Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) in Appalachia: protocol for a group randomized, delayed intervention trial.

Appalachian regions of Kentucky and Ohio are hotspots for colorectal cancer (CRC) mortality in the USA. Screening reduces CRC incidence and mortality; however, screening uptake is needed, especially in these underserved geographic areas. Implementation science offers strategies to address this challenge. The aim of the current study was to conduct multi-site, transdisciplinary research to evaluate and improve CRC screening processes using implementation science strategies. The study consists of two phases (Planning and Implementation). In the Planning Phase, a multilevel assessment of 12 health centers (HC) (one HC from each of the 12 Appalachian counties) was conducted by interviewing key informants, creating community profiles, identifying HC and community champions, and performing HC data inventories. Two designated pilot HCs chose CRC evidence-based interventions to adapt and implement at each level (i.e., patient, provider, HC, and community) with evaluation relative to two matched control HCs. During the Implementation Phase, study staff will repeat the rollout process in HC and community settings in a randomized, staggered fashion in the remaining eight counties/HCs. Evaluation will include analyses of electronic health record data and provider and county surveys. Rural HCs have been reluctant to participate in research because of concerns about capacity; however, this project should demonstrate that research does not need to be burdensome and can adapt to local needs and HC abilities. If effective, this approach could be disseminated to HC and community partners throughout Appalachia to encourage the uptake of effective interventions to reduce the burden of CRC.

We conducted a multi-site study to evaluate and improve CRC screening processes using implementation science strategies at multiple levels including the patient, provider, health center, and community. Our goals were to increase rates of guideline-recommended CRC screening, follow-up, and referral-to-care in an Appalachian, medically underserved population.

Factors related to retention in a longitudinal study of infants at familial risk for autism.

Background: Reporting retention data is critical to determining the soundness of a study's conclusions (internal validity) and broader generalizability (external validity). Although selective attrition can lead to overestimates of effects, biased conclusions, or overly expansive generalizations, retention rates are not reported in many longitudinal studies. Methods: We examined multiple child- and family-level factors potentially associated with retention in a longitudinal study of younger siblings of children with autism spectrum disorder (ASD; n = 304) or typical development (n = 163). The sample was followed from the first year of life to 36 months of age, for up to 7 visits. Results: Of the 467 infant siblings who were consented and participated in at least one research visit, 397 (85.0%) were retained to study completion at 36 months. Retention rates did not differ by familial risk group (ASD-risk vs. Low-risk), sex, race, ethnicity, age at enrollment, number of children in the family, maternal employment, marital status, or parent concerns about the child at enrollment. A stepwise regression model identified 4 variables that, together, provided the most parsimonious predictive model of study retention: maternal education, maternal age at child's birth, travel distance to the study site, and diagnostic outcome classification at the final study visit. Conclusions: The retained and not-retained groups did not differ on most demographic and clinical variables, suggesting few threats to internal and external validity. The significantly higher rate of retention of children diagnosed with ASD (95%) than typically developing children (83%) may, however, present biases when studying recurrence risk. We conclude by describing engagement and tracking methods that can be used to maximize retention in longitudinal studies of children at risk of ASD.

Factors associated with the accurate self-report of cancer screening behaviors among women living in the rural Midwest region of the United States.

This study examines the accuracy of the self-report of up-to-date cancer screening behaviors (Mammography, Papanicolaou (Pap)/Human Papillomavirus (HPV) tests, Fecal Occult Blood Test (FOBT)/Fecal Immunochemical Test (FIT), Colonoscopy) compared to medical record documentation prior to eligibility determination and enrollment in a randomized controlled trial of an intervention to increase cancer screening among women living in rural counties of Indiana and Ohio. Women (n = 1,641) completed surveys and returned a medical record release form from November 2016-June 2019. We compared self-report to medical records for up-to-date cancer screening behaviors to determine the validity of self-report. Logistic regression models identified variables associated with accurate reporting. Women were up-to-date for mammography (75 %), Pap/HPV test (54 %), colonoscopy (53 %), and FOBT/FIT (6 %) by medical record. Although 39.6 % of women reported being up-to-date for all three anatomic sites (breast, cervix, and colon), only 31.8 % were up to date by medical records. Correlates of accurate reporting of up-to-date cancer screening varied by screening test. Approximately-one-third of women in rural counties in the Midwest are up-to-date for all three anatomic sites and correlates of the accurate reporting of screening varied by test. Although most investigators use medical records to verify completion of cancer screening behaviors as the primary outcome of intervention trials, they do not usually use medical records for the routine verification of study eligibility. Study results suggest that future research should use medical record documentation of cancer screening behaviors to determine eligibility for trials evaluating interventions to increase cancer screening.

