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1رسالة جامعية
المؤلفون: Campbell, Evan
مصطلحات موضوعية: R Medicine (General)
الوصف: Progressive Multiple Sclerosis (MS) is a degenerative neurological disease with no known cure. The overall aim of the research within this thesis was to investigate physiotherapy, an important part of the care, for people with progressive MS. This was done in three studies. A systematic review of the current literature for the effectiveness of physiotherapy for the rehabilitation of people with progressive MS; an online survey of people with progressive MS assessing levels of access to, and use of, clinical services across the United Kingdom; and a feasibility study of High Intensity Interval Training (HIIT) for people with progressive MS. The systematic search returned 15 studies, 482 participants in total, which investigated eight different interventions: exercise therapy, multi-disciplinary rehabilitation, functional electrical stimulation, botulinum toxin type A injections and manual stretches, inspiratory muscle training, therapeutic standing, acupuncture and body weight supported treadmill training. All studies, apart from one, produced a positive result, however, only one study was adequately powered. In conclusion, the review found that the evidence was positive for using physiotherapy for rehabilitation in people with progressive MS, but further adequately powered research, is required to strengthen this. In total 1298 people with progressive MS from across the United Kingdom completed the online survey in August to October 2015. Participants were asked regarding access and use of clinical services, delivery and opinion of physiotherapy, and use of complementary and alternative therapies. Access to MS Specialists was high (95%), as was access to a physiotherapist (87%). Seventy seven percent of physiotherapy was delivered by the National Health Service and 32% were currently receiving physiotherapy for their MS. Physiotherapy was very well perceived by people with progressive MS and the most common interventions received were independent (83%) and supervised exercise (71%). Five percent of respondents were currently using disease modifying therapies and 23% had previously taken them. Almost three quarters (74%) received a regular review but 37% received this review less than annually. It was recommended that service providers make steps to address this gap in service provision. Finally, eight weeks of twice weekly HIIT sessions were compared to twice weekly sessions of continuous moderate intensity training. Ten out of twelve participants completed the trial. The HIIT intervention was well tolerated with 93% adherence, 100% compliance with protocol and no adverse events. There were three adverse events in the continuous training group and compliance was 79%. In addition, those who received HIIT improved their maximal heart rate and mental processing speed while no changes were found in the continuous training group. A larger, fully powered trial is required to confirm these results. Overall the studies within this thesis demonstrate that physiotherapy has the potential to be beneficial in the rehabilitation of people with progressive MS, that people with progressive MS are engaging with physiotherapy, and that interventions such as HIIT may provide new avenues for eliciting health benefits from this patient group. However, despite these positive findings, more work is required to strengthen the evidence base and gaps in service provision should be addressed.
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2رسالة جامعية
المؤلفون: Campbell, Eimear
مصطلحات موضوعية: T Technology (General)
الوصف: With dwindling worldwide petroleum supplies, there is an ever increasing pressure on the oil industry to develop new reservoir recovery mechanisms or maximise the effectiveness of those currently utilised. Fluctuations of reservoir recovery as a result of nearby seismic activity has been observed, initiating a range of studies into what is causing this effect. The generation of ultrasonic wave fields due to the dispersion of seismic wave fields as they travel through saturated porous rock has been shown, both analytically and experimentally. The feasibility of these generated ultrasonic waves being capable of this observed modification to reservoir is investigated. For the initial stage of this research, the feasibility of changing the behaviour of fluid in rock using an ultrasonic field is considered. Research into the interaction between acoustic waves, the porous rock and the pore fluid indicates two key areas of permeability enhancement - increasing rock permeability and modifying the fluid behaviour within the pores. By increasing the permeability of the rock, previously unobtainable sources may be recovered and less energy would be necessary to obtain these reserves. Cavitation erosion or localised rock weakening due regions of high stress resulting from complex internal wave interactions are the two mechanisms proposed to increase permeability. Modification of the relative fluid behaviours within the rock as a result of mechanical agitation of the fluid from peristaltic transport and cavitation bubbles generated due to the acoustic field was explored. Sandstone cores saturated partially with tap water were placed in a degassed fluid and a low or high acoustic field applied. Tensile strength measurements are taken following exposure to the acoustic field and measurements compared to control samples. Samples were weighed prior to and following testing to determine fluid and gas motion between the surrounding fluid and pore volume. Samples exposed to the low amplitude acoustic pressure field showed no change in tensile strength when compared to control samples. The high pressure acoustic field caused samples to have an increase of strength when compared to the control batch of samples. The partial saturation of the samples exposed to the acoustic pressure field showed an increased in mass following exposure. An exchange of gas bubbles trapped within the pores and fluid with the surrounding degassed water explains this mass increase during testing.
