Thesis (MEdPsych)--University of Stellenbosch, 2001. / ENGLISH ABSTRACT: In this study an investigation was conducted to determine whether the education in ACE-schools(within the South African context) provides in the development needs of learners. Political changes in South Africa have, on the one hand, led to the perception amongst especially Christian parents, that, due to a strong humanist tendency in state schools, their children experience a lack of adequate Christian education. On the other hand, the education system in South Africa has enabled the establishment of a wide range of different educational institutions from which parents can choose the one that provides in their unique needs. Accelerated Christian Education (ACE) is a Christian education system that originated in the USAbut is now implemented world-wide. The uniqueness of this system lies in the fact that education is mostly provided via written material which every learner can master individually and on his/her own time (within the classroom setting). The advantages are in the individualizing of learning, but a question arises as to the desirability of the lack of interpersonal communication in the learning activities. A literature study was undertaken to establish the psychosocial development needs that have to be provided in to ensure that learners are guided towards effective and balanced adulthood. An overview was also obtained on Christian education in general and on the ACEsystemin particular. To evaluate the ACE-system in practice, the views (and especially criticism) of theorists and authors are supplemented by information gathered from parents, learners and teachers from three ACE schools. This information was gathered by means of individual informal discussions. The research groups consisted of five representatives from each of the sub-groups from each of the three schools (N=45). The most important findings are the following: The ACE school system offers an acceptable alternative to parents who wish to ensure that their children receive education of a more Christian nature, or at least education in a Christian setting. Other benefits include individualizing and the fact that learners set their own learning objectives daily, which simplifiesmotivation and discipline. From an educational psychological perspective, the ACE schoolsystem does, however, have important deficiencies: • Firstly,the nature of education in an ACE school does not make adequate provision for interpersonal communication. The importance of interpersonal communication for effective learning, whether it be in the form of content being mediated to the learner via the teacher, or through classroom discussions (peergroup interaction) iswidely accepted. • Secondly, the exclusive nature of the ACE school leads to the isolation of learners from the wide variety of people, views and religious beliefs that are present in society. • Thirdly, in the ACE school little, if any, provision is made for physical activities, which are important for balanced development of learners. • Lastly, the ability of ACE schools to make provision for learners with special education needs, islimited. Following from these findings, a few recommendations are made. / AFRIKAANSE OPSOMMING: In hierdie studie is 'n ondersoek gedoen om vas te stel of die onderrig in ACE-skole (in die Suid-Afrikaanse konteks) voorsien in die ontwikkelingsbehoeftes van leerders. Politieke veranderinge in Suid-Afrika het meegebring dot veral Christenouers die persepsie het dot hul kinders, weens 'n sterk humanistiese inslag in staatskole, gebrek Iy aan voldoende Christelike opvoeding. Verder het die opvoedingsbestel in Suid-Afrika dit moontlik gemaak dot In wyer verskeidenheid van opvoedingsinstellings gevestig word waaruit ouers die een kan kies wat aan hul unieke behoeftes voldoen. Accelerated Christian Education (ACE) IS In Christelike opvoedingstelsel wat sy ontstaan in die VSA gehad het. maar nou wereldwvd ge'implementeer word. Die uniekheid van hierdie stelsel Ie daarin dot onderrig grootliks geskied via geskrewe materiaal wat elke leerder individueel en op sy eie tyd (binne die klaskamer) bemeester. Die voordele Ie in die individualisering van leer, maar In vraag ontstaan no die wenslikheid van die gebrek aan interpersoonlike kommunikasie in die onderriggebeure. In Literatuurstudie is onderneem om te bepaal in watter psigososiale ontwikkelingsbehoeftes voorsien moet word om te verseker dot leerders begelei word no effektiewe en gebalanseerde volwassenheid. Verder is 'n oorsig verkry van hoe Christelike onderwys in die algemeen, en die ACE-stelselin die besonder, door uitsien. Om die ACE-stelselin die praktyk te evalueer is die menings (en veral kritiek) van teoretici en outeurs aangevul deur inligting wat verkry isvan