Autonomous Molecular Structure Imaging with High-Resolution Atomic Force Microscopy for Molecular Mixture Discovery.

Due to its single-molecule sensitivity, high-resolution atomic force microscopy (HR-AFM) has proved to be a valuable and uniquely advantageous tool to study complex molecular mixtures, which hold promise for developing clean energy and achieving environmental sustainability. However, significant challenges remain to achieve the full potential of the sophisticated and time-consuming experiments. Automation combined with machine learning (ML) and artificial intelligence (AI) is key to overcoming these challenges. Here we present Auto-HR-AFM, an AI tool to automatically collect HR-AFM images of petroleum-based mixtures. We trained an instance segmentation model to teach Auto-HR-AFM how to recognize features in HR-AFM images. Auto-HR-AFM then uses that information to optimize the imaging by adjusting the probe-molecule distance for each molecule in the run. Auto-HR-AFM is the initial tool that will lead to fully automated scanning probe microscopy (SPM) experiments, from start to finish. This automation will allow SPM to become a mainstream characterization technique for complex mixtures, an otherwise unattainable target.

Get SET Early to Identify and Treatment Refer Autism Spectrum Disorder at 1 Year and Discover Factors That Influence Early Diagnosis.

OBJECTIVES: To examine the impact of a new approach, Get SET Early, on the rates of early autism spectrum disorder (ASD) detection and factors that influence the screen-evaluate-treat chain. STUDY DESIGN: After attending Get SET Early training, 203 pediatricians administered 57 603 total screens using the Communication and Symbolic Behavior Scales Infant-Toddler Checklist at 12-, 18-, and 24-month well-baby examinations, and parents designated presence or absence of concern. For screen-positive toddlers, pediatricians specified if the child was being referred for evaluation, and if not, why not. RESULTS: Collapsed across ages, toddlers were evaluated and referred for treatment at a median age of 19 months, and those screened at 12 months (59.4% of sample) by 15 months. Pediatricians referred one-third of screen-positive toddlers for evaluation, citing lack of confidence in the accuracy of screen-positive results as the primary reason for nonreferral. If a parent expressed concerns, referral probability doubled, and the rate of an ASD diagnosis increased by 37%. Of 897 toddlers evaluated, almost one-half were diagnosed as ASD, translating into an ASD prevalence of 1%. CONCLUSIONS: The Get SET Early model was effective at detecting ASD and initiating very early treatment. Results also underscored the need for change in early identification approaches to formally operationalize and incorporate pediatrician judgment and level of parent concern into the process.

Differences in regional brain structure in toddlers with autism are related to future language outcomes.

Language and social symptoms improve with age in some autistic toddlers, but not in others, and such outcome differences are not clearly predictable from clinical scores alone. Here we aim to identify early-age brain alterations in autism that are prognostic of future language ability. Leveraging 372 longitudinal structural MRI scans from 166 autistic toddlers and 109 typical toddlers and controlling for brain size, we find that, compared to typical toddlers, autistic toddlers show differentially larger or thicker temporal and fusiform regions; smaller or thinner inferior frontal lobe and midline structures; larger callosal subregion volume; and smaller cerebellum. Most differences are replicated in an independent cohort of 75 toddlers. These brain alterations improve accuracy for predicting language outcome at 6-month follow-up beyond intake clinical and demographic variables. Temporal, fusiform, and inferior frontal alterations are related to autism symptom severity and cognitive impairments at early intake ages. Among autistic toddlers, brain alterations in social, language and face processing areas enhance the prediction of the child's future language ability.

Examination of the impact of the Get SET Early program on equitable access to care within the screen-evaluate-treat chain in toddlers with autism spectrum disorder.

LAY ABSTRACT: Delays in autism spectrum disorder identification and access to care could impact developmental outcomes. Although trends are encouraging, children from historically underrepresented minority backgrounds are often identified at later ages and have reduced engagement in services. It is unclear if disparities exist all along the screen-evaluation-treatment chain, or if early detection programs such as Get SET Early that standardize, these steps are effective at ameliorating disparities. As part of the Get SET Early model, primary care providers administered a parent-report screen at well-baby examinations, and parents designated race, ethnicity, and developmental concerns. Toddlers who scored in the range of concern, or whose primary care provider had concerns, were referred for an evaluation. Rates of screening and evaluation engagement within ethnic/racial groups were compared to US Census data. Age at screen, evaluation, and treatment engagement and quantity was compared across groups. Statistical models examined whether key factors such as parent concern were associated with ethnicity or race. No differences were found in the mean age at the first screen, evaluation, or initiation or quantity of behavioral therapy between participants. However, children from historically underrepresented minority backgrounds were more likely to fall into the range of concern on the parent-report screen, their parents expressed developmental concerns more often, and pediatricians were more likely to refer for an evaluation than their White/Not Hispanic counterparts. Overall results suggest that models that support transparent tracking of steps in the screen-evaluation-treatment chain and service referral pipelines may be an effective strategy for ensuring equitable access to care for all children.

Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder.

Importance: Caregivers have long captured the attention of their infants by speaking in motherese, a playful speech style characterized by heightened affect. Reduced attention to motherese in toddlers with autism spectrum disorder (ASD) may be a contributor to downstream language and social challenges and could be diagnostically revealing. Objective: To investigate whether attention toward motherese speech can be used as a diagnostic classifier of ASD and is associated with language and social ability. Design, Setting, and Participants: This diagnostic study included toddlers aged 12 to 48 months, spanning ASD and non-ASD diagnostic groups, at a research center. Data were collected from February 2018 to April 2021 and analyzed from April 2021 to March 2022. Exposures: Gaze-contingent eye-tracking test. Main Outcomes and Measures: Using gaze-contingent eye tracking wherein the location of a toddler's fixation triggered a specific movie file, toddlers participated in 1 or more 1-minute eye-tracking tests designed to quantify attention to motherese speech, including motherese vs traffic (ie, noisy vehicles on a highway) and motherese vs techno (ie, abstract shapes with music). Toddlers were also diagnostically and psychometrically evaluated by psychologists. Levels of fixation within motherese and nonmotherese movies and mean number of saccades per second were calculated. Receiver operating characteristic (ROC) curves were used to evaluate optimal fixation cutoff values and associated sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Within the ASD group, toddlers were stratified based on low, middle, or high levels of interest in motherese speech, and associations with social and language abilities were examined. Results: A total of 653 toddlers were included (mean [SD] age, 26.45 [8.37] months; 480 males [73.51%]). Unlike toddlers without ASD, who almost uniformly attended to motherese speech with a median level of 82.25% and 80.75% across the 2 tests, among toddlers with ASD, there was a wide range, spanning 0% to 100%. Both the traffic and techno paradigms were effective diagnostic classifiers, with large between-group effect sizes (eg, ASD vs typical development: Cohen d, 1.0 in the techno paradigm). Across both paradigms, a cutoff value of 30% or less fixation on motherese resulted in an area under the ROC curve (AUC) of 0.733 (95% CI, 0.693-0.773) and 0.761 (95% CI, 0.717-0.804), respectively; specificity of 98% (95% CI, 95%-99%) and 96% (95% CI, 92%-98%), respectively; and PPV of 94% (95% CI, 86%-98%). Reflective of heterogeneity and expected subtypes in ASD, sensitivity was lower at 18% (95% CI, 14%-22%) and 29% (95% CI, 24%-34%), respectively. Combining metrics increased the AUC to 0.841 (95% CI, 0.805-0.877). Toddlers with ASD who showed the lowest levels of attention to motherese speech had weaker social and language abilities. Conclusions and Relevance: In this diagnostic study, a subset of toddlers showed low levels of attention toward motherese speech. When a cutoff level of 30% or less fixation on motherese speech was used, toddlers in this range were diagnostically classified as having ASD with high accuracy. Insight into which toddlers show unusually low levels of attention to motherese may be beneficial not only for early ASD diagnosis and prognosis but also as a possible therapeutic target.

Language, Social, and Face Regions Are Affected in Toddlers with Autism and Predictive of Language Outcome.

Identifying prognostic early brain alterations is crucial for autism spectrum disorder (ASD). Leveraging structural MRI data from 166 ASD and 109 typical developing (TD) toddlers and controlling for brain size, we found that, compared to TD, ASD toddlers showed larger or thicker lateral temporal regions; smaller or thinner frontal lobe and midline structures; larger callosal subregion volume; and smaller cerebellum. Most of these differences were replicated in an independent cohort of 38 ASD and 37 TD toddlers. Moreover, the identified brain alterations were related to ASD symptom severity and cognitive impairments at intake, and, remarkably, they improved the accuracy for predicting later language outcome beyond intake clinical and demographic variables. In summary, brain regions involved in language, social, and face processing were altered in ASD toddlers. These early-age brain alterations may be the result of dysregulation in multiple neural processes and stages and are promising prognostic biomarkers for future language ability.

