This project set out to develop a cognitive training intervention for individuals with attention deficit hyperactivity disorder (ADHD). The thesis builds on research suggesting that reinforcement deficits in the ADHD population give rise to the underdevelopment of a number of cognitive abilities, in particular inhibitory control skills. Arguing that this skill is explicitly trainable and that training inhibitory gaze control is a means of training inhibitory control, this thesis set out to utilise eye-tracking technology to assess inhibitory gaze control performance in ADHD and to develop an engaging intervention in the form of a computer game capable of training the inhibitory gaze control system. Drawing on literature on inhibitory control in ADHD, the saccadic system, game development, and cognitive load theory a training intervention and battery of assessment tasks were developed iteratively across a number of pilot studies. The development process and resultant cognitive training interventions are described. The final proof-of-concept study was trialled for eight one-hour training sessions with an ADHD population (N = 8). Comparisons of pre- and post-training assessments produced strong effects for measures of gaze control, inhibitory control, timing, and attention. The results are interpreted and a number of limitations noted. The potential benefits of such interventions to aid clinicians to diagnose, to monitor, and to treat ADHD are considered. The relevance of cognitive interventions in contributing to research attempting to identify endophenotypes of ADHD is also discussed.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Purpose and Background: Neuroblastomais the most common pediatric extracranialsolid tumor •50% of patients present with metastatic disease typically involving bone and bone marrow •Despite intensive multimodality therapy, 40% of patients with high-risk neuroblastomawill experience relapse •131I-MIBG is an active salvage agent for relapsed and refractory MIBG-avid disease •It is unknown whether disease progression following 131I-MIBG treatment occurs in previously involved vs. new sites of disease •A better understanding of this pattern may inform the use of consolidative focal therapies following 131I-MIBG administration

A high prevalence of malnutrition has been reported in paediatric inpatients both in developed and developing countries, using various methodology and criteria. According to national and international guidelines, all inpatients should be screened for risk of malnutrition on admission using a validated screening tool. However, because of the lack of universally accepted definition for malnutrition, there is no consensus on the measures and methods to use for nutritional screening. There is controversy concerning the validity, reliability and practicality of existing paediatric nutrition screening tools. Moreover, current paediatric screening tools have not been designed and validated for infants. The study aimed to: 1) Validate a novel malnutrition screening scheme for infants - the Infant Paediatric Yorkhill Malnutrition Score (iPYMS) and compare its utility in different hospital settings, in UK and Middle East, Iran. 2) Compare the usefulness of various anthropometric measures to predict malnutrition in infants. 3) Determine the factors that correlated with malnutrition in hospitalised infants. 4) Explore the use of body composition measures in sick infants. The Paediatric Yorkhill Malnutrition Score (PYMS) had already been developed in Glasgow for use in children admitted to hospital. It utilized four elements that were reported as recognized predictors of the past, present or future nutrition risk. An audit was carried out at the beginning of the PhD course and aimed to evaluate the effect of PYMS on collection of anthropometric measurements in the wards. Findings suggested that introduction of a screening tool improved the acquisition of anthropometry by nursing staff, but their utilization by medical staff remained poor. Method: The Infant Paediatric Yorkhill Malnutrition Score (iPYMS) was developed by the research team. The score encompasses 4 rated steps that similar to those used for older children: weight < 2nd and 9th centile was used as opposed to BMI, and 3 elements concerning the history of nutritional issues. A score of 1 classifies a patient at medium risk and ≥2 or ≥3 indicates high risk. Infants were studied at admission to two tertiary children's hospital, 210 (0-12 months) in Glasgow, UK and 187 (1-12 months) in Tabriz, Iran. Convenience sampling was used to recruit equal number of patients in each risk group. Four researchers recruited the samples for the UK cohort and one for the Iran cohort. The diagnostic accuracy and validity of iPYMS in both cohorts were assessed by comparing the iPYMS nutritional risk with the Paediatric Subjective Global Nutritional Assessment (SGNA) that determine malnutrition risk and mean skinfolds z-scores (triceps and subscapular) below <-2SD as the benchmark for low fat stores and acute/chronic malnutrition. Discriminant validity was assessed using body composition and anthropometry measurements, with the hypothesis that infants at high risk of malnutrition will have lower fat and possibly lean mass compared with those at low risk. Results: More infants in Iran (32%) were rated as high risk for undernutrition than UK (7%). The diagnostic performance of iPYMS improved with the cut-off ≥ 3, more so in Iran than the UK. In Iran, only, infants who were classified as being at high risk of malnutrition had longer hospital stay. Infants in the iPYMS moderate and high risk groups all had significantly lower mean SD-score for anthropometry. After excluding patients scored high risk based only on low weight z-score (≤-2 SD), the differences in weight and BMI z-scores remained significant. In Iran 76% infants with raised iPYMS had mean skinfolds <-2SD, but only 5% in the UK. The UK infants may thus not actually be malnourished. They may be ill and just at risk of malnutrition. The first step of iPYMS (weight below <9th or 2nd centile) was a strong predictor of malnutrition risk, more so in Iran; in the Iranian cohort, 91% and in the UK 70% of infants above the high risk threshold of ≥ 3 scored as high risk due to the weight below <9th or 2nd centile. ROC Analysis either with SGNA or sum skinfolds z-score as the main outcomes illustrated that admission weight and growth velocity had almost the same predictive value in predicting malnutrition risk. This suggests that weight velocity is no improvement on weight alone as a predictor of malnutrition. Current breast feeding was found to be an independent predictor of malnutrition in Iran. Socioeconomic factors were weak predictors of malnutrition in this population. There is a lack of validated and suitable methods to assess body composition in infants. To determine whether analysing bio-electrical impedance data is practical in our young age range population, this was compared to skinfolds thicknesses and how the two measures of body composition varied relative to SGNA. The WHO standard for skinfolds only starts at 3 months, excluding nearly one third of infants in the Iran cohort and half in the UK. An iPYMS skinfold reference was thus generated using the iPYMS dataset for the UK cohort, as this was a population with low rates of malnutrition risk who had skinfolds levels mainly within the WHO range beyond age 3 months. In Iran, most high SGNA risk infants (72%) had low skinfolds, but in UK there was no association. Iranian infants had much lower mean lean and fat than the UK infants. Fat measured by BIA varied by SGNA rating risk group with both cohorts, but lean differed between risk groups only for Iran cohort. Conclusion: Malnutrition was common in this tertiary children's hospital in Iran. iPYMS might perform well in this setting and could be used by health professionals to identify infants with malnutrition. In contrast, in the UK, iPYMS would mainly identify infants at risk of malnutrition, because of the low prevalence of under-nutrition. On the other hand, we found that weight alone (the first component of iPYMS) is a robust predictor of malnutrition risk. Therefore iPYMS may not add any advantage over the simple measurement of weight alone to identify infants at risk of malnutrition. This is essential where there are limited resources. Studies should be continued to explore a suitable and appropriate gold standard to test the validity of the tools particularly in low prevalence settings as well as the resources and cost of the introducing the tool in clinical practice. Any screening tool for malnutrition can only be considered effective if it results in early intervention and improved clinical outcomes, so the effectiveness of iPYMS needs to be explored in future intervention studies.