ouers. leerders en onderwysers van drie ACE-skole. Hierdie inligting is verkry deur middel van individuele informele gesprekke. Die ondersoekgroepe het bestaan uit vyf verteenwoordigers uit elk van die subgroepe uit elk van die drie skole (N=45). Die belangrikste bevindinge is die volgende: Die ACE-skoolstelselbied 'n aanvaarbare alternatief vir ouers wat graag wil toesien dot hul kinders meer Christelike opvoeding ontvang, of dan ten minste opvoeding in 'n Christelike omgewing ontvang. Ander voordele sluit in individualisering en die feit dot leerders daagliks hul eie leerdoelwitte stel, wat motivering en dissipline vergemaklik. Vanuit 'n opvoedkundig-sielkundige perspektief bevat die ACEskoolstelselegter belangrike leemtes: • Eerstens maak die aard van onderrig in 'n ACE-skool nie voldoende voorsiening vir interpersoonlike kommunikasie nie. Die belangrikheid van interpersoonlike kommunikasie vir effektiewe leer, hetsy in die vorm van inhoud wat via 'n onderwyser no die leerder gemedieer word, of in klaskamergesprekke (portuurgroepinteraksie) word wyd as gegewe aanvaar. • Tweedens lei die eksklusiewe aard van die ACE-skool daartoe dot leerders ge"isoleerword van die wye verskeidenheid mense, sienswysesen geloofsoortuigings wat in die samelewing bestaan. • Derdens word in die ACE-skool min, indien enige, voorsiening gemaak vir fisieke aktiwiteite; nog 'n belangrike aspek vir die gebalanseerde ontwikkeling van leerders. • Laastens isdie verrnoe van ACE-skoleom voorsiening te maak vir leerders met spesiale onderwysbehoeftes, beperk. Voortspruitend uit hierdie bevindinge word enkele aanbevelings gemaak.

Crohn’s disease (CD) is a chronic inflammatory bowel disease. Once considered rare in the paediatric population, it is recognized with increasing frequency among children of all ages. Approximately 20-30% of all patients with CD present when they are younger than 20 years. With its increasing recognition, CD has become one of the most important chronic diseases that affect children and adolescents. In addition to the common gastrointestinal (GI) symptoms (diarrhoea, rectal bleeding, and abdominal pain) children often experience growth retardation, pubertal delay, and bone demineralization. In these children, maintenance of skeletal health is a complex process that is influenced by a number of different mechanisms including steroid therapy, the disease process, nutritional status, endocrine status and the response of the body to inflammatory mediators. The recent introduction of biologic therapy that targets specific mediators of the proinflammatory process is a promising adjunct in the therapeutic management of the child with chronic inflammation. These drugs may also exert beneficial effects on the adverse effects of inflammation on growth and skeletal development. It is unclear whether these beneficial effects are due to improvement in overall disease or due to a direct ‘anti-cytokine’ effect at the level of the target tissue involved in growth and skeletal development. The hypothesis of this study was that the biologic therapy improves linear growth, puberty, bone health, body composition and muscle function in children with CD and this is associated with changes in the IGF-1 axis and markers of bone formation and bone resorption. Chapter 1 is an extensive literature review about the effects of biologic therapy on growth and skeletal development in paediatric patients with chronic inflammatory conditions particularly inflammatory bowel disease (IBD). The main aim of this review was to summarize and evaluate effects of inflammation and biologic therapy on growth and skeletal development in children with chronic inflammatory conditions and to explore the areas of interest for further research. Chapter 2 is the study about the growth in children receiving contemporary disease specific therapy in children with CD. The aim of this study was to assess the frequency of short stature and poor growth and their relationship to disease course and therapy in children with CD. Clinical records of all children with a confirmed diagnosis of CD, who were between 2yrs and 18yrs at the Royal Hospital for Sick Children, Glasgow were examined retrospectively. Data were collected at diagnosis, 1-yr, 2-yr and 3-yr after diagnosis and at maximum follow-up. The relationship of a number of factors including therapeutic modalities to two commonly used anthropometric markers of growth height velocity standard deviation scores (HVSDS) and change in height standard deviation scores (∆HtSDS) was examined. This study suggested that ∆HtSDS may be a more valid method of assessing and reporting longitudinal growth in children with chronic disease, particularly when there is a high prevalence of children of a peri-pubertal age. This study provides