Amplitude-Integrated EEG in Infants at Risk of Hypoxic-Ischemic Encephalopathy: A Feasibility Study in Road and Air Transport in Western Australia.

Infants at risk of HIE require early identification and initiation of therapeutic hypothermia (TH). Earlier treatment with TH is associated with better outcomes. aEEG is frequently used when making the decision whether to commence TH. As this is often limited to tertiary centers, TH may be delayed if the infant requires transport to a center that provides it. We aimed to provide a method for the application of amplitude-integrated electroencephalogram (aEEG) and to determine the feasibility of acquiring clinically meaningful information during transport. All infants ≥35 weeks, at risk of HIE at referral, were eligible for inclusion. Scalp electrodes were placed in the C3-C4; P3-P4 position on the infant's scalp and connected to the aEEG amplifier. The aEEG amplifier was, in turn, connected to a clinical tablet computer with EEG software to collect and analyze aEEG information. Recordings were reviewed by the chief principal investigator and two independent reviewers (blinded) for background trace and artifact. Predefined criteria for data quality were set to movement artifacts and software impedance notifications. Surveys were completed by healthcare staff and parents for acceptability and ease of use.

'It's not always textbook social anxiety': A survey-based study investigating the nature of social anxiety and experiences of therapy in autistic people.

LAY ABSTRACT: The nature of social anxiety has been widely researched in non-autistic people. This existing research has allowed therapists to develop effective therapy for social anxiety in non-autistic people. Meanwhile, some research suggests that autistic people may have different experiences of anxiety compared to non-autistic people. In addition, there is some evidence that modified therapy may help autistic people with social anxiety, although we also know that many autistic people feel failed by existing mental health services.This article provides a detailed picture of social anxiety in autistic people. This includes similarities and differences compared to non-autistic people. In terms of similarities, people often described feeling afraid that others would judge them, and this would have negative consequences. In terms of differences, autistic people commonly reported a clash between their traits and their social environment, which caused them distress and discomfort. This included factors only rarely reported by non-autistic people (such as struggling with too much sensory stimulation or inaccessible forms of communication and encountering discrimination for these problems). Based on this, we propose a 'distinct' model of social anxiety with particular relevance to autistic people. In addition, many participants reported negative experiences in therapy for social anxiety. They thought therapists wrongly viewed their fears of social situations as irrational and ungrounded. They thought therapists did not adapt the therapy process in an individualised way and did not understand neurodiversity or recognise neurodivergence.Standard approaches for social anxiety may not always suit autistic people, so this needs further exploration. We highlight several practical recommendations for therapists offering therapy for social anxiety to autistic people.

"People are now working together for a common good": The effect on social capital of participatory design for community-level sanitation infrastructure in urban informal settlements.

Communities with higher levels of social capital perform better than communities with lower social capital in community-level water and sanitation interventions and have better health outcomes. Although research recommends bolstering social capital to improve intervention outcomes, few studies provide empirical evidence on the effect of intervention activities on social capital. This study aimed to evaluate the effect of participatory design and community engagement activities on social capital among urban informal settlements in Suva, Fiji and Makassar, Indonesia enrolled in the Revitalizing Informal Settlements and their Environments trial using the Short Adapted Social Capital Assessment Tool. We performed confirmatory factor analyses (CFA) to test tool performance and built structural equation models to assess intervention effect on CFA-informed, sub-scale scores for cognitive and structural social capital. Qualitative in-depth interviews in Fiji and Indonesia and focus group discussions in Fiji provided nuanced understanding of intervention effects on social capital from residents' perspectives. Results confirmed the hypothesized two-factor solution but revealed differences by country and by gender in Indonesia. The intervention appeared positively related to cognitive social capital among men and women in Indonesia and negatively related to cognitive and structural social capital among men and women in Fiji. While effect sizes were small and cluster-adjustment for a small number of settlements yielded non-significant effects, trends were consistent across models and bivariate analyses and were corroborated by qualitative findings. Several contextual factors may explain these results, including timing and duration of intervention activities and influence of COVID-19. Qualitative data suggested that the relationship between participatory design and social capital may be bidirectional, helping to explain why certain settlements appeared to be better equipped to benefit from intervention activities. Practitioners and program designers should carefully consider the social pre-conditions of communities in which they intend to work to optimize program outcomes and avoid unintended consequences.

