Background: Between 1961-1971 vitamin D deficiency was recognized as a public health issue in the UK, because of the lack of effective sunlight and the population mix [1, 2]. In recent years, health care professionals have cited evidence suggesting a re-emergence of the vitamin D deficiency linked to a number of health consequences as a concern [3-6]. Evidence from observational studies has linked low vitamin D status with impairment in glucose homeostasis and immune dysfunction [7-9]. However, interventional studies, particularly those focused on paediatric populations, have been limited and inconsistent. There is a need for detailed studies, to clarify the therapeutic benefits of vitamin D in these important clinical areas. Objective: The aims of this PhD thesis were two-fold. Firstly, to perform preliminary work assessing the association between vitamin D deficiency and bone status, glucose homeostasis and immune function, and to explore any changes in these parameters following short term vitamin D3 replacement therapy. Secondly, to assess the effectiveness of an electronic surveillance system (ScotPSU) as a tool to determine the current incidence of hospital-based presentation of childhood vitamin D deficiency in Scotland. Methods: Active surveillance was performed for a period of two years as a part of an electronic web-based surveillance programme performed by the Scottish Paediatric Surveillance Unit (ScotPSU). The validity of the system was assessed by identifying cases with profound vitamin D deficiency (in Glasgow and Edinburgh) from the regional laboratory. All clinical details were checked against those identified using the surveillance system. Thirty-seven children aged 3 months to 10 years, who had been diagnosed with vitamin D deficiency, were recruited for the bone, glucose and immunity studies over a period of 24 months. Twenty-five samples were analysed for the glucose and bone studies; of these, 18 samples were further analysed for immune study. Treatment consisted of six weeks taking 5000 IU units cholecalciferol orally once a day. At baseline and after completion of treatment, 25 hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), alkaline phosphatase (ALP), collagen type 1 cross-linked C-telopeptide (CTX), osteocalcin (OCN), calcium, phosphate, insulin, glucose, homeostasis model assessment index, estimated insulin resistance (HOMA IR), glycated hemoglobin (HbA1c), sex hormone binding globulin (SHBG), lipids profiles, T helper 1 (Th1) cytokines (interleukin-2 ( IL-2), tumor necrosis factors-alpha (TNF-α), interferon-gamma (INF-γ)), T helper 2 (Th2) cytokines (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6)), T helper 17 (Th17) cytokine (interleukin-17 (IL-17)), Regulatory T (Treg) cytokine (interleukin-10 (IL-10)) and chemokines/cytokines, linked with Th1/Th2 subset balance and/or differentiation (interleukin-8 (IL-8), interleukin-12 (IL-12), eosinophil chemotactic protein ( EOTAXIN), macrophage inflammatory proteins-1beta (MIP-1β), interferon-gamma-induced protein-10 (IP-10), regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein-1(MCP-1)) were measured. Leukoocyte subset analysis was performed for T cells, B cells and T regulatory cells and a luminex assay was used to measure the cytokiens. Results: Between September 2009 and August 2011, 163 cases of vitamin D deficiency were brought to the attention of the ScotPSU, and the majority of cases (n = 82) were reported in Glasgow. The cross-validation checking in Glasgow and Edinburgh over a one-year period revealed only 3 (11%) cases of clearly symptomatic vitamin D deficiency, which had been missed by the ScotPSU survey in Glasgow. While 16 (67%) symptomatic cases had failed to be reported through the ScotPSU survey in Edinburgh. For the 23 children who are included in bone and glucose studies, 22 (96%) children had basal serum 25(OH)D in the deficiency range (< 50 nmol/l) and one (4%) child had serum 25(OH)D in the insufficiency range (51-75 nmol/l). Following vitamin D3 treatment, 2 (9%) children had final serum 25(OH)D lower than 50 nmol/l, 6 (26%) children had final serum 25(OH)D between >50-75 nmol/l, 12 (52%) children reached a final serum 25(OH)D >75-150 nmol/l and finally 3 (13%) exceeded the normal reference range with a final 25(OH)D >150 nmol/l. Markers for remodelling ALP and PTH had significantly decreased (p = 0.001 and <0.0001 for ALP and PTH respectively). In 17 patients for whom insulin and HOMA IR data were available and enrolled in glucose study, significant improvements in insulin resistance (p = 0.04) with a trend toward a reduction in serum insulin (p = 0.05) was observed. Of those 14 children who had their cytokines profile data analysed and enrolled in the immunity study, insulin and HOMA IR data were missed in one child. A significant increase in the main Th2 secreted cytokine IL-4 (p = 0.001) and a tendency for significant increases in other Th2 secreted cytokines IL-5 (p = 0.05) and IL-6 (p = 0.05) was observed following vitamin D3 supplementation. Conclusion: An electronic surveillance system can provide data for studying the epidemiology of vitamin D deficiency. However, it may underestimate the number of positive cases. Improving vitamin D status in vitamin D deficient otherwise healthy children significantly improved their vitamin D deficient status, and was associated with an improvement in bone profile, improvements in insulin resistance and an alteration in main Th2 secreting cytokines.

