Testing SIPA1L2 as a modifier of CMT1A using mouse models.

Charcot-Marie-Tooth disease type 1A (CMT1A) is a demyelinating peripheral neuropathy caused by the duplication of peripheral myelin protein 22 (PMP22), leading to muscle weakness and loss of sensation in the hands and feet. A recent case-only genome-wide association study of CMT1A patients conducted by the Inherited Neuropathy Consortium identified a strong association between strength of foot dorsiflexion and variants in signal induced proliferation associated 1 like 2 (SIPA1L2), indicating that it may be a genetic modifier of disease. To validate SIPA1L2 as a candidate modifier and to assess its potential as a therapeutic target, we engineered mice with deletion of exon 1 (including the start codon) of the Sipa1l2 gene and crossed them to the C3-PMP22 mouse model of CMT1A. Neuromuscular phenotyping showed that Sipa1l2 deletion in C3-PMP22 mice preserved muscular endurance assayed by inverted wire hang duration and changed femoral nerve axon morphometrics such as myelin thickness. Gene expression changes suggest involvement of Sipa1l2 in cholesterol biosynthesis, a pathway that is also implicated in C3-PMP22 mice. Although Sipa1l2 deletion did impact CMT1A-associated phenotypes, thereby validating a genetic interaction, the overall effect on neuropathy was mild.

Facilitating the identification of intellectual disability in schools: A qualitative study of stakeholder views.

BACKGROUND: Many children experience delayed or missed identification of an intellectual disability diagnosis, meaning that key opportunities for early educational intervention may be lost. METHODS: Semi-structured interviews were used to explore the views of teachers, parents, and clinicians (n = 22), about the use of the Child and Adolescent Intellectual Disability Screening Questionnaire (CAIDS-Q) and what could improve screening and identification of intellectual disability in schools. Thematic analysis was used to identify relevant themes. RESULTS: Three themes were identified: the need for, and role of, screening in the context of limited knowledge about intellectual disability; the impact of screening and subsequent identification of intellectual disability; and the context within which participants felt screening should take place in order to maximise its benefits. CONCLUSIONS: The results confirmed the importance and benefits of timely identification of children with an intellectual disability and the positive role that screening might play in this.

Testing SIPA1L2 as a modifier of CMT1A using mouse models.

Charcot-Marie-Tooth 1A is a demyelinating peripheral neuropathy caused by the duplication of peripheral myelin protein 22 (PMP22), which produces muscle weakness and loss of sensation in the hands and feet. A recent case-only genome wide association study by the Inherited Neuropathy Consortium identified a strong association between variants in signal induced proliferation associated 1 like 2 (SIPA1L2) and strength of foot dorsiflexion. To validate SIPA1L2 as a candidate modifier, and to assess its potential as a therapeutic target, we engineered mice with a deletion in SIPA1L2 and crossed them to the C3-PMP22 mouse model of CMT1A. We performed neuromuscular phenotyping and identified an interaction between Sipa1l2 deletion and muscular endurance decrements assayed by wire-hang duration in C3-PMP22 mice, as well as several interactions in femoral nerve axon morphometrics such as myelin thickness. Gene expression changes suggested an involvement of Sipa1l2 in cholesterol biosynthesis, which was also implicated in C3-PMP22 mice. Though several interactions between Sipa1l2 deletion and CMT1A-associated phenotypes were identified, validating a genetic interaction, the overall effect on neuropathy was small.

The views of people using homeless services about learning disability.

AIMS: People with a learning disability are at increased risk of becoming homeless, but little is known about how learning disability is viewed by people accessing homeless services. This study aimed to obtain the views of people experiencing homelessness about learning disability, in the context of a project that was exploring how to increase identification of learning disability. METHODS: A qualitative approach was used, and 19 adults were interviewed who were receiving support from homeless services in the North-East of England. Information from the interviews was analysed using thematic analysis. RESULTS: Four themes were identified relating to understanding of learning disability, the role of identification, day-to-day challenges, and experiences of services. CONCLUSION: There is a need to: promote better understanding of learning disability; for early identification processes that involve the person in a meaningful way; and the provision of support that is non-stigmatising, practical and which addresses health concerns.

Using the learning disability screening questionnaire to help identify people with an intellectual disability in homeless services.

