Identifying crossovers and shared genetic material in whole genome sequencing data from families.

Large, whole-genome sequencing (WGS) data sets containing families provide an important opportunity to identify crossovers and shared genetic material in siblings. However, the high variant calling error rates of WGS in some areas of the genome can result in spurious crossover calls, and the special inheritance status of the X Chromosome presents challenges. We have developed a hidden Markov model that addresses these issues by modeling the inheritance of variants in families in the presence of error-prone regions and inherited deletions. We call our method PhasingFamilies. We validate PhasingFamilies using the platinum genome family NA1281 (precision: 0.81; recall: 0.97), as well as simulated genomes with known crossover positions (precision: 0.93; recall: 0.92). Using 1925 quads from the Simons Simplex Collection, we found that PhasingFamilies resolves crossovers to a median resolution of 3527.5 bp. These crossovers recapitulate existing recombination rate maps, including for the X Chromosome; produce sibling pair IBD that matches expected distributions; and are validated by the haplotype estimation tool SHAPEIT. We provide an efficient, open-source implementation of PhasingFamilies that can be used to identify crossovers from family sequencing data.

Machine learning models using mobile game play accurately classify children with autism.

Digitally-delivered healthcare is well suited to address current inequities in the delivery of care due to barriers of access to healthcare facilities. As the COVID-19 pandemic phases out, we have a unique opportunity to capitalize on the current familiarity with telemedicine approaches and continue to advocate for mainstream adoption of remote care delivery. In this paper, we specifically focus on the ability of GuessWhat? a smartphone-based charades-style gamified therapeutic intervention for autism spectrum disorder (ASD) to generate a signal that distinguishes children with ASD from neurotypical (NT) children. We demonstrate the feasibility of using "in-the-wild", naturalistic gameplay data to distinguish between ASD and NT by children by training a random forest classifier to discern the two classes (AU-ROC = 0.745, recall = 0.769). This performance demonstrates the potential for GuessWhat? to facilitate screening for ASD in historically difficult-to-reach communities. To further examine this potential, future work should expand the size of the training sample and interrogate differences in predictive ability by demographic.

Crowd annotations can approximate clinical autism impressions from short home videos with privacy protections.

Artificial Intelligence (A.I.) solutions are increasingly considered for telemedicine. For these methods to serve children and their families in home settings, it is crucial to ensure the privacy of the child and parent or caregiver. To address this challenge, we explore the potential for global image transformations to provide privacy while preserving the quality of behavioral annotations. Crowd workers have previously been shown to reliably annotate behavioral features in unstructured home videos, allowing machine learning classifiers to detect autism using the annotations as input. We evaluate this method with videos altered via pixelation, dense optical flow, and Gaussian blurring. On a balanced test set of 30 videos of children with autism and 30 neurotypical controls, we find that the visual privacy alterations do not drastically alter any individual behavioral annotation at the item level. The AUROC on the evaluation set was 90.0% ±7.5% for unaltered videos, 85.0% ±9.0% for pixelation, 85.0% ±9.0% for optical flow, and 83.3% ±9.3% for blurring, demonstrating that an aggregation of small changes across behavioral questions can collectively result in increased misdiagnosis rates. We also compare crowd answers against clinicians who provided the same annotations for the same videos as crowd workers, and we find that clinicians have higher sensitivity in their recognition of autism-related symptoms. We also find that there is a linear correlation (r = 0.75, p < 0.0001) between the mean Clinical Global Impression (CGI) score provided by professional clinicians and the corresponding score emitted by a previously validated autism classifier with crowd inputs, indicating that the classifier's output probability is a reliable estimate of the clinical impression of autism. A significant correlation is maintained with privacy alterations, indicating that crowd annotations can approximate clinician-provided autism impression from home videos in a privacy-preserved manner.

