The proliferation of Improvised Explosive Devices during the War in Afghanistan (2001 – 2014) caused many casualties and deaths on all sides of the conflict. Casualty data from the UK field hospital in Afghanistan identified 155 casualties with fractures in 108 femoral long bone segments in 93 femora, and 131 tibial long bone segments in 114 tibiae. The diaphysis was the commonest site of fracture in the tibia (53%) and femur (44%). The head and face (30%) and upper limbs (36%) were the commonest sites of associated injuries. A mechanism of injury analysis of these casualties found that only 3% had tympanic membrane ruptures and 1% had primary blast lung injury, which suggests a low likelihood of primary musculoskeletal blast injuries. There were only eight casualties with fractures caused by metallic fragments alone. Of the remaining casualties, 57 had an axial loading pattern of injuries, 46 had bending and torsional fractures, 15 had a mixed pattern and 29 could not be classified. Twenty-eight casualties with knee ligament injuries were identified, including 17 with tibio-femoral dislocations. These injuries were further characterised in a porcine stifle joint uniaxial tension model through strain rates in the range 0.01 to 100/s. Across the range of strain rates, tensile modulus increased from 288 to 905 MPa and tensile failure stress increased from 39.9 to 77.3 MPa. The strain rate sensitivity of the material properties decreased as deformation rates increased, and reached a limit at approximately 1/s, beyond which there was no further significant change. The effect of knee position on lower limb injury severity was investigated using a traumatic impact simulator capable of reproducing the axial impulse experienced by casualties mounted in vehicles during an IED attack. Cadaveric tests found that the severity of lower limb injuries was less severe when the knee was flexed at ~20 in a standing position.

Chronic wounds are those that fail to proceed through an orderly and timely reparative manner, typically characterised by persistent hypoxia and infection. Since oxygen is essential in every stage of wound healing and has bactericidal activity, wound oxygenation methods including hyperbaric oxygen (HBO) and normobaric oxygen (NBO) have been proposed as therapeutic modalities in the treatment of chronic wounds. These treatments can significantly elevate the oxygen partial pressure at poorly perfused wounded tissues. However, the molecular mechanisms whereby oxygen improves wound healing remain unclear. The aims of this thesis were to explore the cellular and molecular impacts of high oxygen levels, elevated air pressure, chronic hypoxia and infection on reepithelialisation as a critical step in wound healing. It was hypothesised that increasing oxygen tension in the wounded area would improve steps in reepithelialisation process. This hypothesis was tested on human keratinocyte (HaCaT) cells where cell migration, proliferation and differentiation were examined at cellular and molecular levels using scratch assays, Western blotting, ELISA and MTT assays. Data clearly demonstrated that a chronic hypoxic state had a deleterious effect on reepithelialisation via attenuation of the rate of keratinocyte migration with increases in cellular adhesion, metabolic activities and hyperproliferation but no effects were seen on cell differentiation rates. In contrast, oxygenation of the cells via HBO and NBO resulted in a faster rate of cell migration with lower cell proliferation and metabolic activities. However, elevating air pressure alone i.e. hyperbaric air (HBA), did not have any effects on the re-epithelialisation process. Keratinocytes were stimulated with LPS and interleukins (IL-6 and IL-8) or cocultured with THP-1 monocytes to create different inflammatory models under chronic hypoxic and normoxic conditions. Data revealed that IL-6, but not IL-8, attenuated keratinocyte’s migration with a significant increase in cell adhesion and elasticity. Co-culture of monocytes with keratinocytes led to a marginal increase in cell migration under chronic hypoxic conditions. However, LPS stimulation did not lead to any significant effects on migration, proliferation and differentiation of keratinocytes. These findings show that oxygen is critical in re-epithelialisation and the results presented here provide understanding of the cellular and molecular mechanisms by which HBO and NBO improve wound healing.

No description available.

