Hypohydration and fasting are used as means to achieve body mass loss and Ramadan fasting is practised by millions of Muslims as a religious custom. Although both hypohydration and fasting have been studied extensively, the effect of hypohydration and Ramadan style fasting on many aspects of human performance is still unclear. In Chapter 3, the effect of exercise-induced hypohydration on muscle performance was evaluated. The protocol was developed to eliminate masking and exacerbating factors such as changes in muscle glycogen storage, muscle temperature, fatigue and fluid distribution change and acid base status. Muscle strength and endurance decreased due to hypohydration equivalent to 2% of body mass. This suggests that hydration status itself can affect adversely athletes' performance. In Chapter 4, the effect of one day (11 h) of Ramadan style fasting on some aspects of exercise performance during the day was investigated. Participants were tested three times throughout the day: at 7:00 am, 12:00 noon and 7:00 pm. 11 h of Ramadan style fasting decreased body mass by 2.1%. No change was found in exercise performance measurements. The results of this study suggest that this short period of fasting has no measurable effects on performance and/or that any effects are compensated by the circadian rhythm throughout the day. However, most athletes use more intense fasting or several consecutive days of fasting to achieve their weight reduction goal. In Chapter 5, the effect of Ramadan fasting (one month long intermittent fasting) on some aspects of exercise performance of athletes (weight category and non-weight category sports) and recreationally active individuals was studied. Participants were tested before, during (after the first week and in the last week) and after the month of Ramadan. Ramadan style living (involving a change in timing of food intake and sleep pattern) affects most of the anthropometric and physical performance parameters of the athletes and of the recreationally active subjects, with no difference in the pattern of change between groups. Almost all of the differences were recovered a week after the end of fasting. Chapter 6 contains the results of three studies focused on the effects of fasting on cognitive function (study A- breakfast elimination; study B- one day (11 h) of Ramadan style fasting; and study C- one month of Ramadan fasting). Results of these studies make a logical conclusion that fasting has a detrimental effect on memory, reaction time and accuracy of responses. The pattern of the effects showed differences that may be related to various participants' characteristics (age group, gender) and the nature of intervention. In summary, Ramadan style fasting may affect performance of some mental and physical tasks in some, but perhaps not in all individuals.

Hypoglycaemia is a very common side-effect of insulin therapy for diabetes and directly affects cognitive function. It can be identified by the onset of symptoms and by blood glucose monitoring. Impaired awareness of hypoglycaemia is an acquired syndrome in people with insulin-treated diabetes. The definitions, frequency, causes, treatment and prevention of clinical hypoglycaemia and the effects on, and moderators of, cognitive function will be discussed. Two studies have examined the effects of hypoglycaemia on tests of particular cognitive domains in subjects with and without type 1 diabetes. Three further studies have examined the frequency of hypoglycaemia in people with and without impaired awareness, the prevalence of impaired awareness of hypoglycaemia (IAH) and have compared methods of assessing awareness of hypoglycaemia. In study 1 the effect of acute hypoglycaemia on psychomotor function was examined in healthy volunteers (n =20) and adults with type 1 diabetes (n=16). Although acute hypoglycaemia caused significant impairment of several psychomotor functions in nondiabetic adults, a lower magnitude of impairment was observed in those with type 1 diabetes. The potential mechanisms behind this are discussed. In study 2 the effect of acute hypoglycaemia on a simple two-choice reaction time test, which has a model with validated performance parameters, was examined in 14 nondiabetic volunteers. Application of the validated model to the results of this task revealed that hypoglycaemia affected central processing and was not related to the amount of evidence required to make a decision or to peripheral and motor processes. This study is the first to use this method to dissect the effects of hypoglycaemia on cognition and enhances understanding of the mechanism underlying neuroglycopenia in adults. In Study 3 the methods of evaluating awareness of hypoglycaemia were compared in people with type 1 diabetes. Good concordance in clinical characteristics and frequency of biochemical hypoglycaemia was observed between the methods described by Gold et al and Clarke et al but not with a Danish method. In study 4 continuous glucose monitoring (CGM) and home blood glucose monitoring were performed prospectively for 12 months in people with and without IAH. Those with IAH had a 1.6-fold higher incidence of biochemical hypoglycaemia as demonstrated by blood glucose monitoring, but CGM did not identify patients with IAH. In study 5 the prevalence of IAH in a large clinic population with type 1 diabetes was estimated and compared with earlier assessments. The overall prevalence was 20%.

