanding of how to support autistic individuals across adulthood., Competing Interests: No competing financial interests exist., (Copyright 2021, Mary Ann Liebert, Inc., publishers.)

This study examined sex differences in externalizing and internalizing symptoms of children with ASD without intellectual disability (ID). The sample (n = 80) included 40 girls and 40 boys, ages 6-12 years, with ASD (without ID) matched on age and IQ. Externalizing and internalizing symptoms were significantly elevated for this sample (girls and boys) relative to normative estimates for all the scales (hyperactivity, aggression, anxiety, and depression) except conduct problems. No significant differences were found between girls and boys for either externalizing symptoms or internalizing symptoms (based on standard score and raw score analyses). Implications for clinical practice and future research are discussed.

A prior cluster randomized controlled trial (RCT) compared outcomes for a comprehensive school intervention (schoolMAX) to typical educational programming (services-as-usual [SAU]) for 103 children with autism spectrum disorder (ASD) without intellectual disability. The schoolMAX intervention was superior to SAU in improving social-cognitive understanding (emotion-recognition), social/social-communication skills, and ASD-related impairment (symptoms). In the current study, a range of demographic, clinical, and school variables were tested as potential moderators of treatment outcomes from the prior RCT. Moderation effects were not evident in demographics, child IQ, language, or ASD diagnostic symptoms, or school SES. Baseline externalizing symptoms moderated the outcome of social-cognitive understanding and adaptive skills moderated the outcome of ASD-related symptoms (no other comorbid symptoms or adaptive skills ratings moderated outcomes on the three measures). Overall, findings suggest that the main effects of treatment were, with two exceptions, unaffected by third variables.

This study assessed the reliability and criterion-related validity of teacher ratings on the Adapted Skillstreaming Checklist for a sample of 133 children, aged 6-11 years, with autism spectrum disorder (without intellectual disability). Internal consistency for the total sample was 0.93. For a subsample, test-retest reliability was very good ( r  = 0.74; intraclass correlation coefficient = 0.85) at a 9-month interval. Child age, intelligence quotient, language abilities, and sex were not associated with the Adapted Skillstreaming Checklist total score. The Adapted Skillstreaming Checklist total score was inversely and strongly related to teacher ratings of autism spectrum disorder symptom severity. Significant positive correlations (moderate-to-high) were found between the Adapted Skillstreaming Checklist and prosocial skills scales and significant negative correlations (low-to-moderate) with problem behavior scales on a broad measure of child functioning. Implications and suggestions for future study are discussed.

The present study compared parent ratings to self-report ratings of depression, anxiety, hyperactivity, attention problems, and atypical behaviors in youth with high-functioning autism spectrum disorder (HFASD) and typically developing (TD) controls. Measures included parent and self-report forms from the Behavioral Assessment System for Children-Second Edition (BASC-2), and self-report forms from the Children's Depression Inventory (CDI) and the Multidimensional Anxiety Scale for Children (MASC). Results across all five BASC-2 scales indicated parent ratings for the HFASD condition were significantly higher than HFASD self-ratings, and were significantly higher than parent and self-ratings from the TD condition. In addition, average self-report scores did not differ significantly between HFASD and TD conditions on any of the BASC-2 scales, the CDI, or the MASC.

The Adapted Skillstreaming Checklist measures social/social-communication skills and behavioral flexibility/regulation of children with autism spectrum disorder without intellectual disability. Prior studies provided support for the reliability and criterion-related validity of the Adapted Skillstreaming Checklist total score for these children; however, no studies have examined the Adapted Skillstreaming Checklist factor structure. This exploratory factor analysis examined the factor structure and internal consistency of parent ratings on the Adapted Skillstreaming Checklist for a sample of 331 children, ages 6-12 years, with autism spectrum disorder without intellectual disability. Results yielded a correlated three-factor solution. The individual factors and total score demonstrated very good internal consistency reliability. Findings supported the presence and interpretability of three subscales, as well as derivation of a total composite reflecting overall prosocial and adaptive skills and behaviors. Implications for assessment and research are discussed.

Background: The proliferation of computerized neuropsychological assessment devices (CNADs) for screening and monitoring cognitive impairment is increasing exponentially. Previous reviews of computerized tests for multiple sclerosis (MS) were primarily qualitative and did not rigorously compare CNADs on psychometric properties., Objective: We aimed to systematically review the literature on the use of CNADs in MS and identify test batteries and single tests with good evidence for reliability and validity., Method: A search of four major online databases was conducted for publications related to computerized testing and MS. Test-retest reliability and validity coefficients and effect sizes were recorded for each CNAD test, along with administration characteristics., Results: We identified 11 batteries and 33 individual tests from 120 peer-reviewed articles meeting the inclusion criteria. CNADs with the strongest psychometric support include the CogState Brief Battery, Cognitive Drug Research Battery, NeuroTrax, CNS-Vital Signs, and computer-based administrations of the Symbol Digit Modalities Test., Conclusion: We identified several CNADs that are valid to screen for MS-related cognitive impairment, or to supplement full, conventional neuropsychological assessment. The necessity of testing with a technician, and in a controlled clinic/laboratory environment, remains uncertain.

