Study Protocol for the Social Interventions for Support During Treatment for Endometrial Cancer and Recurrence (SISTER) study: a community engaged national randomized trial.

Aim: Social isolation in cancer patients is correlated with prognosis and is a potential mediator of treatment completion. Black women with endometrial cancer (EC) are at increased risk for social isolation when compared with White patients. We developed the Social Interventions for Support during Treatment for Endometrial Cancer and Recurrence (SISTER) study to compare and evaluate interventions to address social isolation among Black women with high-risk EC in USA. The primary objective of the SISTER study is to determine whether virtual support interventions improve treatment completion compared with Enhanced Usual Care. Secondary objectives include comparing effectiveness virtual evidence-based interventions and evaluating barriers and facilitators to social support delivery. Patients & methods: This is a multi-site prospective, open-label, community-engaged randomized controlled trial, consisting of three intervention arms: enhanced usual care, facilitated support group and one-to-one peer support. Primary outcome will be measured using relative dose. Qualitative semi-structured interviews will be conducted with a subset of participants to contextualize the relative degree or lack thereof of social isolation, over time. Data analysis: Primary analysis will be based on an intent-to-treat analysis. Multivariable analysis will be performed to determine the effect of the intervention on the primary and secondary outcomes of interest, relative dose and social isolation score. Semi-structured interviews will be qualitatively analyzed using inductive and deductive approaches of content analysis. Discussion/conclusion: Endometrial cancer mortality disproportionately affects Black women, and social isolation contributes to this disparity. The SISTER study aims to identify whether and to what extent differing social support vehicles improve key outcomes for Black women in the United States with high-risk EC. Clinical Trial Registration: NCT04930159 (ClinicalTrials.gov).

"We Are a Powerful Movement": Evaluation of an Endometrial Cancer Education Program for Black Women.

BACKGROUND: U.S. Black women with endometrial cancer (EC) have a 90% higher mortality rate than White women, driven in part by advanced stage at diagnosis. Black women have expressed reasons for care-seeking delay: misattribution of postmenopausal bleeding, symptom endurance, and community silence regarding vaginal bleeding. OBJECTIVES: In this community-based participatory research study, we adapted, implemented, and evaluated an education program addressing these factors. METHODS: We adapted an evidenced-based education curriculum-Community Empowerment Partners (CEPs©)-using Public Health Critical Race Praxis and the Health Belief Model. Black EC survivors completed CEPs-EC training and committed to lead community sessions. Our mixed-methods evaluation measured baseline and follow-up knowledge (10-point scale) and social and clinical empowerment (three Likert-scaled items) and assessed change in each construct with linear mixed-effects models and Generalized Estimating Equation models, respectively. The process evaluation examined fidelity, feasibility, and acceptability using qualitative data from coaching and national peer educator calls, with directed content analysis. RESULTS: Thirteen ambassadors completed training; 10 completed community sessions with 109 total attendees, 62 with complete data. Among community participants, CEPs-EC participation was associated with increased knowledge of 2.02 points (95% confidence interval [CI], 1.06-2.99; p = 0.0001). Social empowerment increased (odds ratio, 8.85; 95% CI, 1.90-41.20), reinforced by qualitative data. There was no change in clinical empowerment. Process data illustrated facilitators of success: session tailoring, leveraging social networks, mentorship, and group-level motivation. CONCLUSIONS: This is the first intervention addressing EC survival among Black women. Results demonstrate efficacy in improving EC knowledge and empowerment, providing the evidence base for a larger public health campaign.

Identifying prognostic markers in autism spectrum disorder using eye tracking.

While many children with autism spectrum disorder are now detected at young ages given the rise in screening and general awareness, little is known regarding the prognosis of early detected children. The brain is shaped by experience-dependent mechanisms; thus, what a child pays attention to plays a pivotal role in shaping brain development. Eye tracking can provide an index of a child's visual attention and, as such, holds promise as a technology for revealing prognostic markers. In this, 49 children aged 1-3 years with autism spectrum disorder participated in an eye-tracking test, the GeoPref Test, that revealed preference for social versus nonsocial images. Next, children participated in a comprehensive test battery 5-9 years following the initial GeoPref Test. Statistical tests examined whether early age eye tracking predicted later school-age outcomes in symptom severity, social functioning, adaptive behavior, joint attention, and IQ. Results indicated that toddlers with higher preference for geometric images demonstrated greater symptom severity and fewer gaze shifts at school age. This relationship was not found in relation to IQ or adaptive behavior. Overall, the GeoPref Test holds promise as a symptom severity prognostic tool; further development of eye-tracking paradigms may enhance prognostic power and prove valuable in validating treatment progress.