Classifying Autism From Crowdsourced Semistructured Speech Recordings: Machine Learning Model Comparison Study.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that results in altered behavior, social development, and communication patterns. In recent years, autism prevalence has tripled, with 1 in 44 children now affected. Given that traditional diagnosis is a lengthy, labor-intensive process that requires the work of trained physicians, significant attention has been given to developing systems that automatically detect autism. We work toward this goal by analyzing audio data, as prosody abnormalities are a signal of autism, with affected children displaying speech idiosyncrasies such as echolalia, monotonous intonation, atypical pitch, and irregular linguistic stress patterns. OBJECTIVE: We aimed to test the ability for machine learning approaches to aid in detection of autism in self-recorded speech audio captured from children with ASD and neurotypical (NT) children in their home environments. METHODS: We considered three methods to detect autism in child speech: (1) random forests trained on extracted audio features (including Mel-frequency cepstral coefficients); (2) convolutional neural networks trained on spectrograms; and (3) fine-tuned wav2vec 2.0-a state-of-the-art transformer-based speech recognition model. We trained our classifiers on our novel data set of cellphone-recorded child speech audio curated from the Guess What? mobile game, an app designed to crowdsource videos of children with ASD and NT children in a natural home environment. RESULTS: The random forest classifier achieved 70% accuracy, the fine-tuned wav2vec 2.0 model achieved 77% accuracy, and the convolutional neural network achieved 79% accuracy when classifying children's audio as either ASD or NT. We used 5-fold cross-validation to evaluate model performance. CONCLUSIONS: Our models were able to predict autism status when trained on a varied selection of home audio clips with inconsistent recording qualities, which may be more representative of real-world conditions. The results demonstrate that machine learning methods offer promise in detecting autism automatically from speech without specialized equipment.

Improved Digital Therapy for Developmental Pediatrics Using Domain-Specific Artificial Intelligence: Machine Learning Study.

BACKGROUND: Automated emotion classification could aid those who struggle to recognize emotions, including children with developmental behavioral conditions such as autism. However, most computer vision emotion recognition models are trained on adult emotion and therefore underperform when applied to child faces. OBJECTIVE: We designed a strategy to gamify the collection and labeling of child emotion-enriched images to boost the performance of automatic child emotion recognition models to a level closer to what will be needed for digital health care approaches. METHODS: We leveraged our prototype therapeutic smartphone game, GuessWhat, which was designed in large part for children with developmental and behavioral conditions, to gamify the secure collection of video data of children expressing a variety of emotions prompted by the game. Independently, we created a secure web interface to gamify the human labeling effort, called HollywoodSquares, tailored for use by any qualified labeler. We gathered and labeled 2155 videos, 39,968 emotion frames, and 106,001 labels on all images. With this drastically expanded pediatric emotion-centric database (>30 times larger than existing public pediatric emotion data sets), we trained a convolutional neural network (CNN) computer vision classifier of happy, sad, surprised, fearful, angry, disgust, and neutral expressions evoked by children. RESULTS: The classifier achieved a 66.9% balanced accuracy and 67.4% F1-score on the entirety of the Child Affective Facial Expression (CAFE) as well as a 79.1% balanced accuracy and 78% F1-score on CAFE Subset A, a subset containing at least 60% human agreement on emotions labels. This performance is at least 10% higher than all previously developed classifiers evaluated against CAFE, the best of which reached a 56% balanced accuracy even when combining "anger" and "disgust" into a single class. CONCLUSIONS: This work validates that mobile games designed for pediatric therapies can generate high volumes of domain-relevant data sets to train state-of-the-art classifiers to perform tasks helpful to precision health efforts.

A Mobile Game Platform for Improving Social Communication in Children with Autism: A Feasibility Study.

