The aim of this thesis was to investigate the impacts of physical activity (PA), cardiorespiratory fitness (CRF), body composition and lifestyle education on cardiometabolic (CM) risk in 10-11 year old children. This broad aim was approached using three studies. Studies 1 and 2 were cross sectional observational studies, and study 3 was a clustered randomised control trial, with intervention effects assessed at post intervention and again at 8 to 10 weeks after the intervention. Initially, in the first cross sectional study (Chapter 4) the relationships between non- invasive (LV Mass, E/A, E'/A', E/E', trunk fat mass, whole body fat mass) and invasive CM risk markers (CRP, HOMA-IR, adiponectin, TC: HDL-C), and between all risk markers and CRF (V02 peak), time spent sedentary, moderate to vigorous intensity PA (MVPA) and vigorous PA (VPA) were investigated in 10-11 year old children (n=62). The key findings were significant but generally weak relationships present between some of the non- invasive and invasive markers of CM risk and risk markers also had significant correlations with measures of CRF and PA. CRP was significantly positively correlated with whole body fat in boys (rho = 0.486, p < 0.05) and girls (rho = 0.485 , p < O.Ol) and with trunk fat mass in boys (rho = 0.384, p < 0.05) and girls (rho =0.489, p < O.Ol). Adiponectin was negatively correlated with whole body fat (rho = -0.446, p < 0.05, and R=-0.697, p < O.Ol) and trunk fat mass (rho = -0.614, p < O.Ol; rho = -0.475, p < O.Ol) in boys and girls respectively, and in girls adiponectin also correlated positively with E'/A' (r=0.356, p < 0.05). In boys only, TC:HDL-C was positively correlated with whole body fat (rho =0.407, p < 0.01) and trunk fat mass (rho =0.391, p < 0.05). ; V02Peakwas negatively correlated with CRPin boys (Rho = -0.492, p < 0.05) and HOMA-IR in girls (Rho =-0.522, p < 0.01). V02Peak was also negatively correlated with whole body fat (rho =-0.515, p < 0.01; r=-0.697, p < O.Ol) and trunk fat mass (rho=-0.494, p < 0.05; rho =-0.706, p < 0.01) in boys and girls respectively. Both MVPA and VPA correlated negatively with TC: HDL-C in girls (rho= -0.396, p < 0.05; rho =-0.428, p < 0.05) and MVPA correlated with whole body fat (rho= -0.602, p < O.Ol) and trunk fat mass (rho=-0.65, p < 0.01) in boys. VPA also correlated with whole body fat in girls (rho= - 0.544, p < O.Ol) and with trunk fat mass in both boys (rho= -0.428, p < 0.05) and girls (rho= - 0.468, p < 0.01). Time spent sedentary had a positive correlation with whole body fat in boys (rho = 0.429, p < 0.05). This study demonstrated that risk factors clustered in individuals and that relationships were present between invasive and non-invasive markers of cardiometabolic risk, and provided preliminary evidence to investigate this phenomenon further. The correlations described in this study suggest a clustered risk score which includes both invasive and non-invasive measures may add value to predicting overall risk. The second cross sectional study (Chapter 5) investigated clustered CM risk, by combining invasive markers with non-invasive 'pre-clinical' markers of CM risk into a clustered risk score, in a different cohort of 10 - 11 year old children. Clustered risk scores were negatively correlated with CRFand PA. V02 peakshowed a moderate negative correlation with CRSA (r=-0.57, p < 0.01) and CRS B (r= -0.60, p < O.Ol) VPA showed a moderate negative correlation with CRSA (r= -0.51, p= 0.01) and CRSB (r= -0.50, p=O.Ol). MVPA showed a moderate negative correlation with CRSA (r= -0.44, p= 0.03) and CRSB (r= -0.41, p=0.04). Sedentary time showed a moderate positive correlatcorrelation with CRSA (r= 0.414, p= 0.049). The evidence provided by these two observational studies, Study 1 (Chapter 4) and Study 2 (Chapter 5), along with other literature, as discussed throughout this thesis, gave rationale for an intervention with the aim to reduce negative lifestyle behaviours, of low levels of PA, high levels of sedentary behaviour and poor nutritional balance, increase CRF and maintain a healthy body weight.

