This thesis explores the prevalence, nature and pathogenesis of injuries in boxing. Following an introductory chapter and literature review (Chapters 1 and 2 respectively); Chapter 3 examines injuries in the GB boxing squad from 2005 to 2009. There were a total of 66 boxers on the squad during this period 61% were injured, a total of 297 injuries were recorded. The injury rate in competition was at least 460 times higher than in training, and most injuries were new rather than recurrent (246 v 51). The incidence of concussion is comparatively low compared to other studies in amateur boxing (5 in 5 years). Hand and wrist injuries were the most frequent (23.2%). Chapter 4 describes the nature of hand and wrist injuries in more detail. ‘Boxers’ knuckle’, skiers thumb, Bennett’s fracture and carpometacarpal instability were the most frequent hand and wrist injuries and also took the longest time to recover compared to all other hand and wrist injuries that occurred. These injuries occur significantly more frequently in competition than in training (347 injuries per 1,000 hours in competition less than 0.5 per 1000 hours in training). Chapter 5 describes efforts to identify and validate a means to measure the pressure at each knuckle, given that ‘boxers’ knuckle’ was found to be such a debilitating injury. This does differentiate between the proportion of knuckle impact forces (PKIF) displayed during punching and no punching but displays very poor test-re-test reliability. This method might allow the impact of changes in the hand wraps or the gloves to be measured. Chapters 6 and 7 deal with head injury in boxing. Head guards were removed from amateur boxers in 2013. The effect of this removal on boxers’ health was investigated by reviewing the number of bouts stopped due to blows to the head both with and without head guards (Chapter 6). To improve the quality of this analysis, an examination of video from championships with and without head guards (Chapter 7) was carried out. A significant decrease in observable signs of concussion (p < 0.05) and a significant increase in cuts (p < 0.001) was observed when the head guards were removed. This work will have implications for the protection of boxers’ hands and the use of head guards in other contact sports.

The injury risk associated with schoolboy Rugby has been raised as a matter of public concern, leading to calls to formulate appropriate preventive strategies. Consequently, this programme of research was undertaken to investigate characteristics that might influence injury risk in schoolboy rugby players, as well as interventions to reduce injury risk. The first study of this thesis (Chapter Three) presents a two-season prospective cohort study, which identifies several anthropometric characteristics and physical fitness components associated with injury risk in schoolboy Rugby players. Chapter Four outlines a staged approach to formulating a preventive exercise programme for use in schoolboy Rugby based on scientific evidence, expert knowledge, and end user opinion. In Chapter Five, the efficacy of a preventive exercise programme to reduce injury risk in schoolboy Rugby players is evaluated, demonstrating clinically meaningful reductions in concussion risk when compared with a standardised control exercise programme. In addition, greater programme compliance and dose are found to accentuate reductions across many match-derived injury outcomes measures. Finally, Chapter Six highlights meaningful associations between coach-related psychosocial factors and coaches’ compliance with using a preventive exercise programme, which may be useful in future with formulating strategies to enhance compliance with programme use. To summarise, this thesis addresses the identification of potentially modifiable risk factors and applies a novel approach to reduce injury risk in schoolboy Rugby players, emphasises the importance of compliance and dose in moderating the influence of preventive exercise programme efficacy, and outlines the associations between coach-related psychosocial factors and coaches’ compliance with using a preventive exercise programme in a schoolboy Rugby population.