BACKGROUND: We explored the accuracy of using the learning disability screening questionnaire (LDSQ) in services for people experiencing homelessness in the United Kingdom. METHOD: We examined the concordance between the LDSQ outcomes and assessments of intellectual disability. Seventy adults experiencing homelessness completed the LDSQ. Staff completed the LDSQ and a measure of adaptive functioning for 38 of this group. Nine participants received an intellectual assessment. RESULTS: Sensitivity and specificity for the LDSQ when completed by staff was 83% and 96% respectively and 50% and 92% when completed by the individual. Seven people had intellectual and adaptive functioning in the intellectual disability range. CONCLUSION: The results suggest that the LDSQ would be an appropriate and beneficial screening tool to use within services for people experiencing homelessness. More accurate results would be likely if it were completed by staff.

An allelic series of spontaneous Rorb mutant mice exhibit a gait phenotype, changes in retina morphology and behavior, and gene expression signatures associated with the unfolded protein response.

The Retinoid-related orphan receptor beta (RORß) gene encodes a developmental transcription factor and has 2 predominant isoforms created through alternative first exon usage; one specific to the retina and another present more broadly in the central nervous system, particularly regions involved in sensory processing. RORß belongs to the nuclear receptor family and plays important roles in cell fate specification in the retina and cortical layer formation. In mice, loss of RORß causes disorganized retina layers, postnatal degeneration, and production of immature cone photoreceptors. Hyperflexion or "high-stepping" of rear limbs caused by reduced presynaptic inhibition by Rorb-expressing inhibitory interneurons of the spinal cord is evident in RORß-deficient mice. RORß variants in patients are associated with susceptibility to various neurodevelopmental conditions, primarily generalized epilepsies, but including intellectual disability, bipolar, and autism spectrum disorders. The mechanisms by which RORß variants confer susceptibility to these neurodevelopmental disorders are unknown but may involve aberrant neural circuit formation and hyperexcitability during development. Here we report an allelic series in 5 strains of spontaneous Rorb mutant mice with a high-stepping gait phenotype. We show retinal abnormalities in a subset of these mutants and demonstrate significant differences in various behavioral phenotypes related to cognition. Gene expression analyses in all 5 mutants reveal a shared over-representation of the unfolded protein response and pathways related to endoplasmic reticulum stress, suggesting a possible mechanism of susceptibility relevant to patients.

Short Report: Exploring the extent to which Intellectual Disability is undiagnosed within children attending developmental paediatric clinics.

Intellectual Disability is under-ascertained worldwide and is associated with greater physical and mental health difficulties. This research aimed to identify clinical features and characteristics of children with Intellectual Disability in a population of 126 6-18 year olds in mainstream school, attending paediatric developmental clinics. Intellectual Disability was defined according to the DSM-5 (deficits in intellectual and adaptive functioning, present during childhood). Measures used to assess this were WISC-IV IQ (score <70) and ABAS adaptive behaviour (score =<70). Clinical features were compared from a structured clinical records investigation and logistic regression explored which factors were associated with Intellectual Disability. Twenty-eight children (22%) met the criteria for Intellectual Disability. Five variables were associated with higher odds of having Intellectual Disability: no other neurodevelopmental diagnosis, multiple other health problems, prior genetic testing, maternal smoking during pregnancy, and parental unemployment. Routinely-collected paediatric data only predicted Intellectual Disability correctly in two out of five cases. Further research is needed to verify these findings and improve identification. WHAT THIS PAPER ADDS?: Many children with Intellectual Disability, particularly a milder version, still reach adulthood without a diagnosis, despite evidence indicating that diagnosis is generally well received by children and families, and that early intervention leads to improvements in outcomes. This short report, based on a small sample of 126 children aged 6-18 in mainstream school who attended a paediatric development clinic in South East Scotland, provides tentative data on the clinical features and characteristics which are associated with Intellectual Disability. This tentative evidence suggests that the combination of a) having multiple concerns and investigations, alongside b) one or both parents being out of work (which may be related to familial undiagnosed Intellectual Disability), should raise a flag for paediatricians to further investigate the possibility of an Intellectual Disability diagnosis among these children and young people. Further research with larger samples is needed to explore this more robustly, with the potential to create an algorithm to highlight to paediatricians cases requiring formal screening for Intellectual Disability.

An exploration of the impact of contextual information on the emotion recognition ability of autistic adults.

