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Background: The psychological therapies service (PTS) in the Northern Health and Social Care Trust, in Northern Ireland, provides therapies to adults with moderate or severe mental health difficulties. Psychometric outcomes data are routinely collected to assess if a patient demonstrates significant improvement in their main presenting problem area following therapy. The wider impact of therapy is not fully measured in the outcomes database as this would be disproportionately burdensome for both patient and therapist. The present study, to our knowledge, is the first to use data linkage to link patient therapy outcomes data with prescriptions data., Aims: To widen our understanding of patient medication use before and after therapy., Method: Using Health and Care Number as a unique identifier, the Psychological Therapies Service - Routine Outcome Measurement Database ( n = 3625) and data from 72 500 controls were linked with data from the Enhanced Prescribing Database (EPD). The EPD data were sourced from the Honest Broker Service., Results: Key findings from the study were: (a) the odds of PTS clients using antipsychotics in the year before therapy were 25 times greater compared with controls (odds ratio (OR) = 24.53, 95% CI 20.16-29.84); (b) in the 1st year post discharge, PTS clients who clinically improved post therapy discharge were more likely than 'non-engagers' and 'non-improvers' to come off antianxiety medication (OR = 0.61, 95%, CI 0.38-0.98); and (c) therapy did not have an impact on antidepressant use., Conclusions: The results highlight the need for discussion between therapy services, GPs and psychiatry about whether more engagement and collaboration is needed to plan phased reduction in medication.

Background: Globally, children are legally obliged to attend school at a certain age (ranging from 4 to 7 years old). Developmental differences are rarely considered at school entry nor are they always reflected in the teaching and learning environment. Children who start school without being ready to cope may be significantly disadvantaged. Failure at school can impact directly on long-term outcomes such as unemployment, crime, adolescent pregnancy, and psychological and physical morbidity in adulthood. In contrast, experiencing success at school can impact positively on a child's self esteem, behaviour, attitude, and future outcomes. School readiness interventions aim to prepare a child for the academic content of education and the psychosocial competencies considered important for learning such as self-regulation, listening, following instructions and learning to share in play and other social settings. There is a need for evidence of the effectiveness of centre-based school readiness interventions., Objectives: To evaluate the effectiveness of centre-based interventions for improving school readiness in preschool children., Search Methods: In October 2021 we searched CENTRAL, MEDLINE, Embase, ERIC, PsycINFO, ERIC, eight additional databases and three trials registers. Other eligible studies were identified through handsearches of reference lists, reports, reviews and relevant websites., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs comparing centre-based school readiness interventions to no intervention, wait-list control or treatment as usual (TAU) for children (aged three to 7 years before starting compulsory education). The primary outcomes were school readiness and adverse effects., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of evidence., Main Results: We included data from 32 trials involving 16,899 children (6590 included in at least one meta-analysis). Four studies compared centre-based early education interventions with no treatment controls. Twenty-two trials compared an enriched school curriculum to treatment as usual (TAU). Children were aged between 3 and 7 years old (mean age 4.4 years), 51.7% were boys and at least 70% were from a racial/ethnic minority group. Most studies were conducted in the USA and mainly located in areas of high socioeconomic deprivation. Interventions were delivered in centre-based settings (pre-kindergarten or elementary schools), for at least one half day, 4 days per week over the academic year. Follow-up ranged from up to 1 year (short-term), 1-2 years (medium-term) and over 2 years (long-term). We judged the certainty of evidence to be very low to moderate across all outcome measures. We downgraded the certainty of the evidence because the included studies were at an unclear or high risk of bias due to poor reporting, imprecision arising from small sample sizes and wide confidence intervals, and inconsistency due to statistical heterogeneity. Most studies were considered to be low or unclear risk for selection, detection, performance, attrition, selective reporting, and other bias. Allocation bias was at high risk in 10 studies. The US federal government funded most of the studies. Comparison 1. Centre-based early education interventions for improving school readiness versus no intervention Cognitive development . There may be little to no difference in cognitive development between centre-based early education interventions and no intervention at long-term follow-up (MD: 3.28, 95% CI: 0.23 to 6.34; p  = 0.04; 2 studies, 361 participants; low certainty evidence). Emotional well-being and social competence . There may be no clear difference in social skills in centre-based early education interventions compared to the no intervention control group at short-term follow-up (SMD: -0.11, 95% CI: -0.54 to 0.33; p  = 0.63; 3 studies, 632 participants; low certainty evidence). Heterogeneity for this outcome was substantial ( I ² = 71%). Health development . Narrative analysis from a single study showed that centre-based early education interventions may improve health development outcomes such as health checks, immunisation compliance and dental care (1 study, 142 participants; low certainty evidence).None of the studies reported on school readiness, adverse effects, or physical development. Comparison 2. Centre-based early education interventions for improving school readiness versus TAU School readiness . The evidence is very uncertain about the effect of centre-based early education interventions compared to TAU on school readiness up to 1 year post-intervention (SMD: 1.17, 95% CI: -0.61 to 2.95; p  = 0.20; 2 studies, 374 participants; very low certainty evidence). Heterogeneity for this outcome was considerable ( I ² = 95%). Cognitive development . The evidence is very uncertain about the effect on cognitive development between centre-based early education interventions and TAU at long-term follow-up (MD: 9.34, 95% CI: -6.64 to 25.32; p  = 0.25; 2 studies, 136 participants; very low certainty evidence). Heterogeneity for this outcome was considerable ( I ² = 92%). Emotional well-being and social competence . A meta-analysis of 12 studies demonstrated there may be little to no difference in social skills between centre-based early education interventions and TAU at short-term follow-up (SMD: 0.11, 95% CI: -0.05 to 0.28; p  = 0.19; 12 studies, 4806 participants; low certainty evidence). Physical development . Evidence from one study showed that centre-based early education interventions likely have little to no difference in increasing fine motor skills compared to TAU at short-term follow-up (MD: 0.80, 95% CI: -1.11 to 2.71; 1 study, 334 participants; moderate certainty evidence).None of the studies measured adverse effects or health development., Authors' Conclusions: We found very low, low and moderate-certainty evidence that centre-based interventions convey little to no difference to children starting school compared to no intervention or TAU, up to 1 year. More research, measuring relevant outcomes, conducted outside the USA, is required to improve programmes designed to meet the needs of children starting school., (© 2023 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Background: Cross-sectional studies have shown that the COVID-19 pandemic has had a significant impact on the mental health of healthcare staff. However, it is less well understood how working over the long term in successive COVID-19 waves affects staff well-being., Aims: To identify subpopulations within the health and social care staff workforce with differentiated trajectories of mental health symptoms during phases of the COVID-19 pandemic., Method: The COVID-19 Staff Wellbeing Survey assessed health and social care staff well-being within an area of the UK at four time points, separated by 3-month intervals, spanning November 2020 to August 2021., Results: Growth mixture models were performed on the depression, anxiety and post-traumatic stress disorder longitudinal data. Two class solutions provided the best fit for all models. The vast majority of the workforce were best represented by the low-symptom class trajectory, where by symptoms were consistently below the clinical cut-off for moderate-to-severe symptoms. A sizable minority (13-16%) were categorised as being in the high-symptom class, a group who had symptom levels in the moderate-to-severe range throughout the peaks and troughs of the pandemic. In the depression, anxiety and post-traumatic stress disorder models, the high-symptom class perceived communication from their organisation to be less effective than the low-symptom class., Conclusions: This research identified a group of health service staff who reported persistently high mental health symptoms during the pandemic. This group of staff may well have particular needs in terms of the provision of well-being support services.