There are currently no empirically supported, comprehensive school-based interventions (CSBIs) for children with autism spectrum disorder (ASD) without concomitant intellectual and language disability. This study compared outcomes for a CSBI (schoolMAX) to typical educational programming (services-as-usual [SAU]) for these children. A total of 103 children (6-12 years of age) with ASD (without intellectual and language disability) were randomly assigned by school buildings (clusters) to receive the CSBI ( n =  52 completed) or SAU ( n  = 50 completed). The CSBI was implemented by trained school personnel and targeted social competence and ASD symptoms using social skills groups, emotion recognition instruction, therapeutic activities, behavioral reinforcement, and parent training. Outcome measures tested the effects of the CSBI on social competence and ASD symptoms, as well as potential collateral effects on academic achievement. Outcomes (baseline-to-follow-up) were assessed using tests of social cognition and academic skills and behavioral observations (by masked evaluators) and parent-teacher ratings of ASD symptoms and social/social-communication skills (nonmasked; ClinicalTrials.gov, NCT03338530, https://www.clinicaltrials.gov/). The CSBI group improved significantly more than the SAU group on the test of emotion recognition skills and parent-teacher ratings of ASD symptoms (primary outcomes) and social/social-communication skills (secondary outcome). No differences between groups were detected for recess social interactions or academic skills. The CSBI improved several core areas of functioning for children with ASD compared to usual educational programming. Additional intervention elements may be needed to expand the efficacy of the CSBI so that the observed skills/symptom improvements generalize to recess social interactions and/or academic skills are enhanced.

This study examined psychometric characteristics of the Diagnostic Analysis of Nonverbal Accuracy-Second Edition (DANVA-2) in 121 children, ages 6 to 13 years, with high-functioning autism spectrum disorder (HFASD). Internal consistency for adult and child faces subtests were .70 and .75, respectively. Immediate test-retest reliability in the total sample (N = 121) ranged from .78 to .84. Reliability for two subsamples for 5- (n = 21) and 12-week (n = 21) intervals ranged from .75 to .90 and from .43 to .68, respectively. DANVA-2 scores strongly converged with two measures of emotion recognition but were unrelated to parent ratings of social functioning and ASD symptoms. Significant correlations (small to medium) were found between DANVA-2 scores and child age, IQ, and language ability.

In the last decade, the prevalence of children with autism spectrum disorder (ASD) without intellectual disability (ID) in schools has increased. However, there is a paucity of information on special education placement, service use, and relationships between service use and demographic variables for children with ASD without ID. This study aimed to describe and explore variation in type and amount of special education services provided to (N = 89) children with ASD. Results indicated that the largest percentage of children received services under the Autism classification (56.2%) and were in partial-inclusion settings (40.4%). The main services received were speech (70.8%) and occupational (56.2%) therapies, while few children received behavior plans (15.7%) or social skills instruction (16.9%). Correlates with service use are described.

This study examined informant discrepancies for parent and teacher adaptive behavior ratings of 103 children, ages 6-12 years, with ASD (without intellectual disability). Scores on the Adaptive Behavior Assessment System, third edition (Harrison and Oakland, Western Psychological Services, Los Angeles, 2015) General Adaptive Composite (GAC) and practical, social, and conceptual domains were examined for mean differences, level of agreement, and moderators of difference scores between informant groups. Teacher scores were significantly higher (indicating better functioning) than parents for the GAC and practical domain. Parent and teacher scores were moderately correlated and Bland-Altman plots and regression analyses revealed no systematic differences in parent-teacher agreement across the range of scores. None of the tested variables moderated the parent-teacher difference scores. Implications for clinical practice are discussed.

The present meta-analysis synthesizes the emerging literature on the relationship of Big Five personality traits to autism spectrum disorder. Studies were included if they (1) either (a) measured autism spectrum disorder characteristics using a metric that yielded a single score quantification of the magnitude of autism spectrum disorder characteristics and/or (b) studied individuals with an autism spectrum disorder diagnosis compared to individuals without an autism spectrum disorder diagnosis and (2) measured Big Five traits in the same sample or samples. Fourteen reviewed studies include both correlational analyses and group comparisons. Eighteen effect sizes per Big Five trait were used to calculate two overall effect sizes per trait. Meta-analytic effects were calculated using random effects models. Twelve effects (per trait) from nine studies reporting correlations yielded a negative association between each Big Five personality trait and autism spectrum disorder characteristics (Fisher's z ranged from -.21 (conscientiousness) to -.50 (extraversion)). Six group contrasts (per trait) from six studies comparing individuals diagnosed with autism spectrum disorder to neurotypical individuals were also substantial (Hedges' g ranged from -.88 (conscientiousness) to -1.42 (extraversion)). The potential impact of personality on important life outcomes and new directions for future research on personality in autism spectrum disorder are discussed in light of results.

Prior studies of sex-based differences in autism spectrum disorder (ASD) have yielded mixed findings. This study examined ASD symptom severity and functional correlates in a sample of 34 high-functioning females with ASD (HFASD; M age = 8.93; M IQ = 104.64) compared to 34 matched males (M age = 8.96; M IQ = 104.44) using the Social Responsiveness Scale-Second Edition (SRS-2). Results identified non-significant and minimal differences (negligible-to-small) on the SRS-2 total, DSM-5 symptom subscale, and treatment subscale scores. Significant negative (moderate) correlations were found between the SRS-2 Social Cognition subscale and IQ and language scores and between the SRS-2 Social Motivation subscale and receptive language scores for females only; no significant correlations were found for males.

