Дисертації: "R Injury"

1

Mitchell, Margaret. "Recovery from personal injury." Thesis, University of Glasgow, 1991. http://theses.gla.ac.uk/40922/.

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2

Clasper, Jonathan C. "Mortality and orthopaedic injury following military trauma." Thesis, University of Glasgow, 2017. http://theses.gla.ac.uk/8964/.

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This thesis details my contribution to the literature on military surgery, based on both front-line surgical experiences as well as research carried out on causes of death and disability, particularly in relation to limb injuries, the most common site of wounding in conflict. Injury analysis (6 papers). Injury prevention/mitigation (5 papers). Management (8 papers). Outcome (13 papers). Education (9 papers).

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3

Foster, Mark Anthony. "Steroids and immunity from injury through to rehabilitation." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6686/.

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There are over one million deaths from road traffic collisions. In Afghanistan, there have been 2005 UK battle injuries over 10 years. Advances in military trauma care have improved survival, resulting in more severely injured individuals entering the trauma care pathway. Improved understanding of immunoendocrine changes after severe trauma may facilitate novel interventions to improve outcomes. We prospectively recruited 102 severely injured patients at the QEH Birmingham; 52 military and 50 civilian patients with a mean Injury Severity Score of 27.2±13.9. Blood and 24-hr urine were collected at baseline (injury < 24h) and at regular intervals from while in hospital and at 3,4, and 6 months. Results demonstrated a reduced neutrophil function following a surge of DAMPs and cytokines that were released into the circulation. Both DHEA and DHEAS were significantly down-regulated (p < 0.0001). Serum testosterone was initially completely suppressed (p < 0.0001) but normalised after week 4. Protein and muscle loss followed a U-shaped curve; catabolism began to recovery 4-6 weeks following injury. In conclusion, the acute response to severe injury comprises increased glucocorticoid activation and down-regulation of adrenal and gonadal androgens. Delineation of whether the endocrine changes are beneficial or adverse will determine the potential for future intervention studies.

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4

Philp, Fraser Derek. "Validating models of injury risk prediction in football players." Thesis, Keele University, 2018. http://eprints.keele.ac.uk/4993/.

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Association football (soccer) is a popular sport and there is a high risk of injury for participants. Within the context of professional clubs, the risk of injury is also associated with the risk of financial costs. Therefore, injury reduction processes are considered important, and previous studies have sought to identify and model injury risk factors. Although formal screening tests e.g. The Functional Movement Screen (FMS) and monitoring procedures e.g. Union of European Football Associations (UEFA) have been developed for modelling and predicting injuries, the processes in current use, lack precision or clinical usefulness. The aims of this thesis were therefore to explore why existing methods of screening, measuring and modelling are not effective in predicting injuries. In order achieve this the following things were done; Literature review to evaluate the UEFA screening process and advocated variables, Validation of the FMS, the most commonly used exercise screening test, against a 3D photogrammetric system (Vicon (©Vicon Motion Systems Ltd)) Injury modelling on a pre-established database designed in accordance with the UEFA guidelines The literature review confirmed that the established database was compliant with the UEFA screening guidelines. The most commonly used screening measure (FMS) for injury risk was found to be an invalid measure and therefore removed from the modelling process. The models developed were unable to prospectively model injuries accurately (R = 0.23), and the primary problem was a large number of false positives i.e. those predicted as having risk of injury not sustaining injury. Reasons for poor model performance could be attributed to inappropriate screening methods, inadequate datasets or inadequate modelling methods for rare events. Future work should focus on addressing the limitations in the existing UEFA screening framework and simultaneously develop better methods of rare event modelling from small datasets.

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5

McKinlay, William W. "Psychosocial outcome and family burden after traumatic brain injury." Thesis, University of Glasgow, 1996. http://theses.gla.ac.uk/4831/.

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The persistence of psychosocial symptoms after severe head injury has been identified as one of the main long-term difficulties facing such patients and their families. Not only have such problems proved persistent, they have been found to present particular problems for community re-entry including return to work. They have been associated in particular with stress on carers and also with disruption of family activities and health. Given that so many survivors of severe head injury rely on their families for long-term support, this topic has attracted increasing attention. The present study described the psychosocial problems after severe head injury and their relationship to various "burdens" on carers and the wider family based on a group of 54 patients studied at 3, 6, and 12 months post-injury. Replication and extension of some findings is made through study of a multi-centre internationally collected group of 562 survivors of severe head injury. Thepersistence of psychosocial problems is noted alongside their differing relationships to various aspects of "burden". Aspects of burden, and especially of social isolation, present challenges especially for those working in rehabilitation and community re-entry programmes

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6

Khalid, Usman. "The role of microRNAs and ischaemic preconditioning in kidney ischaemia reperfusion injury." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/95843/.

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Successful kidney transplantation transforms outcome for patients with end stage kidney disease. Delayed graft function (DGF) following Ischaemia Reperfusion Injury (IRI) is a major problem, is hard to predict or monitor, and preventative or therapeutic strategies are lacking. Ischaemic Preconditioning (IPC) may limit IRI, but results are variable and potential mechanisms are not well defined. The aims of this thesis were to study the role of microRNAs, which are post-transcriptional regulators of gene expression vital in many physiological and pathophysiological processes, in the context of IRI, IPC and DGF. An in vivo model of IRI and IPC was developed, and histological, biochemical and mRNA kidney injury marker analyses were undertaken. MicroRNAs were then profiled using both Next Generation Sequencing (NGS) and hybridisation arrays, and changes in selected microRNAs confirmed by RTqPCR. Histology scores, serum creatinine and expression of kidney injury markers were significantly reduced in IPC compared with IRI. Microarray and NGS analysis identified a highly reproducible IRI signature, which was attenuated by IPC. Subsequently, microRNAs were profiled using Taqman Low Density Array (TLDA) and validated by RT-qPCR, from urine samples of kidney transplant patients with and without DGF. A DGF microRNA profile was uncovered, with overlap to the results from the IRI model. These data have identified a microRNA signature of IRI that was attenuated by IPC, which also improved outcome. Urinary microRNAs also showed a promising capability to predict DGF in human kidney transplantation. MicroRNAs thus show significant promise as biomarkers and potential therapeutic targets in this context.

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7

Yu, Zanzhe. "Local and systemic endothelial injury in renal failure treated with peritoneal dialysis." Thesis, Keele University, 2013. http://eprints.keele.ac.uk/1828/.

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Excess fluid and waste products of metabolism, as well as protein, are removed from the peritoneal cavity in Peritoneal Dialysis (PD). Increased peritoneal protein clearance (Pcl) is associated with a greater risk of mortality. It is not clear whether this association reflects systemic endothelial injury or local peritoneal capillary damage and inflammation, or both. To investigate this problem a series of analyses were undertaken in different incident, prevalent and longitudinal patient cohorts. Transcapillary escape rate of albumin (TERalb) was measured to determine systemic capillary permeability. Luminex assays combined with principle component analysis were applied to measure endothelial biomarker patterns. It was demonstrated that: (1) Pcl is a function of both local peritoneal inflammation, membrane area (PSTR) and comorbidity (especially cardiovascular) but only its association with the latter predicted survival. (2) There is a progressive uncoupling of the Pcl, (indicative of large pore pathway) and PSTR (effectively the small pore area) with time on PD. (3) Isolated small pore ultrafiltration (due to icodextrin) decreases with prolonged time on PD and is also uncoupled from the increase in peritoneal membrane area. (4) The systemic endothelial barrier function is decreased in PD patients, especially diabetics, but not associated with hypoalbuminaemia which is linked to systemic inflammation. (5) Hydration status is related to plasma albumin concentration but not endothelial dysfunction as measured by soluble biomarkers. Pcl is a function of both local peritoneal factors, e.g. inflammation and progressive fibrosis, and systemic patient characteristics, e.g. age and comorbidity. The influence of comorbidity is complex depending on type, associated patterns of endothelial injury and causes of associated hypoalbuminaemia. The importance of plasma colloidal pressure in determining fluid status was emphasized. Strategies to improve fluid distribution should focus on reducing peritoneal protein loss and increasing albumin synthesis rather than blocking systemic vascular leak.

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8

Low, Emma Louise. "Dissecting transforming growth factor-beta signalling pathways in the context of acute vascular injury." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/30703/.

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Coronary artery bypass grafting (CABG) is a mainstay in the treatment of coronary heart disease (CHD), a leading cause of premature death in the UK. However, fewer than 60 % of saphenous vein grafts remain patent in the long-term due to the formation of a hyperplastic, occlusive neointima within the grafted vessel. Excessive vascular smooth muscle cell (VSMC) proliferation, migration and extracellular matrix (ECM) synthesis are key events in the pathogenesis of vein graft intimal hyperplasia (IH), and subsequent necrotic core formation and intraplaque haemorrhage further accelerate the process of vein graft failure by forming unstable atherosclerotic lesions. Early IH therefore represents an important target for therapeutic interventions aimed at improving clinical outcomes after CABG. The pleiotropic cytokine transforming growth factor-beta (TGFβ) is highly expressed in restenotic vessels from CHD patients and is acutely upregulated following vein graft implantation in large and small animal models of vein graft disease. To date, most studies investigating the role of TGFβ in IH have used global approaches to target TGFβ, or have focused on the canonical activin receptor-like kinase 5 (ALK5), Smad2/3-mediated pathway. However, TGFβ elicits a diverse range of cellular responses by activating several distinct signalling pathways, and in certain cell types can also signal via ALK1, activating a separate set of receptor-regulated Smad proteins (R-Smads; Smad1/5) that can antagonise ALK5 signalling. Importantly, the role of ALK1 in the pathogenesis of vein graft IH remains unclear and studies have yet to conclusively show whether TGFβ is able to signal via ALK1 in VSMCs. Moreover, in vivo studies indicate that the three mammalian TGFβ isoforms have discrete biological functions, especially during wound healing, a process similar to IH involving cell migration, proliferation and ECM formation. Therefore, the principal aim of this thesis was to dissect the roles of ALK5- and ALK1-mediated signalling in VSMCs during vein graft IH. In addition, this thesis aimed to evaluate whether TGFβ1, TGFβ2 and TGFβ3 differentially regulate VSMC behaviour in the context of vein graft IH. Initially, the expression of the TGFβ isoforms, ALK receptors and R-Smads in VSMCs during the development of IH was evaluated in both small and large animal models of arterial injury and vein graft disease. IHC analysis of wire-injured mouse carotid arteries 14 days post-injury revealed that TGFβ1, TGFβ3, ALK5 and ALK1 were expressed in αSMA+ intimal and medial VSMCs. Interestingly, while nuclear localisation of phosphorylated Smad2/3 (pSmad2/3) within αSMA+ VSMCs was observed in both non-injured and injured vessels, nuclear pSmad1/5 was only detected within VSMCs following vascular injury. IHC analysis of TGFβ signalling components in diseased pre-implantation human saphenous vein (HSV) with pre-existing IH showed that TGFβ1, TGFβ3, TβRII (TGFβ type II receptor), ALK5 and ALK1 were expressed in αSMA+ VSMCs within both the intima and media. Importantly, dual staining for TβRII and ALK5 or ALK1 showed strong co-localisation between ALK5/ALK1 and TβRII. Both pSmad2/3 and pSmad1/5 were localised to the nuclei of intimal αSMA+ VSMCs, suggesting that both ALK5 and ALK1 signalling pathways may be active in these cells. Confocal microscopy analysis of three failed vein graft specimens obtained from patients undergoing cardiac transplantation revealed abundant nuclear-localised pSmad2/3 and pSmad1/5 in αSMA+ intimal VSMCs. These data suggest that both the ALK5 and ALK1 pathways may be activated in VSMCs during the development of IH. Having localised TGFβ1, TGFβ3, TβRII, ALK5, ALK1, pSmad2/3 and pSmad1/5 to intimal vein graft SMCs, subsequent mechanistic characterisation of TGFβ signalling via ALK5/ALK1 was performed in SMC outgrowth cultures from pre-implantation HSV segments from CABG patients (HSVSMC). Affinity labelling and crosslinking studies using 125I-TGFβ1 revealed binding of TGFβ1 to ALK5, ALK1 and TβRII, as well as the accessory receptors endoglin and betaglycan in HSVSMC. qRT-PCR confirmed the expression of these receptors at the RNA level, while immunoblotting revealed that treatment with all three TGFβ isoforms could induce a rapid increase in pSmad2 as well as pSmad1/5. Immunocytochemistry demonstrated the nuclear localisation of both pSmad2/3 and pSmad1/5 signalling complexes following stimulation of HSVSMC with TGFβ1, while qRT-PCR evaluation of ALK5 and ALK1 target genes (SERPINE1 and ID1, respectively) confirmed the transcriptional activation of both ALK signalling pathways by all three TGFβ isoforms. Importantly, pharmacological inhibition of ALK5 or ALK1 (using SB525334 or K02288, respectively) or siRNA-mediated knockdown of ALK5 or ALK1 in TGFβ-stimulated HSVSMC, reduced the expression of pSmad2 and pSmad1/5, respectively, confirming that TGFβ can bind to and signal through both ALK5 and ALK1 in HSVSMC. Functional assays performed in HSVSMCs indicated that TGFβ1, TGFβ2 and TGFβ3 regulate VSMC proliferation and migration in a similar manner in vitro. To gain insight into how the ALK5 and ALK1 TGFβ signalling pathways regulate VSMC proliferation, migration and apoptosis, functional assays were performed in HSVSMC treated with TGFβ1 ± SB525334 or K02288. Pharmacological inhibition of ALK5 or ALK1 did not significantly alter HSVSMC proliferation in response to TGFβ1. Interestingly, TGFβ1-mediated HSVSMC migration was significantly attenuated in the presence of ALK1 small molecule inhibitor, K02288, whereas inhibition of ALK5 signalling by SB525334 had no significant effect on HSVSMC migration. TGFβ1 protected from hydrogen peroxide-induced HSVSMC apoptosis and inhibition of ALK5 or ALK1 signalling reversed this effect. These studies indicate that TGFβ signalling via ALK5 and ALK1 differentially regulates HSVSMC migration, but not proliferation or apoptosis. Data output from the Human TGFβ/BMP RT2 Profiler PCR Arrays suggested that several TGFβ signalling pathway genes were differentially expressed following rTGFβ treatment in HSVSMCs, whereby some TGFβ isoform-specific effects on gene expression were observed. However, following validation, no TGFβ isoform-specific effects on gene expression were detected. Whole genome expression profiling of migrating HSVSMCs treated with TGFβ1 ± SB525334 or K02288 was performed in order to compare the gene expression profiles directly regulated by ALK5 and ALK1. In total, the expression of 3,235 genes was modulated by TGFβ1 treatment compared with non-stimulated HSVSMCs, approximately half of which appeared to be co-ordinately dysregulated following ALK5 and ALK1 inhibition. Two groups of putative ALK5- and ALK1-specific transcriptional targets were chosen for more detailed evaluation and validation. qRT-PCR validation in HSVSMC confirmed fibroblast growth factor 2 (FGF2) and Mal, T-cell differentiation protein like (MALL) as ALK5-specific target genes, and fatty acid desaturase 1 (FADS1), H1 histone family member 0 (H1F0) and scavenger receptor class A member 3 (SCARA3) as ALK1-specific target genes. Together, this data indicates that TGFβ regulates HSVSMC behaviour during the pathogenesis of vein graft IH by activating distinct, ALK receptor-specific transcriptional networks. Overall, the findings from this thesis indicate that the ALK1/Smad1/5 TGFβ signalling pathway is activated following vascular injury and induces specific transcriptional changes to promote VSMC migration. Moreover, these studies indicate that TGFβ1, TGFβ2 and TGFβ3 regulate VSMC behaviour in a similar manner in vitro and all isoforms appear to have equivalent effects on the induction of established ALK5 and ALK1 target genes. Together, these findings highlight the potential of targeting non-canonical TGFβ signalling pathways in the setting of vein graft failure.

