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Understanding the basis of fatigue in children with unilateral hearing loss
No full textChildren with hearing loss (CHL) appear to experience greater fatigue than children with normal hearing (CNH). Listening-related fatigue is a type of fatigue often associated with an increase in effortful listening or difficult listening situations. This has been observed in children with bilateral hearing loss (CBHL) and, more recently, in children with unilateral hearing loss (CUHL). Available tools for measuring fatigue in children include general fatigue questionnaires such as the child self-report and parent-proxy versions of the PedsQLTM Multidimensional Fatigue Scale (MFS) and the PROMIS Fatigue Scale. Recently, the Vanderbilt Fatigue Scale (VFS-C: child self-report; VFS-P: parent-proxy report) was introduced with a specific focus on listening-related fatigue. Though CHL experience listening-related fatigue, it is unclear which tools are the best for measuring fatigue in this population, its mechanisms in CUHL and CBHL and how/if they differ, or the nature of the fatigue these children experience.
This PhD aimed to answer the above questions via four approaches. Firstly, semi-structured interviews with CHL and their parents were performed, to help characterise the fatigue experienced by CHL. Data were analysed using the constructivist grounded theory methodology, resulting in four themes: behavioural attributes of fatigue, causes of listening related fatigue, implications of hearing loss and fatigue, and strategies used to cope with fatigue. This study has improved understanding of the lived experience of CHL and provided unique perspectives from both children and parents.
Secondly, fatigue was measured in CHL using the current available questionnaires, comparing responses from the child’s self-report measures and the parent-proxy measures. It was found that all child self-report fatigue measures indicated that CBHL experience greater fatigue than CNH. Only the listening-specific tool (VFS-C) was sufficiently able to show greater fatigue experienced by CUHL compared with CNH. Similarly, all parent-proxy measures of fatigue indicated that CBHL experience significantly greater fatigue than CNH. Data from VFS-P and the PROMIS Fatigue Parent-Proxy also showed that CUHL experienced greater fatigue than CNH. Agreement between the parent-proxy and child self-report measures were found for the PedsQL-MFS and the PROMIS Fatigue Scale. These results suggest that CBHL experience greater daily-life fatigue compared to CNH. CUHL also appear to experience more fatigue than CNH, and listening-specific measures of fatigue may be better able to detect this effect.
Next, exploratory factor analysis (EFA) was performed to examine the validity of these self-report and parent-proxy measures of fatigue in CHL. It was found that all three questionnaires showed acceptable validity, confirming their effectiveness in measuring fatigue. EFA found the VFS-C, VFS-P, PROMIS self-report, and PROMIS parent-proxy report to be predominately unidimensional, whilst the PedsQL MFS was found to be multifactorial.
Finally, to understand more about the mechanisms of fatigue in CHL, and the potential differences in mechanisms between CUHL and CBHL, a collection of listening tasks were performed. This allowed the potential associations between speech in noise and spatial hearing deficits with listening-related fatigue to be tested. This study confirmed that CHL experienced more fatigue after performing listening tasks than before. CHL performed significantly poor than CHL in both localisation tasks. In speech in noise tasks, CNH performed better than those with HL, though no statistical differences were found. A higher degree of asymmetry was associated with poorer performance in localisation tasks. There was also a significant correlation between momentary fatigue (after performing listening tasks) and the VFS and PedsQL-MFS (Cognitive and Total domains) with both localisation tasks, suggesting a relationship between poor localisation ability and listening-related fatigue exists.