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3رسالة جامعية
المؤلفون: Campbell, Esther Jennifer
مصطلحات موضوعية: 616.99, RC0254 Neoplasms. Tumors. Oncology (including Cancer)
الوصف: Over 1 million women a year are diagnosed with Breast Cancer. The majority, approximately 70% express the oestrogen receptor (ER). ER positive breast cancer has historically been perceived as a ‘good cancer’, although many woman with ER+ breast cancer still succumb to their disease and globally breast cancer is the leading cause of female cancer deaths. The advent of gene expression profiling and the definition of the molecular instrinsic subtypes has defined at least two subtypes of ER positive breast cancers (luminal A and luminal B) that differ markedly in terms of biological behaviour, response to adjuvant therapies and most importantly patient outcome. The focus of this research is ER+ breast cancer and targeting patient therapy in this heterogeneous group. This work attempts to translate our understanding of the biology of the ER and cell signalling interactions to aid the correct identification of patients for both current therapy and more novel therapeutic approaches. Following a hypothesis generating pilot study examining whether the level of ER influences response to endocrine therapy, 557 formalin fixed paraffin embedded (FFPE) breast cancer specimens retrieved at time of definitive surgery from early breast cancer patients with available accurate 15 years follow up data were analysed to measure ER, Progesterone receptor (PgR), HER2 and Ki67 expression using immunohistochemistry. Tumour expression of ER, PgR and the combined endocrine receptor (CER), which considers the expression level of both hormone receptors and hypothesised to more accurately quantify endocrine responsiveness by acting as a surrogate marker of a functioning ER signalling pathway, were analysed. The results suggest that in this cohort of ER+ endocrine treated patients CER is a better predictor of endocrine response than either the ER of PgR independently. The CER was thereafter utilised as a surrogate marker of oestrogen receptor signalling pathway to develop a scoring system which included HER2 IHC expression and tumour histological grade, as surrogate markers of the 3 key pathways (ER signalling, HER2 signalling and proliferation). These were chosen as previous studies comparing various gene prognostic profiles indicate commonality in sampling groups of the genes representing their activation. The scoring system, named the Clinical Outcome Score (COS) was developed to represent a pragmatic equivalent of gene prognostic profiles utilising currently routinely measured tumour markers. We hypothesised that COS as an indicator of tumour biology may aid identification of risk in the very challenging group, ER+/HER2 negative patients with intermediate grade and low disease burden, and may help guide adjuvant therapy decisions particularly the indication for chemotherapy. In this exploratory analysis, the distribution of COS scores (2-10) followed a linear response with a notable separation between low scores (2-4) and high scores (5-10). Importantly, when analysed in combination with tumour burden, low COS may help identify patients with nearly 100% long term survival, however in all analysis high COS was associated with a highly significant poorer outcome in terms of early recurrence, late recurrence and 15 year breast cancer specific survival. This group of high risk ER+ breast cancer patients represent a real challenge (and concern) in the treatment of early breast cancer, as there is increasing evidence that ER+ tumours are relatively chemo-in senstive and the response to chemotherapy agents is limited. As a secondary analysis, within our cohort of ER+/ HER2- endocrine treated patients we retrospectively analysed the benefit of chemotherapy in patients with low and high COS scores and the results indicate lack of benefit in the cohort of patients diagnosed 1995-1998. Investigating novel therapeutic targets focusing on the subtypes of breast cancer, and tumour biology involved in endocrine resistance is now beginning to take precedence in breast cancer research. Two potential new therapeutic targets in ER+ breast cancer were studied. The first is the sodium iodide symporter, NIS, a transmembrane glycoprotein which has been exploited for the safe