Default mode-visual network hypoconnectivity in an autism subtype with pronounced social visual engagement difficulties.

Social visual engagement difficulties are hallmark early signs of autism (ASD) and are easily quantified using eye tracking methods. However, it is unclear how these difficulties are linked to atypical early functional brain organization in ASD. With resting state fMRI data in a large sample of ASD toddlers and other non-ASD comparison groups, we find ASD-related functional hypoconnnectivity between 'social brain' circuitry such as the default mode network (DMN) and visual and attention networks. An eye tracking-identified ASD subtype with pronounced early social visual engagement difficulties (GeoPref ASD) is characterized by marked DMN-occipito-temporal cortex (OTC) hypoconnectivity. Increased DMN-OTC hypoconnectivity is also related to increased severity of social-communication difficulties, but only in GeoPref ASD. Early and pronounced social-visual circuit hypoconnectivity is a key underlying neurobiological feature describing GeoPref ASD and may be critical for future social-communicative development and represent new treatment targets for early intervention in these individuals.

Evaluation of the Diagnostic Stability of the Early Autism Spectrum Disorder Phenotype in the General Population Starting at 12 Months.

Importance: Universal early screening for autism spectrum disorder (ASD) in primary care is becoming increasingly common and is believed to be a pivotal step toward early treatment. However, the diagnostic stability of ASD in large cohorts from the general population, particularly in those younger than 18 months, is unknown. Changes in the phenotypic expression of ASD across early development compared with toddlers with other delays are also unknown. Objectives: To examine the diagnostic stability of ASD in a large cohort of toddlers starting at 12 months of age and to compare this stability with that of toddlers with other disorders, such as developmental delay. Design, Setting, and Participants: In this prospective cohort study performed from January 1, 2006, to December 31, 2018, a total of 2241 toddlers were referred from the general population through a universal screening program in primary care or community referral. Eligible toddlers received their first diagnostic evaluation between 12 and 36 months of age and had at least 1 subsequent evaluation. Exposures: Diagnosis was denoted after each evaluation visit as ASD, ASD features, language delay, developmental delay, other developmental issue, typical sibling of an ASD proband, or typical development. Main Outcomes and Measures: Diagnostic stability coefficients were calculated within 2-month age bands, and logistic regression models were used to explore the associations of sex, age, diagnosis at first visit, and interval between first and last diagnosis with stability. Toddlers with a non-ASD diagnosis at their first visit diagnosed with ASD at their last were designated as having late-identified ASD. Results: Among the 1269 toddlers included in the study (918 [72.3%] male; median age at first evaluation, 17.6 months [interquartile range, 14.0-24.4 months]; median age at final evaluation, 36.2 months [interquartile range, 33.4-40.9 months]), the overall diagnostic stability for ASD was 0.84 (95% CI, 0.80-0.87), which was higher than any other diagnostic group. Only 7 toddlers (1.8%) initially considered to have ASD transitioned into a final diagnosis of typical development. Diagnostic stability of ASD within the youngest age band (12-13 months) was lowest at 0.50 (95% CI, 0.32-0.69) but increased to 0.79 by 14 months and 0.83 by 16 months (age bands of 12 vs 14 and 16 months; odds ratio, 4.25; 95% CI, 1.59-11.74). A total of 105 toddlers (23.8%) were not designated as having ASD at their first visit but were identified at a later visit. Conclusions and Relevance: The findings suggest that an ASD diagnosis becomes stable starting at 14 months of age and overall is more stable than other diagnostic categories, including language or developmental delay. After a toddler is identified as having ASD, there may be a low chance that he or she will test within typical levels at 3 years of age. This finding opens the opportunity to test the impact of very early-age treatment of ASD.

Typical Levels of Eye-Region Fixation in Toddlers With Autism Spectrum Disorder Across Multiple Contexts.