clear evidence that despite advances in therapy, short stature and slow growth continue to be encountered in a sub-group of children with CD. Chapter 3 is about the effect of Infliximab therapy on growth, puberty and disease activity in children with CD. The aim of this study was to assess growth, puberty, markers of disease and concomitant therapy over the six months prior to starting Infliximab and for the 6 and 12 months following treatment. Clinical records of all children with IBD who were started on Infliximab therapy between 2003 and 2008 at the Royal Hospital for Sick Children were examined retrospectively. This study has shown an average improvement of approximately 50% in HV in the 6 months after the initiation of Infliximab therapy which was further sustained for a further 6 months. Improvement in growth was found to be better in those children who were responders as compared to non-responders suggests that growth improved as a result of disease control. Improvement in growth was also observed in children who remained pre-pubertal and those who had never been on glucocorticoids (GC) compared to those who had been on GC. This study suggests that increase in height may not be simply due to progress in pubertal status or reduction in glucocorticoid dose. Chapter 4 is about the effect of Adalimumab therapy on growth in paediatric patients with CD. This is the one and only world wide multicentre study that adequately assess the effect of Adalimumab on linear growth in children with CD. The aim of this study was to assess the effect of Adalimumab therapy on growth, puberty and disease activity over the 6 months prior to and 6 months after starting Adalimumab treatment in children with CD. This study provides evidence that Adalimumab is associated with improvement in short term linear growth in children with CD who enter remission but not in those who do not. It is also more likely to happen in children who are on immunosuppression and those in early puberty but seems to be relatively independent of steroid use. These findings suggest that growth improves as a result of several interrelated factors, including improved disease control. It was also interesting to note that the growth response to Adalimumab varied dependent on the reason for discontinuing Infliximab; those who had an allergic reaction to Infliximab fared best. Chapter 5 is Longitudinal observational prospective study of changes in physical growth, IGF-1 axis, bone health, body composition, muscle function and disease activity at baseline (BL), 2 weeks (2wk), 6 weeks (6wk), 6 and 12 months (6M & 12M) following biologic therapy in paediatric patients with CD. The aim of this longitudinal observational prospective study was to assess changes in physical growth, puberty, IGF-1 axis, bone health; body composition and muscle function following biologic therapy in paediatric patients with CD. Patients either newly diagnosed or patients with long-lasting disease in clinical relapse, who started treatment with biologic therapy as part of their standard clinical management, were recruited. A non significant improvement was observed in both ∆HtSDS and HVcms/yr at 12M as compared to BL. Individually, the majority of the children experienced improvement in clinical activity and improvement of the systemic inflammatory markers. A significant increase in biomarker of bone formation bone specific alkaline phosphatase (BALP) and a non-significant increase in a biomarker of bone resorption cross-linked c-terminal telopeptides (CTX-1) was observed from BL to 12M. This observation suggests the beneficial effect of biologic therapy on bone formation. This study showed a significant change in fat mass (FM (kg) in paediatric patients with CD following biologic therapy an effect that has not been reported extensively in previously published studies. A significant change in both fat free mass (FFM (kg) and fat free mass index (FFMI(kg/m²) shows that the treatment with anti-TNF-α therapy also had a significant impact on fat mass accrual. This is the first study that charts the effect of biologic therapy on changes in lower limb muscle function using jumping mechanography in paediatric patients with CD. A non significant change was observed in jump height (m), V-max (m/s), EFI (%), efficiency % from BL to 12M following biologic therapy and a significant increase in both F-max (kN), and P-max (kW) at 12M. Despite the fact that the increase in efficiency % of the movement was not significant but however, the change was likely to be through improvements in jump height and velocity thereby indicating higher muscular flexibility. These data are suggestive of an effect of biologic therapy on lower limb muscle function through improvements in the mechanical efficiency of the muscle.

