This thesis is a study of ministry in the multi-ethnic world of South London. In this setting, language, tradition, custom and culture have become both obstacle and key to ecclesiological understanding and community engagement. At the outset, a theological framework for the study is established. This encompasses church, parish, charism and ministry, all serving the primary task of mission. From an empirical study involving some of the key people who give their time and talent to their local communities in five South London parishes, ministry is seen not as an isolated activity but as something that is a dynamic and significant component within the greater pastoral context. This study highlights the importance of mapping a local theology by listening attentively to the local culture, and engaging with community members as they reflect on life in their context. The research also brings to light the tensions and conflicts that surface internally when the exercise of power by the institutional Church is experienced at parish level. A gulf can be observed between the institution and the people of God in the local faith community. At the heart of this study there emerges an acute awareness of the near-absence of critical theological reflection on parish practice. The empirical evidence also suggests that there is a matrix of issues which are in need of immediate and sustained attention. These include communication, dialogue and formation. It is clear that strategic pastoral planning is required so that the needs of the people can be continually identified, the Sunday Liturgy be meaningfully sustained, catechists be regularly recruited and adequately trained and the young Church be appropriately welcomed and nourished. A review of ministerial formation for both lay and ordained people emerges as fundamentally important in the long-term interests of communion, co-responsibility and accountability for mission.

This thesis explores a return of social and political horizons to the urban church through the political practices of community organising. Organising’s work is contextualised within the changing place of religion in society and Anglican parochial horizons in inner-urban areas. It provides a history of community organising in which its presence in England in recent decades is reflected upon. The social and political standpoint enabled by organising is discussed in relation to issues of embodiment in ecclesiology, liturgical and political theology. Connections between organising, liberation theology, the pluralist tradition, and aspects of Anglican social theology and ethics are also considered.

The development of leaders within church networks, in comparison to mainstream denominations, can appear ad hoc, lacking consistency, theological aptitude and structure. Nevertheless, some of these leaders are seeing remarkable church growth and are maintaining a relevancy in an increasingly pluralistic and fast changing Western society. ‘Life Church Österreich’ is a church network in Austria whose leaders, in contrast to its contemporaries, are almost one hundred percent indigenous. There is evidence that it has effectively developed leaders and pioneered churches in this Central European nation, but has the development been sufficient and can it be sustained? While revealing the significant hindrances of the unique cultural climate of Austria, this paper assesses the means of the network’s advancement to date. The thorough literature review of leadership distinctives and the optimal means of developing leaders led to qualitative empirical research of the entire network’s leadership. Coupled with the author’s exclusive insider-outsider status, this has ensured a thorough analysis and evaluation of Life Church Österreich’s development of leaders. The findings reveal that the development of a leader is a holistic life process and that Life Church Österreich will need to revive its focus on relational input, and training in the context of ministry, if indeed it is to produce the required leaders for the future growth of the network.

No description available.

This qualitative study reviews and documents the activity of Church Planters within the Baptist Union of Great Britain, who have started churches between 1980 and 2010. Two periods of church planting have been identified. From 1980 to the mid 1990s practitioners reacted to the threat of decline and secularisation. From the mid 1990s to 2010 practitioners re-engaged with the missionary task of church planting, drawing on the concept of contextualisation. The difficulty of gathering statistics about church planting within the Baptist Union of Great Britain has been identified by reviewing all the available data. A qualitative study was chosen to give an in-depth analysis of the experience and perspectives of practitioners. Twelve practitioners participated in the study. Each participant was interviewed and the contents of the interview transcribed and analysed. The interviews, along with accounts of church planting from both periods has enabled the practice of planting churches to be set into context. Firstly, into the context of decline in church attendance and the developing social theory of secularisation. Secondly, into the missiological theory of contextualisation. A review of the developing theory of secularisation revealed that current research calls progressive and total secularisation into question. This research suggests that decline in religious practice is evidence of a change in general approaches to spirituality, rather than evidence of a total secularisation. The reality of church decline and the theory of secularisation paved the way for a robust approach to church planting. During this period the need for contextualisation was identified but was practised by a relocation of worship meetings to a different venue. A review of the development of contextualisation in the field of missiology was conducted. The theory of contextualisation has influenced practitioners involved in church planting from the mid 1990s to 2010. During this time practitioners took the process of contextualisation further. Rather than simply relocating their meetings they began to contextualise the content of the meeting. With these developments in mind the practice of planting churches within the Baptist Union of Great Britain has been described, along with events that have influenced church planting practice. As practitioners have engaged with the process of contextualisation it is possible to see how a missionary approach has gathered pace among the practitioners. It is appropriate for practitioners to continue the processes of learning from wider missiological perspectives and developing their own contextualised practice.