This thesis investigates the epidemiology and risk factors for injury in professional Rugby Union with a view to informing injury reduction strategies. Over the last decade, concussion has rapidly become the principal player welfare issue faced by collision sports. Chapter 3 highlights the high and rising incidence of concussion in the professional game and suggests some possible reasons for the changing landscape regarding the reporting of concussion in professional Rugby Union. Given this high incidence, the findings from this study reinforce the importance of further understanding concerning the safe return to play following concussion. Therefore, chapter 4 explores the short and medium term clinical outcomes and return to play of players following a concussion. Players who reported a concussion had a 60% increase in injury risk following return to play when compared with players who did not sustain a concussion. Additionally, 38% of players reported a recurrence of symptoms or failed to match their baseline neurocognitive test score during the return to play protocol. Together, these findings highlight the need to explore an alternative (either a more conservative or different rehabilitation model) return to play pathway. Another prominent player welfare issue in elite Rugby Union is the management of match and training load. Chapter 5 of this thesis was the first study to investigate the training load-injury relationship in professional Rugby Union. Players had an increased risk of injury if they had high one-week cumulative or large week-to-week changes in load. Furthermore, a ‘U-shaped’ relationship was observed for four-week cumulative loads, with an apparent increase in risk associated with lower/higher loads and intermediate loads appeared beneficial in reducing injury risk in this setting. Finally, it has been suggested that the impact of illness on an athlete’s ability to participate can be as significant as that of injury. Chapter 6 provides the first study to investigate the epidemiology of time-loss illness in English professional Rugby Union. Although the burden of illness is significantly less than injury, the high severity and seasonal clustering of illness in this cohort clearly highlights the need for the continued surveillance of illness in this setting. Despite rugby being a collision sport with a primary focus on conditioning and performance, this research programme clearly highlights the potential for modifying existing practice in order to reduce injury risk. Conversely, injuries such as concussion are difficult to prevent without substantial law change, making the practical recommendations put forward in this thesis with reference to possible improvements in the management of players following concussion vital to consider.

In a time of outburst of antibiotic-resistant bacteria, the search for alternatives is essential. Bacteriophages are starting to re-emerge as a viable therapeutic option to treat acute infections where antibiotics are not effective any longer. However, it is key to incorporate bacteriophages into suitable formulations if they are to be applied, for example, topically. Emulsions, and specifically nano-emulsions are well-established vehicles for drug delivery in healthcare applications. This work focuses on the stabilisation of bacteriophages using oil-in-water nano-emulsions in order to develop the basis of a commercial cream or impregnated wound dressing for the treatment of burn wound infections. It was found that nano-emulsions have a dramatic effect on bacterial growth, and such influence was qualitatively determined using a Response Surface Method for design of experiments, followed by a quantitative analysis that allowed for the formulation of a modification of the logistic model of growth. Most importantly, it was discovered that nano-emulsions enhance bacteriophage infectivity both against S. aureus and P. aeruginosa infections in planktonic culture when compared to simple phage suspensions in buffer. The mechanisms why this enhanced infectivity occurs were investigated, and it was concluded that nano-droplets shield bacteriophages against environmental inactivation and they diminish the possible electrostatic repulsion between bacteriophages and bacteria, since they are both negatively charged. Bacteriophage/nano-emulsion formulations were then applied for the eradication of biofilms, which constitute the most common form of existence of bacteria in wounds. A flow system that mimics the continuous but slow supply of nutrients in a wound was used for this purpose. The infectivity of the developed formulations against such biofilms was found to be significant as well, proving the efficacy of stabilised bacteriophages in nano-emulsions. Finally, mathematical modelling approaches were successfully utilised to determine infection parameters and develop a predictive tool for mixed infections treated with bacteriophage 'cocktails'.

Fractures repair by two distinct mechanism; indirect fracture healing via an endochondral stage and direct fracture healing with primary bone formation via osteonal remodelling units ('cutting cones'). Bisphosphonates are recommended by national clinical guidelines to reduce the risk of osteoporotic fractures. Despite bisphosphonate therapy, osteoporotic fractures continue to occur. A proportion of these fractures require rigid fixation, whereby bone repairs by direct fracture healing. The effects of bisphosphonate therapy on direct fracture healing have not been previously reported. With indirect fracture healing, therapeutic doses of bisphosphonate led to a delay in callus remodelling and a larger callus volume without detrimental effects on the physical property of healing fractures. A model of direct fracture healing with rigid tibial plating in the rat was developed. In addition, a non-rigid model of external fixation that used the same number and size of screw holes to that of the plating model was used for comparison. Implants were designed and tested in cadavers prior to preliminary studies in rats. Within these two groups, animals were randomly allocated either to receive daily injections of bisphosphonate (Ibandronate) or saline (Control) for nine weeks. Following three weeks of injections a transverse tibial osteotomy was created and stabilised. Plain radiographs were obtained at fortnightly intervals. Animals were sacrificed at six weeks post fracture stabilisation. On sacrifice, fracture healing was assessed on contact radiographs, with a 4-point bend to failure and histologically. The mechanical properties of the uninjured diaphyseal bone in the contra-lateral limb were also assessed following bisphosphonate therapy. The mean bending stress at failure of diaphyseal bone in the uninjured limb was increased by 20% following only nine weeks of bisphosphonate treatment. The increase in strength of the uninjured diaphyseal bone has relevance when normalising the strength of fracture repair in a limb when comparing it to the unfractured limb as frequently reported in animal studies of fracture repair. In direct fracture healing bisphosphonate therapy resulted in impaired fracture healing as evident on plain radiographs based on the visibility of the fracture line. At six weeks post fracture the failure stress on application of a 4-point bend was decreased and histology revealed delayed bone healing compared to controls. Ibandronate treatment had an inhibitory effect on direct fracture healing in a rodent model. In clinical practice, the treating surgeon may need to consider using non-rigid fixation methods in patients already on bisphosphonate therapy. When rigid fixation is essential patients on bisphosphonates will need to be monitored for features of delayed or non-union and the use of fracture healing adjuncts should be considered.

