Getting to the heart of the matter-are two agents really better than one for the treatment of staphylococcal infective endocarditis?

The recently published European Society of Cardiology guidelines for infective endocarditis management recommends daptomycin combination therapy for the treatment of staphylococcal endocarditis in severe penicillin allergy, rather than daptomycin monotherapy. We discuss the evidence base behind this recommendation, highlighting concerns regarding the lack of robust clinical studies, increased cost and logistical considerations, and adverse effects of combination therapy. Although further studies are required to elucidate the role of combination vs monotherapy in these patients, we propose a pragmatic management approach to reduce the risk of adverse antimicrobial side effects and limit costs, while aiming to maintain treatment efficacy.

Longitudinal Follow-Up Study of Social Intervention Outcomes for Children on the Autism Spectrum.

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].

Physics-informed neural networks as surrogate models of hydrodynamic simulators.

In response to growing concerns surrounding the relationship between climate change and escalating flood risk, there is an increasing urgency to develop precise and rapid flood prediction models. Although high-resolution flood simulations have made notable advancements, they remain computationally expensive, underscoring the need for efficient machine learning surrogate models. As a result of sparse empirical observation and expensive data collection, there is a growing need for the models to perform effectively in 'small-data' contexts, a characteristic typical of many scientific problems. This research combines the latest developments in surrogate modelling and physics-informed machine learning to propose a novel Physics-Informed Neural Network-based surrogate model for hydrodynamic simulators governed by Shallow Water Equations. The proposed method incorporates physics-based prior information into the neural network structure by encoding the conservation of mass into the model without relying on calculating continuous derivatives in the loss function. The method is demonstrated for a high-resolution inland flood simulation model and a large-scale regional tidal model. The proposed method outperforms the existing state-of-the-art data-driven approaches by up to 25 %. This research demonstrates the benefits and robustness of physics-informed approaches in surrogate modelling for flood and hydroclimatic modelling problems.

Natural infection versus hybrid (natural and vaccination) humoral immune response to SARS-CoV-2: a comparative paired analysis.

Objectives: There is substantial immunological evidence that vaccination following natural infection increases protection. We compare the humoral immune response developed in initially seropositive individuals (naturally infected) to humoral hybrid immune response (developed after infection and vaccination) in the same population group after one year. Methods: The study included 197 male individuals who were naturally infected with SARS-CoV-2 and then vaccinated with SARS-CoV-2 vaccine. Trimeric spike, nucleocapsid, and ACE2-RBD blocking antibodies for SARS-CoV-2 were measured. Nasal swabs were collected for SARS-CoV-2 PCR testing. Information on vaccination against SARS-CoV-2 and PCR verified infection was retrieved from official databases (Abu Dhabi Health Data Services- SP LLC. ("Malaffi"), including number of vaccine doses received, date of vaccination, and type of the received vaccine. Results: All the study population were tested PCR-Negative at the time of sample collection. Our results showed that there was a significant rise in the mean (SD) and median (IQR) titers of trimeric spike, nucleocapsid and ACE2-RBD blocking antibodies in the post-vaccination stage. The mean (± SD) and median (IQR) concentration of the anti-S antibody rose by 3.3-fold (+230% ± 197% SD) and 2.8-fold (+185%, 220-390%, p<0.001), respectively. There was an observed positive dose-response relationship between number of the received vaccine doses and having higher proportion of study participants with higher than median concentration in the difference between the measured anti-S and ACE2-RBD blocking antibodies in the post-vaccination compared to pre-vaccination. Conclusion: Our study demonstrates that COVID-19 vaccination post natural infection elicits a robust immunological response with an impressive rise of SARS-CoV-2 antibodies, especially the ACE2-RBD blocking antibodies.

Aerobic exercise attenuates abnormal myelination and oligodendrocyte differentiation in 3xTg-AD mice.

