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Vitamin K acts a cofactor for the gamma-carboxylation of several proteins in the coagulation cascade. The clinical spectrum of vitamin K deficiency (VKD) can be asymptomatic to a significant bleeding. VKD is classically seen in newborns. However, this can manifest later in patients with risks such as sub-optimal nutrition, fat malabsorption, medications including antibiotics. A 17-year-old male with spinal muscular atrophy (SMA) Type 1, tracheostomy with ventilator dependent, gastrostomy tube feeding was seen by the gastroenterologist following treatment for small intestinal bacterial overgrowth (SIBO). Investigations showed coagulopathy following which he was transferred to the Pediatric ICU. Labs revealed prothrombin time (PT) 114 s [Normal 9.4-12.5 s], INR (International normalized ratio) 12.6 [Normal < 1.1] and partial thromboplastin time (PTT) 90 s [Normal 25.1-36.5 s]. Mixing studies and coagulation assays were consistent with VKD (low Factor VII and Factor IX with normal Factor V). His home blenderized feeding regimen met the caloric requirement but not the adequate intake (AI) values for vitamin K and other minerals. He received intravenous vitamin K (phytonadione) for five consecutive days with resolution of the coagulopathy (PT 13.2 s, PTT 37.1 s, INR 1.2). The patient was discharged on enteral vitamin K and additional supplements following dietary review by a nutritionist. Clinicians should be cognizant of VKD in patients on blenderized tube feeds which may not meet the adequate intake (AI) goals. In patients who are not receiving nutritionally complete formulas or receiving inadequate volumes, it is important to monitor macro and micronutrients.

<p>Research statement:</p> <p>To investigate the age specific blood pressure change in South Asian children from childhood to adolescence over a six year period and to determine whether this change of blood pressure varies by baseline characteristics.</p> <p>Rationale:</p> <p>Children exhibit age related incremental changes in blood pressure from birth onwards which reach adult levels during late adolescence. The best way to measure age-related changes in blood pressure from childhood to adolescence is through prospective longitudinal studies.</p> <p>Objectives:</p> <p>to investigate the changes in blood pressure among South Asian children aged 6 to 11 years who were followed for a period of six years.</p> <p>Methods:</p> <p>Blood pressure and anthropometric data were collected from 703 children who were 5 to 11 years of age in 2005 and were re-examined after six years (age range of 11 to 17 years in 2011). Average difference between baseline and follow-up blood pressure measurements was evaluated using the paired t-test. A linear regression model with follow up blood pressure and blood pressure change as outcomes and sex, weight, and height as regressors were fitted to assess whether these predictor variables were associated with the dependent variables.</p> <p>Summary of results:</p> <p>Systolic and diastolic blood pressure increases from childhood to adolescence. Baseline blood pressure appears to be the strongest predictor of follow up blood pressure. Change in body mass index influences blood pressure more than baseline body mass index. Boys showed higher levels of change in systolic blood pressure compared to girls. Age showed an interaction with sex for change in systolic blood pressure. Boys exhibited higher change in systolic blood pressure than girls in older age groups compared to younger age groups.</p> <p>Potential implications:</p> <p>The study findings will increase awareness about high blood pressure in children and lead to preventive strategies to contain the burden of hypertension in future.</p> / Master of Science (MSc)

In the United States, childhood and adolescent obesity is a problem of growing concern. With nearly 17% of children between the ages of two and 19 years classified as obese, healthcare providers, clinical scientists, and program managers must collaborate to reduce the prevalence of obesity. Obese children are more likely to be obese adults, who are at an increased risk to develop type two diabetes and cardiovascular disease, compared to non-obese individuals. Children are classified as obese based on body composition. CDC, WHO, and IOTF have developed definitions to classify the weight status of children; however, these definitions are based on reference populations' data rather than physiological ideal growth and development. Physicians and scientists measure body composition with a variety of direct and indirect techniques. Although there are advantages and disadvantages to each method, there is no database to compare the measurements to determine whether the child has an increased risk for developing a disease based on his or her weight status. While the current literature debates the use of one definition or measurement tool over another, there is a need for longitudinal studies to establish a true definition for obesity and healthy model of child growth and development from birth to adulthood. This review summaries the current arguments and provides suggestions for further research to increase the understanding of obesity in children and adolescents.