A high prevalence of malnutrition has been reported in paediatric inpatients both in developed and developing countries, using various methodology and criteria. According to national and international guidelines, all inpatients should be screened for risk of malnutrition on admission using a validated screening tool. However, because of the lack of universally accepted definition for malnutrition, there is no consensus on the measures and methods to use for nutritional screening. There is controversy concerning the validity, reliability and practicality of existing paediatric nutrition screening tools. Moreover, current paediatric screening tools have not been designed and validated for infants. The study aimed to: 1) Validate a novel malnutrition screening scheme for infants - the Infant Paediatric Yorkhill Malnutrition Score (iPYMS) and compare its utility in different hospital settings, in UK and Middle East, Iran. 2) Compare the usefulness of various anthropometric measures to predict malnutrition in infants. 3) Determine the factors that correlated with malnutrition in hospitalised infants. 4) Explore the use of body composition measures in sick infants. The Paediatric Yorkhill Malnutrition Score (PYMS) had already been developed in Glasgow for use in children admitted to hospital. It utilized four elements that were reported as recognized predictors of the past, present or future nutrition risk. An audit was carried out at the beginning of the PhD course and aimed to evaluate the effect of PYMS on collection of anthropometric measurements in the wards. Findings suggested that introduction of a screening tool improved the acquisition of anthropometry by nursing staff, but their utilization by medical staff remained poor. Method: The Infant Paediatric Yorkhill Malnutrition Score (iPYMS) was developed by the research team. The score encompasses 4 rated steps that similar to those used for older children: weight < 2nd and 9th centile was used as opposed to BMI, and 3 elements concerning the history of nutritional issues. A score of 1 classifies a patient at medium risk and ≥2 or ≥3 indicates high risk. Infants were studied at admission to two tertiary children's hospital, 210 (0-12 months) in Glasgow, UK and 187 (1-12 months) in Tabriz, Iran. Convenience sampling was used to recruit equal number of patients in each risk group. Four researchers recruited the samples for the UK cohort and one for the Iran cohort. The diagnostic accuracy and validity of iPYMS in both cohorts were assessed by comparing the iPYMS nutritional risk with the Paediatric Subjective Global Nutritional Assessment (SGNA) that determine malnutrition risk and mean skinfolds z-scores (triceps and subscapular) below <-2SD as the benchmark for low fat stores and acute/chronic malnutrition. Discriminant validity was assessed using body composition and anthropometry measurements, with the hypothesis that infants at high risk of malnutrition will have lower fat and possibly lean mass compared with those at low risk. Results: More infants in Iran (32%) were rated as high risk for undernutrition than UK (7%). The diagnostic performance of iPYMS improved with the cut-off ≥ 3, more so in Iran than the UK. In Iran, only, infants who were classified as being at high risk of malnutrition had longer hospital stay. Infants in the iPYMS moderate and high risk groups all had significantly lower mean SD-score for anthropometry. After excluding patients scored high risk based only on low weight z-score (≤-2 SD), the differences in weight and BMI z-scores remained significant. In Iran 76% infants with raised iPYMS had mean skinfolds <-2SD, but only 5% in the UK. The UK infants may thus not actually be malnourished. They may be ill and just at risk of malnutrition. The first step of iPYMS (weight below <9th or 2nd centile) was a strong predictor of malnutrition risk, more so in Iran; in the Iranian cohort, 91% and in the UK 70% of infants above the high risk threshold of ≥ 3 scored as high risk due to the weight below <9th or 2nd centile. ROC Analysis either with SGNA or sum skinfolds z-score as the main outcomes illustrated that admission weight and growth velocity had almost the same predictive value in predicting malnutrition risk. This suggests that weight velocity is no improvement on weight alone as a predictor of malnutrition. Current breast feeding was found to be an independent predictor of malnutrition in Iran. Socioeconomic factors were weak predictors of malnutrition in this population. There is a lack of validated and suitable methods to assess body composition in infants. To determine whether analysing bio-electrical impedance data is practical in our young age range population, this was compared to skinfolds