Background: Sedation withdrawal is one of the terms used to describe the behavioural response to stopping or reducing sedative drugs in physically dependent patients. Withdrawal behaviours differ according to the drug involved and may be unpleasant and interfere with recovery. Recognition of sedation withdrawal is challenging due to differences in patient presentation and may be further complicated by the patient’s condition and concomitant drug therapy. Overall Aim of the full thesis: To improve the accuracy of sedation withdrawal assessment in critically ill children. Objectives and Methods: A mixed methods interactive approach comprising six studies. Study 1 evaluates the psychometric properties of the Sedation Withdrawal Score, Studies 2 and 3 examine the complexities/challenges of withdrawal assessment by critiquing existing tool validation studies, A further three studies examine the nurse and parent perspectives of sedation withdrawal assessment in critically ill children. Study 4 investigates how nurses use a sedation withdrawal tool, Studies 5 and 6 investigate what behavioural signs parents recognise and ascertain parents’ willingness to participate in withdrawal assessments. Key findings: Nurses found withdrawal behaviours difficult to interpret in critically ill children and there were differences in how these behaviours were construed. Parents identified a broader range of behaviours than included in existing tools. Most parents were eager to participate in the assessment. The elusive theoretical basis for the existing approach to withdrawal assessment may account for the lack of a standardisation and poor accuracy of the current tools. A model of the causal relationship between dependence and withdrawal is proposed. Recommendations: The model identifies the diagnostic criteria upon which a definition for Pediatric Withdrawal Syndrome may be based. These criteria also provide a novel framework for withdrawal assessment. Focussing on the shared diagnostic criteria and including the parent perspective of the child’s behaviours may aid the assessment and support decision-making.

The Children Act 1989 imposes a duty on Local Authorities in England to ‘safeguard and promote the welfare of children’ and to ‘promote the upbringing of children by their families’ wherever possible. If, during pregnancy, concerns are identified that suggest the child may be at risk of harm a referral may be made to the Local Authority for a pre-birth assessment. When completing a pre-birth assessment social workers and other professionals are often involved in the process of collecting and analysing information, which will ultimately be used as a basis for planning and decision-making and can have life long consequences for the family. Removing a baby at birth brings with it an inevitable impact on the process of attachment and bonding, as well as the impact of subjecting a family to court proceedings and all of the emotions that entails. However, allowing a baby to be discharged from hospital to a family who are unable to provide appropriate care and protection or do not have the necessary support in place to assist them may result in irreparable harm to, or even the death of the baby. Sitting within the context of general child and family social work assessment, pre-birth assessment has received a very limited amount of specific research attention. This thesis comprises a report on the outcomes of my own research, which was exploratory in nature, and details the findings from a mixed methods study of relevant legal and procedural frameworks in England, Local Safeguarding Children Board procedures and a case study of pre-birth social work assessment practice in one Local Authority. The findings were that pre-birth assessment is a complex process guided by a national and local procedural framework which does not recognise the unique status of the unborn child. Having evolved from a historical perspective based on protecting live children, the procedural guidance is contradictory as it does not acknowledge that an unborn child has no legal status and a pregnant woman maintains rights over her own body. The case study also revealed that social workers in the host LA were practising in an environment of managerial systems which aimed to improve accountability and yet the very systems designed to ensure children did not fall through the ‘safety net’ of professional support were, ironically, prompting systems which made practice in (and research into) pre-birth social work assessment a challenge. A narrow forensic approach to pre-birth assessment was found to have developed, with the documentary process of completing pre-birth Initial and Core Assessments (as defined by the Department of Health (2003) documentation) becoming split from the process of actually ‘doing’ a social work pre-birth assessment.

This research project sets out to explore the lived experience of Being and caring for a child with a Life Limiting Condition. This research uses van Manen’s (1990) conceptualisation of hermeneutic phenomenology that is both a research methodology and a method. The first empirical work is a preliminary study using focus groups with professionals. The findings of this work acts as a backdrop to the further two studies that involve interviewing, in-depth, twenty eight parents and five children. The second study details the parents’ lived experiences and the final study looks at five parent-child dyads and their combined lifeworlds. In keeping with the phenomenological methodology, data was analysed using Template Analysis (King, 2004). It is a rare opportunity to observe and speak with children with Life Limiting Conditions and so gain insight into their lives. Their vulnerability is often characterised by rare and difficult-to-diagnose conditions, significantly shortened life spans with compromised quality of life. For the participants, the experience of Life Limiting illness was not only personal, but was also transactional, communicative and profoundly social. The challenge is one of Being thrown into an abnormal unready world which compels one to consider the paradoxical temporality of the here and now. This brings recognition of being the same as others in a lived space, but also being different in a fundamental way that has a significant impact. The challenge is met by adapting to the environment to find new ways of Being. This research encourages readers to thoughtfully reflect on what is it like for these families and those involved in their care, and to consider practice improvements that address the triadic experience (of child, parent and professional). The full significance of such reflection will ideally promote further questioning and inquiry, in keeping with the always provisional nature of phenomenological inquiry.

