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Body composition in childhood obesityHaroun, Dalia January 2008 (has links)
Childhood obesity has been increasing rapidly. Previous work investigating body composition in obese children and adolescents has relied primarily on body mass index (BMI), or on measures that assume constant properties of fat-free mass (FFM). This limits our understanding of the effect of treatment. My PhD is divided into three aims. First, I explored differences in body composition between obese and non-obese children using multi-component models. Second, I investigated the effectiveness of two weight-loss programmes (a randomised controlled trial adopting the traffic-light program (TLP), and a pilot study evaluating treatment using Metformin). Third, I evaluated a bio-electrical impedance analysis (BIA) machine (TANITA BC-418 MA) as a clinical tool for assessing body composition in obese children.;Aim 1: obese children had greater hydration of FFM this limits the accuracy of using techniques that assume constant FFM properties. Taking this into account, obese children had increased fat mass (FM) and FFM, particularly FM in the abdomen region.;Aim 2: analyses from the TLP revealed that treatment and control groups significantly lost 0.1 BMI SDS during the trial but did not significantly differ for any of the body composition outcomes. A further analysis revealed that there was a significant reduction in BMI SDS and FM but an increase in FFM in the period when obese children were treated versus an increase in BMI SDS and FM in the period when they were left. Results from the Metformin programme revealed no significant change in body composition following 6 months or 1 year treatment.;Aim 3: Using a manufacturer's equations, TANITA was not accurate at assessing body composition or its change over time. My new equations had no systematic bias in relation to body fatness, although an error of the FFM estimate of 2.2 kg, and may be used to guide management in clinical practice.
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Biological and environmental factors associated with the stress response in infancy : the role of attachment and geneticsFrigerio, Alessandra January 2008 (has links)
The importance of understanding which environmental and biological factors are involved in determining individual differences in physiological response to stress is widely recognized, as the impact of stress on physical and mental health cannot be ignored. Many researchers believe that our ability to cope with stress originates in infancy through the interaction between our experiences and genes. Several studies have shown how attachment relationships as well as some temperamental traits play a significant role in modulating Hypothalamic Pituitary Adrenal (HPA) axis reactivity to the stress of separation from the mother, as indexed by salivary Cortisol. However, no published studies have investigated their effects on Sympathetic Adreno Medulla (SAM) system reactivity, as indexed by salivary alpha amylase which was recently found to be a marker of SAM activity. Moreover, the contribution of genetics in predicting salivary Cortisol and alpha amylase response to stress in infants has not been investigated yet. In the present study, the child-mother attachment relationship, some genetic polymorphisms (DRD4, DRD4/521, COMT and 5-HTT), and temperamental traits were tested as predictors of both physiological markers during the Strange Situation (SS) procedure in an Italian sample of around 70 healthy infants aged 12 to 18 months. HPA and SAM activity was predicted by a larger number of gene x environment interactions in comparison with the number of separate constitutional (genes and temperament) and environmental (attachment patterns) factors. These results help to disentangle the role played by both biological and environmental factors in determining individual differences in stress response in infancy. The results also shed light on the suggestion that HPA and SAM systems are likely to have different characteristic responses to stress and associations with behaviour.