Background Breast cancer is highly prevalent in older women. Although surgery is the main initial treatment for younger population, research has demonstrated that older women with primary breast cancer have different tumour biology, comorbidities, and patient preferences from younger patients, and hence may benefit from primary endocrine therapy (PETx), such as Tamoxifen and aromatase inhibitors (AIs). However, there is no cost-effectiveness study that compares the use of different treatment strategies in older women. Aim of study This study aimed to evaluate the clinical and cost-effectiveness of using PETx against surgery as the initial treatment strategy in older women with primary breast cancer. Methods This research included four stages. First, a retrospective cohort study was conducted to describe the treatment pathways, and evaluate the effectiveness and costs associated with using different treatment strategies by using a longitudinal database of 1,759 older women, who were diagnosed with primary breast cancer at ages over 70 years old in breast cancer units in Nottingham. Regression analyses, including survival analysis and generalised linear model, were used to identify the covariates, the predict death rates and costs, respectively. Second, a systematic review of economic evaluation studies was conducted using NHS Economic Evaluation Database, Cochrane Library, Ovid Medline, PubMed, and EMBASE to identify full economic evaluations that compared different treatment strategies in postmenopausal women with primary breast cancer. Quality and modelling methodologies of the included studies were assessed and summarised. Finally, a Markov model was conducted from the systematic review to estimate the lifetime costs and quality adjusted life year (QALYs) associated with the use of PETx as against surgery in a hypothetical cohort of older women with primary breast cancer and ER-positive status. The analysis took the UK NHS perspective with a lifetime horizon. Transition probabilities were estimated using parametric survival models derived from the longitudinal database. Resource use and costs were assessed in British pounds of the year 2014 using the longitudinal database. Utilities were derived from literature, including Prescott et al. (2007) (1), Fallowfield et al. (1994), and Peasgood et al. (2010)(2). Both costs and outcomes were discounted by 3.5% annually. A subgroup analysis was conducted for patients with higher oestrogen receptor content (H-score >250 out of 300). PSA was conducted and aggregated results were presented in cost-effectiveness plane and cost-effectiveness acceptability curve. Sensitivity analysis was also conducted to investigate the impact of uncertain parameters and model assumptions. Results Retrospective analysis of the cohort study found that most patients received surgery (n=350; 52.08%) or PETx (n=322; 47.92%) as the initial treatment strategy. The most common adjuvant therapy was endocrine therapy (n=164; 46.86%). Comparing to those received surgery as an initial treatment, patients who received PETx had a significantly higher adjusted risk of breast cancer-related death (HR: 2.15; 95%CI: 1.03, 4.46), and lower costs (mean difference: -£3558.87; 95%CI: -£4018.11, -£3105.39). Overall, 29 economic evaluations were included from the systematic reviews and studies that assessed surgery and none assessed PETx as the initial treatment. Most of the included economic studies used a Markov model with lifetime horizon and one-year cycle length. Nine studies which included subgroup analysis for older women (over 65 years old) used similar economic models and transition states to those that were used for younger women (50 to 65 years old) with primary breast cancer. The key disease-related health states were disease-free, recurrence, and death. Recurrence was mostly separated into locoregional and distant recurrence. These findings were used to design a Markov model in the following decision modelling. In the base-case analysis of decision analytical modelling, the deterministic results showed that patients who received PETx as the initial treatment had lower costs and QALYs compared with patients who received surgery; the mean ICUR was £194 per QALY. However, for patients with H-score >250, PETx was associated with higher costs and lower QALYs; the mean ICUR was -£1849 per QALY. In the probabilistic sensitivity analysis, PETx was associated with lower costs and QALYs. The mean ICUR was £363 per QALY, 95%CI: -6014.99, 5,756.86). However, for patients with H-score >250, PETx was associated with higher costs and lower QALYs. The mean ICUR was -£390.67 per QALY (95%CI: -7,295, 7776.54). The probability of PETx being cost-effective in a situation where the decision-maker is willing to accept (WTA) £21,000 per QALY was 24%. In the subgroup analysis, PETx was associated with slightly lower QALYs and higher costs. The probability of PETx being cost-effective in a situation where the decision-maker is willing to accept £21,000 per QALY was 43%. Conclusion The main findings from this study showed that PETx was not cost-effective compared to surgery. However, this study was mainly based on the effectiveness and cost from a single observational study in a secondary care setting, and other information (evidence) that may bias the effectiveness and cost estimates, including frailty status, adherence, comorbidities, and other unmeasured confounders were not recorded, and thus, may bias the cost-effectiveness results. Future research is recommended to collect further information on patients’ characteristics, including frailty, adherence, and adverse events that may influence the cost-effectiveness results. Moreover, collecting detailed estimation of the resource use in order to provide an accurate estimate for costs.

