The arrival of lifelong learning within nursing constitutes a major conceptual shift that every qualified nurse is expected to adopt to be able to function as a Registered Nurse (RN) throughout their career. In the 1990s, lifelong learning had been appearing sporadically within nursing literature as a fait accompli, and with a seemingly general assumption that there was a shared understanding and acceptance of the concept amongst all nurses. The literature review revealed that lifelong learning is closely linked to the evolving nature of healthcare delivery in the National Health Service (NHS), and that it comprises of a number of related components. However, there was a dearth of empirical literature with regards to its application to day-to-day nursing practice at the time this study started. The study focused on examining the assumptions that seemed extant at the time and the areas that were not documented in the literature. It sought to ascertain the nature of RNs' perceptions of lifelong learning, and took into consideration the underlying philosophy, principles and practicalities of the concept. It also sought to identify both the formal structures required for effective implementation of lifelong learning as well as the day-to-day factors that might facilitate uptake and continuation of learning. Furthermore, the study endeavoured to ascertain the current and likely future impact of lifelong learning on nursing. To explore these issues, the study involved collecting, analysing and interpreting data from twenty-six individual interviews and two focus group discussions along with a comprehensive documentary analysis. The findings revealed that there are positive perceptions as well as reservations about lifelong learning amongst RNs, the latter mainly because mandatory continuous professional development (CPD) is resented by a number of nurses. This could be due to their lack of experience and apprehension related to studying in a university. The study found that structural mechanisms could be more firmly anchored and equitably available. Numerous day-to-day factors such as profession-based and personal networks tend to influence levels of engagement in formal learning. For instance, CPD in the form of workbased formal and informal learning is relatively widely utilised. Additionally, the impact of attitude change towards continuing development of own knowledge and competence yields favourable outcomes for the RN and for patient care.

Der Folsäureantagonist Methotrexat (MTX) wird zur Behandlung onkologischer und rheumatoider Erkrankungen eingesetzt. Die Aufnahme des Methotrexats in die Zielzelle ist dabei Vorraussetzung für die Bindung an seine intrazellulären Zielstrukturen und erfolgt über verschiedene Transportsysteme. In diesem Zusammenhang ist bei entsprechenden Plasma-konzentrationen von MTX der Reduced Folate Carrier (RFC1) von besonderer Bedeutung. 1994 konnte erstmals die cDNA dieses Transporters aus Maus- und Hamstergewebe isoliert werden. Die cDNA für einen mit dem RFC1 identischen hepatozellulären MTX-Transporter der Ratte wurde 2000 kloniert. Vorhergehende Gen-Expressionsstudien zeigten, dass die RFC1-mRNA ubiquitär gebildet wird. Die Proteinexpression wurde jedoch bisher nur in ausgewählten Geweben der Maus untersucht. Systematische Arbeiten, in denen in vergleichender Weise sowohl die RFC1 Gen- als auch die Proteinexpression in allen Geweben mit einer möglichen Relevanz für die