Pathological features of Alzheimer's Disease (AD) include alterations in the structure and function of neurons as well as of myelin sheaths. Accumulated evidence shows that aerobic type of exercise can enhance neuroplasticity in mouse models of AD. However, whether and how aerobic exercise can affect myelin sheath repair and neuroprotection in the AD models remains unclear. In this study we tested the hypotheses that 1) myelin structural alterations in 3xTg-AD mice would be related to abnormalities in oligodendrocyte lineage cells, resulting in impaired learning and memory, and 2) a 6-month aerobic exercise intervention would have beneficial effects on such alterations. Two-month-old male 3xTg-AD mice were randomly assigned to a control (AC) or an exercise (AE) group, and age-matched male C57BL/6;129 mice were also randomly assigned to a normal control (NC) or an exercise (NE) group, with n = 12 in each group. Mice in the exercise groups were trained on a motor-drive treadmill, 60 min per day, 5 days per week for 6 months. Cognitive function was assessed at the end of the intervention period. Then, brain specimens were obtained for assessments of morphological and oligodendrocyte lineage cell changes. The results of electron microscopy showed that myelin ultrastructure demonstrated a higher percentage of loose and granulated myelin sheath around axons in the temporal lobe in the AC, as compared with the NC group, along with greater cognitive dysfunction at 8-months of age. These differences were accompanied by significantly greater myelin basic protein (MBP) expression and less neuron-glial antigen-2 (NG2) protein and mRNA levels in the AC, compared to the NC. However, there were no significant between-group differences in the G-ratio (the ratio of axon diameter to axon plus myelin sheath diameter) and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) protein and mRNA levels. The aerobic exercise ameliorated cognitive deterioration and appeared to keep components of myelin sheath and oligodendrocyte precursor cells stabilized, resulting in a decrease in the percentage of loose and granulated myelin sheath and MBP protein, and an increase in NG2 protein and mRNA levels in the AE group. Therefore, the 6-month exercise intervention demonstrated beneficial effects on myelin lesions, abnormal differentiation of oligodendrocytes and general brain function in the 3xTg-AD mice, providing further insights into the role of aerobic exercise in management of neurodegeneration in AD by maintaining intact myelination.

Preparing for the next pandemic: lessons learnt from the implementation of point-of-care SARS-CoV-2 testing in an emergency department.

Point-of-care testing (POCT) provides rapid, accurate results that facilitate diagnosis and patient management. POCT for infectious agents allows timely infection prevention and control interventions and informs decisions around safe patient placement. However, POCT implementation requires careful governance as they are primarily operated by staff with limited prior education on laboratory quality control and assurance processes. Here, we describe our experience implementing SARS-CoV-2 POCT in the emergency department of a large tertiary referral hospital during the COVID-19 pandemic. We describe collaborative governance between pathology and clinical specialities, quality assurance, testing (volume and positivity rates), impact on patient flow and focus on lessons learnt during implementation that should be incorporated into revised pandemic preparedness planning.

Susceptibility to reinfection with SARS-CoV-2 virus relative to existing antibody concentrations and T cell response.

OBJECTIVES: We investigated the reinfection rate of vaccinated or convalescent immunized SARS-CoV-2 in 952 expatriate workers with SARS-CoV-2 serological antibody (Ab) patterns and surrogate T cell memory at recruitment and follow-up. METHODS: Trimeric spike, nucleocapsid, and neutralizing Abs were measured, along with a T cell stimulation assay, targeting SARS-CoV-2 memory in clusters of differentiation (CD) 4+ and CD8+ T cells. The subjects were then followed up for reinfection for up to 6 months. RESULTS: The seroprevalence positivity at enrollment was greater than 99%. The T cell reactivity in this population was 38.2%. Of the 149 (15.9%) participants that were reinfected during the follow-up period (74.3%) had nonreactive T cells at enrollment. Those who had greater than 100 binding Ab units/ml increase from the median concentration of antispike immunoglobulin G Abs had a 6% reduction in the risk of infection. Those who were below the median concentration had a 78% greater risk of infection. CONCLUSION: Significant immune protection from reinfection was observed in those who retained T cell activation memory. Additional protection was observed when the antispike was greater than the median value.

Coaching to Bedside Shift Report and Its Correlation to Hospital Consumer Assessment of Healthcare Providers and Systems and Value-Based Purchasing Dimension Scores: A Multihospital Implementation Study.