thicknesses and how the two measures of body composition varied relative to SGNA. The WHO standard for skinfolds only starts at 3 months, excluding nearly one third of infants in the Iran cohort and half in the UK. An iPYMS skinfold reference was thus generated using the iPYMS dataset for the UK cohort, as this was a population with low rates of malnutrition risk who had skinfolds levels mainly within the WHO range beyond age 3 months. In Iran, most high SGNA risk infants (72%) had low skinfolds, but in UK there was no association. Iranian infants had much lower mean lean and fat than the UK infants. Fat measured by BIA varied by SGNA rating risk group with both cohorts, but lean differed between risk groups only for Iran cohort. Conclusion: Malnutrition was common in this tertiary children's hospital in Iran. iPYMS might perform well in this setting and could be used by health professionals to identify infants with malnutrition. In contrast, in the UK, iPYMS would mainly identify infants at risk of malnutrition, because of the low prevalence of under-nutrition. On the other hand, we found that weight alone (the first component of iPYMS) is a robust predictor of malnutrition risk. Therefore iPYMS may not add any advantage over the simple measurement of weight alone to identify infants at risk of malnutrition. This is essential where there are limited resources. Studies should be continued to explore a suitable and appropriate gold standard to test the validity of the tools particularly in low prevalence settings as well as the resources and cost of the introducing the tool in clinical practice. Any screening tool for malnutrition can only be considered effective if it results in early intervention and improved clinical outcomes, so the effectiveness of iPYMS needs to be explored in future intervention studies.

Background: The burden of childhood stunting and mortality remains huge in developing countries and in particular in the Sub-Saharan Africa region to which Nigeria is located. Despite the body of evidence supporting an association between neighbourhood contextual influences and health outcomes, few studies have examined the relationship between neighbourhood-level risk factors and childhood undernutrition (stunting) and mortality independent of the individual-level risk factors in a single analytical framework in Nigeria. Most studies to date have focused on individual-level factors overlooking the contribution of neighbourhood or area level factors. Beyond the effect of neighbourhood contextual influences, a child’s health will be influenced by the state, region and national policies and programs that in turn will affect the proximate determinants of his or her survival and health status. Aims: We described the variation that existed between the states in Nigeria using league table, control chart and spatial clustering of childhood stunting (Study I) and examined the contribution of community contextual factors at predicting childhood stunting beyond individual-level factors (Study II). We further identified and examined the predictors of childhood mortality in Nigeria (Study III) and developed prognostic model predicting differences in childhood mortality in Nigeria communities (Study IV). We also quantified the contribution of neighbourhood socioeconomic disadvantage alongside individual-level socioeconomic status to childhood mortality in Nigeria using multilevel analysis (Study V). Methods: We used the Nigeria Demographic and Health Survey (DHS) dataset which comprised of 28,647 and 31,482 under-five children nested within 888 and 896 communities for the 2008 and 2013 surveys respectively from 37 states including the Federal Capital Territory. We used league table, control chart and geospatial analysis to describe variations in childhood stunting that existed between the states in Nigeria (Study I). In study II, we applied multivariable multilevel logistic regression analysis to describe the independent contribution of community contextual influences (factors) alongside the individual level factors on childhood stunting in Nigeria. We applied multivariable logistic regression analysis that included Receiver Operating Characteristics (ROC) Curve to construct a model that examined the factors associated with childhood mortality (Study III). In study IV, we used mixed multivariable Poisson regression analysis to develop a prognostic model predicting differences in childhood mortality in Nigeria communities. In Study V, we applied multivariable multilevel logistic regression analysis and considered three measures of individual socioeconomic status i.e. maternal educational attainment, household wealth status, and employment status of the mothers. At the