Background: Attachment literature indicates attachment status is related to trauma with associations between early trauma and insecure attachment. Links between psychosis and trauma have been established within the literature; however the precise nature of this relationship is still not fully understood. A systematic review was carried out to assess the state of the evidence pertaining to psychosis and attachment. Associations between insecure attachment and psychotic symptoms were identified. Other psychological correlates such as perceived parental care, attachment to services and interpersonal problems were found to relate to insecure attachment status. However due to the early stage of this area of research, small clinical sample sizes and heterogeneity of correlates investigated, firm conclusions cannot currently be drawn. Aim: The aim of this study was to investigate the relationship between trauma, attachment, reflective functioning (RF) and distress for people with psychosis with a view to further understanding these links and the clinical implications. Method: Participants with a diagnosis of psychosis were recruited and measures were completed with the principle investigator pertaining to trauma, attachment and distress in psychosis. Results: The majority of the sample reported insecure attachment and low RF and there were high levels of general, and more specifically, interpersonal trauma within the sample. Results indicated that early interpersonal trauma was associated with higher levels of emotional distress. Exploratory mediation analyses implicated anxious attachment in mediating the relationship between interpersonal trauma and distress. Discussion: The results indicate the need to consider early trauma histories and specifically interpersonal trauma and attachment in the context of emotional distress for people experiencing psychosis. Incorporating trauma and attachment based therapeutic approaches for people with psychosis is as relevant as it is for other trauma populations, where these approaches may be more routinely drawn on for formulation and treatment. Limitations of the methodological approach are considered along with suggestions for future research.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

QC 351 A7 no. 53 / The optical performance of three stereomicroscopes commonly used for photo - interpretation is described in terms of magnification, field of view, and square wave response (SqWR). For a given field size, the SqWR can be used to compare the amount of information in the image of each microscope. The SqWR was determined by scanning a square wave test target at four field positions for each of four field sizes (corresponding to magnifications of 6, 12, 25, and 50X). The measured SqWR was used to evaluate the relative ability of each microscope to perform two typical photointerpretation tasks: (1) detailed viewing of a target, and (2) scanning or searching for a target. For these tasks the Wild M -5 stereomicroscope was found to be somewhat better than the Bausch and Lomb 240 stereomicroscope, and both were found to be superior to the Olympus SZ III stereomicroscope. The SqWR curves are included and can be used to compare the stereo - microscopes for various photointerpretation tasks.

The present study was conducted to clarify and expand knowledge of cognitive functioning in chronic schizophrenia patients (N=21) as compared to a bipolar group (N=20) and a normal group (N=20).

Recently there has been a great interest in the ability to relate the hydro-mechanical properties of soils to their acoustic response. This ability could enhance high resolution non-destructive evaluation of the shallow subsurface, and would have applications in a variety of fields including groundwater and contaminant hydrogeology, oil recovery, soil dynamics, and the detection of buried objects. Groundwater hydrologists and environmental engineers are challenged with the task of characterizing the material, mechanical and hydraulic properties of the subsurface with limited information generally collected from discrete points. Geophysical testing offers a suite of measurement techniques that allow for the non destructive evaluation of potentially large areas in a continuous manner. Acoustic testing is one geophysical method used by many professions to characterize the subsurface. Unsaturated and multiphase flow modeling relies on the relationship between the capillary pressure and the level of saturation of the porous media. It has been previously suggested that this relationship may be non-unique and rate dependent. A theory which relates this dynamic relationship to the acoustic properties of the soil was developed by others. This research attempts to experimentally verify this theory by meeting the following three objectives: (1) develop an apparatus and procedure to collect acoustic waveforms on laboratory sized unsaturated soil samples, (2) develop a forward modeling technique using a one-dimensional wave propagation model as an alternative analysis method for waves collected on relatively small laboratory specimens, and (3) apply the theory to the measured acoustic data in an attempt to predict the dynamic behavior of the capillary pressure relationship. The acoustic data collected showed variation in compressional wave velocity and attenuation with saturation, and the trends were consistent with data collected by others in partially saturated rocks. The forward modeling technique was shown to provide objective results with reasonable accuracy and low computational time. The dynamic effects predicted with these acoustic measurements did not sufficiently explain the dynamic behavior seen in the laboratory. This is attributed to other causes of significant attenuation not accounted for in the wave propagation theory that was evaluated.