This community effectiveness randomized clinical trial examined the feasibility and effectiveness of a comprehensive psychosocial treatment, summerMAX, when implemented by a community agency. Fifty-seven high-functioning children (48 male, 9 female), ages 7-12 years with autism spectrum disorder participated in this study. The 5-week summerMAX treatment included instruction and therapeutic activities targeting social/social-communication skills, interpretation of nonliteral language skills, face-emotion recognition skills, and interest expansion. A behavioral program was also used to increase skills acquisition and decrease autism spectrum disorder symptoms and problem behaviors. Feasibility was supported via high levels of fidelity and parent, child, and staff clinician satisfaction. Significant treatment effects favoring the treatment group over waitlist controls were found on all 5 of the primary outcome measures (i.e., child test of nonliteral language skills and parent ratings of the children's autism spectrum disorder symptoms, targeted social/social-communication skills, broader social performance, and withdrawal). Staff clinician ratings substantiated the improvements reported by parents. Results of this randomized clinical trial are consistent with those of prior studies of summerMAX and suggest that the program was feasible and effective when implemented by a community agency under real-world conditions.

Poultry accounts for a high proportion of human campylobacteriosis cases, and the problem of Campylobacter colonization of broiler flocks has proven to be intractable. Owing to their broad host range and genetic instability, Campylobacter organisms are ubiquitous and adaptable in the broiler farm environment, colonizing birds heavily and spreading rapidly after introduction into a flock. This review examines strategies to prevent or suppress such colonization, with a heavy emphasis on field investigations. Attempts to exclude Campylobacter via enhanced biosecurity and hygiene measures have met with mixed success. Reasons for this are becoming better understood as investigations focus on houses, ventilation, biosecurity practices, external operators, and compliance, among other factors. It is evident that piecemeal approaches are likely to fail. Complementary measures include feed and drinking water treatments applied in either preventive or suppressive modes using agents including organic acids and their derivatives, also litter treatments, probiotics, prebiotics, and alterations to diet. Some treatments aim to reduce the number of Campylobacter organisms entering abattoirs by suppressing intestinal colonization just before slaughter; these include acid water treatment or administration of bacteriophages or bacteriocins. Experimental vaccines historically have had little success, but some recent subunit vaccines show promise. Overall, there is wide variation in the control achieved, and consistency and harmonization of trials is needed to enable robust evaluation. There is also some potential to breed for resistance to Campylobacter. Good and consistent control of flock colonization by Campylobacter may require an as-yet undetermined combination of excellent biosecurity plus complementary measures., (© 2018 Crown copyright. This article Field Interventions Against Colonization of Broilers by Campylobacter was written by Andrew D. Wales, Ana B. Vidal, Robert H. Davies, and John D. Rodgers of Department of Pathology and Infectious Diseases; Veterinary Medicines Directorate; Department of Bacteriology and Food Safety; Bacteriology and Food Safety. It is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)

Autism spectrum disorder (ASD) impacts well-being across the lifespan. Individuals with ASD evidence differences in personality traits and self-concept clarity that are predictors of well-being in typically-developing individuals. The current research replicates a growing body of evidence demonstrating differences in well-being and personality between individuals low in ASD characteristics (n = 207) and individuals high in ASD characteristics (n = 46) collected from the general population using an online survey. Results were consistent in a subsample of demographically matched pairs (n = 39 per group) and relative to norms. Further, the current research provides the first evidence that openness, conscientiousness, emotional stability, and self-concept clarity mediate the relationship between ASD characteristics and well-being.

This study examined the reliability and criterion-related validity of parent ratings on the Adapted Skillstreaming Checklist (ASC) for a sample of 275 high-functioning children, ages 6-12 years, with ASD. Internal consistency for the total sample was 0.92. For two subsamples, test-retest reliability was very good at the 6-week and good at the 9-month intervals. Child age, IQ, and language abilities were unrelated to the ASC score. The ASC total score was inversely and strongly related to parent ratings of ASD symptom severity. Significant positive correlations (moderate-to-high) were found between the ASC and prosocial skills scales and significant negative correlations (low-to-moderate) with problem behavior scales on a broad measure of child functioning. Implications and suggestions for future study are discussed.