This body of research brings together a new understanding of children’s experiences of listening-related fatigue and improves our understanding of why CHL experience greater levels of fatigue compared to their NH peers. Through a combination of qualitative and quantitative methods, the research highlights the significant impact of hearing loss and fatigue on children's daily lives. The findings reveal that CHL experience higher levels of fatigue compared to their peers with normal hearing (CNH), with CUHL experiencing similar levels of fatigue as CBHL. The study underscores the importance of addressing listening-related fatigue in clinical and educational settings to improve the quality of life for these children. It also calls for further research to understand the definitive causes of listening-related fatigue and to develop effective interventions to alleviate this fatigue. By advancing our understanding of the mechanisms behind listening-related fatigue, this research aims to contribute to better support and management strategies for CHL, ultimately enhancing their overall well-being and academic performance
The role of refuges in coral reef ecosystems and biological invasions
Full text linkRefuges play a key role in mediating species interactions, influencing movement patterns and shaping ecological communities. As ecosystems worldwide face increasing pressure from anthropogenic activities, understanding how, and to what extent, refuges contribute to the persistence of biodiversity is crucial for effective conservation management. Using coral reef ecosystems and biological invasions as model systems, this thesis explores whether refuges fulfil their expected roles and how they directly and indirectly influence species behaviour and distribution. First, by reviewing scientific literature on biological invasions, I demonstrate that refuge-mediated processes influence the outcomes of non-native species introductions, revealing common patterns across terrestrial, marine, and freshwater ecosystems. Second, an investigation into depth refuges on coral reefs reveals that mesophotic fish communities have undergone greater compositional changes over time than those in shallower waters, which is inconsistent with the expectations of the deep reef refugia hypothesis. Third, I find no clear evidence that invasive lionfish undergo ontogenetic niche shifts from shallow to deeper waters. This suggests that management efforts at shallow depths will have little impact on deeper populations, which may serve as a refuge from culling efforts. Finally, I show that farming damselfish display different anti-predator behaviours across sites with varying structural complexity. A greater field of view led to more cautious behaviour, while refuge availability had little apparent effect. This suggests that changes in the visual landscape of a reef can shape how fish perceive risk and influence predator-prey dynamics. By examining the role of refuges at multiple ecological levels, from individuals to entire communities, this work provides new insights and suggests future research directions, emphasising the need to acknowledge and integrate refuges into conservation strategies
Morphological and Genetic Variation of Three-spined Stickleback (Gasterosteus aculeatus) in a Hybrid Zone
Full text linkThe mechanisms that contribute to evolutionary divergence between popula-tions are difficult to discern, but may be suggested by patterns in the distribu-tion of morphological traits, alleles and genotypes. Hybrid zones across eco-tones and population variation across environmental gradients can be especial-ly useful in this regard. Here, I analyse changes in morphological traits such as armour plating, standard length and body shape, as well as genetic variation such as the allele frequency of the well-known Eda locus, across environmental gradients within a hybrid zone and between systems. I show the lack of a pat-tern in morphological traits across the hybrid zone, but very strong genetic structure. In addition, I observe allele frequencies of chromosomal inversions across environmental gradients to show a tight link between the chromosome XI inversion and pH in freshwater systems
Pre- and post-operative voice therapy: complex intervention development and feasibility of a voice therapy programme for adults undergoing phonosurgery for benign vocal fold lesions
No full textBackground
Voice disorders affect one in three people during their lifetime. Consequential time off work alone costs the UK £200 million each year and direct healthcare costs are comparable with Chronic Obstructive Pulmonary Disease (COPD) and diabetes. Patients suffer considerable social, emotional and financial consequences as a result.
Benign vocal fold lesions (BVFLs) such as polyps and cysts account for up to half of those seeking help for voice disorders. Over 6500 surgical procedures are undertaken in England each year to remove BVFLs and emerging evidence suggests that the best outcomes occur when surgery is accompanied by voice therapy. Voice therapy is likely to help prepare patients for surgery, speed up recovery (facilitating return to work), reduce permanent disability and prevent recurrence. However, voice therapy is poorly described for patients with BVFLs. No management guidelines exist, and clinical practice varies. Surgical preparation, wound healing and re-establishing vocal fold vibration pose additional complexities in voice therapy programmes for those with BVFLs. There is no robust evidence to determine the effectiveness of voice therapy in this patient group.
This PhD aims to develop and evaluate the feasibility and acceptability of a pre- and post-operative voice therapy intervention (PAPOV) for patients with BVFLs, in preparation for future economic and clinical effectiveness research.