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9

Nesargikar, Prabhu. "Role of leukocytes, complement system and endothelium in rat renal ischaemia-reperfusion injury." Thesis, Cardiff University, 2015. http://orca.cf.ac.uk/85582/.

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Introduction: Renal Ischaemia-Reperfusion injury (IRI) is a complex mechanism involving the interplay between endothelium, leukocytes and the complement system. To evaluate the role of these three key mediators, a rat model was used to evaluate changes seen in renal IRI. Two interventional agents: Anti-Thymocyte Globulin (ATG) and Soluble Complement Receptor-1 (sCR1) were used to modulate leukocyte and complement response in this IRI model with a view to assess, and define IRI mechanism. Methods: The Ischaemia-Reperfusion (IR) model involved unilateral left renal ischemia (n=10) for 40 minutes, followed by 48 hours of reperfusion. ATG (n=8), ATG Isotype (n=8) and sCR1(n=8) were given IV prior to the laparotomy followed by IR model. The sham group (n=6) served as controls. Blood CD3 lymphocyte counts and CH50 complement assay were used to check efficacy of ATG and sCR1 respectively. The kidneys retrieved at 48 hours were analysed for histology, immunohistochemistry and RT-qPCR studies. Results: The IR group showed significant injury compared to the sham group. ATG treatment offered significant histological protection mainly via decreased leukocyte infiltrate and endothelial protection compared to the IR and Isotype controls. CH50 assay showed complete ablation of complement activity at the time of reperfusion, with return to normality at 24 hours. sCR1 treatment conferred protection from IRI predominantly via suppression of the complement cascade (C3, C9), reduced leukocyte infiltrates and V endothelial protection. RT-qPCR showed down-regulation of injury molecules – KIM-1 and NGAL in both the intervention groups. Conclusion: Modulation of leukocytes and complement system using single dose ATG and sCR1 led to significant endothelial protection, resulting in amelioration of renal ischaemia-reperfusion injury. The complement system was ablated at the time of reperfusion and was reconstituted by 24 hours, thus indicating that suppression of complement system during the phase of IR provides an avenue for mitigating IRI.

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10

Al-Mousawi, Abdul-Majeed M. "A study of warm-up and injury in hamstring muscles." Thesis, University of Glasgow, 2005. http://theses.gla.ac.uk/6899/.

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This project is the first to investigate blood perfusion in the human hamstrings during isometric exercise with a near infrared spectroscopy (NIRS). A Kin Com dynamometer has been used to fix the knee positions and to measure torques during contractions. Both the NIRS optodes and the electromyography (EMG) electrodes were attached to the skin over the hamstrings. Previous studies used a NIRS to measure muscle blood flow in the forearm, quadriceps and calf muscles. The changes in haemoglobin concentrations were calculated using Spike 2 software. A total of 46 male volunteers participated in the four series of experiments described in this thesis. The following overall conclusions can be drawn: perfusion decreases in the hamstrings during contractions and then returns to normal levels after a period of time, changing the limb position at which the contractions are made does not affect the perfusion, warm-up exercises increase in blood perfusion for 8 minutes at 30 and 40% of MVC. The perfusion did not significantly change during an episode of DOMS or in the injured and non-injured limbs. These conclusions show the importance of warm-up before sports activities but not necessarily avoid injury. It can be concluded that there is no association between such conditions with hamstring injuries. The maintained perfusion at different conditions is a positive finding as the perfusion is not restricted indicating good delivery of oxygen despite muscle injury.

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11

Zelt, Ronald G. "The electrical injury enigma /." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61745.

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12

McGeoch, Ross James. "The assessment of microvascular injury in patients undergoing emergency PCI for ST - elevation myocardial infarction." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3560/.

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Despite the interventional and pharmacological advances in treatment in ST elevation myocardial infarction in recent decades, it continues to be a significant cause of morbidity and mortality in Scotland and around the world. The diagnosis and treatment of ST-elevation myocardial infarction has been the subject of intense investigation and the focus of numerous randomised clinical trials over past decades. In an attempt to minimise adverse sequelae it is imperative that in patients with ST elevation myocardial infarction (STEMI) the immediate goal of therapy is to rapidly achieve patency of the epicardial infarct related artery (IRA) and consequently reperfusion of the affected myocardium. Thrombolysis achieves normal flow (TIMI grade 3) in the IRA in around 50% of patients compared to around 90% with primary PCI (pPCI). The successful restoration of epicardial coronary artery patency with TIMI grade 3 flow, however, does not necessarily translate into adequate tissue level perfusion. Inadequate tissue level perfusion in ST – elevation myocardial infarction in the presence of a patent epicardial artery is characterised by myocardial microvascular dysfunction. Evidence of microvascular obstruction (MVO) regardless of how it is assessed is associated with adverse clinical outcomes in this patient group. A series of consistent data has clearly shown that MVO has a strong negative impact on outcome. The index of microvascular resistance is a marker of myocardial microvascular resistance which be validated in vitro and in vivo and has been shown to be independent of variations in haemodynamic state. By incorporating collateral flow IMR has been validated in the presence of an epicardial stenosis and therefore can be calculated prior to and following stenting. Calculation of IMR at the time of emergency PCI for STEMI could potentially provide a marker of microvascular and myocardial injury in the very early post infarct period when further potential interventions would be most beneficial to the patient. Cardiac MRI imaging is the current gold standard for assessment of left ventricular ejection fraction and infarct volumes. Using Gadolinium contrast agent CMR can characterise microvascular obstruction and calculate infarct volumes. This useful information is not normally available at the time of emergency PCI. The principle aim of this thesis is to compare pressure wire derived markers of microvascular obstruction, principally IMR, calculated at the time of emergency PCI for STEMI with evidence of microvascular and myocardial damage as assessed by ceCMR scanning at 2 days and 3 months post PCI. In particular I will look at whether IMR at the time of PCI for STEMI can be used as a predictor of myocardial damage on ceCMR.I will also compare IMR the “traditional” indices currently used to assess microvascular perfusion and assess the impact that stenting itself has on the coronary microvasculature by comparing IMR prior and following PCI. CMR imaging is not commonly available in the early post infarct period. I will therefore also look at the safely, feasibility and clinical utility of ceCMR imaging in the 24 to 48 hour period following PCI for STEMI. Patients who were undergoing emergency PCI for STEMI were recruited. They underwent pressure wire assessment at the time of emergency PCI and had ceCMR scans at 2 days and 3 months following their myocardial infarction. A total of 77 patients were consented for the study between 04/01/2007 and 28/02/2008 and 69 patients had successful coronary physiological studies at the time of PCI. Two hundred patients in total underwent early ceCMR post STEMI over a longer time period. In summary the findings of this thesis are:  IMR is significantly higher in patients in whom there is evidence of MVO in ceCMR scanning at 48h but does not predict the amount of MVO present.  IMR is a strong independent predictor of LVEF, infarct volumes and LVESV on ceCMR imaging at 48h and 3 months.  IMR was an independent predictor of transmurality score on ceCMR  IMR does not alter significantly following stenting in emergency PCI indicating that stenting itself does not significantly alter the coronary microvasculature.  IMR correlates closely with the “traditional” markers of myocardial damage and myocardial infarction in ST – elevation myocardial infarction.  Anatomical site if myocardial infarction and therapeutic interventions at the time of emergency PCI do not significantly influence coronary pressure wire derived markers of microvascular obstruction taken immediately post – procedure.  There was a nearly exact relationship between the presence of “early” and “late” MVO assessed by ceCMR imaging 48h post STEMI  CMR in the early post infarct period is safe, feasible and provides useful diagnostic information This was the first study to directly compare IMR with ceCMR assessment of MVO and myocardial damage. I feel that my results complement the other work done in this field both in stable patients and in the STEMI population. I have shown that an elevated IMR is linked to microvascular and myocardial damage as revealed by ceCMR in the early post infarction period and at longer term follow up. Accordingly, I suggest measurement of IMR represents a new approach to risk assessment at the very earliest stage of acute MI management, and potentially, therefore enables triage of higher risk patients to more intensive therapy.

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13

Whalen, Henry R. W. "Investigating the effects of stem cell therapies in experimental models of renal ischemia-reperfusion injury." Thesis, University of Glasgow, 2017. http://theses.gla.ac.uk/8405/.

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The incidence of end-stage renal disease is increasing in Western Society. Renal transplantation is known to be the optimal treatment for ESRD, being associated with significant reduction in morbidity, mortality for patients and cost for wider society when compared to remaining on dialysis. Unfortunately, the growing number of patients listed for renal transplantation has occurred without a matched supply in the number of suitable organs. This has led to longer average waiting times for increased numbers of patients, who consequently suffer adverse outcomes at considerable cost to the National Health Service as a result of organ shortage. One strategy employed by clinicians to meet demand for organs has been to transplant ‘suboptimal’ kidneys’ historically rejected as unsuitable for transplantation, which are usually retrieved from older and less fit donors. Sometimes referred to as ‘extended criteria’ or ‘marginal kidneys’, such allografts are more prone to damage in the peri-transplantation period, with the major pathological process recognised to be ischemia-reperfusion injury (IRI). Although functioning ‘marginal’ allografts have been shown to confer benefit to recipients, early transplant failure is associated with negative outcomes. Consequently, there is a real need to develop treatments to mitigate renal IRI, especially since the use of ‘marginal’ kidneys is likely to increase. Stem cell therapy has been shown to protect solid organs from IRI in a number of different animal models. Consequently, there is great interest in researching the ability of stem cell-based therapies to ameliorate solid organ damage and perhaps to encourage organ regeneration. However, debate exists regarding the exact mechanism by which stem cells produce their effects. Some researchers suggest that stem cells directly differentiate to replace specialised cell types in damage organs. Other investigators conclude that stem cells produce their effects in a paracrine fashion via the release of extracellular vesicles with the horizontal transfer of genetic material between cells. Unfortunately, no therapies are currently in widespread use to reduce damage to allografts in the peri-transplant period. In part, this reflects the lack of robust small animal models for screening potential renal IRI therapies before testing in large animal models. Furthermore, clinical application has been limited by safety concerns, and particularly by the risk of stem cells undergoing malignant transformation and subsequent tumour formation in recipients. However, investigators hypothesise that the use of stem cell-derived, extracellular vesicles may confer similar beneficial therapeutic efficacy, but lack many of the side effects associated with stem cells themselves. This thesis describes experiments in which stem cell-based therapies are tested in conventional and novel animal models of renal IRI and renal transplantation. In Chapter 3, initial experiments unexpectedly demonstrated the potential of ex vivo expanded stem cells to undergo malignant change and induce tumour formation in recipient animals. Therefore, the subsequent research investigated the effects of freshly isolated stem cells or those of novel extracellular vesicle preparations. In Chapter 4, experiments unexpectedly demonstrated the shortcomings of a conventional rat model of renal IRI. Therefore, Chapter 5 describes the development of a novel rat of model of renal IRI, in which stem cell-based therapies may be tested. Using this animal model, Chapters 6 and Chapter 7 describe the investigation of novel stem cell-based therapies and their effects on renal IRI. Some of these treatments were found to protect kidneys from IRI damage with preservation of renal function and structure in the medium to long-term. Chapter 8 describes a rat model of renal transplantation, in which therapies were investigated after being screened for efficacy in the novel rat IRI model. Although no functional difference was demonstrated, renal histology was preserved by treatment, although the mechanisms by which this effect occurred remain unclear. These findings suggest that stem cells and their extracellular vesicles have the potential to reduce peri-transplantation renal IRI and hence improve long-term outcomes of ‘marginal’ allografts. However, clinical translation requires the long-term efficacy and safety of these novel therapies to be investigated in large animal models of renal transplantation, before further testing in pilot studies.

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14

Harder, Susan. "Prognostic factors in whiplash injury." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=68179.

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A historical cohort of 3014 individuals who sustained a whiplash injury resulting from a motor vehicle accident in Quebec in 1987 was assembled and followed up to six years using data obtained from the computerised databases of the province's universal automobile insurance plan. The prognostic factors that were found to be associated with the time to recovery from whiplash were gender, age, number of dependents, marital status, accident severity, vehicle type, seatbelt use, and the presence of multiple injuries. Factors that were predictive of the risk of recurrence of symptoms were age, number of dependents, and accident severity. None of the prognostic factors studied were found to be useful predictors of the amount of medically-related costs reimbursed by the insurance plan.
The results of this study will be used in a future study involving more numerous and precise medical prognostic factors to assess their role in the management of whiplash patients.