The introductory section of this thesis outlines the importance of obtaining accurate and reliable skeletal fracture pattern data. The difficulties commonly encountered by injury epidemiologists in obtaining fracture data are discussed, and a review of the currently available literature is presented. The substantial variation in reported fracture incidence in the literature is further investigated in Section 2. Using a cohort of fracture patients from the Edinburgh population, this study aimed to investigate the effect of employing two different methods of obtaining numerator fracture data on the number and patterns of fractures reported. The results illustrate the marked difference that exists between numerator data obtained from emergency department (ED) sources and data obtained from the orthopaedic trauma unit (OTU). The positive predictive value (PPV) of a correct ED outpatient fracture diagnosis was only 74%, meaning that for every four fractures diagnosed and recorded in the ED, one of these will have been coded incorrectly. Fractures of the carpus, proximal tibia, proximal radius, calcaneus, talus and midfoot were miscoded more frequently than the average, while those of the clavicle, proximal humerus, metacarpus, metatarsus and distal radius were coded with greater accuracy. These results suggest that epidemiological fracture research using ED numerator data is likely to overestimate adult fracture incidence when compared to studies obtaining data from orthopaedic sources. Section 3 examines the range and pattern of acute fractures of the upper limb, lower limb and pelvis that occur in Edinburgh adults. The results of a 12 month longitudinal observational study are presented, including a detailed review of the patterns of fracture types encountered and the modes of injury involved in fracture occurrence. Where possible a comparison is made with historical data from the Edinburgh, as well as the existing fracture epidemiology literature. The socioeconomic status of patients is an important factor in the distribution of morbidity and disability in many areas of medicine. Section 4 of this thesis explores the association between deprivation, as measured by the Scottish Index of Multiple Deprivation (SIMD) and the incidence of fractures in Edinburgh adults. Logistic regression analysis was used to control for the influence of a number of variables known to have an effect on fracture patterns, such as the age and gender of the patient, the injury mode involved and the fracture type. The results show that increasing socioeconomic deprivation correlates with increasing fracture incidence, even after controlling for confounding variables. A stronger correlation exists in men than in women, and the fracture incidence seen in the most affluent decile is only 50% of that seen in the most deprived group. A stronger correlation exists for certain fracture types, namely fractures of the metacarpus, distal radius, proximal humerus and ankle. The final section contains a discussion of the relevance of the findings presented in Sections 2, 3 and 4 and how they relate to the existing fracture epidemiology literature. This section also considers which fracture types should now be considered as fragility fractures. The significant strengths and considerable limitations of this thesis, including issues related to the numerator, the denominator, causation and multiplicity in epidemiological fracture research, are discussed in detail. Suggestions for future work are presented.

