Associations between Social Experiences and Psychological Health for Autistic Youth with Low IQ.

PURPOSE: Social experiences are consistently associated with psychological health among autistic individuals. However, most extant studies on this topic exclude individuals with autism who have lower IQ or are otherwise unable to self-report. The current study addresses this gap by examining associations of negative peer experiences and social participation with psychological health among autistic youth with low IQ. METHODS: An online survey was collected from 268 parents of autistic adolescents and adults ages 15-25. Negative peer experiences included measures of peer victimization and being ignored. Social participation was assessed by the amount of participation and parents' perceptions of whether their youth felt the amount of participation was meeting their needs. Psychological health was assessed by parents' report of their youth's psychological quality of life, as well as whether they felt their son/daughter was currently depressed. RESULTS: Results suggested low rates of social participation in this sample, with relatively high rates of being ignored. Regression analysis found that lower rates of peer victimization and more activities in which parents perceived that the amount of time was meeting their youth's needs was associated with higher psychological quality of life and lower likelihood that parents felt their son/daughter was depressed. CONCLUSION: Though youth with autism and low IQ are often excluded from interventions aimed at improving social experiences, these findings suggest that promoting positive social experiences and ameliorating negative ones might be an avenue to improving psychological health in this group.

Use of Polyurethane-Covered Stents for Exclusion of Pulmonary Arteriovenous Malformations.

PURPOSE: To evaluate the safety, technical success and short-term effectiveness of polyurethane-covered stent (PK Papyrus, BioTronik, Berlin) in the treatment of pulmonary arteriovenous malformations (PAVMs) that are not amenable to embolotherapy. MATERIALS AND METHODS: In this IRB-approved, retrospective study, data from patients who received polyurethane-covered stents for exclusion of PAVMs were analyzed. The study included 5 patients (all women) with a median age of 40 years (range 25-60). Patients presented with hypoxemia, TIAs, and/or epistaxis; 4 were confirmed to have HHT. All had multiple PAVMs diagnosed on chest CT and underwent embolization with other devices in addition to the polyurethane-covered stent. The indication for stent placement in all cases was a short and/or tortuous feeding artery. Safety was assessed by immediate or short-term complications, e.g., migration, stent thrombosis, and fracture. Technical success was defined as the ability to accurately place the stent at the intended location. Effectiveness was defined as successful exclusion of PAVM with no perfusion across the AVM. RESULTS: Technical success of stent placement was 100%. AVM exclusion rate was 80% after single stent deployment; in the case of incomplete exclusion, success was achieved using an overlapping stent to completely cover a second feeding artery. During the median follow-up period of 5 months (range 2-10), all stents remained patent, and AVMs were excluded without other complications. CONCLUSION: Exclusion of PAVMs with polyurethane-covered stents is technically feasible, safe, and shows short-term effectiveness for PAVMs with a short/tortuous feeding artery when traditional embolization techniques are not possible.

Self-reported Everyday Sources of Happiness and Unhappiness in Autistic Adults.

PURPOSE: Daily mood can be influenced by a range of experiences. Identifying everyday life experiences that make autistic adults happy and unhappy holds potential to foster positive mood and tackle mental health problems amongst this group. METHODS: A total of 293 autistic adults between the ages of 18 to 35 years old (mean age of 26.51 years old (SD = 4.62); 43.3% female gender, 4.8% nonbinary) provided open-text responses regarding everyday sources of happiness and unhappiness. Using an iterative process of inductive coding, 14 happy themes and 22 unhappy themes of mood-changing life experiences were identified based on self-report qualitative data. RESULTS: Common themes across the happy and unhappy domain involved social partners, social interactions, and engagement in recreational and employment activities, with additional distinct themes specific to happy or unhappy mood. Top themes identified in the happy domain emphasizes encouraging quality relationships and positive interactions with others and cultivating supportive work/societal environments to build a sense of achievement and value. Meanwhile, emotional tolls accompanied negative relationships and interactions, underscoring the necessity to provide autistic adults with conflict resolution and coping skills to increase feelings of happiness. CONCLUSION: Overall, the wide range of sources of happy and unhappy everyday experiences highlights the importance of considering personal preferences in engagement with others and activities in treatment.