Introduction Obesity is the most common nutritional disorder in the world and is widely acknowledged as having become a global epidemic.(1) The prevalence of childhood obesity in the United Kingdom (UK) dramatically increased over a short number of years in the 1990s.(2-4) There are well-recognised health consequences of childhood obesity, both during childhood as well as those tracking into adulthood affecting health, psychological and economical welfare.(5;6) However, there is a surprising lack of well conducted published research into effective childhood obesity treatment strategies and few with relevance to the UK National Health Service (NHS).(5;7) This thesis describes (a) the Scottish Childhood Obesity Treatment Trial (SCOTT), a randomised controlled trial (RCT) that compared standard NHS dietetic management of childhood obesity with a novel intensive dietetic approach in Scottish primary school aged (5 – 11 years old) children and (b) reports a complementary qualitative study that explored the parents’ perceptions of the dietetic treatments their child received during the SCOTT project. The SCOTT project was conceived to be an easily reproducible treatment programme within the UK NHS system for primary school aged children. Methodology The SCOTT quantitative study was a single-blind RCT involving 134 obese children of primary school age (5 -11 years), 75 females and 59 males. Inclusion criteria were children with ‘simple’ obesity (body mass index (BMI)  98th centile on the UK 1990 charts) and families that perceived the child’s weight as a problem and were motivated to change. The intervention arm involved an evidence-based novel dietetic treatment over 6-months giving 5 hours of treatment and used client-centred behavioural change techniques to increase motivation for changing diet (using a modified traffic light diet), increasing physical activity and reducing sedentary behaviour. The control arm received 1.5 hours of ‘typical’ dietetic weight management delivered in a traditional (educational) manner. Outcomes recorded at baseline, six and 12 months were BMI standard deviation (SD) score, objectively measured physical activity and sedentary behaviour (using accelerometers) and possible adverse effects of treatment (height growth and quality of life). The primary outcome was change in BMI SD score at six months. The complementary qualitative study used in-depth interviews to explore the thoughts and feeling of parents of the children who had completed the dietetic intervention. All interviews took place after the SCOTT 12 month outcome measurements had been completed. Purposive sampling was used and out of the 79 eligible SCOTT parents 17 were interviewed. The interviews were taped and then transcribed by experienced secretaries. Analysis was carried out using the Framework methodology (8) and aided by Nvivo software. Key Results The novel treatment programme had no significant effect relative to the standard dietetic care on BMI SD score from baseline to six months (-0.10 vs -0.06; 95% CI -0.05 to 0.11) and 12 months (-0.07 vs -0.19; 95% CI -0.17 to 0.07). BMI SD score decreased significantly within both groups from baseline to six and 12 months. There were significant differences between the groups in favour of the novel treatment group for changes in total percentage of time spent in physical activity (95%CI 0.8 to 6.3) and light intensity physical activity (95%CI -4.8 to -0.5). In the qualitative study we found themes and concepts both on our original evaluation and emergent data on the parents’ thoughts and feelings on entering, continuing and leaving treatment. Those parents who had taken part in the behavioural change techniques applauded the process finding it child-friendly and talked of ‘forming a partnership’ with the child and dietitian. Developing a rapport with the dietitian was significant for the parents in their perception of a positive experience. Parents appeared to be characterised as being unaware of their child’s weight problem, in denial, or actively seeking treatment. Parents were consistently motivated to enter treatment due to perceived benefits to their child’s self esteem or quality of life, and weight outcomes were considered less important. During treatment parents expressed a lack of support for lifestyle changes outside the clinic, and noted that members of the extended family often undermined changes. Parents generally felt that treatment should have continued beyond six months, and that it had provided benefits to their child’s well-being, self-esteem, and quality of life, and this is what motivated many of them to remain engaged with treatment. Conclusions The modest magnitude of the benefits observed in the SCOTT study perhap suggest that interventions should be longer term and more intense. The results of the qualitative study suggested that longer term interventions would be acceptable to parents. The qualitative study was an informative addition to the SCOTT quantitative study as it allowed exploration of the subtle differences as perceived by the parents who took part in both arms of the study. It may help inform future treatments for childhood obesity by providing insights into the aspects of treatment and approaches applauded by parents. Future treatments may need to consider providing greater support to lifestyle changes within the extended family, and may need to focus more on psychosocial outcomes. This study highlighted skills and qualities required by dietitians and other health professionals to engage with families of obese children.