OBJECTIVE: Unusual eye contact is a common clinical feature in autism spectrum disorder (ASD), yet eye-tracking studies that quantify eye fixation report inconsistent results, possibly because of small samples, varied stimuli, and considerable heterogeneity of eye-region fixation even within typical development. Goals were to examine eye-region fixation levels in a large, very young cohort; the degree to which the presence of speech, hand gestures, and a geometric distractor influence eye-region fixation; and possible developmental changes across time. METHOD: In experiment 1, 385 toddlers (143 with ASD, 242 without ASD, 11-47 months old) watched an actress engaging in child-directed speech with hand gestures against a plain background. Ninety-one toddlers participated approximately 8 months later. In experiment 2, another 231 toddlers (74 with ASD, 157 without ASD, 12-47 months old) watched the same video, but with embedded geometric distractors. Total fixation duration on facial and body regions (eg, eyes, hands) and geometric distractor regions (experiment 2 only) while the actress was speaking or silent, with or without gesturing, was examined, as were relations with clinical traits. RESULTS: Overall, across the 2 experiments and the 2 cross-sectional and longitudinal samples, eye-region fixation duration did not differ between toddlers with and without ASD, although fixation toward the face overall was decreased in toddlers with ASD. This decrease became more apparent with the presence of geometric distractors (experiment 2) as indexed by a geometric preference score, and this score was associated with autism severity. CONCLUSION: Within the context of viewing child-friendly vignettes, decreased eye-region fixation does not reliably characterize toddlers with ASD. An index of competition between faces and external distractors might be a more robust measure.

The geometric preference subtype in ASD: identifying a consistent, early-emerging phenomenon through eye tracking.

Background: The wide range of ability and disability in ASD creates a need for tools that parse the phenotypic heterogeneity into meaningful subtypes. Using eye tracking, our past studies revealed that when presented with social and geometric images, a subset of ASD toddlers preferred viewing geometric images, and these toddlers also had greater symptom severity than ASD toddlers with greater social attention. This study tests whether this "GeoPref test" effect would generalize across different social stimuli. Methods: Two hundred and twenty-seven toddlers (76 ASD) watched a 90-s video, the Complex Social GeoPref test, of dynamic geometric images paired with social images of children interacting and moving. Proportion of visual fixation time and number of saccades per second to both images were calculated. To allow for cross-paradigm comparisons, a subset of 126 toddlers also participated in the original GeoPref test. Measures of cognitive and social functioning (MSEL, ADOS, VABS) were collected and related to eye tracking data. To examine utility as a diagnostic indicator to detect ASD toddlers, validation statistics (e.g., sensitivity, specificity, ROC, AUC) were calculated for the Complex Social GeoPref test alone and when combined with the original GeoPref test. Results: ASD toddlers spent a significantly greater amount of time viewing geometric images than any other diagnostic group. Fixation patterns from ASD toddlers who participated in both tests revealed a significant correlation, supporting the idea that these tests identify a phenotypically meaningful ASD subgroup. Combined use of both original and Complex Social GeoPref tests identified a subgroup of about 1 in 3 ASD toddlers from the "GeoPref" subtype (sensitivity 35%, specificity 94%, AUC 0.75.) Replicating our previous studies, more time looking at geometric images was associated with significantly greater ADOS symptom severity. Conclusions: Regardless of the complexity of the social images used (low in the original GeoPref test vs high in the new Complex Social GeoPref test), eye tracking of toddlers can accurately identify a specific ASD "GeoPref" subtype with elevated symptom severity. The GeoPref tests are predictive of ASD at the individual subject level and thus potentially useful for various clinical applications (e.g., early identification, prognosis, or development of subtype-specific treatments).

EEG mu component responses to viewing emotional faces.

Simulation theories for the perceptual processing of emotional faces assert that observers recruit the neural circuitry involved in creating their own emotional facial expressions in order to recognize the emotions and infer the feelings of others. The EEG mu rhythm is a sensorimotor oscillation hypothesized to index simulation of some actions during perceptual processing of these actions. The purpose of this research was to extend the study of mu rhythm simulation responses during perceptual tasks to the domain of emotional face perception. Subjects viewed happy and disgusted face photos with empathy and non-empathy task instructions while EEG responses were measured. EEG components were isolated and analyzed using a blind source separation (BSS) method. Mu components were found to respond to the perception of happy and disgusted faces during both empathy and non-empathy tasks with an event-related desynchronization (ERD), activation that is consistent with face simulation. Significant differences were found between responses to happy and to disgusted faces across the right hemisphere mu components beginning about 500ms after stimulus presentation. These findings support a simulation account of perceptual face processing based on a sensorimotor mirroring mechanism, and are the first report of distinct EEG mu responses to observation of positively and negatively valenced emotional faces.