Crohn`s Disease (CD) and Ulcerative Colitis (UC), two types of Inflammatory Bowel Disease (IBD), are chronic, relapsing inflammatory conditions of the gastro-intestinal tract. Approximately 25% of cases are diagnosed in childhood and adolescence; affected children suffer from symptoms such as abdominal pain, bloody diarrhoea, fatigue, and poor nutritional state. Poor growth, in terms of both height and weight, precedes diagnosis and further weight may be lost with successive inflammatory exacerbations. Changes in height and weight are used as a marker of both disease severity and response to treatment, but the associated changes in body composition with changes in weight are poorly characterised and understood, and rarely assessed in routine clinical care. Being able to determine the nature and size of any deficits in lean and fat mass may provide a better understanding of the disease process, whilst gains in height and lean tissue, relative to increases in fat mass, could also be used to mark the effectiveness of clinical management and improvement in nutritional state. Exclusive enteral nutrition is now being used in preference to anti-inflammatory therapy in children with IBD, but there are increasing concerns that the focus on weight gain as children move into remission with only modest gains in height reflects an inappropriate mix of tissue deposition with greater gains in fat than lean. The central hypothesis of this thesis is that children with IBD present at diagnosis with a lean deficit, greater that that which can be simply attributed to their lack of height, and that conventional therapy, including exclusive enteral nutrition, may not adequately correct the nutritional state and deficit of lean tissue. In order to test this hypothesis, the work described in this thesis is presented in three parts. Firstly, a cross-sectional study of a convenient sample of children with CD and UC drawn from the regional IBD outpatient clinic to explore the extent and nature of the differences in height, weight and BMI expressed as SD scores, together with simple measures of body composition using anthropometry. This initial study confirmed that whilst as a group, both CD and UC children exhibit only modest deficits in height, weight and BMI there was marked variance across the group with more pronounced deficits in some children. Lower Upper Arm Muscle Area SD scores and higher Triceps skinfold thickness SD scores would support the proposition of a general lean deficit and fat excess, even in children with BMI range within ± 2SD. The second part explored different approaches to assessing body composition by i) determining the concurrent and face validity of different bioelectrical impedance devices using deuterium dilution space as a reference method and ii) the potential of using SIFT-MS to conduct real-time near-patient measures of deuterium abundance on breath vapour was examined in comparison to measures of deuterium abundance in saliva and urine assessed by both SIFT-MS and IRMS. These studies demonstrated important differences in lean mass were evident between devices. Deuterium abundance in saliva and urine by SIFT-MS was directly comparable to that by IRMS although higher levels of D O administration were required for optimal analytical performance; greater imprecision was evident in determining deuterium abundance in breath. The third part described detailed measures of body composition (anthropometry, DXA, deuterium abundance in saliva by IRMS, and BIA) in a prospective inception cohort of eleven children with CD studied at diagnosis, and followed for the first year of treatment from active disease into remission using exclusive enteral nutrition. Lean deficits identified using both DXA and Upper Arm Muscle Area was evident at diagnosis greater than that which could be attributed to shortness. Treatment was associated with gains in height and weight, but in contrast to previous reports where corticosteroids were only used to induce remission, gains in lean mass over the first year of treatment using exclusive enteral nutrition were observed which were greater than that which could be attributed to an increase in height that reflect at least a partial correction of the lean deficit.

No description available.

