A pilot, single-arm feasibility study of an integrated cognitive-behavioral treatment for anxiety in young autistic children.

OBJECTIVE: Anxiety is prevalent in young autistic children under 7 years of age. Yet there is a paucity of empirically based interventions for this age group. DINO Strategies for Anxiety and Uncertainty Reduction (DINOSAUR) is an innovative cognitive behavioral intervention that seeks to optimize treatment response in young autistic children by targeting anxiety and the contributing mechanisms of intolerance of uncertainty and parental accommodation using a telehealth delivery model. This pilot, single-arm study examines the preliminary feasibility of DINOSAUR. METHODS: Fourteen autistic children ages 4-6 years with average language and cognitive skills and their parents received the intervention. Quantitative and qualitative data pertaining to parent satisfaction and treatment outcomes were collected. RESULTS: Attendance, retention, and parent satisfaction ratings offer preliminary support for the feasibility of the treatment model. Change in clinical severity ratings on a semi-structured parent interview of anxiety and parents' qualitative report suggests the potential to benefit young autistic children. CONCLUSIONS: Results support future study of the DINOSAUR model in a larger, randomized controlled trial.

Anxiety in autistic preschool children: Phenomenology and a network analysis of correlates.

Anxiety disorders in autistic children are associated with significant functional impairment. Few studies have examined impairing anxiety presentations in autistic preschool children (i.e., 3-5 years old). This cross-sectional study examined the phenomenology of impairing anxiety and the strongest correlates of anxiety in 75 autistic preschool children. Parents completed a diagnostic interview that assesses two anxiety types, DSM-5 anxiety disorders and impairing distinct anxiety presentations, and measures of anxiety correlates. An exploratory network analysis examined connections between anxiety and its correlates. Forty percent of children had impairing anxiety. Specific phobia followed by 'other social fear,' a type of distinct anxiety, were the most common anxiety types. Child intolerance of uncertainty (IU) was the only correlate that was associated with anxiety in a network analysis framework. Child IU linked anxiety to two other correlates, sensory over-responsivity and somatic symptoms. Findings emphasize the need for early intervention for anxiety and further research on its correlates.

Psychometric Evaluation of the Autism Spectrum Rating Scales (6-18 Years Parent Report) in a Clinical Sample.

ASD is a neurodevelopmental disorder impacting 1 in 44 children and early identification of children with ASD is critical for the intervention. Several screening measures have been developed for early identification, including the Autism Spectrum Rating Scales, 6-18 years Parent Report (ASRS). The ASRS has been understudied, and the current study assessed the validity of the ASRS in a clinical sample of 490 children at a tertiary ASD-specialty clinic. Results indicated that the ASRS demonstrated favorable sensitivity, but poor specificity. True positive screening results were more likely to occur for children with a multiracial background, while they were less likely to occur for children with a high social capital. Overall, though the ASRS has clinical utility as a screening measure, it did not perform effectively to differentiate ASD from Non-ASD clinical disorders.

Exploring the Symptom Profiles of Intolerance of Uncertainty in Autistic Children.

Intolerance of uncertainty (IU) is a multidimensional construct involving maladaptive responses to uncertainty. IU is strongly associated with autism and anxiety, yet no studies have examined its symptom profile in autistic children. This study compares IU symptom profiles in autistic and NT children and in autistic children with and without anxiety using the Intolerance of Uncertainty Scale for Children. Compared to NT peers, autistic children exhibited heightened IU symptoms in all domains, affective, behavioral, and cognitive; affective symptoms had the highest association with autism. Autistic children with anxiety also exhibited elevated IU symptoms in all domains compared to those without anxiety; behavioral IU symptoms had the highest association with anxiety. IU symptom profiles should be considered in assessment and treatment.

Profiles and correlates of language and social communication differences among young autistic children.