Studies of non-autistic individuals and people with an intellectual disability show that contextual information impacts positively on emotion recognition ability, however, this area is not well researched with autistic adults. We investigated this using a static emotion recognition task. Participants completed an emotion recognition task in person or online. In total, 46 autistic participants and 379 non-autistic participants completed the task. A linear mixed model showed that autistic adults had significantly lower accuracy when identifying emotions across all contexts, compared to control participants, even when contextual information was present. No significant effect of context was found in either group, nor was gender shown to be an influential variable. A supplementary analysis showed that higher scores on the Autism-Spectrum Quotient led to lower scores on the emotion recognition task; no effect of context was found here either. This research adds to the limited work investigating the influence of contextual factors in emotion recognition in autistic adults. Overall, it shows that context may not aid emotion recognition in this group in the same way as it does for non-autistic individuals.

Reciprocal Developmental Relations Between ADHD and Anxiety in Adolescence: A Within-Person Longitudinal Analysis of Commonly Co-Occurring Symptoms.

Objective: Significant anxiety often occurs in the presence of ADHD symptoms; however, the reasons are not well understood. We aimed to establish whether the relations between ADHD symptons and anxiety are bidirectional or unidirectional. METHOD: Weexamined the developmental relations between ADHD and anxiety symptoms across adolescence (ages 13, 15, and 17) in a community-ascertained, normative longitudinal sample of 1,483 youth (52% male). We used an autoregressive latent trajectory model with structured residuals (ALT-SR) to examine within-person developmental relations between ADHD and anxiety symptoms to determine whether it is ADHD symptoms that lead to anxiety symptoms and/or the reverse. RESULTS: Results suggested that there are reciprocal within-person developmental relations between ADHD and anxiety symptoms. CONCLUSIONS: Our findings support the recommendation that targeting ADHD symptoms can be fruitful for addressing anxiety symptoms; however, they suggest that targeting anxiety symptoms may also benefit ADHD symptoms. Results also underline the importance of careful assessment for underlying ADHD symptoms among adolescents presenting with anxiety.

A quantitative evaluation of a regional Positive Behavioural Support workforce development approach.

BACKGROUND: Research suggests that providing staff with input in relation to Positive Behavioural Support (PBS) can have beneficial outcomes. Much of this research, however, fails to take account of systemic issues and does not include a control group. METHOD: We used a non-randomised, controlled group design to evaluate accredited PBS programmes, delivered as part of a systemic, regional and workforce development approach. We compared outcomes of those attending the programmes (n = 240) with a control group (n = 54), pre- and post-intervention and at 3-months follow-up. RESULTS: The programme and its wider impact were rated positively. Significant intervention effects were found for staff practice and retention, but not for staff knowledge and attributions, or behaviours that challenge and quality of life of those being supported. CONCLUSIONS: The results are discussed in the context of the study limitations and restrictions resulting from the Covid-19 pandemic.

The impact of COVID-19 restrictions in the United Kingdom on the positive behavioural support of people with an intellectual disability.

The way that people with an intellectual disability are supported is very important.The COVID-19 virus has changed the way that staff help people with an intellectual disability.We wanted to know about those changes and whether learning about positive behavioural support (PBS) helped staff to cope with them.The main changes were that people with an intellectual disability could not go out or see family and friends as often.Staff came up with new things to do for the people they supported, and PBS learning seemed to help staff to cope. Background: It has been suggested that COVID-19 and the associated restrictions are likely to have a negative impact on the provision of positive behavioural support (PBS) to people with an intellectual disability. Methods: Fifty-eight staff, who had recently completed an accredited positive behavioural support (PBS) programme, responded to an online questionnaire, which asked them to rate the impact of COVID-19 on factors related to PBS. Results: Participants reported a neutral or somewhat positive impact on all the areas measured, with the exception of the activities and quality of life of those they supported, which were somewhat negatively affected. The participants rated the learning from their PBS programme as helping them cope with COVID-19 to some extent. Examples of positive and negative effects and ways in which PBS helped staff to cope are presented. Conclusions: Many staff developed creative solutions that allowed them to provide PBS despite the COVID-19 restrictions. PBS learning appeared to help staff cope with the negative impact of the restrictions.

The use of an implementation science theoretical framework to inform the development of a region wide Positive Behavioural Support Workforce Development approach.