Broiler chicken flocks are a significant source of Campylobacter jejuni and Campylobacter coli that result in the major public health problem of campylobacteriosis. Accurate estimates of the prevalence of both C. coli and C. jejuni in flocks would enhance epidemiological understanding, risk assessment and control options. This study combined results from a panel of 10 detection tests (direct culture, enrichment and PCR) on caecal samples from flocks at slaughter. A parallel interpretation approach was used to determine the presence of Campylobacter spp. and for C. jejuni and C. coli individually. The sample was considered positive if at least one method detected the target and this interpretation was taken to represent a 'proxy gold standard' for detection in the absence of a gold standard reference test. The sensitivity of each individual method to detect Campylobacter spp., C. jejuni and C. coli was then estimated relative to the proxy gold standard. Enrichment in adapted Exeter broth (deficient in polymyxin B) with a resuscitation step was 100% sensitive, whilst direct culture on modified charcoal cefoperazone deoxycholate agar (mCCDA) was highly sensitive (97.9%). Enrichment methods using Preston broth and Bolton broth were significantly less sensitive. Enrichment in Exeter broth promoted the recovery of C. jejuni, whilst enrichment in Bolton broth favoured C. coli. A RT-PCR detection test could identify 80% of flocks that were co-colonised with both species. This study found that 76.3% (n = 127) of flocks were colonised with Campylobacter spp. The majority (95.9%) of Campylobacter-positive flocks were colonised with C. jejuni; however, approximately one-third of positive flocks were simultaneously colonised with both C. jejuni and C. coli. The findings highlight the impact of different detection methodologies on the accuracy of the estimated incidence of both C. jejuni and C. coli entering the abattoir within broiler flocks and the associated public health risks., (© 2016 Crown copyright. Zoonoses and Public Health published by Blackwell Verlag GmbH. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)

This study extended the research on correlates of adaptive functioning of high-functioning children with autism spectrum disorder (HFASD) using the Behavior Assessment System for Children-Second Edition (BASC-2). Specifically, this study investigated the relationships between adaptive behavior and age, IQ, and ASD symptomology, in a well-characterized sample of 119 children with HFASD, ages 6-11 years. Results revealed age and IQ were not significantly correlated with adaptive ability. However, total autism symptoms [measured by the Autism Diagnostic Interview-Revised (ADI-R)], as well as ASD-social symptoms were negatively correlated with adaptive ability. Mean comparisons revealed that participants falling into the clinically-significant range of the BASC-2 Adaptive Skills Composite (ASC) displayed significantly greater levels of both overall and social ASD symptoms.

This study examined the feasibility and initial outcomes of a comprehensive outpatient psychosocial treatment (MAXout) for children aged 7-12 years with high-functioning autism spectrum disorder. The 18-week treatment, two 90-minute sessions per week, included instruction and therapeutic activities targeting social/social communication skills, facial emotion recognition, non-literal language skills, and interest expansion. A behavioral system was implemented to reduce autism spectrum disorder symptoms and problem behaviors and increase skills acquisition and maintenance. Feasibility was supported via high levels of treatment fidelity and parent, child, and staff satisfaction. Significant post-treatment improvements were found for the children's non-literal language skills and facial emotion recognition skills, and parent and staff clinician ratings of targeted social/social communication skills, broad social skills, autism spectrum disorder symptoms, and problem behaviors. Results suggested that MAXout was feasible and may yield positive outcomes for children with high-functioning autism spectrum disorder., (© The Author(s) 2016.)

Assessment of clinical symptoms requires information from multiple informants. Discrepancies between informants' ratings can have significant implications in school settings (e.g., access to services, treatment planning, progress monitoring). This study examined parent-teacher discrepancies for ratings of internalizing and externalizing symptoms, and adaptive skills of high-functioning children with autism spectrum disorder. A total of 236 Behavior Assessment System for Children-2nd Edition ratings of children with high-functioning children with autism spectrum disorder from 2 informant groups (parents and teachers) were analyzed. Each informant pair (n = 118 parents/caregivers and n = 118 teachers) rated the same child. Scores on the Internalizing Problems, Externalizing Problems, and Adaptive Skills Composites were examined for mean differences, level of agreement, linear relationship, and moderators of discrepancies. There were no significant mean differences between raters for the Internalizing and Externalizing Composites or their constituent scales (except Hyperactivity). Parent-teacher ratings on these composites and scales were significantly correlated (generally moderate), and the discrepancies were not moderated by the included child or parent variables. In contrast, teacher ratings were significantly higher than parents for the Adaptive Skills Composite and several of its constituent scales. Correlations between informants on the Adaptive Skills Composite were significant (low-to-moderate), with notable variability in the correlations among its constituent scales. The degree of parent-teacher discrepancy differed significantly across the Adaptive Skills Composite score range, but it was not moderated by the included child or parent variables. This study suggests a reduced likelihood of informant discrepancies for externalizing and internalizing symptoms, with larger discrepancies expected when assessing adaptive skills. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

This study compared parent and teacher ratings of ASD-related symptoms of 120 high-functioning children, ages 6-12 years with ASD (HFASD) using the Developmental Social Disorders (DSD) scale of the BASC-2. DSD ratings (parent and teacher) were significantly higher than normative estimates. The cross-informant comparison was significantly higher for parents (vs. teachers), and correlations (ICC and Pearson) between the informant groups were significant (but low in magnitude). Agreement among parents and teachers accurately placed 81 % of cases above the at-risk cutpoint for symptoms of ASD, and agreement was highest in the at-risk range of perceived symptoms. Additional analyses indicated a significant difference in the trend across the parent-teacher discrepancies, and no significant moderators of the discrepancies. Implications for assessment are provided.

The Gilliam Autism Rating Scale-Second Edition (GARS-2) is a widely used screening instrument that assists in the identification and diagnosis of autism. The purpose of this study was to examine the factor structure, internal consistency, and screening sensitivity of the GARS-2 using ratings from special education teaching staff for a sample of 240 individuals with autism or other significant developmental disabilities. Exploratory factor analysis yielded a correlated three-factor solution similar to that found in 2005 by Lecavalier for the original GARS. Though the three factors appeared to be reasonably consistent with the intended constructs of the three GARS-2 subscales, the analysis indicated that more than a third of the GARS-2 items were assigned to the wrong subscale. Internal consistency estimates met or exceeded standards for screening and were generally higher than those in previous studies. Screening sensitivity was .65 and specificity was .81 for the Autism Index using a cut score of 85. Based on these findings, recommendations are made for instrument revision.