Coercive control and related research have progressed significantly in the past number of years, with an ever-growing evidence base adding to its construct. However, currently there is a lack of evidence on young people's knowledge and understanding of coercive control. We included a module of questions in the 2020 Northern Ireland Young Life and Life and Times survey ( n  = 2,069) with the aim of capturing baseline measurable data on understanding of coercive control within intimate relationships among 16-year olds. Only 16% ( n  = 325) of respondents had heard of the term coercive control and knew what it meant. Findings also revealed that females, compared to males, were less likely to have heard of coercive control. When the victim being subjected to the behaviours was portrayed as female as opposed to male there was stronger recognition of the associated risks, need for support, and the seriousness of the situation. Our study findings call to question young people's knowledge of unhealthy intimate relationship behaviours beyond blatant and deliberate acts of harm such as those described in the coercive control scenarios. Gender disparities in awareness of coercive control across the study sample also give cause for concern given the increased risk of intimate partner violence among women and girls as well as lower reporting and help seeking among male victims. Results solidify the necessity for dedicated preventative and intervention efforts which focus on intimate relationships and reflect the diverse needs and experiences of young people. Supporting young people to act on their own behalf is an important step change to empowerment within their own intimate relationships., Competing Interests: Conflict of InterestThe authors have no conflict of interest to declare., (© The Author(s) 2023.)

Coercive control is characterised by negative behaviours which intimidate, threaten, and humiliate a person or restrict a person's liberty. In addition to being a known risk factor for experiencing other forms of violence, research has linked coercive control to symptoms of psychological distress and suicidality. In the UK, coercive and controlling behaviours within intimate and familial relationships have been legislated as offending behaviours. However, there still exists a lack of international evidence on wider public knowledge and understanding of coercive control. The Northern Ireland Life and Times Survey (NILT) is an annual cross-sectional representative survey of social policy topics. Participants are adults aged 18 years or over. Concerning coercive control, respondents were presented with two relationship scenarios: obvious and less obvious coercive control. Following each scenario, respondents indicated their level of agreement to ten statements covering attitudes towards coercive control, victims of coercive control, talking about coercive control, and whether coercive control is a crime. Respondents indicated whether they had heard of the term 'coercive control'. Predictors of coercive control awareness were assessed using multinomial logistic regression. Mixed analysis of variance assessed if agreement levels to the ten statements varied by type of coercive control and victim gender. Most respondents said that they had heard of the term coercive control and knew what it meant. Those who had not heard of coercive control at all were more likely to be on a lower income, less qualified and younger, when compared to those who said they knew what the term meant. Significant interactions between coercive control type and victim gender were evident for all ten statements. While most respondents are aware of the term coercive control, a significant number have not and are therefore unlikely to recognise the signs of this type of abuse., Competing Interests: Conflict of interestThe authors have no conflict of interest to declare., (© The Author(s) 2022.)