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15

Uniacke, Mark. "The natural history of acute kidney injury and its relationship to chronic kidney disease." Thesis, University of Southampton, 2012. https://eprints.soton.ac.uk/361330/.

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16

Teale, Joanna Helen. "Cognitive and affective predictors of participation in rehabilitation after acquired brain injury." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5735/.

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Objective: The present study aimed to investigate the factors relating to mood and cognition which influence a person’s ability to participate in rehabilitation after Acquired Brain Injury (ABI). It was hypothesised that impairment in cognition, including specific impairment in executive functioning and depression would be associated with poorer engagement in rehabilitation. Method: Twenty-nine patients undergoing rehabilitation following stroke (89.7%) or TBI (10.3%) participated. Individuals recruited completed the Hospital Anxiety and Depression Scale as a measure of mood and an executive functioning test battery. Data collection occurred over a two week period as concurrent ratings of participation were gathered from physiotherapists and occupational therapists using the Pittsburgh Rehabilitation Participation Scale. Results: In support of the hypotheses, correlation analysis showed a significant positive correlation between participation in rehabilitation with executive functioning (p < .05) and a significant negative correlation between participation in rehabilitation and low mood (p < .05). No association was found between general cognitive ability, functional disability, time since injury, age, gender and participation.

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17

Griffin, Jacob Peter. "Investigations into long tract function following spinal cord injury and cell transplant therapy." Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/5095/.

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Traumatic spinal cord injury (SCI) leads to severe functional deficits for which there are currently no effective treatments. About 50% of SCIs are incomplete leaving varying numbers of spared axons intact whilst damaging the cells which ensheathe them. These spared fibres provide targets for therapeutic interventions which aim to maximise their potential for supporting residual functions. In preclinical studies, functional outcomes are most commonly assessed using behavioural approaches. However they are unable to provide information on the mechanisms of recovery or differentiate between mechanisms occurring in the spinal cord and compensatory mechanisms occurring in the brain. This study had two main aims: firstly to develop an electrophysiological protocol for assessing transmission in the ascending dorsal column pathway, to use this protocol to characterise the effects of contusion injuries of different severities and to investigate the time course of changes to long tract function following SCI. The second aim of this project was to use this protocol combined with behavioural testing to investigate the use of human lamina-propria mesenchymal stem cells (hLP-MSCs) as a potential therapy for spinal cord injury. An electrophysiological approach was used to investigate function in rats subjected to T9 contusion injuries of the dorsal columns. Changes in the function of this pathway were assessed by recording sensory evoked potentials (SEPs) from the surface of the exposed somatosensory cortex, following stimulation of the contralateral sciatic nerve. Functional effects of increasing injury severities were investigated in normal animals and animals 6 weeks after receiving contusion injuries of increasing severity. Maximum SEP amplitudes and isopotential plot areas were reduced with injury severity, and latency to sciatic SEP onset was seen to increase in a graded fashion with increasing injury severity. SEP mapping revealed that the region of cortex from which SEPs could be recorded at or greater than certain amplitudes remained focused in the same location with increasing injury severity. Animals were investigated at different time points from acute up to 6 months post injury. Acute investigation revealed that sciatic SEPs are ablated immediately following injury and after incomplete recovery stabilise within hours of injury. Maximum sciatic SEP amplitudes and cortical areas both show 2 phases of recovery: One at 2 weeks post injury and one at 6 months. Onset latencies are seen to increase initially before gradually returning nearer to normal levels by 6 months. SEP mapping revealed that the region of cortex from which SEPs could be recorded at or greater than certain amplitudes remained focused in the same location with increasing post injury survival time. Histological observations confirmed that the injury causes substantial damage to the dorsal columns. To assess the effects of potential therapeutic hLP-MSC transplants, the functional effects of T9 150 Kdyn contusion injuries were investigated in medium injected controls and 3 week delayed hLP-MSC transplanted Sprague Dawley rats, at 10 weeks post injury. Behavioural testing was performed throughout, with terminal electrophysiological and immunohistological investigations performed at the end of the study. Animals were behaviourally tested at pre- and post-operative time points for the duration of the experiment. Electrophysiological recordings suggest some recovery of function with time after injury. Two phases of recovery are seen, one at about 2 weeks after injury and the other at about 6 months after injury; however other measurements suggest hLP-MSC transplants had little or no effect on the functional integrity of the dorsal column pathway. Open field locomotor testing using the Basso, Beattie and Bresnahan (BBB) locomotor scale revealed no differences between the recoveries of cell transplanted and control groups. Gait analysis was performed using the Digigait™ Imaging System revealing a trend for earlier recovery of co-ordination between forelimbs and hindlimbs in hLP-MSC transplanted animals compared to control animals. Moreover the step sequence data also suggested a better recovery of co-ordinated stepping in transplanted compared to medium injected animals. Dynamic weight bearing apparatus (BIOSEB) was used to measure the percentage of body weight borne on the forepaws and hindpaws, this demonstrated no effect of transplanted cells on postural changes. hLP-MSC transplants did not increase indicators of neuropathic pain in our model suggesting they are unlikely to exacerbate neuropathic pain following spinal cord injury. At present there are no immunohistochemical (IHC) markers that can be used to differentiate axons which have been remyelinated with central-type myelination from those which survived the injury. Thus, the degree of peripheral-type myelination was investigated as a simple way of assessing remyelination. This suggested that there was a greater degree of remyelination in transplanted animals, and that this was specifically in areas where transplanted cells were located.

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18

Hidalgo, San Jose Lorena. "Microfluidic production of stem-cell microcapsules for spinal cord injury repair." Thesis, Cardiff University, 2017. http://orca.cf.ac.uk/99333/.

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Stem cell therapy demonstrates much promise for the replacement of damaged tissue in several diseases, including spinal cord injury. However, challenges around the control of stem cell fate in situ still hinders effective recovery of the normal tissue function. Stem cell encapsulation permits their immobilization within biocompatible scaffolds, allowing for a better control of parameters such as proliferation, integration, migration and differentiation within the host tissue. A customized microfluidic device was developed for the production of alginate microcapsules. The diameter of such microcapsules could be easily controlled by the modification of the fluids flow rates, allowing for the reproducible production of highly monodisperse microcapsules. This microfluidic method was then successfully applied for the encapsulation of two different types of stem cells: (i) Neural Stem Cells and (ii) Dental Pulp Stem Cells. Both cell types demonstrated survival within the alginate microcapsules for up to three weeks in culture. However, an early egress of cells from inside to outside of the microcapsules was observed 3 days post-encapsulation. In order to delay such cell escape, alginate microcapsules were modified through the addition of type I collagen. The alginate-collagen microcapsules permitted similar rates of cell survival and permitted the delay of cell egress until 10 days after encapsulation. Stem cells demonstrated a retention of their stem cell and neuronal differentiation properties upon selective release from alginate-collagen microcapsules, as demonstrated by high proliferation rates and the production of stem cell and neuronal markers. When cell-laden microcapsules were transplanted into an ex vivo SCI model the microcapsules were able to effectively retain the transplanted stem cells at the site of implantation. Transplanted cells survived up to 10 days in culture after transplantation and demonstrated the production of neuronal markers within the cord cultures. The results presented in this thesis demonstrate the ability of stem cells to retain their viability and neuronal differentiation capacity within alginate-collagen microcapsules, thereby providing a promising future therapy for the treatment of spinal cord injury.

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19

Hearn, Jasmine Heath. "Exploring the experience of neuropathic pain following spinal cord injury : an interpretative phenomenological analysis study." Thesis, University of Buckingham, 2015. http://bear.buckingham.ac.uk/137/.

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Research exploring pain following spinal cord injury (SCI) is largely quantitative, with very little known about what it is like to live with pain after SCI. In response to inconsistencies and the dearth of qualitative literature in this area, this study investigated the lived experience of neuropathic pain (NP), following SCI. This was conducted using semi-structured interviews with 16 people living with SCI-specific NP that had been present for a minimum of three months. Eight participants were inpatients in a rehabilitation centre, aged between 23 and 82, and eight were outpatients living in the community, aged between 26 and 77. Data from each sample were analysed separately using the qualitative methodology of Interpretative Phenomenological Analysis (IPA). For outpatients, three themes emerged: (1) the chasm between biomedical perspectives and patient needs and beliefs; (2) the battle for ultimate agency in life; and (3) the coexistence of social cohesion and social alienation. For inpatients, four themes emerged: (1) using metaphors to describe NP; (2) the spectrum of medication experience; (3) interpreting the hospital environment; and (4) thinking about the future. The results suggest that chronic NP is experienced in a biopsychosocial manner, and should be treated in such a way. In particular, participants felt that medication was heavily relied upon by healthcare professionals, despite limited efficacy, and articulated a desire for collaborative approaches to pain-management. Issues surrounding acceptance of NP, and its social impact, were also discussed. The involvement of significant others in pain management may improve communication and psychosocial outcomes. Promoting acceptance may be effective in facilitating psychological, and social well-being. Cognitive treatment incorporated with acceptance- and mindfulnessbased interventions (MBIs) may encourage adaptive responses to, and interpretation of, pain.

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20

Rogers, Frances. "Personal experience of sufferers from whiplash injury compared to the experience of doctors managing the condition." Thesis, University of Huddersfield, 2010. http://eprints.hud.ac.uk/id/eprint/10159/.

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This qualitative study takes an interpretative phenomenological approach to understand the experience of whiplash injury from the different perspectives of patient and doctor. This was carried out in order to identify what psycho-social consequences might be experienced by patients as a result of that injury and to identify any implications for healthcare provision. The research was conducted in two phases. During Phase One, eight patients were recruited through GP practices using a combined approach of retrospective and prospective sampling. Three semi-structured interviews and one telephone interview were carried out with each participant over a twelve month period. In keeping with phenomenological methodology, data were analysed using Template Analysis (King, 2004) and a set of themes relating to healthcare experience were identified: „embodiment‟ „experience of pain‟ „disruption to lifestyle‟, „making sense‟, „patient as expert‟ and „whiplash: a minor injury?‟. During Phase Two, one semi-structured interview was carried out with eight doctors who worked in either the primary or secondary care settings. Data were analysed using Template Analysis and a set of themes relating to their experiences of treating patients was identified: „expectations regarding what patients will experience‟, „what patients do about their whiplash injury‟, „what doctors do‟ and „blame if things go wrong‟. These findings show how the patient participants‟ physical and psychological experiences of their malfunctioning body had consequences for maintaining their sense of self and their ability to carry out their normal everyday activities at home and work. The doctors‟ own expectations of treating patients with whiplash injury and whether or not they trust the patients‟ account have illustrated three approaches: dismissive, reactive or proactive that have different implications for patients‟ experiences of healthcare. The study shows how the notion of „compensation‟ is implicated in whether or not the doctor feels able to trust the patient‟s account. The implications of these findings can be seen in terms of methodological focus, general practice and policy formulation. Methodologically interpretative phenomenology provides a theoretical foundation that is, at the very least, equal to and able to challenge more „traditional scientific foundations‟ through its focus on meaning. In terms of practice and policy formulation, the findings have provided a unique insight that might prove to be beneficial for understanding the health care experience and assist in the provision of guidelines aimed at the treatment of whiplash injury. Indeed it is advocated that doctors adopt a subjective approach and that this is taken into account in training.

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21

Keeble, Hayley Susan. "Relationship continuity and understanding challenging behaviours in spouses/partners of those with an acquired brain injury." Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7744/.

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This thesis is submitted in partial fulfilment of the requirements for the degree of Doctorate in Clinical Psychology at the University of Birmingham. The thesis consists of two volumes which illustrate research (Volume I) and clinical work (Volume II). All identifying information has been anonymised to ensure confidentiality. Volume I This first volume contains three chapters. The first is a systematic review of the research literature regarding carers’ attributions of challenging behaviour in care-recipients with dementia. The second is a research study examining the association between spousal carers’ perceptions of relationship continuity, and their understanding and management of challenging behaviour, for partners with an acquired brain injury. The third is a public dissemination document providing an accessible overview of the research study. Volume II This second volume contains four clinical practice reports (CPRs) and an abstract of a fifth CPR which was presented orally. The first CPR describes the assessment and formulation of a 48-year-old man with mild learning disabilities who was experiencing anxiety and low mood, from cognitive behavioural and systemic perspectives. The second is a service evaluation of a dementia-friendly inpatient unit, identifying the barriers and facilitators to good care. The third is a single-case experimental design of a 33-year-old man in a medium-secure forensic service who experienced anxiety. The fourth describes a piece of leadership and consultation work, regarding how hospice staff cope with grief. The final CPR is an abstract of an oral presentation of a case study of a graded exposure intervention with a 16-year-old female.

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22

Pankhurst, Tanya. "Heterogeneity of injury in vasculitis : influence of anti neutrophil cytoplasm antibody IgG subclass and endothelial susceptibility." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/718/.

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This study examined IgG subclass in ANCA associated vasculitis and glomerular endothelial cell (GEC) phenotype predisposes to injury. Using the flow model, interaction of neutrophils with normal immunoglobulin subclasses was compared to interaction with subclasses of ANCA IgG. Neutrophils were captured by normal IgG3>IgG1>IgG2/IgG4. Blockade of CD32 affected IgG3, CD16, IgG1/2. Neutrophils exposed to soluble ANCA IgG1/3 adhered to cytokine-activated endothelial cells, as did IgG4, not previously thought to bind constitutively expressed CD16/CD32. Fc blockade reduced binding. GEC were compared with human umbilical vein endothelial cells. Surface VCAM-1 was reduced on GEC and GEC demonstrated reduced leukocyte capture. RNA array analysis demonstrated a reduction in the GEC gene responsible for post translational modification of VCAM-1 to a sialoglycoprotein. VCAM-1 expression by GEC may be a protective mechanism to reduce inflammatory responses, potentially disrupted in disease. ANCA subclass and endothelial phenotype are important vasculitis pathogenesis: this may be useful in designing targeted therapy reducing overall immunsuppressive load. Additionally modification of specific adhesion molecule profiles on endothelial cells may enable alteration of conditions of one vascular bed whilst reducing impact on unaffected sites.

