A novel online assessment of pragmatic and core language skills: An attempt to tease apart language domains in children.

It remains unclear whether pragmatic language skills and core language skills (grammar and vocabulary) are distinct language domains. The present work aimed to tease apart these domains using a novel online assessment battery administered to almost 400 children aged 7 to 13 years. Confirmatory factor analysis indicated that pragmatic and core language domains could be measured separately, but that both domains were highly related (r = .79). However, zero-order correlations between pragmatic tests were quite small, indicating that task-specific skills played an important role in performance, and follow-up exploratory factor analysis suggested that pragmatics might be best understood as a family of skills rather than a domain. This means that these different pragmatic skills may have different cognitive underpinnings and also need to be assessed separately. However, our overall results supported the idea that pragmatic and core aspects of language are closely related during development, with one area scaffolding development in the other.

Sex chromosome trisomies are not associated with atypical lateralization for language.

AIM: To test the hypothesis that sex chromosome trisomies (SCTs) are associated with reduced left lateralization for language. METHOD: Using a cross-sectional design, language laterality was measured during an animation description task using functional transcranial Doppler ultrasonography. Data were available for 75 children with an SCT (47,XXX females [n=26], 47,XXY males [n=25], 47,XYY males [n=24]; mean age 11y 4mo [SD 3y 10mo]) and 132 comparison children with typical karyotypes (69 males, 63 females; mean age 9y 1mo [SD 1y 7mo]). RESULTS: Lateralization for language did not differ between the SCT and comparison groups, either in mean laterality index or relative frequency of each laterality category. There were no differences when splitting the group with an SCT by trisomy. Handedness showed no group effects. INTERPRETATION: Our data provide no evidence for disrupted lateralization for language in SCTs. The brain basis of the cognitive phenotype in SCTs is unlikely to be a failure of the left hemisphere to specialize for language, as previously suggested. WHAT THIS PAPER ADDS: Children with a sex chromosome trisomy (SCT) have typically lateralized language. This disproves theories linking language problems to hemispheric specialization in SCTs.

Synthesis of 2,3-dideoxy-2-fluoro-2,3-endo-methylene- and 2,3-Dideoxy-2-fluoro-3-C-hydroxymethyl-2,3-endo-methylene-pentofuranoses and their use in the preparation of conformationally locked bicyclic nucleosides.

Construction of protected 2,3-dideoxy-2-fluoro-2,3-endo-methylene-pentofuranoses from d-glyceraldehyde and 2,3-dideoxy-2-fluoro-3-C-hydroxymethyl-2,3-endo-methylene-pentofuranoses from d-isoascorbic acid, via Simmons-Smith-type stereoselective cyclopropanations on the respective fluoroallyl alcohols, is described. Synthesis of the corresponding conformationally locked sugar modified uridine and guanosine nucleosides was achieved via Vorbrüggen or Mitsunobu methodologies. Stereochemical confirmation of the novel nucleosides was performed on the basis of 2D NOESY NMR experiments. Analysis of 2',3'-dideoxy-2'-fluoro-3'-C-hydroxymethyl-2',3'-endo-methylene-uridine by X-ray crystallography yielded the principal conformational parameters and indicated that the furanoid ring adopted an (o)E/(o)T1, East pucker. The uridine and guanosine nucleosides were found to be inactive in the hepatitis C virus (HCV) cell-based replicon assay, which was corroborated on examination of the corresponding nucleoside triphosphates against the HCV NS5B polymerase.

'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.

C-branched iminosugars: α-glucosidase inhibition by enantiomers of isoDMDP, isoDGDP, and isoDAB-L-isoDMDP compared to miglitol and miglustat.

The Ho crossed aldol condensation provides access to a series of carbon branched iminosugars as exemplified by the synthesis of enantiomeric pairs of isoDMDP, isoDGDP, and isoDAB, allowing comparison of their biological activities with three linear isomeric natural products DMDP, DGDP, and DAB and their enantiomers. L-IsoDMDP [(2S,3S,4R)-2,4-bis(hydroxymethyl)pyrrolidine-3,4-diol], prepared in 11 steps in an overall yield of 45% from d-lyxonolactone, is a potent specific competitive inhibitor of gut disaccharidases [K(i) 0.081 µM for rat intestinal maltase] and is more effective in the suppression of hyperglycaemia in a maltose loading test than miglitol, a drug presently used in the treatment of late onset diabetes. The partial rescue of the defective F508del-CFTR function in CF-KM4 cells by L-isoDMDP is compared with miglustat and isoLAB in an approach to the treatment of cystic fibrosis.

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.

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.

Glycosidase inhibition by all 10 stereoisomeric 2,5-dideoxy-2,5-iminohexitols prepared from the enantiomers of glucuronolactone.

The enantiomers of glucuronolactone are excellent chirons for the synthesis of the 10 stereoisomeric 2,5-dideoxy-2,5-iminohexitols by formation of the pyrrolidine ring by nitrogen substitution at C2 and C5, with either retention or inversion of configuration; the stereochemistry at C3 may be adjusted during the synthesis to give seven stereoisomers from each enantiomer. A definitive side-by-side comparison of the glycosidase inhibition of a panel of 13 glycosidases showed that 8 of the 10 stereoisomers showed significant inhibition of at least one glycosidase.

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).

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.

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.

Do animated triangles reveal a marked difficulty among autistic people with reading minds?