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How was it for me? : a grounded theory exploration of growing up with attention deficit hyperactivity disorderRoss-Gillies, E. A. January 2005 (has links)
Attention Deficit Hyperactivity Disorder (ADHD) has been one of the most comprehensively studied of all childhood psychiatric conditions. However, most research has focussed on aetiology, diagnostic criteria, or treatment efficacy, and in such research the voices of adult professionals dominate, while the voices of the children remain silent. There has been little research into the everyday lived experiences of children diagnosed with ADHD. The present research is a grounded theory study, of the experiences of nine young adults (aged 14 - 18 yrs. ) previously diagnosed and treated for ADHD. The aims of the study were to explore the experiences of adolescents diagnosed with ADHD, and to understand how personal meaning-making within the context of receiving diagnosis and treatment influenced beliefs about themselves and the world. Analysis of the adolescent's narratives revealed three themes. Firstly `Exclusion', which occurred in relation to friendships and teacher relationships. Secondly `Identity Conflict, ' which described the conflict experienced between three possible perceptions of self as either `normal', `ill' or `weird'. The third theme `Overcoming' details the strategies adopted by adolescents for resolving exclusion and supporting their desired perception of a `normal' self. The study concludes that regardless of aetiology, the felt experience of growing up with ADHD is not one of managing a medical condition, but of striving to overcome social difficulties and engage in normative adolescent developmental tasks
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The effect of bone morphogenetic protein 4 on haematopoietic stem cellsAbeyewickreme, A. January 2009 (has links)
Bone morphogenetic protein-4 (BMP4) is highly expressed at sites of haematopoietic stem cell (HSC) formation. During HSC formation in humans, BMP4 is strongly expressed by cells underlying the ventral floor of the dorsal aorta. BMP4 in combination with other factors has been shown to play a role in haematopoietic differentiation. The genes Runx1, Scl, Gata2 and Lmo2 are vital to the development of the haematopoietic system, and deletion of these genes produces an embryonic lethal phenotype due to the absence of blood formation. This study investigated whether BMP4 alone upregulates the expression of these genes. The role of BMP4 was explored during HSC development in an embryonic stem (ES) cell differentiation model and at later developmental stages using ex vivo foetal liver and bone marrow serum free cultures. Differentiating ES cells cultured in serum-free medium were found to express BMP4 and the BMP receptor endogenously. To establish a model for exogenous BMP4 addition in isolation, lentiviral vectors were used to deliver short hairpin RNA (shRNA) for sustained RNAi knockdown of endogenous Bmp4 expression during ES cell differentiation. Differentiating shRNA treated ES cells were cultured and the expression of Runx1, Scl, Gata2 and Lmo2 was measured over time by real time reverse transcription PCR. With the addition of exogenous BMP4 alone, expression of Runx1, Scl, Gata2 and Lmo2 was unchanged at days 2 and 4 but increased at day 6 of differentiation. This demonstrates that BMP4 up regulates the expression of these genes which are critical to the development of the haematopoietic system. The use of lentiviral shRNA knockdown provides a model for the control of endogenous growth factors in future investigations of growth factors in ES cell differentiation.
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Laparoscopy in children : physiology and outcomePacilli, M. January 2011 (has links)
Background: Nowadays, in paediatric surgery, intra-abdominal procedures are commonly performed with a laparoscopic approach. Nevertheless, the effects and advantages of laparoscopy in children have not been extensively investigated. Aims of this thesis are: 1) To quantify the absorption of carbon dioxide (C02) during laparoscopy; 2) To investigate if laparoscopy provides benefits compared to open surgery in the management of common surgical conditions in children. Methods: The thesis includes two parts: one part focuses on the absorption of C02 during laparoscopy. The second part focuses on the outcome of laparoscopy. Data were obtained by investigating two common surgical procedures: the Nissen fundoplication for treatment of gastro-oesophageal reflux (GOR) and the Ramstedt pyloromyotomy for treatment of pyloric stenosis. For the laparoscopic Nissen fundoplication, a follow-up study on a randomised controlled trial (RCT) including 38 children was performed. Also, a large review on patients who underwent a second operation (redo-Nissen fundoplication) for recurrent GOR was performed. For the laparoscopic pyloromyotomy, a double blind, multicentre, international, RCT was performed enrolling 180 children. Results: the work in this thesis demonstrates that 10-20% of C02 eliminated during laparoscopy in children is derived from the absorption through the peritoneum. The results of the RCT comparing laparoscopic and open Nissen fundoplication shows that this antireflux procedure improves the quality of life and controls GOR independently of the technique used. The laparoscopic technique is associated with an improvement of gastric emptying in the post-operative period and lower incidence of retching at 4-year follow-up. In children requiring redo-Nissen fundoplication, there is a high failure rate and redo-fundoplication after primary laparoscopic Nissen has lower risk of failure. The RCT comparing laparoscopic with open pyloromyotomy reveals that both procedures are successful. The laparoscopic pyloromyotomy provides a shorter post-operative recovery, lower analgesia requirement and higher parental satisfaction.