Cognitive Profile in Autism and ADHD: A Meta-Analysis of Performance on the WAIS-IV and WISC-V.

OBJECTIVE: Previous research has suggested that neurodevelopmental conditions may be associated with distinctive cognitive profiles on the Wechsler intelligence tests (of which the most recent editions are the WAIS-IV and WISC-V). However, the extent to which a cognitive profile can be reliably identified for individuals meeting criteria for autism or ADHD remains unclear. The present review investigated this issue. METHOD: A search was conducted in PsycInfo, Embase, and Medline in October 2022 for papers reporting the performance of children or adults diagnosed with autism or ADHD on the WAIS-IV or the WISC-V. Test scores were aggregated using meta-analysis. RESULTS: Scores were analyzed from over 1,800 neurodivergent people reported across 18 data sources. Autistic children and adults performed in the typical range for verbal and nonverbal reasoning, but scored ~1 SD below the mean for processing speed and had slightly reduced scores on working memory. This provides evidence for a "spiky" cognitive profile in autism. Performance of children and adults with ADHD was mostly at age-expected levels, with slightly reduced scores for working memory. CONCLUSION: Although the pattern of performance on the Wechsler tests is not sufficiently sensitive or specific to use for diagnostic purposes, autism appears to be associated with a cognitive profile of relative strengths in verbal and nonverbal reasoning and a weakness in processing speed. Attention deficit hyperactivity disorder appears less associated with a particular cognitive profile. Autistic individuals may especially benefit from a cognitive assessment to identify and support with their strengths and difficulties.

Social Anxiety in Autistic People: Does the Clark and Wells Model fit?

PURPOSE: Cognitive behaviour therapy based on the Clark and Wells (1995) model is a first-line treatment for neurotypical people seeking support for social anxiety. While autistic people frequently report high social anxiety, it is unclear how appropriate the model is for this population. METHODS: Over 300 autistic and non-autistic adults completed an online survey measuring key variables of the Clark and Wells model (socially-related negative thoughts, safety behaviours, self-focused attention). Using multiple regression and structural equation modelling, we assessed whether these variables accounted for the link between autism and social fears. RESULTS: In multiple regression, autistic people experienced greater social fears than expected based on Clark and Wells variables, and safety behaviours were less predictive of social fears in autistic people. In structural equation modelling, Clark and Wells variables only mediated half the link between autistic traits and social fears. In exploratory analysis, we found that distress relating to uncertainty was an additional variable that needed to be taken into consideration in the relationship between autistic traits and social fears. CONCLUSION: The Clark and Wells variables were relevant in autism, but did not fully explain elevated social fears in autistic people, which suggests that other factors are also important in accounting for social anxiety in autistic people. This means that therapy informed by the model may not be optimal for autistic people. We recommend further research developing adapted therapy for social anxiety in autistic people.

Plasticity of thalamocortical axons is regulated by serotonin levels modulated by preterm birth.

Sensory inputs are conveyed to distinct primary areas of the neocortex through specific thalamocortical axons (TCA). While TCA have the ability to reorient postnatally to rescue embryonic mistargeting and target proper modality-specific areas, how this remarkable adaptive process is regulated remains largely unknown. Here, using a mutant mouse model with a shifted TCA trajectory during embryogenesis, we demonstrated that TCA rewiring occurs during a short postnatal time window, preceded by a prenatal apoptosis of thalamic neurons-two processes that together lead to the formation of properly innervated albeit reduced primary sensory areas. We furthermore showed that preterm birth, through serotonin modulation, impairs early postnatal TCA plasticity, as well as the subsequent delineation of cortical area boundary. Our study defines a birth and serotonin-sensitive period that enables concerted adaptations of TCA to primary cortical areas with major implications for our understanding of brain wiring in physiological and preterm conditions.

Probing Bioactive Chemical Space to Discover RNA-Targeted Small Molecules.