BACKGROUND: Many children with autism cannot receive timely in-person diagnosis and therapy, especially in situations where access is limited by geography, socioeconomics, or global health concerns such as the current COVD-19 pandemic. Mobile solutions that work outside of traditional clinical environments can safeguard against gaps in access to quality care. OBJECTIVE: The aim of the study is to examine the engagement level and therapeutic feasibility of a mobile game platform for children with autism. METHODS: We designed a mobile application, GuessWhat, which, in its current form, delivers game-based therapy to children aged 3 to 12 in home settings through a smartphone. The phone, held by a caregiver on their forehead, displays one of a range of appropriate and therapeutically relevant prompts (e.g., a surprised face) that the child must recognize and mimic sufficiently to allow the caregiver to guess what is being imitated and proceed to the next prompt. Each game runs for 90 seconds to create a robust social exchange between the child and the caregiver. RESULTS: We examined the therapeutic feasibility of GuessWhat in 72 children (75% male, average age 8 years 2 months) with autism who were asked to play the game for three 90-second sessions per day, 3 days per week, for a total of 4 weeks. The group showed significant improvements in Social Responsiveness Score-2 (SRS-2) total (3.97, p <0.001) and Vineland Adaptive Behavior Scales-II (VABS-II) socialization standard (5.27, p = 0.002) scores. CONCLUSION: The results support that the GuessWhat mobile game is a viable approach for efficacious treatment of autism and further support the possibility that the game can be used in natural settings to increase access to treatment when barriers to care exist.

Crowdsourced privacy-preserved feature tagging of short home videos for machine learning ASD detection.

Standard medical diagnosis of mental health conditions requires licensed experts who are increasingly outnumbered by those at risk, limiting reach. We test the hypothesis that a trustworthy crowd of non-experts can efficiently annotate behavioral features needed for accurate machine learning detection of the common childhood developmental disorder Autism Spectrum Disorder (ASD) for children under 8 years old. We implement a novel process for identifying and certifying a trustworthy distributed workforce for video feature extraction, selecting a workforce of 102 workers from a pool of 1,107. Two previously validated ASD logistic regression classifiers, evaluated against parent-reported diagnoses, were used to assess the accuracy of the trusted crowd's ratings of unstructured home videos. A representative balanced sample (N = 50 videos) of videos were evaluated with and without face box and pitch shift privacy alterations, with AUROC and AUPRC scores > 0.98. With both privacy-preserving modifications, sensitivity is preserved (96.0%) while maintaining specificity (80.0%) and accuracy (88.0%) at levels comparable to prior classification methods without alterations. We find that machine learning classification from features extracted by a certified nonexpert crowd achieves high performance for ASD detection from natural home videos of the child at risk and maintains high sensitivity when privacy-preserving mechanisms are applied. These results suggest that privacy-safeguarded crowdsourced analysis of short home videos can help enable rapid and mobile machine-learning detection of developmental delays in children.

Selection of trustworthy crowd workers for telemedical diagnosis of pediatric autism spectrum disorder.

Crowd-powered telemedicine has the potential to revolutionize healthcare, especially during times that require remote access to care. However, sharing private health data with strangers from around the world is not compatible with data privacy standards, requiring a stringent filtration process to recruit reliable and trustworthy workers who can go through the proper training and security steps. The key challenge, then, is to identify capable, trustworthy, and reliable workers through high-fidelity evaluation tasks without exposing any sensitive patient data during the evaluation process. We contribute a set of experimentally validated metrics for assessing the trustworthiness and reliability of crowd workers tasked with providing behavioral feature tags to unstructured videos of children with autism and matched neurotypical controls. The workers are blinded to diagnosis and blinded to the goal of using the features to diagnose autism. These behavioral labels are fed as input to a previously validated binary logistic regression classifier for detecting autism cases using categorical feature vectors. While the metrics do not incorporate any ground truth labels of child diagnosis, linear regression using the 3 correlative metrics as input can predict the mean probability of the correct class of each worker with a mean average error of 7.51% for performance on the same set of videos and 10.93% for performance on a distinct balanced video set with different children. These results indicate that crowd workers can be recruited for performance based largely on behavioral metrics on a crowdsourced task, enabling an affordable way to filter crowd workforces into a trustworthy and reliable diagnostic workforce.

