ABSTRACT
Infant-directed singing is a culturally universal musical phenomenon known to promote the bonding of infants and caregivers. Entrainment is a widely observed physical phenomenon by which diverse physical systems adjust rhythmic activity through interaction. Here we show that the simple act of infant-directed singing entrains infant social visual behavior on subsecond timescales, increasing infants' looking to the eyes of a singing caregiver: as early as 2 months of age, and doubling in strength by 6 months, infants synchronize their eye-looking to the rhythm of infant-directed singing. Rhythmic entrainment also structures caregivers' own cueing, enhancing their visual display of social-communicative content: caregivers increase wide-eyed positive affect, reduce neutral facial affect, reduce eye motion, and reduce blinking, all in time with the rhythm of their singing and aligned in time with moments when infants increase their eye-looking. In addition, if the rhythm of infant-directed singing is experimentally disrupted-reducing its predictability-then infants' time-locked eye-looking is also disrupted. These results reveal generic processes of entrainment as a fundamental coupling mechanism by which the rhythm of infant-directed singing attunes infants to precisely timed social-communicative content and supports social learning and development.
Subject(s)
Attention , Infant Behavior , Music , Singing , Humans , Infant , Communication , Fixation, OcularABSTRACT
As infants develop, caregivers adjust their behaviour to scaffold their infant's emerging skills, such that changes in infants' social abilities are expected to elicit changes in caregiver behaviour. We examined whether changes in the probability of infant-directed caregiving behaviour-specifically, greeting, a ubiquitous signal used by caregivers to initiate reciprocal interactions-differ between infant-caregiver dyads with an infant later diagnosed with autism and dyads with a neurotypically developing infant during infants' first 6 months. Using longitudinal data from 163 dyads, we found that caregivers in autism dyads (n = 40) used greeting less and at later infant ages than caregivers with a neurotypically developing infant (neurotypical dyads, n = 83). Caregivers in dyads with infants at elevated familial genetic likelihood for autism who did not receive an autism diagnosis (EL-non-autism dyads, n = 40) showed no differences in greeting compared with neurotypical dyads. Socioeconomic status partially mediated the difference between autism and neurotypical dyads. These findings show that autism and socioeconomic status were associated with the mutually adapted dynamics of dyadic interaction beginning in the first postnatal weeks. Importantly, differences in caregiver greeting observed in autism dyads are not interpreted as suboptimal behaviour from caregivers but rather indicate how early emerging social differences related to autism, years before overt features are present, may alter social learning opportunities elicited by the infant.
Subject(s)
Autistic Disorder , Caregivers , Humans , Infant , Male , Female , Child Development , Longitudinal Studies , Infant Behavior , Social BehaviorABSTRACT
The mechanisms by which infant-directed (ID) speech and song support language development in infancy are poorly understood, with most prior investigations focused on the auditory components of these signals. However, the visual components of ID communication are also of fundamental importance for language learning: over the first year of life, infants' visual attention to caregivers' faces during ID speech switches from a focus on the eyes to a focus on the mouth, which provides synchronous visual cues that support speech and language development. Caregivers' facial displays during ID song are highly effective for sustaining infants' attention. Here we investigate if ID song specifically enhances infants' attention to caregivers' mouths. 299 typically developing infants watched clips of female actors engaging them with ID song and speech longitudinally at six time points from 3 to 12 months of age while eye-tracking data was collected. Infants' mouth-looking significantly increased over the first year of life with a significantly greater increase during ID song versus speech. This difference was early-emerging (evident in the first 6 months of age) and sustained over the first year. Follow-up analyses indicated specific properties inherent to ID song (e.g., slower tempo, reduced rhythmic variability) in part contribute to infants' increased mouth-looking, with effects increasing with age. The exaggerated and expressive facial features that naturally accompany ID song may make it a particularly effective context for modulating infants' visual attention and supporting speech and language development in both typically developing infants and those with or at risk for communication challenges. A video abstract of this article can be viewed at https://youtu.be/SZ8xQW8h93A. RESEARCH HIGHLIGHTS: Infants' visual attention to adults' mouths during infant-directed speech has been found to support speech and language development. Infant-directed (ID) song promotes mouth-looking by infants to a greater extent than does ID speech across the first year of life. Features characteristic of ID song such as slower tempo, increased rhythmicity, increased audiovisual synchrony, and increased positive affect, all increase infants' attention to the mouth. The effects of song on infants' attention to the mouth are more prominent during the second half of the first year of life.