Access to the world of men can be closely guarded by non-disabled people and so disabled men can be persuaded to either conform, subvert or attempt to create an alternative masculine hegemony. For boys and men with Intellectual Disability (ID) little is known about their attempts to develop their gendered identities. This study aimed to explore whether boys with ID have ideas of what it means to be a boy, what influenced this and what ideas the boys had about their futures as men. Using an approach based on grounded theory, group and individual interviews were conducted with 21 boys in 7 groups from a special school engaged in plans about transition from school to the adult world. Using innovative methods including a sorting exercise and the boys own artwork, interviews were recorded and then transcribed. Analysis of the data revealed a developing construct of masculine identity established both outside and inside the interview room that could be identified as the way we do boy. The way we do boy is described in four themes: changes; ideals; experiences; vicariousness. Findings demonstrate that the four themes were instrumental in assisting the boys to think about their identities. However, the opportunities to practice their developing masculinity was limited and the boys talked about their struggles when their attempt to do this resulted in the uncovering of their difference and vulnerability. The analysis and discussion of this study develops into an explanatory theoretical framework for working with boys and men with ID about their masculinity. With the addition of Thomas’s (1999) work expressed as lenses, it is hoped this will provide a practical framework for use in services for both boys and men with ID.

Acute lymphoblastic leukaemia (ALL) is the commonest childhood malignancy. Once a universally fatal disease, modern therapy has achieved excellent outcome and the majority of children achieve long term cure. Yet relapse remains a challenge. One of the major hurdles in achieving complete cure is the relapse of ALL at extramedullary sites such as the central nervous system (CNS). Despite significant advances in understanding leukaemia biology, most predictors of leukaemic behaviour are accurate for the bone marrow disease only. The precise timing, frequency and properties of CNS infiltrating leukaemic cells are not elucidated. Therefore, the broad aim of this thesis is to develop a better understanding of the mechanisms of leukaemic entry and infiltration patterns of leukaemic cells in the CNS. In order to address the frequency and pattern of CNS infiltration, a xenograft model using primary leukaemic cells from children with B-cell precursor (BCP) ALL in NOD/Scid IL2Rγ null (NSG) mice was established. The majority of samples from children with and without overt CNS disease were able to infiltrate the CNS in NSG mice. CNS infiltration was seen in mice engrafted with small numbers of cells and distinct immunophenotypic subpopulations. The leukaemic samples followed a distinct and reproducible pattern of CNS infiltration with leukaemic infiltrates in the meninges while sparing the CNS parenchyma. To investigate whether a distinct set of leukocyte trafficking molecules provided tissue specificity for entering the CNS, leukaemic cells retrieved from the bone marrow and the CNS were assessed for expression levels of selected chemokine receptors and P-selectin glycoprotein ligand-1 (PSGL1). Additionally, chemotaxis assays were utilized to investigate the function of the chemokine receptor CXCR4. Despite surface expression of chemokine receptors on leukaemic cells and presence of chemokines in the CNS, no evidence for positive selection of a high-expressing subpopulation was seen. Overall, it appears that, unlike the bone marrow, chemokine receptors do not direct leukaemic cell trafficking to the CNS. To investigate the published observation that interleukin-15 (IL-15) expression in leukaemic samples correlates with the risk of CNS disease, the effects of IL-15 stimulation on BCP-ALL cells were assessed. IL-15 and IL-15 receptor subunits were noted to be expressed at mRNA level in samples from BCP-ALL patient and cell lines. Exogenous IL-15 stimulated leukaemic cell proliferation and upregulated genes associated with migration and invasion in SD1 cells. A higher proliferative advantage was observed at low-serum conditions which mimics conditions found in the CNS. Therefore a plausible mechanistic link was established for the association of CNS disease with high IL-15 expression levels. In cerebrospinal fluid (CSF) samples from patients, quantitative PCR (qPCR) was utilized to detect submicroscopic levels of CNS disease. In approximately 40% patients, qPCR using patient specific primers tested positive for the presence of leukaemic DNA. Therefore this test is much more sensitive than conventional diagnostic techniques which only detect CNS disease in 2-5% of patients. CSF supernatants were also tested to assess whether the levels of chemokines could be used to diagnose patients with qPCR positive disease. Although differences in the levels of chemokines between qPCR positive and negative patients were noted, the values are not sufficiently discriminatory to be clinically useful. In conclusion, CNS entry appears to be a much more frequent property of leukaemic cell than previously appreciated. Leukocyte trafficking molecules do not appear to play an instructive role in the CNS entry and therefore, it is unlikely that expression levels of leukocyte trafficking molecules or the levels of chemokines in the CSF will be useful biomarkers of CNS disease. In addition, CNS disease appears to be present at diagnosis in at least 40% of patients. Therefore, attempts at blocking leukaemic entry into the CNS are unlikely to be therapeutically useful. Instead, analysing and targeting factors that allow long-term survival of leukaemic cells in the CNS may be a better strategy to eradicate CNS disease and prevent leukaemic relapse.