Background: The burden of childhood stunting and mortality remains huge in developing countries and in particular in the Sub-Saharan Africa region to which Nigeria is located. Despite the body of evidence supporting an association between neighbourhood contextual influences and health outcomes, few studies have examined the relationship between neighbourhood-level risk factors and childhood undernutrition (stunting) and mortality independent of the individual-level risk factors in a single analytical framework in Nigeria. Most studies to date have focused on individual-level factors overlooking the contribution of neighbourhood or area level factors. Beyond the effect of neighbourhood contextual influences, a child’s health will be influenced by the state, region and national policies and programs that in turn will affect the proximate determinants of his or her survival and health status. Aims: We described the variation that existed between the states in Nigeria using league table, control chart and spatial clustering of childhood stunting (Study I) and examined the contribution of community contextual factors at predicting childhood stunting beyond individual-level factors (Study II). We further identified and examined the predictors of childhood mortality in Nigeria (Study III) and developed prognostic model predicting differences in childhood mortality in Nigeria communities (Study IV). We also quantified the contribution of neighbourhood socioeconomic disadvantage alongside individual-level socioeconomic status to childhood mortality in Nigeria using multilevel analysis (Study V). Methods: We used the Nigeria Demographic and Health Survey (DHS) dataset which comprised of 28,647 and 31,482 under-five children nested within 888 and 896 communities for the 2008 and 2013 surveys respectively from 37 states including the Federal Capital Territory. We used league table, control chart and geospatial analysis to describe variations in childhood stunting that existed between the states in Nigeria (Study I). In study II, we applied multivariable multilevel logistic regression analysis to describe the independent contribution of community contextual influences (factors) alongside the individual level factors on childhood stunting in Nigeria. We applied multivariable logistic regression analysis that included Receiver Operating Characteristics (ROC) Curve to construct a model that examined the factors associated with childhood mortality (Study III). In study IV, we used mixed multivariable Poisson regression analysis to develop a prognostic model predicting differences in childhood mortality in Nigeria communities. In Study V, we applied multivariable multilevel logistic regression analysis and considered three measures of individual socioeconomic status i.e. maternal educational attainment, household wealth status, and employment status of the mothers. At the neighbourhood (level 2) and state (level 3), we included poverty rate, unemployment rate, and illiteracy rate. Results: There were statistically significant variations in the odds of childhood stunting and mortality across the neighbourhoods (Study II, IV & V) and states (I) in Nigeria. This confirmed the evidence of community and state level contextual phenomenon influencing childhood survival and stunting. Children residing in socioeconomically disadvantaged neighbourhoods had higher odds of childhood morbidity and mortality compared to their counterparts living in more socioeconomically advantageous neighbourhoods (Study II, IV & V). The odds of childhood morbidity and mortality were associated with neighbourhood and state socioecological conditions even after adjusting for individual’s household socioecological conditions (Study II, III, IV & V). There was moderate positive correlation between neighbourhood and individual variations in childhood mortality and morbidity (Study II & V). The odds of childhood stunting and mortality were higher in children residing in rural areas (Study II, III, IV & V) and in settings with poor sanitation (Study III & IV). Other factors that increased the odds of childhood mortality included low level of maternal health seeking behaviour, not breastfed for >18 months, being from a polygamous family setting, large family and high birth order, non-usage of contraceptive by mother, and mother having first marriage during their teenage years(Study III). Good household wealth status, adequate birth interval, being a female child and having normal birth weight, increasing maternal educational attainment were all associated with odds of not suffering from childhood stunting and surviving beyond five years of age (Study II & V). Conclusions: By adopting several modelling approaches including the multilevel modelling, we added to the growing body of evidence the effects of the neighbourhood contextual influences on childhood stunting and survival in Nigeria. Our study revealed that individual i.e. children and parental factors; neighbourhood and socioecological environment were associated with childhood stunting and mortality. Efforts at reducing the burden of childhood stunting and mortality should be directed at establishment of poverty alleviation programmes, effective publicly funded health care delivery, promotion of hygienic environmental practices and health education more importantly at the neighbourhood level. Lastly, given the importance of socioecological factors at influencing the lifestyles of neighbourhoods and individuals, interventions targeting structural make up of these two entities are vital in order to meet the MDGs 1 and 4 regarding childhood stunting and mortality in Nigeria and in particular developing countries in general.