Longitudinal study of stool-associated microbial taxa in sibling pairs with and without autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder influenced by both genetic and environmental factors. Recently, gut dysbiosis has emerged as a powerful contributor to ASD symptoms. In this study, we recruited over 100 age-matched sibling pairs (between 2 and 8 years old) where one had an Autism ASD diagnosis and the other was developing typically (TD) (432 samples total). We collected stool samples over four weeks, tracked over 100 lifestyle and dietary variables, and surveyed behavior measures related to ASD symptoms. We identified 117 amplicon sequencing variants (ASVs) that were significantly different in abundance between sibling pairs across all three timepoints, 11 of which were supported by at least two contrast methods. We additionally identified dietary and lifestyle variables that differ significantly between cohorts, and further linked those variables to the ASVs they statistically relate to. Overall, dietary and lifestyle features were explanatory of ASD phenotype using logistic regression, however, global compositional microbiome features were not. Leveraging our longitudinal behavior questionnaires, we additionally identified 11 ASVs associated with changes in reported anxiety over time within and across all individuals. Lastly, we find that overall microbiome composition (beta-diversity) is associated with specific ASD-related behavioral characteristics.

Training Affective Computer Vision Models by Crowdsourcing Soft-Target Labels.

Background/Introduction: Emotion detection classifiers traditionally predict discrete emotions. However, emotion expressions are often subjective, thus requiring a method to handle compound and ambiguous labels. We explore the feasibility of using crowdsourcing to acquire reliable soft-target labels and evaluate an emotion detection classifier trained with these labels. We hypothesize that training with labels that are representative of the diversity of human interpretation of an image will result in predictions that are similarly representative on a disjoint test set. We also hypothesize that crowdsourcing can generate distributions which mirror those generated in a lab setting. Methods: We center our study on the Child Affective Facial Expression (CAFE) dataset, a gold standard collection of images depicting pediatric facial expressions along with 100 human labels per image. To test the feasibility of crowdsourcing to generate these labels, we used Microworkers to acquire labels for 207 CAFE images. We evaluate both unfiltered workers as well as workers selected through a short crowd filtration process. We then train two versions of a ResNet-152 neural network on soft-target CAFE labels using the original 100 annotations provided with the dataset: (1) a classifier trained with traditional one-hot encoded labels, and (2) a classifier trained with vector labels representing the distribution of CAFE annotator responses. We compare the resulting softmax output distributions of the two classifiers with a 2-sample independent t-test of L1 distances between the classifier's output probability distribution and the distribution of human labels. Results: While agreement with CAFE is weak for unfiltered crowd workers, the filtered crowd agree with the CAFE labels 100% of the time for happy, neutral, sad and "fear + surprise", and 88.8% for "anger + disgust". While the F1-score for a one-hot encoded classifier is much higher (94.33% vs. 78.68%) with respect to the ground truth CAFE labels, the output probability vector of the crowd-trained classifier more closely resembles the distribution of human labels (t=3.2827, p=0.0014). Conclusions: For many applications of affective computing, reporting an emotion probability distribution that accounts for the subjectivity of human interpretation can be more useful than an absolute label. Crowdsourcing, including a sufficient filtering mechanism for selecting reliable crowd workers, is a feasible solution for acquiring soft-target labels.

Feature replacement methods enable reliable home video analysis for machine learning detection of autism.

Autism Spectrum Disorder is a neuropsychiatric condition affecting 53 million children worldwide and for which early diagnosis is critical to the outcome of behavior therapies. Machine learning applied to features manually extracted from readily accessible videos (e.g., from smartphones) has the potential to scale this diagnostic process. However, nearly unavoidable variability in video quality can lead to missing features that degrade algorithm performance. To manage this uncertainty, we evaluated the impact of missing values and feature imputation methods on two previously published autism detection classifiers, trained on standard-of-care instrument scoresheets and tested on ratings of 140 children videos from YouTube. We compare the baseline method of listwise deletion to classic univariate and multivariate techniques. We also introduce a feature replacement method that, based on a score, selects a feature from an expanded dataset to fill-in the missing value. The replacement feature selected can be identical for all records (general) or automatically adjusted to the record considered (dynamic). Our results show that general and dynamic feature replacement methods achieve a higher performance than classic univariate and multivariate methods, supporting the hypothesis that algorithmic management can maintain the fidelity of video-based diagnostics in the face of missing values and variable video quality.

