Introduction This thesis describes a research study designed to examine the consequences of disability arising out of spinal cord compression secondary to cancer, and to examine the rehabilitation services available to patients. Research aims and questions The study was intended to achieve the following: 1. To ascertain what might constitute effective rehabilitation interventions for patients with metastatic spinal cord compression. 2. To identify the conditions in which these intervention might be delivered. 3. To ground proposals in spinal cord compression patients’ experience of disability. The following research questions were posed: 1. What are the consequences of disability for patients with metastatic spinal cord compression? 2. What strategies do patients themselves use to manage disability? 3. What do health care staff, particularly rehabilitation professionals, understand to be the consequences of disability for this patient group, and correspondingly, what are their views on the significance and provision of rehabilitation? 4. To what extent is rehabilitation being provided to these patients, and with what effect? 5. Where rehabilitation is not being provided, why is this the case? Study design The study had two components: • A series of nine in-depth interview-based case studies, which involved talking to patients about their experiences of living with spinal cord compression, as well as gaining the perspectives of family members and the health professionals who provided care and services. • A retrospective audit of the medical records of 73 spinal cord compression patients admitted to a radiotherapy in-patient unit (the Frank Ellis Unit at the Churchill Hospital in Oxford) over a two year period (July 2003 – June 2005), identifying disability-related problems and the measures taken to address them. This was a Phase I modelling study in terms of the Medical Research Council’s framework for evaluating complex interventions, with Pawson and Tilley’s (1997) Context-Mechanism-Outcome configuration adopted as a conceptual basis for data collection. Within-case analysis was informed by George and Bennett’s (2004) account of process tracing, and between-case analysis was modelled on the constant comparative method of Glaser and Strauss (1967) with an analysis of narrative as a variation on that theme. Results Disability is a serious problem for patients with spinal cord compression, but it is one problem among many others, not the least of which are the physical and emotional consequences of life-threatening illness. In response to disability, patients ‘twin-track’ their attitudes to it, acknowledging but also resisting the idea of themselves as disabled, and adopting a series of psychological devices to manage the tension. In effect, patients recognise that something significant has changed and that, as a consequence, new self-management skills must be learned, functional boundaries must be explored, useful information must be sought. At the same time, they display a determination to hold on to an established identity, associated with a sense of normality. This identity embraces the idea of competence and resourcefulness, the events, activities and pleasures that one looks forward to, and the wish to avoid burdening others. It is not a ‘disabled’ identity. To some extent, these two attitudes are in tension, as one acknowledges disability while the other, implicitly or explicitly, resists it. Consequently, patients try to find ways of resolving this tension, by ‘revising downwards’ their expectations, by constantly deferring the anticipated pleasures, and by avoiding situations in which their abilities might be put to the test, or the sense of normality be disconfirmed. Health care professionals are likely to construe the patient’s response as indicative of a certain type of character – ‘realistic’ on one hand, and ‘unrealistic’ on the other. They do not see ‘acknowledging / not acknowledging’ as twin facets of a complex response to circumstances, or as something which every patient engages in to one degree or another. Patients are motivated not to recognise rehabilitation as something they need, a view which is confirmed by the cursory form of rehabilitation experienced in hospital, and by the marginal significance attributed to it by nursing and medical staff. On discharge, hospital staff assume that rehabilitation needs will be identified in the community, although the way in which community rehabilitation services are organised virtually guarantees that this will not happen, unless a specific referral is made (as it is in only 5% of cases). The patient, meanwhile, remains unaware of the potential value of rehabilitation, and has no incentive to request rehabilitation if no-one offers it. They are consequently unprepared for life post-discharge, and assume that they (and their families) must manage on their own. Conclusions Like the patients, health care professionals may have to ‘twin-track’ if they are to provide rehabilitation in a way that is acceptable to patients with metastatic spinal cord compression. Instead of categorising patients as ‘realistic’ or ‘unrealistic’, they should work towards sustaining patients’ ‘positive illusions’, while at the same time taking whatever opportunities arise to enhance the patient’s day-to-day ability to function in a ‘safe’ space. This entails revising some deeply entrenched ideas about working with patients who have a disability: patient-centredness, the importance of goal setting, and the need for adjustment.

No description available.