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23

Wang, He 1965. "Extracellular matrix metabolism in injury-induced atherosclerosis." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40277.

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Remodelling of extracellular matrix (ECM) is a prominent feature of atherosclerotic lesions and contributes to lipoprotein retention as well as smooth muscle cell (SMC) activation. To gain further knowledge about ECM, certain ECM components and their degrading enzymes were studied in injury-induced arterial neointima, which shares features with early atherosclerotic lesions.
It has been shown that synthesis of collagen and syndecan-1, a hybrid heparan/chondroitin sulfate proteoglycan, is enhanced. In situ hybridization indicates that syndecan positive cells are restricted to the arterial neointima. These data confirm the importance of arterial SMC in ECM metabolism and indicate that increased synthesis contributes to ECM accumulation in neointima.
Remodelling of ECM in atherogenesis refers not only to increased ECM deposition, but also involves enhanced ECM catabolism. A family of zinc-containing proteinases, termed matrix metalloproteinases (MMPs) has recently been implicated in atherosclerosis. Subsequently, we examined expression of two common MMPs, MMP-2 and MMP-9 in our model. The mRNAs for both MMPs are up-regulated, but their tissue distribution is different: MMP-2 positive cells are visible in neointima and in aortic media; whereas cells positive for MMP-9 are located only in neointima. MMPs are active at neutral pH and in tissue, their activity is regulated by tissue inhibitors of metalloproteinases (TIMPs) including TIMP-1. The enhanced MMP expression in neointima makes it relevant to examine the simultaneous expression of TIMP-1. To do this, we cloned rabbit TIMP-1 from neointima using a PCR-cloning technique. Transformation of the cloned gene resulted in synthesis of a TIMP-1 protein in E. Coli. The concentration of TIMP-1 in neointima was examined and a significant increase of both mRNA and protein levels was observed. It is suggested that the proteolytic activity of MMPs contributes to ECM breakdown. However, this digestion is limited, as continuous augmentation of TIMP-1 expression is observed after aortic de-endothelialization.

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24

Wosik, Karolina. "Impact of injury mediators on CNS glia." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85105.

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Multiple Sclerosis (MS) is an inflammatory disorder of the central nervous system (CNS). It is characterized by the infiltration of immune cells into the brain, leading to myelin destruction and the demise of oligodendrocytes (OLs), the myelinating cells of the CNS. The mechanisms of tissue destruction are still being elucidated. We have looked at the effects of two putative injury mediators on resident CNS glia. Firstly, we investigated the functional consequences of signaling via death receptors Fas, DR4 and DR5 and their ligands Fas ligand (FasL) and tumor necrosis factor related apoptosis inducing factor (TRAIL) in astrocytes isolated from fetal CNS and in OLs from human adult brain. We find astrocytes express these receptors but are resistant to apoptosis upon their ligation due to the expression of FLICE inhibitory protein (FLIP). Receptor expression is however not silent as distinct signaling pathways are activated as a result of receptor ligation. In OLs, we find receptor expression can be induced upon upregulation of the stress induced protein p53, at which point OLs become susceptible to FasL and TRAIL killing. In situ in MS lesions displaying oligodendrogliopathy, we demonstrate that a high proportion of OLs are immunopositive for p53, suggesting p53 may play a role in OL demise. Secondly, we investigated the effects of the excitatory amino acid glutamate, acting through ionotropic glutamate receptors, on human adult OLs. Based on animal models, excitotoxicity has been proposed to play a role in OL destruction in MS. We find human OLs are in fact resistant to excitotoxicity mediated by AMPA or kainate receptors and this is in sharp contrast to their rodent counterparts. We propose this resistance is due to the lack of expression of glutamate receptors on human OLs both in vitro and in situ. These results indicate that glutamate is not directly responsible for the killing of otherwise healthy OLs in MS. These studies demonstrate

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25

Zargham, Ramin. "[Alpha]8[beta]1 integrin and vascular injury : role of [alpha]8[beta]1 integrin in restenosis after balloon injury." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111876.

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Restenosis is the major cause of the failure of reconstruction methods to restore the blood flow in atherosclerotic arteries. Restenosis results from neointima formation and consequent constrictive remodelling. Vascular smooth muscle cell (VSMC) migration from the tunica media toward the intima is crucial in neointima genesis. The prerequisite for VSMC migratory activity is the modulation from the differentiated (contractile) to the de-differentiated (noncontractile) phenotype. VSMC phenotype change is associated with the altered expression of integrins. alpha8beta1 integrin is upregulated in cell types with contractile properties, including myofibroblasts and mesangial kidney cells. It is one of the integrins that is intensely expressed in mature VSMCs. alpha8beta1 integrin expression during vascular injury and its role in VSMC function have not been studied so far.
In this work, a rat model of carotid angioplasty was used to mimic vascular injury in humans. alpha8beta1 integrin was downregulated in the tunica media concomitantly with loss of the contractile phenotype. In vitro study revealed that it is a differentiation marker of VSMCs. To test the functional significance of the association between alpha8 integrin and the VSMC phenotype, short interference RNA was deployed to silence the alpha8 integrin gene. alpha8 integrin gene silencing heightened VSMC migratory activity as well as modulation of the VSMC phenotype in favour of the noncontractile state. In addition, alpha8 integrin overexpression induced re-differentiation of VSMCs and attenuated their migratory activity. It is, therefore, suggested that alpha8 integrin overexpression after vascular injury might control VSMC migration and neointima formation. On the other hand, alpha8 integrin gene silencing led to a reduced growth rate, which indicated a dichotomy between VSMC migration and proliferation.
In the later stages of neointima formation, constrictive remodeling plays a major role in late lumen loss. Our data demonstrated that alpha8 integrin is upregulated in the neointima during constrictive remodeling with concomitant luminal narrowing. The importance of this finding was highlighted by results showing that alpha8 integrin was required for the VSMC contractile phenotype evoked by transforming growth factor-beta (TFG-beta) and TFG-beta-induced myofibroblastic differentiation of Rat1 fibroblasts. Thus, it appears that alpha8 integrin expression blockade might reduce contractile remodeling and late lumen loss. Although the mechanism of alpha8 integrin signaling is not yet clear, our findings demonstrate that the alpha8 integrin-induced contractile phenotype is blocked by RhoA inhibitors. Furthermore, alpha8 integrin and RhoA are co-immunoprecipitated, and alpha8 integrin gene silencing reduces RhoA activity. Hence, it is postulated that alpha8-RhoA signaling might be closely intertwined.
Altogether, these studies indicate that alpha8 integrin is a contractile marker of VSMCs and a negative regulator of VSMC migration. Therefore, forced alpha8 integrin expression may be applied to reduce neointima formation. However, alpha8 integrin upregulation during constrictive remodeling concomitant with late lumen loss suggest that it could be involved in lumen narrowing. It seems likely that in therapeutic strategies to reduce restenosis the timeline of interference might be very important. Therefore, alpha8 integrin gene silencing in the later stages of neointima formation might be beneficial.

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26

Sheppard-Jones, Nicolas. "Ocular impairment in pediatric mild traumatic brain injury." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121355.

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Mild Traumatic Brain Injuries (mTBI) and concussions are complex injuries with high incidence rates in children and adolescents. There currently exists no 'gold standard' for the diagnosis of concussions, and detection and monitoring are made challenging by highly variable clinical presentations. There is growing evidence that mTBI is associated with oculomotor impairment in adults, and that this type of deficit may serve as a marker for the injury. The literature indicates the question has never been addressed in pediatric mTBI. The research presented here sought to address this knowledge gap by first evaluating smooth pursuit and fixational eye movement integrity in a cohort of children and adolescents suffering from mTBI, and then comparing their performances to control participants not having sustained a head injury. The research yielded mixed findings. On the one hand, we found that fixational eye movements are not impaired in pediatric mTBI; measures of fixational eye movement integrity were comparable across groups. On the other hand, selective deficits in smooth pursuit eye movements were found. Synchronization of eye movement with target motion was significantly poorer for mTBI patients. Their abilities to trace target trajectory accurately and to match target velocity, however, were not found to be impaired. It remains unclear whether the observed deficits were caused by disrupted function of the smooth pursuit system proper, by damage to areas that modulate smooth pursuit through top-down influence, or by a combination of both. These preliminary results suggest that select smooth pursuit paradigms could play a role for diagnosing pediatric mTBI, and reinforce the need for further studies in this novel area of research.
Les Traumatismes Crâniens Légers (TCL) et les commotions cérébrales sont des blessures complexes auxquelles les enfants et les adolescents sont particulièrement à risque. Il n'existe pas actuellement d'outil objectif pour le diagnostic et le monitorage de ces blessures, qui sont difficiles à gérer en raison de la grande hétérogénéité clinique qui les caractérise. Un nombre grandissant d'études indique que les TCL peuvent engendrer une dysfonction au niveau des mouvements oculaires chez les adultes, et que ces troubles visuels pourraient servir de marqueurs efficaces pour la détection. La question n'a jamais été posée chez les enfants. Ce projet tente d'apporter une réponse préliminaire, d'abord en évaluant l'intégrité des Mouvements de Poursuite Visuelle (MPV) et de fixation chez des enfants et adolescents atteints d'un TCL, puis en comparant leur performance à celle de sujets contrôles n'ayant pas subi de blessure à la tête. Les résultats obtenus sont mixtes. Aucune dysfonction au niveau des mouvements de fixation n'a été décelée; toutes les mesures utilisées pour évaluer les capacités de fixation étaient comparables par groupe. En revanche, des troubles sélectifs ont été détectés au niveau des MPV. Les patients atteints de TCL éprouvaient en moyenne plus de difficulté à synchroniser le mouvement de leurs yeux avec le mouvement d'une cible. La précision et la vélocité du mouvement ne semblaient pas toutefois affectées. Les résultats ne permettent pas de trancher sur la nature exacte du trouble observé, ce dernier pouvant être causé à la fois par une dysfonction au niveau des circuits visuo-moteurs propre, et par une dysfonction au niveau de structures de plus haut niveau modulant les MPV. Ces résultats préliminaires indiquent que l'évaluation des MPV pourrait contribuer au diagnostic et au monitorage de TCL pédiatriques, et renforcent le besoin d'investigations additionnelles dans ce domaine.

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27

Baillie, Andrew G. S. "Skeletal muscle metabolism after nerve crush injury." Thesis, University of Aberdeen, 1994. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU059079.

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A model was developed in the rat using a nerve crush procedure, as a form of temporary denervation, to block neural input to the hindlimb muscle of one leg. The nerve crush has the advantage of allowing self-reinnervation of the muscles after regrowth of the damaged nerve, which occurred (in this study) after approximately 14 days. The initial denervation-like phase resulted in a large loss of muscle mass over the subsequent few days which was mostly through a loss of muscle protein. The results demonstrate the correlation between the concentration of glutamine in the muscles and the rate of protein synthesis over the first 3 days after the nerve crush, but other metabolites (alanine, lactate, and glutamate) were seen to react much more rapidly, with significant changes recorded in the first hour after injury. Further studies were undertaken in an attempt to find a link between these acute changes and the later changes in protein and glutamine metabolism. It was demonstrated that these rapid changes were not as a result of a local hypoglycemia, although a reduction in the rate of in vivo glucose uptake was reduced within 4 hours of the nerve crush. Similarly, measurement of activities of key glycolytic enzymes suggested that there were no acute changes in flux through the glycolytic pathway. Finally, a difference in regional blood flow was demonstrated in the experimental muscles and it was concluded that the acute changes in metabolite concentrations might result from simple physiological changes, in response to the anaesthesia and/or the surgical procedure, which subsequently resolved in the innervated, but not the nerve-deprived, muscles.

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28

Gurumoorthy, Dhakshinamoorthy. "A study of neck injury arising from motor vehicle accidents and its clinical management." Curtin University of Technology, School of Physiotherapy, 1996. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=11854.

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The syndrome commonly referred to as whiplash injury" resulting from motor vehicle accidents is complex and remains a challenge to clinicians, as is evidenced by the recent report of the Quebec task force on the "whiplash syndrome". The main objective of this prospective randomised study was to evaluate two conservative treatment regimens (early immobilisation-experimental group-1, early active mobilisation experimental group-2) which are based on accepted physiological rationale and then to compare their effectiveness with existing treatment regimens that are commonly practiced (control group) in the management of "whiplash" type of injuries. To this stage, the current study is the only prospective randomised clinical trial of its type conducted with a sufficiently large sample size and over a long study period. The results of the current study clearly demonstrated that the subjects in the immobilised group recovered from their pain-related symptoms and returned to their normal duties sooner than those in the other two treatment groups. In addition to this, those subjects who received the immobilisation regimen did not show adverse effects on either the range of motion or the strength of the neck muscles. Thus, the immobilisation regimen was clearly shown to be the preferred option when compared to the other two treatment methodologies investigated in the current study.Although the primary interest of the current study was to compare the efficacy of three different treatment regimens, a series of statistical analyses were performed to establish the prognostic significance of several factors associated with "whiplash" injury. This showed that factors such as gender, age, speed of the vehicles involved, paraesthesia, intensity of pain at the time of the initial examination, interscapular pain, blurred vision and difficulty in focusing, all had prognostic value. ++
Similarly, the type of collision, seating position, presence of headache within 24 hours post injury, pre-existing degenerative changes in the cervical spine, loss of lordosis and litigation factors had no prognostic significance. Another major emphasis of the current study has been to concentrate on the pain related symptoms of the neck which are of major concern to "whiplash" subjects and to those clinicians treating them. A paucity of such information is considered to be one of the most notable causes of difficulties encountered in the management of "whiplash" injuries.As an adjunct to the main study, the morphology of the deep pre- and post vertebral muscles of the neck region using embalmed cadavers and fresh post-mortem specimens was investigated, as the literature is deficient in--this regard. Similarly, a longitudinal study of 45 subjects was also performed using Magnetic Resonance Imaging (MRI) technology. The longitudinal nature of the M.R.I. study provided for the first time an account of the details associated with the progressive pathological changes that occurred in some disc lesions, at defined points in time following a MVA. The observations made from the adjunct studies help develop a better understanding of the pathoanatomy associated with the deep muscles of the neck region and the pathological changes that occur following a traumatic disc lesion as evidenced within 2 weeks, after 3 months and 12 months post- injury. On the basis of the observations made in the current study, a classification of the "whiplash" injury has been proposed for the consideration of clinicians. Similarly, the questionnaire used for data collection in the current study, can be readily modified and utilised in a clinical situation for establishing documentation, planning treatment strategies and for evaluation of the treatment outcomes of "whiplash" type of injuries.