Perspectives on Employer-Initiated Terminations Among Young Adults on the Autism Spectrum.

Job instability is high among autistic adults, with employer-initiated terminations a common reason for job loss. The current study used qualitative methods to code reasons that autistic adults identified for their employer-initiated termination. From 315 autistic individuals ages 18-35 who completed an online survey, 93 (29.5%) reported having been terminated from a job. These individuals were asked about the reasons for their termination and responses were coded into thematic categories. Common reasons included work performance, social difficulties, attendance, and mental health challenges. Adults were more likely to attribute terminations to internal causes (related to the individual) than to external causes (environment-related). A good fit between workplace, individual preferences, skills, and abilities is likely key to promoting job continuity for autistic adults.

Associations between social activities and depressive symptoms in adolescents and young adults with autism spectrum disorder: Testing the indirect effects of loneliness.

LAY ABSTRACT: Previous studies have found that social activities and depressive symptoms in adolescents and young adults with autism spectrum disorder are related. To better understand the relationship between these issues, this study examined the frequency of various types of social activities as well as if the participants felt that the frequency of time spent in the activity met their personal needs. In addition, the role of loneliness was tested as a possible way to understand the relationship between activities and depressive symptoms. To test these ideas, 321 participants who were recruited from the Simons Foundation Powering Autism Research for Knowledge (SPARK) research match registry and completed online measures of social activities, depressive symptoms, and loneliness. While the specific pattern was different for individual activities, it was found that those who felt that their current frequency of activities did not meet their needs had higher rates of depressive symptoms than those who felt they did meet their needs. Also, loneliness helps to understand relationship between social activities and depressive symptoms. The findings were discussed in light of previous study findings, interpersonal theories of depression, and clinical implications.

Exposure-response analyses of efzofitimod in patients with pulmonary sarcoidosis.

Background: Preliminary evidence for efficacy in pulmonary sarcoidosis has been shown for efzofitimod. Here we present supportive evidence of efficacy based on an exposure-response analysis. Methods: Data from two studies (Phase 1, N = 24, single dose in healthy volunteers, and Phase 1b/2a, N = 25, multiple doses over 24 weeks in participants with pulmonary sarcoidosis) were used to build a population pharmacokinetic model. Using this model, the relationship between efzofitimod exposure and three prespecified efficacy parameters [mean daily oral corticosteroid (OCS) dose, percent-predicted forced vital capacity (ppFVC) and King's Sarcoidosis Questionnaire-Lung (KSQ-Lung) score] was explored. Linear regression described the relationship of efzofitimod exposure and OCS reduction, ppFVC and KSQ-Lung score. Logistic regression related efzofitimod exposure to the probability of achieving a minimal clinically important difference for ppFVC and KSQ-Lung score. Due to the small study size, trends (not statistical significance) in relationships are reported. Results: In patients with pulmonary sarcoidosis, as efzofitimod exposure increased, the mean daily OCS dose decreased, and ppFVC and KSQ-Lung score improved over baseline. The slope for all the endpoints by both linear and logistic regression showed an improving trend with increased exposure. Conclusion: These preliminary findings of a positive exposure-response across multiple efficacy endpoints support the claim that proof of concept has been established for the use of efzofitimod in pulmonary sarcoidosis. Clinical Trial Registration: clinicaltrials.gov, identifier NCT03824392.

Projection of extreme heat- and cold-related mortality in Sweden based on the spatial synoptic classification.