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Congenital muscular dystrophy in 2010Clement, E. January 2011 (has links)
Congenital Muscular Dystrophies (CMDs) are a heterogeneous group of conditions that usually present in the first months of life with weakness and hypotonia. Extramuscular manifestations are common and may include brain, skin and eye abnormalities. CMDs are relatively rare disorders and despite the major progress made over the last 2 decades in identifying, mapping and investigating these conditions, there remains a lot to be learned. Little is known about the relative frequency of the various forms of CMD in the UK population. Experience had shown that founder mutations are common in different ethnic populations and epidemiological studies performed in other countries are of limited value in this regard. Since 2001, the Dubowitz Neuromuscular Centre (DNC) has been the National Commissioning Group UK Centre for CMD. As such we are in the privileged position to have access to a large number of UK patients with CMD. I analysed a cohort of 214 CMD referrals to the DNC between 2001 and 2008 with a view to reporting the diagnostic outcome and the frequency of the various forms of CMD encountered in our patient population. The second part of the thesis is concerned with the dystroglycanopathies, a recently described group of CMDs associated with aberrant glycosylation of alpha dystroglycan. To date, 7 genes have been identified, some of which give rise to multiple dystroglycanopathy phenotypes. I studied the genotype-phenotype relationship in a large group of dystroglycanopathy patients, reporting new clinical phenotypes and establishing the mutation frequency in this group. I also report in detail the spectrum of MRI brain changes seen in 27 dystroglycanopathy patients. In summary, this work reports the diagnostic outcome in the largest cohort of UK CMD cases studied and refines the genotype-phenotype correlation in patients with dystroglycanopathies.
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Diffusion imaging and tractography in the paediatric neurosurgical populationBull, J. G. January 2011 (has links)
Diffusion MRI uses magnetic field gradients to sensitise a MR sequence to in vivo water diffusion. Application of these gradients in specific directions (20 in this work) enables a 3D representation of diffusion on a voxel basis. Quantitative diffusion measures are derived; using the voxel maximal diffusion direction and linking neighbouring voxels iteratively based on this creates a visual construct of the white matter: tractography. It is not possible, currently, to non-invasively determine the histological nature of an intracranial tumour. We recruited paediatric patients with radiological evidence of such lesions from April 2006 to January 2008 and retrospectively to August 2003. We used diffusion MR metrics to discriminate paediatric central nervous system tumours based on existing histological diagnoses. Using apparent diffusion coefficient histograms, common posterior fossa childhood tumours were differentiated with 93% success; Primitive neuroectodermal tumours (PNET) and supratentorial atypical teratoid rhabdoid tumours (ATRT) were separated in 100% of cases. Development of these methods with a larger population may facilitate the obviation of surgical biopsy and its attendant risks. Diffusion data was used to reconstruct the cerebellar white matter anatomy using tractography. Initially a population of normal subjects were investigated using single region of interest (ROI) analysis. DTI metrics were implemented, demonstrating the existence of white matter asymmetry where lateralisation corresponded to handedness in 17 right-handed subjects. To asses functional significance of changes in DTI metrics; clinical cerebellar dysfunction was correlated with changes in cerebellar white matter DTI metrics in a patient population with posterior fossa tumours and with the normal population. Fractional anisotropy of the tracts was reduced in patients with tumours d clinical cerebellar signs as compared to healthy individuals. This work demonstrates that diffusion MRI and tractography metrics may enable discrimination of paediatric CNS tumour type and are related to the functional integrity of cerebellar white matter tracts.
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Attachment in institutionalised and community children in ChinaArcher, M. January 2012 (has links)
INTRODUCTION: This thesis critically applies Attachment Theory concepts and methodology with two large and previously understudied populations: family and institutionally reared infants in Mainland China. METHOD: Study 1, assessing 61 infants (aged 12-38 months, mean = 21) with their mothers, provides both an exploration/validation of the Strange Situation Procedure (SSP) in a Chinese cultural context and a community comparison group for Study 2, which assesses 78 infants (12-37 months, mean = 20) with caregivers in institutional care. The institutionalised sample includes 4 different units with differing qualities of care, across 3 cities. RESULTS: Study 1. As predicted, upon the basis of previous findings, the majority (57%) of infants assessed with their mothers demonstrated secure attachment patterns, and only 13% were found to be disorganised. Study 2. For the entire institutionalised sample, prevalence of secure attachments was extremely low (average 17%, range = 8-50% across Units) and disorganised classifications extremely high (average 50%, range = 42-70% across Units), consistent with similar studies in other countries. Whilst among family-reared infants insecure-avoidant attachments were low by comparison to Western norms, they were markedly high among institutionally-reared infants compared to previous studies. Neither caregiver-to-infant ratio nor the provision of a dedicated caregiver was significantly associated with attachment classification. Only the unanticipated variable of previous placement in a foster care family was significantly associated with organised, but not secure, attachment. DISCUSSION: The findings provide support for the utilisation of Attachment Theory within these settings, whilst suggesting the need for both conceptual and methodological adaptation. Overall, the findings confirm that resources should be channelled into enhancing caregiving across institutions where they are necessary – increasing the valuation, training, and benefits to caregivers which is likely to enhance their role and retention – whilst reducing exposure to high numbers of transient caregivers, minimizing transitions, and moving toward early and stable family-based care wherever possible.