Background: Utilizing proxy report is a common solution to gathering quality-of-life information from people who are not capable of reliably answering questionnaires, such as people with dementia. Proxy report could, however, also provide information about patients' implicit processes of understanding, which we define as automatic, schema-driven cognitive processes that allow one to have a better understanding of oneself and of one's body, make oneself known and knowable to members of the social network, and allow one to react proactively in response to cues. We investigated whether implicit processes of understanding explain some of the association between reserve and healthy lifestyle behaviors., Methods: We operationalized three implicit processes of understanding: (a) psychosocial understanding; (b) insight into physical disability; and (c) somatic awareness. This secondary analysis involved a cohort of multiple sclerosis patients and their caregiver informants (n = 118 pairs). Measures included a neurologist-administered Expanded Disability Status Scale, patient- and informant-completed survey measures, and a heartbeat perception test (interoception). Patient-other congruence assessed implicit processes of understanding: psychosocial understanding (neurocognitive and personality); physical-disability insight; and somatic awareness (interoception)., Results: Effect sizes (ES) for the inter-correlations between the three implicit processes were small. Psychosocial understanding was associated with higher past reserve-building activities (small ES). Psychosocial understanding explained variance in healthy lifestyle behaviors over and above the variance explained by current reserve-building activities (∆R (2) = 0.04; model R Adjusted (2) = 0.18)., Conclusions: Proxy versus patient report can provide information about underlying interpretational processes related to insight. These processes are distinct from reserve, predict health outcomes, and can inform lifestyle-changing interventions.

This randomized controlled trial evaluated the efficacy of a computer software (i.e., Mind Reading) and in vivo rehearsal treatment on the emotion decoding and encoding skills, autism symptoms, and social skills of 43 children, ages 7-12 years with high-functioning autism spectrum disorder (HFASD). Children in treatment (n = 22) received the manualized protocol over 12 weeks. Primary analyses indicated significantly better posttest performance for the treatment group (compared to controls) on 3 of the 4 measures of emotion decoding and encoding and these were maintained at 5-week follow-up. Analyses of secondary measures favored the treatment group for 1 of the 2 measures; specifically, ASD symptoms were significantly lower at posttest and follow-up.

Background: Unemployment is common in multiple sclerosis (MS) and detrimental to quality of life. Studies suggest disclosure of diagnosis is an adaptive strategy for patients. However, the role of cognitive deficits and psychiatric symptoms in disclosure are not well studied., Objective: The goals of this paper were to (a) determine clinical factors most predictive of disclosure, and (b) measure the effects of disclosure on workplace problems and accommodations in employed patients., Methods: We studied two overlapping cohorts: a cross-sectional sample (n = 143) to determine outcomes associated with disclosure, and a longitudinal sample (n = 103) compared at four time points over one year on reported problems and accommodations. A case study of six patients, disclosing during monitoring, was also included., Results: Disclosure was associated with greater physical disability but not cognitive impairment. Logistic regression predicting disclosure status retained physical disability, accommodations and years of employment (p < 0.0001). Disclosed patients reported more work problems and accommodations over time. The case study revealed that reasons for disclosing are multifaceted, including connection to employer, decreased mobility and problems at work., Conclusion: Although cognitive impairment is linked to unemployment, it does not appear to inform disclosure decisions. Early disclosure may help maintain employment if followed by appropriate accommodations., (© The Author(s), 2014.)

The objective of this study was to estimate the sensitivity and specificity of a culture method and a polymerase chain reaction (PCR) method for detection of two Campylobacter species: C. jejuni and C. coli. Data were collected during a 3-year survey of UK broiler flocks, and consisted of parallel sampling of caeca from 436 batches of birds by both PCR and culture. Batches were stratified by season (summer/non-summer) and whether they were the first depopulation of the flock, resulting in four sub-populations. A Bayesian approach in the absence of a gold standard was adopted, and the sensitivity and specificity of the PCR and culture for each Campylobacter subtype was estimated, along with the true C. jejuni and C. coli prevalence in each sub-population. Results indicated that the sensitivity of the culture method was higher than that of PCR in detecting both species when the samples were derived from populations infected with at most one species of Campylobacter. However, from a mixed population, the sensitivity of culture for detecting both C. jejuni or C. coli is reduced while PCR is potentially able to detect both species, although the total probability of correctly identifying at least one species by PCR is similar to that of the culture method.

Work disability is common in multiple sclerosis (MS) and cognitive disorder discriminates disabled from employed patients. Our goal was to develop and validate an online vocational status monitoring tool measuring negative work events and use of accommodations. We enrolled 52 employed patients completing an online survey and a clinical examination including tests of motor function, cognitive abilities, and depression. The survey recorded a wide range of reported work problems. Regression models predicting negative work events, and use of accommodations, retained measures of ambulation, cognition, and depression. These data provide preliminary support for the validity of online vocational monitoring in MS.