Background: Healthcare staff represent a high-risk group for mental health difficulties as a result of their role during the COVID-19 pandemic. A number of wellbeing initiatives have been implemented to support this population, but remain largely untested in terms of their impact on both the recipients and providers of supports. Objective: To examine the experience of staff support providers in delivering psychological initiatives to healthcare staff, as well as obtain feedback on their perceptions of the effectiveness of different forms of support. Method: A mixed methods design employing a quantitative survey and qualitative focus group methodologies. An opportunity sample of 84 psychological therapists providing psychological supports to Northern Ireland healthcare staff participated in an online survey. Fourteen providers took part in two focus groups. Results: The majority of providers rated a number of supports as useful (e.g. staff wellbeing helplines, Hospital In-reach) and found the role motivating and satisfying. Thematic analysis yielded five themes related to provision of support: (1) Learning as we go, applying and altering the response; (2) The 'call to arms', identity and trauma in the collective response; (3) Finding the value; (4) The experience of the new role; and (5) Moving forward. Conclusions: While delivering supports was generally a positive experience for providers, adaptation to the demands of this role was dependent upon important factors (e.g. clinical experience) that need to be considered in the planning phase. Robust guidance should be developed that incorporates such findings to ensure effective evidence-based psychological supports are available for healthcare staff during and after the pandemic.

The current feline genotyping array of 63 k single nucleotide polymorphisms has proven its utility for mapping within breeds, and its use has led to the identification of variants associated with Mendelian traits in purebred cats. However, compared to single gene disorders, association studies of complex diseases, especially with the inclusion of random bred cats with relatively low linkage disequilibrium, require a denser genotyping array and an increased sample size to provide statistically significant associations. Here, we undertook a multi-breed study of 1,122 cats, most of which were admitted and phenotyped for nine common complex feline diseases at the Cornell University Hospital for Animals. Using a proprietary 340 k single nucleotide polymorphism mapping array, we identified significant genome-wide associations with hyperthyroidism, diabetes mellitus, and eosinophilic keratoconjunctivitis. These results provide genomic locations for variant discovery and candidate gene screening for these important complex feline diseases, which are relevant not only to feline health, but also to the development of disease models for comparative studies., Competing Interests: Hill's Pet Nutrition Inc., United States, was affiliated with this study, employing author JB and funding the costs of the arrays. The funder was not involved in study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hernandez, Hayward, Brockman, White, Mouttham, Wilcox, Garrison, Castelhano, Loftus, Gomes, Balkman, Brooks, Fiani, Forman, Kern, Kornreich, Ledbetter, Peralta, Struble, Caligiuri, Corey, Lin, Jordan, Sack, Boyko, Lyons and Todhunter.)

Aims: To provide public health-related research evidence on types and usage patterns of new psychoactive substances (NPS), developmental pathways into NPS and decision-making factors for, and associated harms of, NPS use., Design: Three-phase mixed-methods design, including a latent class analysis (LCA) of the longitudinal Belfast Youth Development Study (BYDS), a narrative analysis of interviews with NPS users and a three-step approach manual method modelling using regressions to reveal classes of substance use and their associated predictors and outcomes., Setting: Northern Ireland., Participants: A total of 2039 people who responded to the questions on 'ever use' of the drug variables included at wave 7 (aged 21 years) of the BYDS. Eighty-four narrative interviews with NPS users., Measurements: Categories of drug use identified by LCA. Predictors and outcomes included measures of family, partners, peers, substance use, school, delinquency and mental health., Findings: A four-class solution provided the best fit for the data: alcohol; alcohol and tobacco; alcohol, tobacco and cannabis; and polydrug (the latter including NPS). The qualitative analysis yielded a taxonomy that distinguished how NPS operate within a wider range of drug repertoires from experimental to problematic., Conclusions: In Northern Ireland, new psychoactive substances appear to be a feature of broader polydrug use rather than a standalone class of drug use., (© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Throughout the coronavirus disease 2019 (COVID-19) pandemic, health and social care workers have faced unprecedented professional demands, all of which are likely to have placed considerable strain on their psychological well-being., Aims: To measure the national prevalence of mental health symptoms within healthcare staff, and identify individual and organisational predictors of well-being., Method: The COVID-19 Staff Wellbeing Survey is a longitudinal online survey of psychological well-being among health and social care staff in Northern Ireland. The survey included four time points separated by 3-month intervals; time 1 (November 2020; n = 3834) and time 2 (February 2021; n = 2898) results are presented here. At time 2, 84% of respondents had received at least one dose of a COVID-19 vaccine. The survey included four validated psychological well-being questionnaires (depression, anxiety, post-traumatic stress and insomnia), as well as demographic and organisational measures., Results: At time 1 and 2, a high proportion of staff reported moderate-to-severe symptoms of depression (30-36%), anxiety (26-27%), post-traumatic stress (30-32%) and insomnia (27-28%); overall, significance tests and effect size data suggested psychological well-being was generally stable between November 2020 and February 2021 for health and social care staff. Multiple linear regression models indicated that perceptions of less effective communication within their organisation predicted greater levels of anxiety, depression, post-traumatic stress and insomnia., Conclusions: This study highlights the need to offer psychological support to all health and social care staff, and to communicate with staff regularly, frequently and clearly regarding COVID-19 to help protect staff psychological well-being., Competing Interests: The authors (J.-A.J., C.S., D.B., E.C., J.M., K.K., S.H., T.M., C.M., K.F.W.D.) are employed by the health and social care trusts in Northern Ireland (Northern Health and Social Care Trust; Belfast Health and Social Care Trust; Southern Health and Social Care Trust, South Eastern Health and Social Care Trust; Western Health and Social Care Trust) – staff from these organisations took part in the COVID-19 Staff Wellbeing Study, (© The Author(s) 2021.)