Folat- und Antifolataufnahme, Speicherung und Eliminierung untersucht werden, fehlten bisher. Insbesondere die Expression des RFC1-Proteins der Ratte (rRFC1) mittels immunologischer Verfahren ist bisher nicht beschrieben worden. Ziel dieser Arbeit war es daher, die Gen- und Proteinexpression des rRFC1 in ausgewählten Geweben der Ratte darzustellen. Dieses schließt die Generierung spezifischer Antiseren gegen den rRFC1 als ersten Schritt mit ein. Es wurden geeignete antigene Aminosäuresequenzen des rRFC1 bestimmt und die entsprechenden cDNA Sequenzen wurden amplifiziert und in einen geeigneten Expressionsvektor kloniert. Rekombinante rRFC1 Fusionsproteine konnten mittels E. coli Zellen hergestellt und anschließend aufgereinigt werden. Nachfolgend wurden entweder die rRFC1 Fusionsproteine oder die rRFC1 spezifischen Peptide, welche von dem Affinitätspeptid separiert worden waren, für die Immunisierung von Kaninchen verwendet Drei Antiseren mit ausreichender Reaktivität und Spezifität konnten gewonnen und mittels Affinitätschromatographie aufgereinigt werden. Die erhaltenen Antiseren sind gegen die intrazellulären N- und C-terminalen Regionen (ID1, ID7) bzw. gegen die erste extrazelluläre Schleife (OD1) gerichtet. In Western-Blot Studien konnte mittels dieser Antiseren für den rRFC1, der in transfizierten Nierenepithelzellen (MDCK-rRFC-HA) stabil exprimiert wurde, ein Molekulargewicht von 71 kD für die glykosylierte Form und von 53 kD für die unglykosylierte Form ermittelt werden. Weiter konnte belegt werden, dass das Protein in MDCK-rRFC1-HA Zellen überwiegend in der glycosylierten Form vorliegt. Mittels RT-PCR Analysen wurde die Genexpression des rRFC1 in allen untersuchten Geweben nachgewiesen. Besonders hohe mRNA-Gehalte waren in Thymus, Niere und Milz vorhanden, während in Herz- und Muskelgewebe sowie in Leukozyten nur ein Signal nahe der Nachweisgrenze detektierbar war. Durch immunhistologische Untersuchungen konnten die rRFC1 Proteinexpression und beträchtliche Unterschiede in der Signalintensität bestätigt werden. Zusätzlich konnten neue Informationen über die unterschiedliche subzelluläre Lokalisation gewonnen werden: so konnte eine starke Expression des Transporters in der apikalen Membran von Dünn- und Dickdarmmukosa dargestellt werden, während die ebenfalls starke Färbung in der Niere auf den Bereich der basolateralen Membran der Tubuli beschränkt war. In der Leber war eine Expression mittlerer Intensität im Bereich der Lebertrias erkennbar. Während in der Milz nur in der roten Pulpa das RFC1-Protein detektiert wurde, konnten im Thymus sowohl in der Rinde als auch im Mark positive Zellen nachgewiesen werden. Im Hoden konnte der Transporter in den Sertoli-Zellen dargestellt werden. Eine starke Expression des Transporters wurde im Gehirn im Bereich der apikalen Membran der Ependymzellen des Plexus choroideus nachgewiesen. In der Skelettmuskulatur und im Herzgewebe beschränkte sich die Expression des rRFC1 auf das Perimysium des Muskelgewebes und auf kleinere Gefäße des Muskel- und Herzgewebes. In dieser Arbeit konnte somit gezeigt werden, dass der RFC1 der Ratte ubiquitär exprimiert wird, wobei die Expressionsstärke jedoch stark variiert. Die beobachtete Gewebslokalisation des RFC1 belegt sowohl dessen zentrale Rolle in der Folathomöostase als auch in der MTX vermittelten Organtoxizität und Pharmakokinetik, insbesondere bei der intestinalen Resorption sowie der hepatischen und renalen Exkretion.

