Twins often show signs of physical and cognitive developmental delays compared with singletons at school age, but tend to catch up by young adulthood. Many previous studies focused on early childhood and beyond, and twins with health issues. In this thesis, I investigated the infancy period of healthy twins in the Birmingham Registry for Twin and Heritability Studies. More specifically, I explored twins’ developmental trajectories compared with singleton standards; ante-, peri-, and postnatal factors related to developmental skills; and the association of maternal occupation with twin pregnancy outcomes. Additionally, I studied the heritability of body mass index (BMI) over a lifespan in a meta-analysis of twin studies. Twins had worse developmental skills and were small for their age compared with singleton standards. Birth weight was not strongly associated with developmental skills as in previous studies; however, larger antenatal head circumference was negatively associated with postnatal development. Higher occupational psychological strain was related to shorter gestations. Finally, heritability of BMI remained high over a lifespan. Results were discussed in light of current clinical and health and safety guidelines. Suggestions for further research and dissemination of findings to parents of multiples were also discussed in the final chapter of this thesis.

To date, no research has explored the relationship between UK school experience and self-identity for young people with Autism Spectrum Disorder (ASD). Within this study, it is argued that identity is an adaptive process that utilises experience of the sociocultural context to generate a 'self'. Reviewed literature additionally suggests that school may be an important domain of identity development. Using a Narrative Orientated Inquiry (NOI) methodology, this research examines identity constructs within school experience narratives produced by young people who have a diagnosis of ASD. Participants were five mainstream secondary school (MSS) students (four males and one female) with a diagnosis of ASD (including Asperger Syndrome), sound expressive language skills and no additional diagnoses. Narrative Interviews (Mishler 1986a, 1986b) were conducted. Three interpretive perspectives, in accordance with NOI, were used to analyse transcripts: Separation of 'fabula' from 'sjuzet' (Hiles and Čermák, 2008); The Holistic-Content interpretive perspective (Lieblich, Tuval-Mashiach and Zilber, 1998); and Critical Narrative Analysis (Emerson and Frosh, 2004). Member checks were carried out. The stories imply that being a young person with ASD at an MSS can be restrictive and disempowering. Findings can be seen to support the proposed theory of identity, suggesting the relationship between school experience and self-identity for young people with a diagnosis of ASD may be an adaptive one, where school experience is the material subject to the process of identity. Findings appear to show that school experience may hinder, through restrictive systems and structures, or help the development of self-identity for young people with ASD. Where young people with ASD can experience free choice and receive support, not least through school staff empathy and understanding, findings suggest they may be aided in developing self-identity. Peer friendships may also potentially afford the opportunity for young people with ASD to learn about themselves, although further research is required in this area.

Background: The effectiveness of World Health Organization (WHO) guidelines for pneumonia case management in sub-Saharan Africa has been contested. This thesis aims to determine the clinical effectiveness of these guidelines among children admitted to Kenyan hospitals in a period after the introduction of the pneumococcal and Haemophilus influenzae type B (Hib) conjugate vaccines. The studies focus on the treatment of children with chest indrawing pneumonia, who were previously regarded to be at high-risk requiring inpatient treatment but were reclassified as lowrisk (non-severe) in the WHO guidelines updated in 2013. Methods: This thesis consists of: (i) A systematic review linked to a national guidelinedevelopment exercise appraising the evidence for the WHO pneumonia guidelines, (ii) a prospective observational study evaluating adherence to, and effectiveness of the pneumonia guidelines in the national referral hospital in Kenya, (iii) a multi-centre pragmatic randomised controlled trial (RCT) comparing amoxicillin versus benzyl penicillin for chest indrawing pneumonia (iv) a cohort study comparing treatment effects among children enrolled in the antibiotic RCT with a similar group who received routine care, and (v) a multi-centre retrospective cohort study of children hospitalised with pneumonia describing factors associated with mortality, focusing on characteristics that increase risk of death among children who would, under current guidance, be assigned a non-severe classification. Results: Although evidence from clinical trials supported the adoption of oral amoxicillin for severe pneumonia over benzyl penicillin (the standard treatment) for chest indrawing pneumonia, a Kenyan guideline development panel raised concerns of generalizability citing the limited data from sub-Saharan African populations in whom mortality was argued to be high. This concern was explored using prospectively collected observational data from 385 children. Treatment failure and mortality were infrequent (< 2%) for chest indrawing pneumonia where strict definitions requiring documented evidence of clinical deterioration were applied. In comparison, high rates of treatment failure (21.4%) and mortality (10.5%) were observed for severe pneumonia (formerly very severe pneumonia). Using propensity scores to model treatment effects comparing guideline recommended regimens with more costly, broad-spectrum alternatives, similar risks of treatment failure were observed in both groups. Amoxicillin was compared with benzyl penicillin in a pragmatic clinical trial of 527 children that also revealed low and comparable risks of treatment failure (8%) and mortality (< 1%) for the two treatments. Consistent results were observed in an observational cohort of children hospitalised at the same health facilities over the period the trial was conducted. However, analyses of data from > 16000 children suggested that the presence of commonly-occurring clinical signs may be associated with increased risk among children with non-severe pneumonia. Specifically, very low weight-for-age Z score (WAZ) or pallor in children with non-severe pneumonia were shown to be associated with absolute risks of mortality as high as those for severe pneumonia. Conclusions: Findings from locally-conducted observational studies and a clinical trial indicate low risks of treatment failure and mortality among children with chest indrawing pneumonia following treatment with benzyl penicillin monotherapy or amoxicillin. In contrast, mortality for severe pneumonia was greater than 10 percent. These results are consistent with the updated WHO recommendations and have more recently informed the revision of the national policy for pneumonia case management in Kenya. However, these guidelines may apply to sub-populations of children with non-severe pneumonia and either very low WAZ or pallor. This evidence is expected to contribute to ongoing debates on the adoption of WHO guidance for pneumonia case management in similar settings across sub-Saharan Africa where coverage of the Hib and pneumococcal conjugate vaccines is high.