Background: Aspects of the school environment, such as school attachment levels, are linked to adolescent offending. Previous research has not clarified whether a school- or individual-level intervention approach to improving pupil school attachment and commitment is most likely to reduce adolescent offending., Aim: The present study assessed the impact of individual- and school-level variables on offending behaviour from ages 14-16 years., Sample: The participants were 4,049 young people from 42 mainstream schools who took part in the Belfast Youth Development Study., Method: Multilevel modelling was used to examine the relative influence of individual- and school-level variables on offending behaviour in adolescence., Results: Pupils who had high levels of school commitment and attachment and were involved in fewer fights at age 13 reported lower levels of offending at age 14 years. Differences between schools accounted for 7% of the variation in offending. Lower individual-level commitment was associated with higher initial levels of offending at age 14 if the school-level ethos was of higher commitment. Lack of safety at the school level appeared to be detrimental for young people not exposed to socio-economic deprivation., Conclusions: Individual-level targeted interventions are likely to be a more cost-effective approach of reducing offending behaviour in adolescence. Additional, albeit smaller, reductions in offending levels could be achieved through school-level interventions in some school types (e.g., deprived areas)., (© 2020 The Authors. British Journal of Educational Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Purpose: The aim of the study was to identify the mechanisms relating to parental control, adolescent secrecy, and school context that shape patterns of adolescent drinking frequency and appraise the implications for systems-level intervention., Methods: The Belfast Youth Development Study collected information on friendship networks in schools, alcohol use, and Stattin and Kerr's parental monitoring subscales across 5 years of postprimary school education in annual waves from age 11-15 years. Stochastic Actor-Oriented Models were fitted to 22 schools (N = 3,220) to assess friendship formation and peer influence processes related to drinking frequency and their variation by parental control or child secrecy. Meta-regressions and summary statistic ego-alter selection tables assessed how network and behavior co-evolution varied according to school gender and the proportion of weekly or more frequent drinkers in each school., Results: Adolescents tended to mimic their peers' drinking levels, and frequent drinkers befriended those who drank similarly to them. Those with high parental control were less likely to befriend low-control peers, whereas low-control pupils were more likely to befriend each other. Adolescents with low-control parents nominated fewer friends in schools with higher proportions of drinking frequently. There was a tendency toward befriending highly secretive peers in boys schools only., Conclusions: Our results suggest that the optimal strategy for selecting seed nodes in a diffusion of innovations network intervention may vary according to school context, and that targeting family interventions around parent characteristics may modify the wider school network, potentially augmenting network intervention processes., (Copyright © 2019 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Canine hip dysplasia and developmental dysplasia of the human hip share demographic, phenotypic, and clinical features including the predisposition to develop osteoarthritis in affected joints. To support the results of genetic mapping studies for CHD and its concomitant osteoarthritis with functional information, we performed RNA-seq on hip capsule and teres ligament of affected and unaffected dogs. RNA seq showed that expressed genes segregated according age, capsule or ligament, and hip phenotype. Expression of HHIP, DACT2, and WIF1 was significantly higher in capsule from control hips than dysplastic hips indicating a disruption of the hedgehog signaling pathway. Expression of SPON 1, a key component of the WNT pathway, was increased significantly in both dysplastic capsule and ligament while FBN2 and EMILIN3 were significantly increased in dysplastic capsule. Of genes associated with human hip osteoarthritis, expression of ACAN, IGF1, CILP2, COL11A1, COL8A1, and HAPLN was increased significantly in dysplastic capsule. The significant increase in expression of PLA2F, TNFRSF, TMEM, and IGFBP in dysplastic capsule indicated an injury response. Gene set enrichment analysis revealed that genes involved in extracellular matrix structure, epithelial to mesenchymal transition, myogenesis, growth factor signaling, cancer and immune pathways were enriched in dysplastic capsule. For teres ligament from dysplastic joints, genes in retinoic signaling pathways and those encoding extracellular matrix molecules, but not proteoglycans, were enriched. Hip tissues respond to abnormal mechanics early in dysplastic hip development and these pathways present targets for intervention in the early synovitis and capsulitis secondary to canine and human hip dysplasia. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:313-324, 2019., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Substance misuse persists as a major public health issue worldwide with significant costs for society. The development of interventions requires methodologically sound studies to explore substance misuse causes and consequences. This Cohort description paper outlines the design of the Belfast Youth Development (BYDS), one of the largest cohort studies of its kind in the UK. The study was established to address the need for a long-term prospective cohort study to investigate the initiation, persistence and desistance of substance use, alongside life course processes in adolescence and adulthood. The paper provides an overview of BYDS as a longitudinal data source for investigating substance misuse and outlines the study measures, sample retention and characteristics. We also outline how the BYDS data have been used to date and highlight areas ripe for future work by interested researchers., Methods: The study began in 2000/1 when participants (n = 3,834) were pupils in their first year of post-primary education (age 10/11 years, school year 8) from over 40 schools in Northern Ireland. Children were followed during the school years: Year 9 (in 2002; aged 12; n = 4,343), Year 10 (in 2003; aged 13; n = 4,522), Year 11 (in 2004; aged 14; n = 3,965) and Year 12 (in 2005; aged 15; n = 3,830) and on two more occasions: 2006/07 (aged 16/17; n = 2,335) and 2010/11 (aged 20/21; n = 2,087). Data were collected on substance use, family, schools, neighbourhoods, offending behaviour and mental health. The most novel aspect of the study was the collection of detailed social network data via friendship nominations allowing the investigation of the spread of substance use via friendship networks. In 2004 (school year 11; respondents aged 14), a sub-sample of participants' parents (n = 1,097) and siblings (n = 211) also completed measures on substance use and family dynamics., Results: The most recent wave (in 2010/2011; respondents aged 20/21 years) indicated lifetime use of alcohol, tobacco and cannabis among the cohort was 94, 70 and 45 per cent, respectively. The paper charts the development of drug use behaviour and some of the key results to date are presented. We have also identified a number of key areas ripe for analysis by interested researchers including sexual health and education., Conclusions: We have established a cohort with detailed data from adolescence to young adulthood, supplemented with parent and sibling reports and peer network data. The dataset, allowing for investigation of trajectories of adolescent substance use, associated factors and subsequent long-term outcomes, constitutes an important resource for longitudinal substance misuse research. A planned further wave as the cohort enter their late twenties and potential to link to administrative data sources, will further enrich the datasets., Competing Interests: The authors have declared that no competing interests exist.