BACKGROUND: Climate change is projected to result in increased heat events and decreased cold events. This will substantially impact human health, particularly when compounded with demographic change. This study employed the Spatial Synoptic Classification (SSC) to categorize daily weather into one of seven types. Here we estimated future mortality due to extremely hot and cold weather types under different climate change scenarios for one southern (Stockholm) and one northern (Jämtland) Swedish region. METHODS: Time-series Poisson regression with distributed lags was used to assess the relationship between extremely hot and cold weather events and daily deaths in the population above 65 years, with cumulative effects (6 days in summer, 28 days in winter), 1991 to 2014. A global climate model (MPI-M-MPI-ESM-LR) and two climate change scenarios (RCP 4.5 and 8.5) were used to project the occurrence of hot and cold days from 2031 to 2070. Place-specific projected mortality was calculated to derive attributable numbers and attributable fractions (AF) of heat- and cold-related deaths. RESULTS: In Stockholm, for the RCP 4.5 scenario, the mean number of annual deaths attributed to heat increased from 48.7 (CI 32.2-64.2; AF = 0.68%) in 2031-2040 to 90.2 (56.7-120.5; AF = 0.97%) in 2061-2070, respectively. For RCP 8.5, heat-related deaths increased more drastically from 52.1 (33.6-69.7; AF = 0.72%) to 126.4 (68.7-175.8; AF = 1.36%) between the first and the last decade. Cold-related deaths slightly increased over the projected period in both scenarios. In Jämtland, projections showed a small decrease in cold-related deaths but no change in heat-related mortality. CONCLUSIONS: In rural northern region of Sweden, a decrease of cold-related deaths represents the dominant trend. In urban southern locations, on the other hand, an increase of heat-related mortality is to be expected. With an increasing elderly population, heat-related mortality will outweigh cold-related mortality at least under the RCP 8.5 scenario, requiring societal adaptation measures.

A cluster analysis of daily living skills in school aged children with autism spectrum disorder.

For individuals with autism spectrum disorder (ASD) daily living skills (DLS) fall below chronological age and have been linked to factors such as language. Given the impact of DLS on daily life, it is critical to gain a comprehensive understanding of DLS profiles in children to guide effective treatment. Using a large dataset from the Autism Speaks Autism Treatment Network, the current study sought to (1) examine whether there are subgroups of children with ASD defined by both their Vineland-II DLS scores and language abilities and (2) explore the relationship between internalizing and externalizing symptoms on subgroups using the Child Behavior Checklist. A five-cluster solution was found, but one group was subsequently dropped. Four clusters were examined: Low Language-Low DLS (n = 143); Low-Language High DLS (n = 170); High Language-Low DLS (n = 189); and High Language-High DLS (n = 203). The High Language-Low DLS group had significantly higher internalizing and externalizing symptoms as compared to the other groups. The results highlight the importance of targeting DLS in school-age children with ASD, especially for those with comorbid internalizing and externalizing symptom to ensure that the gap between age and functional DLS does not continue to widen.

Looking Outside the Square: The Growth, Structure, and Resilient Two-Dimensional Surface Electron Gas of Square SnO2 Nanotubes.

Nanotechnology has delivered an amazing range of new materials such as nanowires, tubes, ribbons, belts, cages, flowers, and sheets. However, these are usually circular, cylindrical, or hexagonal in nature, while nanostructures with square geometries are comparatively rare. Here, a highly scalable method is reported for producing vertically aligned Sb-doped SnO2 nanotubes with perfectly-square geometries on Au nanoparticle covered m-plane sapphire using mist chemical vapor deposition. Their inclination can be varied using r- and a-plane sapphire, while unaligned square nanotubes of the same high structural quality can be grown on silicon and quartz. X-ray diffraction measurements and transmission electron microscopy show that they adopt the rutile structure growing in the [001] direction with (110) sidewalls, while synchrotron X-ray photoelectron spectroscopy reveals the presence of an unusually strong and thermally resilient 2D surface electron gas. This is created by donor-like states produced by the hydroxylation of the surface and is sustained at temperatures above 400 °C by the formation of in-plane oxygen vacancies. This persistent high surface electron density is expected to prove useful in gas sensing and catalytic applications of these remarkable structures. To illustrate their device potential, square SnO2 nanotube Schottky diodes and field effect transistors with excellent performance characteristics are fabricated.

Learning to Learn Functions.

