A Measurement Invariance Analysis of the Anxiety Scale for Autism-Adults in a Sample of Autistic and Non-Autistic Men and Women.

The Anxiety Scale for Autism-Adults (ASA-A) captures the autistic anxiety experience, but we do not know whether it is structurally equivalent for men and women, or non-autistic people. Measurement invariance analysis considered gender and diagnostic status (342 cis-gender autistic men (N = 105) and women (N = 237), 316 cis-gender non-autistic men (N = 104) and women (N = 212)). Strict invariance was achieved between autistic men and women and between non-autistic men and women, but the ASA-A structure is quantitatively different in autistic compared to non-autistic adults. Therefore, this tool cannot be used to directly compare anxiety between these groups. Autistic women scored significantly higher on the ASA-A than autistic men and Uncertainty was the highest scoring factor for autistic participants. Future research should include alternative gender identities.

Exploring the mediating effect of camouflaging and the moderating effect of autistic identity on the relationship between autistic traits and mental wellbeing.

Mental health difficulties are prevalent among autistic adults. Camouflaging (behaving differently to fit in) may be a mechanism by which autistic traits and mental health difficulties relate to each other, but little research has considered the role of different facets of camouflaging. Additionally, autistic identity might buffer against camouflaging and mental health difficulties. This research aims to explore the mediating effects of camouflaging behaviours on the relationship between autistic traits and both positive and negative mental wellbeing, as well as how autistic identity might moderate the relationship between autistic traits and camouflaging, and also mental health. Data were available for 627 autistic adults, recruited through volunteer databases and social media. Participants completed measures of autistic traits, anxiety, depression, positive wellbeing, camouflaging behaviours (compensating for difficulties, masking, and assimilating/putting on an act) and autistic identity. Mediation and moderated mediation models were tested, applying 95% bootstrapped CIs (10,000 resamples) and including age, gender and diagnosis as covariates. There were no significant direct effects between autistic traits and mental wellbeing. Assimilation was a significant mediator of all mental wellbeing measures, and compensation was a significant mediator of positive wellbeing only. Autistic identity was not a significant moderator. Assimilation and compensation should be considered when offering psychological interventions to support mental wellbeing of autistic people. Additional research into external drivers of camouflaging (e.g. stigma) and mechanisms by which camouflaging impacts mental wellbeing, such as autonomy, authenticity, skill mastery and community, may identify other areas of support. Concurrently, societal change is necessary to reduce the need to camouflage.

Inclusion of person-centred care in UK postgraduate medical education curricula: Interviews and documentary analysis.

BACKGROUND: Person-centred care (PCC) involves placing people at the centre of their healthcare decision making to ensure it meets their needs, values, and personal circumstances. Increasingly, PCC is promoted in healthcare policy and guidance, but little is known about how this is embedded in postgraduate medical training. The aim of this research was to understand how PCC is embedded in UK postgraduate medical training and explore factors influencing inclusion of PCC in curricula content. METHODS: To explore this, we interviewed senior professionals with key roles in the curricula from four UK Royal Colleges (Psychiatrists; Physicians; Surgeons; and GPs) and used framework analysis on interviews and relevant curricula documents to identify themes. RESULTS: Legislation and professional/educational guidance influenced inclusion. PCC definitions and terminology differed and placement within curricula was variable. Royal Colleges defined the curriculum and provided training to ensure competence, but local deaneries independently implemented the curriculum. Trainer engagement was greater than trainee buy in. Quality assurance focused on feedback from trainers and trainees rather than patients, and patient and public involvement in curriculum development, teaching, and assessment was limited. CONCLUSIONS: There is a need for cross-organisation collaboration to develop a PCC competence framework that defines the skills and level of competence required at different points in training, with clarity around the differences between undergraduate and postgraduate requirements. Greater auditing and quality assurance of programme delivery would help identify successful practices to share within and across Royal Colleges, while still maintaining the flexibility of local provision. Engagement with patients and the public in this work can only strengthen provision.

What is the concordance between parent- and education professional-reported adaptive functioning in autistic children using the VABS-II?