Small molecules have become increasingly recognized as invaluable tools to study RNA structure and function and to develop RNA-targeted therapeutics. To rationally design RNA-targeting ligands, a comprehensive understanding and explicit testing of small molecule properties that govern molecular recognition is crucial. To date, most studies have primarily evaluated properties of small molecules that bind RNA in vitro, with little to no assessment of properties that are distinct to selective and bioactive RNA-targeted ligands. Therefore, we curated an RNA-focused library, termed the Duke RNA-Targeted Library (DRTL), that was biased towards the physicochemical and structural properties of biologically active and non-ribosomal RNA-targeted small molecules. The DRTL represents one of the largest academic RNA-focused small molecule libraries curated to date with more than 800 small molecules. These ligands were selected using computational approaches that measure similarity to known bioactive RNA ligands and that diversify the molecules within this space. We evaluated DRTL binding in vitro to a panel of four RNAs using two optimized fluorescent indicator displacement assays, and we successfully identified multiple small molecule hits, including several novel scaffolds for RNA. The DRTL has and will continue to provide insights into biologically relevant RNA chemical space, such as the identification of additional RNA-privileged scaffolds and validation of RNA-privileged molecular features. Future DRTL screening will focus on expanding both the targets and assays used, and we welcome collaboration from the scientific community. We envision that the DRTL will be a valuable resource for the discovery of RNA-targeted chemical probes and therapeutic leads.

Examining the Molecular Origins of Anomalously High H2O Generation at Oxide-Passivated Metal Surfaces for Plasma Applications.

Elucidating the mechanisms responsible for sub-microsecond desorption of water and other impurities from electrode surfaces at high heating rates is crucial for understanding pulsed-power behavior and optimizing its efficiency. Ionization of desorbed impurities in the vacuum regions may create parallel loads and current loss. Devising methods to limit desorption during the short time duration of pulsed-power will signficantly improve the power output. This problem also presents an exciting challenge to and paradigm for molecular length-scale modeling and theories. Previous molecular modeling studies have strongly suggested that, under high vacuum conditions, the amount of water impurity adsorbed on oxide surfaces on metal electrodes is at a sub-monolayer level, which appears insufficient to explain the observed pulsed-power losses at high current densities. Based on Density Functional Theory (DFT) calculations, we propose that hydrogen trapped inside iron metal can diffuse into iron (III) oxide on the metal surface in sub-microsecond time scales, explaining the extra desorbed inventory. These hydrogen atoms react with the oxide to form Fe(II) and desorbed H2O at elevated temperatures. Cr2O3 is found to react more slowly to form Cr(II). H2 evolution is also predicted to require higher activation energies, so H2 may be evolved at later times than H2O. A one-dimensional diffusion model, based on DFT results, is devised to estimate the water outgassing rate under different conditions. This model explains outgassing above 1 ML for surface temperatures of 1 eV often assumed in pulsed-power systems. Finally, we apply a suite of characterization techniques to demonstrate that when iron metal is heated to 650 Celsius, the dominant surface oxide component becomes alpha-Fe2O3. We propose such specially-prepared samples will lead to convergence between atomic modeling and measurements like temperature-programmed desorption. .

Quinapril treatment curtails decline of global longitudinal strain and mechanical function in hypertensive rats.

BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) has been proposed as an early imaging biomarker of cardiac mechanical dysfunction. OBJECTIVE: To assess the impact of angiotensin-converting enzyme (ACE) inhibitor treatment of hypertensive heart disease on LV GLS and mechanical function. METHODS: The spontaneously hypertensive rat (SHR) model of hypertensive heart disease ( n  = 38) was studied. A subset of SHRs received quinapril (TSHR, n  = 16) from 3 months (mo). Wistar Kyoto rats (WKY, n  = 13) were used as controls. Tagged cardiac MRI was performed using a 4.7 T Varian preclinical scanner. RESULTS: The SHRs had significantly lower LV ejection fraction (EF) than the WKYs at 3 mo (53.0 ±â€Š1.7% vs. 69.6 ±â€Š2.1%, P  < 0.05), 14 mo (57.0 ±â€Š2.5% vs. 74.4 ±â€Š2.9%, P  < 0.05) and 24 mo (50.1 ±â€Š2.4% vs. 67.0 ±â€Š2.0%, P  < 0.01). At 24 mo, ACE inhibitor treatment was associated with significantly greater LV EF in TSHRs compared to untreated SHRs (64.2 ±â€Š3.4% vs. 50.1 ±â€Š2.4%, P  < 0.01). Peak GLS magnitude was significantly lower in SHRs compared with WKYs at 14 months (7.5% ±â€Š0.4% vs. 9.9 ±â€Š0.8%, P  < 0.05). At 24 months, Peak GLS magnitude was significantly lower in SHRs compared with both WKYs (6.5 ±â€Š0.4% vs. 9.7 ±â€Š1.0%, P  < 0.01) and TSHRs (6.5 ±â€Š0.4% vs. 9.6 ±â€Š0.6%, P  < 0.05). CONCLUSIONS: ACE inhibitor treatment curtails the decline in global longitudinal strain in hypertensive rats, with the treatment group exhibiting significantly greater LV EF and GLS magnitude at 24 mo compared with untreated SHRs.

Stable isotopes and foraging behaviors support the role of antipredator benefits in driving the association between two marine fishes.

Research from terrestrial communities shows that diminished predation risk is a principal driver of heterospecific grouping behavior, with foraging ecology predicting the roles that species play in groups, as more vulnerable foragers preferentially join more vigilant ones from whom they can benefit. Meanwhile, field studies examining the adaptive significance of heterospecific shoaling among marine fish have focused disproportionately on feeding advantages such as scrounging or prey-flushing. Juvenile bonefish (Albula vulpes) occur almost exclusively among mojarras (Eucinostomus spp.) and even elect to join them over conspecifics, suggesting they benefit from doing so. We evaluated the roles of risk-related and food-related factors in motivating this pattern of affiliation, estimating: (1) the relative levels of risk associated with each species' search and prey capture activities, via behavioral vulnerability traits discerned from in situ video of heterospecific shoals, and (2) resource use redundancy, using stable isotopes (δ13C, δ15N, and δ34S) to quantify niche overlap. Across four distinct metrics, bonefish behaviors implied a markedly greater level of risk than those of mojarras, typified by higher activity levels and a reduced capacity for overt vigilance; consistent with expectations if their association conformed to patterns of joining observed in terrestrial habitats. Resource use overlap inferred from stable isotopes was low, indicating that the two species partitioned resources and making it unlikely that bonefish derived substantive food-related benefits. Collectively, these findings suggest that the attraction of juvenile bonefish to mojarras is motivated primarily by antipredator advantages, which may include the exploitation of risk-related social cues.

Gene-level association analysis of bivariate ordinal traits with functional regressions.

In genetic studies, many phenotypes have multiple naturally ordered discrete values. The phenotypes can be correlated with each other. If multiple correlated ordinal traits are analyzed simultaneously, the power of analysis may increase significantly while the false positives can be controlled well. In this study, we propose bivariate functional ordinal linear regression (BFOLR) models using latent regressions with cumulative logit link or probit link to perform a gene-based analysis for bivariate ordinal traits and sequencing data. In the proposed BFOLR models, genetic variant data are viewed as stochastic functions of physical positions, and the genetic effects are treated as a function of physical positions. The BFOLR models take the correlation of the two ordinal traits into account via latent variables. The BFOLR models are built upon functional data analysis which can be revised to analyze the bivariate ordinal traits and high-dimension genetic data. The methods are flexible and can analyze three types of genetic data: (1) rare variants only, (2) common variants only, and (3) a combination of rare and common variants. Extensive simulation studies show that the likelihood ratio tests of the BFOLR models control type I errors well and have good power performance. The BFOLR models are applied to analyze Age-Related Eye Disease Study data, in which two genes, CFH and ARMS2, are found to strongly associate with eye drusen size, drusen area, age-related macular degeneration (AMD) categories, and AMD severity scale.