Humans can learn complex functional relationships between variables from small amounts of data. In doing so, they draw on prior expectations about the form of these relationships. In three experiments, we show that people learn to adjust these expectations through experience, learning about the likely forms of the functions they will encounter. Previous work has used Gaussian processes-a statistical framework that extends Bayesian nonparametric approaches to regression-to model human function learning. We build on this work, modeling the process of learning to learn functions as a form of hierarchical Bayesian inference about the Gaussian process hyperparameters.

Lymphocytic Extracellular Signal-Regulated Kinase Dysregulation in Autism Spectrum Disorder.

OBJECTIVE: Extracellular signal-regulated kinase (ERK1/2) is a conserved central intracellular signaling cascade involved in many aspects of neuronal development and plasticity. Converging evidence support investigation of ERK1/2 activity in autism spectrum disorder (ASD). We previously reported enhanced baseline lymphocytic ERK1/2 activation in autism, and now we extend our work to investigate the early phase kinetics of lymphocytic ERK1/2 activation in idiopathic ASD. METHOD: Study participants included 67 individuals with ASD (3-25 years of age), 65 age- and sex-matched typical developing control (TDC) subjects, and 36 age-, sex-, and IQ-matched developmental disability control (DDC) subjects matched to those with ASD and IQ <90. We completed an additional analysis comparing results from ASD, TDC, and DDC groups with data from 37 individuals with Fragile X syndrome (FXS). All subjects had blood lymphocyte samples analyzed by flow cytometry following stimulation with phorbol ester and sequentially analyzed for ERK1/2 activation (phosphorylation) at several time points. RESULTS: The ASD group (mean = 5.81 minutes; SD = 1.5) had a significantly lower (more rapid) mean ERK1/2 T1/2 activation value than both the DDC group (mean = 6.78 minutes; SD = 1.6; p = .00078) and the TDC group (mean = 6.4 minutes; SD = 1.5; p = .025). More rapid ERK1/2 T1/2 activation times did correlate with increased social impairment across all study groups including the ASD cohort. Differences in ERK1/2 T1/2 activation were more pronounced in younger than in older individuals in the primary analysis. The ASD group additionally had more rapid activation times than the FXS group, and the FXS group activation kinetics did not differ from those of the TDC and DDC groups. CONCLUSION: Our findings indicate that lymphocytic ERK1/2 activation kinetics are dysregulated in persons with ASD, marked by more rapid early phase activation. Group differences in ERK1/2 activation kinetics appear to be driven by findings from the youngest children analyzed. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

A Multi-Objective Active Learning Platform and Web App for Reaction Optimization.

We report the development of an open-source experimental design via Bayesian optimization platform for multi-objective reaction optimization. Using high-throughput experimentation (HTE) and virtual screening data sets containing high-dimensional continuous and discrete variables, we optimized the performance of the platform by fine-tuning the algorithm components such as reaction encodings, surrogate model parameters, and initialization techniques. Having established the framework, we applied the optimizer to real-world test scenarios for the simultaneous optimization of the reaction yield and enantioselectivity in a Ni/photoredox-catalyzed enantioselective cross-electrophile coupling of styrene oxide with two different aryl iodide substrates. Starting with no previous experimental data, the Bayesian optimizer identified reaction conditions that surpassed the previously human-driven optimization campaigns within 15 and 24 experiments, for each substrate, among 1728 possible configurations available in each optimization. To make the platform more accessible to nonexperts, we developed a graphical user interface (GUI) that can be accessed online through a web-based application and incorporated features such as condition modification on the fly and data visualization. This web application does not require software installation, removing any programming barrier to use the platform, which enables chemists to integrate Bayesian optimization routines into their everyday laboratory practices.

Patterns of sleep disturbances and associations with depressive symptoms in autistic young adults.