Over 1.1 million fractures are estimated to occur annually in England and Wales. Up to 10% of these are likely be complicated by a delay or failure to heal with significant health and financial implications. Definitions of fracture non-union are not clear and although the Weber and Cech classification is still the definitive, misinterpretations remain common. Current treatment is surgical but the morbidity, particularly where autologous bone grafting is used, can be as high as 30%. Novel approaches are being tried but few of the strategies have made the translational impact that the laboratory and animal model data suggested. The work presented here investigates the feasibility of quantifying the biological potential of non-unions in patients and in a validated, in vivo model. Hypothesis: there is quantifiable biological potential in fracture non-union tissue that can be stimulated leading to osseous union by closed percutaneous injection of induction factors. Tissue from patients with non-infected fracture non-union undergoing treatment was examined to determine the feasibility of quantifying gene activity in small samples of non-union gap tissue. Non-union tissue from the animal model of an established non-union was examined to assess its osteoblastic potential by culture of extracted cells. Ortho bio logical agents that have shown great potential in gap models of non-union (BMP2 delivered in a viral construct (AdBMP2) and the thrombin peptide, TP508) were assessed to determine their efficacy in a clinically analogous model of fracture non-union. Quantifiable metabolic activity was found in the small samples of human non-union tissue. There was potential to correlate this to the histomorphometric architecture of the tissue. Cells extracted from the gap tissue of a non-union site in the rat model demonstrated osteoblastic potential in vitro. However, percutaneous injection of the orthobio logical agents into the non-union site in vivo failed to stimulate healing. The tissue at the site of a fracture non-union has a quantifiable metabolic activity that may have great clinical application and research benefits. Tissue from the non-union site of the animal model did demonstrate osteoblastic capacity but attempts to effect healing using percutaneously injected orthobiological agents that have previously shown potential, failed. This may be due to the chronic timepoint chosen to replicate the clinical situation. Further work is necessary to determine the prognostic potential of the gene assays and to continue to characterise the biological potential of the non-union tissue so that interventions can be more accurately directed.

No description available.

Epidermal layer is crucial for organism’s survival as its ability to close the wound is essential for tissue recovery. Planarian epidermis enables animal recovery and survival after virtually any body part amputation. Nevertheless, neither the epidermis nor the mechanisms endowing such a remarkable wound healing capacity is described in detail in planarians. Our work introduces live imaging methodology, which allows following epidermal cells and their response to tissue damage or tissue loss for extended time (hours) and in high resolution. Using our methods, we followed planarian cells live for the first time and in conjunction with electron microscopy analysis we described epidermal cell behaviors during tissue maintenance, response to tissue damage and tissue loss. Our data provides comprehensive description of cellular wound response, wound closure as well as preexisting tissue contribution to tissue restoration. In addition, we performed epidermal expression profile analysis to identify the candidate list of epidermally expressed genes to depict the machinery endowing these epidermal cell behaviors. In the pilot functional (RNAi) screen an array of transcription factors with a tissue maintenance phenotypes were identified. Our work established tools for subsequent functional studies of other epidermal expressed genes and paved the way to dissect the mechanisms of the epidermis’ maintenance and efficient wound healing in planarians.

Burn injuries can be one of the most traumatic experiences of a young person’s life. Research has documented a wide range of effects that a burn injury can have on both the children and young people (CYP) who sustain the injury and their family, including depression, anxiety, social difficulties, and appearance-related concerns. However, while it is acknowledged that these issues may be far-reaching and long-lasting, little research has explored interventions to facilitate healthy psychosocial adjustment after a burn injury. The majority of previous research in this area has focused on camps for CYP with burn injuries but has tended to neglect other interventions, as well as support for other family members. This thesis considered a range of interventions relating to different levels of psychosocial need according to the Centre for Appearance (CAR) framework for appearance-related interventions, which suggests that as the intensity of an intervention increases, the number of people requiring that intervention decreases. This thesis employed a mixed methods approach across four studies to investigate a range of psychosocial interventions for CYP with burn injuries and their families. Study 1A utilised photo elicitation techniques to explore seven families’ (n=21 participants in total) experiences of attending a specialised family burn camp. Study 1B aimed to further research into CYP’s burn camps, by addressing a number of methodological flaws identified in previous research. Standardised outcome measures and open-ended questions were used to evaluate CYP’s (n=23) and their parents’ (n=22) expectations and experiences of camp. A feasibility study of a newly developed online support programme was then undertaken with CYP (n=3), one guardian and clinical psychologists (n=10) to investigate whether it could help to improve care provision within paediatric burns. The final study was exploratory in nature, and involved qualitative interviews with clinical psychologists working within paediatric burns (n=14), to consider their current practices when providing face-to-face support to CYP with burn injuries and their families. The thesis ends with a consideration of these interventions and their place within psychosocial burn care, followed by a discussion of the clinical and research implications generated from the four studies. The current research indicated that the psychosocial needs of CYP with burn injuries and their family can be demonstrated using the CAR framework, and met using a tiered model of care. Key terms are defined throughout the thesis and in the glossary (appendix 1). Copyright permissions for all images used are located in appendix 34.