BACKGROUND: Concern about the poor care of some people with an intellectual disability has highlighted the need for systemic, large-scale interventions to develop a skilled workforce. METHOD: We outline how an implementation science theoretical model informed the development of a region-wide Positive Behavioural Support (PBS) Workforce Development (WFD) approach. RESULTS: We provide an example of the application of the model in practice and demonstrate how this enabled us to understand the competencies and development needs of the workforce; engage effectively with stakeholders; and develop, deliver and evaluate a PBS WFD model. CONCLUSION: The application of the model helped us to identify, prioritise, and address the multiple and complex factors that were relevant to the implementation of the PBS WFD approach.

Developmental Cascades from Aggression to Internalizing Problems via Peer and Teacher Relationships from Early to Middle Adolescence.

Previous research has provided evidence for developmental cascades between externalizing and internalizing problems via mechanisms such as peer and academic problems; however, there remains a need to illuminate other key mediating processes that could serve as intervention targets. This study, thus, evaluated whether developmental associations between aggression and internalizing are mediated by teacher-as well as peer-relationships. Using data from z-proso, a longitudinal study of Swiss youth (n = 1523; 785 males), an autoregressive latent trajectory model with structured residuals (ALT-SR) was fit over ages 11, 13, and 15 to examine within-person developmental links between aggression, internalizing problems, and the mediating role of peer and teacher relationships, while disaggregating between- and within-person effects. Teacher and peer relationships did not play a role in the progression of externalizing to internalizing problems or vice versa, however, teacher and peer relationships showed a protective effect against developing internalizing problems at ages 13. The results suggest that good quality relationships with teachers in early adolescence can help prevent internalizing problems from developing.

'It's been adapted rather than impacted': A qualitative evaluation of the impact of Covid-19 restrictions on the positive behavioural support of people with an intellectual disability and/or autism.

BACKGROUND: We used a qualitative approach to explore the experiences of social care staff regarding the provision of positive behavioural support (PBS) to people with an intellectual disability at the height of the Covid-19 restrictions. METHOD: We conducted semi-structured interviews with 19 staff who had recently completed a PBS workforce development programme. Data were analysed using thematic analysis. RESULTS: Three themes were identified in the context of the restrictions: The challenges to maintaining quality of life and PBS of the people being supported and staff attempts to overcome these; the ways in which PBS and behaviour support plans were implemented and the impact on behaviours that challenge; the ways in which PBS principles were applied at organisational levels to help to understand and address staff stress and distress. CONCLUSIONS: Overall, the staff identified many unexpected benefits of the restrictions. The results are discussed in the context of the study limitations.

The use of therapeutic untruths by staff supporting people with an intellectual disability who display behaviours that challenge.

BACKGROUND: Therapeutic untruths (TU) are used in dementia services to de-escalate distressing situations. The present authors explored the use of TU by care staff supporting people with an intellectual disability who displayed behaviours that challenged. METHOD: Data were collected from 126 staff (female = 72.2%; mean age = 41.9 years, SD = 10.7) via an online survey in relation to three areas: responses to three scenarios, reported use of different forms of TU and ratings of perceived effectiveness of, and level of comfort using, each type. RESULTS: 96% of participants reported using TU themselves and observing their colleagues doing likewise. Models that included perceived effectiveness of, and level of staff comfort with using, different TU were significant, although only perceived effectiveness significantly independently contributed to the model. CONCLUSION: The use of TU was common, with levels consistent with those found in dementia services. The limitations and implications of the findings are discussed.

Validation of a Brief Self-Report Measure of Adolescent Bullying Perpetration and Victimization.

Although a wide range of measures of bullying have been developed, there remains a need for brief psychometrically supported measures for use in contexts in which there are constraints on the number of items that can be administered. We thus evaluated the reliability and validity of scores from a 10-item self-report measure of bullying victimization and perpetration in adolescents: the Zurich Brief Bullying Scales. The measure covers social exclusion, property destruction, verbal and physical aggression, and sexual bullying in both traditional and cyber forms. We evaluated factorial validity, internal consistency, developmental invariance, gender invariance, and convergent and divergent validity of the measure. Our sample was the normative longitudinal Zurich Project on Social Development from Childhood to Adulthood (z-proso) sample (N = 1,304). The study involved the administration of Zurich Brief Bullying Scales to participants aged 11, 13, 15, and 17 years. Strengths and weaknesses of the measure and recommendations for utilizing and improving the measure were identified. Overall, results suggest that the items provide a reasonable general but brief measure of bullying victimization and perpetration that can be used across early to late adolescence and in both males and females.

Validation of the English Language Version of the Violent Ideations Scale.