Autistic individuals are at an increased risk for both sleep disturbances and depression. While studies in the general population and in autistic adults have drawn general links between sleep disturbances and mental health, few studies have examined the extent to which specific sleep problems may be implicated in the extremely high rates of depression among autistic adults. This study aimed to describe the patterns of sleep disturbances in autistic young adults, and their associations with depressive symptoms while controlling for relevant demographic factors. A sample of 304 legally independent adults (age 18-35 years old) with a childhood diagnosis of autism spectrum disorder self-reported on their average sleep behaviors during the past week and depressive symptoms on the Beck Depressive Inventory-II. A significant proportion (86.01%) of autistic young adults experienced at least one of the primary sleep disturbances of interest, including short total sleep time (39.59%), poor sleep efficiency (60.07%), and delayed sleep phase (36.18%). Additionally, lower sleep efficiency and delayed sleep phase were both associated with higher depressive symptoms. The associations between sleep and depressive symptoms identified in our study suggest that sleep treatments may hold potential for ameliorating depressive symptoms in autistic adults who also experience sleep problems. Further research using daily sleep diaries and objective measures of sleep behaviors, as well as longitudinal studies, are needed to understand how changes in sleep may relate to changes in depressive symptoms in autistic adults.

Child Protective Custody Placement for Children with Developmental Disorders.

OBJECTIVE: The purpose of this study was to determine whether children with developmental disorders (DDs) in protective custody are more likely to experience specific placement types and stay in care longer than their typically developing peers. Furthermore, in the DD-only group, we examined whether the likelihood of each placement type differed by specific DD diagnosis. METHODS: This observational retrospective study used child welfare administrative data linked to electronic health records in a large Ohio county. Participants were aged 5 to 20 years (N = 2787). DD diagnoses were determined using problem list and encounter diagnosis codes. RESULTS: Children with versus without DD were less likely to be in kinship placement (adjusted odds ratio [aOR], 0.79; 95% confidence interval [CI]: 0.66-0.94) and more likely to be in congregate care (aOR, 1.26; 95% CI: 1.04-1.53) and nonrelative foster care (aOR, 1.20; 95% CI: 1.00-1.45). A likelihood of independent living placement did not differ for those with and without DD. Those with versus without DD had longer lengths of stay in protective custody ( p ≤ 0.001), but the number of placement changes did not differ after accounting for length of stay. The pattern of results differed somewhat by individual DD diagnosis. CONCLUSION: Compared with their typically developing peers, children with DD are less likely to be in kinship care and tend to have longer lengths of stay in protective custody. If replicated, these findings suggest the need to identify and address mechanisms to support children with DD across placement settings and to better understand factors prolonging their protective custody stay.

Factors Associated With Bullying Victimization and Bullying Perpetration in Children and Adolescents With ADHD: 2016 to 2017 National Survey of Children's Health.

OBJECTIVE: To identify characteristics associated with bullying involvement in pediatric ADHD. METHODS: Data from the 2016 to 2017 National Survey of Children's Health for children aged 6 to 17 years with ADHD were evaluated to assess the association between parent-reported bullying victimization or perpetration and the following potential predictors: demographic characteristics, family factors, school factors, and child conditions/behaviors. RESULTS: Among children with ADHD, 46.9% were bullying victims and 16.2% were perpetrators. Factors associated with victimization included having family financial strain, developmental delay or intellectual disability, friendship difficulties, and school reports about problems. Factors linked to perpetration included being male, receiving government assistance, lack of school engagement, school reports about problems, and having difficulties with friendships, staying calm, and arguing. CONCLUSIONS: Children with ADHD frequently were bullying victims and sometimes bullying perpetrators. Factors related to family financial strain, developmental disabilities, emotional regulation, peer relationships, and school functioning may help to identify risk for bullying and opportunities for anti-bullying interventions.

Diverse events have transferred genes for edible seaweed digestion from marine to human gut bacteria.

Humans harbor numerous species of colonic bacteria that digest fiber polysaccharides in commonly consumed terrestrial plants. More recently in history, regional populations have consumed edible macroalgae seaweeds containing unique polysaccharides. It remains unclear how extensively gut bacteria have adapted to digest these nutrients. Here, we show that the ability of gut bacteria to digest seaweed polysaccharides is more pervasive than previously appreciated. Enrichment-cultured Bacteroides harbor previously discovered genes for seaweed degradation, which have mobilized into several members of this genus. Additionally, other examples of marine bacteria-derived genes, and their mobile DNA elements, are involved in gut microbial degradation of seaweed polysaccharides, including genes in gut-resident Firmicutes. Collectively, these results uncover multiple separate events that have mobilized the genes encoding seaweed-degrading-enzymes into gut bacteria. This work further underscores the metabolic plasticity of the human gut microbiome and global exchange of genes in the context of dietary selective pressures.