The aim in this thesis was to gain an understanding of changes in gene expression in the hypothalamus of postpartum beef cows during the period of transition from suppressed ovarian follicular growth to increased follicular growth, and the resumption of ovulation. Beef cows tend to have an extended period of anoestrus after calving. This trait is particularly pronounced in tropically-adapted Zebu breeds. In addition to a genetic component, the postpartum anoestrous period can be influenced by age, body condition, the nutrient requirement of lactation, suckling stimulus, and maternal bonding. An extended postpartum anoestrous period is particularly evident in primiparous beef cows. This is understandable given that primiparous cows have yet to reach their mature body size which means there is a requirement to maintain maternal tissue growth whilst at the same time directing nutrients for milk production. Weaning removes maternal bonding, the suckling stimulus and nutrient requirement of milk production and, provided that nutrient supply and body condition are appropriate, primiparous cows show increased ovarian activity and resume ovulation after weaning. In the present thesis, groups of primiparous Zebu cows were weaned to promote increased ovarian follicular growth and hypothalamic gene expression was compared for weaned cows and contemporary cows that continued to lactate. Candidate genes were studied using quantitative real-time PCR (qRT-PCR) and a gene expression microarray was used to discover new genes and gene networks. Gene expression was examined in the anterior hypothalamic-preoptic area (sub-region H1) and posterior ventral hypothalamus (sub-region H2). The demarcation between H1 and H2 was a vertical line from the mid-point of the median eminence-pituitary stalk to the thalamus. Candidate genes studied by qRT-PCR included, gonadotrophin releasing hormone (GNRH1), kisspeptin (KISS1), neuropeptide Y (NPY), oestrogen receptor alpha (ESR1) and leptin receptor (LEPR). Marked regional expression was demonstrated for these genes. The expression of GNRH1 was greatest in the anterior hypothalamic region (sub-region H1) whilst the expression of KISS1 was greatest in the ventral posterior hypothalamic region (sub-region H2). Relative expression of LEPR, ESR1 and NPY was greater in H2 than H1. The regional gene expression patterns for GNRH1, KISS1, LEPR, ESR1 and NPY in the hypothalamus of cows were consistent with regional expression reported for other species. Weaning was associated with a decrease in the expression of LEPR, ESR1 and NPY. With regard to ovarian phenotype, there was a greater LEPR expression associated with ovarian phenotype 1 (OP1, follicles to 5mm) compared with ovarian phenotype 2 (OP2, follicles to 10mm) and ovarian phenotype 3 (OP3, recently ovulated) in sub-region H1. Relative expressions for ESR1, LEPR and NPY were highly correlated, particularly in sub-region H2. The evaluation of gene expression by microarray for cows with different ovarian phenotypes provided evidence of interactions between hormonal regulation and cell-cell signalling within the hypothalamus. Genes that were differentially expressed for different ovarian phenotypes were associated with reproduction, energy balance, the immune system and stress. Other genes that showed differential expression were involved with cell adhesion, synaptic transmission, ion signalling and neuronal development. The latter findings were interpreted to suggest that neuronal and glial cell plasticity is a feature of changes in reproductive functions of the hypothalamus. The evaluation of gene expression by microarray for weaned and suckled cows, irrespective of ovarian phenotype, identified differentially expressed genes associated with energy balance, fluid homeostasis, milk synthesis, stress, and oestrogen signalling. With regard the latter, thirty seven genes involved in oestrogen signalling through ESR1, or in other ways associated with oestrogen, were found to be differentially expressed between weaned and lactating cows. ESR1 occupied the central position of a primary gene network based on the present study. Six differentially expressed genes were shown by gene network analysis to be centred in nodes interacting closely with ESR1. Phospholipase-C-gamma (PLCG2), vitronectin (VTN) and endopin 1 (SERPINA3) are three genes associated with hypothalamic plasticity and neurotransmission that were differentially expressed between cows with OP1 and OP2, indicating a possible role in the shift to increased ovarian follicular growth and ovulation. The findings for ESR1 were consistent with the major role of oestrogen in female reproduction and in particular the known actions of oestrogen in regulating the hypothalamus during reproductive transition phases in females associated with puberty, seasonality and postpartum. Gonadotrophin inhibitory hormone (GnIH) is derived from Neuropeptide VF precursor (NPVF), which is encoded by NPVF gene transcripts. NPVF had reduced expression in cows that had ovulated (OP3) compared with OP1 and OP2. GnIH inhibits gonadotrophin secretion by directly acting on GnRH neurons as well as modulating the suppressive effects of oestrogen negative feedback. In addition, GnIH has been shown to play a role in seasonal regulation of reproduction in birds. The lesser expression of NPVF in cows that had resumed ovulation, particularly evident in sub-region H2, provides initial evidence that GnIH has an important role in maintaining the suppressive effects on reproduction during postpartum anoestrus in cattle. In summary, the studies in this thesis have identified hypothalamic genes and gene networks that potentially are important in the control of reproductive function in the postpartum cow. The thesis has also established that the postpartum cow can be used as an experimental model for fundamental studies that generate new knowledge on the reproductive biology of the postpartum period.