Children with the congenital heart defect TOF require surgical repair. Their myocardium is exposed to chronic hypoxia due to insufficiently oxygenated blood shunted from the right to the left side of the heart through the VSD, resulting in cyanosis. Such corrective surgery often requires the use of CPB. During these procedures the aortic clamp is applied to allow access to the heart for the surgical correction creating an ischemic environment. When the clamp is removed and blood flow returned, the heart is reperfused. This exposes the myocardium to IR injury. Super-high oxygen (O2) levels are often used in the bypass circuit after the cross-clamp is released. This means during reperfusion the myocardium is exposed to high levels of O2. This is thought to be harmful, especially to children with cyanosis pre-operatively. A growing body of evidence suggests that these high levels of O2 may be damaging to the infant myocardium but the mechanisms are not that well understood. The first aim of this project was to investigate the molecular changes that occur within the infant myocardium in the context of congenital heart disease by comparing myocardium from the cyanotic patient group (TOF patients) and acyanotic patient group (patients with sub-aortic stenosis or truncus arteriosus i.e. disorders requiring myocardial resection but where the myocardium is acyanotic) during the ischemic phase. This was performed to reflect as near to pre-operative gene expression levels as possible. This thesis focused on the expression of inflammatory mediators (TLRs) and stress proteins (HSPs). It was found that TLR4 (p=0.0303), TLR2 (p=0.0177) and HSP27 (0.0303) mRNA expression were significantly higher in the myocardium from the cyanotic patient group compared to the acyanotic patient group. This could indicate a consequence of the hypoxic environment within such myocardium. HSPs are stress proteins, which are induced upon cellular stress. The Aplein receptor (APJ) is upregulated in the heart during ischemia and IR injury and thought to be cardio- protective. Additional work was performed that investigated the protein expression of HSP27 and APJ during the ischemic phase in cyanotic and non-cyanotic TOF myocardium. This expression was compared with various measurements of cardiac function. HSP27 protein expression was significantly elevated in cyanotic myocardium pre-operatively. It was also associated with improved right ventricle function and systemic perfusion. This supports a cardio-protective effect of HSP27 in cyanotic TOF. APJ was found to be associated with 2 improved systemic perfusion when both cyanotic and non-cyanotic patient data were combined. In order to determine if stress genes (HSPs) were inducible in the infant myocardium, they were exposed to classic heavy metal inducers sodium arsenite and cadmium chloride. Of the six HSPs investigated, all were shown to be present within the ischemic myocardium. Myocardial HSP32 (p=0.0156), HSP72 (p=0.0156) and HSP90 (p=0.0156) mRNA expression were significantly increased by exposure to heavy metals. Therefore, HSPs were shown to be inducible in infant myocardium. This was a good experimental control for the re-oxygenation experiment. The expressions of the same genes were also examined in vitro during an attempt to mimic re-oxygenation of the ischemic myocardium when the aortic-clamp is removed. Tissue was removed during the ischemic phase from both cyanotic and acyanotic patients and exposed to differential O2 levels. It was found exposure to 20% and 60% O2 for 4 hours induced mRNA expression of HSP32 (p=0.0391 and p=0.0078 respectively) and HSP72 (p=0.0078 and p=0.0078 respectively). This could indicate cellular stress during re- oxygenation of infant myocardium during surgical correction. No difference was indicated between the cyanotic and acyanotic patient group. The work of this thesis was focused on myocardial mRNA/ protein expression. Whether there is an alteration in circulating inflammatory mediators was not the focus of the present study but the results within this thesis highlighted the need for future studies to look at the effect of circulating factors on myocardial inflammation. This project is novel because it allowed a better understanding of the molecular mechanisms at work within infant myocardium and how they are influenced by re- oxygenation injury. It also examined how they are affected by cyanosis. It has highlighted the best ways in which such investigations could be extended. It has contributed important molecular data to the area of research and could potentially help lead to an improvement in myocardial protection during cardiac surgery with CPB.