Recent research indicates that cognitive reserve mitigates the clinical expression of neuropsychological impairment in multiple sclerosis (MS). This literature primarily uses premorbid intelligence and lifetime experiences as indicators. However, changes in current recreational activities may also contribute to the maintenance of neural function despite brain atrophy. We examined the moderation effects of current changes in recreational activity on the relationship between brain atrophy and information processing speed in 57 relapsing-remitting MS patients. Current enrichment was assessed using the Recreation and Pastimes subscale from the Sickness Impact Profile. In patients reporting current declines in recreational activities, brain atrophy was negatively associated with cognition, but there was no such association in participants reporting stable participation. The MRI metric-by-recreational activity interaction was significant in separate hierarchical regression analyses conducted using third ventricle width, neocortical volume, T2 lesion volume, and thalamic volume as brain measures. Results suggest that recreational activities protect against brain atrophy's detrimental influence on cognition.

Study Design: Cadaveric imaging study., Objective: We sought to compare the fluoroscopic images produced by 4 different fluoroscopes for image quality and radiation exposure when used for imaging the spine., Summary of Background Data: There are no previous published studies comparing mobile C-arm machines commonly used in clinical practice for imaging the spine., Methods: Anterior-posterior and lateral images of the cervical, thoracic, and lumbar spine were obtained from a cadaver placed supine on a radiolucent table. The fluoroscopy units used for the study included (1) GE OEC 9900 Elite (2010 model; General Electric Healthcare, Waukesha, WI), (2) Philips BV Pulsera (2009 model; Philips Healthcare, Andover, MA), (3) Philips BV Pulsera (2010 model; Philips Healthcare, Andover, MA), and (4) Siemens Arcadis Avantic (2010 model; Siemens Medical Solutions, Malvern, PA). The images were then downloaded, placed into a randomizer program, and evaluated by a group of spine surgeons and neuroradiologists independently. The reviewers, who were blinded to the fluoroscope the images were from, ranked them from best to worst using a numeric system. In addition, the images were rated according to a quality scale from 1 to 5, with 1 representing the best image quality. The radiation exposure level for the fluoroscopy units was also compared and was based on energy emission., Results: According to the mean values for rank, the following order of best to worst was observed: (1) GE OEC > (2) Philips 2010 > (3) Philips 2009 > (4) Siemans. The exact same order was found when examining the image quality ratings. When comparing the radiation exposure level difference, it was observed that the OEC was the lowest, and there was a minimum 30% decrease in energy emission from the OEC versus the other C-arms studied., Conclusion: This is the first time that the spine image quality and radiation exposure of commonly used C-arm machines have been compared. The OEC was ranked the best, produced the best quality images, and had the least amount of radiation.

We examined cognitive predictors of speech and articulation rate in 50 individuals with multiple sclerosis (MS) and 23 healthy controls. We measured speech and articulation rate from audio-recordings of participants reading aloud and talking extemporaneously on a topic of their choice (i.e., self-generated speech). Articulation rate was calculated for each speech sample by removing lexically irrelevant vocalizations and pauses of >200 ms. Speech rate was similarly calculated including pauses. Concurrently, the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery, as well as standardized tests of sentence intelligibility and syllable repetition were administered. Analysis of variance showed that MS patients were slower on three of the four rate measures. Greater variance in rate measures was accounted for by cognitive variables for the MS group than controls. An information processing speed composite, as measured by the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT), was the strongest predictor among cognitive tests. A composite of memory tests related to self-generated speech, above and beyond information processing speed, but not to oral reading. Self-generated speech, in this study, was not found to relate more strongly to cognitive tests than simple reading. Implications for further research are discussed.

Detection and enumeration of Campylobacter spp. in broiler chicken flocks are key components of research and surveillance studies aimed at reducing Campylobacter infections in people. Direct culture of caecal contents onto selective agar is the typical method used to confirm flock colonisation. Modified charcoal cefoperazone deoxycholate agar (mCCDA) is commonly used for this method, although alternative selective media have been used. Additionally, PCR methods to detect Campylobacter DNA from caecal contents may provide a rapid alternative. However comparative performance data for these methods is limited and therefore required to ensure optimal detection methods for this sample type. In this study, 306 broiler caeca were tested for Campylobacter using direct culture on mCCDA, Skirrows and Preston agars and two real-time PCR methods, one specific for mapA/ceuE regions and another for the flaA gene region. Additionally, the suitability of spread plating and spiral plating methods for enumeration of Campylobacter and the impact of sample storage were assessed. This study confirmed modified CCDA as an optimal media for detection of Campylobacter in broiler caeca. It was significantly more sensitive than Skirrows or Preston agars. This study also demonstrated that the mapA/ceuE PCR had excellent agreement with culture on mCCDA and is a genuine alternative method. Spread plating and spiral plating methods were suitable for enumeration although spiral plating appeared more sensitive for stored samples (72 h). A 1 log reduction in viable Campylobacters was observed in stored samples, therefore storage effects should be considered for quantitative studies with broiler caeca., (Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.)