Dyslexia has been associated with a range of psychological well-being issues in childhood. However, it is unclear if these difficulties stem from coping with academic struggles at school, or from other pre-existing diagnoses that sometimes co-occur with dyslexia. Using UK Millennium Cohort Study data (n = 7224) from 2003 to 2011, the present study compared psychological well-being development from ages 3-11 years for children with (1) dyslexia only; (2) special educational needs excluding dyslexia; (3) comorbid dyslexia and other special educational needs; and (4) no special educational needs. Growth curve modelling results controlling for race, gender, age and family income suggested that with the exception of conduct difficulties, psychological well-being issues related to dyslexia do not occur preschool; rather, they commence upon starting school. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Having well-trained staff is key to ensuring good quality autism services, especially since people affected with autism generally tend to have higher support needs than other populations in terms of daily living, as well as their mental and physical health. Poorly-trained staff can have detrimental effects on service provision and staff morale and can lead to staff burn-out, as well as increased service user anxiety and stress. This paper reports on a survey with health, social care, and education staff who work within the statutory autism services sector in the UK that explored their knowledge and training with regards to autism. Interview data obtained from staff and service users offer qualitative illustrations of survey findings. Overall, the findings expose an acute lack of autism-specific training that has detrimental impacts. At best, this training was based on brief and very basic awareness raising rather than on in-depth understanding of issues related to autism or skills for evidence-based practice. Service users were concerned with the effects that the lack of staff training had on the services they received. The paper concludes with a discussion of policy routes to achieving quality staff training based on international best practice. The focus is on improving the quality of life and mental health for services users and staff, as well as making potentially significant cost-savings for governments.

Background: Children with autism spectrum disorder are increasingly educated in mainstream classrooms in the United Kingdom (Wilkinson & Twist, Autism and Educational Assessment: UK Policy and Practice. NFER, Slough, 2010), and some employers are now specifically seeking out staff on the autism spectrum. Does that mean that we are living in an 'inclusive society' [United Nations Department of Economic and Social Affairs (UNDESA), Creating an Inclusive Society: Practical Strategies to Promote Social Integration 2008], in the sense that inequalities are reduced and full economic, social and cultural participation is advanced for individuals with autism?, Methods: A general population survey was conducted to assess how close we, as a society, are to an inclusive society for individuals with autism in Northern Ireland. Public attitudes were examined to (i) visibility and social interaction, (ii) aetiology, needs and interventions, and (iii) rights and resources., Results: A stratified, representative sample of 1204 adults took part in the survey; of these, 989 were aware of autism and their attitudes and behavioural projections reflected a mix of acceptance and denunciation. The level of confusion with regard to interventions reflected the general uncertainty within UK policy regarding meeting the needs of individuals on the autism spectrum (International Journal of Disability, Development and Education 61, 134, 2014a)., Conclusion: Therefore, it seems that inclusion is working to an extent, but more clarity is needed with regard to adequate education, intervention and support for individuals with autism., (© 2015 John Wiley & Sons Ltd.)

Linguistic influences in mathematics have previously been explored through subtyping methodology and by taking advantage of the componential nature of mathematics and variations in language requirements that exist across tasks. The present longitudinal investigation aimed to examine the language requirements of mathematical tasks in young children aged 5-7 years. Initially, 256 children were screened for mathematics and reading difficulties (RDs) using standardized measures. Those scoring at or below the 35th percentile on either dimension were classified as having difficulty. From this screening, 115 children were allocated to each of the mathematical difficulty (MD; n = 26), MDRD (n = 32), RD (n = 22) and typically achieving (n = 35) subtypes. These children were tested at four time points, separated by 6 monthly intervals, on a battery of seven mathematical tasks. Growth curve analysis indicated that, in contrast to previous research on older children, young children with MD and MDRD had very similar patterns of development on all mathematical tasks. Overall, the subtype comparisons suggested that language played only a minor mediating role in most tasks, and this was secondary in importance to non-verbal skills. Correlational evidence suggested that children from the different subtypes could have been using different mixes of verbal and non-verbal strategies to solve the mathematical problems.