Application of the Updated WCRF/AICR Cancer Prevention Score as an Outcome for Cancer Survivors Participating in a Tailored and Intensive Dietary and Physical Activity Intervention.

The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) has defined evidence-based guidelines for cancer prevention. These recommendations have been operationalized into a quantitative index for individual assessment. Survivors of cancer are increasingly desiring guidance for diet and lifestyle, and in the absence of research in survivors, are often instructed to follow cancer prevention and public health guidelines. In this study, we examine the utility of the quantitative updated WCRF/AICR scoring criteria to assess change among cancer survivors with overweight/obesity (OW/OB) following an intensive behavioral intervention. We applied the WCRF/AICR scoring criteria (range 0−7) to examine changes over the duration of the study by paired t-tests. Two cancer survivor cohorts with OW/OB (n = 91) completed a six-month phase II clinical trial designed to improve dietary and physical activity patterns. At enrollment and post-intervention, participants completed assessments including anthropometrics, food frequency questionnaires, and objective evaluation of physical activity. Participants improved adherence to all scored recommendations, with a significant increase in mean score from enrollment (3.22 ± 1.06) to post-intervention (4.28 ± 1.04) (p < 0.001). Mean BMI and waist circumference improved (both p < 0.001). The greatest improvements were noted for fruit and non-starchy vegetable intakes (+39%, p < 0.001); the greatest decreases were observed for processed meat consumption (−70%, p < 0.001). The updated WCRF/AICR Score can be applied to cancer survivor intervention studies and provides a tool to compare trials in regard to the baseline status of populations enrolled and the success of the intervention. Future interventions incorporating standardized assessments will help guide effective strategies to improve the health and quality of life for cancer survivors.

Early predictors of language skills at 3 years of age vary based on diagnostic outcome: A baby siblings research consortium study.

While previous work has identified the early predictors of language skills in infants at elevated familial risk (ER) and low familial risk (LR) for autism spectrum disorder (ASD), no studies to date have explored whether these predictors vary based on diagnostic outcome of ASD or no ASD. The present study used a large, multisite dataset to examine associations between a set of commonly studied predictor variables (infant gesture abilities, fine motor skills, nonverbal cognition, and maternal education level), measured at 12 months, and language skills, measured at 3 years, across three diagnostic outcome groups-infants with ASD ("ASD"), ER infants without ASD ("ER-no ASD"), and LR infants without ASD ("LR-no ASD"). Findings revealed that the predictors of language skills differed across groups, as gesture abilities were positively associated with language skills in the ER-no ASD group but negatively associated with language skills in the ASD group. Furthermore, maternal education level was positively associated with language skills in the ASD and LR-no ASD groups only. Variability in these early predictors may help explain why language skills are heterogeneous across the autism spectrum, and, with further study, may help clinicians identify those in need of additional and/or specialized intervention services that support language development. LAY SUMMARY: The present study identified predictors of language skills in infants with and without autism spectrum disorder (ASD). Maternal education level and 12-month gesture abilities predicted 3-year language skills in infants with ASD. Measuring these predictors early in life may help identify infants and families in need of additional and/or specialized intervention services that support language development.

Social orienting and initiated joint attention behaviors in 9 to 12 month old children with autism spectrum disorder: A family home movies study.