Introduction: Insulin Pump Therapy has gained worldwide acceptance for the treatment of Type 1 diabetes mellitus (T1D), offering a new method of insulin delivery, which circumvents the need for Multiple Daily Injections (MDI). It is thought to improve quality of life (QoL) by facilitating an increase in lifestyle flexibility, independence and glycaemic control (Scottish Intercollegiate Guidelines Network, 2010; National Institute for Clinical Excellence, 2008). These benefits have resulted in the National Health Service (NHS) Scotland pledging funding of at least £1million to deliver insulin pumps to under 18s (Scottish Government, 2012). Currently, investigations regarding the impact of Insulin Pump Therapy on QoL have resulted in conflicting findings (Barnard et al., 2007). This study aims to explore the impact of Insulin Pump Therapy on the QoL of children and adolescents, using Interpretative Phenomenological Analysis. Method: Eight participants with T1D, aged between 8 and 13 years and using an insulin pump, were recruited from the Glasgow Royal Hospital for Sick Children Diabetes Clinic. Each participant completed an in-depth interview, which explored their beliefs and attitudes towards Insulin Pump Therapy including its impact on their QoL. Results: Analysis of the transcripts led to the identification of six super-ordinate themes: ‘Physical Impact’, ‘Mood and Behaviour’, ‘Lifestyle Flexibility’, ‘Practicalities’, ‘Peer Reactions’, and ‘Support’. It is suggested that these six factors are not mutually exclusive and together inform the complexity of individuals’ experiences and the impact that the insulin pump has had on many aspects of their lives. These findings suggest a framework to help clinicians understand how young people with T1D perceive and conceptualise their treatment regimes. Conclusions: There was general agreement amongst participants that switching to Insulin Pump Therapy resulted in improvements to their QoL. Additional concerns were outlined but reportedly none of the participants regretted switching to an insulin pump.

The present study of all cases of substantiated child sexual abuse received by a local social service agency in 1981 examined (a) the relationship of early contact between perpetrator and victim to such mitigating factors as attachment and intergenerational boundaries (b) the impact of the incest taboo on the severity of abuse and (c) a variety of descriptive variables to identify various characteristics of incestuous families and the services they recieve. Chi square analyses failed to identify differences between groups in the severity of sexual abuse. However, the sample was not similar to those reported in the literature--containing a high percentage of unemployment, prior marriages, criminal history and prior referrals for child abuse, suggesting that this sample of perpetrators did differ significantly from the general population and from the populations which have been reported in other studies.

No description available.

Trafficking in persons in general and in children in particular is a phenomenon that affects each and every country in the world. No African country is immune from trafficking, the quasi-totality of them are simultaneously countries of origin, transit and destination of trafficked children. They are trafficked internally or trans-nationally for all types of exploitations, such as sexual exploitation, labour exploitation, and removal of body parts. In spite ofjoint efforts by the international community to eradicate trafficking in children, research reveals that this modem form of slavery is a phenomenon on the rise instead of decreasing. The situation is more alarming on the African continent where most countries have not yet found appropriate solutions to the problem. Child trafficking is fought through prevention and criminalization. The former entails measures such as awareness raising and the alleviation of factors that make children vulnerable to trafficking and the demand that fosters all forms of exploitation of children. Criminalization measures tress the enactment of comprehensive anti-trafficking legislation, investigation and prosecution of traffickers and protection of child victims of trafficking. This dissertation evaluates the best solutions to prevent and eradicate child trafficking. It seeks to recommend practices which are effective for African countries by taking into consideration the continent's realities, such as resource limitations and underdevelopment. / Thesis (LL.M.)-University of KwaZulu-Natal, Durban, 2009.

