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This thesis aims to explore the personal and professional experiences of self-care in the clinical psychology profession, with a focus on personal therapy. In doing so, it seeks to add to the small literature base that explores the use of self-care by clinical psychologists. Paper one is a review of the current literature that aims to synthesise the factors that contribute to the wellbeing of qualified and trainee clinical psychologists practicing in the United Kingdom. A total of 11 papers were included in the thematic review. Six themes were identified: Social Support, Predisposing Vulnerabilities, Organisational Change, Shame and Stigma, Being a Clinical Psychologist and Enhancing the Self. Overall, findings suggest that mindfulness, accessing personal therapy and seeking positive social support aid psychological wellbeing. Barriers to wellbeing include stigma and shame in disclosing distress, stressful working environments and avoidance behaviours. Positive training course relationships, supportive supervision, active behavioural strategies, and peer support are factors that could reduce these barriers. Paper two is an empirical paper that explores the self-care experiences of a group of qualified clinical psychologists. Interpretative Phenomenological Analysis was used to develop the themes of The Toxic Environment, Identity, Self-Care, and Personal Therapy. The findings highlight the internal and external conflicts that clinical psychologists face when implementing self-care. Findings are discussed in relation to the clinical implications, in particular how to add to future research.

Cancer stem cells (CSC) are thought to be responsible for the initiation, propagation and tumour re-occurrence. CSC have been identified in most solid and haematological cancers and account for ~1% of the total cell population. Culturing cancer cell lines in monolayers enriches for the most dominant subpopulation which in most cases does not represent the slow dividing CSC population. We investigated the expression of CSC markers in 2D vs. 3D cell culture with the aim of identifying CSC-like cells via a nanog-reporter cell line and enable the subsequent targeting of these cells with CSC-targeting agents. SUM159 and MCF7 cell lines cultured in 3D cell culture significantly enriched for the CD44+/CD24- breast cancer stem cell phenotype when compared against 2D cell culture (p < 0.05 and 0.001 respectively) and also enriched for expression of CD181 (p < 0.05 and 0.001 respectively). However, this method did not enrich for the prostate CSC with the CD44+/CD133+ phenotype in PC3, DU145 and LNCAP cells. Using reporter cell lines to further identify the CSC population in SUM159 cell line that express GFP in response to Nanog (NRE-GFP), found that these cells were GFP+ve in the absence of Nanog protein. As these reporters were selected based on GFP that was supposedly Nanog driven other mechanistic studies were examined to determine how GFP is expressed in the NRE-GFP and control cell line. It was found that GFP could be induced in apoptosis, CSC enriching medium, hypoxia and by inhibiting the proteasome in the absence of Nanog protein. It was concluded that reporter cell lines that respond to a response element may not identify the CSC population as other factors can induce GFP expression. Compounds related to Withaferin A have been proposed to specifically target CSCs. Prostate and breast cancer cell lines cultured in 2D and 3D were treated with a novel withanolide derivative (LG-02) and Withanilode E to determine if these compounds were more effective at inducing cell cycle arrest and apoptosis using flow cytometry and microscopy. It was determined that LG-02 and WE primary mode of action is cell cycle inhibition and both compounds are more potent cell cycle inhibitors than Withaferin A. G1 phase accumulation was observed in the SUM159, PC3 and LNCAP cell lines and G2/M phase accumulation in the DU145 cell line. Cell cycle arrest was inconclusive in the MCF7 cell line. An apoptotic morphology was only significantly induced at higher concentrations in MCF7, PC3, DU145 and LNCAP. Withanolide derivatives also target the androgen response pathway, demonstrated by a decrease in PSA and androgen receptor in prostate cancer cell lines. LG-02 slowed growth of breast cancer cell lines cultured in 3D and inhibited spheroid formation of prostate cancer cell lines, however the androgen-dependent cell line LNCAP was consistently able to form 3D colonies, most likely via pAkt activation. We conclude that 3D cell culture does enrich for the CSC population in breast cancer cell lines but using a reporter cell line expressing GFP under the control of a NRE is not a suitable model for identifying the CSC population for subsequent drug treatment. In addition, Withanolide derivatives have potential anti-tumour activity and may represent a novel class of anti-androgenic agents.

Conduct problems (CPs) in young children have been widely studied but mainly in 'High Income' Countries (HICs) raising the question of whether the processes are the same in 'Low and Middle-Income' Countries (LMICs). This PhD study was conducted in Colombia, a LMIC historically conflict affected. Its aims were to identify whether there are general and culture specific processes regarding the role of Callous-Unemotional (CU) traits -characterised by disregard for others and lack of empathy- in relation to CPs, and to examine the role of parenting in relation to CU traits in the context of exposure to community violence. I established the La Sabana Parent-child Study with 235 children at ages 3.5 years from three Colombian regions and assessed them via parent report and observations of parents and children in standard play and tidy-up procedures. Measurement paralleled that of the UK Wirral Child Health and Development Study to allow for cross-cultural analyses. I reassessed 220 (93.6%) at age 5 years. The main findings reported in the four papers presented here are: 1) Commonly used measures of CU traits (ICU - Inventory of Callous-Unemotional Traits) and parenting (Alabama Parenting Questionnaire) have similar psychometric properties in this sample as in HIC samples and show predicted patterns of association (Paper 1). The ICU is valid as evidenced in incremental prediction of later aggression (Paper 2). 2) In a novel finding for HIC and LMIC research, prediction from CU traits at age 3.5 to aggression at age 5 was substantially greater in the presence of pre-existing aggression suggesting a synergistic effect and replicated across Colombian and UK samples (Paper 2). 3) Vulnerability for later aggression created by CU traits is ameliorated by maternal praise and positivity (Paper 3). 4) Children's exposure to community violence is associated with elevated CU traits at age 5, but only among mothers with low levels of positivity at age 3.5 (Paper 4). In conclusion, CU traits is a valid construct in a sample of young children from a LMIC and have a role in the maintenance and amplification of early aggression. Also, positive parenting has a protective role in the interplay between aggression and CU traits and in the association between community violence and CU traits. The novel finding Diana Paola Obando Posada ©University of Reading 2021sábado, 18 septiembre 2021 Page 13 that most, and perhaps all, of the effect of CU traits on young children's aggression, is confined to those who are already aggressive, requires replication and further investigation. Further research about the role of parenting on CPs and CU traits must involve additional parenting dimensions to identify those of relevance in children immersed in contexts with differential features, as well as work on the relative importance of positive and negative parenting in CU traits.