According to the Social Motivation model children with autism show deficits in social orienting (looking at faces and responding to name) at the end of their first year of life. In this model, those deficits are both the earliest behavioral consequences of an alteration in the dopamine reward system balance and the foundation of the social impairments that characterize this neurodevelopmental disorder. The current study tests two of the main predictions of this model: that social orienting deficits are the first behavioral manifestation of autism, and that they are developmentally related to joint attention deficits. We retrospectively analyzed family home movies of 9- to 12-month-old infants, 29 of whom were later diagnosed with autism and 16 of whom were typically developing. After confirming that the videotapes of both groups were similar in content of the scenes recorded (contexts, type of social activity, etc.), we compared their social orienting (social gaze and responding to name) and joint attention behaviors (gaze alternation and gestures). No significant differences between groups were found in looking at faces, but the group with autism showed deficits in responding to name and initiations of joint attention (IJA). Looking at people was not significantly correlated with IJA behaviors, but response to name was. The lack of group differences in looking at faces between 9 and 12 months, and the existence of IJA difficulties in the ASD group without concurrent impairment in looking at faces, do not support predictions of the Social Motivation model. LAY SUMMARY: Various theories have been proposed to explain the emergence of autism symptoms early in life. This study tested two key predictions of the Social Motivation model. Comparing family movies of children 9- to 12-months-old later diagnosed with autism or with typical development, we did not observe difficulties in looking at other people's faces but children with autism responded to name and used gaze and gestures to direct the adult's attention to events of interest less frequently. This absence of difficulties in looking at faces does not fit with what the Social Motivation model of autism predicts and therefore we must develop alternative explanations.

Repetitive behavior with objects in infants developing autism predicts diagnosis and later social behavior as early as 9 months.

We evaluated repetitive behavior with objects in infants at risk for autism spectrum disorder (ASD) from 9 to 36 months of age, and associations between early repetitive behavior and social engagement. Infant siblings of children with ASD (high-risk) or typical development (low-risk) were administered a task eliciting repetitive object use at 9, 12, 15, 18, 24, and 36 months of age. Infants (n = 147) were classified into 1 of 3 outcome groups at 36 months: Low-Risk Non-ASD (n = 58), High-Risk Non-ASD (n = 72), and ASD (n = 17). Behavior was coded from video for frequencies of unusual visual inspection, spinning, and rotating behaviors. Differences in unusual visual inspection were most prominent, consistent, and present earliest: At 9 months, the ASD group engaged in this behavior more frequently than both other groups, persisting through 36 months. Differences in frequencies of spinning and rotating were later-appearing, more time-limited, and/or related to familial ASD risk rather than ultimate diagnosis. Sensitivity and specificity estimates for the presence of unusual visual inspection at 9 months of age were in the moderate range (.60 and .68, respectively) for ASD versus Low-Risk Non-ASD comparisons, generally increasing over time. Unusual visual inspection at 9 months predicted 12-month social behavior controlling for 9-month social behavior, but not vice versa, with no evidence of moderation by ASD diagnosis. In summary, unusual visual inspection of objects is present and stable by 9 months of age in infants developing ASD and predicts reduced social engagement three-months later. Close monitoring of this behavior may aid early detection. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Altered Gray-White Matter Boundary Contrast in Toddlers at Risk for Autism Relates to Later Diagnosis of Autism Spectrum Disorder.

BACKGROUND: Recent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the contrast of the gray-white matter boundary is decreased in adults with ASD. To determine how gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index of gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD. MATERIALS AND METHODS: We used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n = 20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at 3 years of age for diagnostic outcome. Three outcome groups were defined (ASD, n = 9; typical development, n = 8; non-typical development, n = 3). RESULTS: ASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e., prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network. LIMITATIONS: Our study is the first to measure maturational changes in GWC in toddlers who developed autism, but given the limited size of our sample results should be considered exploratory and warrant further replication in independent and larger samples. CONCLUSION: These preliminary results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread brain regions. Early onset of ASD diagnosis constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.

Measuring social-communication difficulties in school-age siblings of children with autism spectrum disorder: Standardized versus naturalistic assessment.