In chapter 1, bone structure, bone growth and development, osteoporosis in children and skeletal morbidities in children with acute lymphoblastic leukaemia (ALL) are discussed. After that, the mechanostat and the effect of whole body vibration (WBV) on bone health are considered. Finally, I examine diagnostic approaches to assess the musculoskeletal system. In chapter 2, the incidence and risk factors for skeletal morbidity in ALL children are determined. The medical records of all (n,186, male,110) children presenting with ALL between 1997 and 2007 and treated on UKALL97, UKALL97/01 or UKALL2003 were studied. Skeletal morbidity included musculoskeletal pain (MSP), fractures and osteonecrosis (ON). MSP was classified as any event of limb pain, muscle pain, joint symptoms or back pain that required radiological examination. Fractures and ON were confirmed by X-rays and MRI respectively. We found that skeletal morbidity, presenting as MSP, fractures or ON were reported in 88(47%) children of whom 56(63%) were boys. Of 88 children, 49(55%), 27(30%) and 18(20%) had MSP, fracture(s) or ON, respectively. Six (7%) had both fractures and ON. The median(10th,90thcentiles) age at diagnosis of ALL children without skeletal morbidity was 3.9years(1.4,12), which was lower than in those with skeletal morbidity at 8.2years(2.2,14.3) (p<0.00001,95%CI:1.7,4.4). Children with ALL diagnosed over 8years of age were at increased risk of developing fracture(s) (p=0.01,odds ratio(OR)=2.9,95%CI:1.3,6.5), whereas the risk of ON was higher in those who were diagnosed after 9years of age (p<0.0001,OR=15,95%CI:4.1,54.4). There was no gender-difference in the incidence of skeletal morbidity. Children who received dexamethasone had a higher incidence of skeletal morbidity than those who were treated with prednisolone (p=0.027,OR=2.6,95%CI:1.1,5.9). We concluded that the occurrence of skeletal morbidity in ALL children may be influenced by age and the type of glucocorticoids (GCs). These findings may facilitate the development of effective bone protective intervention. In chapter 3, the aim is to investigate the influence of physical activity, age and mineral homeostasis over the first 12months of chemotherapy on subsequent skeletal morbidity. We reviewed 56 children who presented with ALL between 2003 and 2007 and treated only on iv UKALL2003. The number of in-patient days over the first 12months of chemotherapy was collected and used as a surrogate marker of inactivity and lack of well-being. Data for serum calcium (Ca), phosphate (Pho), magnesium (Mg) and albumin were also collected over this period. Skeletal morbidity was defined as any episode MSP or fractures. We found that the median duration of in-patient days over the first 12months of treatment in children with no skeletal morbidity was 58days(40,100), whereas the median number of in-patient days during the first 12months in those children with any skeletal morbidity, MSP only or fractures only was 83days(54,131), 81days(52,119) and 91days(59,158), respectively (p=0.003). Children with skeletal morbidity and fractures particularly had lower levels of serum Ca, Mg and Pho compared with those without skeletal morbidity over the first 12 months of chemotherapy. There was a higher risk of skeletal morbidity in those who were diagnosed after the age of 8years (p=0.001,OR=16,CI:3,80). Multiple regression analysis showed that the incidence of skeletal morbidity only had a significant independent association with age at diagnosis (p=0.001) and the number of inpatient days (p=0.03) over the first 12months (r=23). All children who were diagnosed after the age of 8years with an inpatient stay of greater than 75 days in the first 12 months of the chemotherapy (n,14) had some form of skeletal morbidity (OR=64). The conclusion was that the incidence of skeletal morbidity in children receiving chemotherapy for UKALL2003 is associated with a higher likelihood of being older and having longer periods of inpatient stay. The close link between age and changes in bone mineral status may be one explanation for the increased bone morbidity in ALL children In chapter 4, the effects of two WBV regimens on endocrine status, muscle function and markers of bone turnover are compared. We recruited 10adult men with a median age of 33years(29,49), who were randomly assigned to stand on the Galileo platform (GP) (frequency (f)=18-22Hz, peak to peak displacement (D)=4mm, peak acceleration (apeak) =2.6-3.8g) or Juvent1000 (f=32-37Hz, 0.085mm,0.3g) platform (JP) three times/week for a period of eight weeks. The measurements were performed at five time points (T0, T1, T2, T3, T4) and performed in a four week period of run-in (No WBV), eight weeks of WBV and a four-week period of washout (No WBV). The measurements included anthropometries, body composition measured by Tanita, muscle function measured by Leonardo mechanography and biochemical markers of endocrine status and bone turnover. The immediate term effect of WBV at 22Hz was associated with an increase in serum growth hormone (GH), increasing v from 0.07μg/l(0.04,0.69) to 0.52μg/l(0.06,2.4) (p=0.06),0.63μg/l(0.1,1.18)(p=0.03) ,0.21μg/l (0.07,0.65) (p=0.2) at 5minutes, 20minutes and 60minutes after WBV, respectively in the GP group. The immediate term effect of GP at 18Hz was associated with a reduction in serum cortisol from 316nmol/l (247,442) at 60minutes pre-WBV to 173nmol/l(123,245)(p=0.01), 165nmol/l(139,276)(p=0.02) and 198nmol/l(106,294)(p=0.04) at 5minutes, 20minutes and 60minutes post-WBV, respectively. At 22 Hz, GP was associated with a reduction in serum cortisol from 269nmol/l(115,323) at 60minutes before WBV to 214nmol/l(139,394)(p=0.5), 200nmol/l(125,337)(p=0.08) and 181nmol/l(104,306)(p=0.04) at 5minutes, 20minutes and 60minutes post-WBV, respectively. Median serum cortisol decreased after eight weeks of WBV from 333nmol/l(242,445) to 270nmol/l(115,323)(p=0.04). Median serum of the carboxy-terminal telopeptide (CTX, bore resorption marker) reduced significantly