OBJECTIVE: The objective of this multihospital study was to investigate how the intervention of coaching to bedside shift report (BSR) correlates with Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) outcomes and relates to Centers for Medicare and Medicaid Services (CMS) Hospital Value-Based Purchasing (VBP) Program points over a 4-year period (2017-2020) for an acute care hospital health system. BACKGROUND: Hospital leaders' responsibilities include intertwined areas of patient experience and fiscal accountability. Coaching to BSR is reported to have numerous benefits to the patient's experience. Published studies completed with hospital systems evaluating the intervention of coaching to BSR and how it correlated to patient experience and VBP are limited. METHODS: Coaching to BSR was implemented at 16 adult acute care hospitals. Patient-reported BSR rates were collected in tandem with HCAHPS for 4 years. Statistical correlations were assessed between patient-reported BSR and HCAHPS and consequential effect on VBP dimension scores. RESULTS: Coaching to BSR had a significant impact on top- and bottom-box "rate the hospital" HCAHPS scores at a system and hospital level. Value-based purchasing points and percentages increased over 2017-2020, potentially leading to lower CMS penalty claims over the period the BSR was implemented. CONCLUSIONS: Coaching is a key factor when creating a favorable patient experience. The implementation and sustainability of coaching to BSR may result in improved patient experience ratings and increase VBP point accumulation to hospital systems.

Repurposing Antimalarial Pyronaridine as a DNA Repair Inhibitor to Exploit the Full Potential of Gold-Nanoparticle-Mediated Radiation Response.

Radiation therapy (RT) is frequently used to locally treat tumors. One of the major issues in RT is normal tissue toxicity; thus, it is necessary to limit dose escalation for enhanced local control in patients that have locally advanced tumors. Integrating radiosensitizing agents such as gold nanoparticles (GNPs) into RT has been shown to greatly increase the cure rate of solid tumors. The objective of this study was to explore the repurposing of an antimalarial drug, pyronaridine (PYD), as a DNA repair inhibitor to further enhance RT/GNP-induced DNA damage in cancerous cell lines. We were able to achieve inhibitory effects of DNA repair due to PYD at 500 nM concentration. Our results show a significant enhancement in DNA double-strand breaks of 42% in HeLa cells treated with PYD/GNP/RT in comparison to GNP/RT alone when irradiated with a dose of 2 Gy. Furthermore, there was a significant reduction in cellular proliferation for both HeLa and HCT-116 irradiated cells with the combined treatment of PYD/GNP/RT. Therefore, the emergence of promising novel concepts introduced in this study could lay the foundation for the transition of this treatment modality into clinical environments.

Gaussian process emulation of spatio-temporal outputs of a 2D inland flood model.

The computational limitations of complex numerical models have led to adoption of statistical emulators across a variety of problems in science and engineering disciplines to circumvent the high computational costs associated with numerical simulations. In flood modelling, many hydraulic and hydrodynamic numerical models, especially when operating at high spatiotemporal resolutions, have prohibitively high computational costs for tasks requiring the instantaneous generation of very large numbers of simulation results. This study examines the appropriateness and robustness of Gaussian Process (GP) models to emulate the results from a hydraulic inundation model. The developed GPs produce real-time predictions based on the simulation output from LISFLOOD-FP numerical model. An efficient dimensionality reduction scheme is developed to tackle the high dimensionality of the output space and is combined with the GPs to investigate the predictive performance of the proposed emulator for estimation of the inundation depth. The developed GP-based framework is capable of robust and straightforward quantification of the uncertainty associated with the predictions, without requiring additional model evaluations and simulations. Further, this study explores the computational advantages of using a GP-based emulator over alternative methodologies such as neural networks, by undertaking a comparative analysis. For the case study data presented in this paper, the GP model was found to accurately reproduce water depths and inundation extent by classification and produce computational speedups of approximately 10,000 times compared with the original simulator, and 80 times for a neural network-based emulator.

Modulation of ERCC1-XPF Heterodimerization Inhibition via Structural Modification of Small Molecule Inhibitor Side-Chains.