Methods
A mixed methods research plan, comprising four sequential studies was undertaken. A systematic review of pre- and post-operative voice therapy explored and synthesised the current evidence around the content, timing and intensity of voice therapy delivered to individuals with BVFLs. The second study involved triangulating findings from the systematic review with three other intervention development data sources to identify where convergence and divergence existed regarding potential components of a best practice pre- and post-operative voice therapy intervention (PAPOV). An international electronic Delphi study recruited expert voice therapists to seek consensus on the outstanding questions relating to components of the PAPOV intervention. The final study was a non-randomised, multi-centre feasibility trial with embedded process evaluation. This tested the feasibility of the PAPOV intervention and explored the acceptability of the intervention from the perspective of the participants and clinicians.
Results
The systematic review (n=35) found heterogeneity in the participants, outcome measures, and voice therapy intervention delivered to individuals undergoing phonosurgery. Detailed information on the content, timing and intensity of pre- and post-operative voice therapy was limited. In the triangulation study, areas of convergence, dissonance and silence across four sources of data were identified. There was evidence for the inclusion of 27/61 possible components into the PAPOV intervention. The triangulation study also highlighted outstanding questions which could be further explored. In the Delphi study, an international sample of expert voice therapists (n=42), reached consensus on 33 statements relating to the PAPOV intervention. Qualitative data offered further insights into aspects of dosing and tailoring. These, combined with findings from the triangulation study facilitated the development of a detailed protocol, described according to treatment theory using the RTSS-Voice. The PAPOV intervention was found to be feasible and acceptable to clinicians (n=4) and participants (n=41). Treatment fidelity and adherence to the PAPOV intervention was good, and clinical outcomes showed statistically significant changes post treatment in all patient reported outcome measures and clinician reported measures.
Conclusions
The aims of the thesis were met, and an intervention (PAPOV) was developed by following a structured intervention development framework and applying a mixed methods research approach. The intervention was feasible and acceptable when tested in two NHS departments. There are a number of avenues for further research in light of the findings of this PhD. This includes progressing to clinical and cost effectiveness research
At the intersection of technology and law: distributed ledger technology and its impact on private law
No full text2009 gave us Bitcoin, a new virtual currency that was the first example and the starting point of a novel and disruptive technology, distributed ledger technology (DLT). Since then, the law of commerce has been getting more intertwined with the technology each day. A prominent aspect is the creation of a new type of asset, DLT assets. These assets are being bought and sold, and new business models are being created around them.
From a legal perspective, their novelty lies in the fact that they are purely intangible assets that can be subject to an exclusive control by an individual. This thesis aims to explore the implications of DLT assets in private law, particularly property, secured transactions and insolvency law. It will address each subject of law in separate chapters and identify issues that might arise due to the novelty of the assets. The goal is to identify the common themes that arise regarding the effective accommodation of DLT assets within the relevant legal frameworks. The thesis will inquire whether DLT assets undermine or challenge any of the established principles of the chosen subjects of law, and assess the most recent developments and explore possible solutions via a theoretical and a comparative analysis
Evaluation of Oxygen-Enhanced MRI for the identification of hypoxia induced treatment resistant tumours in patients with head and neck cancer
Full text linkTumour hypoxia is a recognised cause of radiotherapy treatment resistance in head and neck squamous cell carcinoma (HNSCC). Although potential hypoxia modification therapeutic strategies exist, they are not widely used in clinical practice in part due to a lack of a readily available method to identify patients who may benefit from such treatments. Imaging of tumour hypoxia is an appealing solution to this issue due to its ability to repeatedly provide information on the spatial distribution of oxygen. This thesis evaluates the potential use of the hypoxia imaging technique of oxygen-enhanced MRI (OE-MRI) for the assessment of tumour hypoxia in HNSCC.
A scoping review of the use of OE-MRI for the assessment of tumour hypoxia revealed strong pre-clinical evidence of the utility of OEMRI in assessing tumour hypoxia but limited clinical translation of this work with no published clinical studies of the use of OE-MRI in HNSCC at the start of this research.