neighbourhood (level 2) and state (level 3), we included poverty rate, unemployment rate, and illiteracy rate. Results: There were statistically significant variations in the odds of childhood stunting and mortality across the neighbourhoods (Study II, IV & V) and states (I) in Nigeria. This confirmed the evidence of community and state level contextual phenomenon influencing childhood survival and stunting. Children residing in socioeconomically disadvantaged neighbourhoods had higher odds of childhood morbidity and mortality compared to their counterparts living in more socioeconomically advantageous neighbourhoods (Study II, IV & V). The odds of childhood morbidity and mortality were associated with neighbourhood and state socioecological conditions even after adjusting for individual’s household socioecological conditions (Study II, III, IV & V). There was moderate positive correlation between neighbourhood and individual variations in childhood mortality and morbidity (Study II & V). The odds of childhood stunting and mortality were higher in children residing in rural areas (Study II, III, IV & V) and in settings with poor sanitation (Study III & IV). Other factors that increased the odds of childhood mortality included low level of maternal health seeking behaviour, not breastfed for >18 months, being from a polygamous family setting, large family and high birth order, non-usage of contraceptive by mother, and mother having first marriage during their teenage years(Study III). Good household wealth status, adequate birth interval, being a female child and having normal birth weight, increasing maternal educational attainment were all associated with odds of not suffering from childhood stunting and surviving beyond five years of age (Study II & V). Conclusions: By adopting several modelling approaches including the multilevel modelling, we added to the growing body of evidence the effects of the neighbourhood contextual influences on childhood stunting and survival in Nigeria. Our study revealed that individual i.e. children and parental factors; neighbourhood and socioecological environment were associated with childhood stunting and mortality. Efforts at reducing the burden of childhood stunting and mortality should be directed at establishment of poverty alleviation programmes, effective publicly funded health care delivery, promotion of hygienic environmental practices and health education more importantly at the neighbourhood level. Lastly, given the importance of socioecological factors at influencing the lifestyles of neighbourhoods and individuals, interventions targeting structural make up of these two entities are vital in order to meet the MDGs 1 and 4 regarding childhood stunting and mortality in Nigeria and in particular developing countries in general.

The aim of this thesis is to discuss the issue of public legitimization of new medical technology, through a case of antenatal screening for Down's syndrome in Britain. It is based on ethnographic study of agents involved with the technology; inventors of the technology, medical practitioners, pregnant women, and people with disability and their families, especially parents. The thesis is interdisciplinary based on mainly two frames of reference; Science and Technology Studies and Disability Studies. The former equips the thesis with the basis to understand the process of invention and promotion of the technology, in the social context I will especially focus on transformation of rhetoric to legitimate the technology in its process. The latter provides the critical standpoint to observe the fundamental idea of antenatal screening that it is better to prevent life with disability. Today, provision of antenatal screening is commonly legitimated for its ability to enhance autonomous decision of women in the clinical setting. However it is questionable whether women can make reliable autonomous decisions, when they can only imagine the immediate consequences of their decision (Rapp and Ginsburg, 2001). Based on the idea of disability studies, I will argue that the key to the public legitimization of antenatal screening technology lies in the approach towards life with disability that society should take. I will show that an important problem in the process of social acceptance of antenatal screening for Down's syndrome in Britain is the lack of serious examination of alternatives to the preventive medical approach towards disability that this technology offers. I conclude that in order to generate the public legitimization of antenatal screening technology in the future, it is necessary for the public to consider a variety of possible approaches that society can take towards life with the targeted condition.