It is recognised that research in paediatric palliative and complex care is in the early stages. Chapter One examines the available literature of fathering a child with a chronic, life threatening or life limiting illness. The research reviewed supports the notion that fathers are under-represented in paediatric palliative and complex care. The findings highlight that men express their vulnerability in gender specific ways, which has implications for support and service provision. Particular gaps in the research on fathers are highlighted, in relation to the long term impact of fathering a child with life limiting, life threatening, or chronic condition, fathers’ needs in the marital dyad, and studies on the efficacy of father focused interventions. Chapter Two explores health professionals’ experiences of managing boundaries, in the context of paediatric complex and palliative care in the community. The findings indicate that there are a number of issues relating to boundaries that require balancing and which have an impact on service provision and professional wellbeing. Chapter Three is a reflection on the research journey, particularly developing the boundary discussion with regard to ethics. This includes reflections on research in paediatric palliative care, the boundaries of this research, overlaps with clinical practice, and personal and professional learning.

Children with disruptive behaviour disorders include a complex pattern of causation and comorbidity. As such, it is important to identify problems at early stages of development so that intervention can target relevant areas. Computerised assessments and interventions for children with disruptive behaviour disorders offer several advantages over traditional approaches. These include speed, accuracy, engagement, agreeability, and cost. The first chapter of this thesis discusses the utility of five computerised packages that could be used to screen populations for the disorders. It examines issues relating to test administration, reliability, agreeability, cost, and validity and makes appropriate recommendations. The second chapter describes an empirical study, which examined the effectiveness of a computerised token economy system to encourage learning in children with emotional and behavioural difficulties. This study also investigated the role of self-esteem in relation to learning problems and the disruptive behaviour disorders. The final chapter involves a discussion of new frontiers of mental health technology based on personal practice and reflection.

Type I diabetes effects over 16,500 children in the UK. For these young people, care is needed to maintain 'near normal' blood glucose levels in order to relieve the unpleasant symptoms of high and low blood glucose. Although good metabolic control may decrease the risk of severe long term complications, adolescents often have difficulty juggling all the aspects of a complex and demanding treatment regimen, and poor adherence is commonplace. The literature review proposes a theoretical framework for understanding the role of responsibility in the management of type 1 diabetes during adolescence. The pattern of responsibility is explored in relation to the individual and their interpersonal context. In terms of health outcome, the effects of individual and shared responsibility are considered, necessitating a balance between the adolescent's assumption of responsibility and their level of parental involvement. Suggestions for clinical practice are discussed, methodological limitations raised, and future research opportunities identified. The role of dietary self efficacy in predicting self care during adolescence is established. Using data for two distinct phases of adolescence, paper 1 examines whether social support from family and friends makes any additional contribution to the prediction of dietary self care, over and above that of self efficacy. For the younger group (aged 12-13), the prediction of self care is improved by better perceived support from friends. An interactive effect of shared family responsibility is also reported, confirming the importance of shared responsibility, between parent and child, to facilitate good self management as highlighted in the literature review. None of the variables are significant predictors of self care in the older group (14-18 year olds).

Mestre -- Escola Nacional de Saude Publica, Rio de Janeiro, 2001. / SAUDE PUBLICA.

Mestre -- Escola Nacional de Saude Publica, Rio de Janeiro, 2001. / SAUDE PUBLICA.

Mestre -- Escola Nacional de Saude Publica, Rio de Janeiro, 2001. / SAUDE PUBLICA.