Younger siblings of children with autism spectrum disorder (ASD; high-risk siblings) are at elevated risk for developing the broader autism phenotype (BAP), which consists of subclinical features of ASD. We examined conversational skills in a naturalistic context and standardized assessments of pragmatic language and communication skills in high-risk and low-risk school-age children with BAP (n = 22) and ASD (n = 18) outcomes, as well as comparison children without ASD or BAP (n = 135). Children with BAP characteristics exhibited lower conversational skills than comparison children, but did not differ on any of three standardized measures. Only the conversational ratings significantly predicted membership in the BAP versus Comparison group. This suggests that naturalistic tasks are crucial when assessing social-communication difficulties in children with a family history of ASD. LAY SUMMARY: The broader autism phenotype (BAP) consists of subclinical features of autism spectrum disorder (ASD) and is more common among family members of those with ASD. School-age children with BAP characteristics exhibited lower conversational skills than comparison children, but did not differ on standardized language measures tapping similar abilities. This suggests that naturalistic tasks may be more sensitive to the social-communication difficulties seen in some children with a family history of ASD than the standardized language tests used in most evaluations.

Development of a multilevel intervention to increase colorectal cancer screening in Appalachia.

BACKGROUND: Colorectal cancer (CRC) screening rates are lower in Appalachian regions of the United States than in non-Appalachian regions. Given the availability of various screening modalities, there is critical need for culturally relevant interventions addressing multiple socioecological levels to reduce the regional CRC burden. In this report, we describe the development and baseline findings from year 1 of "Accelerating Colorectal Cancer Screening through Implementation Science (ACCSIS) in Appalachia," a 5-year, National Cancer Institute Cancer MoonshotSM-funded multilevel intervention (MLI) project to increase screening in Appalachian Kentucky and Ohio primary care clinics. METHODS: Project development was theory-driven and included the establishment of both an external Scientific Advisory Board and a Community Advisory Board to provide guidance in conducting formative activities in two Appalachian counties: one in Kentucky and one in Ohio. Activities included identifying and describing the study communities and primary care clinics, selecting appropriate evidence-based interventions (EBIs), and conducting a pilot test of MLI strategies addressing patient, provider, clinic, and community needs. RESULTS: Key informant interviews identified multiple barriers to CRC screening, including fear of screening, test results, and financial concerns (patient level); lack of time and competing priorities (provider level); lack of reminder or tracking systems and staff burden (clinic level); and cultural issues, societal norms, and transportation (community level). With this information, investigators then offered clinics a menu of EBIs and strategies to address barriers at each level. Clinics selected individually tailored MLIs, including improvement of patient education materials, provision of provider education (resulting in increased knowledge, p = .003), enhancement of electronic health record (EHR) systems and development of clinic screening protocols, and implementation of community CRC awareness events, all of which promoted stool-based screening (i.e., FIT or FIT-DNA). Variability among clinics, including differences in EHR systems, was the most salient barrier to EBI implementation, particularly in terms of tracking follow-up of positive screening results, whereas the development of clinic-wide screening protocols was found to promote fidelity to EBI components. CONCLUSIONS: Lessons learned from year 1 included increased recognition of variability among the clinics and how they function, appreciation for clinic staff and provider workload, and development of strategies to utilize EHR systems. These findings necessitated a modification of study design for subsequent years. TRIAL REGISTRATION: Trial NCT04427527 is registered at https://clinicaltrials.gov and was registered on June 11, 2020.

Immediate effects of treadmill walking in individuals with Lewy body dementia and Huntington's disease.

BACKGROUND: Treadmill training may improve gait disorders associated with neurodegenerative diseases. In Parkinson's disease (PD), treadmill training alters gait patterns after one session, and long-term training improves gait parameters, fall risk, and quality of life. RESEARCH QUESTION: What is the feasibility and safety of using this intervention for people with Lewy body dementia (LBD) or Huntington's disease (HD)? METHODS: In this observational study, 10 individuals with HD, 8 individuals with LBD, and 10 control individuals walked for 20 min on a treadmill using a speed dependent protocol starting at a slow comfortable speed and increasing incrementally toward their normal overground speed. Feasibility was determined by compliance to protocol and safety by no incidents of abnormal vital signs or expressions of distress. Changes in gait measures, Timed Up and Go (TUG) scores and quantitative motor function measures (Q-Motor; precision grasp force variability, finger and foot tapping frequency) before and after treadmill walking were analyzed using linear models. RESULTS: Treadmill training is feasible and safe in LBD and HD; although, participants could not initiate treadmill walking at their comfortable overground speeds, and only 3 participants with HD were able to achieve their overground walking speed within the 20-minute session. No changes in gait measures, TUG times, and Q-Motor measures were found among LBD and HD participants after treadmill walking, although control participants demonstrated significant increases in several gait measures, and foot tap frequency (estimated difference = 0.290; p = 0.026). SIGNIFICANCE: Longer and more frequent treadmill sessions may be needed to see gait and motor function effects in LBD and HD. Motor and cognitive impairments associated with these diseases may make them less amenable to the effects of treadmill training.

