Equine athletes participate in a wide range of equestrian disciplines. Performance analysis in sport is the collection and subsequent analysis of data, or key information sets, related to facets of training and / or competition, to accelerate and improve athletic performance. Equine performance analysis research aims to optimise the potential competition success of the horse whilst concurrently promoting health and welfare and increasing career longevity. Despite the benefits associated with performance analysis, its application is limited in equine sport. Surface electromyography (sEMG) is a non-invasive technique which illustrates recruitment patterns of superficial skeletal muscle and can provide quantitative data on the activity within muscle during dynamic motion. sEMG has the potential to contribute to equine performance analysis particularly via assessment of muscle recruitment, activity and adaptation within training regimens and during competition. The critical commentary demonstrates the potential of surface electromyography (sEMG) as an effective performance analysis tool that could be used to assess the physiological response of muscle during field-based exercise in the horse and provides examples of how sEMG data obtained could guide improvements in the efficacy of training regimens for the equine athlete. Critical reflection on four peer-reviewed evidence sources was conducted to establish their contribution to equine performance research and to facilitate debate of future research directions for equine sEMG. The research demonstrates the validity of telemetric sEMG as an emerging technology that could be used to analyse muscle performance in the equine athlete for defined events, for example jumping a fence, and to assess performance over time, for example monitoring muscle activity during interval training. Opportunities also exist to determine the efficacy of muscle-related clinical and therapeutic interventions such as prophylactic dentistry or physiotherapy. The preliminary research presented suggests the use of equine sEMG as a performance analysis tool has most value to assess and compare muscle performance during exercise within individual horses. However further research is required to substantiate this. Future studies integrating larger sample sizes, horses selected from specific equestrian disciplines and breeds, and further exploration of the impact of coat length and sEMG sensor placement on data obtained would be worthwhile to standardise and validate the protocols employed here. Equine performance is a complex area; future work needs to focus on the individual characteristics that contribute to desired performance goals, but should also evaluate performance as a holistic entity. It is essential for progression in the performance field that research undertaken is shared with the equine industry to enable practical implementation. The use of sEMG in the equine athlete has the potential to increase understanding of how muscle responds to exercise and could help create an evidence-base to inform individual and discipline-specific training regimens. Increased efficacy in training should promote success, enhancing performance and extending career longevity for the equine athlete, whilst indirectly benefiting the horse’s health and welfare through improved management practices and injury reduction.

Arthritis is a term which encompasses a number of diseases characterised by cartilage degradation and joint destruction which represents an enormous and growing healthcare burden. Matrix metalloproteinases (MMPs) are a family of enzymes involved in cleavage of extracellular matrix proteins. They have many roles in both development and normal tissue homeostasis. As well as this they have been shown to be important in a number of diseases, including arthritis. MMP-1 and -13 in particular have been shown to be important in arthritis, due to their ability to cleave type II collagen, a key component of cartilage. A greater understanding of the regulation of these MMPs could lead to the potential for new therapeutic arthritis treatments. Tribbles (Trb) 1-3 are a group of proteins linked with diseases including diabetes, multiple sclerosis and cancer. Trb 1-3 are reported to play a role in regulating many cellular signalling pathways, such as mitogen-activated protein kinase (MAPK), phosphoinositide-3-kinase/Akt (PI3K/Akt) and nuclear factor kappa B (NFκB). These pathways are considered important in mediating gene expression changes, including MMPs. Both Trb1 and Trb3 were shown to regulate MMPs in chondrocytes, with a greater effect being on MMP-13 regulation. Trb1 and Trb3 were both shown to regulate the major MMP transcription factor AP-1, as well as the ATF3 and NFκB transcription factors. Both Trb1 and Trb3 interacted with MAP2Ks MEK1, MKK4, MKK6 and MKK7, and in addition were shown to regulate MAPK activation, with Trb3 protein levels appearing to be affected by MAP2K levels. Trb3 also had the ability to affect both Akt and STAT activation. These data demonstrate that Trb1 and Trb3 can regulate signalling pathways that have the ability to alter MMP expression and transcription factors within chondrocytes. This would suggest that Trb1 and Trb3 have the ability to affect cartilage degradation. This greater understanding of MMP regulation by Trb1 and Trb3 may help in the development of potential future therapeutic targets for arthritic disease.