Objective: Most of what we know about children with autism spectrum disorder (ASD) is based on post-diagnostic, retrospective, self-select studies. Oftentimes, there is no direct comparison between trajectories of children with ASD and children without ASD., Methods: To circumvent both of these problems, the present secondary data analysis utilised a large-scale longitudinal general population survey of children born in the year 2000 (i.e. the Millennium Cohort Study; MCS; n = 18,522). Bi-annual MCS data were available from five data sweeps (children aged 9 months to 11 years of age)., Results: Pre-diagnostic data showed early health problems differentiated children later diagnosed with autism from non-diagnosed peers. Prevalence was much higher than previously estimated (3.5% for 11-year olds). Post-diagnosis, trajectories deteriorated significantly for the children with ASD and their families in relation to education, health and economic wellbeing., Conclusion: These findings raise many issues for service delivery and the rights of persons with disabilities and their families.

Introduction: Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome., Method: To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice. Subsequently, emulating the human scenario, all mice underwent complete tumor excision and were allowed to recover, with attendant metastasis development. Tumor growth, lung metastasis, circulating tumor cell (CTC) levels, variation in gene expression, composition of the tumor microenvironment, and changes in immunologic markers were compared in biopsied and non-biopsied mice., Results: Mice with biopsied tumors developed significantly more lung metastases compared to non-biopsied mice. Tumors from biopsied mice contained a higher frequency of myeloid-derived suppressor cells (MDSCs) accompanied by reduced CD4 + T cells, CD8 + T cells, and macrophages, suggesting biopsy-mediated development of an increasingly immunosuppressive tumor microenvironment. We also observed a CNB-dependent up-regulation in the expression of SOX4, Ezh2, and other key epithelial-mesenchymal transition (EMT) genes, as well as increased CTC levels among the biopsy group., Conclusion: CNB creates an immunosuppressive tumor microenvironment, increases EMT, and facilitates release of CTCs, all of which likely contribute to the observed increase in development of distant metastases.

This study examined levels of mathematics and statistics anxiety, as well as general mental health amongst undergraduate students with dyslexia (n = 28) and those without dyslexia (n = 71). Students with dyslexia had higher levels of mathematics anxiety relative to those without dyslexia, while statistics anxiety and general mental health were comparable for both reading ability groups. In terms of coping strategies, undergraduates with dyslexia tended to use planning-based strategies and seek instrumental support more frequently than those without dyslexia. Higher mathematics anxiety was associated with having a dyslexia diagnosis, as well as greater levels of worrying, denial, seeking instrumental support and less use of the positive reinterpretation coping strategy. By contrast, statistics anxiety was not predicted by dyslexia diagnosis, but was instead predicted by overall worrying and the use of denial and emotion focused coping strategies. The results suggest that disability practitioners should be aware that university students with dyslexia are at risk of high mathematics anxiety. Additionally, effective anxiety reduction strategies such as positive reframing and thought challenging would form a useful addition to the support package delivered to many students with dyslexia., (Copyright © 2014 John Wiley & Sons, Ltd.)

Purpose: To identify the causative mutations in two early-onset canine retinal degenerations, crd1 and crd2, segregating in the American Staffordshire terrier and the Pit Bull Terrier breeds, respectively., Methods: Retinal morphology of crd1- and crd2-affected dogs was evaluated by light microscopy. DNA was extracted from affected and related unaffected controls. Association analysis was undertaken using the Illumina Canine SNP array and PLINK (crd1 study), or the Affymetrix Version 2 Canine array, the "MAGIC" genotype algorithm, and Fisher's Exact test for association (crd2 study). Positional candidate genes were evaluated for each disease., Results: Structural photoreceptor abnormalities were observed in crd1-affected dogs as young as 11-weeks old. Rod and cone inner segment (IS) and outer segments (OS) were abnormal in size, shape, and number. In crd2-affected dogs, rod and cone IS and OS were abnormal as early as 3 weeks of age, progressing with age to severe loss of the OS, and thinning of the outer nuclear layer (ONL) by 12 weeks of age. Genome-wide association study (GWAS) identified association at the telomeric end of CFA3 in crd1-affected dogs and on CFA33 in crd2-affected dogs. Candidate gene evaluation identified a three bases deletion in exon 21 of PDE6B in crd1-affected dogs, and a cytosine insertion in exon 10 of IQCB1 in crd2-affected dogs., Conclusions: Identification of the mutations responsible for these two early-onset retinal degenerations provides new large animal models for comparative disease studies and evaluation of potential therapeutic approaches for the homologous human diseases.

Purpose: To identify the causative mutation of canine progressive retinal atrophy (PRA) segregating as an adult onset autosomal recessive disorder in the Basenji breed of dog., Methods: Basenji dogs were ascertained for the PRA phenotype by clinical ophthalmoscopic examination. Blood samples from six affected cases and three nonaffected controls were collected, and DNA extraction was used for a genome-wide association study using the canine HD Illumina single nucleotide polymorphism (SNP) array and PLINK. Positional candidate genes identified within the peak association signal region were evaluated., Results: The highest -Log10(P) value of 4.65 was obtained for 12 single nucleotide polymorphisms on three chromosomes. Homozygosity and linkage disequilibrium analyses favored one chromosome, CFA25, and screening of the S-antigen (SAG) gene identified a non-stop mutation (c.1216T>C), which would result in the addition of 25 amino acids (p.*405Rext*25)., Conclusions: Identification of this non-stop SAG mutation in dogs affected with retinal degeneration establishes this canine disease as orthologous to Oguchi disease and SAG-associated retinitis pigmentosa in humans, and offers opportunities for genetic therapeutic intervention.