The aim in this thesis was to gain an understanding of changes in gene expression in the hypothalamus of postpartum beef cows during the period of transition from suppressed ovarian follicular growth to increased follicular growth, and the resumption of ovulation. Beef cows tend to have an extended period of anoestrus after calving. This trait is particularly pronounced in tropically-adapted Zebu breeds. In addition to a genetic component, the postpartum anoestrous period can be influenced by age, body condition, the nutrient requirement of lactation, suckling stimulus, and maternal bonding. An extended postpartum anoestrous period is particularly evident in primiparous beef cows. This is understandable given that primiparous cows have yet to reach their mature body size which means there is a requirement to maintain maternal tissue growth whilst at the same time directing nutrients for milk production. Weaning removes maternal bonding, the suckling stimulus and nutrient requirement of milk production and, provided that nutrient supply and body condition are appropriate, primiparous cows show increased ovarian activity and resume ovulation after weaning. In the present thesis, groups of primiparous Zebu cows were weaned to promote increased ovarian follicular growth and hypothalamic gene expression was compared for weaned cows and contemporary cows that continued to lactate. Candidate genes were studied using quantitative real-time PCR (qRT-PCR) and a gene expression microarray was used to discover new genes and gene networks. Gene expression was examined in the anterior hypothalamic-preoptic area (sub-region H1) and posterior ventral hypothalamus (sub-region H2). The demarcation between H1 and H2 was a vertical line from the mid-point of the median eminence-pituitary stalk to the thalamus. Candidate genes studied by qRT-PCR included, gonadotrophin releasing hormone (GNRH1), kisspeptin (KISS1), neuropeptide Y (NPY), oestrogen receptor alpha (ESR1) and leptin receptor (LEPR). Marked regional expression was demonstrated for these genes. The expression of GNRH1 was greatest in the anterior hypothalamic region (sub-region H1) whilst the expression of KISS1 was greatest in the ventral posterior hypothalamic region (sub-region H2). Relative expression of LEPR, ESR1 and NPY was greater in H2 than H1. The regional gene expression patterns for GNRH1, KISS1, LEPR, ESR1 and NPY in the hypothalamus of cows were consistent with regional expression reported for other species. Weaning was associated with a decrease in the expression of LEPR, ESR1 and NPY. With regard to ovarian phenotype, there was a greater LEPR expression associated with ovarian phenotype 1 (OP1, follicles to 5mm) compared with ovarian phenotype 2 (OP2, follicles to 10mm) and ovarian phenotype 3 (OP3, recently ovulated) in sub-region H1. Relative expressions for ESR1, LEPR and NPY were highly correlated, particularly in sub-region H2. The evaluation of gene expression by microarray for cows with different ovarian phenotypes provided evidence of interactions between hormonal regulation and cell-cell signalling within the hypothalamus. Genes that were differentially expressed for different ovarian phenotypes were associated with reproduction, energy balance, the immune system and stress. Other genes that showed differential expression were involved with cell adhesion, synaptic transmission, ion signalling and neuronal development. The latter findings were interpreted to suggest that neuronal and glial cell plasticity is a feature of changes in reproductive functions of the hypothalamus. The evaluation of gene expression by microarray for weaned and suckled cows, irrespective of ovarian phenotype, identified differentially expressed genes associated with energy balance, fluid homeostasis, milk synthesis, stress, and oestrogen signalling. With regard the latter, thirty seven genes involved in oestrogen signalling through ESR1, or in other ways associated with oestrogen, were found to be differentially expressed between weaned and lactating cows. ESR1 occupied the central position of a primary gene network based on the present study. Six differentially expressed genes were shown by gene network analysis to be centred in nodes interacting closely with ESR1. Phospholipase-C-gamma (PLCG2), vitronectin (VTN) and endopin 1 (SERPINA3) are three genes associated with hypothalamic plasticity and neurotransmission that were differentially expressed between cows with OP1 and OP2, indicating a possible role in the shift to increased ovarian follicular growth and ovulation. The findings for ESR1 were consistent with the major role of oestrogen in female reproduction and in particular the known actions of oestrogen