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29

White, Rebecca Lucy. "The recruitment mechanisms and beneficial roles of haematopoietic stem cells in murine acute kidney injury." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/4788/.

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Haematopoietic stem cells (HSCs) can migrate to the injured kidney and aid in tissue repair, however clinical success remains poor and is partially attributed to limited HSC recruitment. This study determined the molecular mechanisms governing HSC recruitment to the ischaemia-reperfusion (IR) injured kidney, whether this recruitment could be enhanced and also any immuno-modulatory effects HSCs may be having on surrounding injured microvasculature. HSC adhesion was significantly enhanced to the IR injured kidney compared to sham; this recruitment was governed by CD49d/VCAM-1 and CD44/HA. KC or SDF-1α pre-treatment enhanced HSC adhesion to the IR kidney. KC and SDF-1α also increased CD44 and CD49d surface clusters on HSCs respectively, and therefore increased HSC adhesion to HA and VCAM-1. Following injection into IR injured mice, HSCs improved blood flow and kidney function in the injured kidney compared to sham. This may be related to inflammatory modulation, as neutrophil recruitment and number of platelet microthrombi were reduced following HSC administration. This is the first study to show that pre-treatment of HSCs increases their recruitment to the site of injury, and that recruitment of HSCs can reduce inflammatory cell infiltration following injury.

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30

McRae, Calum George Alexander. "Approaches to functional electrical stimulation induced cycling and application for the child with a spinal cord injury." Thesis, University of Glasgow, 2006. http://theses.gla.ac.uk/1526/.

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In the hope of more compact and user-friendly approaches to FES-cycling through the incorporation of modern sensor and computing technology, two new hip-angle-based strategies (both of which utilise a limb-mounted sensor) and a “traditional” crank-angle-based strategy have been developed and incorporated into a PDA-based multi-functional FES system. Through both simulation and tricycle-based experiments, all three approaches have been shown to provide practical stimulation activation timing. The second research focus concerns the development of two FES-cycling systems which are suitable for a spinal cord injured child, and methods to facilitate the intended use of both devices. A standard child’s tricycle has been modified with appropriate instrumentation for FES-cycling and testing involving its target population was carried out at a US-based paediatric research hospital. These experiments culminated in the demonstration of FES-cycling by an untrained seven year old T4/T6 (motor complete) subject, and the evolution of the device into one which should be able to meet the specific needs of spinal cord injured children. A second system with integrated motor has also been developed. As well as offering motor assistance, this device incorporates additional instrumentation to allow investigation into exercise and training capabilities. Experiments have been undertaken to validate this equipment and it is now ready for future pilot work involving paediatric subjects. The two research foci in this thesis represent what are, in our opinion, important routes that FES-cycling should take to progress into the home environment and also allow participation of a population who have potentially the most to gain from using it.

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31

Du, Xiaojian. "Regulation of EphA2 expression in renal ischemia-reperfusion injury." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111599.

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Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury in both native kidneys and renal allografts. Previous studies in our lab have shown that a subset of Eph family receptor tyrosine kinases, including EphA2, is strongly and persistently upregulated in renal tubular cells in both in vitro and in vivo models of the renal IRI. Src kinases are necessary and sufficient for upregulation of EphA2. We have proposed that IRI-induced EphA2 upregulation may serve as a necessary step in renal tubular remodelling.
In this study, we have further defined the mechanism of Src kinase-induced EphA2 upregulation by identifying the -145/+137 EphA2 promoter region as the minimal region required for basal and Src kinase-induced activation of the promoter. Moreover, we have identified within this region, at position -45, a canonical cAMP response element (CRE) (Nowakowski et al.), which is essential for EphA2 promoter activation. However, we also found that the prototypical CRE-binding transcription factor, CREB, was not necessary for activation of the EphA2 promoter, suggesting that CREB-related or -unrelated transcription factors are responsible for EphA2 upregulation.

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32

Campbell, Holly R. 1976. "Chlorine-induced lung injury and the role of iNOS." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111574.

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Reactive airways dysfunction syndrome (RADS), a form of irritant-induced asthma (IIA) has been observed in humans following acute chlorine (Cl 2) gas exposure in occupational and domestic settings. Following Cl 2 injury, subepithelial fibrosis, mucous hyperplasia, and non-specific airway hyperresponsiveness have been reported. Based on the disease profile, we hypothesized that pulmonary damage may be oxidative in nature.
The aim of this work was to develop a murine model of irritant-induced asthma in order to investigate the pathogenic processes and potential oxidative mechanisms involved in response to Cl2 exposure, with a secondary aim of examining the role of iNOS in response to Cl2 inhalation.
A/J, C57BI/6J (wild type) and iNOS-1- mice exposed to various concentrations of Cl2 were mechanically ventilated for measurement of lung mechanics and responses to i.v. methacholine (MCh). Bronchoalveolar lavage was performed to examine total protein, cell populations and nitrate/nitrates. Tissues were harvested for histology and immunocytochemistry for iNOS, 3NT and carbonyl residues. To examine the role of iNOS, a subset of animals were treated with a selective iNOS inhibitor (1400W) and non-selective NOS inhibitor LNAME.
Chlorine exposure caused airway hyperresponsiveness, which appeared to be mitigated by iNOS blockade with 1400W, however this was not the case in iNOS-1- mice. Cl2 exposure also caused increases in total BAL protein, total cells, NOx, neutrophils, iNOS, 3NT and carbonyl residues.
In conclusion, chlorine exposure causes lung injury, similar to reactive airways dysfunction syndrome, characterized by airway hyperresponsiveness, epithelial sloughing, inflammatory cell influx, oxidative injury and increases in both the activity and expression of iNOS. Chlorine-induced airway hyperresponsiveness is mitigated, in part, by selective blockade of iNOS with the use of pharmacological intervention.

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33

MacArthur, Colin. "Evaluation of the quality of an injury surveillance system." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40187.

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The health care burden associated with childhood injury is huge. Surveillance--the collection, analysis, interpretation, and dissemination of data--is seen as an important step towards understanding and controlling the injury problem. The usefulness of surveillance data, however, depends on their quality. Quality may be defined as the collection of reliable and valid data along with an unbiased capture of events. (An important issue in paediatric injury surveillance is that proxy respondents are often used to provide data on behalf of the child.) Previous evaluations of paediatric injury surveillance data, however, have not directly estimated the reliability and validity of proxy respondent information nor assessed the relative importance of factors associated with system capture.
Given these gaps in knowledge, this thesis examines the reliability and validity of proxy respondent information on childhood injuries. In addition, the importance of precise definition of the surveillance population of interest is described, along with identification of factors associated with failure of injury capture by a national paediatric injury surveillance system. The sensitivity, specificity, and representativeness of injury capture by this system is estimated for three different, but not mutually exclusive, populations of childhood injury.
The results from the proxy respondent studies provide important information on the utility of proxy data on childhood injury, while the studies on injury capture highlight the influence of process and health services utilization on surveillance system function. The implications of these findings for researchers and policy makers are discussed, with examination of the cautions necessary when drawing inferences from surveillance data.

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34

Herrera, Daniel Gustavo. "Neurochemical correlates of cortical brain injury in the rat." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41043.

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Application of potassium chloride (KCl) to a brain surface, a procedure which consistently elicits spreading depression, resulted in a marked induction of the proto-oncogene c-fos in the treated cerebral cortex in a rapid and transient manner. Most of the cerebral cortex throughout the treated hemisphere showed an increase in c-fos-like immunoreactivity (IR). The only area spared was that immediately below the exposed surface. On the other hand, ubiquitin-like IR appeared to increase in pyramidal-shaped cells in the damaged area as early as 90 minutes and persisted up to 2 days after treatment. Mechanical cortical brain injury was accompanied by a similar widespread expression of c-fos protein(s) throughout the wounded cortex even far from the lesion site. Rats with a mechanical cortical injury, which were sacrificed 1.5 hours later, showed an increase in c-fos immunoreactive nuclei in the piriform cortex ipsilateral to the lesion at post-natal day (PD) 22, but not PD 10 or 15. This pattern was maintained up to at least PD 90. Similarly, the presence of c-fos IR cells was observed in the ipsilateral cingulate cortex since PD 22. The pattern of c-fos expression after mechanical wound was compared with topical potassium application to a cortical surface. Though both models generated c-fos expression far from the lesion site, K+ application resulted in a higher number of c-fos immunoreactive cells, particularly in the cingulate cortex.
High potassium concentrations are generally used to induce neurotransmitter release. In order to establish a possible link between c-fos expression and stimulating conditions for neurotransmitter release in microdialysis procedures, we administered KCl (100 mM) into the hippocampus. C-fos-like IR was up regulated in the dentate gyrus and pyramidal cells of the hippocampus. The expression of c-fos induced by KCl was not altered in the animals with fimbria-fornix (FF) lesions despite the marked decrease of ACh releaae in the hippocampus. Glutamate concentrations measured in the same superfusates showed that a significantly greater glutamate release occurs in denervated hippocampi. Administration of pentobarbital (1ml/kg i.p.) in order to abolish any seizure-like activity induced by KCl, did not alter expression of c-fos IR in the K$ sp+$-stimulated hippocampi.
The topical application of high K$ sp+$ concentrations to a brain surface (parietal cortex), which induced c-fos expression, preceded an increase in both NGF mRNA and NGF-like protein(s). A maximal increase in c-fos was detected within 3 hours, whereas NGF mRNA levels peaked at 12 hours and NGF-like protein(s) reached its maximum at 24 hours after KCl application. The most prominent increase in NGF mRNA was measured in the entorhinal cortex (50 fold) but it was also moderately increased in other cortical areas (2-3 fold).
Application of K+ to the cortex induced the expression of glial fibrillary acidic protein (GFAP) in astrocytes, as assessed by immunohistochemical techniques, throughout the cortex ipsilateral to K+ exposure. Administration of the non- competitive NMDA antagonist MX-801 (4mg/kg i.p.) prior to the injury prevented the rise in GFAP IR at 2 but not 7 days after the treatment. GFAP IR was also studied after disruption of a restricted area of the pia-arachnoid which compromises vascular irrigation of the underlying cortex. GFAP+ cells were present in the ipsilateral remaining cortex, distant from the wound, between days 4 and 15.
These findings suggest selective changes in gene expression following different types of cortical brain injury. The interpretation of these observations is given in the discussion of this thesis.

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35

Hall, Margaret. "Process evaluation of a child pedestrian injury prevention intervention." Curtin University of Technology, School of Public Health, 2000. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=11727.

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The Child Pedestrian Injury Prevention Project (CPIPP) is a rigorous school- and community-based intervention trial delivered to 2,500 children in their second, third and fourth year of schooling in three communities in Perth, Western Australia, from 1995 to 1997. The CPIPP was designed to improve children's pedestrian safety knowledge, their road related behaviors - crossing and playing, and to reduce their risk in, and exposure to, traffic. This thesis addresses the process evaluation of the CPIPP school-based intervention. The Curtin University Human Research Ethics Committee provided ethics approval for this project.Evaluation of previous school-based pedestrian safety programs has focused mainly on assessing outcomes with little or no process evaluation. An absence of process evaluation increases the likelihood of Type III error, that is, incorrectly attributing null or weak outcomes to a program that has not been adequately implemented.In each of the three study years, following a teacher training, teachers were asked to implement the school-based intervention. Each year this comprised nine 40-minute pedestrian safety lessons and home activities. Lessons included road crossing practise on real and simulated roads.Data were collected from the student cohort (n=1049) and their Grade 2, 3 and 4 teachers. Four process evaluation instruments were developed and administered in each of the three study years. These included one student instrument (work samples) and three teacher instruments (lesson log, teacher post-implementation questionnaire and classroom observation). Student outcome data including their pedestrian-related knowledge and road crossing and playing behaviours were assessed using a pre- and post-test self report questionnaire.The majority of teachers (70-97%) and students (72-84%) responded positively to questions about their satisfaction with the ++
CPIPP Grades 2, 3 and 4 curricular. Evidence in student work samples demonstrated that teachers taught 76% (seven of nine lessons) of the Grades 2 and 3 curricular, and 68% (six of the nine lessons) of the Grade 4 curricular. Teacher self-reported implementation rates using a 'lesson log' were 88%, 81% and 60% respectively for the three curricular. Teachers reported practising road crossing on a real road in 21% (one lesson) of six designated crossing practise lessons in 1996 and 36% (two lessons) in 1997.Multivariate analyses revealed students pedestrian safety knowledge was significantly associated with teacher implementation of the classroom curriculum. This relationship was one of dose-response. It demonstrated students who, each year, received at least 7 lessons (81% or more) of the three CPIPP curricular showed a greater improvement in pedestrian safety knowledge than those students who received a lower dose of the curriculum. Significant effects on pedestrian safety knowledge were also observed for students who, each year, practised crossing a real road in at least one lesson (17%) of the curriculum. The relationship between implementation and student road crossing and road playing behaviours was not one of dose-response.Student work samples, teacher lesson logs and to a lesser extent teacher self-report questionnaires, were found to be valid measures of curriculum implementation. This study also found that implementation of the CPIPP curriculum achieved a modest improvement in student pedestrian safety knowledge and possibly arrested the decline of safe road crossing behaviour. It also demonstrated that classroom pedestrian safety education alone, while necessary, is not sufficient to positively modify children's road crossing behaviours.The findings of this study demonstrate the importance of measuring teacher implementation. A process evaluation is ++
essential to determine if an intervention has been implemented and to help explain the impact this level of implementation had on program outcomes. However, more research needs to explore the link between other factors in the process of curriculum delivery and program effects. Further research also needs to determine how to develop and measure an intervention that includes the key procedures and content that theoretically promote the desired behaviour, but also allows teachers to make adjustments to the program to suit their teaching style and the needs of their students.Child pedestrian injury is a complex problem that requires a multifaceted intervention, of which a classroom curriculum can form part.

