The clinico-pathological phenotype of sporadic Creutzfeldt-Jakob disease

Creutzfeldt -Jakob Disease (CJD) is a rare neurodegenerative disorder of the human central nervous system. It occurs in four main forms, defined essentially according to aetiology: sporadic, variant, iatrogenic and familial. All forms of the disease are characterised by the deposition of an abnormal cellular protein, the prion protein (PrPSO), within the brain. Definitive diagnosis depends on identifying this along with other neuropathological changes such as spongiform degeneration and astrocytic gliosis.To date variant CJD has followed a relatively stereotyped clinical course with fairly consistent pathological findings. However, various clinico- pathological phenotypes of sporadic CJD have been described. It is believed the disease phenotype is influenced by a number of factors including agent strain (PrP' isotype being used as a surrogate marker), and genotype (particularly a polymorphism at codon 129 of the prion protein gene).Data on 99 cases of sporadic CJD and 43 cases of variant CJD were analysed. The sporadic CJD cases were divided into 6 sub -groups, according to genotype at codon 129 (either methionine homozygous, valine homozygous or heterozygous) and PrPfes isotype (either type 1 or 2A). Some trends in clinico- pathological phenotype were found. Notably, the methionine homozygous cases with type 1 PrP`eS isotype formed the majority of cases and followed a reasonably uniform disease course. The other groups tended to include atypical cases. These differences did not achieve statistical significance and there was considerable overlap amongst cases.14 -3 -3 protein and the use of MR imaging were analysed. The results suggest that these investigations may improve the diagnostic classification of sporadic CJD. 2 The variant CJD cases followed a relatively consistent clinico- pathological course, consistent with a distinct aetiology and probably a distinct strain. The data do not support the hypothesis that different strains of the sporadic CJD agent cause distinct clinico- pathological phenotypes

The idea of antiquity in visual images of the Highlands and Islands c.1700-1880

This thesis addresses the textual bias inherent in the historiography by exploring the value of visual images as a source of evidence for cultural perceptions of the Gàidhealtachd. Visual images stood at the sharp end of the means by which stereotypes were forged and sustained. In part, this was a direct result of the special role afforded to the image in the cultural and intellectual climate of Enlightenment and post-Enlightenment Europe. This thesis looks at the evolution of visual interest in the Highlands and Islands on two fronts, documentary and aesthetic, and pays particular attention to the way in which the two main functions of the image in society came to be intertwined. This thesis argues that the concept of antiquity was the single most powerful influence driving the visual representation of the Highlands and Islands during a long period from c. 1700 to around 1880, and indeed into the twentieth century. If something could be regarded as ancient, aboriginal, dead, or even dying, it acquired both documentary and aesthetic value. This applied to actual antiquities, to customs and manners perceived as indigenous and ‘traditional’ to the region, and, ultimately, even to the physical landscape. Successive chapters explore what might now be classified as the archaeological, ethnological and geological motives for visualising the Highlands and Islands, and the bias in favour of antiquity which resulted from the spread of intellectual influences into the fine arts. The shadow of time which hallmarked visual representations of the region resulted in a preservationist mentality which has had powerful repercussions down to the present day. The body of evidence considered – which embraces maps, plans, paintings, drawings, sketches and printed images by both professionals and amateurs – must be viewed as a rich and valuable companion to the written word

An experimental approach to analysing rain droplet impingement on wind turbine blade materials

Leading edge erosion of wind turbine blades is an important issue within the industry and has been found to have a substantial impact on the annual energy output of generators. This forces operators to make blade repair a necessity, adding to the operation and maintenance costs of a project. A wind turbine’s tip speed can in some cases have an upper limit based on the erosion exhibited on the leading edge. This paper explores the variables of rainfall rate and impact velocity of the impinging droplets in an attempt to explore the recovery time of the tri-axial composite material used. It is shown that an increase in impact velocity results in a higher mass loss than an increase in the rainflow rate. Analysis using a scanning electron microscope reveals that pin holes in the laminate surface are exploited by the droplets, acting as initiation point for erosion of the composite. Overall the results suggest that the tip speed of the wind turbine blade is of greater importance when compared to the relevant rainfall conditions as to where the wind turbine is situated