A volumetric OE-MRI protocol for dynamic T1 relaxation time mapping was developed and implemented on 1.5T clinical scanners using only routinely available clinical equipment. Initial testing of the protocol yielded results that were considered adequate to proceed to a clinical study. 25 participants were scanned breathing room air and during high flow oxygen administration. Oxygen induced changes in T1 times (ΔT1) and R2* rates (ΔR2*) were measured in malignant tissue and healthy organs. Patients were surveyed on their experience of the OE-MRI protocol.
The developed OE-MRI sequence took only 10 mins to acquire and was well tolerated. A non-rigid image co-registration approach was applied and its effect on OE-MRI derived data evaluated. A total of 15 histologically confirmed primary tumours and 41 malignant nodal masses were identified in the scanned participants. The OE-MRI sequence was able to discern differing response of healthy tissues and tumours to oxygen challenge. Estimates of tumour hypoxic fractions were obtained in all patient participants with a statistically non-significant greater magnitude of hypoxic fractions present for radiotherapy treatment resistant tumours. Exploratory analysis was performed to investigate potential novel OE-MRI derived biomarkers and to explore the feasibility of using OE-MRI derived hypoxic maps to aid radiotherapy treatment planning contouring.
In summary, a well-tolerated clinical implementation of dynamic, volumetric OE-MRI of the head and neck region using only routinely available equipment that allows discernment of differing oxygen responses within biopsy confirmed HNSCC is presented. Novel OEMRI analysis methods are discussed and suggestions made for future work in order to fully translate this technique into a clinically utilised resource in the management of HNSCC.
Trial registration: ClinicalTrials.gov, NCT04724096.
Registered 26 January 2021.
https://www.clinicaltrials.gov/study/NCT0472409
Inferential and predictive modelling of transition success in dairy cows on automatic milking systems
Full text linkThe health and welfare of the transition cow impacts the economic, environmental and social sustainability of the dairy industry. Despite significant improvements in our understanding of the physiological challenges this period poses, limited improvement in the morbidity and mortality rates associated with transition have been reported in the
previous two decades. Transition cow monitoring programs (TMPs) are a commonly advocated means of reducing the impact of poor transition health. To date, such programs have been largely diagnostic in nature, focusing on the detection of specific disease states utilising labour intensive monitoring techniques. Automatic milking systems (AMS) offer an opportunity to develop fully automated monitoring systems which may be applied using a prognostic rather than diagnostic approach.
Prognostic TMPs provide dairy producers with predictions relating to long-term performance outcomes which may be used to facilitate pre-emptive management practices aimed at preventing or mitigating the losses associated with poor transition health. The aim of this thesis was to investigate the relationship between production and behaviour data
as collected by AMS in the early post-partum period, and subsequent performance assessed using milk production relative to expected, reproductive performance and the risk of removal from the herd in early lactation. An emphasis was placed on the predictive power of this data and its potential utility within a prognostic transition cow monitoring program.
A convenience sample of 46 herds was recruited on a voluntary basis from the UK and Republic of Ireland. Criteria for inclusion was the use of a Lely Astronaut milking robot under free-flow traffic conditions in conjunction with rumination and physical activity monitoring technology. Production variables analysed relating to milk quantity and quality included milk yield, milk yield acceleration, fat and protein content as well as conductivity. Behaviour parameters available via AMS included the number and nature of cow-robot interactions. In addition to this, auxiliary data sources including daily rumination and activity parameters, recorded using a neck mounted accelerometer and, historical cow-level production data as recorded by farm management software were also available. Within this thesis four outcomes were investigated. Chapters 3 and 4 explore the relationship between AMSdata collected over days 1-3 post-partum and Yield Deviation, defined as the disparity between recorded milk production and expected milk production over the first 30 days post-partum. Chapters 5 and 6 examine the relationship between data collected from 1-21 days in milk (DIM) and two reproductive outcomes, Expression of Oestrus or Insemination (EOI); The recording of an oestrus or insemination event between DIM 22 and 65, and Conception to First Insemination (CFI), the conception rate to a first insemination between DIM 22 and 80. Finally, Chapter 7 examines data collected over days 1-3 post-partum and subsequent survival using removal from the herd by 100 DIM.