The origins of respiratory disease, such as asthma in childhood and COPD in later life are unclear. Maternal smoking during pregnancy and low birth weight is associated with increased risk of asthma, poor lung function in adults and COPD in old age. Exposure to oxidative stress and poor nutrition in utero is thought to cause damage to the lung and alter the normal course of lung development. Glutathione S-transferases (GST) are potent antioxidants. In this work, genetic polymorphisms that alter GST enzyme activity were genotyped in a family-based childhood asthma cohort (341 families, n = 1508) and analysed to investigate whether they alter the risk of developing asthma when individuals are exposed to environmental tobacco smoke. Real-time PCR based copy number variation methodology was developed to genotype the common gene deletion polymorphism of GSTT1 and GSTM1 genes, for other GST genes (GSTP1 and GSTO2) SNP haplotypes were constructed. A rare GSTO2 haplotype was negatively associated with asthma susceptibility, atopy severity, and FEV1 values. Asthmatic children with a GSTT1 gene deletion, or a common GSTP1 haplotype, developed more severe asthma compared to individuals with a GSTT1 gene or non-carriers of the GSTP1 haplotype. Total IgE levels were increased in GSTT1*0 individuals when exposed to tobacco smoke in early life, suggesting a gene-environment interaction. GSTO2 may be a shared susceptibility locus for asthma in childhood and COPD in later life. Animal models of maternal protein-restriction during pregnancy can induce hypertension, diabetes and endothelial dysfunction in offspring and in some of these models alterations to lung gene expression and lung architecture have been reported. This work established that a rat model of maternal dietary protein-restriction during pregnancy known to induce hypertension in the offspring, results in persistent alterations to the expression of genes in the lungs of adult offspring (120 days), including genes involved in glucocorticoid action (Hsd11b2), growth (Igf1 & 2 and Pcdh1) and alveolar development (Tp53). Lung microRNA expression profiles were also altered in response to exposure to protein restriction in utero. These findings suggest a role for nutritional programming in respiratory disease susceptibility in later life and a role for microRNAs in the study of the developmental origins of health and disease in general. Further work will include the investigation of epigenetic mechanisms that control nutritional programming in lungs of animals exposed to protein-restriction in utero. This work has demonstrated that GST polymorphism is a risk factor for childhood asthma and certain genotypes can offer some protection against the development of severe asthma. There was little evidence to suggest that GST polymorphism modulates the effects of smoke exposure in early life. In addition, we have demonstrated that maternal diets that are poor in nutrition could predispose her offspring to respiratory disease in later life by altering the course of normal lung development in early life or response to environmental stimuli in later life.

This study aimed to explore children’s experiences of art therapy in order to create a theory of change processes within school-based art therapy. A total of 14 children were interviewed at two different schools, along with their parents, teachers, and art therapists. All children had received art therapy within the last 12 months. Semi-structured individual interviews were undertaken with 40 participants. Children completed a craft activity within their interview as a visual expression of their therapy experience. Interview data was analysed using grounded theory methodology. The results generated three theoretical models. The first model highlighted the systemic nature of the art therapy as well as describing it as mysterious. Model 2 described the processes within art therapy, focusing on the individualised child-centred nature of the intervention. Art doing was considered central to the children’s expressions and developing understandings. Model 3 described the trajectory of change for the children. The study recommends that psychologists consider art therapy for children who are struggling to verbalise their difficulties; that clinicians focus on therapeutic experiences being fun and enjoyable for the child, as well as embedded within the child’s system; and lastly that clear target problems are identified at the start of therapy.

Scotland has the highest rates of child obesity in Europe with more than 1 in every 4 children aged between 2 and 15 being overweight or obese in 2008. The need to curb the nation’s unhealthy eating habits through Scottish public health policy has been acknowledged, although there remains a shortage of policy addressing the eating habits of infants and young children as they develop in the context of family life. This is matched by a shortage of empirical research which uses nationally representative longitudinal data on Scottish children, to look at how diets of children under five develop within the home. This doctoral research seeks to explain how children’s nutritional trajectories develop from birth through infancy and into early childhood in contemporary Scotland within the context of maternal resources, maternal use of nutrition advice, and family meal habits. Theoretical concepts pertaining to social constructionism and the symbolic meaning of meal rituals, as well as theories of risk and responsibilisation, human capital and health behaviours, and discussions about agency and structure, frame the research questions and the interpretation of results. The research draws on the first three annual sweeps of the Growing Up in Scotland nationally representative, longitudinal survey of families and young children. The analysis is based on multivariate proportional hazards regression and logistic regression models. The empirical analysis shows that maternal education is a consistently superior predictor of children’s nutritional outcomes, when compared to maternal occupational classification and household income, and that children of more educated mothers have healthier diets throughout infancy and childhood. This points to the utility of human capital theories which stress the importance of education, rather than income, and also reflects on the need for policy to recognise the structural nature of nutritional inequalities. More educated mothers are also more likely to be proactive in using healthy eating advice, resonating with theories of risk awareness and medicalised childhoods. Surprisingly, mothers from disadvantaged backgrounds are more likely to use advice from health professionals, possibly as a result of health professionals actively targeting their support to more ‘at risk’ families. Yet these mothers are also more apprehensive about the interference of health professionals in aspects of childrearing. Relevant policy reflections pointed to the need to identify how support for mothers from more disadvantaged backgrounds can be provided in formats which help to overcome the culture of mistrust towards health professionals prevalent among disadvantaged parents. Nevertheless, positive associations between infant diet and maternal use of breastfeeding advice from health professionals are found, in line with theories of power-knowledge, lending support to information-based policy initiatives as a tool for improving infant nutrition. The analysis also indicates that children who are breastfed, and children who are weaned later have healthier diets in their toddler years, which contributes to the proposal of a theoretical typology explaining how young children’s nutritional trajectories evolve from the pre-partum period through infancy and childhood. Finally, the analysis suggests that communal patterns of eating play an important role in children’s dietary quality, attesting to the importance of the meal ritual as a vehicle for socialising children into developing particular tastes for food. Thus, there seems to be room for policy initiatives which address not only what children eat, but how young children and families eat in the context of everyday family life.