Myocardial Segmentation of Tagged Magnetic Resonance Images with Transfer Learning Using Generative Cine-To-Tagged Dataset Transformation.

The use of deep learning (DL) segmentation in cardiac MRI has the potential to streamline the radiology workflow, particularly for the measurement of myocardial strain. Recent efforts in DL motion tracking models have drastically reduced the time needed to measure the heart's displacement field and the subsequent myocardial strain estimation. However, the selection of initial myocardial reference points is not automated and still requires manual input from domain experts. Segmentation of the myocardium is a key step for initializing reference points. While high-performing myocardial segmentation models exist for cine images, this is not the case for tagged images. In this work, we developed and compared two novel DL models (nnU-net and Segmentation ResNet VAE) for the segmentation of myocardium from tagged CMR images. We implemented two methods to transform cardiac cine images into tagged images, allowing us to leverage large public annotated cine datasets. The cine-to-tagged methods included (i) a novel physics-driven transformation model, and (ii) a generative adversarial network (GAN) style transfer model. We show that pretrained models perform better (+2.8 Dice coefficient percentage points) and converge faster (6×) than models trained from scratch. The best-performing method relies on a pretraining with an unpaired, unlabeled, and structure-preserving generative model trained to transform cine images into their tagged-appearing equivalents. Our state-of-the-art myocardium segmentation network reached a Dice coefficient of 0.828 and 95th percentile Hausdorff distance of 4.745 mm on a held-out test set. This performance is comparable to existing state-of-the-art segmentation networks for cine images.

What parents want in an autism diagnostic report: An interview-based study of parents accessing a neurodevelopmental assessment service.

Diagnostic reports are a key outcome of autism assessment services. However, there is limited evidence regarding what key stakeholders, including families, want to see in reports. In this project, 30 parents whose young person had recently received a diagnosis of autism from a Neurodevelopmental Assessment Service in the North East of England took part in a telephone-based interview to explore what they want from a report. Interviews were analysed using thematic analysis. Ten key recommendations for reports were identified. Parents indicated that they want a detailed, balanced, sensitively written report. They highlighted that reports needed to be accessible and clearly structured. In this respect, it might be helpful to include a parent-driven summary of key points at the top, clear signposting of the structure of the report, and a description of what happened in the assessment process. Parents also valued practical, personalised recommendations based on the young person's strengths and difficulties. Future research might explore perspectives on reports in families accessing other services, in other client groups (e.g., families of pre-schoolers diagnosed with autism), and with different stakeholders, including schools, referrers and autistic people.

Does the autism phenotype differ when selecting groups by neurodevelopmental versus genetic diagnosis? An observational study comparing autism and sex chromosome trisomy.

Background: Autism is diagnosed on the basis of social and non-social behavioural features that are assumed to cluster together, and assumed to be distinct from other aspects of development, such as language ability. It is unclear, however, if these assumptions are valid. This study presents a novel approach to answering this question by investigating whether correlations between autism features are similar for groups selected on behavioural versus genetic diagnosis. Methods: The autism phenotype was assessed by diagnostic interview in young people aged 7 to 14 diagnosed with autism ( N=61) or sex chromosome trisomy (SCT; N=49). Data were analysed by confirmatory factor analysis and MANOVA. Results: Autism features showed a similar factor structure and were distinct from language ability in both groups. However, the SCT group was more likely to show clinically-significant difficulties in just some aspects of autism and a lower level of non-social autism features for their social-communication disabilities. Conclusions: We suggest the group differences emerged because autism diagnostic criteria do not map exactly on the autism phenotype as it manifests "naturally". Conventional diagnostic criteria for autism miss those with uneven profiles of difficulty and those with relatively low levels of restricted and repetitive behaviours and interests.

Development and validation of the conversation questionnaire: A psychometric measure of communication challenges generated from the self-reports of autistic people.

