Abstract not available

<p> </p><p>Platelets play a key role in primary haemostasis but are also related to the pathogenesis of arterial thrombosis. Thrombin is the most effective agonist inducing platelet activation. Human platelets express two G-protein coupled thrombin receptors (GPCRs), called protease activated receptor (PAR)1 and PAR4. The aim of this study was to clarify differences in the activities of PAR1 and PAR4, especially focusing on their resistance towards the platelet inhibitor nitric oxide (NO) and their ability to undergo desensitization. For this, PAR1- and PAR4- activating peptides (APs) (SFLLRN and AYPGKF, respectively) were used. Different aspects of platelet activities were studied: aggregation and the rise in intracellular Ca²⁺ concentrations ([Ca²⁺]_i). Aggregation was analyzed with lumiaggregometry, and [Ca²⁺]_i were studied using the fura-2 method. PKC substrate phosphorylation and the expression of PAR1 surface receptors were also analyzed, using Western blot and flow cytometry, respectively. The results from this study showed that NO exerted similar inhibitory effects on the two thrombin receptors. However, PAR1 and PAR4 differed in their ability to undergo desensitization. In cumulative dose-response studies, a low concentration of PAR1-AP induced desensitization of platelets towards higher PAR1-AP concentrations. This was not the case when studying PAR4-AP. The mechanism behind the desensitization of PAR1 to some part involved PKC, at least when studying the mobilization of intracellular Ca²⁺. PAR1 desensitization did not seem to involve receptor internalization and neither did it affect the activity of PAR4. This thus suggests that PAR4 might be a more suitable therapeutic target in the future management of thrombosis.</p><p> </p>

The current study attempted to discern the extent to which a gender bias influences the adult ratings of observed childhood pain. While gender differences in pain sensation are well documented in physiologically mature individuals, there seems to be no such difference in children. The effect of manipulating gender on the procedural pain ratings of 201 university undergraduate and nursing students was examined via a deceptive pain observation task. Results demonstrated no significant difference between gender conditions; however a strong link was established between prior exposure to painful pediatric medical procedures and lower pain ratings. The results suggest that, while a gender bias failed to alter pain ratings, desensitization to viewing painful procedures could alter how much pain healthcare professionals believe a patient is experiencing.

Reducing variation in key product features is a very important goal in process improvement. Finding and trying to control the cause(s) of variation is one way to reduce variability, but is not cost effective or even possible in some situations. In such cases, Robust Parameter Design (RPD) is an alternative. The goal in RPD is to reduce variation by reducing the sensitivity of the process to the sources of variation, rather than controlling these sources directly. That is, the goal is to find levels of the control inputs that minimize the output variation imposed on the process via the noise variables (causes). In the literature, a variety of experimental plans have been proposed for RPD, including Robustness, Desensitization and Taguchi’s method. In this thesis, the efficiency of the alternative plans is compared in the situation where the most important source of variation, called the “Dominant Cause”, is known. It is shown that desensitization is the most appropriate approach for applying the RPD method to an existing process.

Platelets play a key role in primary haemostasis but are also related to the pathogenesis of arterial thrombosis. Thrombin is the most effective agonist inducing platelet activation. Human platelets express two G-protein coupled thrombin receptors (GPCRs), called protease activated receptor (PAR)1 and PAR4. The aim of this study was to clarify differences in the activities of PAR1 and PAR4, especially focusing on their resistance towards the platelet inhibitor nitric oxide (NO) and their ability to undergo desensitization. For this, PAR1- and PAR4- activating peptides (APs) (SFLLRN and AYPGKF, respectively) were used. Different aspects of platelet activities were studied: aggregation and the rise in intracellular Ca2+ concentrations ([Ca2+]i). Aggregation was analyzed with lumiaggregometry, and [Ca2+]i were studied using the fura-2 method. PKC substrate phosphorylation and the expression of PAR1 surface receptors were also analyzed, using Western blot and flow cytometry, respectively. The results from this study showed that NO exerted similar inhibitory effects on the two thrombin receptors. However, PAR1 and PAR4 differed in their ability to undergo desensitization. In cumulative dose-response studies, a low concentration of PAR1-AP induced desensitization of platelets towards higher PAR1-AP concentrations. This was not the case when studying PAR4-AP. The mechanism behind the desensitization of PAR1 to some part involved PKC, at least when studying the mobilization of intracellular Ca2+. PAR1 desensitization did not seem to involve receptor internalization and neither did it affect the activity of PAR4. This thus suggests that PAR4 might be a more suitable therapeutic target in the future management of thrombosis.

Reducing variation in key product features is a very important goal in process improvement. Finding and trying to control the cause(s) of variation is one way to reduce variability, but is not cost effective or even possible in some situations. In such cases, Robust Parameter Design (RPD) is an alternative. The goal in RPD is to reduce variation by reducing the sensitivity of the process to the sources of variation, rather than controlling these sources directly. That is, the goal is to find levels of the control inputs that minimize the output variation imposed on the process via the noise variables (causes). In the literature, a variety of experimental plans have been proposed for RPD, including Robustness, Desensitization and Taguchi’s method. In this thesis, the efficiency of the alternative plans is compared in the situation where the most important source of variation, called the “Dominant Cause”, is known. It is shown that desensitization is the most appropriate approach for applying the RPD method to an existing process.

The current study attempted to discern the extent to which a gender bias influences the adult ratings of observed childhood pain. While gender differences in pain sensation are well documented in physiologically mature individuals, there seems to be no such difference in children. The effect of manipulating gender on the procedural pain ratings of 201 university undergraduate and nursing students was examined via a deceptive pain observation task. Results demonstrated no significant difference between gender conditions; however a strong link was established between prior exposure to painful pediatric medical procedures and lower pain ratings. The results suggest that, while a gender bias failed to alter pain ratings, desensitization to viewing painful procedures could alter how much pain healthcare professionals believe a patient is experiencing.

"It is thought that phobias are caused by a fear of the unknown and can be overcome by self-help learning resulting in better understanding. Observation and scientific investigation have been used to create a body of artwork for the purpose of helping to desensitize people who suffer from arachnophobia. Field trip collections, photography, printmaking and installations have been used to capture, explore and create visual artworks that have been designed to highlight fact-based features of spiders and their webs." / Master of Arts (Visual Arts)

"It is thought that phobias are caused by a fear of the unknown and can be overcome by self-help learning resulting in better understanding. Observation and scientific investigation have been used to create a body of artwork for the purpose of helping to desensitize people who suffer from arachnophobia. Field trip collections, photography, printmaking and installations have been used to capture, explore and create visual artworks that have been designed to highlight fact-based features of spiders and their webs." / Master of Arts (Visual Arts)

Thesis (Ph.D.)--Murdoch University, 2006. / Thesis submitted to the Division of Health Sciences. Bibliography: leaves 176-207.