Precision Telemedicine through Crowdsourced Machine Learning: Testing Variability of Crowd Workers for Video-Based Autism Feature Recognition.

Mobilized telemedicine is becoming a key, and even necessary, facet of both precision health and precision medicine. In this study, we evaluate the capability and potential of a crowd of virtual workers-defined as vetted members of popular crowdsourcing platforms-to aid in the task of diagnosing autism. We evaluate workers when crowdsourcing the task of providing categorical ordinal behavioral ratings to unstructured public YouTube videos of children with autism and neurotypical controls. To evaluate emerging patterns that are consistent across independent crowds, we target workers from distinct geographic loci on two crowdsourcing platforms: an international group of workers on Amazon Mechanical Turk (MTurk) (N = 15) and Microworkers from Bangladesh (N = 56), Kenya (N = 23), and the Philippines (N = 25). We feed worker responses as input to a validated diagnostic machine learning classifier trained on clinician-filled electronic health records. We find that regardless of crowd platform or targeted country, workers vary in the average confidence of the correct diagnosis predicted by the classifier. The best worker responses produce a mean probability of the correct class above 80% and over one standard deviation above 50%, accuracy and variability on par with experts according to prior studies. There is a weak correlation between mean time spent on task and mean performance (r = 0.358, p = 0.005). These results demonstrate that while the crowd can produce accurate diagnoses, there are intrinsic differences in crowdworker ability to rate behavioral features. We propose a novel strategy for recruitment of crowdsourced workers to ensure high quality diagnostic evaluations of autism, and potentially many other pediatric behavioral health conditions. Our approach represents a viable step in the direction of crowd-based approaches for more scalable and affordable precision medicine.

The Performance of Emotion Classifiers for Children With Parent-Reported Autism: Quantitative Feasibility Study.

BACKGROUND: Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits in social communication and interaction, and restricted and repetitive behaviors and interests. The incidence of ASD has increased in recent years; it is now estimated that approximately 1 in 40 children in the United States are affected. Due in part to increasing prevalence, access to treatment has become constrained. Hope lies in mobile solutions that provide therapy through artificial intelligence (AI) approaches, including facial and emotion detection AI models developed by mainstream cloud providers, available directly to consumers. However, these solutions may not be sufficiently trained for use in pediatric populations. OBJECTIVE: Emotion classifiers available off-the-shelf to the general public through Microsoft, Amazon, Google, and Sighthound are well-suited to the pediatric population, and could be used for developing mobile therapies targeting aspects of social communication and interaction, perhaps accelerating innovation in this space. This study aimed to test these classifiers directly with image data from children with parent-reported ASD recruited through crowdsourcing. METHODS: We used a mobile game called Guess What? that challenges a child to act out a series of prompts displayed on the screen of the smartphone held on the forehead of his or her care provider. The game is intended to be a fun and engaging way for the child and parent to interact socially, for example, the parent attempting to guess what emotion the child is acting out (eg, surprised, scared, or disgusted). During a 90-second game session, as many as 50 prompts are shown while the child acts, and the video records the actions and expressions of the child. Due in part to the fun nature of the game, it is a viable way to remotely engage pediatric populations, including the autism population through crowdsourcing. We recruited 21 children with ASD to play the game and gathered 2602 emotive frames following their game sessions. These data were used to evaluate the accuracy and performance of four state-of-the-art facial emotion classifiers to develop an understanding of the feasibility of these platforms for pediatric research. RESULTS: All classifiers performed poorly for every evaluated emotion except happy. None of the classifiers correctly labeled over 60.18% (1566/2602) of the evaluated frames. Moreover, none of the classifiers correctly identified more than 11% (6/51) of the angry frames and 14% (10/69) of the disgust frames. CONCLUSIONS: The findings suggest that commercial emotion classifiers may be insufficiently trained for use in digital approaches to autism treatment and treatment tracking. Secure, privacy-preserving methods to increase labeled training data are needed to boost the models' performance before they can be used in AI-enabled approaches to social therapy of the kind that is common in autism treatments.