Adaptive functioning of autistic children is traditionally measured through informant-report, often from parents. Behaviour varies across settings though, and context-specific reports should be considered. Limited and inconsistent results show low parent-education professional concordance, but no research has yet explored item level response variation. We investigated Vineland Adaptive Behaviour Scales-II concordance using 233 lower ability autistic children from the PACT-G sample. Domain and item level agreement was low, but better on objectively measured behaviours. Higher child nonverbal ability improved concordance. Where disagreements occurred, education professionals identified emergent skills more and parents were more likely to rate present/absent. Parents and education professionals view the adaptive abilities of autistic children differently and both should be considered when developing personalised interventions and support.

Combined social communication therapy at home and in education for young autistic children in England (PACT-G): a parallel, single-blind, randomised controlled trial.

BACKGROUND: Autistic children can have difficulty generalising treatment effects beyond the immediate treatment context. Paediatric Autism Communication Therapy (PACT) has been successful when delivered in the clinic. Here we tested the Paediatric Autism Communication Therapy-Generalised (PACT-G) intervention combined between home and education settings for its overall effect and mechanistic transmission of effect across contexts. METHODS: In this parallel, single-blind, randomised, controlled trial, we recruited autistic children aged 2-11 years in urban or semi-urban areas in Manchester, Newcastle, and London, England. Children needed to meet core autism criteria on Autism Diagnostic Observation Schedule-second edition (ADOS-2) and parent-rated Social Communication Questionnaire (SCQ-lifetime), and children older than 5 years were included if they had intentional communication but expressive language equivalent of age 4 years or younger. Eligible children were randomly assigned (1:1), using block randomisation (random block sizes of 2 and 4) and stratified for site, age (2-4 years vs 5-11 years), and gender, to either PACT-G plus treatment as usual or treatment as usual alone. Research assessors were masked to treatment allocation. The PACT-G intervention was delivered by a therapist in parallel to the child's parents at home and to learning-support assistants (LSA) at their place of education, using both in-person and remote sessions over a 6 month period, to optimise adult-child social interaction. Treatment as usual included any health support or intervention from education or local community services. The primary outcome was autism symptom severity using the ADOS-2, as measured by researchers, at 12 months versus baseline. Secondary outcomes were Brief Observation of Social Communication Change (BOSCC) and dyadic social interaction between child and adult across contexts, both at 12 months. Other secondary outcome measures were assessed using the following composites: language, anxiety, repetitive behaviour, adaptive behaviour, parental wellbeing, child health-related quality of life, and disruptive behaviour. Assessments were done at baseline, 7 months, and 12 months. We used an intention-to-treat (ITT) analysis of covariance for the efficacy outcome measures. Adverse events were assessed by researchers for all trial families at each contact and by therapists in the PACT-G group at each visit. This study is registered with the ISRCTN Registry, ISRCTN 25378536. FINDINGS: Between Jan 18, 2017, and April 19, 2018, 555 children were referred and 249 were eligible, agreed to participate, and were randomly assigned to either PACT-G (n=122) or treatment as usual (n=127). One child in the PACT-G group withdrew and requested their data be removed from the study, giving an ITT population of 248 children. 51 (21%) of 248 children were female, 197 (79%) were male, 149 (60%) were White, and the mean age was 4·0 years (SD 0·6). The groups were well balanced for demographic and clinical characteristics. In the PACT-G group, parents of children received a median of 10 (IQR 8-12) home sessions and LSAs received a median of 8 (IQR 5-10) education sessions over 6 months. We found no treatment effect on the ADOS-2 primary outcome compared with treatment as usual (effect size 0·04 [95% CI -0·19 to 0·26]; p=0·74), or researcher-assessed BOSCC (0·03 [-0·25 to 0·31]), language composite (-0·03 [-0·15 to 0·10]), repetitive behaviour composite (0·00 [-0·35 to 0·35]), adaptive behaviour composite (0·01 [-0·15 to 0·18]), or child wellbeing (0·09 [-0·15 to 0·34]). PACT-G treatment improved synchronous response in both parent (0·50 [0·36 to 0·65]) and LSA (0·33 [0·16 to 0·50]), mediating increased child communication with parent (0·26 [0·12 to 0·40]) and LSA (0·20 [0·06 to 0·34]). Child dyadic communication change mediated outcome symptom alteration on BOSCC at home (indirect effect -0·78 [SE 0·34; 95% CI -1·44 to -0·11]; p=0·022) although not in education (indirect effect -0·67 [SE 0·37; 95% CI -1·40 to 0·06]; p=0·073); such an effect was not seen on ADOS-2. Treatment with PACT-G also improved the parental wellbeing composite (0·44 [0·08 to 0·79]) and the child disruptive behaviour composite in home and education (0·29 [0·01 to 0·57]). Adverse events on child behaviour and wellbeing were recorded in 13 (10%) of 127 children in the treatment as usual group (of whom four [31%] were girls) and 11 (9%) of 122 in the PACT-G group (of whom three [33%] were girls). One serious adverse event on parental mental health was recorded in the PACT-G group and was possibly study related. INTERPRETATION: Although we found no effect on the primary outcome compared with treatment as usual, adaptation of the 12-month PACT intervention into briefer multicomponent delivery across home and education preserved the positive proximal outcomes, although smaller in effect size, and the original pattern of treatment mediation seen in clinic-delivered therapy, as well as improving parental wellbeing and child disruptive behaviours across home and school. Reasons for this reduced efficacy might be the reduced dose of each component, the effect of remote delivery, and the challenges of the delivery contexts. Caution is needed in assuming that changing delivery methods and context will preserve an original intervention efficacy for autistic children. FUNDING: National Institute for Health Research and Medical Research Council Efficacy and Mechanism Evaluation Award.