after eight weeks of WBV from 0.42ng/ml(0.29,0.90) to 0.29ng/ml(0.18,0.44)(p=0.03). None of these changes were observed in the JP group. Therefore, WBV at a certain magnitude can stimulate GH secretion, reduce circulating cortisol and reduce bone resorption. These effects are independent of clear changes in muscle function and depend on the type of WBV that is administered. In chapter 5, the effect of WBV using GP on the bone health of children receiving chemotherapy for ALL was assessed. We recruited 16children with ALL with a median age of 7.8years(5-13.8; 9males), who were randomized either to receive side-alternating WBV (f=16-20Hz,D=2mm, apeak =1-1.6g)(n,9) or to stand on a still platform as a control group (n,7) for 9minutes, once/week for four months. Measurements were performed at baseline, two-month and four-month assessing bone health (DXA and p.QCT), body composition and muscle function by imaging and biochemical assessment. DXA BMC data were corrected for bone area and presented as BMC z-score. We found that the median compliance rate measured as a ratio of actual completed minutes and expected minutes of WBV was 55%(17,100). The median percentage change of total body BMC z score in the WBV group from baseline to four months dropped by 10%(-25,10)(p=0.1), whereas it was 87%(-203,4)(p=0.07) in the control group. The median lumbar spine BMC z-score (L2-L4) in the WBV group was -0.4(-1.3,0.3) and -0.3(-1.4,1.5) at baseline and four months, whereas the respective data in the control group were 0.04(-0.6,2.4) and -0.1(-1.1,1), respectively. The median percentage change in LS-BMC z-score declined from baseline to four-month by19%(-349,365)(p=0.1) vi and 75%(-1016,178)(p=0.1) in the WBV and control groups, respectively. We concluded that WBV is tolerated by children receiving chemotherapy.

Participation in physical activity (PA) of at least moderate intensity may yield important health benefits for children. A popular behavioural tool used to promote increased PA is the pedometer. There is however limited evidence regarding pedometer-based strategies in children. This thesis reports on a series of anthropometric and accelerometer-measurement issue studies which inform the methods used to address the primary aim of this thesis- to determine the effectiveness of goal-setting, selfmonitoring and step-feedback pedometer-based interventions for increasing PA in 10- 11-year-old children. In addition, each study in their own right provides an original contribution to knowledge within their specific area of scholarship. The first objective of this thesis was therefore to determine diurnal variation of height and weight and the combined effect upon body mass index (BMI) weight status in children via a field based study. Next, the reliability of the Actiwatch 4 (AW4) accelerometer was tested in a mechanical laboratory experiment. Following this laboratory trial a second field based study examined the impact of placement site upon AW4 output, and the validity of a regression equation to predict hip-derived AW4 data from wrist-derived data. Finally, a brief intervention mapping approach was used to develop goal-setting, selfmonitoring and step-feedback pedometer-based interventions, the effectiveness of which was evaluated in a small scale controlled trial involving two primary schools. The main findings of this thesis were a) that diurnal variation in height (and in girls alone, weight) impact upon increased BMI and BMI percentile in afternoon versus morning measurements b) AW4 activity counts exhibit acceptable reliability statistics (comparable to other accelerometer models), which improve when raw activity counts are reduced into derived activity intensity variables c) wrist and hip derived AW4 data are not comparable, and the derived regression equation may not be suitable for group level prediction due to inaccurate individual level prediction and the large standard error of the estimate observed d) pilot testing pedometer wear and intervention materials may highlight practical pedometer issues (i.e. pedometer attachment, wearing compliance and acceptability of instruction sheets) that inform intervention implementation and e) pedometer-based goal-setting, self-monitoring and step-feedback interventions did not increase PA in 10-11-year-old children. However, individual-standardised goal setting may be more promising as this appeared to mitigate any decline in moderate-to-vigorous physical activity (MVPA) in moreactive children, and increased MVPA in less-active. To summarise, the findings of this thesis highlight important issues for physical activity scientists to consider when using BMI-determined weight status as a grouping variable and accelerometers as an outcome measure, when evaluating physical activity interventions in children. With regard to the primary aim of this thesis, future researchers should further examine the effectiveness of the individual-standardised against the group-standardised goal type in a longer-duration intervention and using a larger sample of children, which may permit sub-group analyses to be conducted. Of primary importance is future clarification on the effectiveness of goal setting, self-monitoring and step-feedback pedometer-based interventions per se for changing PA in children.