The aim of this thesis is to compare effects of respiratory distress syndrome (RDS) on the myocardial function of newborn preterm infants and the later effects of chronic lung disease of prematurity on pulmonary artery stiffness in school age children. The first study in this thesis compared global and regional myocardial function in preterm infants with respiratory distress syndrome (RDS) with preterm and term-born controls (30 with RDS, 30 preterm control ≤34 weeks, 60 term control) using conventional and tissue Doppler echocardiography at birth, at term, one month, and one year of age. The second study compared the pulmonary artery stiffness, an early preclinical marker of pulmonary hypertension, in children (aged 8-12 years) who had chronic lung disease of prematurity (CLD) with preterm and term-born controls. Pulmonary artery pulse wave velocity (PA PWV) was assessed in 59 children: 13 with CLD, 21 preterm (≤ 32 weeks gestation) and 25 term controls) using velocity encoded MRI technique while breathing room air and after 20 minutes of breathing 12% oxygen. At birth, infants with RDS had lower pulmonary artery AT:ET (p < 0.001), long axis shortening (p < 0.01), RV systolic velocity (p < 0.001) and higher TR (p < 0.01) compared to preterm and term control groups. The preterm groups was also noted to have diastolic dysfunction (lower mitral E:A) at birth (p < 0.001). At term corrected age, pulmonary artery AT:ET was still lower in the RDS group but no differences detected in TR between the groups. There were no differences in all parameters measured between the groups at one month and one year. 2 PA PWV was similar in all three groups at baseline when assessed at school age. However, following hypoxic challenge, PA PWV in children who had CLD increased significantly compared to preterm (p=0.025) and term controls (p=0.042). The findings in this thesis suggest that infants with RDS had mildly elevated pulmonary arterial pressure as a result of milder respiratory disease with improvement in antenatal and neonatal care. The RV global dysfunction in infants with RDS resolved with resolution of the respiratory condition. Both preterm groups underwent postnatal maturation of myocardial function and caught up with the term control group by one month corrected age. At school age, children who had CLD displayed increased pulmonary vascular reactivity to hypoxia and are at greater risk of developing pulmonary hypertension earlier.

Aims: Since 2008, in England, all sudden unexpected deaths in infancy (SUDI) must be investigated jointly by police, health and social care. This thesis aims to learn of parents’ and professionals’ experiences of this joint agency approach (JAA) and use this knowledge to improve these investigations. Methods: 1. Systematic literature review of bereaved parents’ experiences. 2. Systematic literature review of different models of SUDI investigation. 3. A mixed methods study of JAA investigation of SUDI cases; involving case note analysis, questionnaires and in-depth interviews with parents and professionals. 4. A descriptive study of outcomes of JAA SUDI investigation using Child Death Overview Panel (CDOP) data. Results: In the mixed methods study, 23/111 families were recruited giving theoretical saturation; the median time between death and parental study participation was 33 weeks. Parents felt that the JAA provided information about the death but offered minimal emotional support; they were often distressed by non-specialist police attending their home as part of the investigation. The joint home visit by police and paediatrician was shown to be a key investigative process. Social care were only involved in 13/23 JAA investigations. Some coroners were reluctant to share information with paediatricians preventing effective JAA investigations. In the CDOP study were obtained for 93% SUDI cases. Final case discussions were used to discuss risk factors but not to determine the cause of death; in nearly all cases the final cause of death relied on post-mortem examination alone and ignored death scene examination findings. Many deaths were labelled as unascertained despite fulfilling diagnostic criteria for SIDS. Conclusion: Ideally, SUDI investigations should be carried out only by specialist clinicians who do this work frequently and the JAA should be fully integrated with social care and coroners’ investigations. There needs to be a clearer system for classifying unexplained SUDI. Police should reconsider their immediate response to SUDI; parents would like more follow-up and bereavement support from professionals.