delivery of radio-iodide in the treatment of thyroid cancers for many years. NIS is expressed in many breast cancers, however most breast cancers expressing NIS lack functional uptake as demonstrated by scintography studies and in vivo animal work. In vitro results suggest that the ER is important in NIS regulation and function. In addition MAPK and PI3K-Akt signalling pathways may have a role in NIS regulation- both these pathways are often activated in ER+ breast cancer and known to have extensive crosstalk with the ER. Utilising ER+ and ER negative breast cancer cell lines we examined NIS function following gene delivery with a human NIS (hNIS) transfected plasmid and assessed function and expression of NIS following ER knockdown by siRNA. Our results suggest that the ER phenotype is important but not necessarily the ER per say. We examined NIS expression in a mixed ER+ and ER- cohort (n=50) of patient tumour samples using real time RT-PCR, and report high levels of NIS mRNA expression was limited to ER+ breast tumours. Prompting analysis of NIS expression, cellular location and correlations with cell signalling proteins in 300 ER+ breast cancers using IHC. Significant correlations were identified with key members of the PI3K-Akt and MAPK supporting their role in NIS regulation in vivo. Importantly, in both patient cohorts NIS was found to be significantly associated with poor outcome, and we hypothesis that this is an effect of enhanced growth factor signalling and activation of pathways in biologically more aggressive ER+ cancer (ER+/PgR-) may also regulate NIS and suggest future directions of research. Lastly, as a pilot study expression of Src kinase, a non receptor tyrosine kinase implicated in tamoxifen resistance and breast cancer virulence, was analysed by IHC in the ER+ breast cancer patient cohort. Interestingly nuclear Src kinase was found to be associated with improved outcome and hypothesise that Src Kinase expression in breast cancer may have varying roles in the different subtypes of breast cancer, an important consideration as Src Kinase inhibitors are currently in clinical trials. This pilot study formed a hypothesis that was subsequently examined in another student’s PhD thesis.
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4رسالة جامعية
المؤلفون: Campbell, Elizabeth
مصطلحات موضوعية: 371.9, LC Special aspects of education
الوصف: This thesis is about the story of the development of Adult Literacy and Numeracy policy and practice in Scotland. It includes some of my personal experiences over the past thirty years working in the field of adult education and particularly in literacies. However, the focus is primarily on the years 2000 –2006 when major developments took place in this field of adult learning. One of the tenets of the ‘new literacies’ policy and practice is that it is predicated on a social practice model. This thesis explores whether this assertion is rhetoric or reality. In the process the thesis outlines what the term social practice means to theorists, academics and those involved in the direct delivery of literacies. It examines the policy documents and the practices of managers and tutors and learner outcomes. The thesis argues that, while a learner centred approach is integral to any good adult education practice, it does not equate to the use of a social practice model and more requires to be done before it can be claimed that Scotland truly operates a social practice model in the delivery of Adult Literacy and Numeracy. The first five chapters of the thesis outline the historical context of literacies development in Scotland, locate my methodological approach, explore what is meant by social practices, sketch the development of policy and practice in Scotland and describe the methods used to gather data. The following three chapters explore the responses of the managers, tutors and learners that informed the outcomes of the research. The final chapters analyse the data and address three pertinent questions. Firstly, is it possible/likely that a full social practice model can become the norm in Scotland, secondly, whether it is possible to develop this model at a national level anywhere considering the current global situation and thirdly, how can the good practice recorded in this research be sustained.
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5رسالة جامعية