Patterns of Care Received by Women With Breast Cancer Living in Affluent and Deprived Areas

Breast cancer occurs less commonly in socio-economically deprived women than in affluent women. Following diagnosis however, deprived women have poorer survival rates from breast cancer. Previous research suggests that their poorer survival is not due to the stage of the cancer at time of presentation. If poorer outcomes are not due to more advanced stage of disease at time of presentation alternative explanations are that the difference may be due to variations in treatment or host response mechanisms or environmental factors. The research described in this thesis explores whether the known poorer survival of deprived women is related to the care they receive for breast cancer from the National Health Service. The process of care is described from presentation through referral, treatment and follow up, and comparison is made between patterns of care received by affluent and deprived women. Patterns of care were described and compared by means of a three phase study: hospital records data collection, general practice records data collection and a postal questionnaire study. The review of case records in hospital and general practice produced data regarding diagnosis, delays, surgical and oncological treatment and follow-up in primary and secondary care. The postal questionnaire to patients provided further information on health status, current anxieties, sources of information about breast cancer, help seeking behaviour and life style changes as a result of a diagnosis with breast cancer. The process of care is investigated for women diagnosed with breast cancer in 1992 and 1993 in the most affluent and deprived areas in Greater Glasgow Health Board. The data presented in this thesis show that women from affluent and deprived areas received similar surgical and oncological care and had the same access to services. Previous studies, which showed no relationship between stage at presentation and deprivation, are challenged by data demonstrating a greater proportion of advanced and metastatic presentations in women from deprived areas compared to women from affluent areas. Evidence from all three phases of data collection (hospital records data collection, general practice records data collection, questionnaire study) point to women from deprived areas experiencing greater physical and psychological co-morbidity than those from affluent areas. Women from deprived areas were admitted to hospital for conditions not related to breast cancer more often than women from affluent areas. Although an increase in consultations with GPs were seen for all women, this increase was greater for deprived women. Deprived women had poorer SF-36 scores indicating greater psychological morbidity several years after diagnosis and reported greater anxiety than affluent women regarding health problems unrelated to breast cancer. Women living in deprived areas also expressed a greater degree of anxiety than women living in affluent areas about financial and family problems. These indications of greater co-morbidity may help to explain the poorer survival of deprived women with breast cancer. This study produces evidence that the National Health Service in Glasgow delivered health care equitably to affluent and deprived women with breast cancer in 1992 and 1993. The presence of other co-existing physical and psychological morbidities in the context of greater social adversity may explain the known poorer survival of deprived women with breast cancer

The morality of Ignazio Silone as developed through his narrative

This thesis aims to examine the ways in which the morality of Ignazio Silone is developed throughout the body of his narrative work. The dissertation is divided into three chapters, each reflecting a different time in the author's life and each containing a certain number of texts, eight of which are discussed in total. In each of these chapters the moral code which was so important to Silone is defined and developed through the actions and beliefs of his protagonists: their devotion to man, their regard for the tenets of love, truth, freedom and companionship, and their desire to oppose tyranny at all levels are fundamental principles of Silone's utopia. Chapter One focuses on the period spent in exile, the establishment of what is referred to as his morality and the novels produced upon his departure from the Communist Party in 1931. Chapter Two deals with the novels he wrote after his return to Italy in 1944 and the critical debate that surrounded his literary style. Finally, Chapter Three focuses on the two works which were instrumental in securing domestic recognition for the author and which are generally regarded as representing the pinnacle of his literary career. Although the texts examined in this study are divided into different chapters the hypothesis behind it is that each work is an autonomous part of the whole body of Silone's writing. Through close textual analysis this thesis aims to illustrate that each work is of itself reflective of a consistent, coherent moral vision which was defined at the very beginning of his career and which remained unwavering for almost forty years