Impaired self-awareness is a common consequence following a brain injury in adults, particularly when the brain injury is moderate or severe. Impaired self-awareness affects engagement in rehabilitation and results in poor long term functional outcomes. There is a paucity of literature regarding self-awareness following a brain injury in childhood. Consequently, little is known about the differences between children and adults in the domain of self-awareness following brain injury. Children and young people are at different stages of development when their injury occurs and this study investigates the impact of the brain injury on the development of self-awareness. The aim of this research study is to gather quantitative and qualitative longitudinal data from children and young people who have experienced a moderate to severe traumatic brain injury in order to understand their level of self-awareness. This study used a longitudinal multiple case study design with mixed methodology. Fifteen children and young people with a moderate/severe traumatic brain injury were recruited and data were collected from the children and young people, their parents and their teacher over an eighteen month period. The results show that children and young people have an interruption to the development of self-awareness following a traumatic brain injury. Impaired self-awareness is not chronic in this group and they continue to make developmental gains in time. This study adds to our understanding of the interruption of self-awareness development following a brain injury in childhood. Occupational therapists have a particular role to play while engaging with children and young people in the everyday context of their lives, which is supportive of greater self-awareness. As children and young people become more able to assess their own performance, they may be in a better position to set realistic rehabilitation goals. Implications for future clinical and academic children’s neurorehabilitation are outlined.

Acute lymphoblastic leukaemia (ALL) is the commonest childhood malignancy. Once a universally fatal disease, modern therapy has achieved excellent outcome and the majority of children achieve long term cure. Yet relapse remains a challenge. One of the major hurdles in achieving complete cure is the relapse of ALL at extramedullary sites such as the central nervous system (CNS). Despite significant advances in understanding leukaemia biology, most predictors of leukaemic behaviour are accurate for the bone marrow disease only. The precise timing, frequency and properties of CNS infiltrating leukaemic cells are not elucidated. Therefore, the broad aim of this thesis is to develop a better understanding of the mechanisms of leukaemic entry and infiltration patterns of leukaemic cells in the CNS. In order to address the frequency and pattern of CNS infiltration, a xenograft model using primary leukaemic cells from children with B-cell precursor (BCP) ALL in NOD/Scid IL2Rγ null (NSG) mice was established. The majority of samples from children with and without overt CNS disease were able to infiltrate the CNS in NSG mice. CNS infiltration was seen in mice engrafted with small numbers of cells and distinct immunophenotypic subpopulations. The leukaemic samples followed a distinct and reproducible pattern of CNS infiltration with leukaemic infiltrates in the meninges while sparing the CNS parenchyma. To investigate whether a distinct set of leukocyte trafficking molecules provided tissue specificity for entering the CNS, leukaemic cells retrieved from the bone marrow and the CNS were assessed for expression levels of selected chemokine receptors and P-selectin glycoprotein ligand-1 (PSGL1). Additionally, chemotaxis assays were utilized to investigate the function of the chemokine receptor CXCR4. Despite surface expression of chemokine receptors on leukaemic cells and presence of chemokines in the CNS, no evidence for positive selection of a high-expressing subpopulation was seen. Overall, it appears that, unlike the bone marrow, chemokine receptors do not direct leukaemic cell trafficking to the CNS. To investigate the published observation that interleukin-15 (IL-15) expression in leukaemic samples correlates with the risk of CNS disease, the effects of IL-15 stimulation on BCP-ALL cells were assessed. IL-15 and IL-15 receptor subunits were noted to be expressed at mRNA level in samples from BCP-ALL patient and cell lines. Exogenous IL-15 stimulated leukaemic cell proliferation and upregulated genes associated with migration and invasion in SD1 cells. A higher proliferative advantage was observed at low-serum conditions which mimics conditions found in the CNS. Therefore a plausible mechanistic link was established for the association of CNS disease with high IL-15 expression levels. In cerebrospinal fluid (CSF) samples from patients, quantitative PCR (qPCR) was utilized to detect submicroscopic levels of CNS disease. In