LAY ABSTRACT: Autistic people are thought to have difficulty with mentalising (our drive to track and understand the minds of other people). Mentalising is often measured by the Frith-Happé Animations task, where individuals need to interpret the interactions of abstract shapes. This review article collated results from over 3000 people to assess how autistic people performed on the task. Analysis showed that autistic people tended to underperform compared to non-autistic people on the task, although the scale of the difference was moderate rather than large. Also, autistic people showed some difficulty with the non-mentalising as well as mentalising aspects of the task. These results raise questions about the scale and specificity of mentalising difficulties in autism. It also remains unclear how well mentalising difficulties account for the social challenges diagnostic of autism.

"Second guessing yourself all the time about what they really mean ": Cognitive differences between autistic and non-autistic adults in understanding implied meaning.

This study investigated cognitive differences between autistic and non-autistic people in understanding implied meaning in conversation using a novel computerized test, the Implicature Comprehension Test. Controlling for core language ability, autistic participants (N = 66) were over twice as likely to endorse a non-normative interpretation of an implied meaning and over five times as likely to select "do not know" when asked about the presence of an implied meaning, compared to non-autistic participants (N = 118). A further experiment suggested that the selection of "do not know" reflected a cognitive preference for certainty and explicit communication, and that the normative inference could often be made when the test format was more constrained. Our research supports the hypothesis that autistic individuals can find it challenging to process language in its pragmatic context, and that cognitive preferences play a role in this. LAY SUMMARY: We investigated differences between autistic and non-autistic people in understanding implied meanings in conversation. We found that autistic people were more likely to select a different interpretation of implied meanings compared to other people, and also much more likely to avoid processing implied meanings when the task allowed this. Our research supports the view that autistic people can find it challenging to process indirect meanings, and that they tend to prefer explicit forms of communication.

6-De-oxy-6-fluoro-d-galactose.

The crystal structure unequivocally confirms the relative stereochemistry of the title compound, C(6)H(11)FO(5). The absolute stereochemistry was determined by the use of d-galactose as the starting material. The compound exists as a three-dimensional O-H⋯O hydrogen-bonded network with each mol-ecule acting as a donor and acceptor for four hydrogen bonds.

1-De-oxy-1-fluoro-l-galactitol.

The crystal structure unequivocally confirms the relative stereochemistry of the title compound, C(6)H(13)FO(5) [6-de-oxy-6-fluoro-d-galactitol or (2S,3R,4R,5S)-6-fluoro-hexane-1,2,3,4,5-penta-ol]. The absolute stereochemistry was determined from the use of d-galactose as the starting material. In the crystal, the molecules are linked by O-H⋯O and O-H⋯F hydrogen bonds, forming a three-dimensional network with each mol-ecule acting as a donor and acceptor for five hydrogen bonds.

Registered report: investigating a preference for certainty in conversation among autistic adults compared to dyslexic adults and the general population.

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 test 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 will test this hypothesis by comparing the performance of 100 autistic and 100 non-autistic adults on a test of implied meaning, using a test of grammaticality judgements as a control task. We hypothesise that autistic adults will report substantially lower confidence, allowing for differences in accuracy, than non-autistic adults on the test of implied meaning compared to the grammaticality test. In addition, we hypothesise that reduced confidence in drawing inferences will relate to the cognitive trait Intolerance of Uncertainty and self-reported social communication challenges. Finally, we will conduct exploratory analysis to assess the specificity of the communication profile of the autistic adults by comparing their performance to that of dyslexic adults, who might also be expected to experience challenges with language and communication.

Enantioselective synthesis of tetrafluorinated ribose and fructose.

A perfluoroalkylidene lithium mediated cyclisation approach for the enantioselective synthesis of a tetrafluorinated aldose (ribose) and of a tetrafluorinated ketose (fructose), both in the furanose and in the pyranose form, is described.

(1S)-1,2-O-Benzyl-idene-α-d-glucurono-6,3-lactone.

X-ray crystallographic analysis has established that the major product from the protection of d-glucoronolactone with benzaldehyde is (1S)-1,2-O-benzyl-idene-α-d-glucurono-6,3-lactone, C(13)H(12)O(6), rather than the R epimer. The crystal structure exists as O-H⋯O hydrogen-bonded chains of mol-ecules lying parallel to the a axis. The absolute configuration was determined by the use of d-glucuronolactone as the starting material.

"If you catch my drift...": ability to infer implied meaning is distinct from vocabulary and grammar skills.

Background: Some individuals with autism find it challenging to use and understand language in conversation, despite having good abilities in core aspects of language such as grammar and vocabulary. This suggests that pragmatic skills (such as understanding implied meanings in conversation) are separable from core language skills. However, it has been surprisingly difficult to demonstrate this dissociation in the general population. We propose that this may be because prior studies have used tasks in which different aspects of language are confounded. Methods: The present study used novel language tasks and factor analysis to test whether pragmatic understanding of implied meaning, as part of a broader domain involving social understanding, is separable from core language skills. 120 adult participants were recruited online to complete a 7-task battery, including a test assessing comprehension of conversational implicature. Results: In confirmatory analysis of a preregistered model, we compared whether the data showed better fit to a two-factor structure (including a "social understanding" and "core language" factor) or a simpler one-factor structure (comprising a general factor). The two-factor model showed significantly better fit. Conclusions: This study supports the view that interpreting context-dependent conversational meaning is partially distinct from core language skills. This has implications for understanding the pragmatic language impairments reported in autism.