This study compared cortisol concentrations yielded using three saliva collection methods (passive drool, salivette, and sorbette) in both in vitro and in vivo conditions, as well as method acceptability for a sample of children (n = 39) with High Functioning Autism Spectrum Disorders. No cortisol concentration differences were observed between passive and sorbette samples obtained in vitro or in vivo. The salivette derived concentration was lower than the other two methods for the in vitro derived comparisons but did not differ from the other methods when collected in vivo. Cross-day comparison for the salivettes was also found to differ significantly, whereas the cross-day comparisons did not differ for the passive method or the sorbette method. Overall, passive drool and sorbettes were found to produce similar and stable readings of cortisol, whereas the salivette yielded unstable and variable concentrations. Ratings suggested that the children generally perceived all methods as acceptable.

JAKs are required for signaling initiated by several cytokines (e.g., IL-4, IL-12, IL-23, thymic stromal lymphopoietin (TSLP), and IFNγ) implicated in the pathogenesis of inflammatory skin diseases such as psoriasis and atopic dermatitis (AD). Direct antagonism of cytokines, such as IL-12 and IL-23 using ustekinumab, has proven effective in randomized studies in psoriasis patients. We hypothesized that local inhibition of cytokine signaling using topical administration of INCB018424, a small molecule inhibitor of JAK1 and JAK2, would provide benefit similar to systemic cytokine neutralization. In cellular assays, INCB018424 inhibits cytokine-induced JAK/signal transducers and activators of transcription (STAT) signaling and the resultant production of inflammatory proteins (e.g., IL-17, monocyte chemotactic protein-1, and IL-22) in lymphocytes and monocytes, with half-maximal inhibitory concentration values <100  nM. In vivo, topical application of INCB018424 resulted in suppression of STAT3 phosphorylation, edema, lymphocyte infiltration, and keratinocyte proliferation in a murine contact hypersensitivity model and inhibited tissue inflammation induced by either intradermal IL-23 or TSLP. Topical INCB018424 was also well tolerated in a 28-day safety study in Gottingen minipigs. These results suggest that localized JAK1/JAK2 inhibition may be therapeutic in a range of inflammatory skin disorders such as psoriasis and AD. Clinical evaluation of topical INCB018424 is ongoing.

This RCT examined the efficacy of a manualized social intervention for children with HFASDs. Participants were randomly assigned to treatment or wait-list conditions. Treatment included instruction and therapeutic activities targeting social skills, face-emotion recognition, interest expansion, and interpretation of non-literal language. A response-cost program was applied to reduce problem behaviors and foster skills acquisition. Significant treatment effects were found for five of seven primary outcome measures (parent ratings and direct child measures). Secondary measures based on staff ratings (treatment group only) corroborated gains reported by parents. High levels of parent, child and staff satisfaction were reported, along with high levels of treatment fidelity. Standardized effect size estimates were primarily in the medium and large ranges and favored the treatment group.

Aims: To evaluate the culture specifications of the 2008 EU baseline survey for Campylobacter spp. in broiler flocks at slaughter, by assessing the detection of thermophilic Campylobacter in chicken caecal contents by culture on selective agar with or without enrichment culture. Additionally, to assess the impact of sample storage time on Campylobacter detection., Methods and Results: Serial dilutions of pooled caeca samples in phosphate-buffered saline or Campylobacter-negative caecal contents were cultured micro-aerobically at 41.5°C on mCCDA, Karmali and Preston agars before and after enrichment in Exeter broth. Direct culture on mCCDA showed a higher isolation rate than for Karmali or Preston agars, but a similar isolation rate to enrichment. Enumeration of samples showed the numbers of viable bacteria dropped slightly during storage., Conclusions: Direct culture on mCCDA was the most sensitive method for detection of Campylobacter, and samples with 10(4) CFU g(-1) were still detectable after 6 days., Significance and Impact of the Study: Comparison of prevalence results from the 2008 EU baseline survey will need careful interpretation as the different media specified vary in their sensitivity to detect thermophilic Campylobacter. Delayed culture for up to 80 h after collection should have little impact on detection rate., (© 2010 Crown copyright, c/o the Librarian, Veterinary Laboratory Agency. Journal compilation © 2010 The Society for Applied Microbiology.)

The purpose of this study was to: (1) examine symptom levels of anxiety and depression in children with high-functioning autism spectrum disorders (HFASDs) compared with matched control children using child self-reports and parent ratings; and (2) examine source differences within the two condition groups. An overall multivariate effect indicated significantly elevated depression and anxiety symptoms for children with HFASDs based on parent reports; however no significant between-group differences based on child self-reports. Within-condition source comparisons (parent vs. child) revealed a significant multivariate effect indicating a significant difference in symptoms of depression and anxiety for the HFASD group but none for the control. Correlations between parent and child reports for the HFASD group suggested some positive association between child-reports and parent-reports for depressive symptoms only; however, the difference in average scores reflected a substantial discrepancy in the magnitude of symptoms by rater. Implications for clinical assessment and future research are provided.