Job loss predicts worsening depressive symptoms for young adults with autism: A COVID-19 natural experiment.

Adults with autism spectrum disorder (ASD) experience high rates of both unemployment and depression. Though job loss predicts increased risk of depression in the general population, studies have yet to directly examine this relationship among individuals with ASD. With the backdrop of rising unemployment due to COVID-19, we used a longitudinal design to examine whether employment changes predicted increasing depressive symptoms among young adults with ASD. Online surveys were collected from young adults with ASD at two times: just before widespread social distancing measures were adopted in the United States, and again 10 weeks later. Both time points included measurement of depressive symptoms (Beck Depression Inventory-2). At Time 2, COVID-related employment changes and the perceived impact of those changes on well-being were collected. Of the young adults who were employed at Time 1 (n = 144), over one-third (37.5%) reported employment changes during the first 2 months of COVID-19. Most of this change was job loss or reductions in hours or pay ("job loss/reduction"). Controlling for Time 1 depressive symptoms, young adults who experienced job loss/reduction had significantly higher depressive symptoms at Time 2 than those without an employment change. Individuals' perceived impact of employment change also predicted depressive symptoms. These findings suggest that losing a job or experiencing reductions in hours or pay leads to worsening depressive symptoms among adults with ASD. Better supporting autistic adults in the workplace may not only decrease the likelihood of job loss, but also combat the exceedingly high rates of depression in this group. LAY SUMMARY: Though unemployment has been linked to mental health problems in the general population, this relationship is seldom considered among adults with autism. In this study, we found that adults on the autism spectrum who lost their jobs or experienced reductions in pay or hours during the first 2 months of COVID-19 had worsening depression compared to adults who did not have job changes. Our findings suggest that increasing access to employment may help alleviate poor mental health among autistic adults.

Current Thoughts of Notch's Role in Myoblast Regulation and Muscle-Associated Disease.

The evolutionarily conserved signaling pathway Notch is unequivocally essential for embryogenesis. Notch's contribution to the muscle repair process in adult tissue is complex and obscure but necessary. Notch integrates with other signals in a functional antagonist manner to direct myoblast activity and ultimately complete muscle repair. There is profound recent evidence describing plausible mechanisms of Notch in muscle repair. However, the story is not definitive as evidence is slowly emerging that negates Notch's importance in myoblast proliferation. The purpose of this review article is to examine the prominent evidence and associated mechanisms of Notch's contribution to the myogenic repair phases. In addition, we discuss the emerging roles of Notch in diseases associated with muscle atrophy. Understanding the mechanisms of Notch's orchestration is useful for developing therapeutic targets for disease.

Indirect effects of HPA axis dysregulation in the association between peer victimization and depressed affect during early adolescence.

OBJECTIVE: Previous research has identified a link between peer victimization and depressive symptoms during adolescence. The goal of the current study is to examine the possible indirect effects of HPA axis dysregulation in the link between adolescent peer victimization and depressive symptoms. METHOD: A total of 113 boys (n = 61) and girls (n = 52) participants from grade 5 (M age = 10.31 years) and grade 6 (M age = 11.33 years) who were predominantly European-Canadian completed self-report measures of peer victimization and depressed affect as well as, measures of salivary cortisol and self-reports of negative experiences collected in conjunction with one another five times per day over the course of four school days. RESULTS: Multi-level structural equation modeling found that peer victimization was indirectly associated with depressive symptoms via blunted cortisol reactivity (i.e. increases in cortisol in response to a negative event) but only at high rates of chronic peer victimization. CONCLUSION: The findings suggest that future studies should focus on HPA axis dysregulation for better understand the development, as well as the stability of depression over time and that interventions targeting peer victimization may want to put a special focus on those who are chronically experiencing peer victimization over time.