Existing measures of communication challenges in autism are based on diagnostic criteria and research/clinical observations of autistic people, rather than what autistic people themselves identify as difficulties. In this study, the Conversation Questionnaire (CQ) was developed based on community engagement with autistic people to identify what they find challenging about conversation. This new tool was then administered online to autistic, dyslexic and neurotypical people (N = 312) in a validation phase of the study. Item-response theory modelling indicated that a two-dimensional structure accounted for response patterns. These dimensions reflected difficulties knowing what to say (15 items) and engaging in behaviours possibly disruptive to neurotypical conversation (21 items). The dimensions showed good internal consistency and convergent and discriminant validity, and could distinguish between autistic and neurotypical people (d = 1.59 and d = 2.07 respectively). The CQ might help contribute to diagnostic assessment for autism in adults as part of a holistic assessment. The questionnaire might also be useful with other neurodiverse groups, and provide a tool for clinicians and researchers to identify individuals' strengths and difficulties in conversation (e.g., as part of interventions in speech and language therapy).

Myocardial mesostructure and mesofunction.

The complex and highly organized structural arrangement of some five billion cardiomyocytes directs the coordinated electrical activity and mechanical contraction of the human heart. The characteristic transmural change in cardiomyocyte orientation underlies base-to-apex shortening, circumferential shortening, and left ventricular torsion during contraction. Individual cardiomyocytes shorten ∼15% and increase in diameter ∼8%. Remarkably, however, the left ventricular wall thickens by up to 30-40%. To accommodate this, the myocardium must undergo significant structural rearrangement during contraction. At the mesoscale, collections of cardiomyocytes are organized into sheetlets, and sheetlet shear is the fundamental mechanism of rearrangement that produces wall thickening. Herein, we review the histological and physiological studies of myocardial mesostructure that have established the sheetlet shear model of wall thickening. Recent developments in tissue clearing techniques allow for imaging of whole hearts at the cellular scale, whereas magnetic resonance imaging (MRI) and computed tomography (CT) can image the myocardium at the mesoscale (100 µm to 1 mm) to resolve cardiomyocyte orientation and organization. Through histology, cardiac diffusion tensor imaging (DTI), and other modalities, mesostructural sheetlets have been confirmed in both animal and human hearts. Recent in vivo cardiac DTI methods have measured reorientation of sheetlets during the cardiac cycle. We also examine the role of pathological cardiac remodeling on sheetlet organization and reorientation, and the impact this has on ventricular function and dysfunction. We also review the unresolved mesostructural questions and challenges that may direct future work in the field.

Targeted Sequencing of Candidate Regions Associated with Sagittal and Metopic Nonsyndromic Craniosynostosis.

Craniosynostosis (CS) is a major birth defect in which one or more skull sutures fuse prematurely. We previously performed a genome-wide association study (GWAS) for sagittal non-syndromic CS (sNCS), identifying associations downstream from BMP2 on 20p12.3 and intronic to BBS9 on 7p14.3; analyses of imputed variants in DLG1 on 3q29 were also genome-wide significant. We followed this work with a GWAS for metopic non-syndromic NCS (mNCS), discovering a significant association intronic to BMP7 on 20q13.31. In the current study, we sequenced the associated regions on 3q29, 7p14.3, and 20p12.3, including two candidate genes (BMP2 and BMPER) near some of these regions in 83 sNCS child-parent trios, and sequenced regions on 7p14.3 and 20q13.2-q13.32 in 80 mNCS child-parent trios. These child-parent trios were selected from the original GWAS cohorts if the probands carried at least one copy of the top associated GWAS variant (rs1884302 C allele for sNCS; rs6127972 T allele for mNCS). Many of the variants sequenced in these targeted regions are strongly predicted to be within binding sites for transcription factors involved in craniofacial development or bone morphogenesis. Variants enriched in more than one trio and predicted to be damaging to gene function are prioritized for functional studies.

Gene-level association analysis of ordinal traits with functional ordinal logistic regressions.