Delays in early language development are characteristic of young autistic children, and one of the most recognizable first concerns that motivate parents to seek a diagnostic evaluation for their child. Although early language abilities are one of the strongest predictors of long-term outcomes, there is still much to be understood about the role of language impairment in the heterogeneous phenotypic presentation of autism. Using a person-centered, Latent Profile Analysis, we first aimed to identify distinct patterns of language and social communication ability in a clinic-based sample of 498 autistic children, ranging in age from 18 to 60 months (M = 33 mo, SD = 12 mo). Next, a multinomial logistic regression analysis was implemented to examine sociodemographic and child-based developmental differences among the identified language and social communication profiles. Three clinically meaningful profiles were identified from parent-rated and clinician-administered measures: Profile 1 (48% of the sample) "Relatively Low Language and Social Communication Abilities," Profile 2 (34% of the sample) "Relatively Elevated Language and Social Communication Abilities," and Profile 3 (18% of the sample) "Informant Discrepant Language and Relatively Elevated Social Communication Abilities." Overall, young autistic children from the lowest-resource households exhibited the lowest language and social communication abilities, and the lowest non-verbal problem-solving and fine-motor skills, along with more features of attention-deficit/hyperactivity disorder and atypical auditory processing. These findings highlight the need for effective community-based implementation strategies for young autistic children from low-resource households and underrepresented communities to improve access to individualized quality care.

Replication study for ADOS-2 cut-offs to assist evaluation of autism spectrum disorder.

The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) has been widely used for ASD assessment. While prior studies investigated sensitivity and specificity of ADOS-2 Modules 1-3, there has been limited research addressing algorithm cut-off scores to optimize ADOS-2 classification. The goal of this study was to assess algorithm cut-off scores for diagnosing ASD with Modules 1-3, and to evaluate alignment of the ADOS-2 classification with the best estimate clinical diagnosis. Participants included 3144 children aged 31 months or older who received ADOS-2 Modules 1-3, as well as the best estimate clinical diagnosis. Five classification statistics were reported for each module: sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (i.e., Receiver Operator Classification Statistic), and these statistics were calculated for the optimal cut-off score. Frequency tables were used to compare ADOS-2 classification and the best estimate clinical diagnosis. Half of the sample received Module 3, 21% received Module 2, and 29% received Module 1. The overall prevalence of ASD was 60%; the male-to-female ratio was 4:1, and half of the sample was non-White. Across all modules, the autism spectrum cut-off score from the ADOS-2 manual resulted in high sensitivity (95%+) and low specificity (63%-73%). The autism cut-off score resulted in better specificity (76%-86%) with favorable sensitivity (81%-94%). The optimal cut-off scores for all modules based on the current sample were within the autism spectrum classification range except Module 2 Algorithm 2. In the No ASD group, 29% had false positives (ADOS-2 autism spectrum classification or autism classification). The ADOS-2 autism spectrum classification did not indicate directionality for diagnostic outcome (ASD 56% vs. No ASD 44%). While cut-off scores of ADOS-2 Modules 1-3 in the manual yielded good clinical utility in ASD assessment, false positives and low predictability of the autism spectrum classification remain challenging for clinicians.

Analysis of Race and Sex Bias in the Autism Diagnostic Observation Schedule (ADOS-2).

Importance: There are long-standing disparities in the prevalence of autism spectrum disorder (ASD) across race and sex. Surprisingly, few studies have examined whether these disparities arise partially out of systematic biases in the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), the reference standard measure of ASD. Objective: To examine differential item functioning (DIF) of ADOS-2 items across sex and race. Design, Setting, and Participants: This is a cross-sectional study of children who were evaluated for ASD between 2014 and 2020 at a specialty outpatient clinic located in the Mid-Atlantic region of the US. Data were analyzed from July 2021 to February 2022. Exposures: Child race (Black/African American vs White) and sex (female vs male). Main Outcomes and Measures: Item-level biases across ADOS-2 harmonized algorithm items, including social affect (SA; 10 items) and repetitive/restricted behaviors (RRBs; 4 items), were evaluated across 3 modules. Measurement bias was identified by examining DIF and differential test functioning (DTF), within a graded response, item response theory framework. Statistical significance was determined by a likelihood ratio χ2 test, and a series of metrics was used to examine the magnitude of DIF and DTF. Results: A total of 6269 children (mean [SD] age, 6.77 [3.27] years; 1619 Black/African American [25.9%], 3151 White [50.3%], and 4970 male [79.4%]), were included in this study. Overall, 16 of 140 ADOS-2 diagnostic items (11%) had a significant DIF. For race, 8 items had a significant DIF, 6 of which involved SA. No single item showed DIF consistently across all modules. Most items with DIF had greater difficulty and poorer discrimination in Black/African American children compared with White children. For sex, 5 items showed significant DIF. DIF was split across SA and RRB. However, hand mannerisms evidenced DIF across all 5 algorithms, with generally greater difficulty. The magnitude of DIF was only moderate to large for 2 items: hand mannerisms (among female children) and repetitive interests (among Black/African American children). The overall estimated effect of DIF on total DTF was not large. Conclusions and Relevance: These findings suggest that the ADOS-2 does not have widespread systematic measurement bias across race or sex. However, the findings raise some concerns around underdetection that warrant further research.