Background and objectives: An increasing number of cancer patients have described experiencing cognitive dysfunctions which are associated with their chemotherapy treatment. This has been called “chemobrain” in patient forums and articles. It has been shown in animal models treated with a range of chemotherapy agents that chemotherapy induces cognitive deficits and a decrease in hippocampal neurogenesis. Antidepressants, anti-inflammatory drugs and physical activity have been proposed to counteract the effect of chemotherapy and provide protection against cognitive impairment associated with cancer treatments. This thesis has used in vivo studies, in rats and Sox1-GFP transgenic mice to firstly evaluate the effect of acute and chronic 5-Fluoruracil (5-FU) treatment on different subpopulations of neural stem cells in the hippocampus. Secondly, the effect of prior treatment with the antidepressant fluoxetine and the anti-inflammatory indomethacin on the impact of chronic treatment with chemotherapy was measured in terms of their effect on cell proliferation, inflammation and DNA damage. The effect of prior physical exercise on acute treatment with 5-Fluoruracil was measured in terms of cell proliferation and differentiation. Methods: Animals were administrated either acute (single injection) or chronic (4 to 6 injections) of 5-FU with or without fluoxetine and indomethacin or physical exercise. Cell proliferation (Ki67), early neural differentiation (DCX), neural stem cells markers (GFAP, Sox1), inflammation (Iba1, Cox2) and DNA damage (γ-H2AX) were quantified by immunostaining either 24hr or 1 week after the last injection of chemotherapy. Morphological studies, to differentiate different stages of neural stem cells development and the state of microglia activation were conducted using confocal imaging. 3 Results: Acute treatment of Sox1-GFP mice with 5-FU caused a decrease in cell proliferation while chronic treatment induced a depletion of the neural stem cell pool and a reduction of the number of microglia. Prior chronic treatment with indomethacin did not prevent the decrease in the number of neural stem cells but did prevent the decline in cell proliferation and microglia. Rats chronically injected with chemotherapy and allowed to recover for 1 week, showed a decreased proliferation and number of microglia, an increased microglia activation, Cox-2 expression and DNA damage. Prior chronic treatment with fluoxetine prevent the decrease in proliferation and number of microglia, the increased microglia activation and DNA damage. Prior treatment with fluoxetine and indomethacin prevented these effects. Physical exercise prior to acute treatment with 5-FU enhanced the overall amount of neurogenesis but, possibly, due to a low dose of chemotherapy it was not possible see a significant effect of the chemotherapy. Conclusions: The chemotherapy agent 5-FU affected the neural stem cell pool and the number of proliferating cells in the hippocampus. Chronic administration with fluoxetine can prevent the decrease in the number of proliferating cells, microglia activation and DNA damage while treatment with Indomethacin protects only against the effect of 5-FU on proliferating cells and microglia activation.

Plant natural products have played a pivotal role in the discovery and development of many new drugs for the treatment of various infectious diseases and cancers. The present study was therefore aimed at isolation and identification of novel bioactive compounds from selected plants collected in Malaysia with anti-cancer activity. Plant crude extracts were obtained using solvent extraction methods, while various chromatographic and spectroscopic methods were employed for compound isolation and structure elucidation. Evaluation of pure compounds and crude extracts for anti-cancer activity involved the use of Neutral Red assay (NR), acradine orange – ethidium bromide (AO/EB) staining and cell cycle analysis. Phytochemical investigations of five Malaysian plants, namely, Ficus hispida, F. fistulosa, F. schwarzii, Artocarpus heterophyllus x integer and Macaranga hypoleuca, with the focus on alkaloids and flavonoids, have resulted in the isolation of a total of 24 compounds, of which six are new. The leaf and stem-bark extracts of Ficus hispida yielded two new alkaloids, hispidacine (1) and hispiloscine (2), and a known alkaloid, 13a(S)-(+)-deoxypergularinine (3). Hispidacine represents the first example of an 8,4'-oxyneolignan incorporated an unusual 2-hydroxyethylamine moiety, while hispiloscine represents the first naturally occurring phenanthroindolizidine alkaloid with acetoxy substitution. The leaf and bark extracts of Ficus fistulosa provided two new septicine alkaloids, fistulopsines A and B (4 and 5), together with four known phenanthroindolizidine alkaloids, 13a(R)-(–)-3,6-didemethylisotylocrebrine (6), 13a(S)-(+)-tylocrebrine (7), 13a(S)-(+)-tylophorine (8) and 13a(S)-(+)-septicine (9), and one known non-alkaloid (vomifoliol, 10). The leaves of Ficus schwarzii gave two novel tri-nor-sesquilignan alkaloids, schwarzinicines A and B (11 and 12). The bark of Artocarpus heterophyllus x integer yielded five known compounds, of which four are prenylated flavonoids, namely, cudraflavone C (13), artocarpetin A (14), cycloheterophyllin (15) and artonin J (16), and one natural xanthone, lichexanthone (17). The leaves of Macaranga hypoleuca provided seven known compounds, of which three are flavonoid glycosides, namely, quercetin-3-O--L-arabinopyranoside (18), quercetin-3-O--L-arabinofuranoside (19) and quercetin-3-O-β-D-galactoside (20), three are flavonoid aglycones, namely, quercetin (21), kaempherol (22), and 5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)chroman-4-one (23), and one sterol 3-epi-taraxerol (24). Preliminary screening by NR assay found that the crude extracts (except for Artocarpus heterophyllus x integer) showed growth inhibitory activities against human breast (MDA-MB-231 and MCF-7), lung (A549), and colon (HCT-116) cancer cell lines. Of the 24 pure compounds obtained, hispiloscine (2), fistulopsine A (4), fistulopsine B (5) and cudraflavone C (13) were found to show growth inhibitory activity against colon (HCT-116) and breast (MCF-7) cancer cells. Furthermore, 4 and 5 were found to dominantly arrest cells in G1 phase of the cell cycle without the induction of apoptosis. Cell cycle perturbation of these compounds was found to be reversible for HCT-116 cells at the onset of 72 hours. These results suggest that 4 and 5 have the potential to be further exploited for the development of new anti-cancer agents.