The aim of this thesis is to discuss the issue of public legitimization of new medical technology, through a case of antenatal screening for Down's syndrome in Britain. It is based on ethnographic study of agents involved with the technology; inventors of the technology, medical practitioners, pregnant women, and people with disability and their families, especially parents. The thesis is interdisciplinary based on mainly two frames of reference; Science and Technology Studies and Disability Studies. The former equips the thesis with the basis to understand the process of invention and promotion of the technology, in the social context I will especially focus on transformation of rhetoric to legitimate the technology in its process. The latter provides the critical standpoint to observe the fundamental idea of antenatal screening that it is better to prevent life with disability. Today, provision of antenatal screening is commonly legitimated for its ability to enhance autonomous decision of women in the clinical setting. However it is questionable whether women can make reliable autonomous decisions, when they can only imagine the immediate consequences of their decision (Rapp and Ginsburg, 2001). Based on the idea of disability studies, I will argue that the key to the public legitimization of antenatal screening technology lies in the approach towards life with disability that society should take. I will show that an important problem in the process of social acceptance of antenatal screening for Down's syndrome in Britain is the lack of serious examination of alternatives to the preventive medical approach towards disability that this technology offers. I conclude that in order to generate the public legitimization of antenatal screening technology in the future, it is necessary for the public to consider a variety of possible approaches that society can take towards life with the targeted condition.