Declining Gaze to Faces in Infants Developing Autism Spectrum Disorder: Evidence From Two Independent Cohorts.

Two independent cohorts (N = 155, N = 126) of infants at high and low risk for autism spectrum disorder (ASD) were followed prospectively between 6 and 36 months of age, when n = 46 were diagnosed with ASD. Gaze to adult faces was coded-during a developmental assessment (Cohort 1) or a play interaction (Cohort 2). Across both cohorts, most children developing ASD showed sharp declines in gaze to faces over time, relative to children without ASD. These findings suggest that declining developmental trajectories may be more common than previously recognized by retrospective methods. Trajectory-based screening methods could potentially identify children in the early stages of symptom onset and allow for early intervention before the full disorder has developed.

Trajectories of Autism Symptom Severity Change During Early Childhood.

Autism symptom severity change was evaluated during early childhood in 125 children diagnosed with autism spectrum disorder (ASD). Children were assessed at approximately 3 and 6 years of age for autism symptom severity, IQ and adaptive functioning. Each child was assigned a change score, representing the difference between ADOS Calibrated Severity Scores (CSS) at the two ages. A Decreased Severity Group (28.8%) decreased by 2 or more points; a Stable Severity Group (54.4%) changed by 1 point or less; and an Increased Severity Group (16.8%) increased by 2 or more points. Girls tended to decrease in severity more than boys and increase in severity less than boys. There was no clear relationship between intervention history and membership in the groups.

Can Familial Risk for ADHD Be Detected in the First Two Years of Life?

Objective: We evaluated trajectories of attention-deficit/hyperactivity (ADHD)-relevant behaviors in a sample of infants at high and low familial risk for ADHD who were prospectively evaluated at 12, 18, and 24 months of age.Method: Participants included 43 infants at risk for ADHD based on family history (i.e., diagnosed first-degree relative) and 40 low-risk infants (i.e., no family history of ADHD). Instances of inattention, out-of-seat, and grabbing behavior were coded from video; analogous constructs were rated by examiners unaware of familial risk status after completing structured standardized assessments with the infants/toddlers. At the end of each study visit, examiners solicited parents' concerns about their child's behavior. Differences in ADHD-related behaviors and parent concerns were examined between 12 and 24 months of age.Results: Infants with an older sibling or parent diagnosed with ADHD were distinguishable from infants with no family history of ADHD as early as 12 months of age based on directly observed and examiner reports of behavior, particularly with respect to hyperactive-impulsive behavior. Parents of infants at familial risk for ADHD also reported significantly more behavior/temperament concerns as early as 12 months of age compared to parents of infants at low risk for ADHD.Conclusions: These findings highlight the ability to detect genetic liability for ADHD by the end of the first year of life, suggesting that well-designed family risk studies of ADHD are feasible and may be clinically valuable. They also suggest the potential for earlier detection of risk for ADHD than has previously been possible.

Dyadic Synchrony and Responsiveness in the First Year: Associations with Autism Risk.