in regulating the hypothalamus during reproductive transition phases in females associated with puberty, seasonality and postpartum. Gonadotrophin inhibitory hormone (GnIH) is derived from Neuropeptide VF precursor (NPVF), which is encoded by NPVF gene transcripts. NPVF had reduced expression in cows that had ovulated (OP3) compared with OP1 and OP2. GnIH inhibits gonadotrophin secretion by directly acting on GnRH neurons as well as modulating the suppressive effects of oestrogen negative feedback. In addition, GnIH has been shown to play a role in seasonal regulation of reproduction in birds. The lesser expression of NPVF in cows that had resumed ovulation, particularly evident in sub-region H2, provides initial evidence that GnIH has an important role in maintaining the suppressive effects on reproduction during postpartum anoestrus in cattle. In summary, the studies in this thesis have identified hypothalamic genes and gene networks that potentially are important in the control of reproductive function in the postpartum cow. The thesis has also established that the postpartum cow can be used as an experimental model for fundamental studies that generate new knowledge on the reproductive biology of the postpartum period.

The aim in this thesis was to gain an understanding of changes in gene expression in the hypothalamus of postpartum beef cows during the period of transition from suppressed ovarian follicular growth to increased follicular growth, and the resumption of ovulation. Beef cows tend to have an extended period of anoestrus after calving. This trait is particularly pronounced in tropically-adapted Zebu breeds. In addition to a genetic component, the postpartum anoestrous period can be influenced by age, body condition, the nutrient requirement of lactation, suckling stimulus, and maternal bonding. An extended postpartum anoestrous period is particularly evident in primiparous beef cows. This is understandable given that primiparous cows have yet to reach their mature body size which means there is a requirement to maintain maternal tissue growth whilst at the same time directing nutrients for milk production. Weaning removes maternal bonding, the suckling stimulus and nutrient requirement of milk production and, provided that nutrient supply and body condition are appropriate, primiparous cows show increased ovarian activity and resume ovulation after weaning. In the present thesis, groups of primiparous Zebu cows were weaned to promote increased ovarian follicular growth and hypothalamic gene expression was compared for weaned cows and contemporary cows that continued to lactate. Candidate genes were studied using quantitative real-time PCR (qRT-PCR) and a gene expression microarray was used to discover new genes and gene networks. Gene expression was examined in the anterior hypothalamic-preoptic area (sub-region H1) and posterior ventral hypothalamus (sub-region H2). The demarcation between H1 and H2 was a vertical line from the mid-point of the median eminence-pituitary stalk to the thalamus. Candidate genes studied by qRT-PCR included, gonadotrophin releasing hormone (GNRH1), kisspeptin (KISS1), neuropeptide Y (NPY), oestrogen receptor alpha (ESR1) and leptin receptor (LEPR). Marked regional expression was demonstrated for these genes. The expression of GNRH1 was greatest in the anterior hypothalamic region (sub-region H1) whilst the expression of KISS1 was greatest in the ventral posterior hypothalamic region (sub-region H2). Relative expression of LEPR, ESR1 and NPY was greater in H2 than H1. The regional gene expression patterns for GNRH1, KISS1, LEPR, ESR1 and NPY in the hypothalamus of cows were consistent with regional expression reported for other species. Weaning was associated with a decrease in the expression of LEPR, ESR1 and NPY. With regard to ovarian phenotype, there was a greater LEPR expression associated with ovarian phenotype 1 (OP1, follicles to 5mm) compared with ovarian phenotype 2 (OP2, follicles to 10mm) and ovarian phenotype 3 (OP3, recently ovulated) in sub-region H1. Relative expressions for ESR1, LEPR and NPY were highly correlated, particularly in sub-region H2. The evaluation of gene expression by microarray for cows with different ovarian phenotypes provided evidence of interactions between hormonal regulation and cell-cell signalling within the hypothalamus. Genes that were differentially expressed for different ovarian phenotypes were associated with reproduction, energy balance, the immune system and stress. Other genes that showed differential expression were involved with cell adhesion, synaptic transmission, ion signalling and neuronal development. The latter findings were interpreted to suggest that