Subject(s)
Speech Perception , Humans , Infant , Female , Adult , Speech , Mouth , Language Development , FaceABSTRACT
Long before infants reach, crawl or walk, they explore the world by looking: they look to learn and to engage, giving preferential attention to social stimuli, including faces, face-like stimuli and biological motion. This capacity-social visual engagement-shapes typical infant development from birth and is pathognomonically impaired in children affected by autism. Here we show that variation in viewing of social scenes, including levels of preferential attention and the timing, direction and targeting of individual eye movements, is strongly influenced by genetic factors, with effects directly traceable to the active seeking of social information. In a series of eye-tracking experiments conducted with 338 toddlers, including 166 epidemiologically ascertained twins (enrolled by representative sampling from the general population), 88 non-twins with autism and 84 singleton controls, we find high monozygotic twin-twin concordance (0.91) and relatively low dizygotic concordance (0.35). Moreover, the characteristics that are the most highly heritable, preferential attention to eye and mouth regions of the face, are also those that are differentially decreased in children with autism (χ2 = 64.03, P < 0.0001). These results implicate social visual engagement as a neurodevelopmental endophenotype not only for autism, but also for population-wide variation in social-information seeking. In addition, these results reveal a means of human biological niche construction, with phenotypic differences emerging from the interaction of individual genotypes with early life experience.
Subject(s)
Attention , Autistic Disorder/genetics , Autistic Disorder/physiopathology , Child Development , Face , Fixation, Ocular/genetics , Interpersonal Relations , Autistic Disorder/psychology , Child, Preschool , Endophenotypes , Eye , Face/anatomy & histology , Female , Humans , Infant , Male , Mouth , Siblings , Twins, Dizygotic/genetics , Twins, Monozygotic/geneticsABSTRACT
BACKGROUND: There is an ongoing need for research to support the practice of high quality family medicine. The Family Medicine Discovers Rapid Cycle Scientific Discovery and Innovation (FMD RapSDI) program is designed to build capacity for family medicine scientific discovery and innovation in the United States. Our objective was to describe the applicants and research questions submitted to the RapSDI program in 2019 and 2020. METHODS: Descriptive analysis for applicant characteristics and rapid qualitative analysis using principles of grounded theory and content analysis to examine the research questions and associated themes. We examined differences by year of application submission and the applicant's career stage. RESULTS: Sixty-five family physicians submitted 70 applications to the RapSDI program; 45 in 2019 and 25 in 2020. 41% of applicants were in practice for five years or less (n = 27), 18% (n = 12) were in in practice 6-10 years, and 40% (n = 26) were ≥ 11 years in practice. With significant diversity in questions, the most common themes were studies of new innovations (n = 20, 28%), interventions to reduce cost (n = 20, 28%), improving screening or diagnosis (n = 19, 27%), ways to address mental or behavioral health (n = 18, 26%), and improving care for vulnerable populations (n = 18, 26%). CONCLUSION: Applicants proposed a range of research questions and described why family medicine is optimally suited to address the questions. Applicants had a desire to develop knowledge to help other family physicians, their patients, and their communities. Findings from this study can help inform other family medicine research capacity building initiatives.