Which Factors Influence Teacher Report of Adaptive Functioning in Autistic Children?

A wealth of parent-report research shows adaptive functioning difficulties in autistic children, with parent-report influenced by a number of child factors. Adaptive functioning in autistic children is known to vary across settings; however, no research has yet explored factors influencing education professional-report. This study investigated the rate and profile of impairment, and child factors influencing education professional-reported adaptive skills in 248 autistic children. Twelve children were < 3 years (min age for available normative data on the adaptive function measure), so were removed from the analyses. Results replicated parent-literature; adaptive skills were negatively associated with age and informant-reported autism severity, and positively associated with nonverbal ability and expressive language. Adaptive functioning is important for real-world outcomes, e.g. educational attainment, independence, and support needs. Improving our understanding of adaptive functioning in the education context may support opportunities for shared learning and enhance personalised support .

The Mediating Effects of Alexithymia, Intolerance of Uncertainty, and Anxiety on the Relationship Between Sensory Processing Differences and Restricted and Repetitive Behaviours in Autistic Adults.

Distress caused by sensory processing differences for autistic individuals may be reduced by repetitive behaviours (RRB), including repetitive motor (RMB) and insistence on sameness (ISB) behaviours. Intolerance of uncertainty (IU) and anxiety mediate the relationship between sensory processing and RRB in autistic children. We replicated this model in autistic adults, extending it to include alexithymia. Serial mediation, using data from 426 autistic adults, identified significant direct effects from sensory processing to RMB and ISB, and indirect effects through alexithymia-IU-anxiety for RMB, and IU alone, and alexithymia-IU for ISB. Different mechanisms may underpin RMB and ISB. Alexithymia alongside, IU and anxiety, should be considered when understanding the relationship between sensory processing and RRB, and when offering interventions to support autistic people.

Inclusion of person-centred care in medical and nursing undergraduate curricula in the UK: Interviews and documentary analysis.

OBJECTIVE: We aimed to understand how person-centred care (PCC) is represented in UK professional standards for undergraduate medical/nursing education and explored how these are reflected in programme provision. METHODS: We identified PCC components in medical (GMC) and nursing (NMC) professional standards and university curricula documents provided. We also identified themes from interviews with high-level informants for medical/nursing undergraduate programmes using framework analysis. RESULTS: The GMC appears to promote a more paternalistic model of care with discrete PCC components in specific sections and the NMC a more collaborative model with PCC distributed throughout. These differences persisted into education delivery. Medical educators perceived greater barriers to inclusion of PCC than nursing educators; however, both consistently identified cultural and organisational attributes. Clarity was lacking regarding PCC definition, how to teach/assess PCC, and competence expectations. CONCLUSION: Development of a PCC skills competence framework would increase consistency and support teaching and assessment in undergraduate curricula. Further research to understand the perspectives of healthcare professionals involved in placements would help inform PCC teaching recommendations. PRACTICE IMPLICATIONS: High-level support from senior HEI leaders; multi-disciplinary approaches to curricula development, teaching, and assessment; and greater inclusion of service users would ensure higher quality PCC education for undergraduate students.