Most mutations in SCN1A-related epilepsies are novel and when an infant presents with febrile seizures (FS) it is uncertain if they will have simple FS, FS+ or develop a severe epilepsy such as Dravet Syndrome. The main aim of this work has been to translate specific genetic findings in SCN1A related epilepsies not only to the phenotype, but to examine the implications this has on treatment and quality of life in children and their families. Clinical and genetic data were collected from 273 individuals with SCN1A mutations identified in our laboratory between November 2005 and February 2010. I examined whether the mutation class, distribution or nature of amino acid substitution correlated with the epilepsy phenotype, using the Grantham Score (GS) as a measure of physicochemical difference between amino acids. From structured referral data I analysed a range of clinical characteristics including epilepsy phenotype, seizure precipitants, EEG data, imaging studies, mutation class and response to medication and determined predictors of developmental outcome. I developed novel ideas on how to characterise mutations in SCN1A related epilepsies, showing that phenotypes are not determined by chance, but are in part determined by defined physico-chemical changes affecting a specific location in the protein structure. I was able to demonstrate that these principles not only apply to the SCN1A gene but also to the wider voltage gated sodium channel family and related diseases. This study has been the largest to date to systematically examine the prognostic, clinical and demographic features of Dravet syndrome. The overall incidence of Dravet syndrome was found to be at least one in every 28,600 UK births. Clinical features predicting a worse developmental outcome included status epilepticus, interictal EEG abnormalities in the first year of life and a motor disorder. No significant effect was seen for seizure precipitants, MRI abnormalities or mutation class (truncating vs. missense). Sodium valproate, benzodiazepines and topiramate were reported the most helpful medications and aggravation of seizures was reported for carbamazepine and lamotrigine. Health related quality of life (HRQOL) has emerged as a widely accepted measure to evaluate how chronic disease impacts on an individual’s well-being and I examined in detail the comorbidities and predictors of health related quality of life in Dravet syndrome. HRQOL was evaluated with two epilepsy-specific instruments, the Impact of Pediatric Epilepsy Scale (IPES) and the Epilepsy & Learning Disabilities Quality of Life Questionnaire (ELDQOL), a generic HRQOL instrument the Pediatric Quality of Life Inventory (PedsQL) and a behavioural screening tool, the Strength and Difficulties Questionnaire (SDQ). 163 individuals with Dravet syndrome and their families participated in the questionnaire study. HRQOL was significantly lower for children with Dravet syndrome compared to normative data. One third of children had conduct problems and two thirds had hyperactive or inattentive behaviour. Regression analysis revealed that behavioural problems were the strongest predictors of poorer HRQOL. Identification of specific comorbidities will help us to better recognise and understand the needs of children and families with Dravet syndrome and facilitate a distinct multi-disciplinary approach to management. Genetic testing in the epilepsies has become an increasingly accessible clinical tool and this is the first study to assess the impact of SCN1A testing on patient management from both carer and physician perspectives. The vast majority of parents whose children tested positive for a mutation reported genetic testing helpful, leading to treatment changes resulting in fewer seizures, and improved access to therapies and respite care. Nearly half of the physicians reported that a positive test facilitated diagnosis earlier than with clinical and EEG data alone. In two thirds it prevented additional investigations and altered the treatment approach; it influenced medication choice in three quarters of cases and through medication change improved seizure control in forty percent. In addition to confirming a clinical diagnosis, a positive SCN1A test enabled early diagnosis, influenced treatment choice and facilitated improvements in clinical management, especially in the very young. Finally I hope that this work will contribute to a better understanding of the causes of SCN1A related epilepsies. Furthermore I hope that it will provide evidence to aid earlier diagnosis and treatment of children with severe infantile epilepsies and that it will offer more information for genetic counselling. These improvements in epilepsy care and seizure control could help prevent or reduce the disability associated with SCN1A related epilepsies such as learning and behaviour problems and would improve the quality of life for children and families.