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Characterisation of lentiviral transgene expression in muscle precursor cells : towards a potential therapy for Duchenne Muscular DystrophyJonuschies, J. January 2012 (has links)
Duchenne Muscular Dystrophy is an X-linked genetic disorder characterised by progressive muscle degeneration due to the absence of functional dystrophin protein. Damaged muscle fibres are initially regenerated by satellite cells, the principal muscle-resident stem cells, which give rise to committed progenitor cells that differentiate and fuse with the damaged muscle fibre to introduce new functional myonuclei. Satellite cells also self-renew to replenish the stem cell pool. Autologous transplantation of genetically-corrected satellite cells presents an attractive strategy to introduce a functional dystrophin copy into dystrophic muscles and to replenish the stem cell pool with corrected satellite cells for a long-term therapeutic benefit. Lentiviral vectors are suitable gene transfer vectors that integrate their genome into the host chromosome and mediate stable transgene expression in dividing and non-dividing cells. Long-term gene expression can be hampered by promoter inactivation and undesirable position effects. Tissue-specific promoters have been shown to reduce the risk of transcriptional silencing and to increase the overall biosafety of transgene expression. In this study, I investigated the potential of integrating lentiviral vectors to efficiently infect quiescent satellite cells in order to confer stable expression of GFP in vitro and in vivo. The effect of viral transduction and GFP overexpression on stem cell properties was assessed. The performance of tissue-specific promoters was directly compared with the strong viral promoter of the spleen focus-forming virus and revealed the desmin promoter as an attractive non-viral alternative to confer stable, high-level, muscle-specific expression in myoblasts and myofibres. An ubiquitously-acting chromatin opening element (UCOE) has been reported to negate position effects in hematopoeitic cells. Here, the UCOE failed to prevent promoter down-regulation and did not significantly increase transgene expression when it was combined with the desmin promoter. In summary, this work provides useful information on suitable promoters to achieve stable transgene expression in the myogenic linage.
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Dentinal ultrastructure in Osteogenesis Imperfecta and Dentinogenesis ImperfectaHarith, N. S. B. January 2013 (has links)
Osteogenesis Imperfecta (OI) associated with Dentinogenesis Imperfecta, type I (DI) is a rare genetic condition, where mutations of COL1A1 and COL1A2 genes result in variations of the collagen α-chains. The collagen fibrils are expected to be abnormally thin. These alterations have been shown to affect the bones, but have not yet been elucidated in the dentinal collagen. Objectives: Evaluation of demineralisation protocols to expose dentinal collagen for permanent and primary teeth and to characterise the morphology of dentinal collagen ultrastructure in primary DI type I using Atomic Force Microscopy (AFM). Methods: Primary (6) and permanent (6) control teeth plus one DI type I primary tooth have been used. To reveal the dentinal collagen structure, four demineralisation approaches have been evaluated: 1) two blocks of dentine were treated with 10 vol% citric acid for 15seconds and 6.5 vol% NaOCLaq for 120s; 2) dentine blocks treated with commercial etchant and 6.5 vol% NaOCLaq. These demineralised dentine were characterized using Raman spectrocopy and AFM ; 3) teeth demineralised in 17% Ethylenediaminetetraacetic acid (EDTA) for 12 months before being histology sectioned and stained with Picrosirius red; and 4) dentine block was treated with 17% EDTA for 10 minutes. Both demineralised samples were characterised using scanning electron microscopy (SEM). Results: All demineralisation protocols achieved partial or complete demineralisation of the dentine. Demineralisation with commercial etchant and NaOCI produced visibly defined collagen fibrils in primary and permanent teeth. A shorter time was sufficient for demineralisation in primary teeth. In OI associated DI primary tooth; AFM images revealed an area of thickened dentinal collagen fibrils that distributed at only one a direction with a wide distribution of D-banding distance, suggesting less regular banding pattern. Conclusion: The difference in dentinal collagen fibril arrangement and D-banding distance in the affected primary tooth may lead explain the altered mineralization.
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