Mixed-effect multivariable models reported in Chapters 3, 5, and 7 serve to quantify the statistically significant associations between AMS production and behaviour data, and their respective outcomes while accounting for the random effect of herd and confounding variables.
The development, and external validation of machine learning models for the prediction of production and fertility outcomes, described in Chapters 4 and 6 respectively, assess the degree to which AMS data,in combination with auxiliary data sources, may be leveraged into
meaningful improvements in animal health through predictive TMPs. Chapter 6 also examine the marginal effects of auxiliary data sources on model performance by assessing the accuracy with which AMS data can predict reproductive performance with and without rumination, activity and historical production data. Chapter 7 provides a direct comparison of mixed-effect inferential modelling and machine learning predictive models for the odds of removal from the herd by DIM 100 using AMS production and behaviour data in isolation.
In Chapters 3 and 7 we demonstrate that AMS production and behaviour data collected overs days 1-3 post-partum has significant association with Yield Deviation at 30 DIM, and the risk of removal from the herd by 100 DIM. Likewise, in Chapter 5, data collected prior to day 22 post-partum demonstrated significant association with reproductive outcomes up to 80 DIM. Across all outcomes, variables relating to milk yield, rate of milk yield acceleration and fat-to-protein ratio were found to be statistically significant. These associations highlight the transition period, and in particular days 1-3 post-partum as a critical inflection point within the lactation cycle. Furthermore, it demonstrates the potential for AMS sensor data collected during this time to be
incorporated into a prognostic TMP. However, the coefficient of determination attributed to the fixed effects within the final models for both reproductive and survival outcomes were found to be low, indicating that the explanatory power of these variables is limited.
Assessed in Chapters 4, 6, and 7, transition cow data demonstrated moderate group level-predictive power for Yield Deviation at 30 DIM, and reproductive outcomes EOI and CFI, but failed to demonstratepredictive power for the risk of removal by 100 DIM. The predictive power of AMS and auxiliary data sources examined in Chapters 4 and 6 represents a critically important finding in support of the premise of prognostic TMPs. While predictive performance is moderate, these findings highlight the potential utility of this data to identify animals likely
to experience poor production or fertility performance in the early stages of lactation and should encourage further investigation of how this data may be applied within TMPs. However, the absence of predictive power for the risk of removal in early lactation, reported in Chapter 7 highlights a potential limitation of this approach to transition cow monitoring, particularly where the lag between observations and outcomes is prolonged. These results also serve to demonstrate the risks in the use of inferential models to imply predictive power and the need for externally validated predictive models to be incorporated into the assessment of the potential utility of novel data sources. The failure to demonstrate a statistically significant increase in model performance following the incorporation of auxiliary data sources, as reported in Chapter 6, highlights the challenges of balancing model accuracy with generalisability and ease of deployment in an environment of rapidly increasing data complexity.
The work presented within this thesis examines a novel means of transition cow monitoring, one which seeks to assess transition health using subsequent production, fertility and survival outcomes. The inferential models reported demonstrate significant statistical association between AMS data and each outcome of interest. However, the predictive power of this data remains limited when applied at the level of the individual, particularly as it relates to the risk of removal within the first 100 days post-partum. Despite this, group level classification of milk production and fertility outcomes demonstrated potential for incorporation into prognostic TMPs. This represents a critical advancement in the field of transition cow monitoring and may
offer an effective means to improve the health of transition cows and hence, the sustainability of the dairy industry
Postoperative exercise rehabilitation after elective colorectal cancer surgery
Full text linkIntroduction
Colorectal cancer (CRC) is common, accounting for approximately 11% of all new cancer cases, and is primarily a cancer associated with increasing age (Cancer Research UK, 2021). Surgery is usually the most appropriate option (if feasible and depending on staging) to try to achieve cancer free status. However, it carries significant morbidity, especially given the generally older patient population in which colorectal cancer presents (Argillander et al., 2021; Kolarsick et al., 2020). Appropriately stratifying preoperative risk to improve immediate outcomes is an appropriate strategy, but after a significant physiological insult through surgery, patients are not given clear guidance on how to regain their preoperative physical state (Karlsson et al., 2020). A structured exercise programme, such as proposed within this thesis, aims to assess the use of both aerobic and resistance exercises to safely improve postoperative patients’ physical and mental fitness and wellbeing, looking at objective measures through cardiorespiratory exercise testing (CPET) but also milestones important to the patient such as the ability to carry out their activities of daily living in order to improve not only their speed of recovery but maintain their mental well-being during a difficult period.
