Anxiety in young people with Asperger's syndrome (AS) is of serious concern. With a greater prevalence of girls with AS than previously considered, there is a paucity of research into experiences of anxiety in this population. Girls with AS and their parents may seek help through professional Western Herbal Medicine (WHM), the practice of which has little research evidence. The aim of this study is to explore experiences of girls in Scotland with AS and anxiety during a course of WHM treatment, described by the girls, their mothers and the herbalists. A Hermeneutical or Interpretive Phenomenological longitudinal case-study approach included a purposive sample of 3 girls, their mothers and 3 Western Medical Herbalists (WMH) (n=9). Innovative methods developed to address specific needs of the girls comprised of licensed computer interview software ‘In My Shoes' and an online diary facility. Individual interviews took place with all participants, second interviews held with girls and mothers, were transcribed verbatim and thematic analysis carried out. The study was endorsed by Edinburgh Napier University Faculty of Health, Life and Social Sciences Research Ethic and Governance Committee and the National Autistic Society. Informed consent was given by all participants. Where can we be what we are? was identified as a theme within a narrative of marginalisation in which individuals whose needs are marginalised turn to a treatment marginalised within the prevailing biomedical health care model. Anxiety manifests in girls with AS in a number of ways including chronic insomnia, emotional outbursts and school refusal. The WHM treatment had beneficial effects. However, access to, and compliance with, the treatment, may be inequitable. There is an urgent need for greater support for girls with AS and families, with an evidence base underpinning appropriate intervention. Diagnosis needs to be accompanied by acceptance in society and the availability of future opportunities. Further qualitative research in this area would increase insight and understanding and provide support for the development of larger scale studies. The creation of ‘best practice' guidelines in WHM for the treatment of girls with AS is recommended as is a pragmatic clinical trial of WHM for girls with AS and anxiety. key terms: Girls, Asperger's, anxiety, Western Herbal Medicine, hermeneutic interpretive phenomenology, methods, In My Shoes

Thesis (M.S.)--Boston University

Thesis (M.D.)—Boston University

Thesis (M.D.)—Boston University

INTRODUCTION: The Modified Blalock Taussig (BT) shunt is the most common palliative procedure in neonatal cardiac repair to secure pulmonary blood flow (3-6) despite high mortality and morbidity rates of 4-14% (3,5) and 9-18% (4,5) respectively. The high risk of thrombosis and stenosis associated with the polytetrafluoroethylene (PTFE) material that is currently used for BT shunts significantly contributes to these high mortality and morbidity rates. Thrombosis and stenosis occur in 3-12% of patients (1,5), primarily due to the lack of endothelium of the synthetic PTFE graft. This study hypothesizes that a preserved autologous umbilical vein could be a feasible replacement for the PTFE graft. Experiments were performed to examine and optimize preservation methods of umbilical veins for use as BT shunts. METHODS: Umbilical cords (n=45) were collected from healthy neonates and umbilical vein segments were preserved in either static (n=145) or flow conditions (n=84) for 7 days or 14 days in varying media. Samples of each vein were collected at time of harvest (Day 0) and at the end of culture and compared by burst pressure, histopathology, platelet adhesion and scanning electron microscopy (SEM). RESULTS: Burst pressure strength of veins from Day 0 to up to two weeks of preservation did not significantly differ (431 ± 229 mmHg vs 438 ± 244 mmHg). Overall histology demonstrated an improved morphology in endothelial and medial layers of the segments preserved in flow culture with UW + 5% HPL for 7 days. Platelet adhesion testing demonstrated significantly less platelet attachment in flow samples compared to static, indicating less endothelial injury. SEM showed greater cellular flow-alignment and consistency of the endothelium in flow samples. CONCLUSION: Flow culture utilizing UW plus 5% HPL adequately preserves morphology and function of the endothelium. Preserved autologous umbilical veins stand as a viable option to replace the current PTFE graft used for BT shunts due to the presence of an endothelium.

In order to understand and interact with the world, our brains must integrate information from multiple sensory modalities to create coherent representations of scenes and events. The integration of visual, tactile and proprioceptive inputs underpins the subjective sense of self and body ownership. This, in turn, underlies the development of social processes including self-awareness, imitation and empathising, which are impaired in autism spectrum disorders (ASD). Evidence suggests that the social functioning deficits characterising ASD could contribute to atypical sensory integration underlying body representation. However, the exact mechanisms underlying sensory integration difficulties have not been specified. Moreover, it is not clear when, and how, visual, tactile and proprioceptive integration matures in typical development. This is important to establish, in order to compare how and why this integration may differ in ASD populations. This thesis firstly aimed to investigate the typical development of multisensory integration underlying body representation. Experiment One found that the ability to optimally integrate visual and proprioceptive inputs during hand localisation increases with age from very little integration in 4-year-olds to almost adult-like in typically developing 10- to 11-year-olds. Experiments Two and Three showed that sensitivity to the spatial constraints of visuo-proprioceptive integration, and sensitivity to the temporal constraints of visuo-tactile integration, develops with age in 4 to 11-year-olds. Together these studies suggest that the maturation of adult-like multisensory integration for body representation follows a protracted time course over childhood. The second aim of this thesis was to investigate the evidence for two prominent theories of atypical sensory integration underlying body representation in ASD. These are 1) an over-reliance on proprioception and 2) temporally extended sensory binding. Experiment Four examined whether trypically developing (TD) adults with a high number of autistic traits exhibit an over-reliance on proprioception. No evidence was found for this, which could indicate that atypical sensory integration is only present in individuals with a clinical diagnosis of ASD. Experiments Five and Six found evidence for temporally extended visuo-tactile integration in children with ASD, compared to TD control participants. Though no evidence was found for a fundamental over-reliance on proprioception, extended binding may have led to reduced processing of temporal synchrony over modality-specific information (i.e. proprioception). Experiment Seven and Eight found no evidence of proprioceptive over-reliance or temporally extended sensory binding in adults with ASD, relative to a TD control group. I conclude that children with ASD demonstrate temporally extended visuo-tactile binding. This represents a developmental delay rather than a life-long deficit; however, it could have a life-long impact on sensory sensitivities and social processing.