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36

Fairnie, Helen Margaret. "Occupational injury, disease and stress in the veterinary profession." Curtin University of Technology, Australian Telecommunications Research Institute, 2005. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=17084.

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Scant attention has been given to occupational health hazards of Australian veterinarians. This study aimed to identify the major risk factors for occupational injury and disease, emotional health and suicide rates of veterinarians. Qualitative in-depth interviews with 45 veterinarians were carried out which revealed that a significant proportion of veterinarians were both injured, stressed and had incurred zoonotic diseases. Data linkage of the names of registered veterinarians in Western Australia with four Health Department of Western Australia databases was undertaken to provide supportive statistics on the conditions identified as being important in the interviews. The results of this latter analysis were inconclusive. Therefore a self-administered questionnaire was developed, which collected quantitative data on injuries, disease, stress and risk factors from 419 veterinarians. Since the in-depth interviews had identified stress and suicide ideation as being very significant for many of those interviewed, the Kessler 10+ scale for measuring psychological distress was included in the self-administered questionnaire. The data linkage was unable to provide accurate data about numbers of deaths of veterinarians and the records of coroners in Victoria and Western Australia which provided data on 89 veterinarians, were analysed to determine suicide rates. Despite the interviews providing considerable information about rates and risk factors for injuries, disease and stress, no statistical analyses were undertaken because they provided insufficient data for quantitative analyses.
Nevertheless, statistics derived from the morbidity database using data-linkage, will be useful in comparing injuries in any future studies of this type. Data collected from the self-administered questionnaire were subjected to Chi square, and non-parametric tests and logistic regression analyses using multiple imputation for missing values. Age-standardised and age-specific rates (ASR) were calculated for data on suicide in veterinarians derived from coroners' records obtained from Western Australia and Victoria using the Rates Calculator developed by Codde.' The interviews and the survey of 464 veterinarians showed that a significant proportion of veterinarians incurred injuries and zoonotic diseases, and were highly stressed and distressed. The interviews showed that a significant proportion of veterinarians expected to be injured and/or contract zoonotic diseases. It is suggested that this acceptance may, in part, account for the number of injuries that occur. Some of these injuries, especially in mixed animal veterinarians, may be attributable to poor facilities on farms and a lack of competent support in restraint of animals. There needs to be a cultural change with regard to safety if injury is to be reduced. Using the Chi-squared analyses of the survey data, injury was associated with several risk factors including being a practice owner and being in mixed animal practice, being younger and with having taken drugs such as marijuana in the past 12 months.
When all these variables were input into a logistic regression model, several of these risk factors were eliminated providing only three risk factors as predictors of injury. These were: having a back injury; taking drugs in the previous 12 months; and being between 35 and 54 years of age. Having high distress levels was not a predictor for injury. Analyses of responses to the KlOi- scale in the self-administered questionnaire revealed that the proportion of highly distressed respondents was double that of the Western Australian, New South Wales and Australian general populations which supports the findings from the interviews. Logistic regression provided three predictors for distress: being less than 35 years of age, having taken drugs in the past 12 months, and having a back injury, however having other workplace injuries was not a predictor. The findings that the suicide rate in this study was about four times that of the general Australian adult population, should be of major concern and signal that there may be factors specific to the veterinary profession that account for this high rate. This study has shown that there are high levels of psychological distress in veterinarians, especially practitioners, which suggests that veterinary practice may, in itself, be a stressful occupation. However, it may also be that some individuals with a predilection for distress, are being recruited into the veterinary profession.
Better selection techniques for recruiting veterinary students using an aptitude test as well as interviews, could identify those who were unsuited for becoming veterinarians or who required additional mentoring and support upon graduation. This could reduce stress, distress and suicide in the veterinary profession. Overall, 17 recommendations were made directed at improving the quality of data collection to obtain more reliable statistical outcomes, and suggesting ways of reducing injury, distress and zoonotic disease in veterinarians.

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37

Swaminathan, Ramesh. "An investigation to establish how the evolution of rugby influences the risk of spinal injury during scrummaging." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/93563/.

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The rugby scrum results in a large number of injuries to the players of the front row, particularly the hooker. Front row players have been known to suffer from acute and chronic injuries of the cervical spine as well as low back pain. The principal goal of this research was to develop a method to measure spinal biomechanics of the hooker’s role during rugby scrummaging and use this method to address the question of whether recent changes in rugby affect the risk on hooker spinal injury. In recent years, a number of changes have occurred in rugby which may have an effect in injury risk, however, little is currently known about the effect of these changes. This was accomplished through three experimental stages. Firstly, a review of kinematic measurement techniques was undertaken in order to determine the most feasible measurement technique. Inertial sensors were chosen and validated for orientation output against high precision digital encoders with high levels of concordance for each axis of each sensor ( > 0.95). In addition to this, a method of using electromyography to predict muscle force production was investigated. Determined force and recorded force were found to be insignificantly different (p > 0.05) across the 12 participants investigated. Having proved this to be a feasible method, it was put into practise in-field. Inertial sensor technology was combined with a laboratory tested force-EMG correlation to assess spinal biomechanics during live, contested, training scrums for an initial sample of 9 rugby union hookers. No significant differences (p > 0.05) were observed for peak kinematic variables or EMG data. The second study assessed whether a change in playing surface affects hooker spinal kinematics by evaluating key variables such as peak range of motion and angular velocity as there has been a recent shift towards the use of artificial surfaces. Twenty-two participants took part in this study with 11 participants in each group. The groups were not significantly different (p>0.05) in terms of anthropometric and background information. The results of this study indicated that key kinematic variables did not differ significantly (p>0.05) between playing surfaces. There was, however, a large effect (d>0.8) for certain peak angular velocity measurements of the thoracic region. THESIS SUMMARY iii The final study investigated how different engagement techniques affected hooker spinal biomechanics since a recent law change was introduced governing the scrum. These techniques included machine scrummaging and live scrummaging of two different engagement sequences. Twenty-nine participants took part in the live-vs-live comparison with 14 of those taking part in all three experimental conditions. The results of this final study indicate significant biomechanical differences (p < 0.05) between machine and live scrummaging indicating that machine scrummaging is a much more constrained environment. Live scrummaging of the two different sequences did not yield any significant differences (p > 0.05) for both kinematic and muscle activity/determined force data indicating that the sequences do not affect hooker spinal biomechanics. These results suggest that the recent changes in rugby do not significantly affect the risk of spinal injury of the rugby union hooker.

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38

Germain, Geneviève. "Effect of hyperbaric oxygen therapy on exercise-induced muscle injury." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=29504.

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The purpose of this study was to examine the effects of HBO2 therapy on exercise-induced muscle damage. Subjects (n = 16 university student volunteers) were randomly divided into an experimental group that received HBO2 therapy and a control group that did not receive any treatments. HBO2 treatments consisted of 5 sessions of breathing 95% oxygen at 2.5 atm abs for 100 min. Temporary muscle soreness was created using a single-leg eccentric exercise task involving the quadriceps femoris. Over the next 14 days, measurements were obtained on muscle soreness, leg circumference, quadriceps peak torque, quadriceps average power, fatigue and plasma creative kinase. After eccentric exercise, plasma CK levels and perceived muscle soreness were elevated but were not different between HBO2 and control groups. HBO2 therapy did not alter leg circumference, quadriceps peak torque, average power or fatigue compared to the control group. The data indicated that five HBO2 treatments did not speed recovery following eccentric exercise that induced temporary muscle damage.

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39

Lee, SangKyu. "Image-based dose correlation studies on radiation- induced lung injury." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97013.

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The goal of this work is to develop an accurate and automatic tool to evaluate normal lung tissue response to radiotherapy (RT) and its correlation with local dose. Manifestation of radiation-induced lung disease (RILD)in radiography is a measurable endpoint for RT-induced normal tissue complication. Follow-up CT images from RT-received non-small-cell lung cancer patients were registered to a corresponding planning CT image. Followingimage intensity calibration, the extent of RILD was segmented based on the change in physical density during the follow-up period. Dose coverage to the RILD segmentation and healthy lung was calculated based on retrievedtreatment plans. Normal tissue response in terms of RILD volume and local dose-response showed dependency on patients and follow-up periods. Monte-Carlo dose calculation was found to be important to obtain bettercorrelation. Provided the improved accuracy in CT calibration and image registration, this tool can facilitate further normal tissue toxicity studies.
Le but de ce travail est de développer un outil automatisé de haute précision permettant d'evaluer la réponse de tissus de poumons sains à la radiothérapie (RT), ainsi que leurs corrélation avec la dose locale. Les complications de tissus de poumons sains induites par RT peuvent être mesurées à l'aide des manifestations de maladies pulmonaires induites par radiations (MPIR) en radiographie. Le suivi des images CT par des cellules de poumons cancéreuses provenant de la RT a été enregistré à leur image CT de planication correspondante. à l'aide du suivi de la calibration de l'intensité de l'image, l'etendue des MPIR a été segmentée en se basant sur le changement de densité physique durant la période de suivi. La dose reliée à la segmentation des MPIR et aux tissus de poumons sains a été calculée en se basant sur des planications de traitements établis. La réponse des tissus sains en termes de volume MPIR et la réponse de la dose locale ont démontrées une dépendance signicative par rapport aux patients et aux périodes de suivi. Le calcul de dose par simulations Monte-Carlo sest révélé être important an d'obtenir de meilleures corrélations. En tenant compte de l'amélioration de l'exactitude des calibrations CT et des enregistrements d'image, cet outil peut faciliter le déroulement des futures études de toxicité des tissus sains.

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40

Thomas, Daniel Stewart. "Muscle preservation in denervation injury using continuous implantable electrical stimulation." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61297.

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Using a dog model, two experimental groups were defined. In group 1, the common peroneal nerve of the right hind limb was cut and repaired microsurgically 12 cm from the tibialis anterior muscle (fast muscle). Electrodes (applied to the muscle) and an Itrel pulse generator were implanted, and electrical stimulation (ES) was delivered at 85 Hz,.45 msec pulse duration, 10.5 V, 1.5 sec every 24 sec (n = 4). Group 2 was similar except there was no ES (n = 5).
Comparing the experimental side to the normal contralateral muscle, ES versus no ES resulted in a preservation of muscle weight--73% vs 39% (p $<$.01); twitch tension--21% vs 7% (p $<$.001); nerve stimulated tetanic tension--23% vs 7% (p $<$.05); direct muscle stimulated tetanic tension--43% vs 11% (p $<$.01); Type I fiber area--69% vs 46% (p $<$.05); and Type II fiber area of 63% vs 34% (p $<$.05). There was no statistically significant difference between the two groups in the fiber type proportions.
The results of this project support the hypothesis that continuous, implantable ES delivered over an extended period of time has a positive functional and morphological impact on denervated muscle. (Abstract shortened by UMI.)

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41

Cohen, Daniel 1980. "Role of iPLA₂ in complement (C5b-9) mediated GEC injury." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101711.

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There are a number of isoforms in the PLA2 superfamily, including secretory PLA2s (sPLA2) cytosolic PLA2s (cPLA 2), and calcium independent PLAS (iPLA2beta-short, beta-long, and gamma). In membranous nephropathy, glomerular epithelial cell (GEC) injury by complement C5b-9 leads to morphological changes in GEC and proteinuria, in association with cPLA2alpha activation. The present study addresses the role of iPLA2 in GEC injury. Complement-mediated release of [3H] arachidonic acid was most significantly augmented in GEC overexpressing iPLA2gamma (GEC-iPLA2gamma) as compared with GEC-Neo control. The accelerated AA release was inhibited by the iPLA2-directed catalytic inhibitor bromoenol lactone (BEL). For comparison, GEC-iPLA2gamma also amplified [3H]AA release after incubation of GEC with H2O2, or chemical anoxia followed by re-exposure to glucose, whereas stable clones overexpressing iPLA2gamma only amplified [3H]AA release after incubation with H2O2. Complement-mediated cytotoxicity (measured by release of lactate dehydrogenase) was attenuated significantly in GEC-iPLA2gamma, as compared with GEC-Neo, and the cytoprotective effect of iPLA2gamma was reversed by BEL and partially by Indomethacin. In keeping with previous results, incubation of GEC-cPLA2alpha with complement increased free [3H]AA. This increase in [ 3H]AA was blocked by BEL, although BEL did not block cPLA2alpha activity in cell extracts in vitro. Thus, in addition to cPLA2alpha, iPLA2gamma may be involved in complement-mediated release of AA. Moreover, activation of cPLA2alpha by complement appears to be, at least in part, dependent on iPLA2gamma. Modulation of iPLA2gamma activity may provide a new approach to reducing GEC injury.

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42

Damestoy, Nicole. "Injury mortality among the Cree of northern Quebec, 1982-91." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=55489.

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This study describes the mortality from injuries in the Cree communities of northern Quebec for the period 1982-91. Comparison of different data sources for the completeness of ascertainment of injury mortality showed that no single source of information provided a complete count of deaths. Coroners' reports provided some details on the circumstances of fatal events but would gain usefulness if police and coroners employed a more structured approach to the collection of information on the circumstances of injury deaths. Circumstances of deaths were obtained from mortality interviews with relatives of victims. Drownings were the most common cause of injury death. Groups at high risk of drowning were adult males during boating and snowmobile transport for hunting and toddlers not supervised during their play near the water. None of the victims had worn a personal flotation device. Motor vehicle fatalities affected adult males and were often associated with acute alcohol ingestion. Few victims wore safety belts. Suicides affected mostly males. Half of the suicides resulted from gunshot wounds and 70 percent of victims had ingested alcohol prior to the event. Detailed information on the determinants of injury mortality should help in establishing injury prevention strategies.