This study investigated the personal experience of sustaining a minor facial injury in an assault. Research has highlighted the existence of psychological difficulties following assault related facial injury. However, little is known about the relative contributions of the `circumstances of the injury' and the `facial injury' itself, to the experience of psychological distress. The aim of this research was to explore the personal experience of sustaining a minor facial injury (in the form of a laceration) during an assault, in order to understand its impact on life and the ways in which people cope with and adjust to this traumatic event and potentially appearance altering injury. The study employed a qualitative methodology. Six men and one woman participated in the research. Participants were interviewed using a semi-structured interview schedule and the discussions were tape-recorded. The transcripts were analysed using an interpretative phenomenological analysis. Six super-ordinate themes emerged from the analysis: `Immediate and transient impact of assault and minor facial laceration', `Psychological & behavioural aftermath of assault and minor facial laceration', `Strong sense of morality and need for justice', `Altered social interaction', `Self-reflection and evaluation' and `Managing the impact of the assault and altered appearance'. Participants reported an altered sense of psychological awareness during the assault and a strong desire for self-preservation. Following the assault, feelings of fear, anger and insecurity were described. Reactions to facial lacerations varied amongst participants, but there was a general appraisal that less visible scars have less of an impact. Participants expressed a strong need for justice, together with an expectation that the police and criminal justice system would hold the perpetrators accountable for their actions. Social interactions were felt to have changed as a result of their altered appearance and participants described being stared at and feeling judged by others. A period of self reflection was reported whereby participants attempted to make sense of the assault experience. Finally, participants described different ways in which they managed the impact of the assault and minor facial laceration. These findings are discussed in relation to the relevant literature. 2

There is an extensive literature exploring the effects of trauma, and the variables which moderate reactions following a stressful experience. Emotional responses can vary in response to numerous factors, and one area receiving increasing attention is that of coping. It has been acknowledged that there is an important relationship between how individuals cope and their psychological wellbeing following a trauma. Highly stressful experiences can impact on coping styles, and at times this can lead to maladaptive coping, exacerbating the original symptoms and potentially invoking additional difficulties. Existing coping styles also appear to impact on how individuals cope with events, possibly predicting future symptomatology. It is known that some populations, for example combat veterans, the homeless and refugees, experience a higher than average exposure to trauma, but less is known about they cope with these experiences. On the basis of this, this study aimed to investigate trauma and coping styles in street and hostel homeless adults, and additionally explore the relationship between coping and trauma symptomatology on the basis of existing research findings. It found that the street homeless reported more approach coping skills than those living in hostels, and this group also displayed higher levels of trauma symptomatology. Furthermore, it was shown that there is an association between avoidant coping and trauma, complex trauma and PTSD, supporting existing literature. Due to the cross-sectional design, causal associations could not be drawn, but the research gives suggestions for future research and potentially beneficial psychotherapeutic interventions for those who have experienced trauma, including homeless populations. 3.

Burns surgeons have long recognised the association between the depth of dermal injury and the speed of healing and degree of subsequent scarring. The work described in this thesis set out to study this relationship using a controlled wound healing model in healthy volunteers. A new model was developed that used a surgical jig to produce a standardised and reproducible wound in human skin. Pilot studies in cadaveric skin and ex vivo breast skin demonstrated that the model produced a graded, partial-thickness dermal wound, deep at one end and superficial end at the other, with a shallow gradient to enable a clinical distinction to be made between different depths of injury. This wound was made on the lateral aspect of the hip in 113 healthy volunteers. The progress of wound healing and scar development was studied using digital photography and image analysis software, high frequency ultrasound scanning and laser Doppler imaging, The deep end of the wound healed with. the formation of a scar and the superficial end healed without detectable scarring. Dermal injury was associated with an increase in dermal thickness and blood flow that was dependent on the depth of injury and the time after injury. The early inflammatory phase of wound healing was studied in 16 subjects prior to breast reduction. The acute inflammatory response was studied using immunohistochemistry. Leukocyte infiltration varied with the depth of dermal injury, with significantly greater numbers of all leukocyte subtypes at the deep end of the wound. The ultimate goal of wound healing research is to modify wound healing towards a non- scarring response. The results presented in this thesis might inform further work to identify potential targets for the development of anti-scarring agents.

