Brain growth and development in fetuses with congenital heart disease

Introduction and Objectives: In the current era of excellent surgical results for congenital heart disease (CHD), focus has become directed on quality of life for these children. Previous studies have shown that neurodevelopmental outcome in CHD is impaired. The mechanisms are incompletely understood but there is increasing evidence that the origins of this are in fetal life. This thesis aims to describe the in utero brain growth in a cohort of fetuses with CHD and relate this to the circulatory abnormalities and fetal Doppler parameters. Methods: Pregnant women with a fetus with CHD were prospectively recruited. The congenital heart defect was phenotyped using fetal echocardiography and patients subdivided into three physiological groups on the basis of the anticipated abnormality of cerebral blood flow and oxygen delivery: (1) isolated reduced flow to the brain; 2) reduced oxygen saturation of cerebral blood flow; (3) combination of reduced oxygen and flow. Fetal brain MRI was performed. In addition to standard biometric measurements, snapshot to volume reconstruction (SVR) was used to construct a 3D data set from the oversampled raw data. From these 3D volumes the total brain volume and ventricular volumes were measured by manual segmentation. Serial measurements of fetal growth were also made and umbilical artery and middle cerebral artery Doppler parameters were analysed. Results: 29 women were included; comparison was made with 83 normal MRI controls. Fetuses with CHD were found to have smaller brain volumes compared to controls when adjusting for advancing gestation (p<0.01). This difference becomes more pronounced with advancing gestation, suggesting a slower rate of in utero brain growth. Measurements of growth found that the fetuses with CHD were smaller throughout gestation with a highly significant difference at the later growth scan. (p<0.001). Cerebral and umbilical artery Doppler data showed evidence of reduced cerebrovascular resistance in fetuses with CHD but did not show a difference in the umbilical artery Doppler. Conclusion: Fetuses with CHD have evidence of impaired brain growth with advancing pregnancy and an increased rate of overall growth restriction. Doppler evidence of cerebral vasodilation supports the mechanism of reduced oxygen delivery as an underlying cause.Open Acces

Macroporous Fluorine Doped Tin Oxide Photoelectrodes for Solar Water Splitting

Fluorine doped tin oxide (FTO) is widely used as a back contact transparent conducting oxide (TCO) in photoelectrodes for solar energy applications. Using relatively complex methods, a variety of materials can be deposited over FTO to form porous electrodes, which are desired for their higher surface areas. The present work shows how it is conceptually much simpler to template the TCO electrode, producing macroporous electrodes, which allows relatively simple methods to be used to deposit secondary materials for solar water splitting. Macroporous FTO electrodes (macFTO) were fabricated to give highly conductive and structurally ordered electrodes. The fluorine content was analysed using solid state NMR and was found to be as low as 0.5 atom%, 100 times smaller than the precursor Sn:F ratio. The capacitance of electrodes was used to determine the surface area enhancement of macFTO compared to planar FTO (pFTO), which was found to be 12 times greater. As macFTO is an ordered porous, or photonic, electrode, there is a possibility that an increase in light absorption efficiency could be observed. An investigation found that the stop band of macFTO was angular dependent, and the electrode could enhance the lifetime of embedded dyes. The emission lifetime of embedded Rudcbpy, a ruthenium based dye, was found to increase by a factor of 1.8, while the lifetime of coumarin 440/460 was increased by a factor of 1.4 when the stop band overlapped the emission profile of the dye, consistent with literature. Finally, visible light absorbing materials and catalysts for water oxidation were deposited over macFTO, showing that simple techniques could be used to deposit a variety of useful materials. Independently, both BiVO4 and CdS nanoparticles were successfully deposited over macFTO. Only a low CdS nanoparticle loading was required to show that the macFTO electrodes were conductive and capable of supporting photocurrents, with up to a 100 fold increase in the photocurrent density observed compared to equivalent planar electrodes due to the surface area enhancement. The activity of macFTO-BiVO4 electrodes towards water oxidation was then tested with the use of a co-catalyst (CoPi). It was found that the activity of the macroporous electrode was substantially better than equivalent planar electrode, with oxygen evolution rates of 74 μL hr-1 produced with a bias of 1.6 VRHE, and faradaic efficiencies for oxygen evolution reaching 100%

What works in recovery? Alcohol and other drug professionals lived experiences of addiction, treatment and recovery in New Zealand : a thesis presented in partial fulfilment of the requirements for the degree of Master of Social Work at Massey University, Manawatū, New Zealand

The New Zealand Government’s health surveys consistently identify that alcohol and other drug (AOD) addiction is an issue for New Zealanders. However, there is a lack of qualitative research on the lived experiences of people who have previously or currently experience AOD addiction in New Zealand. This research provides insight into the factors that contribute to, and create barriers to, successful AOD addiction recovery. The qualitative method of constructivism was the approach used to conduct the research. Eight participants took part in semistructured interviews, sharing their stories in a narrative style and recounting experiences from the time their addictions began, their entry into AOD addiction recovery and their entry into the AOD workforce. Interview transcripts were analysed using thematic analysis, themes were identified that highlighted what contributed to participant’s successful AOD addiction recovery and what created barriers to AOD addiction recovery. Nine themes emerged through the data analysis process these were: stigma; defining your own recovery; reconstruction of the self; the role of social learning; opportunities for career progression; specific populations including youth, people with co-existing mental health and AOD addiction issues, women, and families; strengths and limitations of the health, social service and AOD workforce; addiction and the law; and barriers to accessing AOD support services. A consistent finding across these nine themes was that the barriers to AOD addiction recovery in New Zealand experienced by the research participants were systemic, and preventable. The recommendations of this thesis are that the barriers to recovery, and contributors to successful recovery identified in this research are addressed; in particular the themes of stigma and systemic barriers to wellbeing