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43

La, Novara Pina. "Factors affecting occupational injury rates : an analysis of Canadian data." Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61120.

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This thesis focuses on the issue of occupational injuries. There are four different explanations of why accident rates vary. A set of research hypotheses were created based on these explanations. Multivariate regression analyses of aggregate secondary data were used to test four hypotheses. The findings of these analyses indicate that establishment size, unionization rates and strike and lockout rates are related to injury rates but earnings are not. A fifth hypothesis was tested using the mining industry of Ontario as a case study. This analysis indicates that safety-related legislative and regulatory changes were not effective in reducing either fatal injuries or non-fatal injuries.

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44

Tasneem, Azra. "Postharvest treatments to reduce chilling injury symptoms in stored mangoes." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=81444.

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The market life of many fruits and vegetables can be extended through storage at low temperatures. Chilling injury (CI) is a major postharvest storage problem for tropical commodities. Storing these products at temperatures below their critical temperature may result in severe physiological disorders known as CI symptoms. Mangoes (Mangifera indica. L) are susceptible to CI when stored below 12 °C. Visual CI symptoms include uneven ripening, surface pitting, discoloration, shriveling and scalding. Research has been conducted to overcome these serious problems using various postharvest treatments such as hot water, methyl jasmonate (MJ) or diphenylamine (DPA) with some reduction of the incidence of CI symptoms in fruits and vegetables.
Experiments were performed to assess and compare the potential of the above-mentioned postharvest treatments to reduce the CI symptoms on mango cv. Kent. The obtained results indicated that MJ- and DPA-treatments gave significantly greater percentage of marketable fruits.
Experiments were also conducted with mangoes cv. Tommy Atkins treated with MJ and DPA before storing at low temperatures (1, 4, 7 and 10°C). The chemical treatments were successful at reducing CI symptoms of mangoes. Fruit decay was reduced during subsequent ripening. MJ-treated fruits had lower mass loss and higher total soluble solids (TSS) than the control treatment. The overall quality of MJ- and DPA-treated fruits was good with lower surface pitting and scalding compared with the control treatment. The best results were obtained at storage temperatures of 7 and 10°C. Both MJ and DPA postharvest treatments can reduce CI symptoms in mangoes cvs. Kent and Tommy Atkins when the mangoes are stored at below critical temperature.

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45

Bousette, Nicolas. "Thermal injury increases TMR induced angiogenesis in the ischemic myocardium." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=31198.

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Background. A growing number of patients suffering from ischemic cardiomyopathy are not eligible for conventional revascularization. This has prompted new research in the field of angiogenesis. This study hypothesized that since inflammation is probably the mechanism behind TMR induced angiogenesis; a larger inflammatory response induced by thermal injury may lead to increased angiogenesis.
Methods. The model used for this study was coronary artery ligation in the Rat. Four groups of animals were used to compare the novel experimental approach with conventional TMR and with ischemia alone. Neovascularization was determined by immunohistochemical techniques using anti-Factor VIII antibody. Evaluation of VEGF, Ang-1 and Ang-2 expression was also carried out using immunohistochemistry.
Results. The experimental "HOT" TMR technique resulted in significantly increased angiogenesis presumably due to the thermal injury induced by the novel technique. Also a significant increase in VEGF expression was observed in all ischemic groups. Ang-1 expression was decreased in the experimental group while it was similar in the other groups. Finally Ang-2 was induced by ischemia as evidenced by increased expression among all ischemic groups. However Ang-2 expression did not significantly vary among ischemic groups.
Conclusions. The addition of thermal injury by heating of the needle led to an increased angiogenic response compared to ischemia alone and compared to conventional TMR. This increased angiogenesis was associated with increased VEGF expression at one week, however there was a significant inverse correlation between VEGF expression and angiogenesis among the ischemic groups. Also angiopoietin expression was in agreement with expression characteristics described in the literature.

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46

Strauss, Jillian. "Cyclist injury risk and pollution exposure at urban signalized intersections." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107775.

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Cycling as a mode of travel is becoming more popular especially in urban areas like Montreal, Canada. With this reality come serious concerns for cyclist safety and health. These concerns have initiated the need to study the determinants of cyclist injury risk as well as cyclist exposure to traffic-related air pollution. These two issues are particularly important at intersections where cyclists are exposed to high vehicular traffic and as a result are exposed to the risk of collisions and air pollution. With the goal of improving road safety and reducing cyclist exposure to air pollution, this report seeks to meet the following objectives, to: i) investigate the impact of motor-vehicle traffic, geometric design and built environment factors on cyclist injury occurrence and bicycle activity at signalized intersections in Montreal and ii) study the association between bicycle activity (volume) and traffic-related air pollution concentrations. As an application environment, this research makes use of a large sample of signalized intersections on the island of Montreal. In this work, cyclist injury risk was examined looking not only at aggregate cyclist and motor-vehicle flows passing through intersections but also at disaggregate traffic movements and potential conflicts. It was found that a 10% increase in bicycle flow is associated with a 5.3% increase in the frequency of cyclist injuries whereas a 10% increase in motor-vehicle flow would result in a 3.2% increase in cyclist injury occurrence. When disaggregating motor-vehicle flows into its constituent movements it becomes apparent that right turn movements have the greatest effect on injury occurrence. The conflict measure again confirms this result. Regarding the geometric design and built environment factor analysis, the presence of an arterial and bus stops were found to increase cyclist injury occurrence whereas protected left turn signals, pedestrian signals with countdown and there being three approaches instead of four were found to have the opposite effect on cyclist injury risk. From a health perspective, applying the nitrogen dioxide (NO2) land use regression model for Montreal, has revealed some interesting results. It was found that NO2 levels are highest in the central neighbourhoods of the island of Montreal which is also where cyclist flows are the greatest. The central neighbourhoods are also where Montreal's bicycle network is most dense and most frequented. Also, the corridor analysis revealed that corridors with a bicycle facility have more than twice as many cyclists as those without any facility but they also have, on average, higher air pollution levels. To investigate the indirect impact of built environment and bicycle infrastructure on the two variables of interest (cyclist injury risk and air pollution exposure at intersections), the determinants of bicycle activity were investigated. For this purpose, a bicycle activity modeling framework was developed to measure the impact of built environment, road and transit network attributes and bicycle facilities on bicycle activity. Regression models accounting for spatial autocorrelation between intersections were developed and it was found that land use mix, metro (subway) stations, schools and bicycle facilities all have a positive effect on bicycle activity whereas average street length and presence of parking entrances have a negative impact. Knowledge of the factors that increase or decrease cyclist injury occurrence combined with the knowledge of the factors that increase or decrease bicycle activity through intersections can guide engineering countermeasures and recommendations of land use strategies as well as the location of new facilities. This report provides initial insight into the currently limited body of research into cyclist injury risk and pollution exposure at urban signalized intersections.
De nos jours, le vélo gagne en popularité dans les milieux urbains surtout dans les grandes villes telles que Montréal, Canada. Cette réalité présente des inquiétudes sérieuses pour la sécurité et la santé des cyclistes et exigent la nécessité d'étudier les déterminants des risques de blessure ainsi que l'exposition des cyclistes aux polluants dans l'air. Les cyclistes y sont exposés à des débits de circulation élevés qui augmentent le risque d'accidents ainsi que l'exposition aux polluants. Dans le but d'améliorer la sécurité routière et de réduire l'exposition des cyclistes aux polluants, ce rapport vise à étudier: i) l'impact du débit des véhicules motorisés, de la conception géométrique des intersections et de l'environnement dans lequel se trouvent les intersections sur l'occurrence des blessures chez les cyclistes et les volumes de cyclistes aux intersections signalisées à Montréal et ii) la relation qui existe entre le volume de cyclistes et les polluants émis par les véhicules motorisés. Ce projet fait l'étude d'un large échantillon d'intersections signalisées sur l'île de Montréal. L'occurrence des blessures chez les cyclistes aux intersections n'est pas seulement examinée en évaluant les volumes totaux mais aussi en fonction des trois mouvements (gauche, droite et tout droit) et les conflits potentiels. D'après les résultats, si le volume de cyclistes augmente de 10%, il y aura une augmentation du nombre de blessures de 5.3% alors qu'une hausse de 10% dans les débits de circulation se traduira par une hausse de blessures de 3.2%. En désagrégeant les mouvements des véhicules motorisés, il est apparent que les virages à droite représentent le plus grand danger pour les cyclistes aux intersections. En prenant en considération la conception géométrique des intersections et l'environnement bâti, nous sommes arrivés à la conclusion suivante: la fréquence des accidents cyclistes augmente autour des intersections aux artères et des arrêts d'autobus. En revanche, les virages protégés à gauche, les signaux lumineux piétonniers munis de décompte et les intersections avec trois approches au lieu de quatre, diminuent le risque d'accidents. Les concentrations de dioxyde d'azote (NO2), qui ont été obtenues en appliquant la méthode de régression sur l'aménagement du territoire à Montréal, ont servi à réaliser l'impact de la pollution sur la santé des cyclistes. Les quartiers du centre qui comptent une haute densité d'aménagements cyclables, sont fréquentés par un grand nombre de cyclistes et comptent les plus grands niveaux de concentration de NO2. D'autre part, les corridors équipés d'aménagements cyclables sont fréquentés par plus que deux fois plus de cyclistes que les corridors n'en possédant pas. Le taux de pollution de ces corridors est plus élevé que la moyenne de ceux qui n'en possèdent pas. Les facteurs affectant les volumes de cyclistes sont examiné pour étudier l'impact indirect de l'environnement bâti et des aménagements cyclables sur les deux variables qui nous intéressent. Dans ce but, une méthodologie est proposée pour mesurer l'impact de l'environnement bâti, des caractéristiques de routes et de celles du transport en commun et des aménagements cyclables sur le nombre de cycliste qui traverse les intersections. Les résultats démontrent un effet positif de la mixité du territoire, des stations de métro, des écoles et de la présence des aménagements cyclables sur l'activité des cyclistes. Cependant, la longueur moyenne des routes et la présence des entrées de stationnement à proximité des intersections ont un effet négatif. Sachant les facteurs qui impactent l'occurrence des blessures et en prenant connaissance des facteurs affectant l'activité des cyclistes aux intersections aident à identifier des traitements efficaces, à faire des recommandations d'aménagement du territoire et aident aussi avec la localisation des nouveaux aménagements cyclables.

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47

Babcock, Alicia A. "The innate response to injury in the central nervous system /." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111817.

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Innate responses in the central nervous system (CNS) provide first-line defense against infection and injury. Microglia and astrocytes may direct leukocyte infiltration to the injured CNS. The signaling mechanisms that orchestrate this response are ill-defined. Innate roles for microglia and astrocytes are supported by reports demonstrating glial expression of Toll-like receptors (TLRs). TLRs recognize conserved pathogen-associated motifs and generate innate immune responses, usually by signaling through the adaptor protein, MyD88. TLRs may also generate innate responses to tissue damage. The data in this thesis implicate TLR2/MyD88 as key mediators of innate response to brain injury in mice. Transection of axons in the entorhinal cortex causes tissue damage analogous to a stab injury at the lesion site, and axonal degeneration distal from the wound, in the denervated, lesion-reactive hippocampus. A significant increase in leukocyte proportions was detected by 3h in the stab-injured entorhinal cortex, but not until 12h in the denervated hippocampus. This identified a window of CNS-directed innate response in the denervated hippocampus, without influence of infiltrating cells. Expression of numerous cytokines and chemokines was induced during this time. Microglia and astrocytes were identified as major sources of the chemokine CCL2. Macrophage infiltration to the stab-injured entorhinal cortex and the denervated hippocampus was dependent on MyD88-dependent CCL2/CCR2 signaling, but not TLR2-signalled response. T cell entry to the denervated hippocampus was regulated by TLR2 signaling and required MyD88-mediated response, whereas T cell recruitment to the stabinjured entorhinal cortex was only partially dependent on MyD88 signaling and did not require TLR2-mediated response. TLR2 signaling also regulated expansion of the hippocampal microglial population 5 days after lesion. Microglia were supplemented by circulating bone marrow-derived precursors, but this occurred predominantly at later times post-injury. No parameter measured was dependent on TLR4. These data identify novel signaling pathways that link glial responses to brain injury with subsequent neuroinflammation.

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48

Ghassemi, Rezwan. "MRI measures of brain injury in children with Multiple Sclerosis." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=123023.