Understanding educators' perspectives and experiences of COVID-19 in schools serving children with intellectual/developmental disabilities.

The COVID-19 pandemic has significantly impacted educators, both personally and professionally. However, very little is known about the extent of these impacts among educators' serving children with intellectual and developmental disabilities (IDD). The present study surveyed 230 educators (teachers, staff, and administrators) to assess their wellbeing, concerns during the pandemic, and perceived importance of various COVID-19 school mitigation strategies. Data were gathered May/June of 2021 from two separate school districts, one in the Midwest and the other in the Mid-Atlantic, serving children with IDD. Nearly half of all survey respondents reported poor wellbeing. Almost all educators reported health of themselves, students, and family members was their greatest concern when compared to pandemic-related disruption of their duties or benefits (e.g., not having enough sick time). Most educators felt disinfecting routines, vaccinations, and daily health checks were the most helpful in preventing the spread of COVID-19 in schools, while in-school mask mandates and weekly testing of students and staff were perceived as less helpful. Our findings suggest that efforts are needed to support the wellbeing of educators during these challenging times. When pandemic-related policies and procedures are decided by administrators, our data suggest educators will review decisions within the framework of health and safety of themselves, their students, and families. Understanding this framework may be particularly valuable when considering implementation of COVID-19 policies, like masking and COVID-19 testing, that are less preferred.

Dysregulation in Children and Adolescents Presenting to a Multidisciplinary Autism Clinic.

Research indicates that children with autism spectrum disorder (ASD) frequently exhibit dysregulation, which refers to poorly coordinated affective, behavioral, and cognitive responses to a given situation. We examined the characteristics of dysregulation in children presenting to a multidisciplinary ASD clinic for an ASD diagnostic evaluation. Sixty percent of children presenting for an ASD evaluation exhibited dysregulation. Dysregulation prevalence was higher in children without ASD versus with ASD (69% versus 56%). Severe dysregulation was higher in children without ASD (29% versus 16%). Both groups with severe dysregulation were equally likely to be taking psychiatric medications, however, children with ASD were less likely to be receiving therapy. These findings highlight the importance of implementing dysregulation screening and treatment protocols in ASD centers.

Psychiatric problems during the COVID-19 pandemic in children with autism spectrum disorder.

Children with autism spectrum disorder (ASD) are at elevated risk for psychiatric problems in response to the COVID-19 pandemic. This risk is due to their high rates of pre-pandemic psychiatric comorbidities and the pandemic's disruption to routines and access to necessary supports. Prior research has indicated that children with ASD may experience a worsening of specific psychiatric symptoms in response to COVID-19, though this body of work is limited in scope. The present study expands this literature by examining specific types of psychiatric problems that emerged about 2 months after the onset of the pandemic, and risk factors predicting changes in these psychiatric symptoms. Parents of children with a confirmed ASD diagnosis (N = 257), who enrolled in a clinic registry at an outpatient specialty autism center, were included in this study. All data were gathered online via customized and standardized questionnaires. Results showed that 59% of children experienced either a worsening of their pre-pandemic psychiatric diagnoses and/or the development of new psychiatric symptoms during the pandemic. Multivariable regression models indicated that risk factors for increased psychiatric problems included child understanding of COVID-19, COVID-19 illness in the family, low family income, and elevated parental depression and anxiety symptoms (all p < 0.05). Findings from this study emphasize the urgent need to provide effective and accessible psychiatric services for children with ASD and their families during and after the pandemic. LAY SUMMARY: Children with ASD are at high risk for psychiatric problems during the COVID-19 pandemic. We found that 59% of children in our clinical sample are experiencing increased psychiatric problems. The child's understanding of COVID-19, COVID-19 illness in the family, low family income, and depression and anxiety symptoms in the parent increase the risk for poor mental health during the pandemic. These findings indicate the importance of helping children with ASD access mental health treatment during COVID-19.

Replication study of ADOS-2 Toddler Module cut-off scores for autism spectrum disorder classification.