neuronal and glial cell plasticity is a feature of changes in reproductive functions of the hypothalamus. The evaluation of gene expression by microarray for weaned and suckled cows, irrespective of ovarian phenotype, identified differentially expressed genes associated with energy balance, fluid homeostasis, milk synthesis, stress, and oestrogen signalling. With regard the latter, thirty seven genes involved in oestrogen signalling through ESR1, or in other ways associated with oestrogen, were found to be differentially expressed between weaned and lactating cows. ESR1 occupied the central position of a primary gene network based on the present study. Six differentially expressed genes were shown by gene network analysis to be centred in nodes interacting closely with ESR1. Phospholipase-C-gamma (PLCG2), vitronectin (VTN) and endopin 1 (SERPINA3) are three genes associated with hypothalamic plasticity and neurotransmission that were differentially expressed between cows with OP1 and OP2, indicating a possible role in the shift to increased ovarian follicular growth and ovulation. The findings for ESR1 were consistent with the major role of oestrogen in female reproduction and in particular the known actions of oestrogen in regulating the hypothalamus during reproductive transition phases in females associated with puberty, seasonality and postpartum. Gonadotrophin inhibitory hormone (GnIH) is derived from Neuropeptide VF precursor (NPVF), which is encoded by NPVF gene transcripts. NPVF had reduced expression in cows that had ovulated (OP3) compared with OP1 and OP2. GnIH inhibits gonadotrophin secretion by directly acting on GnRH neurons as well as modulating the suppressive effects of oestrogen negative feedback. In addition, GnIH has been shown to play a role in seasonal regulation of reproduction in birds. The lesser expression of NPVF in cows that had resumed ovulation, particularly evident in sub-region H2, provides initial evidence that GnIH has an important role in maintaining the suppressive effects on reproduction during postpartum anoestrus in cattle. In summary, the studies in this thesis have identified hypothalamic genes and gene networks that potentially are important in the control of reproductive function in the postpartum cow. The thesis has also established that the postpartum cow can be used as an experimental model for fundamental studies that generate new knowledge on the reproductive biology of the postpartum period.

Background: In the United States, minorities are numerous and account for 28% of the population. It is well known that some of the cultural elements are related to the patients’ health. Therefore, it is an obligation of healthcare providers to become culturally competent to improve minorities’ overall healthcare. PURPOSE: This study was conducted to assess the cultural attitudes, skills, and knowledge of undergraduate and graduate respiratory therapy (RT) students at an urban university located in the southeastern United States. METHODS: The study used a descriptive exploratory design with a self-reporting survey. The survey instrument used was a short version of the Cultural Competence Self-Assessment “ASK” (Attitude–Skills–Knowledge) Scale. The survey was administered to a convenience sample of first and second-year BSRT and MSRT students attending an accredited RT program. The survey consisted of 24 items on a five-point Likert scale. The collected data were analyzed using descriptive statistics and independent samples t-test. RESULTS: Fifty-three students were surveyed; around two-thirds of the respondents were female. Sixty-eight percent of respondents were BSRT and 22% were MSRT students. First-year students accounted for 56.6% of the respondents and second-year students accounted for 43.4%. The majority of the respondents were under the age of 25. The respondents reported to be ready to practice in the attitude and skills subscale (4.49±.49, 4.20±.62 respectively) but they need practice based on the knowledge subscale (3.80±.86). The statistically significant findings were found between first-year and second-year respondents in the skills subscale, knowledge subscale, and the total scale. However, there were no statistically significant difference between BSRT and MSRT students. CONCLUSION: This study found that respondents made progress throughout the RT program. Also, it found that level of education has no effect on cultural competency. This may be because student’s level of cultural competence improves as they advance in their clinical course work and their educational training. The results may assist RT educators to recognize the students’ needs for more information to improve their cultural competency.