Osteoarthritis (OA) is a common disease characterised by the progressive loss of the articular cartilage of synovial joints. It is multifactorial and polygenic. Candidate genebased association studies and genome-wide association scans (GWAS) have been used to identify OA risk alleles with over 10 regions of the human genome so far reported as harbouring OA susceptibility. Expression quantitative trait loci (eQTLs) demonstrate a correlation between gene expression levels and DNA polymorphism, the assumption being that the polymorphism resides within a regulatory element of the gene. The functional polymorphism can be cis-acting (within or close to the gene) or trans-acting (located a distance from the gene). It has become apparent for many common diseases that the majority of risk alleles are eQTLs rather than polymorphisms that alter amino acid sequences. The aim of this thesis was to investigate whether genes proximal to or harbouring OA-associated polymorphisms identified by GWAS are subject to cisregulation, which could therefore be contributing to the association signal. The expression levels of the genes were analysed in joint tissues from OA patients who had undergone joint replacement. Overall gene expression was measured by quantitative PCR whilst allelic expression was assessed using assays that can distinguish mRNA output from each allele of a transcript SNP. The functional effect of SNPs was tested in vitro using luciferase reporter assays. Expression analysis of genes at the OA-associated chromosome 7q22 locus identified HBP1 as the likely target of the OA susceptibility mapping to this region. Expression analysis of SMAD3 and GNL3 identified eQTLs active in OA joint tissues for both genes, whilst luciferase reporter assays identified two 3´UTR SNPs as potential mediators of the SMAD3 eQTL. Overall, this thesis demonstrates that OA tissues are subject to a range of regulatory elements that can influence disease during development or ageing.

As rheumatoid arthritis (RA) is a heterogeneous disease whose course and treatment response varies between patients, a stratified approach to its management is required. This thesis aimed to facilitate the risk prediction that underpins stratified medicine in RA. Its primary aim was to improve the knowledge of which clinical and genetic factors predict RA’s onset, disease course and treatment responses. Its secondary aim was to develop a prediction modelling framework that harnessed these factors to inform clinical care. There were five key findings. Firstly, it demonstrated a significant inverse association between alcohol consumption and RA development when the evidence across published studies was pooled using meta-analytical techniques. This suggests alcohol may protect against RA. Secondly, it demonstrated that only HLA RA susceptibility variants associated with radiological progression in a clinical trial cohort of early, active RA patients. This suggests the non-HLA genetic architectures of RA susceptibility and severity may, at least partially, differ. Thirdly, it provided evidence that anti-citrullinated protein antibodies (ACPA) can identify patients with early, active RA that are most likely to benefit from combination treatments. Fourthly, it demonstrated that estimating an asymptomatic individual’s risk of RA is possible, through developing and validating a risk prediction model that uses computer simulation to improve upon the discriminative abilities of existing RA prediction models. Finally, it highlighted the importance of considering RA’s heterogeneity when assessing its predictive factors; alcohol’s likely protective effect was predominantly seen in ACPA-positive disease and genetic and environmental factors had different impacts on the risk of developing younger and older onset RA. In conclusion this thesis has contributed to stratified medicine in RA by better characterising which predictive factors are relevant to its development, severity, treatment needs and responses and developing a risk prediction modelling framework that may be applicable to many aspects of stratified care.

No description available.

The clinical and epidemiological characterisation of symptomatic osteoarthritis (OA) in the foot has been neglected in relation to other peripheral joint sites. The midfoot complex in particular, has a central role in the regulation of all load-bearing forces that enter the body during locomotion, and yet the contribution of OA to pain and dysfunction in this region is unclear. Cross-sectional analysis revealed that midfoot pain and symptomatic mid foot OA are common, affecting approximately 19% and 12% of community-dwelling older adults respectively. Most individuals reported functional limitation and the pattern of joint involvement, and the association with selected risk factors was consistent with mechanical loading as a contributing cause. Although only about half of adults with symptomatic mid foot OA had consulted a general practitioner (GP) for foot pain in the last 12 months, many were accessing care through allied health professionals and taking oral pain medication. An interviewed subsample of participants with symptomatic mid foot OA (n=ll) reported that GP consultation for foot pain was often triggered by increased, unexplained pain and associated functional limitation. Following consultation, individuals often described being dissatisfied with they perceived as an overemphasis on analgesics and brief, cursory GP assessment. A literature search and narrative synthesis confirmed adequate clinimetric properties for a selection of brief clinical assessments that were then used to examine the clinical recognition of symptomatic midfoot OA in primary care.

Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy that affects males. Muscle deterioration leads to increasing levels of disability during childhood and adolescence, with death commonly occurring in the late teens or early twenties, although changes in care and treatment are leading to increasing numbers of boys with DMD living into adulthood. Parents and parent-led charities are raising funds to find effective treatments and a cure, and much of the medical research they promote requires the participation of those with DMD. This raises questions about children and young people’s involvement in research, including their role and approach to consent and how willing they are to be involved in the medical research their parents and DMD charities advocate. Through qualitative interviews with nine boys and young men with DMD and one young woman with muscular dystrophy, I explored their thoughts on medical research and the broader issue of how they live and cope with their condition. As part of this discussion I examined how they might make a decision to participate in medical research, focusing on the processes, interactions and individuals they consider important in helping them to decide. My approach privileges the participants’ thoughts and opinions, positioning them as able social actors (James & Prout 1997) who can provide insight into their experiences. Currently little is known about the lives of children and young people with a significant, degenerative disability, particularly around their thoughts on medical research participation and decision-making (Dixon-Woods 2006). The views of my participants provide the basis for this research, with work from the sociology of childhood and from disability studies informing and contextualising it. The way in which parents are involved in daily life is discussed to gain an understanding of how the participants work with those they trust. This relationship may provide understandings of how decisions are influenced by family input and how support assists those who are young and have a degenerative condition. It is possible that this model of working with the significant people in their lives promotes agency and independence, aiding the participants towards, rather than away from autonomy.

Dysphagia is common after stroke and leads to worse outcome. Previous studies have claimed benefits of biofeedback with surface Electromyography (sEMG) in swallowing therapy, but due to methodological weaknesses the findings are difficult to interpret. Feasibility studies are lacking regarding its application in therapy. Current approaches in dysphagia therapy in stroke were examined through a nationwide survey of Speech and Language Therapists (n=138). Variability in practice and poor uptake of existing guidelines and evidence was revealed, highlighting the need for more research and measures to promote consistency and best practice. The commonly used Kay Digital Swallow Workstation was validated against a reference sEMG system and found to provide appropriate measurement of amplitude of muscle activity, justifying its use in swallow biofeedback and in subsequent studies of this thesis. The reliability of submental swallowing sEMG amplitudes was found to be poor in 14 stroke and 85 healthy participants, confirming the need to normalise data for fair comparison. Normalising data to the mean normal swallow amplitude significantly reduced variability, supporting its use as a normalisation reference measure. No age-related changes were found in the variability of muscle activity for swallowing or the ability to increase submental activity for the effortful swallow (ES) in 85 healthy participants. Dysphagic acute stroke patients and healthy controls significantly increased submental muscle activity for the ES compared to the normal swallow (NS) and for the ES with sEMG biofeedback than without. A questionnaire found that participants considered the ES was significantly easier with sEMG biofeedback. Limited inter-rater agreement was found between SLTs’ clinical assessment of the ES and there was no relationship between clinical rating and sEMG measurements. A pilot Randomised Controlled Trial (RCT) investigating the effect of the ES with and without sEMG biofeedback in dysphagic acute stroke patients (n=10) demonstrated feasibility of the study protocol. These studies confirm the potential benefit of incorporating sEMG biofeedback with the ES for dysphagic acute stroke patients and justify a subsequent RCT to determine its effect on outcome.

The ultimate aim of this six study research programme was to develop and evaluate an intervention to promote medication adherence for osteoporosis patients. Mixed methods were used, with a combination of qualitative, quantitative and interventional approaches. Each study involved the investigation of the psychological factors which contributed to adherence to osteoporosis medication. In addition to data collection through interviews and questionnaires, participants were asked to draw how they visualized their osteoporosis. This research drew on Leventhal’s Self-Regulation Model (Leventhal et al, 1984) and Witte’s Extended Parallel Process Model (Witte, 1992). The first three studies explored the role of psychological factors in osteoporosis medication adherence. The following factors were found to be related to adherence: concerns about medication (studies 1 and 3), motivation (study 3) and self-efficacy (study 3). Further, study 2 suggested that misconceptions about osteoporosis may also contribute to treatment non-adherence. Study 4 tested the psychological impact of the intervention materials. The drawing element of the research indicated that drawing the condition enabled patients to express their emotional response it (study 2). Findings from the first four studies led to the design of a theory-based psychological intervention. The intervention comprised: psycho-education, motivational interviewing and plan-setting and was tailored to the needs of each individual. Medication adherence increased for seven of the eight study participants. Post-intervention, patients reported increased understanding of osteoporosis, a greater perceived need for medication and a stronger belief that osteoporosis medication could reduce the risk of osteoporotic fractures. Further, the evaluation suggested that the tailored element of the intervention was largely responsible for the increases in adherence (study 6). The key findings were that i) osteoporosis patients have misconceptions about their bone health and their medication ii) psychological factors are related to osteoporosis medication adherence iii) creating a drawing of osteoporosis may elicit an emotional response to the condition and iv) a psychological intervention has the potential to increase adherence to osteoporosis medication. Further research with a larger sample is required to assess the intervention’s effectiveness.

No description available.