When a child is diagnosed with cancer, the roles and responsibilities of family members change to accommodate the demands of the illness. The current study aimed to explore the experiences of mothers of children with cancer, focusing on their constructed roles within the family context and their social support. A case study design within the qualitative research approach was employed, underpinned by social constructionism as a theoretical framework. Three mothers were selected, using a combination of purposive and snowball sample techniques. Rich descriptive data were collected from three mothers through semi-structured interviews and reflective essays, and analysed using thematic analysis techniques. Results showed that although mothers of children with cancer experience some common themes, there are contextual differences influencing how they construct their stories. The following main themes were identified in the comparative analysis: events leading to the diagnosis, emotions, life changes, the effect of the illness and coping. / Psychology / M.A. (Psychology)

This insider research journey explores the meaning-making processes of female spousal caregivers in anticipatory mourning and the knowledges which they have gained in retrospect. The research traces the social constructions of meaning and how they influence the process of meaning-making. A phenomenological study was undertaken in which unstructured interviews were conducted with five bereaved participants, highlighting the unique way in which each woman made meaning of loss in anticipatory mourning. The main phenomenological themes to emerge from their meaning-making were: a) the significance of time; b) challenges and gifts; c) witnessing the decline; d) paradoxes; e) the significance of the spousal relationship; and f) spirituality. The therapeutic effect of telling the life story is explored in this study and the need for contextual pastoral care that is specific to the state of anticipatory mourning is highlighted. Finally, possibilities for co-constructive pastoral care are raised in the light of the research findings. / Philosophy, Practical and Systematic Theology / M. Th. ( Practical Theology, with Specialisation in Pastoral Therapy)

The purpose of this research is to explore how narrative practices can be meaningful in pastoral conversations with women living with breast cancer. A theoretical collaboration between narrative therapy, feminism and pastoral theology has been used in order to facilitate meaning-making, to give ‘voice’ to local knowledge, and to co-create a more holistic understanding of the experiences of illness narratives and breast cancer. The methodology of this research is ‘interdisciplinary’ and uses qualitative, co-participatory action research and reflexivity as its research design. Conversations with the co-researchers explore illness narratives, breast cancer, spirituality and faith, life-giving relationships, femininity and body image, socially constructed discourses and pivotal moments that enable alternative stories. Values of respect, curiosity and listening have been upheld in order to provide a safe place for the co-researchers to give voice to their stories and experiences of breast cancer in a way that supports the researcher position of ‘witness’. / Philosophy, Practical and Systematic Theology / M. Th. (Practical Theology, with specialisation in Pastoral Therapy)

O propósito desta dissertação é examinar como mulheres percebem e vivenciam a experiência de serem diagnosticadas com câncer de mama. A pesquisa social de campo envolve um universo de oito mulheres que passaram por esta trajetória sendo uma delas a própria autora, que traça uma auto-análise de sua experiência com este diagnóstico. Um aspecto específico com o qual a pesquisa busca se ocupar é identificar o lugar que a espiritualidade ocupa na história das mulheres entrevistadas. O câncer de mama apresenta um alto índice da doença no Rio Grande do Sul. Conforme a Revista Gaúcha de Enfermagem, o câncer de mama é a maior causa de morte de mulheres entre 30 a 50 anos de idade. De acordo com as estatísticas do Instituto Nacional do Câncer, o câncer de mama é o segundo tipo mais freqüente de câncer do mundo. Assim sendo, o câncer de mama ainda é uma doença que leva à morte, mesmo com o enorme avanço da medicina. Mas, há quem sobreviva o temido e assustador processo da descoberta e tratamento do câncer. Com a doença do câncer vem também a angústia da finitude. O presente trabalho baseia suas reflexões teóricas em Eugen Drewermann e Paul Tillich e como os mesmos descrevem a angústia existencial do ser humano, diferenciando-a do medo real, que tem o seu objeto definido, enquanto que a angústia existencial tem como fonte de sua permanente ameaça o nada. A angústia e a culpa estão relacionadas, estando a culpa ligada ao afastamento de Deus. A aceitação do ser finito, através da coragem do ser, ato de fé por graça divina, substitui, em última análise, a angústia por confiança no Deus da Vida. Os autores, ambos os teólogos, apontam para a interdisciplinaridade. A proposta dessa pesquisa é de atuar em colaboração com outras ciências, de maneira especial com a Psicologia Analítica. Uma pessoa em crise, que trabalha seus processos interiores, poderá ter facilitado sua entrega confiante a Deus. É ainda sucintamente apresentado, conforme Drewermann, como o patológico se manifesta na vida de pessoas que, assim como todas as demais pessoas, carecem da experiência da graça de Deus para sua libertação. A pesquisa finaliza trazendo a abordagem de Erika Schuchardt, formulada no modelo de uma espiral de oito fases, pelas quais passam as pessoas em crise. / The purpose of this dissertation is to examine how women perceive and live the experience of receiving a diagnostic of breast cancer. Field research involves a total of eight women who have experienced this situation, one of them being the authors self-reflection on a cancer diagnostic. A specific aspect of the present research is to identify the place that spirituality takes in the life history of the interviewed women. The State of Rio Grande do Sul presents a high rate of breast cancer. According to the agency Revistal Gaúcha de Enfermagem, breast cancer is the death main cause among women between thirty and fifty years old. Statistics of the National Cancer Institute indicates that breast cancer occupies the second place among the different sorts of cancer. Even though medicine has shown great advance in the last decades, breast cancer still continues to be a deadly disease. However, there are people who survive the fearsome and frightening fatal process caused by this disease. With cancer comes along the human finitude anxiety. The present work bases its reflection on how Eugen Drewermann and Paul Tillich describe the human existential anxiety distinguishing it from real fear. According to the authors real fear has its object defined, while existential anguish has as source of its permanent threat, the nothingness. Anguish and guilt are connected, but guilt is associated to the alienation from God. Acceptance of the existence as finite, through the courage of Being, which is an act of faith by divine grace, replaces anguish by trust in the God of Life. The authors above, both theologians, aim at interdisciplinarity. The purpose of this research is to act in collaboration with other sciences, specially with Analytical Psychology. A person in crisis working her/his interior processes might have facilitated the confident surrender to God. It is also briefly presented, according to Drewermann, how pathology evidences itself in the life of a person who, as all other persons, lacks the experience of the grace of God to his/her liberation. Concluding, the research approaches Erika Schuchartds theory formulated in the model for working through crisis in eight spiral phases.