Feature Selection and Dimension Reduction of Social Autism Data.

Autism Spectrum Disorder (ASD) is a complex neuropsychiatric condition with a highly heterogeneous phenotype. Following the work of Duda et al., which uses a reduced feature set from the Social Responsiveness Scale, Second Edition (SRS) to distinguish ASD from ADHD, we performed item-level question selection on answers to the SRS to determine whether ASD can be distinguished from non-ASD using a similarly small subset of questions. To explore feature redundancies between the SRS questions, we performed filter, wrapper, and embedded feature selection analyses. To explore the linearity of the SRS-related ASD phenotype, we then compressed the 65-question SRS into low-dimension representations using PCA, t-SNE, and a denoising autoencoder. We measured the performance of a multilayer perceptron (MLP) classifier with the top-ranking questions as input. Classification using only the top-rated question resulted in an AUC of over 92% for SRS-derived diagnoses and an AUC of over 83% for dataset-specific diagnoses. High redundancy of features have implications towards replacing the social behaviors that are targeted in behavioral diagnostics and interventions, where digital quantification of certain features may be obfuscated due to privacy concerns. We similarly evaluated the performance of an MLP classifier trained on the low-dimension representations of the SRS, finding that the denoising autoencoder achieved slightly higher performance than the PCA and t-SNE representations.

Identification and Quantification of Gaps in Access to Autism Resources in the United States: An Infodemiological Study.

BACKGROUND: Autism affects 1 in every 59 children in the United States, according to estimates from the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network in 2018. Although similar rates of autism are reported in rural and urban areas, rural families report greater difficulty in accessing resources. An overwhelming number of families experience long waitlists for diagnostic and therapeutic services. OBJECTIVE: The objective of this study was to accurately identify gaps in access to autism care using GapMap, a mobile platform that connects families with local resources while continuously collecting up-to-date autism resource epidemiological information. METHODS: After being extracted from various databases, resources were deduplicated, validated, and allocated into 7 categories based on the keywords identified on the resource website. The average distance between the individuals from a simulated autism population and the nearest autism resource in our database was calculated for each US county. Resource load, an approximation of demand over supply for diagnostic resources, was calculated for each US county. RESULTS: There are approximately 28,000 US resources validated on the GapMap database, each allocated into 1 or more of the 7 categories. States with the greatest distances to autism resources included Alaska, Nevada, Wyoming, Montana, and Arizona. Of the 7 resource categories, diagnostic resources were the most underrepresented, comprising only 8.83% (2472/28,003) of all resources. Alarmingly, 83.86% (2635/3142) of all US counties lacked any diagnostic resources. States with the highest diagnostic resource load included West Virginia, Kentucky, Maine, Mississippi, and New Mexico. CONCLUSIONS: Results from this study demonstrate the sparsity and uneven distribution of diagnostic resources in the United States, which may contribute to the lengthy waitlists and travel distances-barriers to be overcome to be able to receive diagnosis in specific regions. More data are needed on autism diagnosis demand to better quantify resource needs across the United States.

Addendum to the Acknowledgements: Validity of Online Screening for Autism: Crowdsourcing Study Comparing Paid and Unpaid Diagnostic Tasks.

[This corrects the article DOI: 10.2196/13668.].

Validity of Online Screening for Autism: Crowdsourcing Study Comparing Paid and Unpaid Diagnostic Tasks.