This longitudinal study sought to identify developmental changes in strategy use between 5 and 7 years of age when solving exact calculation problems. Four mathematics and reading achievement subtypes were examined at four time points. Five strategies were considered: finger counting, verbal counting, delayed retrieval, automatic retrieval, and derived fact retrieval. Results provided unique insights into children's strategic development in exact calculation at this early stage. Group analysis revealed relationships between mathematical and/or reading difficulties and strategy choice, shift, and adaptiveness. Use of derived fact retrieval by 7 years of age distinguished children with mathematical difficulties from other achievement subtypes. Analysis of individual differences revealed marked heterogeneity within all subtypes, suggesting (inter alia) no marked qualitative distinction between our two mathematical difficulty subtypes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To identify the causative mutation in a canine cone-rod dystrophy (crd3) that segregates as an adult onset disorder in the Glen of Imaal Terrier breed of dog., Methods: Glen of Imaal Terriers were ascertained for crd3 phenotype by clinical ophthalmoscopic examination, and in selected cases by electroretinography. Blood samples from affected cases and non-affected controls were collected and used, after DNA extraction, to undertake a genome-wide association study using Affymetrix Version 2 Canine single nucleotide polymorphism chips and 250K Sty Assay protocol. Positional candidate gene analysis was undertaken for genes identified within the peak-association signal region. Retinal morphology of selected crd3-affected dogs was evaluated by light and electron microscopy., Results: A peak association signal exceeding genome-wide significance was identified on canine chromosome 16. Evaluation of genes in this region suggested A Disintegrin And Metalloprotease domain, family member 9 (ADAM9), identified concurrently elsewhere as the cause of human cone-rod dystrophy 9 (CORD9), as a strong positional candidate for canine crd3. Sequence analysis identified a large genomic deletion (over 20 kb) that removed exons 15 and 16 from the ADAM9 transcript, introduced a premature stop, and would remove critical domains from the encoded protein. Light and electron microscopy established that, as in ADAM9 knockout mice, the primary lesion in crd3 appears to be a failure of the apical microvilli of the retinal pigment epithelium to appropriately invest photoreceptor outer segments. By electroretinography, retinal function appears normal in very young crd3-affected dogs, but by 15 months of age, cone dysfunction is present. Subsequently, both rod and cone function degenerate., Conclusions: Identification of this ADAM9 deletion in crd3-affected dogs establishes this canine disease as orthologous to CORD9 in humans, and offers opportunities for further characterization of the disease process, and potential for genetic therapeutic intervention.

Breast cancer continues to be one of the leading causes of cancer death in women. Mortality is primarily due to the development of metastases. Although therapies exist, they lack efficacy in preventing metastatic growth. As a result, novel agents are being investigated. In particular, treatments that target the immune system are being examined as potential anti-neoplastic agents. Cordyceps sinensis (Cs) is a fungus that has been used for over 2,000 years in China as a treatment for a variety of conditions including neoplasms. The available evidence suggests that efficacy of Cs as an anti-neoplastic therapeutic agent is related to a role as an activator of innate immune responses. The objectives of this study were: to investigate the ability of Cs to activate macrophages to produce factors that will induce protective responses against tumour growth; to study the ability of Cs to reduce primary tumour growth in vivo; and to examine the ability of Cs to reduce lung metastasis growth in vivo. We found that oral Cs does not reduce primary tumour growth but can reduce lung metastasis occurrence in a surgical excision model of metastatic mammary carcinoma. The evidence we have shown to date suggests that the reduction in metastases growth may be due to the effects of macrophage-derived factors on tumour cell cycle.

The present longitudinal study sought to investigate the impact of poor phonology on children's mathematical status. From a screening sample of 256 five-year-olds, 82 children were identified as either typically achieving (TA; N = 31), having comorbid poor phonology and mathematical difficulties (PDMD; N = 31), or having only poor phonology (phonological difficulty, PD; N = 20). Children were assessed on eight components of informal and formal mathematics achievement at ages 5-7 years. PD children were found to have significant impairments in some, mainly formal, components of mathematics by age 7 compared to TA children. Analysis also revealed that, by age 7, approximately half of the PD children met the criteria for PDMD, while the remainder exhibited less severe deficits in some components of formal mathematics. Children's mathematical performance at age 5, however, did not predict which PD children were more likely to become PDMD at age 7, nor did they differ in terms of phonological awareness at age 5. However, those PD children who later became PDMD had lower scores on verbal and non-verbal tests of general ability.