Large scale validation of an early-age eye-tracking biomarker of an autism spectrum disorder subtype.

Few clinically validated biomarkers of ASD exist which can rapidly, accurately, and objectively identify autism during the first years of life and be used to support optimized treatment outcomes and advances in precision medicine. As such, the goal of the present study was to leverage both simple and computationally-advanced approaches to validate an eye-tracking measure of social attention preference, the GeoPref Test, among 1,863 ASD, delayed, or typical toddlers (12-48 months) referred from the community or general population via a primary care universal screening program. Toddlers participated in diagnostic and psychometric evaluations and the GeoPref Test: a 1-min movie containing side-by-side dynamic social and geometric images. Following testing, diagnosis was denoted as ASD, ASD features, LD, GDD, Other, typical sibling of ASD proband, or typical. Relative to other diagnostic groups, ASD toddlers exhibited the highest levels of visual attention towards geometric images and those with especially high fixation levels exhibited poor clinical profiles. Using the 69% fixation threshold, the GeoPref Test had 98% specificity, 17% sensitivity, 81% PPV, and 65% NPV. Sensitivity increased to 33% when saccades were included, with comparable validity across sex, ethnicity, or race. The GeoPref Test was also highly reliable up to 24 months following the initial test. Finally, fixation levels among twins concordant for ASD were significantly correlated, indicating that GeoPref Test performance may be genetically driven. As the GeoPref Test yields few false positives (~ 2%) and is equally valid across demographic categories, the current findings highlight the ability of the GeoPref Test to rapidly and accurately detect autism before the 2nd birthday in a subset of children and serve as a biomarker for a unique ASD subtype in clinical trials.

The Influence of Patient-Provider Language Concordance in Cancer Care: Results of the Hispanic Outcomes by Language Approach (HOLA) Randomized Trial.

PURPOSE: Delivering linguistically competent care is critical to serving patients who have limited English proficiency (LEP) and represents a key national strategy to help reduce health disparities. Current acceptable standards of communication with patients who have LEP include providers communicating through professional interpretive services or bilingual providers speaking the patients' preferred language directly. This randomized clinical trial tests the effect of patient-provider language concordance on patient satisfaction. METHODS AND MATERIALS: Eighty-three adult Spanish-speaking patients with cancer were randomly assigned to receive care from either (1) 1 of 2 bilingual physicians speaking to the patient directly in Spanish or (2) the same physicians speaking English and using a professional interpreter service. Validated questionnaires were administered to assess patient-reported satisfaction with both provider communication and overall care. Transcripts of initial consultations were analyzed for content variations. RESULTS: Compared with patients receiving care through professional interpretive services, patients cared for in direct Spanish reported significantly improved general satisfaction, technical quality of care (mean composite score [MCS], 4.41 vs 4.06; P = .005), care team interpersonal manner (MCS, 4.37 vs 3.88; P = .004), communication (MCS, 4.50 vs 4.25; P = .018), and time spent with patient,(MCS, 4.30 vs 3.92; P = .028). Specific to physician communication, patients rated direct-Spanish care more highly in perceived opportunity to disclose concerns (MCS 4.91 vs 4.62; P = .001), physician empathy (MCS, 4.94 vs 4.59; P <.001), confidence in physician abilities (MCS, 4.84 vs 4.51; P = .001), and general satisfaction with their physician (MCS, 4.88 vs 4.59; P <.001). Analyzing the content of consultation encounters revealed differences between study arms, with the direct-Spanish arm having more physician speech related to patient history verification (mean number of utterances, 13 vs 9; P = .01) and partnering activities (mean utterances, 16 vs 5; P <.001). Additionally, patients in the direct-Spanish arm were more likely to initiate unprompted speech (mean utterances, 11 vs 3; P <.001) and asked their providers more questions (mean utterances, 11 vs 4; P = .007). CONCLUSIONS: This study shows improved patient-reported satisfaction among patients with cancer who had LEP and were cared for in direct Spanish compared with interpreter-based communication. Further research into interventions to mitigate the patient-provider language barrier is necessary to optimize care for this population.