Methods
A systematic review was performed to assess the impact of postoperative aerobic exercise training in patients undergoing surgery for intra-abdominal cancers which included studies that began the exercise regimen within 3 months of surgery and reported on outcomes that included cardiorespiratory fitness. A cohort study (PHYSPAL) was performed to evaluate the quantity and type of immediate in-hospital postoperative activity that patients did was performed. Finally, a randomised controlled trial (RCT) (POSTEX) was undertaken to explore whether a combined aerobic and resistance programme improved physical fitness as well as quality of life parameters in postoperative colorectal cancer patients.
Results
The systematic review showed that there is benefit in exercise training in the immediate postoperative period and is safe. However, due to the heterogenous study designs and exercise regimens, there is no one clear programme that confers the most benefit. The PHYSPAL study showed some increase in activity over time in the immediate postoperative period, but overall step count is low and sedentary time is high. The POSTEX study conferred a potential benefit in preserving muscle strength and fatiguability, likely in response to the resistance component of the exercise regimen. Patients in the exercise group gave excellent feedback with regards to the programme delivery and ability to complete the exercises at home.
Conclusions
The work presented in this thesis shows the importance of and potential benefits in providing patient-focussed, achievable postoperative goal-directed exercise targets to maintain and/or improve activity levels after surgery. Multimodal exercise programmes can be safely performed with indirect supervision, which is an important consideration in a resource-limited healthcare setting. Both functional and patient-related factors, especially with regards to quality of life, are positively impacted but greater focus needs to be on integrating this into direct guidance with enhanced recovery after colorectal surgery protocols
Osteoarthritis and multimorbidity in male retired professional footballers compared to men in the general population
Full text linkBackground: Football is one of the most popular sports world-wide. Professional footballers are at higher risk of injuries of lower limb joints and the head due to the nature of the game. This can lead to short- and long-term health consequences such as osteoarthritis (OA) and cognitive disorders. However, whether footballers are at higher risk of developing knee pain, multimorbidity and OA of the foot/ankle after retirement remains unknown.
Objectives: [1] to systematically review published observational studies on multimorbidity and long-term conditions in professional footballers only or compared to the general population; [2] to examine the incidence of knee pain in male retired professional footballers (referred to as footballers) compared to men in the general population (referred to as controls) and associated risk factors in each group; [3] to examine the association between knee pain at baseline and incidence of multimorbidity at follow-up in footballers and controls; [4] to examine the incidence of multimorbidity in footballers compared to controls and associated risk factors in each group; and [5] to examine the association between radiographic knee OA and foot and/or ankle OA in footballers and controls.
Method: A systematic literature review of observational studies for multimorbidity in professional footballers was undertaken in 3 databases in addition to the Google Scholar until 31st December 2021. The Newcastle-Ottawa Scale was used to assess the quality of the observational studies. The prevalence, incidence and associated risk factors of multimorbidity, or specific long-term conditions were extracted or calculated for footballers compared to the general population. The pooled prevalence of multimorbidity and each long- term condition and 95% confidence interval (CI) were calculated.