Inhibition of DNA repair enzymes is an attractive target for increasing the efficacy of DNA damaging chemotherapies. The ERCC1-XPF heterodimer is a key endonuclease in numerous single and double strand break repair processes, and inhibition of the heterodimerization has previously been shown to sensitize cancer cells to DNA damage. In this work, the previously reported ERCC1-XPF inhibitor 4 was used as the starting point for an in silico study of further modifications of the piperazine side-chain. A selection of the best scoring hits from the in silico screen were synthesized using a late stage functionalization strategy which should allow for further iterations of this class of inhibitors to be readily synthesized. Of the synthesized compounds, compound 6 performed the best in the in vitro fluorescence based endonuclease assay. The success of compound 6 in inhibiting ERCC1-XPF endonuclease activity in vitro translated well to cell-based assays investigating the inhibition of nucleotide excision repair and disruption of heterodimerization. Subsequently compound 6 was shown to sensitize HCT-116 cancer cells to treatment with UVC, cyclophosphamide, and ionizing radiation. This work serves as an important step towards the synergistic use of DNA repair inhibitors with chemotherapeutic drugs.

Effect of COVID-19 Stay-at-Home Restrictions on Parent Reported Symptom Severity and Adaptive Functioning of Youth with ASD.

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.

Evaluation of post-vaccination immunoglobulin G antibodies and T-cell immune response after inoculation with different types and doses of SARS-CoV-2 vaccines: A retrospective cohort study.

Introduction: The induction and speed of production of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) immune biomarkers may vary by type and number of inoculated vaccine doses. This study aimed to explore variations in SARS-CoV-2 anti-spike (anti-S), anti-nucleocapsid (anti-N), and neutralizing immunoglobulin G (IgG) antibodies, and T-cell response by type and number of SARS-CoV-2 vaccine doses received. Methods: In a naturally exposed and SARS-CoV-2-vaccinated population, we quantified the anti-S, anti-N, and neutralizing IgG antibody concentration and assessed T-cell response. Data on socio-demographics, medical history, and history of SARS-CoV-2 infection and vaccination were collected. Furthermore, nasal swabs were collected to test for SARS-CoV-2 infection. Confounder-adjusted association between having equal or more than a median concentration of the three IgG antibodies and T-cell response by number and type of the inoculated vaccines was quantified. Results: We surveyed 952 male participants with a mean age of 35.5 years ± 8.4 standard deviations. Of them, 52.6% were overweight/obese, and 11.7% had at least one chronic comorbidity. Of the participants, 1.4, 0.9, 20.2, 75.2, and 2.2% were never vaccinated, primed with only one dose, primed with two doses, boosted with only one dose, and boosted with two doses, respectively. All were polymerase chain reaction-negative to SARS-CoV-2. BBIBP-CorV (Sinopharm) was the most commonly used vaccine (92.1%), followed by rAd26-S + rAd5-S (Sputnik V Gam-COVID-Vac) (1.5%) and BNT162b2 (Pfizer-BioNTech) (0.3%). Seropositivity to anti-S, anti-N, and neutralizing IgG antibodies was detected in 99.7, 99.9, and 99.3% of the study participants, respectively. The T-cell response was detected in 38.2% of 925 study participants. Every additional vaccine dose was significantly associated with increased odds of having ≥median concentration of anti-S [adjusted odds ratio (aOR), 1.34; 95% confidence interval (CI): 1.02-1.76], anti-N (aOR, 1.35; 95% CI: 1.03-1.75), neutralizing IgG antibodies (aOR, 1.29; 95% CI: 1.00-1.66), and a T-cell response (aOR, 1.48; 95% CI: 1.12-1.95). Compared with boosting with only one dose, boosting with two doses was significantly associated with increased odds of having ≥median concentration of anti-S (aOR, 13.8; 95% CI: 1.78-106.5), neutralizing IgG antibodies (aOR, 13.2; 95% CI: 1.71-101.9), and T-cell response (aOR, 7.22; 95% CI: 1.99-26.5) although not with anti-N (aOR, 0.41; 95% CI: 0.16-1.08). Compared with priming and subsequently boosting with BBIBP-CorV, all participants who were primed with BBIBP-CorV and subsequently boosted with BNT162b2 had ≥median concentration of anti-S and neutralizing IgG antibodies and 14.6-time increased odds of having a T-cell response (aOR, 14.63; 95% CI: 1.78-120.5). Compared with priming with two doses, boosting with the third dose was not associated, whereas boosting with two doses was significantly associated with having ≥median concentration of anti-S (aOR, 14.20; 95% CI: 1.85-109.4), neutralizing IgG (aOR, 13.6; 95% CI: 1.77-104.3), and T-cell response (aOR, 7.62; 95% CI: 2.09-27.8). Conclusion: Achieving and maintaining a high blood concentration of protective immune biomarkers that predict vaccine effectiveness is very critical to limit transmission and contain outbreaks. In this study, boosting with only one dose or with only BBIBP-CorV after priming with BBIBP-CorV was insufficient, whereas boosting with two doses, particularly boosting with the mRNA-based vaccine, was shown to be associated with having a high concentration of anti-S, anti-N, and neutralizing IgG antibodies and producing an efficient T-cell response.