Subject(s)
Family Practice , Physicians, Family , Humans , Capacity Building , Grounded Theory , KnowledgeABSTRACT
Importance: In the US, children with signs of autism often experience more than 1 year of delay before diagnosis and often experience longer delays if they are from racially, ethnically, or economically disadvantaged backgrounds. Most diagnoses are also received without use of standardized diagnostic instruments. To aid in early autism diagnosis, eye-tracking measurement of social visual engagement has shown potential as a performance-based biomarker. Objective: To evaluate the performance of eye-tracking measurement of social visual engagement (index test) relative to expert clinical diagnosis in young children referred to specialty autism clinics. Design, Setting, and Participants: In this study of 16- to 30-month-old children enrolled at 6 US specialty centers from April 2018 through May 2019, staff blind to clinical diagnoses used automated devices to measure eye-tracking-based social visual engagement. Expert clinical diagnoses were made using best practice standardized protocols by specialists blind to index test results. This study was completed in a 1-day protocol for each participant. Main Outcomes and Measures: Primary outcome measures were test sensitivity and specificity relative to expert clinical diagnosis. Secondary outcome measures were test correlations with expert clinical assessments of social disability, verbal ability, and nonverbal cognitive ability. Results: Eye-tracking measurement of social visual engagement was successful in 475 (95.2%) of the 499 enrolled children (mean [SD] age, 24.1 [4.4] months; 38 [8.0%] were Asian; 37 [7.8%], Black; 352 [74.1%], White; 44 [9.3%], other; and 68 [14.3%], Hispanic). By expert clinical diagnosis, 221 children (46.5%) had autism and 254 (53.5%) did not. In all children, measurement of social visual engagement had sensitivity of 71.0% (95% CI, 64.7% to 76.6%) and specificity of 80.7% (95% CI, 75.4% to 85.1%). In the subgroup of 335 children whose autism diagnosis was certain, sensitivity was 78.0% (95% CI, 70.7% to 83.9%) and specificity was 85.4% (95% CI, 79.5% to 89.8%). Eye-tracking test results correlated with expert clinical assessments of individual levels of social disability (r = -0.75 [95% CI, -0.79 to -0.71]), verbal ability (r = 0.65 [95% CI, 0.59 to 0.70]), and nonverbal cognitive ability (r = 0.65 [95% CI, 0.59 to 0.70]). Conclusions and Relevance: In 16- to 30-month-old children referred to specialty clinics, eye-tracking-based measurement of social visual engagement was predictive of autism diagnoses by clinical experts. Further evaluation of this test's role in early diagnosis and assessment of autism in routine specialty clinic practice is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03469986.
Subject(s)
Autistic Disorder , Eye-Tracking Technology , Social Behavior , Visual Perception , Child, Preschool , Humans , Infant , Ambulatory Care Facilities , Asian , Autistic Disorder/diagnosis , Autistic Disorder/physiopathology , Autistic Disorder/psychology , Eye Movements/physiologyABSTRACT
BACKGROUND: Despite widespread recommendations for early surveillance of risk for autism spectrum disorder (ASD), no research to date has shown that early surveillance leads to better clinical outcomes. Preliminary research has suggested that children with ASD ascertained via prospective follow-up have better outcomes than those ascertained via community referral. Because prospective studies include early surveillance, by comparing outcomes of children with ASD across ascertainment strategies, we may gain insight into the effects of early surveillance relative to its absence. METHODS: A systematic review was conducted to identify studies reporting outcomes of 24- to 36-month-olds with ASD ascertained via prospective follow-up, community referral, or universal screening. A meta-analysis using a random effects model was used to calculate overall effect size estimates for developmental level and symptom severity across ascertainment cohorts. RESULTS: Eleven prospective, ten community referral, and eight universal screening studies were identified, reporting on 1,658 toddlers with ASD. We found no differences in outcomes between community referral and universal screening studies. Relative to both, prospective studies reported significantly higher developmental levels and lower symptom severities. CONCLUSIONS: Outcomes of young children with ASD ascertained via prospective follow-up are better than those of children with ASD recruited via community referral or universal screening. Although we discuss why sampling bias is not likely the driving force behind these findings, we cannot rule out the possibility that sampling bias contributes to the observed differences; future studies should probe the effects of sociodemographic variables on clinical outcomes as a function of ascertainment strategy. This limitation notwithstanding, our results raise the possibility that prospective follow-up may confer a 'surveillance effect' that contributes to improved developmental and diagnostic outcomes in children with ASD. Future research should test this hypothesis and determine the specific mechanism by which surveillance may improve outcomes.