Tumour development is a complex process involving susceptibility loci (oncogenes) and the accumulation of spontaneous somatic mutations in tumour suppressor genes that interact to result in cancer. Tumours may require the accumulation of a variety of mutations before developing but the general principle is that the mutations result in an imbalance between the oncogene and tumour suppressor gene function (Berger et al., 2011). This multi-hit process can be tested by subjecting strains of mice susceptible to certain types of tumours to chemical mutagens, thereby inducing further mutations. This technique is used in this study to identify loci resulting in the susceptibility to thymic lymphoma in the C57BL/6J strain in order to further our understanding of the processes involved in the development of such tumours.

Mounting evidence from imaging studies, developmental disorders and typically-developing children suggests that different domains of functioning are more closely related than previously considered. This is reflected in theories of development which are increasingly recognising that developmental progression should be considered as an integrated process, with associations between domains. The extent of the interrelation between cognitive and motor skills remains unclear despite previous investigations. Examination of this relationship in typically-developing children is important to clarify the nature of this link, thereby informing theories of development for both typical and atypical populations. This thesis investigated the underlying nature of the association between cognitive and motor domains to establish the extent of interrelation and whether this link alters across development. As the cerebellum has been hypothesised to be instrumental in this relationship (Diamond, 2000), the role of the cerebellum was investigated by examining cognitive and motor development in children treated for cerebellar tumour in the preschool years (N=15). The impact of cerebellar injury on development of scholastic and attentional skills was also investigated, together with the influence of factors affecting prognosis. The interrelation of cognitive and motor skills in typically-developing children (N=248; 4-11 years) was found to be underpinned by a link between visual processing abilities and fine manual motor skills. Despite fluctuations in correlations between other aspects of cognitive and motor functioning, this core relationship remained constant, furthering evidence that cognitive and motor development are linked from an early age. A similar pattern of correlations was seen for the patient sample, suggesting that development in these domains remains tightly linked despite damage to an underlying component of the anatomical network. This suggests that the patients are demonstrating a developmental delay, rather than deviation; their trajectory does not appear to be qualitatively different from that of typically-developing children, rather development appears to be more constrained than suggested by some hypotheses (e.g. Karmiloff-Smith, 1992). Cerebellar damage was therefore found to impact on the two domains similarly, offering support to a „universal cerebellar transform‟ (Schmahmann, 2000b) conceptualisation of cerebellar functioning. Both cognitive and motor skills were found to be compromised following a cerebellar tumour, although no specific impact of cerebellar damage was reported on scholastic skills, above and beyond general cognitive deficit. Attention was found to be impaired in the patient sample, with sustained attention most closely related to functioning in cognitive, academic and motor skills, suggesting that a deficit in this basic underlying process underlies difficulties in other domains. In addition, sustained attention was implicated in the association between visual processing and fine manual control in the patient sample, suggesting that this core link may be further underpinned by more basic cognitive processes. Effective rehabilitation may therefore target sustained attention, as this appears to be related to functioning in the other domains assessed in this study, as well as recognising that an integrated approach across domains is likely to yield maximum benefits. Of the potential moderating factors investigated, age at diagnosis and tumour type/treatment were found to be the most reliable predictors of outcome. This research highlights the importance of a case-study approach, and the clinical importance of individual investigation of each child‟s needs for rehabilitation.