Charles University, Faculty of pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucie Ženklová Supervisors: Prof. Fabio Altieri and PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: Involvement of PDIA3 in oxidative stress response PDIA3 is a member of the protein disulfide isomerase family (PDI) and it is a stress- responsive protein. It is also involved in various cellular signalling pathways and has various functions in the cell. The best-known location is in the endoplasmic reticulum where it plays a major role mainly in the proper folding and quality control of glycoproteins, and participation in the assembly of the major histocompatibility complex class I. However, its existence has also been described in many other cell compartments, such as nucleus, mitochondria, cell surface or cytosol, where it interferes in various processes. While in some instances these roles need to be confirmed by further studies, a lot of observations confirmed its involvement in the signal transduction (for example releated with STAT protein) from the cell surface and the regulatory processes in the nucleus. Recent studies have also confirmed its increased expression in various pathological states. The aim of our work was to find out what is its role in the exposure of the MDA-MB 468...

The dominant political ideology emphasises the patient as a consumer and partner in health care. Correspondingly, the move towards patient-centred nursing, based on the principles of humanism and individualism, emphasise the central role patients' should play in the nurse-patient encounter. Additionally, changing social and demographic trends highlight the importance of medication as a health care issue. Thus, current health care policy and practice contexts highlight the importance of patients' participation in health care as consumers and partners and, nurses' ability to make an effective contribution to educating patients about medication as part of their role in health education and promotion. However, despite the significance of this context, little is known about the extent and manner of patient participation, or the contribution that nurses make to this important health promotion activity. Therefore the purpose of this study is to extend knowledge in this area by describing and explaining patient participation in medication interactions, as it occurs within the reality of the clinical context. In order to study patient participation in medication interactions in the reality of the clinical context, a case study approach was adopted. Three case sites were sampled and included: 1) an acute medical ward, 2) a community hospital rehabilitation unit, and 3) a community mental health service. Data collection methods employed to explore and describe patient participation in medication interactions included: non-participant observation, audio-recording of nurse-patient interactions, nurse interviews, patient interviews, reflective field notes, focus groups and documentation. The data analysis framework included the use of conversation analysis for nurse-patient interaction data and content analysis for other qualitative data. The findings indicate that patient participation can be understood at least in part by the communicative practices and choices that nurse and patients/clients make. More specifically a range of conversational strategies were employed by nurses to initiate and control conversations and by doing so inhibited patients' participation. However a comparison of findings across sites indicates that there were both differences and similarities in the extent to which nurses facilitated and inhibited patient participation. A number of influencing factors were identified that helped to explain these findings. These include: power, nurses' communicative style, knowledge, skills and experience, patients' age, acuity of illness and level of knowledge, and the organisation and philosophy of care. The findings from the study make a unique contribution to the body of knowledge in a number of ways. First, as the only study to describe patient participation in medication interactions between nurses and patients, it identifies that participation can occur at an interactional level, as well as a more practical level via, for example, the potential to self medicate and independently manage medications. Related to this, it has also contributed to the conceptual clarity and development of the concept of patient participation. This study has highlighted that patient participation may be realised and understood more fundamentally, at the level of the nurse-patient interaction, in contrast to previous research that conceptualises participation as making choices and involvement in decisionmaking. Furthermore, by the successful use of conversation analysis, this study has also advanced knowledge about potential ways to investigate patient participation at the level of nurse-patient discourse. Finally, this study provides a contribution to advancing theoretical explanations of patient participation through the construction of a framework of explanatory factors influencing patient participation. A framework for enabling participation has been developed based on the specific conclusions and principles for action drawn from the findings and from the philosophy of Freire (1972; 1983), which acknowledges an individual's potential to be empowered and assume control. The framework proposes that addressing attitudinal, interactional, relational, educational and contextual issues, might facilitate patient participation. Implications and recommendations reflect the practice and education requirements needed to implement such a framework.