BACKGROUND: Obtaining a diagnosis of neuropsychiatric disorders such as autism requires long waiting times that can exceed a year and can be prohibitively expensive. Crowdsourcing approaches may provide a scalable alternative that can accelerate general access to care and permit underserved populations to obtain an accurate diagnosis. OBJECTIVE: We aimed to perform a series of studies to explore whether paid crowd workers on Amazon Mechanical Turk (AMT) and citizen crowd workers on a public website shared on social media can provide accurate online detection of autism, conducted via crowdsourced ratings of short home video clips. METHODS: Three online studies were performed: (1) a paid crowdsourcing task on AMT (N=54) where crowd workers were asked to classify 10 short video clips of children as "Autism" or "Not autism," (2) a more complex paid crowdsourcing task (N=27) with only those raters who correctly rated ≥8 of the 10 videos during the first study, and (3) a public unpaid study (N=115) identical to the first study. RESULTS: For Study 1, the mean score of the participants who completed all questions was 7.50/10 (SD 1.46). When only analyzing the workers who scored ≥8/10 (n=27/54), there was a weak negative correlation between the time spent rating the videos and the sensitivity (ρ=-0.44, P=.02). For Study 2, the mean score of the participants rating new videos was 6.76/10 (SD 0.59). The average deviation between the crowdsourced answers and gold standard ratings provided by two expert clinical research coordinators was 0.56, with an SD of 0.51 (maximum possible SD is 3). All paid crowd workers who scored 8/10 in Study 1 either expressed enjoyment in performing the task in Study 2 or provided no negative comments. For Study 3, the mean score of the participants who completed all questions was 6.67/10 (SD 1.61). There were weak correlations between age and score (r=0.22, P=.014), age and sensitivity (r=-0.19, P=.04), number of family members with autism and sensitivity (r=-0.195, P=.04), and number of family members with autism and precision (r=-0.203, P=.03). A two-tailed t test between the scores of the paid workers in Study 1 and the unpaid workers in Study 3 showed a significant difference (P<.001). CONCLUSIONS: Many paid crowd workers on AMT enjoyed answering screening questions from videos, suggesting higher intrinsic motivation to make quality assessments. Paid crowdsourcing provides promising screening assessments of pediatric autism with an average deviation <20% from professional gold standard raters, which is potentially a clinically informative estimate for parents. Parents of children with autism likely overfit their intuition to their own affected child. This work provides preliminary demographic data on raters who may have higher ability to recognize and measure features of autism across its wide range of phenotypic manifestations.

Detecting Developmental Delay and Autism Through Machine Learning Models Using Home Videos of Bangladeshi Children: Development and Validation Study.

BACKGROUND: Autism spectrum disorder (ASD) is currently diagnosed using qualitative methods that measure between 20-100 behaviors, can span multiple appointments with trained clinicians, and take several hours to complete. In our previous work, we demonstrated the efficacy of machine learning classifiers to accelerate the process by collecting home videos of US-based children, identifying a reduced subset of behavioral features that are scored by untrained raters using a machine learning classifier to determine children's "risk scores" for autism. We achieved an accuracy of 92% (95% CI 88%-97%) on US videos using a classifier built on five features. OBJECTIVE: Using videos of Bangladeshi children collected from Dhaka Shishu Children's Hospital, we aim to scale our pipeline to another culture and other developmental delays, including speech and language conditions. METHODS: Although our previously published and validated pipeline and set of classifiers perform reasonably well on Bangladeshi videos (75% accuracy, 95% CI 71%-78%), this work improves on that accuracy through the development and application of a powerful new technique for adaptive aggregation of crowdsourced labels. We enhance both the utility and performance of our model by building two classification layers: The first layer distinguishes between typical and atypical behavior, and the second layer distinguishes between ASD and non-ASD. In each of the layers, we use a unique rater weighting scheme to aggregate classification scores from different raters based on their expertise. We also determine Shapley values for the most important features in the classifier to understand how the classifiers' process aligns with clinical intuition. RESULTS: Using these techniques, we achieved an accuracy (area under the curve [AUC]) of 76% (SD 3%) and sensitivity of 76% (SD 4%) for identifying atypical children from among developmentally delayed children, and an accuracy (AUC) of 85% (SD 5%) and sensitivity of 76% (SD 6%) for identifying children with ASD from those predicted to have other developmental delays. CONCLUSIONS: These results show promise for using a mobile video-based and machine learning-directed approach for early and remote detection of autism in Bangladeshi children. This strategy could provide important resources for developmental health in developing countries with few clinical resources for diagnosis, helping children get access to care at an early age. Future research aimed at extending the application of this approach to identify a range of other conditions and determine the population-level burden of developmental disabilities and impairments will be of high value.