Subject(s)
Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/therapy , Outcome and Process Assessment, Health Care , Child, Preschool , Humans , InfantABSTRACT
The national priority to advance early detection and intervention for children with autism spectrum disorder (ASD) has not reduced the late age of ASD diagnosis in the US over several consecutive Centers for Disease Control and Prevention (CDC) surveillance cohorts, with traditionally under-served populations accessing diagnosis later still. In this review, we explore a potential perceptual barrier to this enterprise which views ASD in terms that are contradicted by current science, and which may have its origins in the current definition of the condition and in its historical associations. To address this perceptual barrier, we propose a re-definition of ASD in early brain development terms, with a view to revisit the world of opportunities afforded by current science to optimize children's outcomes despite the risks that they are born with. This view is presented here to counter outdated notions that potentially devastating disability is determined the moment a child is born, and that these burdens are inevitable, with opportunities for improvement being constrained to only alleviation of symptoms or limited improvements in adaptive skills. The impetus for this piece is the concern that such views of complex neurodevelopmental conditions, such as ASD, can become self-fulfilling science and policy, in ways that are diametrically opposed to what we currently know, and are learning every day, of how genetic risk becomes, or not, instantiated as lifetime disabilities.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Brain/diagnostic imaging , Child , HumansABSTRACT
Deficits in eye contact have been a hallmark of autism since the condition's initial description. They are cited widely as a diagnostic feature and figure prominently in clinical instruments; however, the early onset of these deficits has not been known. Here we show in a prospective longitudinal study that infants later diagnosed with autism spectrum disorders (ASDs) exhibit mean decline in eye fixation from 2 to 6 months of age, a pattern not observed in infants who do not develop ASD. These observations mark the earliest known indicators of social disability in infancy, but also falsify a prior hypothesis: in the first months of life, this basic mechanism of social adaptive action--eye looking--is not immediately diminished in infants later diagnosed with ASD; instead, eye looking appears to begin at normative levels prior to decline. The timing of decline highlights a narrow developmental window and reveals the early derailment of processes that would otherwise have a key role in canalizing typical social development. Finally, the observation of this decline in eye fixation--rather than outright absence--offers a promising opportunity for early intervention that could build on the apparent preservation of mechanisms subserving reflexive initial orientation towards the eyes.
Subject(s)
Autistic Disorder/diagnosis , Autistic Disorder/physiopathology , Eye Movements , Case-Control Studies , Child Development , Child, Preschool , Disease Susceptibility , Eye Movements/physiology , Female , Fixation, Ocular/physiology , Humans , Infant , Longitudinal Studies , Male , Risk , Social BehaviorABSTRACT
OBJECTIVES: To describe hospital utilization and costs associated with preterm or low birth weight births (preterm/LBW) by payer prior to implementation of the Affordable Care Act and to identify areas for improvement in the quality of care received among preterm/LBW infants. METHODS: Hospital utilization-defined as mean length of stay (LOS, days), secondary diagnoses for birth hospitalizations, primary diagnoses for rehospitalizations, and transfer status-and costs were described among preterm/LBW infants using the 2009 Nationwide Inpatient Sample. RESULTS: Approximately 9.1 % of included hospitalizations (n = 4,167,900) were births among preterm/LBW infants; however, these birth hospitalizations accounted for 43.4 % of total costs. Rehospitalizations of all infants occurred at a rate of 5.9 % overall, but accounted for 22.6 % of total costs. This pattern was observed across all payer types. The prevalence of rehospitalizations was nearly twice as high among preterm/LBW infants covered by Medicaid (7.6 %) compared to commercially-insured infants (4.3 %). Neonatal transfers were more common among preterm/LBW infants whose deliveries and hospitalizations were covered by Medicaid (7.3 %) versus commercial insurance (6.5 %). Uninsured/self-pay preterm and LBW infants died in-hospital during the first year of life at a rate of 91 per 1000 discharges-nearly three times higher than preterm and LBW infants covered by either Medicaid (37 per 1000) or commercial insurance (32 per 1000). CONCLUSIONS: When comparing preterm/LBW infants whose births were covered by Medicaid and commercial insurance, there were few differences in length of hospital stays and costs. However, opportunities for improvement within Medicaid and CHIP exist with regard to reducing rehospitalizations and neonatal transfers.