The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) has been regarded as the gold standard assessment of autism spectrum disorder (ASD). While clinical validity of ADOS-2 Modules 1-4 have been extensively studied, there has been very limited research examining the clinical validity of ADOS-2 Toddler Module. The goal of this study was to examine alignment of the ADOS-2 Toddler Module classification with clinicians' determination of ASD, with assessing cut-off scores for diagnosing ASD in toddlers. A total of 412 toddlers ages 12-30 months who received ADOS-2 Toddler Module as well as a best estimate clinical (BEC) diagnosis, were included in this study. ADOS-2 Toddler Module cut-off scores were determined using the appropriate algorithms (Algorithm 1 for toddlers aged 12-20 months and those aged 21-30 months with <5 words, Algorithm 2 for toddlers aged 21-30 months with 5 words or more). Receiver operating characteristic (ROC) curves were used to assess cut-off scores that optimized sensitivity and specificity when compared against BEC diagnosis. The selected cut-off scores were examined using frequency tables to compare ADOS-2 classification against BEC diagnosis. For Algorithm 1, classification statistics were optimized at the cut-off score of 12 with an area under the curve (AUC) of 0.92. For Algorithm 2, classification statistics were optimized at the cut-off score of 10 with an AUC of 0.96. The ADOS-2 Toddler Module classification is strongly aligned with BEC diagnosis. The optimal cut-off scores identified in the current study reflect the same results configured by the prior study. LAY SUMMARY: ADOS-2 Toddler Module has been widely used for the ASD assessment, but there have been limited research on its clinical validity. This study is the first replication of the ADOS-2 Toddler Module with a large independent sample. We examined alignment of the ADOS-2 Toddler Module classification with clinicians' determination of ASD, with assessing cut-off scores, and confirmed the clinical validity of ADOS-2 Toddler Module. Cut-off scores of ADOS-2 Toddler Module cited in the manual yielded best clinical utility for diagnosing ASD in toddlers.

Attention Deficit Hyperactivity Disorder Symptoms in Young Children with Autism Spectrum Disorder.

The purpose of the current study was to examine the prevalence of attention deficit hyperactivity disorder (ADHD) symptoms among young children with autism spectrum disorder (ASD), child and parent-related demographic and clinical correlates of ADHD symptoms, and the relationships between co-occurring mental health problems and ADHD symptoms. Data for this cross-sectional study came from 979 toddlers and preschoolers, ages 1.5-5 years, with ASD. The primary outcome, ADHD symptoms, was measured using the Child Behavior Check List 1.5-5 (CBCL). Additional information from the medical record included demographics, parenting stress, and Autism Diagnostic Observation Schedule Second Edition. Descriptive and bivariate (ANOVA, Chi-Square) statistics and multivariate, multinomial regression analyses were used to examine demographic and clinical differences between low, moderate, and high ADHD symptom groups, as defined by 2 ADHD-related subscales. There were 418 (43%) children in the low ADHD symptom group, 294 (30%) in the moderate ADHD symptom group, and 267 (27%) in the high ADHD symptom group. Those with high ADHD symptoms were less likely to be Black or Hispanic and less likely to have parents with a graduate-level education compared to those with low ADHD symptoms. Parenting stress and all CBCL DSM-oriented subscales were positively associated with increasing ADHD symptoms. Among young children with ASD, ADHD symptoms were highly prevalent. The presence of ADHD symptoms was associated with increasing parenting stress and greater levels of other psychopathologies. These data suggest that young children with ASD should be evaluated for ADHD, and mental health as a whole. LAY SUMMARY: We investigated attention deficit hyperactivity disorder (ADHD) symptoms in toddlers and preschoolers with autism spectrum disorder (ASD) from a large sample with diverse race and socioeconomic background. In our study, we found that ADHD symptoms are highly prevalent in young children with ASD and are associated with increasing parenting stress and greater level of other psychopathologies, both internalizing and externalizing problems.

Ultrasensitive quantum dot-coupled-surface plasmon microfluidic aptasensor array for serum insulin detection.

Monitoring insulin levels in complex clinical matrices such as serum, holds immense importance in diagnosing type of diabetes. The present study reports the development of surface plasmon resonance aptamer based insulin sensor array in a four-channel microfluidic format which utilizes antibody attached to magnetic nanoparticles for capturing insulin from diabetic patient serum samples and surface immobilized plasmon enhancing quantum dots for signal amplification. The aptasensor gives minimal non-specific binding due to the immobilization of high molecular weight dendrimers on a cysteamine monolayer. The aptamer-insulin-antibody sandwich microarray monitors insulin levels in two-fold diluted serum and offers a detection limit 800 fM with a linear dynamic range 0.8-250 pM. Its clinical applicability on measuring serum insulin levels in 24 diabetic patient samples and correlation with ELISA is demonstrated.