In the first year of life, the ability to engage in sustained synchronous interactions develops as infants learn to match social partner behaviors and sequentially regulate their behaviors in response to others. Difficulties developing competence in these early social building blocks can impact later language skills, joint attention, and emotion regulation. For children at elevated risk for autism spectrum disorder (ASD), early dyadic synchrony and responsiveness difficulties may be indicative of emerging ASD and/or developmental concerns. As part of a prospective developmental monitoring study, infant siblings of children with ASD (high-risk group n = 104) or typical development (low-risk group n = 71), and their mothers completed a standardized play task when infants were 6, 9, and/or 12 months of age. These interactions were coded for the frequency and duration of infant and mother gaze, positive affect, and vocalizations, respectively. Using these codes, theory-driven composites were created to index dyadic synchrony and infant/maternal responsiveness. Multilevel models revealed significant risk group differences in dyadic synchrony and infant responsiveness by 12 months of age. In addition, high-risk infants with higher dyadic synchrony and infant responsiveness at 12 months received significantly higher receptive and expressive language scores at 36 months. The findings of the present study highlight that promoting dyadic synchrony and responsiveness may aid in advancing optimal development in children at elevated risk for autism. LAY SUMMARY: In families raising children with an autism spectrum disorder (ASD), younger siblings are at elevated risks for social communication difficulties. The present study explored whether social-communication differences were evident during a parent-child play task at 6, 9, and 12 months of age. For infant siblings of children with ASD, social differences during play were observed by 12 months of age and may inform ongoing monitoring and intervention efforts.

Suppressive myeloid cells are expanded by biliary tract cancer-derived cytokines in vitro and associate with aggressive disease.

BACKGROUND: BTC is an aggressive disease exacerbated by inflammation and immune suppression. Expansion of immunosuppressive cells occurs in biliary tract cancer (BTC), yet the role of BTC-derived cytokines in this process is unclear. METHODS: Activated signalling pathways and cytokine production were evaluated in a panel of human BTC cell lines. Human peripheral blood mononuclear cells (PBMCs) were cultured with BTC supernatants, with and without cytokine neutralising antibodies, and analysed by flow cytometry or immunoblot. A human BTC tissue microarray (TMA, n = 69) was stained for IL-6, GM-CSF, and CD33+S100a9+ cells and correlated with clinical outcomes. RESULTS: Immunomodulatory factors (IL-6, GM-CSF, MCP-1) were present in BTC supernatants. BTC supernatants expanded CD33dimCD11b+HLA-DRlow/- myeloid-derived suppressor cells (MDSCs) from human PBMCs. Neutralisation of IL-6 and GM-CSF in BTC supernatants inhibited activation of STAT3/5, respectively, in PBMCs, with heterogeneous effects on MDSC expansion in vitro. Staining of a BTC TMA revealed a positive correlation between IL-6 and GM-CSF, with each cytokine and more CD33+S100a9+ cells. Increased CD33+S100a9+ staining positively correlated with higher tumour grade, differentiation and the presence of satellite lesions. CONCLUSION: BTC-derived factors promote suppressive myeloid cell expansion, and higher numbers of CD33+S100a9+ cells in resectable BTC tumours correlates with more aggressive disease.

High Psychopathology Subgroup in Young Children With Autism: Associations With Biological Sex and Amygdala Volume.

OBJECTIVE: The aims of this study were to identify a subset of children with autism spectrum disorder (ASD) and co-occurring symptoms of psychopathology, and to evaluate associations between this subgroup and biological sex and amygdala volume. METHOD: Participants included 420 children (ASD: 91 girls, 209 boys; typically developing controls: 57 girls, 63 boys). Latent profile analysis was used to identify ASD subgroups based on symptoms of psychopathology, adaptive functioning, cognitive development, and autism severity. Differences in the proportions of girls and boys across subgroups were evaluated. Magnetic resonance imaging scans were acquired (346 children); amygdala volumes were evaluated in relation to subgroups and problem behavior scores. RESULTS: Three ASD subgroups were identified. One group was characterized by high levels of psychopathology and moderate impairment on other measures (High Psychopathology Moderate Impairments [HPMI], comprising 27% of the sample). The other two subgroups had lower symptoms of psychopathology but were differentiated by high and low levels of impairment on other measures. A higher proportion of girls were classified into the HPMI subgroup (40% of girls versus 22% of boys). Relative to controls, amygdala volumes were enlarged only in the HPMI subgroup. There was a positive association between right amygdala volume and internalizing behaviors in girls but not in boys with ASD. CONCLUSION: A higher proportion of girls with ASD faced greater challenges with psychopathology, suggesting a need for closer evaluation and potentially earlier intervention to help improve outcomes. Amygdala enlargement was associated with co-occurring symptoms of psychopathology, and sex-specific correlations with symptoms were observed.