Using a clinically relevant, fully disparate, allogeneic aortic transplant mouse model of allograft vasculopathy, we have demonstrated that neointimal proliferation is dependent on CD8(+) T cell effector pathways in the presence of therapeutic doses of calcineurin inhibitor (CNI) immunosuppression. CD4(+) T cell pathways are ablated by CNI immunosuppression. In the current study, we examined the relationship between CD8(+) T cell activities, medial SMC loss and neointimal hyperplasia. We demonstrate that at 5-6wk post transplantation in a wild type/wild type transplant CD8(+) T cell infiltration, CD8(+) CTL effector cell mediator expression and medial SMC loss all occur within aortic interposition grafts in the face of CNI immunosuppression. Both IFN-gamma and CTL mediated effector function is required for SMC loss and lesion formation under these conditions. Using strain combinations and reconstitution models, we provide data that blockade of the perforin/granzyme pathway does not prevent lesion formation but that blockade of the Fas/FasL pathway of cytotoxicity dramatically reduces SMC loss and prevents neointimal lesion formation. Both of these blockade strategies are in the face of an active IFN-gamma pathway. These data suggest a cooperative role between Fas/FasL and IFN-gamma mediated effector functions in medial SMC loss and neointimal lesion formation., (Copyright 2009 Elsevier B.V. All rights reserved.)

The arithmetical performance of typically achieving 5- to 7-year-olds (N=29) was measured at four 6-month intervals. The same seven tasks were used at each time point: exact calculation, story problems, approximate arithmetic, place value, calculation principles, forced retrieval, and written problems. Although group analysis showed mostly linear growth over the 18-month period, analysis of individual differences revealed a much more complex picture. Some children exhibited marked variation in performance across the seven tasks, including evidence of difficulty in some cases. Individual growth patterns also showed differences in developmental trajectories between children on each task and within children across tasks. The findings support the idea of the componential nature of arithmetical ability and underscore the need for further longitudinal research on typically achieving children and of careful consideration of individual differences.

Objectives: Interstitial cystitis is a chronic, debilitating disease of the bladder. Treatments using intravesicular inoculation of long-chain polysaccharide formulations, such as hyaluronic acid or anti-inflammatory agents, have been used to some effect. The objective of this study was to test a long-chain polysaccharide derivative of chitosan as a vehicle for delivery of the anti-inflammatory agent 5-aminosalicylic acid (5-ASA) for treatment of inflammation in the bladder., Methods: Bladder inflammation was induced in rats by intravesicular inoculation of protamine sulfate and lipopolysaccharide. Groups of rats were randomly assigned to the treated or control groups, which received either the treatment agents or saline 24 hours after induction. The animals were killed 5 days after inoculation, and the bladders harvested for histologic examination of inflammation by a blinded observer. Four parameters of inflammation were measured using a 6-point scale. In another experiment, urinary frequency was measured 4 days after inoculation., Results: The most potent treatment agent was 3% N-sulphonato-N,O-carboxymethylchitosan plus 5-ASA, with a mean reduction in inflammation, as measured by histologic examination, of up to 75%. This level of reduction was significantly greater than that seen by treatment with the commercially available product Cystistat. In a separate experiment, 3% N-sulphonato-N,O-carboxymethylchitosan plus 5-ASA ameliorated the increase in urinary frequency seen in induced, untreated animals., Conclusions: The combination of 3% N-sulphonato-N,O-carboxymethylchitosan and 5-ASA reduced bladder inflammation as measured by histologic examination and by the lower urinary frequency.

Purpose: To clone, map, and determine the site of expression (mRNA and protein) of the alpha subunit of the receptor for ciliary neurotrophic factor (CNTFRalpha) in the normal adult canine retina., Methods: The complete coding sequence of the canine CNTFRalpha cDNA was cloned, and radiation hybrid (RH) mapping was used to determine the chromosomal localization of the gene. CNTFRalpha mRNA expression in retina and other tissues was examined by reverse transcription-polymerase chain reaction. The cellular distribution of CNTFRalpha in the canine retina was studied by in situ hybridization and immunocytochemistry., Results: Canine CNTFRalpha shares a high degree of homology with the human, mouse, and rat coding sequences, both at the nucleotide and amino acid level, but has lower homology with the chicken. CNTFRalpha was RH mapped to CFA 11 (Canis familiaris autosome 11) in the dog, a region showing homology to the short arm of human chromosome 9 (9p13). The gene is transcribed in retina, brain, spleen, lung, liver, and kidney. In the retina, CNTFRalpha was highly expressed by photoreceptors, but both the transcript and protein were also found in the RPE, inner nuclear layer, and ganglion cells., Conclusions: These findings demonstrate that CNTFRalpha is expressed by rods and cones in the normal adult canine retina and suggest that ciliary neurotrophic factor (CNTF) could have a direct photoreceptor rescue effect by binding to CNTFRalpha in these cells. This could open novel pathways for the treatment of retinal degeneration in animal models and humans.

To determine the nature of the proliferative lesion in obliterative airway disease, heterotopic tracheal allograft transplantation was performed between fully disparate Brown Norway and Lewis rat strains. Four weeks after transplantation, the resulting lumenal occlusive lesion was stripped from the underlying tissue. The lesion was probed using immunohistochemical analysis with monoclonal antibodies and for DNA using strain-specific primers for Brown Norway or Lewis major histocompatibility complex Class I alleles. The lesions were alpha-actin positive, and polymerase chain reaction probing revealed only recipient DNA in the lesion tissue, regardless of the direction of transplantation, with no amplification of donor DNA. From this, we conclude that the proliferative lesion in the rat heterotopic tracheal model is of recipient origin a finding with important implications for the pathobiology of obliterative airway disease.