Investigating the factor structure of the child behavior checklist dysregulation profile in children and adolescents with autism spectrum disorder.

Dysregulation has been identified as an important risk factor for the development of psychiatric disorders in individuals with autism spectrum disorder (ASD). Therefore, it is necessary to empirically characterize dysregulation and identify psychometrically sound and readily available assessment methods in the ASD population. We sought to evaluate the factor structure of the Child Behavior Checklist-Dysregulation Profile (CBCL-DP), an established dysregulation measure in neurotypical children that is derived from the CBCL, in a large, clinically referred sample of children, ages 6-18 years, with ASD (n = 727). Confirmatory factor analysis was used to characterize dysregulation and assess the validity of the CBCL-DP in children with ASD. Our findings support a bi-factor model of dysregulation in which dysregulation is a broad and distinct syndrome that is associated with the three subdomains of the CBCL-DP, anxiety/depression (AD), attention problems (AP), and aggressive behavior (AGG). Dysregulation was associated with most items in the AD and AGG domains and few items in the AP domain. This association with AD and AGG indicates that dysregulation in ASD may be conceptualized as the combined experience of internalized, negative mood states and externalized, reactive behaviors. These findings provide support as well as important caveats for the use of the CBCL-DP as a measure of dysregulation in the ASD population. Autism Res 2020, 13: 436-443. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Dysregulation is a risk factor for psychiatric disorders in ASD. This study examined if the CBCL-DP, an established measure of dysregulation in neurotypical children, can be used to assess dysregulation in children with ASD. Findings provide evidence that in ASD, dysregulation is a broad construct that exists alongside anxiety/depression, attention problems, and aggression. These findings indicate that the CBCL-DP can be considered a valid measure of dysregulation in the ASD population and could be used in clinical settings.

Child and Family Characteristics that Predict Autism Spectrum Disorder Specialty Clinic Appointment Attendance and Alignment with Providers.

We examined factors contributing to initial appointment attendance, alignment between parents' pre-visit and clinicians' diagnostic impressions, and family commitment to follow-ups at an autism spectrum disorder (ASD) specialty clinic. Sample sizes were n = 6558 (initial), n = 1430 (alignment), and n = 1353 (follow-up). Parents completed surveys and clinicians provided their ASD diagnostic impressions. When children were not receiving intervention, families were less likely to keep their initial appointment. Families residing long distances and having older children were less likely to keep their initial and follow-up appointments. African American families were less likely to keep their initial appointment and expressed initial doubts with providers about the diagnosis. Findings suggest that some children are not getting diagnostic clarity or accessing timely services.

Exploring Relationships Between Negative Cognitions and Anxiety Symptoms in Youth With Autism Spectrum Disorder.

Although cognitions are central to the conceptualization and treatment of anxiety in typically developing (TD) youth, there is scant research investigating automatic thoughts and their relationship with anxiety in youth with autism spectrum disorder (ASD). We sought to examine the types of automatic thoughts experienced by youth with ASD and co-occurring anxiety as well as the predictive relationship of anxiety to different types of automatic thoughts in 97 children, ages 8-14 years. We also explored the relationship of automatic thoughts and intolerance of uncertainty. Consistent with prior data, there was a strong relationship between anxiety and automatic thoughts pertaining to social and physical threat. Anxiety and IU were independently associated with thoughts pertaining to personal failure which raises the hypothesis that personal failure may serve as a common pathway between anxiety, IU, and depression in ASD youth. These findings highlight the importance of assessing and treating negative cognitions in youth with ASD and anxiety.

Electrochemical and surface plasmon insulin assays on clinical samples.

Diabetes is a complex immune disorder that requires extensive medical care beyond glycemic control. Recently, the prevalence of diabetes, particularly type 1 diabetes (T1D), has significantly increased from 5% to 10%, and this has affected the health-associated complication incidences in children and adults. The 2012 statistics by the American Diabetes Association reported that 29.1 million Americans (9.3% of the population) had diabetes, and 86 million Americans (age ≥20 years, an increase from 79 million in 2010) had prediabetes. Personalized glucometers allow diabetes management by easy monitoring of the high millimolar blood glucose levels. In contrast, non-glucose diabetes biomarkers, which have gained considerable attention for early prediction and provide insights about diabetes metabolic pathways, are difficult to measure because of their ultra-low levels in blood. Similarly, insulin pumps, sensors, and insulin monitoring systems are of considerable biomedical significance due to their ever-increasing need for managing diabetic, prediabetic, and pancreatic disorders. Our laboratory focuses on developing electrochemical immunosensors and surface plasmon microarrays for minimally invasive insulin measurements in clinical sample matrices. By utilizing antibodies or aptamers as the insulin-selective biorecognition elements in combination with nanomaterials, we demonstrated a series of selective and clinically sensitive electrochemical and surface plasmon immunoassays. This review provides an overview of different electrochemical and surface plasmon immunoassays for insulin. Considering the paramount importance of diabetes diagnosis, treatment, and management and insulin pumps and monitoring devices with focus on both T1D (insulin-deficient condition) and type 2 diabetes (insulin-resistant condition), this review on insulin bioassays is timely and significant.

