Positive pressure mechanical ventilation (MV) has been utilised in the care of critically ill patients for over 50 years. MV essentially provides for oxygen delivery and carbon dioxide removal by the lungs in patient with respiratory failure or insufficiency from any cause. However, MV can be injurious to the lungs, particularly when high tidal pressures or volumes are used in the management of Acute Respiratory Distress Syndrome (ARDS) or similar acute lung injuries. The hallmark of ARDS is extensive alveolar collapse resulting in hypoxemia and carbon dioxide retention. Application of Positive End Expiratory Pressure (PEEP) is used to prevent derecruitment of alveolar units. Hence, there is a delicate trade-off between applied pressure and volume and benefit of lung recruitment. Current clinical practice lacks a practical method to easily determine the patient specific condition at the bedside without excessive extra tests and intervention. Hence, individual patient treatment is primarily a mixture of "one size- fits-all" protocols and/or the clinician's intuition and experience. A quasi-static, minimal model of lung mechanics is developed based on fundamental lung physiology and mechanics. The model consists of different components that represent a particular mechanism of the lung physiology, and the total lung mechanics are derived by combining them in a physiologically relevant and logical manner. Three system models are developed with varying levels of physiological detail and clinical practicality. The final system model is designed to be directly relevant in current ICU practice using readily available non-invasive data. The model is validated against a physiologically accurate mechanical simulator and clinical data, with both approaches producing clinically significant results. Initial validation using mechanical simulator data showed the model's versatility and ability to capture all physiologically relevant mechanics. Validation using clinical data showed its practicality as a clinical tool, its robustness to noise and/or unmodelled mechanics, and its ability to capture patient specific responses to change in therapy. The model's capability as a predictive clinical tool was assessed with an average prediction error of less than 9% and well within clinical significance. Furthermore, the system model identified parameters that directly indicate and track patient condition, as well as their responsiveness to the treatment, which is a unique and potentially valuable clinical result. Full clinical validation is required, however the model shows significant potential to be fully adopted as a part of standard ventilator treatment in critical care.

This thesis extends the literature on the dynamics of firm growth and failure by testing the robustness of past findings for capitalist firms to alternative ownership structures. While the theoretical results are altered by the internal organisation of the firm, the empirical findings are unchanged. This suggests that the theoretical models place excessive emphasis on the organisational structure and inadequate emphasis on more basic and fundamental factors affecting firm growth. The thesis applies the learning models of growth to the case of the Illyrian labour managed firm, where members maximise profits per worker. The critical efficiency-size relationship is indeterminate under labour management. Thus, the majority of the clear cut empirical predictions of the model for profit maximisation no longer hold. Three possible explanations for the breakdown of the results are examined. One explanation is that the Illyrian model is overly simplistic and does not accurately reflect the actual behaviour of cooperatives. This is rejected using an institutional structure model of the French producer cooperative which yields predictions which are remarkably similar to those of the Illyrian model. The second explanation considered is that the growth and survival of cooperatives in fact substantially differs from capitalist firms. This explanation is rejected in the empirical section which tests the actual growth and survival relationships using a dataset of French producer cooperatives. The estimated survival-size relation is convexly positive and the growth-size relation convexly negative, exactly as they have been found previously for conventional firms. The final remaining explanation is that the theoretical models are structured so as to overemphasize the internal structure of the firm to the neglect of more generic factors affecting growth and survival. This is accepted in a final section which proposes new directions for theoretical research on the growth and survival of all firms.

No description available.

No description available.

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The effects of the rate of distraction and of local infusion of IGF-1 upon bone deposition during mandibular distraction osteogenesis was studied in a rabbit model. Five groups of rabbits were studied. All rabbits, except sham operated controls, underwent distraction to 15 mm. The variables studied were the rate of distraction (0.5 mm twice a day versus 1.5 mm twice a day) and the effects of local IGF-1 infusion via osmotic infusion pumps. Analysis by DEXA scanning and three point bending 28 days after the end of distraction demonstrated no difference in density or strength of bone between the experimental groups. Histological examination demonstrated non-union across the distraction gap to be more common in rapidly distracted rabbits. Histomorphometric analysis demonstrated higher mineral apposition rates and less un-mineralised osteoid with slow as opposed to rapid distraction (p = 0.0001). Infusion of exogenous IGF-1 also resulted in a small increase in mineral apposition rate which was significant at slow but not a rapid distraction. Bone densitometry and three point bending results did not reveal any effect of distraction rate or IGF-1 infusion other than greater stiffness associated with IGF-1 infusion during rapid distraction (p = 0.01). It seems probable that the overwhelming stimulus to new bone formation produced by distraction renders the anabolic effects of IGF-1 less significant making it detectable by only the more sensitive analysis. This may be due to maximal stimulation of IGF-1 production by slow distraction thus rendering the administration of exogenous IGF-1 relatively superfluous. Rapid distraction may produce less stimulus to growth factor synthesis or the level of production maybe insufficient to cope with a higher requirement. The complete union of rapidly distracted rabbits who received exogenous IGF-1 may be as a result of levels being restored to optimal.

It has been reported that the presence of Fc receptor blocking antibodies is associated with normal pregnancy and improved cadaver donor renal transplant survival. The demonstration of the development of such antibody activity in the animal model during one or more pregnancies and the effect of these pregnancies on the survival of a subsequent renal allograft form the major aims of the studies presented in this thesis.A microsurgical laboratory was therefore established at Aberdeen University and the rat renal transplant model developed. Fc receptor blocking activity was assessed using the EA inhibition assay.The results indicate that:I Fc receptor blocking activity was not found in the sera of virgin rats.2 Significant levels of these antibodies were only found after two pregnancies and they occurred in 50% of such cases3 Primiparous animals and those multiparous animals which did not develop EA inhibiting activity rejected renal allografts from the paternal strain in the same time as virgin animals.4 Only multiparous rats sharing over 30% EA inhibition failed to reject transplants carrying paternal specificities. Those animals were capable of rejecting grafts from third party donors suggesting that the Fc receptor blocking antibodies were directed towards paternal antigens.It is therefore suggested that Fc receptor blocking activity occurring as a result of pregnancy in the rat renal transplant model may enhance a renal allograft from the paternal strain. These antibodies may therefore represent a form of donor specific immunosuppression.

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No description available.