An observational cohort study was undertaken in retired male professional footballers and aged matched general population controlled men aged ≥ 40 years using a postal questionnaire to examine the incidence of knee pain and multimorbidity over the 6-year period, and radiographic examination in a sample from each group to examine the association between radiographic knee and foot/ankle OA. Knee pain was defined as anterior knee pain experienced for most days of the previous month using body pain mannequin. Multimorbidity was defined as having at least 2 long-term conditions in an individual from 45 conditions included. Risk factors for incident knee pain and multimorbidity were examined per group. Radiographic knee OA was defined using Kellgren and Lawrence grade ≥ 2 in either tibiofemoral or patellofemoral compartments irrespective of the side. Foot and/or ankle OA was defined using the La Trobe Atlas (i.e., the presence of at least ≥2 in osteophytes (OP) plus joint space narrowing (JSN) at any joint of foot/ankle). Incidence (%) of knee pain and multimorbidity was estimated for both groups and adjusted odd ratio (aOR) and 95% CI was calculated using logistic regression. Risk factors for knee pain and multimorbidity were examined using multivariable logistic regression. OR and
95% CI was calculated using logistic regression for association between radiographic OA at the knee and foot/ankle joints. Correlation coefficient β was calculated using linear regression for summated radiographic OP and JSN scores at both sites.
Results
56 studies (42 cross-sectional studies, 4 case-control studies, 8 cohort studies, and 2 mixed design studies (cross-sectional and case-control)) were eligible for the systematic review from 18 different countries. There were 24 studies for footballers versus controls, and 32 studies for footballers only. The age ranged from 18 to 93 years old. Quality of included studies was regarded as medium quality. Most of the retrieved studies focused on a single long-term condition, and some studies reported on more than one long-term condition but did not report on multimorbidity. OA was found to be the most common condition being investigated, followed by neurodegenerative diseases, hip or knee pain, psychological and cardiovascular diseases. Methods used to examine long-term conditions or their risk factors were highly heterogenous. Of the 14 studies provided prevalence of knee OA in footballers, the pooled prevalence was 31% in male retired footballers (95% CI 20 – 42%). Of the 6 studies provided prevalence of knee OA, the pooled prevalence was 26% in male controls (95% CI 7 – 44%). Of the 4 studies provided prevalence of knee pain in footballers, the pooled prevalence was 53% in male retired footballers (95% CI 0 – 100%). Of the two studies provided prevalence of knee pain, the pooled prevalence was 27% in male controls (95% CI 26 – 28%). Of the 4 studies provided prevalence of ankle OA, the pooled prevalence was 9% (95% CI 7 - 10%) in male retired footballers. Of the 7 studies provided prevalence of hip OA in footballers, the pooled prevalence was 7% (95% CI 4 - 11%) in male retired footballers. Of the two studies provided prevalence of hip OA in controls, the pooled prevalence was 2% (95% CI 1 - 4%) in controls. Joint injury was the major risk factor associated with the increased risk of OA in footballers. For neurodegenerative disease, only one comparative study was identified from the literature, the incidence of neurodegenerative disease was higher in footballers (5.0%) compared to the general population controls (1.6%) over 18 years follow-up (p<0.001). Playing position (midfielder and defender), head injury and career duration might increase risk for neurodegenerative disease. For the following conditions, only one comparative study was identified from the literature, the prevalence of self-reported acute myocardial infarction was 3.08% in male retired footballers and 9.46% in controls (p<0.001), hypertension was 22.98% in footballers and 34% in controls (p<0.001), and diabetes was 3.77% in footballers and 11.47% in controls (p<0.001).
Of 486 footballers and 610 controls with data collected at two waves, 222 footballers and 402 controls were at risk for knee pain. There was no significant difference in the incidence of knee pain between footballers and controls (24.0% and 28.8% respectively, p=0.18) (aOR 0.77, 95% CI 0.52 – 1.16). Whilst body mass index (BMI) (aOR 1.17, 95% CI 1.04 – 1.31) and football-related knee injury (aOR 2.42, 95% CI 1.22 – 4.79) were risk factors for incident knee pain in footballers, BMI (aOR 1.08, 95% CI 1.01 – 1.14) and higher socioeconomic status (aOR 0.88, 95% CI 0.81 – 0.95) were associated with incident knee pain in controls. No association was observed between knee pain at baseline and incidence of multimorbidity at follow-up in footballers and controls.