This study used a within-participant design to evaluate the concurrent validity and test-retest reliability of the Violent Ideations Scale in a general population, English-speaking opportunistic sample. Data from 116 adult participants (M age = 33.7, SD = 11.9, male = 30 [25.9%]) were used to compare scores on the Violent Ideations Scale and Aggression Questionnaire and responses to the Schedule of Imagined Violence. A subgroup of 27 participants (M age = 37.2, SD = 13.6, male = 8 [29.6%]) completed the Violent Ideations Scale on a second occasion, 2 weeks later. The Violent Ideations Scale was found to correlate significantly with the Aggression Questionnaire subscale and total scores, with the strongest correlations being with physical aggression and total scores. Participants were more likely to be categorized as having experienced a violent ideation based on responses to the Violent Ideation Scale, compared with the Schedule of Imagined Violence, most likely due to the Schedule of Imagined Violence underestimating the prevalence of violent ideation. A significant, strong correlation was found between total Violent Ideations Scale scores at Time 1 and Time 2. Overall, the Violent Ideations Scale was found to have concurrent validity when compared with the Aggression Questionnaire and good test-retest reliability, suggesting that it would be suitable for use with a nonclinical, English-speaking sample.

The use of therapeutic untruths by learning disability nursing students.

BACKGROUND: The use of therapeutic untruths raises a number of ethical issues, which have begun to be explored to some extent, particularly in dementia care services, where their use has been found to be high. Little is known, however, about their use by health professionals working in learning disability services. RESEARCH QUESTION: The study aimed to explore the frequency of use of therapeutic untruths by student learning disability nurses, and by their colleagues; how effective the students perceived them to be as a means of responding to behaviours that challenge; and their level of comfort with using them. RESEARCH DESIGN: A correlational design was used to gather data from an online version of the Best Interest Scale, adapted for a learning disability context. Participants were 30 learning disability student nurses (female = 28, ages 18-48 years, M = 26.8, standard deviation = 7.3) studying at a university in the North-East of England. ETHICAL CONSIDERATIONS: The study was reviewed and received ethical approval from the first author's university ethics committee. FINDINGS: Overall, 96% of participants reported using therapeutic untruths. 'Omission' was the most frequently used type of therapeutic untruths, the most effective and the type that the students felt most comfortable using. Frequency of use of therapeutic untruths correlated significantly and positively with perceived effectiveness and the level of comfort that the students felt when using them, for all types of therapeutic untruths. CONCLUSION: The use of therapeutic untruths by the student nurses was consistent with that found in research in dementia care services in the United Kingdom and abroad. Further research to explore the generalisability of the results to the wider context of learning disability services is needed. The study highlights that there may be a need for more formal guidance and educational input to student nurses in the use of therapeutic untruths with people with a learning disability.

"Look, all our hard work is paying off": A qualitative evaluation of a system-wide, workforce development model to promote positive behavioural support.

BACKGROUND: Positive behavioural support (PBS) has been identified as a means of improving the quality of life and support of people with an intellectual disability. This qualitative study explored the views of service providers about a regional PBS programme, that was underpinned by a workforce development approach. METHOD: Semi-structured interviews were conducted with senior staff (n = 42), from organizations which provided services to people with an intellectual disability, about their views about, and perceived impact of, the PBS programme, Data were analysed using thematic analysis. RESULTS: Two themes were identified: "It's what PBS is about, isn't it?" emphasized the importance of the programme being systemic- and evidence-based; "Macro to micro" highlighted the different points in the systems of care at which the programme was seen to impact. CONCLUSIONS: We discuss the results in the context of the study limitations.

An evaluation of the distribution properties, factor structure, and item response profile of an assessment of emotion recognition.

Many people with developmental disabilities, such as autism spectrum disorder and intellectual disability have emotion recognition (ER) difficulties compared with typically developing (TD) peers. Accurate assessment of the extent and nature of differences in ER requires an understanding of the response profiles to ER assessment stimuli. We analysed data from 504 TD individuals in response to an ER assessment in respect of distribution properties, factor structure, and item response profile. Eighteen emotion items discriminated better at lower levels of ER ability in TD participants. Neutral expressions were the hardest to interpret; surprise, anger, happy, and bored were easiest. The amount of contextual information in combination with the emotion being depicted also appeared to influence level of difficulty. Similar psychometric research is needed with people with developmental disabilities.