Doctorat en sciences psychologiques / info:eu-repo/semantics/nonPublished

La voie de signalisation mTOR (mammalian Target Of Rapamycin) joue un rôle central dans la croissance cellulaire, le métabolisme, et l'homéostasie des lymphocytes T (LT). Lors de la transplantation d'organes, l'administration de rapamycine, un inhibiteur de mTOR (mTORi), bloque l'activation des LT et promeut la polarisation des lymphocytes T CD4 régulateur (Treg). En cancérologie, des mTORi sont utilisés pour leur action inhibitrice sur la prolifération et l'angiogenèse tumorales. Cependant l'immunosuppression via l'induction de Treg nécessaire à la prévention du rejet de greffe pourrait être délétère pour la réponse anti-tumorale. Notre hypothèse est que l'efficacité clinique des mTORi serait également dépendante de la modulation de l'immunité adaptative T induite par ces traitements chez les patients atteints de cancer.Au cours de cette thèse, nous avons abordé cette question immunologique dans une cohorte prospective de patients atteints de cancer rénal métastatique (mRCC) traités par évérolimus. L'analyse du taux de Treg et de la réponse spontanée T CD4 Thl anti-tumorale (anti-télomérase TERT) par Elispot-IFN-y a été effectuée au moment de l'inclusion des patients et tous les deux mois après le début du traitement. Nous avons observé chez la majorité des patients une augmentation du taux de Treg après traitement par évérolimus. Ces Treg expriment Hélios, suggérant un phénotype Treg naturel. La fréquence et la qualité de la réponse Thl anti-TERT sont également augmentées suite au traitement. Nous avons montré que conjointement ces deux paramètres immunologiques corrèlent avec l'efficacité clinique du traitement. Les patients présentant précocement une diminution des Treg associée à une augmentation des Thl anti-TERT ont une meilleure survie par rapport aux patients dont les paramètres immunitaires ne variaient pas, ou variaient dans une même direction (13,2 mois vs 8 et 4 mois). De plus, au moment de la progression la plupart des patients perdaient leur réponse Thl anti-TERT, et cet effet était associé à une augmentation des Treg. Les Treg traités par mTORi in vitro inhibent plus fortement la prolifération de LT allogéniques, par un mécanisme contact dépendant. Par l'utilisation d'anticorps monoclonaux déplétant les LT chez la souris et par l'utilisation de souris DEREG, nous avons montré que la présence de Treg in vivo altère l'efficacité anti-tumorale des mTORi, par un mécanisme impliquant l'inhibition des réponses T CD8 anti-tumorales. En conséquence, l'efficacité des mTORi a pu être augmentée par sa combinaison avec des agents bloquant les Treg. En addition, l'administration de temsirolimus améliore l'efficacité anti-tumorale d'un vaccin thérapeutique, en favorisant la différenciation des LT CD8 anti-tumoraux centraux mémoires (CD62L+CD127+) et précurseurs mémoires (CD127+KLRGl'°) induits par la vaccination.En conclusion, ces études ont montré pour la première fois le rôle de l'immunité T anti-tumorale sur l'efficacité clinique des mTORi et soulignent ainsi l'intérêt potentiel de combiner les mTORi avec des immunothérapies anti-tumorales / The mammalian Target of Rapamycin (mTOR) pathway plays a central role in the regulation of cell growth andmetabolism, and is involved in oncogenesis. Everolimus and temsirolimus are two mTOR inhibitors (mTORi) approvedfor renal and breast carcinoma treatments. However, accumulating evidence highlights a central role for mTOR pathwayin T cell immunity. We showed that 21 out of 23 metastatic renal cell carcinoma patients under everolimus treatmenthad an increase of Tregs atter everolimus treatment. Paradoxically, strong antitumor Th 1 responses were detected andthen greatly decreased at the time of disease progression when high expansion of Tregs occurred. Furthermore, weidentified three immune groups based on the early modulation of both Treg and anti-tumor Thl cells and found thatpatients with {low Tregs plus high anti-tumor Thl cells} showed the best survival. In vitro, mTORi-exposed Tregs highlysuppressed T cell proliferation and Thl-associated cytokines production. We showed in vivo that T cells depletiondifferentially modulated the antitumor efficacy of mTORi. Although anti-mTOR effect was loss in B16-OVA-bearingmice lacking CD8 T cells, CD4 T depletion increased mTORi efficacy. The studies conducted in mice demonstratedthat the presence of Tregs in vivo altered the responses to mTORi via a mechanism involving the inhibition of antitumorCD8 T cell responses. Finally the efficacy of mTORi was improved by combination with Tregs depleting agents andvaccines. Altogether, our results describe for the first time a dual impact of host adaptive antitumor T cell immunity onthe clinical effectiveness of mTQRi and prompt their association with immunotherapies.