Advances in treatment and prolonged survival times mean that increasingly individuals are living with advanced cancer, yet services remain disease orientated. This thesis has documented the process of undertaking a longitudinal qualitative study to explore the everydayness of living with locally advanced rectal cancer. The study has identified how this can influence individual’s day to day lives when the focus of care moves away from cure, but prior to the transition to ‘end of life’ care. The aim was to obtain data in which to situate local service development based on those aspects which were accorded primacy by the participants. This interpretive study used a longitudinal qualitative approach which was informed by phenomenology. The philosophical works of Heidegger, Merleau Ponty and Van Manen were influential in this work which involved ten participants, with locally advanced rectal cancer. Successive interviews with ten individuals were undertaken over a two year period. The 38 interviews were analysed using a combination of frameworks offered by Miles and Huberman and Saldana. Individuals during much of this time concentrated on maintaining normality in their everyday lives. The drive for stasis and focus on day to day living allowed the individual to remain in the present and distance a future which was associated with illness and annihilation. Crucial to this was the ability to self-manage. This allowed space to create a self-definition of health. Uncertainty during this time was life affirming. Avoiding those who may challenge this, was desirable for as long as possible. As illness progressed there was an inverse relationship between the ‘boundness’ of the body and the ‘boundness’ of the individual. Insights from this study raise the need for further research and exploration of alternative models of supportive care whilst focusing on the wellness of individuals and self-management within their daily lives.

This study was carried out following observation from health professionals in the paediatric intensive care community that the incidence of chylothorax development in infants and children in the United Kingdom was unknown. Furthermore, treatment strategies were based on limited international evidence from single centre, small scale, retrospective cohort studies or case series. The aim of this study was therefore to determine the size and extent of the problem by establishing the current incidence, patient profile, management strategies and discharge destination or outcome of infants and children who developed a chylothorax in the UK. Infants and children ≥ 24 weeks gestation to ≤ 16 years, who developed a chylothorax in the UK were prospectively reported through the British Paediatric Surveillance Unit (BPSU). Clinicians completed a questionnaire on the presentation, diagnosis, management and discharge destination or outcome of these children. Three further additional data sources were accessed to confirm this data. A total of 219 questionnaires were returned with 173 cases meeting the eligibility criteria for inclusion. The incidence in children in the UK was 1.4 in 100,000 (0.0014%), in infants ≤ 12 months 16 in 100,000 (0.016%) and for those developing a chylothorax following cardiac surgery it was 3.1% (3,100 in 100,000). The majority of chylothoraces were reported following cardiac surgery (65.3%). Chylothorax was most frequently confirmed by laboratory verification of triglyceride content of the pleural fluid ≥ 1.1 mmol/litre (66%). Although a variety of management strategies were employed, treatment with an intercostal pleural catheter (86.5%) and a Medium Chain Triglyceride (MCT) diet (89%) were most commonly reported. The majority of the children had a prolonged hospital stay (median 29.5 days), with a reported mortality of 12.5%. The results of this study indicate that the development of a chylothorax in infants and children in the UK is not common; although incidence is higher in children having cardiac surgery. The duration of hospital stay is lengthy and therefore the impact on the child, family and hospital resources are significant. Common management strategies exist, but the variation in these and the lack of an outcome based rationale suggest national guidance is required.