A total of 317 footballers and 362 controls were at risk for multimorbidity. The incidence of multimorbidity was lower in footballers (37.5%) than controls (52.0%) (p<0.001) (aOR 0.64, 95% CI 0.45 - 0.89). Whilst age (aOR 1.04, 95% CI 1.01 – 1.07), the presence of one condition at baseline (aOR 2.98, 95% CI 1.78 – 4.99) and analgesic use (aOR 2.88, 95% CI 1.53 – 5.40) were risk factors for incidence of multimorbidity in footballers, age (aOR 1.05, 95% CI 1.03 – 1.08), the presence of one condition at baseline (aOR 2.73, 95% CI 1.73 – 4.31) and higher socioeconomic status (aOR 0.88, 95% CI 0.81 – 0.95) were associated with the incidence of multimorbidity in controls.
A total of 72 footballers and 147 controls underwent radiographs for both knee and foot/ankle joints. The association between knee OA and foot/ankle OA was not statistically significant in footballers (aOR 4.13, 95% CI 0.72 – 23.66; p=0.111), but was significant in controls (aOR 2.57, 95% CI 1.01 – 6.53; p=0.046). Similar finding were observed using the linear regression analysis for summated radiographic scores of OP and JSN.
Conclusions
Although professional footballers may be more likely to develop OA and neurodegenerative disease, they may be less likely to develop other long-term conditions, such as diabetes and cardiovascular diseases, and multimorbidity. In addition to the constitutional risk factors such as BMI, football-related head and joint injuries may explain the additional risks of OA and neurodegenerative disease. However, the general health and physical fitness may also explain the lower risk of other conditions and multimorbidity in footballers compared to controls. The results of this PhD project suggest the preventative strategy should be tailored to the population specifications to mitigate the specific risks and improve the general health status
Investigation of Triose Phosphate Isomerase dysfunction and Redox Stress in a Drosophila Melanogaster model of Neurodegenerative Disease
Full text linkNeurodegenerative diseases have been extensively associated with increased redox stress, often this is linked to aberrant production of reactive species such as advanced glycation end products (AGEs). AGEs, and smaller reactive species like nitric oxide (NO), have been shown to increase redox stress, promoting protein and DNA modification, often via post translational modifications such as 3-Nitrotyrosination. Triose phosphate isomerase (TPI) is one protein that has been shown to undergo such modifications. TPI is an important, but non-essential, glycolytic enzyme whose main role is in the conversion of dihydroxyacetone phosphate (DHAP) to glyceraldyhyde-3-phosphate (G3P). This is an important conversion as it controls levels of methylglyoxal (MGO) which when increased significantly has also been directly linked to increased redox stress, protein modification, and DNA modification via AGE production. Thus, TPI dysfunction has been reported to lead to increased redox stress, enhancing glycation signalling, neuroinflammation, and neurodegeneration, and to be sensitive to redox stress itself, containing multiple sites for 3-nitrotyrosination. The resulting physiological mechanisms of TPI dysfunction are not yet well understood. TPI dysfunction has in turn been linked to various neurodegenerative disorders, including Alzheimer’s disease. Glyoxalase (Glo) is another key enzyme which provides an innate protective mechanism against MGO build up. This work aims to use Drosophila melanogaster to identify impacts of altered TPI on neuronal physiology linking aberrant TPI function and redox stress to synaptic deficits at the glutamatergic Drosophila neuromuscular junction (NMJ). A Drosophila mutant expressing reduced Glo activity is also reported to further investigate this metabolic pathway, and subsequent connection to neurodegeneration. Electrophysiology and immunohistochemistry, among other techniques, are utilised to investigate this pathology.
This work suggests that the phenotype arising from dysfunctional TPI is in part due to altered vesicle dynamics, possibly in vesicle pool organisation of the presynaptic neuron or endo/exocytosis, thus expanding our knowledge of the resultant mechanisms of TPI dysfunction. The data presented here implies that there are various mechanisms of dysfunction, likely to be via exacerbated redox stress, and compensatory mechanisms, suggested to be primarily via altered vesicle dynamics, leading to distinct pathologies with different mutations of the TPI protein. Impaired TPI and Glo activity are suggested to enhance protein glycation, redox stress, and post translational modifications, implying a possible route of pathology and presenting a potential target for therapies
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