In this paper, we develop functional ordinal logistic regression (FOLR) models to perform gene-based analysis of ordinal traits. In the proposed FOLR models, genetic variant data are viewed as stochastic functions of physical positions and the genetic effects are treated as a function of physical positions. The FOLR models are built upon functional data analysis which can be revised to analyze the ordinal traits and high dimension genetic data. The proposed methods are capable of dealing with dense genotype data which is usually encountered in analyzing the next-generation sequencing data. The methods are flexible and can analyze three types of genetic data: (1) rare variants only, (2) common variants only, and (3) a combination of rare and common variants. Simulation studies show that the likelihood ratio test statistics of the FOLR models control type I errors well and have good power performance. The proposed methods achieve the goals of analyzing ordinal traits directly, reducing high dimensionality of dense genetic variants, being computationally manageable, facilitating model convergence, properly controlling type I errors, and maintaining high power levels. The FOLR models are applied to analyze Age-Related Eye Disease Study data, in which two genes are found to strongly associate with four ordinal traits.

Stage 2 registered report: investigating a preference for certainty in conversation among autistic adults.

Social communication difficulties are a diagnostic feature in autism. These difficulties are sometimes attributed, at least in part, to impaired ability in making inferences about what other people mean. In this registered report, we tested a competing hypothesis that the communication profile of adults on the autism spectrum can be more strongly characterised by reduced confidence in making inferences in the face of uncertain information. We tested this hypothesis by comparing the performance of 102 autistic and 109 non-autistic adults on a test of implied meaning, using a test of grammaticality judgements as a control task. We hypothesised that autistic adults would report substantially lower confidence, allowing for differences in accuracy, than non-autistic adults on the test of implied meaning compared to the grammaticality test. However, our results did not suggest this. Instead, we found that accuracy and confidence were both reduced to a similar extent on the test of implied meaning in the autistic group compared to the control group, although these were only subtle differences. This pattern of results was specific to inference-making, as the autistic and non-autistic groups did not differ on the grammar test. This supports the idea that specific differences in pragmatic language processing can exist in autism in the absence of core language problems. Importantly, this pattern of results (differences on the test of implied meaning and no differences on the grammar test) was reversed in a group with self-reported reading difficulties, indicating that the differences in inference-making were specific to the autistic group. Lastly, we found relationships between Intolerance of Uncertainty, performance on the test of implied meaning, and self-reported social communication challenges. This supports the idea that discomfort with uncertainty plays a role in the pragmatic language and communication challenges in autism.

Orbital and Periorbital Dysmorphology in Untreated Pfeiffer Syndrome.

BACKGROUND: Visual impairment secondary to orbital and periorbital dysmorphology is frequent in Pfeiffer syndrome patients. The etiopathogenesis of this aberrancy, however, remains unclear. METHODS: Untreated Pfeiffer syndrome patients (n = 31) and normal control subjects (n = 43) were compared. Craniometric and volumetric analyses related to the orbital and periorbital anatomy were performed using Materialise (Leuven, Belgium) software. RESULTS: Overall, orbital cavity volume of Pfeiffer patients is reduced by 28 percent (p < 0.001), compared to normal, starting before 3 months of age (p = 0.004). Globe volume was diminished by 10 percent (p = 0.041) before 3 months of age, yet tended to catch up thereafter. However, the retrobulbar soft-tissue volume remained smaller beyond 1 year of age (17 percent, p = 0.003). Globe volume projection beyond the bony orbit increased in all observed ages (82 percent, p < 0.001). The volumes of sphenoid bone, maxilla, and mandible proportionately were restricted by 24 to 25 percent (p = 0.003 to 0.035) before 3 months of age. The volume of maxilla and mandible gradually approximate normal; however, the sphenoid bone volume in Pfeiffer patients remains less than normal (p = 0.002) into childhood. The anteroposterior length of both the zygoma and the maxilla was reduced by 14 percent (p < 0.001). Anterior positioning of the zygoma is less by 23 percent (p < 0.001) in Pfeiffer patients overall, with anterior positioning of maxilla reduced similarly by 23 percent (p < 0.001). CONCLUSIONS: Pfeiffer syndrome patients develop decreased retrobulbar soft-tissue and globe volume, along with a restricted orbital cavity volume in infancy. Significant hypoplasia of the sphenoid bone is associated with more severe central facial (maxilla) retrusion, compared to lateral facial structures (zygoma). CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.