Subject(s)
Delivery of Health Care/economics , Health Services/statistics & numerical data , Hospitalization/economics , Infant, Low Birth Weight , Infant, Premature , Premature Birth/economics , Female , Health Care Surveys , Health Services/economics , Humans , Infant, Newborn , Medicaid , Patient Protection and Affordable Care Act , Pregnancy , Premature Birth/epidemiology , Quality of Health Care , United StatesABSTRACT
BACKGROUND: Reciprocal social behavior (RSB) is a developmental prerequisite for social competency, and deficits in RSB constitute a core feature of autism spectrum disorder (ASD). Although clinical screeners categorically ascertain risk of ASD in early childhood, rapid methods for quantitative measurement of RSB in toddlers are not yet established. Such measurements are critical for tracking developmental trajectories and incremental responses to intervention. METHODS: We developed and validated a 20-min video-referenced rating scale, the video-referenced rating of reciprocal social behavior (vrRSB), for untrained caregivers to provide standardized ratings of quantitative variation in RSB. Parents of 252 toddler twins [Monozygotic (MZ) = 31 pairs, Dizygotic (DZ) = 95 pairs] ascertained through birth records, rated their twins' RSB at two time points, on average 6 months apart, and completed two developmental measures, the Modified Checklist for Autism in Toddlers (M-CHAT) and the MacArthur Communicative Development Inventory Short Form (MCDI-s). RESULTS: Scores on the vrRSB were fully continuously distributed, with excellent 6-month test-retest reliability ([intraclass correlation coefficient] ICC = 0.704, p < .000). MZ twins displayed markedly greater trait concordance than DZ twins, (MZ ICC = 0.863, p < .000, DZ ICC = 0.231, p < .012). VrRSB score distributions were highly distinct for children passing versus failing the M-CHAT (t = -8.588, df = 31, p < .000), incrementally improved from 18-24 months, and were inversely correlated with receptive and expressive vocabulary on the MCDI-s. CONCLUSIONS: Like quantitative autistic trait ratings in school-aged children and adults, toddler scores on the vrRSB are continuously distributed and appear highly heritable. These ratings exhibited minimal measurement error, high inter-individual stability, and developmental progression in RSB as children matured from 18-24 months, supporting their potential utility for serially quantifying the severity of early autistic syndromes over time and in response to intervention. In addition, these findings inform the genetic-environmental structure of RSB in early typical development.
Subject(s)
Child Behavior/physiology , Child Development/physiology , Neuropsychological Tests/standards , Psychometrics/instrumentation , Social Behavior , Child, Preschool , Female , Humans , Infant , MaleABSTRACT
Typically developing human infants preferentially attend to biological motion within the first days of life. This ability is highly conserved across species and is believed to be critical for filial attachment and for detection of predators. The neural underpinnings of biological motion perception are overlapping with brain regions involved in perception of basic social signals such as facial expression and gaze direction, and preferential attention to biological motion is seen as a precursor to the capacity for attributing intentions to others. However, in a serendipitous observation, we recently found that an infant with autism failed to recognize point-light displays of biological motion, but was instead highly sensitive to the presence of a non-social, physical contingency that occurred within the stimuli by chance. This observation raised the possibility that perception of biological motion may be altered in children with autism from a very early age, with cascading consequences for both social development and the lifelong impairments in social interaction that are a hallmark of autism spectrum disorders. Here we show that two-year-olds with autism fail to orient towards point-light displays of biological motion, and their viewing behaviour when watching these point-light displays can be explained instead as a response to non-social, physical contingencies--physical contingencies that are disregarded by control children. This observation has far-reaching implications for understanding the altered neurodevelopmental trajectory of brain specialization in autism.
Subject(s)
Attention/physiology , Autistic Disorder/physiopathology , Movement/physiology , Social Behavior , Acoustic Stimulation , Calibration , Child, Preschool , Computers , Fixation, Ocular/physiology , Humans , Light , Motion , Motion Pictures , Photic Stimulation , Video RecordingABSTRACT
Dietary lipids serve as important sources of energy and essential fatty acids for aquatic animals. Sources of animal and plant oils are increasingly limited as well as expensive, and dietary requirements associated with the inclusion of these oils must be carefully evaluated to facilitate sustainable and affordable formulations. In this study, we investigated quantities of menhaden oil (MO) with and without soybean lecithin or soybean oil (SO) to determine appropriate levels for optimal somatic growth for pre-gonadal juvenile Lytechinus variegatus. We prepared semi-purified diets that varied in neutral lipid content (0, 2, 4, or 8% dry matter) and soy lecithin (0 or 2%) and exchanged lipids reciprocally with purified starch while holding constant all other nutrients. We maintained laboratory-reared juvenile L. variegatus (average initial wet weight 82 ± 0.7 mg, mean ± SE , n = 9 treatment-1) in recirculating seawater systems and fed each daily a sub-satiation ration for five weeks. We assessed wet weights and test diameters every two weeks and at the end of the experiment (5 wk). Level of MO with or without soybean lecithin did not significantly affect wet weight gain; however, increasing levels of SO in the diet reduced wet weight gain and dry matter production efficiency and increased feed conversion ratio. Dry gut weight was positively correlated with level of MO. Lipid level in the gut increased with increasing dietary lipid level, regardless of source. These data suggest the composition of the SO is inhibitory for either nutrient absorption or metabolic processes associated with growth at this life stage. Diets containing total lipid levels of approximately 5 to 6% that include sources of n-3 fatty acids may support optimal growth for pre-gonadal juvenile L. variegatus.