Transforming chronic wounds into wounds that close by secondary intention (through the formation of normal granulation tissue) is one of the goals of manipulating wound healing induced angiogenesis. In this thesis, the contribution of new blood vessel formation in the process of closure of a small heat induced wound in the panniculus carnosus is examined. Wound healing in skeletal muscle is a temporally restricted process. A detailed ultrastructural analysis of individual burn wounds in the panniculus carnosus revealed that by day 3 after injury, inflammatory polymorphonuclear cells were the predominant cell type. Angiogenic sprouts were apparent in histological sections from days 5 to 7 post injury, when numerous fibroblasts and regenerating myofibres were also observed. Progressive maturation of the myotubes took place from day 9 post-wounding onwards but, persistent necrosis and fibrosis in BALB/c mice was still apparent by day 15 post-injury. Angiogenesis is a highly dynamic process, in which plexus geometry and blood vessel permeability vary both temporally and spatially. Thus, intravital microscopy was used to image wound revascularization within the dorsal skinfold chamber in situ. Wound area was measured 3, 6 and 9 days after injury and stereological principles used to systematically measure vascular sprouting and functional vessel density at fixed 250~m distance increments towards the wound centre. The wounded panniculus carnosus began to revascularise by day 3, when vasodilation of the surviving vessel segments was noted even in more distal areas of the plexus. The steepest decline in wound area occurred between days 3 and 6, when numerous blind-ended vessels, in addition to tortuous and disorganized newly developed vascular plexi were observed. Complete wound closure did not occur by day 9 but a more organized, albeit less dense, plexus spanned most of the previous avascular area. In blind-ending vessels (BEVs), which develop at the leading edge of the growing vascular plexus, luminal content correlated with internal surface area, as described by our group (Guerreiro-Lucas et al., 2008). Additionally, in situ Fluorescence Recovery after Photobleaching (FRAP) in three different functional areas of the remodelling plexus (i.e., BEV s, angiogenic plexus and pre-existing vessels), quantitated the £lux of £Iuorescently labelled plasma into the vessels and across the vessel wall, highlighting different levels of maturity in these vessel types. Recovery of fluorescence intensity in the interstitial space adjacent to plasma-filled BEV s was significantly slower than close to £lowing vessels. Luminal recovery became faster from days 5 to 7 post injury. In mice bearing skeletal muscle wounds, administration of a potent angio- inhibitory agent (TNP-470) delayed wound closure and microvascular ingrowth into healing wounds. The diameter of pre-existing vessels and leakage of FITC- dextran increased in animals treated with TNP-470. The combined results from this study reveal that sprouting was inhibited but the newly-formed vessels were more closely aligned with the axis of myofibres, leading to a "normalized" vasculature. The coupling of in situ temporal imaging of angiogenesis during wound healing with stereological analysis of vascular morphology represents unique longitudinal data that can be used to inform mathematical models of wound healing-induced angiogenesis. Furthermore, perturbing the development of these vascular plexi (e.g. with TNP-470), provides a method of experimental validation of the modelling predictions arising from in silica simulations and establishes a new experimental paradigm.

Injury surveillance is essential for reducing injury incidence in sport, and methods for surveillance have been the focus of a growing number of researchers in the last 15 years. However, work is still required to evaluate the impact of social phenomena on injury surveillance data. This thesis represents one of the first studies of its kind to incorporate both injury surveillance data and investigate psychological and sociocultural phenomena. It explores the impact of these factors on the reporting of injury in professional sport. The first study reported in this thesis compares versions 8 and 10 of the Orchard Sports Injury Classification System (OSICS) for completeness and accuracy, using data from a surveillance study in professional football, cricket and rugby union. It is the first study to evaluate inter-rater reliability of OSICS-10. All injury diagnoses could be assigned an appropriate code with OSICS-10, compared to 87% of diagnoses that could be assigned an OSICS-8 code. Contusions comprised almost half of diagnoses that could not be assigned an accurate OSICS-8 code. Interrater reliability of OSICS-10 was shown to be moderate (k=0.56). The findings of the study suggest that OSICS-10 is a better system to use than OSICS-8 when classifying injury diagnoses from injury surveillance studies, and a key recommendation from this study has been incorporated into the development of an interim system, OSICS-9, which has since been published. The second study examines weaknesses of an injury surveillance system implemented in professional football, cricket and rugby union by recording issues that arose with implementing the surveillance model, with particular emphasis on instances where psychological or sociocultural issues prevented the accurate recording of injury data. Seven keys groupings emerged of reasons for issues that adversely affected the reporting of injury through traditional surveillance methods. These were: 'High importance games', 'Approaching contract signing time', 'Carrying injuries through the season', 'Awaiting insurance payout and retirement', 'Overuse injuries', 'Friendly games' and 'Availability of other players'. There were several impacts of these issues that included under- and over-reporting of injury, and impacts on the reporting of injury severity. The findings of this I -I study suggest that psychological and sociocultural phenomena affect the findings of injury surveillance, and that further work in this area is warranted.

No description available.

No description available.