Record Linkage: Applied to a Clinical Trial and Cohort Study

The main aim of this thesis is to investigate the role of computerised record linkage in clinical trial and epidemiological follow-up. This is illustrated using the West of Scotland Coronary Prevention Study (WOSCOPS). This study is placed in context by reviewing the results of previous clinical trials and epidemiological studies. Details of the probabilistic basis for record linkage techniques and the practical methods used to set up a computerised record linkage system are also given. The above ideas are brought together in the application of record linkage techniques, as employed in the Scottish Record Linkage System, to link the WOSCOPS subjects to their morbidity and mortality records on the Scottish national databases. The data resulting from the linkages are considered in various ways. A comparative study was carried out for the subjects randomised into WOSCOPS. The availability of two separate adverse event databases, one produced by routine subject follow-up and the other derived by computerised record linkage, provided a unique opportunity to assess the completeness and accuracy of each of the follow-up methods, and the benefits of a system incorporating both methods. This study found that record linkage compared well with traditional methods of follow-up in terms of completeness, accuracy, speed and cost. Record linkage provided the only feasible method by which adverse event records could be obtained for the large cohort of subjects screened for WOSCOPS. The data for the screened cohort were analysed in relation to categories of baseline risk factors. Data were categorised to maintain subject anonymity since informed consent was not available for all screenees. Analysis of this large cohort provided results which were in agreement with the previous studies. The mortality rates observed for the screened cohort using record linkage were finally compared to the mortality rates for the general population in the screening area. This provides an assessment of how representative the screened cohort is of the general population. It was found that the general population in the screening area tended to have higher mortality rates than the screened cohort

Prenatal alcohol exposure and childhood balance ability:findings from a UK birth cohort study

OBJECTIVE: To investigate the association of prenatal alcohol exposure with balance in10-year-old children. DESIGN: Population-based prospective longitudinal study. SETTING: Former Avon region of UK (Southwest England). PARTICIPANTS: 6915 children from the Avon Longitudinal Study of Parents and Children who had a balance assessment at age 10 and had data on maternal alcohol consumption. OUTCOME MEASURES: 3 composite balance scores: dynamic balance (beam-walking), static balance eyes open, static balance eyes closed (heel-to-toe balance on a beam and standing on one leg, eyes open or closed). RESULTS: Most mothers (95.5%) consumed no-to-moderate amounts (3-7 glasses/week) of alcohol during pregnancy. Higher total-alcohol consumption was associated with maternal-social advantage, whereas binge drinking (≥4 units/day) and abstinence were associated with maternal social disadvantage. No evidence was found of an adverse effect of maternal-alcohol consumption on childhood balance. Higher maternal-alcohol use during pregnancy was generally associated with better offspring outcomes, with some specific effects appearing strong (static balance eyes open and moderate total alcohol exposure at 18 weeks, adjusted OR 1.23 (95% CI 1.01 to 1.49); static balance eyes closed and moderate total alcohol exposure at 18 weeks, adjusted OR 1.25 (95% CI 1.06 to 1.48). Similar results were found for both paternal and postnatal maternal alcohol exposure. A Mendelian-randomization approach was used to estimate the association between maternal genotype and offspring balance using the non-synonymous variant rs1229984*A (ADH1B) to proxy for lower maternal alcohol consumption; no strong associations were found between this genotype/proxy and offspring balance. CONCLUSIONS: No evidence was found to indicate that moderate maternal alcohol consumption in this population sample had an adverse effect on offspring balance at age 10. An apparent beneficial effect of higher total maternal alcohol consumption on offspring balance appeared likely to reflect residual confounding

Deep Learning Based Inversion of Locally Anisotropic Weld Properties from Ultrasonic Array Data

The ability to reliably detect and characterise defects embedded in austenitic steel welds depends on prior knowledge of microstructural descriptors, such as the orientations of the weld’s locally anisotropic grain structure. These orientations are usually unknown but it has been shown recently that they can be estimated from ultrasonic scattered wave data. However, conventional algorithms used for solving this inverse problem incur a significant computational cost. In this paper, we propose a framework which uses deep neural networks (DNNs) to reconstruct crystallographic orientations in a welded material from ultrasonic travel time data, in real-time. Acquiring the large amount of training data required for DNNs experimentally is practically infeasible for this problem, therefore a model based training approach is investigated instead, where a simple and efficient analytical method for modelling ultrasonic wave travel times through given weld geometries is implemented. The proposed method is validated by testing the trained networks on data arising from sophisticated finite element simulations of wave propagation through weld microstructures. The trained deep neural network predicts grain orientations to within 3° and in near real-time (0.04 s), presenting a significant step towards realising real-time, accurate characterisation of weld microstructures from ultrasonic non-destructive measurements. The subsequent improvement in defect imaging is then demonstrated via use of the DNN predicted crystallographic orientations to correct the delay laws on which the total focusing method imaging algorithm is based. An improvement of up to 5.3 dB in the signal-to-noise ratio is achieved