ABSTRACT
The burdens faced by military families who have a child with autism are unique. The usual challenges of securing diagnostic, treatment, and educational services are compounded by life circumstances that include the anxieties of war, frequent relocation and separation, and a demand structure that emphasizes mission readiness and service. Recently established military autism-specific health care benefits set the stage for community-viable and cost-effective solutions that can achieve better outcomes for children and greater well-being for families. Here we argue for implementation of evidence-based solutions focused on reducing age of diagnosis and improving access to early intervention, as well as establishment of a tiered menu of services, individualized to the child and family, that fit with the military ethos and system of health care. Absence of this new model of care could compromise the utility and sustainability of the autism-specific benefit.
Subject(s)
Autism Spectrum Disorder/economics , Autism Spectrum Disorder/therapy , Cost-Benefit Analysis , Military Family/economics , Autism Spectrum Disorder/diagnosis , Behavior , Evidence-Based Medicine , Humans , Treatment OutcomeABSTRACT
Spontaneous eye blinking serves a critical physiological function, but it also interrupts incoming visual information. This tradeoff suggests that the inhibition of eye blinks might constitute an adaptive reaction to minimize the loss of visual information, particularly information that a viewer perceives to be important. To test this hypothesis, we examined whether the timing of blink inhibition, during natural viewing, is modulated between as well as within tasks, and also whether the timing of blink inhibition varies as a function of viewer engagement and stimulus event type. While viewing video scenes, we measured the timing of blinks and blink inhibition, as well as visual scanning, in a group of typical two-year-olds, and in a group of two-year-olds known for attenuated reactivity to affective stimuli: toddlers with Autism Spectrum Disorders (ASD). Although both groups dynamically adjusted the timing of their blink inhibition at levels greater than expected by chance, they inhibited their blinking and shifted visual fixation differentially with respect to salient onscreen events. Moreover, typical toddlers inhibited their blinking earlier than toddlers with ASD, indicating active anticipation of the unfolding of those events. These findings indicate that measures of blink inhibition can serve as temporally precise markers of perceived stimulus salience and are useful quantifiers of atypical processing of social affective signals in toddlers with ASD.
Subject(s)
Attention/physiology , Blinking/physiology , Child Development Disorders, Pervasive/physiopathology , Child Development/physiology , Cognition/physiology , Eye Movements/physiology , Child, Preschool , Fixation, Ocular , Humans , Pattern Recognition, Visual/physiology , Photic Stimulation , Time Factors , Video RecordingABSTRACT
Differences in looking at the eyes of others are one of the earliest behavioral markers for social difficulties in neurodevelopmental disabilities, including autism. However, it is unknown how early visuo-social experiences relate to the maturation of infant brain networks that process visual social stimuli. We investigated functional connectivity (FC) within the ventral visual object pathway as a contributing neural system. Densely sampled, longitudinal eye-tracking and resting state fMRI (rs-fMRI) data were collected from infant rhesus macaques, an important model of human social development, from birth through 6 months of age. Mean trajectories were fit for both datasets and individual trajectories from subjects with both eye-tracking and rs-fMRI data were used to test for brain-behavior relationships. Exploratory findings showed infants with greater increases in FC between left V1 to V3 visual areas have an earlier increase in eye-looking before 2 months. This relationship was moderated by social status such that infants with low social status had a stronger association between left V1 to V3 connectivity and eye-looking than high status infants. Results indicated that maturation of the visual object pathway may provide an important neural substrate supporting adaptive transitions in social visual attention during infancy.