This PhD thesis explored the experiences of dependent children and children care-givers facing challenges with their parent s cancer. The aim was to understand children s information experience including their perception of cancer and information culture; information needs, information seeking behaviour, barriers and enablers. The research used a six-stage process. This was informed by an extensive literature review and discussions with cancer specialists, psychologists and researchers from United Kingdom, United States, Australia and Malaysia. This study used a three-cycle, eight-step process of Participative Action Research (PAR) with participation from ten Malay breast cancer patients and their dependent children. Three bilingual (English and Bahasa Malaysia) instruments were developed; 1) An Inquiry to Participate Form to select participants who had dependent children, 2) Three opened-ended questions to obtain children s cancer experience and information needs where drawing was used to encourage children s responses and, 3) A 15-question questionnaire to understand children s experience and information preference. Cancer affected parenting abilities and challenging experiences identified the lack of culturally relevant information and the shift in caregiving responsibilities to dependent children. Children s understanding of cancer was influenced by their experiences and observations, many of which resulted in misconceptions about cancer, its causes, treatment and preventative measures. Children participant s reaction to a health situation triggered their information behaviour. The burden of caregiving and the consequences of a lack of information were greater than anticipated; children had many dimensions of concern and experienced many challenges. This advocated for a more assessable, attractive and sensitive information system. Data synthesis contributed to the development of a Children s Reactive Information Seeking Behaviour An Integrated Model that seeks to explain the relationship between children participants reaction to a health situation and the subsequent processes they undergo to resolve their state of information need.

The thesis discusses the methods of determination of tumor markers and their clinical importance in medical diagnostics. The theoretical part describes clinically important tumor markers and also the chemiluminescent immunoassay methods used for their determination. The practical part of the thesis describes the introduction of new chemiluminescent methods for the determination of tumor markers in routine operation, evaluates its basic analytical parameters and compares it with the existing immunoturbidimetric method. The practical part also presents results of monitoring of cancer patients with various tumors, which is performed by evaluation of the values of tumor markers. Comparison of our method with other methods within the context of System of external quality control is also documented.