The aim of this thesis is to compare effects of respiratory distress syndrome (RDS) on the myocardial function of newborn preterm infants and the later effects of chronic lung disease of prematurity on pulmonary artery stiffness in school age children. The first study in this thesis compared global and regional myocardial function in preterm infants with respiratory distress syndrome (RDS) with preterm and term-born controls (30 with RDS, 30 preterm control ≤34 weeks, 60 term control) using conventional and tissue Doppler echocardiography at birth, at term, one month, and one year of age. The second study compared the pulmonary artery stiffness, an early preclinical marker of pulmonary hypertension, in children (aged 8-12 years) who had chronic lung disease of prematurity (CLD) with preterm and term-born controls. Pulmonary artery pulse wave velocity (PA PWV) was assessed in 59 children: 13 with CLD, 21 preterm (≤ 32 weeks gestation) and 25 term controls) using velocity encoded MRI technique while breathing room air and after 20 minutes of breathing 12% oxygen. At birth, infants with RDS had lower pulmonary artery AT:ET (p < 0.001), long axis shortening (p < 0.01), RV systolic velocity (p < 0.001) and higher TR (p < 0.01) compared to preterm and term control groups. The preterm groups was also noted to have diastolic dysfunction (lower mitral E:A) at birth (p < 0.001). At term corrected age, pulmonary artery AT:ET was still lower in the RDS group but no differences detected in TR between the groups. There were no differences in all parameters measured between the groups at one month and one year. 2 PA PWV was similar in all three groups at baseline when assessed at school age. However, following hypoxic challenge, PA PWV in children who had CLD increased significantly compared to preterm (p=0.025) and term controls (p=0.042). The findings in this thesis suggest that infants with RDS had mildly elevated pulmonary arterial pressure as a result of milder respiratory disease with improvement in antenatal and neonatal care. The RV global dysfunction in infants with RDS resolved with resolution of the respiratory condition. Both preterm groups underwent postnatal maturation of myocardial function and caught up with the term control group by one month corrected age. At school age, children who had CLD displayed increased pulmonary vascular reactivity to hypoxia and are at greater risk of developing pulmonary hypertension earlier.

Aims: Since 2008, in England, all sudden unexpected deaths in infancy (SUDI) must be investigated jointly by police, health and social care. This thesis aims to learn of parents’ and professionals’ experiences of this joint agency approach (JAA) and use this knowledge to improve these investigations. Methods: 1. Systematic literature review of bereaved parents’ experiences. 2. Systematic literature review of different models of SUDI investigation. 3. A mixed methods study of JAA investigation of SUDI cases; involving case note analysis, questionnaires and in-depth interviews with parents and professionals. 4. A descriptive study of outcomes of JAA SUDI investigation using Child Death Overview Panel (CDOP) data. Results: In the mixed methods study, 23/111 families were recruited giving theoretical saturation; the median time between death and parental study participation was 33 weeks. Parents felt that the JAA provided information about the death but offered minimal emotional support; they were often distressed by non-specialist police attending their home as part of the investigation. The joint home visit by police and paediatrician was shown to be a key investigative process. Social care were only involved in 13/23 JAA investigations. Some coroners were reluctant to share information with paediatricians preventing effective JAA investigations. In the CDOP study were obtained for 93% SUDI cases. Final case discussions were used to discuss risk factors but not to determine the cause of death; in nearly all cases the final cause of death relied on post-mortem examination alone and ignored death scene examination findings. Many deaths were labelled as unascertained despite fulfilling diagnostic criteria for SIDS. Conclusion: Ideally, SUDI investigations should be carried out only by specialist clinicians who do this work frequently and the JAA should be fully integrated with social care and coroners’ investigations. There needs to be a clearer system for classifying unexplained SUDI. Police should reconsider their immediate response to SUDI; parents would like more follow-up and bereavement support from professionals.

Impaired self-awareness is a common consequence following a brain injury in adults, particularly when the brain injury is moderate or severe. Impaired self-awareness affects engagement in rehabilitation and results in poor long term functional outcomes. There is a paucity of literature regarding self-awareness following a brain injury in childhood. Consequently, little is known about the differences between children and adults in the domain of self-awareness following brain injury. Children and young people are at different stages of development when their injury occurs and this study investigates the impact of the brain injury on the development of self-awareness. The aim of this research study is to gather quantitative and qualitative longitudinal data from children and young people who have experienced a moderate to severe traumatic brain injury in order to understand their level of self-awareness. This study used a longitudinal multiple case study design with mixed methodology. Fifteen children and young people with a moderate/severe traumatic brain injury were recruited and data were collected from the children and young people, their parents and their teacher over an eighteen month period. The results show that children and young people have an interruption to the development of self-awareness following a traumatic brain injury. Impaired self-awareness is not chronic in this group and they continue to make developmental gains in time. This study adds to our understanding of the interruption of self-awareness development following a brain injury in childhood. Occupational therapists have a particular role to play while engaging with children and young people in the everyday context of their lives, which is supportive of greater self-awareness. As children and young people become more able to assess their own performance, they may be in a better position to set realistic rehabilitation goals. Implications for future clinical and academic children’s neurorehabilitation are outlined.

Abstract available in the Journal of Investigative Medicine.

No description available.