Subject(s)
Autistic Disorder , Visual Pathways , Animals , Humans , Infant , Macaca mulatta , Social Status , Brain , Magnetic Resonance Imaging/methodsABSTRACT
Importance: Autism spectrum disorder is a common and early-emerging neurodevelopmental condition. While 80% of parents report having had concerns for their child's development before age 2 years, many children are not diagnosed until ages 4 to 5 years or later. Objective: To develop an objective performance-based tool to aid in early diagnosis and assessment of autism in children younger than 3 years. Design, Setting, and Participants: In 2 prospective, consecutively enrolled, broad-spectrum, double-blind studies, we developed an objective eye-tracking-based index test for children aged 16 to 30 months, compared its performance with best-practice reference standard diagnosis of autism (discovery study), and then replicated findings in an independent sample (replication study). Discovery and replication studies were conducted in specialty centers for autism diagnosis and treatment. Reference standard diagnoses were made using best-practice standardized protocols by specialists blind to eye-tracking results. Eye-tracking tests were administered by staff blind to clinical results. Children were enrolled from April 27, 2013, until September 26, 2017. Data were analyzed from March 28, 2018, to January 3, 2019. Main Outcomes and Measures: Prespecified primary end points were the sensitivity and specificity of the eye-tracking-based index test compared with the reference standard. Prespecified secondary end points measured convergent validity between eye-tracking-based indices and reference standard assessments of social disability, verbal ability, and nonverbal ability. Results: Data were collected from 1089 children: 719 children (mean [SD] age, 22.4 [3.6] months) in the discovery study, and 370 children (mean [SD] age, 25.4 [6.0] months) in the replication study. In discovery, 224 (31.2%) were female and 495 (68.8%) male; in replication, 120 (32.4%) were female and 250 (67.6%) male. Based on reference standard expert clinical diagnosis, there were 386 participants (53.7%) with nonautism diagnoses and 333 (46.3%) with autism diagnoses in discovery, and 184 participants (49.7%) with nonautism diagnoses and 186 (50.3%) with autism diagnoses in replication. In the discovery study, the area under the receiver operating characteristic curve was 0.90 (95% CI, 0.88-0.92), sensitivity was 81.9% (95% CI, 77.3%-85.7%), and specificity was 89.9% (95% CI, 86.4%-92.5%). In the replication study, the area under the receiver operating characteristic curve was 0.89 (95% CI, 0.86-0.93), sensitivity was 80.6% (95% CI, 74.1%-85.7%), and specificity was 82.3% (95% CI, 76.1%-87.2%). Eye-tracking test results correlated with expert clinical assessments of children's individual levels of ability, explaining 68.6% (95% CI, 58.3%-78.6%), 63.4% (95% CI, 47.9%-79.2%), and 49.0% (95% CI, 33.8%-65.4%) of variance in reference standard assessments of social disability, verbal ability, and nonverbal cognitive ability, respectively. Conclusions and Relevance: In two diagnostic studies of children younger than 3 years, objective eye-tracking-based measurements of social visual engagement quantified diagnostic status as well as individual levels of social disability, verbal ability, and nonverbal ability in autism. These findings suggest that objective measurements of social visual engagement can be used to aid in autism diagnosis and assessment.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Female , Humans , Male , Autism Spectrum Disorder/diagnosis , Autistic Disorder/diagnosis , Cognition , Early Diagnosis , Prospective Studies , Infant , Child, Preschool , Double-Blind MethodABSTRACT
Simple tuberculosis (TB) treatment monitoring tools are needed. We assessed the performance of fluorescein-diacetate (FDA) smear microscopy for detection of viable Mycobacterium tuberculosis in sputum specimens (n = 288) of TB cases under treatment compared to culture (17.4% culture positivity). FDA sensitivity was moderate (83.7% [95% confidence interval {CI}, 70.3 to 92.6]), and specificity was low (66.1% [59.5 to 72.2]). The good negative predictive value (94.8% [90.1 to 97.8]) and negative likelihood ratio (0.2) suggest using this method to rule out treatment failure in settings without access to culture.