Relationships between autism spectrum disorder and intolerance of uncertainty.

Intolerance of uncertainty (IU) is a dispositional risk factor involving maladaptive responding under conditions of uncertainty. Recent data indicate that IU is likely elevated in youth with autism spectrum disorder (ASD) and is positively correlated with anxiety. This study examined whether IU may be associated with ASD independent of anxiety. Relationships between anxiety, ASD, and IU were examined in 57 children with ASD without co-occurring intellectual disability and 32 control participants, ages 7-16 years. Hierarchal linear regressions were run to examine whether ASD variables, including emotion dysregulation, were predictive of IU when controlling for anxiety. Severity of social communication deficits, repetitive behaviors, and emotion dysregulation were each related to IU when controlling for the effects of anxiety. When these variables were entered into the regression model together, emotion dysregulation was the only significant predictor of IU. These findings suggest that IU is directly related to features of ASD possibly due to shared genetic, neurological, or psychological underpinnings. Autism Res 2018, 11: 636-644. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Youth with ASD without co-occurring intellectual disability experience high levels of intolerance of uncertainty (IU), which is related to anxiety. This study found that IU may also have a relationship with certain aspects of ASD, particularly emotion dysregulation.

Magnetite-Quantum Dot Immunoarray for Plasmon-Coupled-Fluorescence Imaging of Blood Insulin and Glycated Hemoglobin.

New microarray chip strategies that are sensitive and selective and that can measure low levels of important biomarkers directly in a blood sample are significant for improving human health by allowing timely diagnosis of an abnormal condition. Herein, we designed an antibody-aptamer immunoarray chip to demonstrate simultaneous measurement of blood insulin and glycated hemoglobin (HbA1c) levels relevant to diabetic and prediabetic disorders using a surface plasmon microarray with validation by fluorescence imaging. To accomplish both surface plasmon and fluorescence imaging on the same sample, we decorated magnetite nanoparticles with quantum dots for covalent immobilization of aptamers for subsequent capture and isolation of the aptamers specific for insulin and HbA1c markers from 20-times diluted whole blood samples. Direct clinically relevant analysis, along with fluorescent imaging of the two markers, was achieved by this new immunoarray platform. The limit of detection was 4 pM for insulin and 1% for HbA1c. Examination of cross-talk using thrombin and platelet-derived growth factor confirmed that the designed immunoarray was highly selective for insulin and HbA1c. Surface plasmon kinetic analysis provided apparent binding constants of 0.24 (±0.08) nM and 37 (±3) µM, respectively, for the binding of insulin and HbA1c onto their surface immobilized monoclonal antibodies. Thus, quantitative imaging of ultralow levels of blood biomarker levels with binding kinetics is uniquely obtained in the designed immunoarray chip. In conclusion, this report demonstrates considerable significance of the developed magnetite-quantum dot-bioconjugate strategy for clinical diagnostics of whole blood biomarkers with characterization of molecular binding interactions.

Intolerance of Uncertainty Predicts Anxiety Outcomes Following CBT in Youth with ASD.

Modified cognitive-behavioral therapy (MCBT) has been demonstrated to reduce anxiety in youth with autism spectrum disorder (ASD). However, non-response rates are fairly high. Few studies have investigated factors associated with response. Intolerance of uncertainty (IU) is a treatment target for anxiety and worry in neurotypical populations and has been linked to anxiety and ASD. We sought to examine whether IU affects outcomes following MCBT in 43 children, ages 8-14 years, with ASD without intellectual disability. Consistent with prior data, there was a significant reduction in parent reported anxiety following MCBT. Higher levels of pre-intervention IU predicted higher anxiety and worry pre- and post-intervention. These findings suggest that targeting IU may improve outcomes following MCBT in youth with ASD and anxiety.