Facilitated group work for people with long-term conditions: a systematic review of benefits from studies of group-work interventions

Background About 15.4 million people in the UK live with a long-term condition. Of the health and social care spend, 70% is invested in caring for this population. Evidence suggests that group-work interventions offer patient support, improved outcomes, and reduce the costs of care. Aim To review the current evidence base examining the effectiveness of group work in long-term physical disease where such groups are facilitated by healthcare professionals. Design and setting Systematic review and narrative synthesis of studies of group-work interventions led by health professionals for adults with specified long-term illnesses. Method MEDLINE, EMBASE, PsycINFO, and Cochrane databases were systematically searched using terms relating to group work and long-term conditions. Studies were included if they were randomised controlled trials (RCTs) with a control group that did not include group work. Results The 14 included studies demonstrated a high degree of heterogeneity in terms of participant characteristics, interventions, and outcome measures and were of varying quality. The studies demonstrated some statistically significant improvements in pain, psychological outcomes, self-efficacy, self-care, and quality of life resulting from intervention. Conclusion This review demonstrates significant benefits resulting from group participation, in adults with long-term disease. Results were mixed and some benefits were short-lived. Nevertheless, these results suggest that group work should be more widely used in the management and support of adults with long-term illness. There is a need for larger and better-quality studies to explore this potentially important area further

Acute synovitis and intra-articular methylprednisolone acetate in ponies

AbstractObjective: To determine how acute synovitis, with and without intra-articular methylprednisolone acetate (MPA), affect synthesis of proteoglycan, total protein, and collagen in articular cartilage and total protein synthesis in synovial membrane.Design: Synovitis was induced in 10 ponies by the injection of 0.5 ng lipopolysaccharide (LPS) into the left radiocarpal and midcarpal joints every 2 days for a total of four treatments. Synovitis was documented by clinical examination and synovial fluid analyses. Two days before euthanasia, MPA (0.1 mg/kg) was injected with the last dose of LPS into both the left and right radiocarpal and midcarpal joints of five of these ponies. Proteoglycan synthesis in articular cartilage explants from these joints was measured by incorporation of sodium [35S]sulfate. The size of the proteoglycan monomers and their aggregation with hyaluronan was assessed by size-exclusion chromatography. Protein synthesis in articular cartilage was measured by incorporation of [3H]proline and collagen synthesis by conversion of [3H]proline into [3H]hydroxyproline. Protein synthesis was measured in synovial membrane explants by incorporation of [35S]methionine.Results: Ponies developed carpal effusion and mild lameness accompanied by increased total nucleated cell count and total solids in synovial fluid in response to the LPS injections. Moderate to severe synovial membrane proliferation and inflammation were observed histopathologically in joints injected with LPS but no consistent light-microscopical changes were observed in the articular cartilage from these joints. Intra-articular MPA alone was associated with decreased proteoglycan synthesis and increased protein and collagen synthesis in the cartilage explants. Total protein synthesis by synovial membrane was also increased by MPA alone. In contrast, no differences in protein or proteoglycan synthesis were observed in explants from the joints with synovitis, with or without intra-articular MPA. Treatment with MPA, LPS, and LPS/MPA did not alter proteoglycan aggregate size, but LPS-induced synovitis resulted in an increase in the second largest population of monomers. MPA increased the synthesis of small proteoglycan monomers.Conclusion: Based on the methods used, acute synovitis prevented changes induced by intra-articular MPA alone. Results suggested that the effect of intra-articular MPA on joint metabolism was different between inflamed and normal joints. Experimental studies must consider the effect of inflammation, as well as the potential to introducein vitroculture artifacts when investigating the effect of intra-articular corticosteroids on chondrocyte function