Infant regulatory problems (crying, sleeping, feeding) are a common concern for parents and practitioners. Although there is now good evidence of the long-term adverse influences of infant regulatory problems on mental health, in particular if they co-occur together (multiple regulatory problems), important gaps remain regarding the precursors of regulatory problems. In particular, it is unclear whether and how sensitive parenting and/or neurodevelopmental vulnerability are involved in the development of multiple regulatory problems. Furthermore, do regulatory problems impair the development of the infants’ relationship to their mothers, i.e. attachment? This thesis explores neurodevelopmental vulnerability and sensitive parenting as precursors of multiple regulatory problems, and whether multiple regulatory problems increase the likelihood of insecure and/or disorganised attachment. The thesis consists of four studies and uses preterm birth as a natural model to assess neurodevelopmental vulnerability due to the interruption caused by preterm birth on the key processes of brain development. Study 1, a meta-analysis, explored the relationship between neurodevelopmental vulnerability and maternal sensitivity by comparing maternal sensitivity in preterm and full-term infants. Findings indicate that having an infant with neurodevelopmental vulnerability does not alter mothers’ sensitive parenting. In Study 2, using the Growth of at risk Infants (GAIN) study, the effect of neurodevelopmental vulnerability on regulatory problems across the first 18 months was investigated. Very preterm/very low birth weight infants experienced more multiple regulatory problems at term and 18 months compared to full-term infants. In Study 3, the longitudinal relationship between neurodevelopmental vulnerability, maternal sensitivity and multiple regulatory problems across infancy was explored allowing for reciprocal associations between maternal sensitivity and multiple regulatory problems across infancy. Both maternal sensitivity and multiple regulatory problems were moderately persistent from term to 18 months. Consistent with our previous findings, it was revealed that neurodevelopmental vulnerability had an enduring impact on multiple regulatory problems. On the other hand, maternal sensitivity at term had only a short-term negative impact on multiple regulatory problems at 3 months. No evidence for a reciprocal influence of maternal sensitivity and multiple regulatory problems was found. Finally, Study 4 examined whether early multiple regulatory problems at 3 and 6 months increase the likelihood of insecure and/or disorganised attachment. Findings revealed that multiple regulatory problems as early as 3 months increased the risk of both insecure and in particular, disorganised attachment at 18 months. In conclusion, neurodevelopmental vulnerability increases the risk of multiple regulatory problems, which are moderately persistent across the first 18 months of life. Furthermore, multiple regulatory problems do not impair maternal sensitivity but have adverse effects on the infants’ relationship with their mothers by increasing the risk of insecure and disorganised attachment. Clinicians should be aware that multiple regulatory problems are a significant potential risk factor for poorer infant-mother relationship.

Raising a child is not easy for any parent, however for those whose child also has a disability, the process is even more complex. The papers presented here explore the experiences of parents who have a child with a disability. From understanding parents’ experiences in more details, it is hoped that support can be tailored to serve the needs of parents better and improve the outcomes for children. Chapter one details a meta-synthesis, reviewing qualitative articles which address the experience of parents’ with a child with congenital heart disease. Twelve overarching themes are presented, capturing parents’ responses, the parent-child attachment and parental resilience. Recommendations are made for how to support parents and areas of development for healthcare professionals are identified. Chapter two details a qualitative study examining the experiences of eight fathers of children with autism. Interpretative Phenomenological Analysis is used to provide an in-depth account of their lived experiences and three superordinate themes are presented. The results identify resilience and challenges fathers experience, both within themselves and within their relationships. Clinical implications and future directions are discussed. Chapter three provides a reflective account of the research process. It addresses the issue of reflexivity, considering how the researcher’s position may have influenced the research and how the process of undertaking the research influenced the researcher.

Developing trust and security with a new primary caregiver may be particularly difficult for children who have experienced trauma, separation and loss within their birth families and through the care system. However, the development of a secure attachment can protect against future psychosocial and emotional difficulties, prevalent in fostered and adopted children. It is important to better understand the influences upon, and experiences of, attachment relationships that develop within this context, in order to inform policy and practice in promoting attachment security within new families. Chapter one is a systematic review of the literature exploring the links between maternal sensitivity, mind-mindedness and attachment security in children who are adopted and fostered. Twelve studies were included in the review following database and manual searches. In line with studies in birth families, maternal sensitivity was shown to have a partial influence on attachment security. Stronger relationships were found in foster care and longitudinal adoption studies. The impact of mind-mindedness may be related to the developmental stage of the child. Methodological limitations are suggested to have limited the strength of findings, and are considered in addition to future research, policy and practice implications. Chapter two is an in-depth exploration of the lived experiences of seven mothers who adopted an older child, aged four to seven. The study focuses upon the experience within the first years after placement of developing mother-child relationships, using an Interpretative Phenomenological Analysis approach. Three overarching themes emerged from the data. These pertained to the sense of fragility experienced within relationships as a consequence of children_ïs rejection and challenging behaviours; mothers_ï commitment to their children; and the process of acceptance. Implications for future research, clinical practice and policy are discussed with particular regard to the need for increased support and training. Chapter three is a reflective account of experience during the research process. The reflexive process is explored, and parallels are drawn between the researcher and the participant ïs experience, and issues of reflexivity as a researcher and clinician. Attention is given to the process of developing acceptance across the journey of research.

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