The Developmental Sequence and Relations Between Gesture and Spoken Language in Toddlers With Autism Spectrum Disorder.

In typical development, gestures precede and predict language development. This study examines the developmental sequence of expressive communication and relations between specific gestural and language milestones in toddlers with autism spectrum disorder (ASD), who demonstrate marked difficulty with gesture production and language. Communication skills across five stages (gestures, word approximations, first words, gesture-word combinations, and two-word combinations) were assessed monthly by blind raters for toddlers with ASD participating in an randomized control trial of parent-mediated treatment (N = 42, 12-30 months). Findings revealed that toddlers acquired skills following a reliable (vs. idiosyncratic) sequence and the majority of toddlers combined gestures with words before combining words in speech, but in contrast to the pattern observed in typical development, a significant subset acquired pointing after first words.

A video-based measure to identify autism risk in infancy.

BACKGROUND: Signs of autism are present in the first 2 years of life, but the average age of diagnosis lags far behind. Instruments that improve detection of autism risk in infancy are needed. This study developed and tested the psychometric properties of a novel video-based approach to detecting ASD in infancy. METHODS: A prospective longitudinal study of children at elevated or lower risk for autism spectrum disorder was conducted. Participants were 76 infants with an older sibling with ASD and 37 infants with no known family history of autism. The Video-referenced Infant Rating System for Autism (VIRSA) is a web-based application that presents pairs of videos of parents and infants playing together and requires forced-choice judgments of which video is most similar to the child being rated. Parents rated participants on the VIRSA at 6, 9, 12, and 18 months of age. We examined split-half and test-retest reliability; convergent and discriminant validity; and sensitivity, specificity, and negative and positive predictive value for concurrent and 36-month ASD diagnoses. RESULTS: The VIRSA demonstrated satisfactory reliability and convergent and discriminant validity. VIRSA ratings were significantly lower for children ultimately diagnosed with ASD than children with typical development by 12 months of age. VIRSA scores at 18 months identified all children diagnosed with ASD at that age, as well as 78% of children diagnosed at 36 months. CONCLUSIONS: This study represents an initial step in the development of a novel video-based approach to detection of ASD in infancy. The VIRSA's psychometric properties were promising when used by parents with an older affected child, but still must be tested in community samples with no family history of ASD. If results are replicated, then the VIRSA's low-burden, web-based format has the potential to reduce disparities in communities with limited access to screening.

Onset, Trajectory, and Pattern of Feeding Difficulties in Toddlers Later Diagnosed with Autism.

OBJECTIVE: To examine the emergence and trajectory of feeding difficulties in young children who are later diagnosed with autism spectrum disorder (ASD). METHODS: The Behavioral Pediatrics Feeding Assessment Scale (BPFAS) was administered to a sample of 93 toddlers with an older sibling with ASD-the high-risk group-and 62 toddlers with no known familial ASD-the low-risk group-as part of a larger infant sibling study. The BPFAS was completed by parents at 15, 18, 24, and 36 months of age. At 36 months, participants underwent a diagnostic assessment and were classified into 1 of the following 4 outcome groups: ASD, nontypical development, high-risk typically developing, and low-risk typically developing. The BPFAS was scored for total frequency of feeding difficulties and autism-specific factor scores previously described in the literature. RESULTS: The frequency of feeding difficulties increased significantly more rapidly in the ASD group between 15 and 36 months of age, and by 36 months, they exhibited a significantly higher total frequency score than all other groups. Analysis of the factor scores revealed a similar pattern for the food acceptance and mealtime behavior domains but no significant differences in the medical/oral motor domain. CONCLUSION: Feeding difficulties develop significantly more rapidly in children with ASD, with longitudinal monitoring revealing the steeper trajectory earlier than can be detected with cross-sectional analysis. Children with ASD are at risk of health and social consequences of poor feeding behavior that may potentially be minimized if addressed early and appropriately.