Enhancing Survivorship Care Planning for Patients With Localized Prostate Cancer Using a Couple-Focused mHealth Symptom Self-Management Program: Protocol for a Feasibility Study.

BACKGROUND: This project explores a new model of care that enhances survivorship care planning and promotes health for men with localized prostate cancer transitioning to posttreatment self-management. Survivorship care planning is important for patients with prostate cancer because of its high incidence rate in the United States, the frequent occurrence of treatment-related side effects, and reduced quality of life (QOL) for both men and their partners. A key component of comprehensive survivorship care planning is survivorship care plans (SCPs), documents that summarize cancer diagnosis, treatment, and plans for follow-up care. However, research concerning the effectiveness of SCPs on patient outcomes or health service use has thus far been inconclusive. SCPs that are tailored to individual patients' needs for information and care may improve effectiveness. OBJECTIVE: This study aims to examine the feasibility of an enhanced survivorship care plan (ESCP) that integrates a symptom self-management mHealth program called Prostate Cancer Education and Resources for Couples (PERC) into the existing standardized SCP. The specific aims are to (1) examine the feasibility of delivering ESCPs and (2) to estimate the magnitude of benefit of ESCPs. METHODS: We will use a two-group randomized controlled pretest-posttest design and collect data at baseline (T1) and 4 months later (T2) among 50 patients completing initial treatment for localized prostate cancer and their partners. First, we will assess the feasibility of ESCP by recruitment, enrollment, and retention rates; program satisfaction with the ESCP; and perceived ease of use of the ESCP. To achieve the secondary aim, we will compare the ESCP users with the standardized SCP users and assess their primary outcomes of QOL (overall, physical, emotional, and social QOL); secondary outcomes (reduction in negative appraisals and improvement in self-efficacy, social support, and health behaviors to manage symptoms); and number of visits to posttreatment care services between T1 and T2. We will assess the primary and secondary outcomes using measurements with sound psychometrical properties. We will use a qualitative and quantitative mixed methods approach to achieve the research aims. RESULTS: This project is ongoing and will be completed by the end of 2018. CONCLUSIONS: The results from this study will help design a definitive randomized trial to test the efficacy of the ESCPs, a potentially scalable program, to enhance supportive care for prostate cancer patients and their families.

Neural mechanisms of negative reinforcement in children and adolescents with autism spectrum disorders.

BACKGROUND: Previous research has found accumulating evidence for atypical reward processing in autism spectrum disorders (ASD), particularly in the context of social rewards. Yet, this line of research has focused largely on positive social reinforcement, while little is known about the processing of negative reinforcement in individuals with ASD. METHODS: The present study examined neural responses to social negative reinforcement (a face displaying negative affect) and non-social negative reinforcement (monetary loss) in children with ASD relative to typically developing children, using functional magnetic resonance imaging (fMRI). RESULTS: We found that children with ASD demonstrated hypoactivation of the right caudate nucleus while anticipating non-social negative reinforcement and hypoactivation of a network of frontostriatal regions (including the nucleus accumbens, caudate nucleus, and putamen) while anticipating social negative reinforcement. In addition, activation of the right caudate nucleus during non-social negative reinforcement was associated with individual differences in social motivation. CONCLUSIONS: These results suggest that atypical responding to negative reinforcement in children with ASD may contribute to social motivational deficits in this population.