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Multiple sclerosis (MS) is thought to be an autoimmune disease that affects the central nervous system of young adults. Although an uncommon disease in children, recent research has examined the effect of this disease upon a younger demographic group. This patient population has attracted the attention of MS researchers, as it promises a better understanding of the pathophysiology of MS at its earliest stage. Magnetic resonance imaging (MRI), a sensitive tool for detecting white matter (WM) pathology, has improved the diagnosis and appreciation of the pathogenesis of MS in adults. However, little is known about its use in children. Therefore, the main objective of this thesis is to contribute and to increase knowledge in this important new area. For this purpose, specific image processing methodologies were developed, and pathology on MRI was compared between patients with adult- and pediatric-onset MS. Comparing the spatial distribution, frequency, and volume of lesions on T2-weighted (T2w) MR images among patients with pediatric- and adult-onset MS, who had similar disease duration, showed a similar total T2w lesions between the two groups. However, children exhibited a higher T2w lesion volume and frequency in the infratentorial region, particularly in the pontine region. Persistent T1-weighted (T1w) lesions, a marker of permanent tissue damage and axonal loss, were assessed to determine whether MS lesions in children are as destructive as those in adults. To obtain a fair comparison using the scans available, normalization of intensity was essential. We showed the limitations of the currently available techniques for intensity normalization, and the need for a WM independent methodology. We proposed and developed a novel WM-independent intensity normalization method for T1w images and assessed inter-scanner, between-scanner and within subject variation before and after normalization. We also calculated the sample size required for detecting recovery of T1w intensity using our methodology and the most commonly used intensity normalization method. Then we used our methodology to assess recovery of normalized T1w intensity within new lesions in children with relapsing remitting MS (RRMS) compared to adults. We found that MS lesions recover better in children, suggesting a greater reparative capacity in younger patients. We also used our intensity normalization method to perform a quantitative comparison of T1w intensity recovery in new lesions between children with MS and children with monophasic inflammatory demyelinating syndromes (monoADS). We found that new MS lesions recover more poorly than of those in children with monoADS. This may suggest that new MS lesions are more destructive than new lesions in monophasic inflammatory demyelinating diseases.
La sclérose en plaques (MS) est considérée comme une maladie auto-immune qui affecte le système nerveux central de l'adulte jeune. Bien que d'une maladie rare chez les enfants, des recherches récentes ont examiné l'effet de cette maladie sur une population plus jeune. Cette population de patients a attiré l'attention des chercheurs en SP, car elle promet une meilleure compréhension de la physiopathologie de la SEP au stade le plus précoce . Imagerie par résonance magnétique (IRM), un outil sensible pour la détection de la substance blanche (WM) pathologie, a amélioré le diagnostic et l'appréciation de la pathogenèse de la SEP chez les adultes. Cependant, peu a été connu au sujet de son utilisation chez les enfants. Par conséquent, l'objectif principal de cette thèse est de contribuer et d'accroître les connaissances dans ce nouveau domaine important. A cet effet, des méthodologies spécifiques de traitement d'image ont été développés, et de la pathologie à l'IRM ont été comparées entre les patients atteints de l'adulte et pédiatrique apparition MS. La comparaison de la répartition spatiale, la fréquence et le volume des lésions sur T2 (en T2) images IRM chez les patients atteints de la SP pédiatrique et adulte-début, qui ont eu la durée de la maladie similaire , ont montré un nombre total de lésions en T2 similaires entre les deux groupes. Cependant, les enfants présentaient un volume plus élevé de lésion en T2 et la fréquence dans la région infratentorial, en particulier dans la région pontique. (T1) des lésions pondérées en T1 persistants, un marqueur des dommages permanents aux tissus et la perte axonale, ont été évalués pour déterminer si les lésions de SP chez les enfants sont aussi destructrices que celles des adultes. Pour obtenir une comparaison équitable en utilisant les analyses disponibles, la normalisation de l'intensité était essentiel. Nous avons montré les limitations des techniques disponibles actuellement pour la normalisation de l'intensité, et le besoin d'une méthode indépendante WM. Nous avons proposé et développé une nouvelle méthode de normalisation de l'intensité WM- indépendante pour les images T1 et évalué inter- scanner, entre - scanner et dans l'objet variation avant et après normalisation. Nous avons également calculé la taille de l'échantillon nécessaire pour détecter la reprise de l'intensité T1w utilisant notre méthodologie et la méthode de normalisation de l'intensité la plus couramment utilisée. Ensuite, nous avons utilisé notre méthode pour tester notre hypothèse et la récupération assesed d'intensité T1w normalisée dans de nouvelles lésions chez les enfants sclérose en plaques rémittente (SEP-RR) par rapport aux adultes. Nous avons constaté que les lésions de SP mieux récupérer les enfants qui peuvent suggérer une plus grande capacité réparatrice chez les patients plus jeunes. Nous avons également utilisé notre méthode de normalisation de l'intensité pour effectuer une comparaison quantitative de la récupération de l'intensité T1w dans de nouvelles lésions entre enfants atteints de SP et les enfants atteints de syndromes inflammatoires démyélinisantes monophasiques (de monoADS). Nous avons constaté que de nouvelles lésions de SP récupérer plus mal que de ceux des enfants avec monoADS. Cela peut suggérer que les lésions New MS sont plus destructeur que de nouvelles lésions dans les maladies démyélinisantes inflammatoires monophasique.

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49

Fadaak, Raad. "Of the currently forming: an anthropology of traumatic brain injury." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119718.

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Of The Currently Forming is an ethnographic exploration of a relatively recent diagnosis in clinical biomedicine – 'traumatic brain injury' or TBI. TBI has become a central preoccupation for researchers, clinicians, trauma centers, and public health departments across North America and Europe. Its epidemiological character is of startling concern, as its prevalence among the population is extraordinarily high. TBI is one of the most common causes of death in adults, and the leading cause of death and disability amongst young persons. Furthermore, TBI has become the "signature injury" of the US military in the Iraq and Afghanistan conflicts. Yet, the way we have come to know injury to the head and brain has changed fundamentally in the last thirty years. This has situated TBI as an important category for public and political debate; hospitals, neuroscientists, the CDC, and the WHO have all, within the last decade, narrowed their focus to traumatic brain injury – the "invisible injury" - as a cause for concern for both the public health sector as well as the clinical and laboratory sciences. The first section attempts to bring into focus why and how this problematic generated this kind of interest; it is one mode of understanding the dramatic visibility of an 'invisible' injury. The second section is about the conceptual and practical changes in clinical and experimental work on TBI and mild TBI today. Mild TBI, for instance, remains without widespread consensus as to its underlying pathophysiology or clinical presentation. Such indeterminacy has effectively opened up a new conceptual space for TBI research - particularly in the areas of neurological imaging and its relationship to neuropathology, applied clinical practices, post-injury assessments, and rehabilitation. Fundamental biomedical concepts – such as the 'normal' and 'pathological' – take on particular conceptual form in the midst of these spaces of uncertainty. Here, a series of ethnographic vignettes trace the interconnections and arrangements as certain clinical technologies and practices converge, giving shape to this dynamic and emergent diagnostic category. By superimposing the historical account of TBI's emergence alongside its ongoing clinical and experimental re-negotiations, Of The Currently Forming attempts to give a glimpse into the spaces of the incomplete – an exploration of the complexity, heterogeneity, and creativity that underpins contemporary brain injury medicine.
De l'actuellement en formation est une exploration ethnographique d'un diagnostic médical d'origine récente, soit le 'traumatisme craniocérébral' ou TCC. Le TCC détient aujourd'hui une place prépondérante dans le travail des chercheurs, médecins, hôpitaux spécialisés, et départements de santé publique à travers l'Amérique du Nord et l'Europe. Le profil épidémiologique du TCC peut être qualifié d'effrayant puisque sa prévalence au sein de la population est incroyablement élevée. Le TCC constitue simultanément l'une des plus fréquentes causes de mortalité chez l'adulte et la principale cause de mortalité et source d'handicap chez les jeunes. Par ailleurs, le TCC est devenue la 'blessure caractéristique' des soldats américains engagés dans les conflits armés en Irak et en Afghanistan. Cependant, la manière de penser et connaître les blessures à la tête et au cerveau a radicalement changé dans les trente dernières années. Cela a propulsé le TCC à l'avant-scène des débats publics et politiques. Depuis dix ans, hôpitaux, neurologues, le Centre pour le Contrôle et la Prévention des Maladies, ainsi que l'OMS, ont tous concentrés leurs efforts sur le TCC, cette « blessure invisible », considérée comme une source de préoccupation à la fois pour la santé publique et les sciences médicales. Dans le but de comprendre la visibilité spectaculaire d'une blessure 'invisible', la première partie de ce mémoire documente pourquoi and comment cette problématique a généré cet important intérêt. Dans une deuxième partie, nous présentons les changements conceptuels et pratiques advenant aujourd'hui dans le travail clinique et expérimental concernant le TCC et le TCC léger. À titre d'exemple, il n'y a toujours pas de consensus par rapport à la physiopathologie et aux symptômes entourant le TCC léger. Cet état d'indétermination a généré de nouvelles avenues conceptuelles pour la recherche sur le TCC, particulièrement dans les domaines de l'imagerie neurologique et ses liens avec la neuropathologie, la pratique clinique, les évaluations post-traumatiques, et la rééducation. Des concepts médicaux fondamentaux, tels que le 'normal et le pathologique', prennent des formes conceptuelles uniques au sein de ces espaces d'indétermination. Dans cette deuxième partie, une série de vignettes ethnographiques tracent les liens et suit les configurations qui se dessinent alors que certaines technologies et pratiques convergent, donnant forme à cette catégorie de diagnostic, elle-même dynamique et émergente. En présentant parallèlement l'histoire de l'émergence de la TCC ainsi que les négociations expérimentales et cliniques qui l'entourent actuellement, nous visons à offrir un récit des 'espaces de l'incomplet', comme une exploration de la complexité, hétérogénéité et créativité au cœur de la médicine du cerveau contemporaine.

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50

Hughes, Jonathon. "Biomechanics of skull fracture and intracranial injury in young children as a consequence of a low height fall." Thesis, Cardiff University, 2014. http://orca.cf.ac.uk/73344/.

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A challenge for clinicians when presented with a significant head injury in a young child and a postulated fall height is to determine the plausibility of such an injury. Previous authors have aimed to determine the head injuries that can result from a low height fall, however due to a lack of clarity it is difficult to determine a fall height at which certain head injuries including skull fracture and intra cranial injury (ICI) becomes more likely. Biomechanical thresholds aimed at young children exist for skull fracture and adult thresholds for subdural haemorrhage, however they have not been assessed against the injuries seen in a clinical setting. Consequently this study investigated low height falls in a paediatric clinical setting to determine differentiating variables and characteristics in the mechanism of head injury between children with a minor head injury and those with a skull fracture and / or ICI. The primary aim of which was to determine a fall height threshold for skull fracture and / ICI in young children. Following this, biomechanical methods were used to include, the development of an accurate anthropomorphic testing device (ATD) and a finite element model of an infant head, to investigate the differentiating variables and ultimately the clinical fall height threshold. Method A case control study of children ≤ 48 months of age who had a minor head injury and those with a skull fracture and / or ICI, to identify variables and characteristics of falls that influenced injury severity. Children were ascertained from those who attended the University Hospital of Wales Cardiff from a low height fall. The clinical characteristics and biomechanical variables evaluated included the mechanism of injury, surface of impact, site of impact and fall height (taking into consideration height of object and centre of gravity of the child’s body and head mass). Categorical variables were assessed using a Chi Square test and continuous variables using Student t-test or the non parametric equivalent. A modified logistic regression was used to evaluate the likelihood of sustaining a skull fracture and /or ICI based on fall height. Initially to investigate the differentiating variables a biofidelic infant headform was designed via image processing and segmentation of computed tomography (CT) datasets and manufactured using materials with similar properties to the bone and soft tissues of the head. The headform impact response was initially validated against infant cadaver data and then it was subject to tests classed as sub-injurious based on the clinical data collected from the hospital. The headform was dropped at impact angles of 90o, 75o and 60o at three velocities (2.4m/s, 3m/s, 3.4m/s) corresponding to three heights (0.3m, 0.45m, 0.6m), onto four domestic surfaces (carpet, carpet & underlay, laminate and wood) using two skin friction surrogates (latex, polyamide). A Student t-test was used to measure the affect of the coefficient of static friction and a three factorial ANOVA to measure the affect of impact velocity, surface type and angle of impact had on kinematic variables (peak g, HIC, rotational acceleration, change in rotational velocity and duration of impact). Finally to investigate the differentiating variables a finite element (FE) model of an infant head was developed, again through image processing of infant head CT datasets. The FE model consisted of the scalp, sutures, cranial bones, dura membranes, cerebral spinal fluid, bridging veins and the brain and the impact response was also initially validated against infant cadaver data. Post validation a parametric test across four different scenarios (0.3m impact onto the occipital, frontal, vertex and parietal areas of the head) was conducted to assess the affect material properties have on impacted response of the model. Finally the FE was used to assess the affect height (0.3m, 0.6m, 1.2m) and anatomical site of impact have on the impact response of the head, including kinematic variables and material response variables. Results Identified cases included 416 children with a minor head injury and 47 with a skull fracture and / or ICI. The mean fall height for minor head injuries was significantly lower than for a fall causing skull fracture and / or ICI (P<0.001). Utilising the height of centre of gravity of the head, no skull fracture and / or ICI was sustained in children who fell <0.6m (2ft). Skull fractures and / or ICI were more likely in children ≤12 months (P<0.001), following impacts to the temporal/parietal or occipital region of the head (P<0.01), and impacts onto wood (P<0.05). All tests using the biofidelic headform were conducted with impact velocities corresponding to fall heights ≤0.6m, where an increase in impact velocity, increase in surface stiffness and a decrease in impact angle significantly affected both rotational and translation kinematic variables (P<0.05). Peak rotational accelerations at 90 degrees were 11, 363 rad/s2 on wood at an impact velocity corresponding to a height of 0.6m and significantly increased to 16,980 rad/s2 with a 30 degree decrease in impact angle (P<0.001). However head injury criterion (HIC) decreased for wood at impact velocity corresponding to 0.6m from 245 to 121 for a 30degree decrease in impact angle (P<0.001). The parametric test using the finite element model indicated that the skull stiffness has the greatest affect on the dynamic response of the head, an increase in the skull stiffness of 7% increased HIC by 26%. Height and anatomical site of impact affected kinematic and material response variables. The mean value of peak G and HIC at the clinical defined threshold of 0.6m fall height was 85g and 284g, respectively. An increase in fall height to The stiffest parts of the head were the frontal areas and the least stiff were impacts focal to the sutures. Impacts focal to sutures indicated high stress zones on adjacent bones, for example an impact to the vertex indicated high stress zones on the left and right parietal bones. The greatest strain on the connectors used to model the bridging veins was at the most focal impact point, the vertex. For a 1.2m fall the greatest peak stretch ratio for a vertex impact was 1.31. Conclusion A threshold above which skull fracture and / or ICI of 0.6m was proposed. The corresponding mean values for peak g and HIC using the finite element models at a 0.6m fall corresponded well with current biomechanical thresholds for skull fracture, particularly the current National Highway Transport Safety Administration standard. This study highlights the importance of developing threshold specific to young children that are both clinically and biomechanically relevant. A clinical finding was that head injury severity was influence by anatomical site of impact. This was supported by the biomechanical analysis where skull fracture risk and strain on the bridging veins were both influenced by site of impact. The high stress on adjacent bones from a single impact focal to the sutures, suggest the potential for fracture on multiple cranial bones from a single point of impact. Whilst further research is required to validate fracture patterns, it highlights the potential for a bi-parietal fracture from a vertex impact.

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