In the absence of readily available physiological models of human growth, the effects of oestradiol on the human C28/I2 chondrocyte cell line were studied. The classical oestrogen receptors, ERα and ERβ, were shown to be expressed in both murine and human chondrocyte cell lines. Oestradiol and related chemicals, which alter the function of the oestrogen receptors (ER), were exploited to tease out the different functions of each ER in the growth plate. In the absence of foetal bovine serum, oestradiol had no effect on proliferation, differentiation or apoptosis of chondrocyte cells in monolayer culture or on the growth of the foetal metatarsal culture system. In addition, oestradiol did not convey a protective effect on chondrocytes exposed to the pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in monolayer culture. However, endogenous oestrogen appears to play an important role in maintaining chondrocyte proliferation in monolayer culture and mineralisation in metatarsal culture as reflected by the inhibitory effects of Faslodex, the non-specific ER antagonist, on chondrocytes and metatarsals in culture. In the presence of methyl-piperidino-pyrazole (MPP), a selective ERα antagonist, and raloxifene, a selective oestrogen receptor modulator with higher ERβ binding affinity, a reduction in chondrocyte proliferation and increase in apoptosis was observed in murine and human chondrocytes. Similarly, a marked reduction in linear growth occurred when foetal murine metatarsals were exposed to MPP and raloxifene in combination. A less marked reduction in growth was observed in MPP-treated metatarsals. These findings suggest that the oestrogen receptors may have opposing actions in the growth plate with ERβ acting like a brake on chondrocyte growth and ERα promoting growth. ERβ may regulate cell proliferation through control of cell cycle modulators affecting G1/S phase transition as MPP and raloxifene in combination reduced cyclin E and p53 levels on Western blot analysis. The aim of the second part of my thesis was to investigate the effect of oral oestrogen on linear growth in girls with primary ovarian insufficiency (POI). A retrospective review of girls with POI treated at a tertiary endocrinology clinic over an 11 year period was performed. As expected the majority of girls with POI had Turner syndrome (TS; 83.7%). Non-TS associated POI was rare and the leading cause was iatrogenic secondary to the effects of total body irradiation for bone marrow transplantation (12.8%). A significant proportion of these girls developed POI after full pubertal development so few cases were available to investigate the effect of oestrogen on growth. The oral oestrogen regime followed in individual patients with TS was highly variable so it was not possible to assess the effects of dose on height velocity or bone maturation in this retrospective audit. However, the second clinical study examined in detail the effect of oestrogen on growth in TS girls who received a standardised course of oral ethinylestradiol for pubertal induction and a standard dose of growth hormone (10 mg/m2/week). These girls participated in a prospective randomised double-blind placebo-controlled multi-centre study of growth promoting treatment in TS. The girls were initially randomised to oxandrolone or placebo at 9 years of age and further randomised to oral ethinylestradiol at 12 or 14 years of age. The results of this study are embargoed until published. The laboratory effects of oestradiol found in this thesis suggest that ERα may stimulate or maintain growth, and ERβ may inhibit growth. The obvious question is how these observations might be involved in the complex relationship between puberty, oestrogen and height velocity in humans. As affinity studies show that the half maximal effective concentration (EC50) of ERα is achieved at slightly lower concentrations of oestradiol than ERβ it is conceivable that the ERα effect could predominate at lower systemic oestradiol concentrations and that ERβ could become more important at higher concentrations for example in later puberty. Alternatively, it is possible that the expression of ERα reduces or ERβ increases in the growth plate after reaching peak height velocity.