Background Important developments in the research literature exploring extrafamilial victimisation have been made in the USA. However, the comparable literature from the UK is underdeveloped, limiting our understanding of the prevalence and characteristics of extrafamilial victimisation in UK settings. In addition, greater understanding of the risk and protective factors for extrafamilial victimisation is needed to develop the most effective preventative interventions. Objectives/ research questions To address these gaps within the literature, two studies are presented within this thesis; one cross-sectional survey and one systematic literature review. The aims of study one were to provide a comprehensive assessment of all forms of extrafamilial victimisation with an English sample of young people, exploring; the prevalence, characteristics and location of extrafamilial victimisation, associated factors relating to routine activities, and the impact of extrafamilial victimisation on psychological well-being. Study two was designed to synthesise the research findings from longitudinal cohort studies regarding the predictive factors for all forms of extrafamilial victimisation, and to explore the quality of research in this area. This research was carried out within the theoretical context of the routine activities theory (RAT) and ecological systems theory. This provided a coherent structure to aid understanding of the processes involved in extrafamilial victimisation, as well as a way in which the different elements of the young person’s ecology could be brought together to encourage exploration and to interpret the research findings. Study design, participants and setting Study one explores the extrafamilial victim experiences of 730 young people from eight mainstream secondary schools within one county in England. This incorporated one smaller case study of young people (N = 214) attending three secondary schools in one English town. Two pilot studies were carried out with two separate samples of young people (N= 27 & N= 30) in order to test, develop and refine the methods and procedures used in this study. The second study provided a narrative synthesis of the findings of 37 longitudinal (>1 year follow-up) cohort studies which investigated the risk factors for, and protective factors against, extrafamilial victimisation during childhood. Main findings The findings from study one revealed how widespread extrafamilial victimisation was amongst the young people taking part. Many of the characteristics of the young persons’ activities within the community were found to increase their risk of extrafamilial victimisation, providing support for the RAT of extrafamilial victimisation. However, the characteristics of the young persons’ journey home from school were not found to influence the prevalence of victimisation on this journey and some research findings based on the RAT of extrafamilial victimisation were not found to be significant predictors of community-based victimisation. Geographical victimisation ‘hotspots’ were identified in the case study, which revealed how the geographical distribution of community-based victimisation was located within close proximity to the young person’s school. Finally, different categories of extrafamilial victimisation were significant negative predictors of psychological well-being, as was past-year poly-victimisation and victimisation in more than one location. Finally, social support was identified as a potential moderator of the relationship between victimisation and psychological well-being. Findings from the systematic review (study two) highlighted a number of areas of bias within the cohort studies carried out in this area, particularly population bias and outcome (i.e., extrafamilial victimisation) measurement bias. A large number of risk factors (N= 56) were investigated in the included studies, the significance of which differed according to the extent of the extrafamilial victimisation explored and the definition of extrafamilial victimisation used. Less attention was given to protective factors (N= 18) within the included studies, yet a small number of individual characteristics were identified as potentially important predictors of peer victimisation. Crucially, interaction effects were identified between predictors (mediating and moderating variables) and between risk and protective factors. These findings highlight the complexity of the network of risk and protective factors for extrafamilial victimisation. They also reveal interaction effects between predictors operating across a number of different levels of the young person’s ecology (e.g., individual predictors, environmental predictors, etc.). Conclusion The two studies presented within this thesis highlight the complex, multidimensional nature of extrafamilial victimisation. The thesis concludes by drawing upon the research findings and theories outlined within the literature to propose a new model of extrafamilial victimisation. This takes account of the different vulnerabilities and processes involved in victimisation, as well as recognising the reciprocal relationship between predictors and outcome. As such, recommendations for the development of prevention and intervention are outlined, as is the need for future research in this area.