Autism Characteristics and Self-Reported Health in Older Adulthood.

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 Relationship of Age with the Autism-Spectrum Quotient Scale in a Large Sample of Adults.

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.

Psychometric properties of the Cambridge-Mindreading Face-Voice Battery for Children in children with ASD.

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.

Path Analysis of the Mediating Roles of Personality, Distress, and Cognitive Flexibility in the Subjective Well-Being of Combat Veterans With Traumatic Brain Injury.

OBJECTIVE: To determine the interrelationships among traumatic brain injury (TBI), maladaptive personality traits (MPT), psychological distress, and cognitive flexibility in the prediction of subjective well-being of post-9/11 veterans concurrently and over time. SETTING: Five Veterans Affairs (VA) medical centers and 1 VA outpatient clinic in urban, suburban, and rural areas. PARTICIPANTS: Five hundred Operation Enduring Freedom/Operation Iraqi Freedom veterans at baseline (219 with TBI), 292 at 18-month follow-up (108 with TBI), drawn from a regional registry and clinic referrals. DESIGN: Path analysis of data from a prospective cohort study. MAIN MEASURES: Satisfaction with Life Scale, 36-ltem Short-Form Health Survey (SF-36) Health Scale, Personality Assessment Screener, Beck Depression Inventory-II, Beck Anxiety Inventory, Posttraumatic Stress Disorder Checklist-Military, Trail Making Test, Part B, Delis-Kaplan Executive Function System (D-KEFS) Category-Switching Verbal Fluency, and D-KEFS Color-Word Interference Test. RESULTS: There was no direct effect of TBI on well-being at baseline or 18 months later. Psychological distress, MPT, and cognitive flexibility had significant direct effects on well-being at baseline and 18 months. Baseline model accounted for 66% of the variance in well-being; follow-up model accounted for 43% of well-being variance. Negative influence of distress significantly decreased from baseline to follow-up. Direct negative effect of MPT diminished slightly over 18 months; effect of cognitive flexibility increased. Significant relationships were estimated in prediction of distress by MPT, cognitive flexibility, and TBI. TBI predicted MPT. MPT, cognitive flexibility, and TBI had indirect effects on well-being. TBI had a positive indirect influence on distress. Total effects included 4 significant predictors of well-being at baseline and 18 months: distress, MPT, cognitive flexibility, and TBI. CONCLUSION: Experience of TBI alone did not predict subjective well-being at baseline or 18 months later. Psychological distress, MPT, and cognitive flexibility had direct effects on well-being at both time points. Interventions aimed at reducing distress and bolstering resilience and cognitive flexibility are recommended to increase subjective well-being in this population.

Feasibility and Associated Physical Performance Outcomes of a High-Intensity Exercise Program for Children With Autism.

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 (ds 0.83 and 1.05, respectively) and on three exercise tests (sit ups, air squats, and long jump; ds 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.

RCT of a Comprehensive Outpatient Treatment for Children with Autism Spectrum Disorder.

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.

Moderators of School Intervention Outcomes for Children with Autism Spectrum Disorder.

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.