Cognitive deficits in adult m.3243A>G- and m.8344A>G-related mitochondrial disease: importance of correcting for baseline intellectual ability.

OBJECTIVE: To determine the cognitive profile of adult patients with mitochondrial disease, and the effect of disease severity on cognition. METHODS: Using a prospective case-control design, we compared cognition of patients to normative data and to matched controls, assessed three times over 18 months. Forty-nine patients with m.3243A>G (N = 36) and m.8344A>G (N = 13) mtDNA mutations and 32 controls, matched by age (±5 years) and premorbid cognition (±10 WTAR FSIQ points), participated. Participants completed neuropsychological assessments of general cognition (WAIS-IV), executive function (D-KEFS), and memory (WMS-IV). Potential predictors of cognition were explored. RESULTS: Patients show mild-to-moderate premorbid cognitive impairment, but substantial impairment in current general cognition and distinct domains, including verbal comprehension, perceptual reasoning, working memory, processing speed, and memory retrieval. Executive dysfunction may be caused by slower decision-making. Patients performed worse than controls, except on memory tasks, indicating intact memory, when premorbid cognition is controlled for. Premorbid cognition and disease severity were consistent predictors of cognition in patients; however, cognitive decline appears slow and is unlikely in the short-term, when other disease-specific factors remain stable. INTERPRETATION: Patients should be monitored to facilitate early identification of a complex profile of cognitive deficits and individuals with higher disease burden should be followed up more closely. On development of cognitive difficulties, appropriate compensatory strategies should be determined through in-depth assessment. Using strategies such as slower presentation of information, multiple modes of presentation, active discussion to aid understanding and decision-making, and use of memory aids, may ameliorate difficulties.

Synthetic models of the reduced active site of superoxide reductase.

We report the synthesis, structural and spectroscopic characterization, and magnetic and electrochemical studies of a series of iron(II) complexes of the pyridyl-appended diazacyclooctane ligand L(8)py(2), including several that model the square-pyramidal [Fe(II)(N(his))(4)(S(cys))] structure of the reduced active site of the non-heme iron enzyme superoxide reductase. Combination of L(8)py(2) with FeCl(2) provides [L(8)py(2)FeCl(2)] (1), which contains a trigonal-prismatic hexacoordinate iron(II) center, whereas a parallel reaction using [Fe(H(2)O)(6)](BF(4))(2) provides [L(8)py(2)Fe(FBF(3))]BF(4) (2), a novel BF(4)(-)-ligated square-pyramidal iron(II) complex. Substitution of the BF(4)(-) ligand in 2 with formate or acetate ions affords distorted pentacoordinate [L(8)py(2)Fe(O(2)CH)]BF(4) (3) and [L(8)py(2)Fe(O(2)CCH(3))]BF(4) (4), respectively. Models of the superoxide reductase active site are prepared upon reaction of 2 with sodium salts of aromatic and aliphatic thiolates. These model complexes include [L(8)py(2)Fe(SC(6)H(4)-p-CH(3))]BF(4) (5), [L(8)py(2)Fe(SC(6)H(4)-m-CH(3))]BF(4) (6), and [L(8)py(2)Fe(SC(6)H(11))]BF(4) (7). X-ray crystallographic studies confirm that the iron(II)-thiolate complexes model the square-pyramidal geometry and N(4)S donor set of the reduced active site of superoxide reductase. The iron(II)-thiolate complexes are high spin (S = 2), and their solutions are yellow in color because of multiple charge-transfer transitions that occur between 300 and 425 nm. The ambient temperature cyclic voltammograms of the iron(II)-thiolate complexes contain irreversible oxidation waves with anodic peak potentials that correlate with the relative electron donating abilities of the thiolate ligands. This electrochemical irreversibility is attributed to the bimolecular generation of disulfides from the electrochemically generated iron(III)-thiolate species.