approximately 40% patients, qPCR using patient specific primers tested positive for the presence of leukaemic DNA. Therefore this test is much more sensitive than conventional diagnostic techniques which only detect CNS disease in 2-5% of patients. CSF supernatants were also tested to assess whether the levels of chemokines could be used to diagnose patients with qPCR positive disease. Although differences in the levels of chemokines between qPCR positive and negative patients were noted, the values are not sufficiently discriminatory to be clinically useful. In conclusion, CNS entry appears to be a much more frequent property of leukaemic cell than previously appreciated. Leukocyte trafficking molecules do not appear to play an instructive role in the CNS entry and therefore, it is unlikely that expression levels of leukocyte trafficking molecules or the levels of chemokines in the CSF will be useful biomarkers of CNS disease. In addition, CNS disease appears to be present at diagnosis in at least 40% of patients. Therefore, attempts at blocking leukaemic entry into the CNS are unlikely to be therapeutically useful. Instead, analysing and targeting factors that allow long-term survival of leukaemic cells in the CNS may be a better strategy to eradicate CNS disease and prevent leukaemic relapse.

The ability to take another person’s perspective is highly important for social interaction. People with autism have particular difficulty with taking someone else’s point of view. This thesis aimed to examine whether people with autism are impaired at visual perspective taking and the processes which underlie this ability and how this could impact on social interaction. Chapter two examined body representation in children with autism and results showed no significant difference between these and the control groups in regards to performance. Chapter three investigated mental rotation and egocentric spatial transformations in adults with autism compared to typically developing (TD) adults. Results showed that participants with autism were slower but equally accurate in the mental rotation task and slower and less accurate in the egocentric task. Comparisons across tasks suggested that the participants with autism may have general differences in perception compared to typical people. The experiments in Chapter 4 examined level 2 visual perspective taking (VPT2) and the processes which underlie this ability in TD children. The results showed that in typical children VPT2 is driven by the ability to represent bodies from different points of view. Chapter five examined whether children with autism were impaired at VPT2 and whether the same processes predicted this ability in children with and without autism. Results showed that VPT2 in children with autism is predicted by mental rotation ability and not body representation. In the final experiment, level 1 VPT was examined in children with autism. Whilst previous studies have suggested that this ability may be intact in autism, the results of this chapter suggested otherwise. Overall it was found that people with autism have problems in perspective taking which could impact on their social skills.

This research examined relationships and positive growth in families of children who have a developmental disability. Chapter one is a critical review of the literature relating to positive growth in parents of children who have a developmental disability. Past studies have indicated that having a child with a developmental disability can be both stressful for parents and place increased pressures on their time, energy and resources. However, this review of more recent research about the experience of having a child with a developmental disability highlights the range of positive growth experiences parents undergo and some of the possible processes involved. Positive growth experiences reported included changes in parental perceptions of their growth, changes in belief systems, increased sense of coherence and increased hope. Resilience, reframing coping strategies, meaning-making and social support were all implicated in this positive growth process. Clinically, the value of strengths-based services for families emerged. Chapter two is an empirical study, focusing on the maternal experience of a family based Lego Therapy intervention amongst five families who have a child who is on the autism spectrum. Qualitative analysis of interview data resulted in themes of family specific factors (communication, new perspectives, deeper relationships), child-specific factors (impact of the child's ASD, child-specific developments) and intervention-specific factors (ambivalence about the intervention, time). Methodological· and clinical implications are discussed, alongside recommendations for future research. Chapter three is a reflective paper focusing on the individual differences to emerge amongst families and the clinical and methodological implications of this.