Atopic dermatitis, AD (synonym eczema) is a chronic inflammatory skin disease. It affects between 10 to 20% of children and 1 to 3% of adults worldwide. It is an important cause of morbidity and is estimated to cost £465 million per annum to the UK. AD is part of a family of Th-2 driven diseases and is often the first of these atopic diseases to manifest. The development of AD is often followed by asthma and allergic rhinitis later in life (a phenomenon known as the ‘atopic march’). Up to 50% of moderate to severe AD cases have been associated with genetic mutations affecting the epidermal barrier protein filaggrin. Filaggrin aggregates keratin filaments during terminal keratinocyte differentiation, allowing normal epidermal stratification. The role of filaggrin in maintaining a functional skin barrier is further supported by a clinical study conducted by ourselves. This is the first clinical study on a European cohort (58 participants) which showed that FLG mutations were associated with experimentally demonstrable defects of skin barrier function (increased baseline transepidermal water loss), more so following exposure to a chemical irritant. However, the majority of patients with AD, especially the milder cases, do not have FLG mutations. Some of the wild-type patients in our study were noticed to have accumulation of the large filaggrin proprotein and a lack of filaggrin monomers, indicating defective proteolysis of profilaggrin into the functional monomers. Our study also found disproportionately raised protease inhibitory activities amongst the AD participants. This inappropriately raised protease inhibition may interfere with profilaggrin proteolysis, leading to the development of AD in some wild-type patients. Having demonstrated that deficiency of filaggrin monomers is associated with a defective skin barrier, we focused on the function of filaggrin in the skin and attempted to improve the skin barrier function. In addition to keratin aggregation, filaggrin constitutes the natural moisturizing factors in the epidermis following its natural breakdown into amino acids. We note that filaggrin is disproportionately rich in amino acid histidine, implying that this amino acid may have a particular significance in maintaining a functional epidermal barrier. Using an in-house skin-equivalent model, we have shown that by increasing the histidine content in the cell culture media, we could increase the expression of filaggrin monomers and reduce the penetration of a fluorescent dye into the skin-equivalents. The latter indicates improved barrier function. Finally, we conducted a pilot human study which showed that histidine, when applied to mechanically damaged skin in AD and healthy participants, was associated with a faster recovery of the skin barrier function. These studies suggest that histidine is of therapeutic benefits in AD. A histidine-based treatment may be developed as an alternative to current anti-inflammatory and immunosuppressive agents used to treat AD.

Halogenated alkenes are a group of commercially important chemicals. For example tetrafluoroethylene is the monomer used for the production of poly- tetrafluoroethylene, hexachloro-1:3-butadiene is a by-product from the manufacture of chlorinated solvents and perchloroethylene is widely used as a dry cleaning agent. Due to possible exposure to haloalkenes and the nephrotoxicity observed in animal studies, concern has been expressed for the potential of these compounds to cause toxicity to man. Animal studies have shown that these compounds undergo inter-organ metabolism and are bioactivated by enzymes of glutathione processing. The metabolites are delivered to the kidney where they cause proximal tubular cell necrosis. This site-specific toxicity is due to accumulation of the metabolites via specific transport mechanisms and bioactivation via the enzyme C-S lyase present in high amounts in the proximal tubules. The aim of this research was to investigate the mechanisms of toxicity of haloalkene S'-conjugates in vitro using cultures of rat and human proximal tubular cells. This study demonstrates that human proximal tubular cells are sensitive to haloalkene. -conjugate toxicity, particularly DC VC. Human exposuredata has shown that workers exposed to trichloroethylene (Bimer et al, 1993) and perchloroethylene (Mutti et al, 1992) excrete nephrotoxic metabolites and markers of renal damage respectively. In the light of these findings and the toxicity of DCVC in HPT cells, exposure to halogenated alkenes should be controlled and those exposed monitored.

The purpose of this project was to assess techniques which could be implemented in clinical cardiac MRI using a moderate gradient performance imaging system in order to aid in the assessment of myocardial function. Possible improvements in image contrast were assessed using four different magnetisation preparation schemes applied prior to MR image acquisition in order to aid in the delineation of myocardial borders, and therefore improve cardiac image assessment quality. The usefulness of several novel T2*-weighted acquisition techniques were assessed in clinical cardiac applications in order to indirectly assess myocardial perfusion. Four magnetisation preparation schemes were applied in order to attempt to improve image contrast in short axis gradient-echo cardiac MRI; T2, T1, Magnetisation Transfer Contrast (MTC), and Double Inversion (DI). The T2, and preparation schemes proved to be the most effective, showing an initial improvement in image contrast by approximately 100% and proving effective in improving image contrast over the entire imaging duration {550 ms through the cardiac cycle). The MTC preparation scheme showed a 50% improvement in image contrast, again being effective over the entire imaging duration. The DI preparation scheme proved useful in creating a black blood gradient-echo image but showed no improvement in contrast throughout the imaging duration (since the DI preparation technique is essentially a 'snapshot' technique). Recent developments in cardiac MRI have moved towards assessment of myocardial perfusion, using first-pass contrast-enhancement imaging. This approach requires assessment of a large enough volume of the heart to allow assessment of perfusion as well as retaining a high temporal resolution of 7 or 2 seconds, and therefore a more modem high performance imaging system. For moderate performance gradient MR systems an alternative method of assessing myocardial perfusion is therefore required. Several novel techniques to assess myocardial T2* values in order to indirectly infer myocardial perfusion are introduced. The use of an original multi-echo gradient-echo imaging sequence to acquire T2* pixel-maps was investigated in phantoms and compared with commercially available sequences in order to validate its use.