Teacher–Student relationship quality as a barometer of teaching and learning effectiveness: Conceptualization and measurement

Background. The teacher-student relationship (TSR) is instrumental for young children and adolescents’ socio-emotional development and wellbeing as well as academic engagement and progress. Aims. The primary aim of this study was to test the psychometric properties, including reliability and factorial, convergent, and predictive validity, of the Teacher-Student Relationship Quality Questionnaire (TSRQ-Q) with two samples of students. Sample(s). Participants were 294 students from secondary schools in the East Midlands and the East of England. Participants were separated into two samples; those who completed the TSRQ-Q with their physical education teacher in mind (n = 150 students) and those who completed it with their mathematics teacher in mind (n = 144 students). Method. A multi-section questionnaire comprised of the TSRQ-Q and other validated measures was completed on one occasion by students in both samples to assess their perceptions of the quality of the TSR, positive and negative affect, intrinsic motivation, physical self-concept, enjoyment, and perceived competence. Results. In both samples, the TSRQ-Q demonstrated good internal consistency, factorial, convergent, and predictive validity. The quality of the TSR had both direct and indirect effects through positive affect on student outcomes in mathematics and physical education. Conclusions. The TSRQ-Q is a valid measure for assessing students’ perceptions of the quality of the relationship with their teacher. The conceptual and practical significance of this unique relationship was reflected by its dual pathway effect on a range of student outcomes and via influencing students’ positive affect in the classroom

COVID-19 in congenital heart disease (COaCHeD) study

Background: COVID-19 has caused significant worldwide morbidity and mortality. Congenital heart disease (CHD) is likely to increase vulnerability and understanding the predictors of adverse outcomes is key to optimising care.// Objective: Ascertain the impact of COVID-19 on people with CHD and define risk factors for adverse outcomes.// Methods: Multicentre UK study undertaken 1 March 2020–30 June 2021 during the COVID-19 pandemic. Data were collected on CHD diagnoses, clinical presentation and outcomes. Multivariable logistic regression with multiple imputation was performed to explore predictors of death and hospitalisation.// Results: There were 405 reported cases (127 paediatric/278 adult). In children (age <16 years), there were 5 (3.9%) deaths. Adjusted ORs (AORs) for hospitalisation in children were significantly lower with each ascending year of age (OR 0.85, 95% CI 0.75 to 0.96 (p<0.01)). In adults, there were 24 (8.6%) deaths (19 with comorbidities) and 74 (26.6%) hospital admissions. AORs for death in adults were significantly increased with each year of age (OR 1.05, 95% CI 1.01 to 1.10 (p<0.01)) and with pulmonary arterial hypertension (PAH; OR 5.99, 95% CI 1.34 to 26.91 (p=0.02)). AORs for hospitalisation in adults were significantly higher with each additional year of age (OR 1.03, 95% CI 1.00 to 1.05 (p=0.04)), additional comorbidities (OR 3.23, 95% CI 1.31 to 7.97 (p=0.01)) and genetic disease (OR 2.87, 95% CI 1.04 to 7.94 (p=0.04)).// Conclusions: Children were at low risk of death and hospitalisation secondary to COVID-19 even with severe CHD, but hospital admission rates were higher in younger children, independent of comorbidity. In adults, higher likelihood of death was associated with increasing age and PAH, and of hospitalisation with age, comorbidities and genetic disease. An individualised approach, based on age and comorbidities, should be taken to COVID-19 management in patients with CHD

Structure and immunogenicity of alternative forms of the simian immunodeficiency virus gag protein expressed using Venezuelan equine encephalitis virus replicon particles

Venezuelan equine encephalitis virus replicon particles (VRP) were engineered to express different forms of SIV Gag to compare expression in vitro, formation of intra- and extracellular structures and induction of humoral and cellular immunity in mice. The three forms examined were full-length myristylated SIV Gag (Gagmyr+), full-length Gag lacking the myristylation signal (Gagmyr-), or a truncated form of Gagmyr- comprising only the matrix and capsid domains (MA/CA). Comparison of VRP-infected primary mouse embryo fibroblasts, mouse L929 cells and primate Vero cells showed comparable expression levels for each protein, as well as extracellular virus-like particles (VRP-Gagmyr+), and distinctive cytoplasmic aggregates (VRP-Gagmyr-) with each cell type. VPR were used to immunize BALB/c mice, and immune responses were compared using an interferon (IFN)-γ ELISPOT assay and a serum antibody ELISA. Although all three VRP generated similar levels of IFN-γ-producing cells at 1 week post-boost, at 10 weeks post-boost the MA/CA-VRP-induced response was maintained at a significantly higher level relative to that induced by Gagmyr+-VRP. Antibody responses to MA/CA-VRP and Gagmyr+-VRP were not significantly different