Inhibiting signal transduction induced by inflammatory cytokines offers a new approach for the treatment of autoimmune diseases such as rheumatoid arthritis. Kinase inhibitors have shown promising oral disease-modifying antirheumatic drug potential with efficacy similar to anti-TNF biologics. Direct and indirect inhibition of the JAKs, with small molecule inhibitors like CP-690,550 and INCB018424 or neutralizing Abs, such as the anti-IL6 receptor Ab tocilizumab, have demonstrated rapid and sustained improvement in clinical measures of disease, consistent with their respective preclinical experiments. Therefore, it is of interest to identify optimized JAK inhibitors with unique profiles to maximize therapeutic opportunities. INCB028050 is a selective orally bioavailable JAK1/JAK2 inhibitor with nanomolar potency against JAK1 (5.9 nM) and JAK2 (5.7 nM). INCB028050 inhibits intracellular signaling of multiple proinflammatory cytokines including IL-6 and IL-23 at concentrations <50 nM. Significant efficacy, as assessed by improvements in clinical, histologic and radiographic signs of disease, was achieved in the rat adjuvant arthritis model with doses of INCB028050 providing partial and/or periodic inhibition of JAK1/JAK2 and no inhibition of JAK3. Diminution of inflammatory Th1 and Th17 associated cytokine mRNA levels was observed in the draining lymph nodes of treated rats. INCB028050 was also effective in multiple murine models of arthritis, with no evidence of suppression of humoral immunity or adverse hematologic effects. These data suggest that fractional inhibition of JAK1 and JAK2 is sufficient for significant activity in autoimmune disease models. Clinical evaluation of INCB028050 in RA is ongoing.

Constitutive JAK2 activation in hematopoietic cells by the JAK2V617F mutation recapitulates myeloproliferative neoplasm (MPN) phenotypes in mice, establishing JAK2 inhibition as a potential therapeutic strategy. Although most polycythemia vera patients carry the JAK2V617F mutation, half of those with essential thrombocythemia or primary myelofibrosis do not, suggesting alternative mechanisms for constitutive JAK-STAT signaling in MPNs. Most patients with primary myelofibrosis have elevated levels of JAK-dependent proinflammatory cytokines (eg, interleukin-6) consistent with our observation of JAK1 hyperactivation. Accordingly, we evaluated the effectiveness of selective JAK1/2 inhibition in experimental models relevant to MPNs and report on the effects of INCB018424, the first potent, selective, oral JAK1/JAK2 inhibitor to enter the clinic. INCB018424 inhibited interleukin-6 signaling (50% inhibitory concentration [IC(50)] = 281nM), and proliferation of JAK2V617F(+) Ba/F3 cells (IC(50) = 127nM). In primary cultures, INCB018424 preferentially suppressed erythroid progenitor colony formation from JAK2V617F(+) polycythemia vera patients (IC(50) = 67nM) versus healthy donors (IC(50) > 400nM). In a mouse model of JAK2V617F(+) MPN, oral INCB018424 markedly reduced splenomegaly and circulating levels of inflammatory cytokines, and preferentially eliminated neoplastic cells, resulting in significantly prolonged survival without myelosuppressive or immunosuppressive effects. Preliminary clinical results support these preclinical data and establish INCB018424 as a promising oral agent for the treatment of MPNs.

BASC-2 PRS profiles of 62 children with high-functioning autism spectrum disorders (HFASDs) were compared with those of 62 typically-developing children matched by age, gender, and ethnicity. Results indicated that, except for the Somatization, Conduct Problems, and Aggression scales, significant differences were found between the HFASD and typically-developing groups on all PRS scores. Mean HFASD scores were in the clinically significant range on the Behavioral Symptoms Index, Atypicality, Withdrawal, and Developmental Social Disorders scales. At-risk range HFASD means were obtained on the Adaptive Skills composite, all adaptive scales, remaining content scales (except Bullying), and Hyperactivity, Attention Problems, and Depression clinical scales. Screening indices suggested that the Developmental Social Disorders scale was highly effective in differentiating between the two groups.

Purpose: Deregulation of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway is a hallmark for the Philadelphia chromosome-negative myeloproliferative diseases polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We tested the efficacy of a selective JAK1/2 inhibitor in cellular and in vivo models of JAK2-driven malignancy., Experimental Design: A novel inhibitor of JAK1/2 was characterized using kinase assays. Cellular effects of this compound were measured in cell lines bearing the JAK2V617F or JAK1V658F mutation, and its antiproliferative activity against primary polycythemiavera patient cells was determined using clonogenic assays. Antineoplastic activity in vivo was determined using a JAK2V617F-driven xenograft model, and effects of the compound on survival, organomegaly, body weight, and disease-associated inflammatory markers were measured., Results: INCB16562 potently inhibited proliferation of cell lines and primary cells from PV patients carrying the JAK2V617F or JAK1V658F mutation by blocking JAK-STAT signaling and inducing apoptosis. In vivo, INCB16562 reduced malignant cell burden, reversed splenomegaly and normalized splenic architecture, improved body weight gains, and extended survival in a model of JAK2V617F-driven hematologic malignancy. Moreover, these mice suffered from markedly elevated levels of inflammatory cytokines, similar to advanced myeloproliferative disease patients, which was reversed upon treatment., Conclusions: These data showed that administration of the dual JAK1/2 inhibitor INCB16562 reduces malignant cell burden, normalizes spleen size and architecture, suppresses inflammatory cytokines, improves weight gain, and extends survival in a rodent model of JAK2V617F-driven hematologic malignancy. Thus, selective inhibitors of JAK1 and JAK2 represent a novel therapy for the patients with myeloproliferative diseases and other neoplasms associated with JAK dysregulation.