The parasite Plasmodium falciparum is the causative agent of the most severe form of human malaria. During its intraerythocytic life cycle, P. falciparum transports red blood cell contents to its acidic organelle, known as the food vacuole, where a series of proteases degrade a majority of the host hemoglobin. Two metalloaminopeptidases, PfAPP and PfA-M1, have been previously localized to the food vacuole (in addition to distinct secondary locations for each), implicating them in the final stages of hemoglobin catabolism. Prior genetic work has determined these enzymes are necessary for efficient parasite proliferation, highlighting them as potential anti-malarial drug targets. This study presents the biochemical basis for the catalytic roles of these two enzymes in the hemoglobin degradation pathway. PfAPP, an aminopeptidase P homolog, is specific for hydrolyzing the N-termini of peptides containing penultimate prolines. PfA-M1 is a member of the expansive M1 family of proteases and exhibits a broad specificity towards substrates. The two enzymes are ubiquitous, found in organisms across all kingdoms of life. Their presence in an acidic environment is unique for aminopeptidase P proteins and rare for M1 homologs. Our immunolocalization results have confirmed the dual distribution of these two enzymes in the parasite. Vacuolar targeting was found to be associated with the Plasmodium specific N-terminal extension found in the PfA-M1 sequence by yellow fluorescent protein fusion studies. Kinetic analysis of recombinant forms of PfAPP and PfA-M1 revealed both enzymes are stable and catalytically efficient in the substrate rich, acidic environment of the parasite food vacuole. In addition, mutagenic exploration of the PfA-M1 active site has determined a residue important in dictating substrate specificity among homologs of the same family. These results provide insight into the parasite's functional recruitment of these enzymes to deal with the final stages of hemoglobin catabolism and necessary considerations for inhibitor design. / Ph. D.

Background: Dogs with acquired chronic liver disease often have hemostatic derangements. It is currently unknown whether dogs with acquired chronic liver disease have decreased platelet function and alterations in von Willebrand factor (vWF) that may contribute to hemostatic abnormalities. Hypothesis: Dogs with chronic liver disease have prolonged platelet closure time (CT), assessed with the PFA-100®, and buccal mucosal bleeding time (BMBT), and increased vWF concentration compared to healthy dogs. Animals: Eighteen dogs with chronic acquired liver disease undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy and eighteen healthy age-matched control dogs. Methods: Prospective study. BMBT, CT using the PFA-100®, and vWF antigen were measured in dogs with chronic liver enzyme elevation undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy. After undergoing ultrasound-guided needle biopsy, dogs were monitored for hemorrhage with serial packed cell volume measurements and focused assessment with sonography. An unpaired t-test was used for normally distributed data and the Mann-Whitney test was used when non-Gaussian distribution was present. The level of significance was set at P <0.05. Results: The CT was not different between the two groups (P = 0.27). The BMBT was significantly longer in the liver disease group compared to the control group (P = 0.019). There was no difference in the mean vWF antigen of the two groups (P = 0.077). Conclusions and clinical relevance: These results demonstrate mild impairment of primary hemostasis in dogs with chronic liver disease based on prolongation of BMBT. / Master of Science / Background: Dogs with chronic liver disease often have abnormal blood clotting activity. It is currently unknown whether dogs with chronic liver disease have decreased platelet function and alterations in von Willebrand factor (vWF) that may contribute to blood clotting abnormalities. Platelet function can be assessed using the PFA-100®, which measures platelet closure time (CT), and buccal mucosal bleeding time (BMBT). The PFA-100 simulates blood in circulation to assess platelet function. BMBT is a crude but readily available test to assess platelet function in practices without sophisticated methods of assessing platelet function. Hypothesis: Dogs with chronic liver disease have prolonged CT and BMBT, which both suggest platelet dysfunction. Additionally, dogs with chronic liver disease have increased vWF concentration compared to healthy dogs. Animals: Eighteen dogs with chronic acquired liver disease undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy and eighteen healthy age-matched control dogs. Methods: Prospective study. BMBT, CT, and vWF antigen were measured in dogs with chronic liver disease undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy. After undergoing ultrasound-guided needle biopsy, dogs were monitored for hemorrhage. Results: The CT was not different between the two groups but the BMBT was significantly longer in the liver disease group compared to healthy dogs. There was no difference in the mean vWF antigen between the two groups. Conclusions and clinical relevance: These results demonstrate mild impairment of blood clotting activity in dogs with chronic liver disease based on prolongation of BMBT compared to healthy dogs. Prolongation of BMBT compared to healthy dogs is suggestive of endothelial dysfunction and/or platelet dysfunction in dogs with chronic liver disease.

Fouling is a chronic problem in many heat transfer systems and results in the need for frequent heat exchanger (HEX) cleaning. In the dairy industry, the associated operating cost and environmental impact are substantial. Antifouling coatings are one mitigation option. In this work, the fouling behaviour of fluoropolymer, polypropylene and stainless steel heat transfer surfaces in processing raw milk and whey protein solution are studied. Methodologies to assess the economics of antifouling coatings are developed and applied. Two experimental apparatuses were designed and constructed to study fouling at surface temperatures around 90 °C. A microfluidic system with a 650 x 2000 µm flow channel enables fouling studies to be carried out by recirculating 2 l of raw milk. The apparatus operates in the laminar flow regime and the capability to probe the local composition of delicate fouling deposit $\textit{in-situ}$ with histological techniques employing confocal laser scanning microscopy. A larger bench-scale apparatus with a 10 x 42 mm flow channel was built to recirculate 17 l of solution in the turbulent flow regime which is more representative of conditions in an industrial plate HEX. Experimental results demonstrate that fluoropolymer coatings can reduce fouling masses from raw milk and whey protein solution by up to 50 %. Surface properties affect the structure and composition of the deposit. At the interface with apolar surfaces raw milk fouling layers are high in protein, whereas a strongly attached mineral-rich layer is present at the interface with steel. Whey protein deposits generated on apolar surfaces are more spongy and have a lower thermal conductivity and/or density than deposits on steel. The attraction of denatured protein towards apolar surfaces and the formation of a calcium phosphate layer on steel at later stages of fouling are explained with arguments based on the interfacial free energy of these materials in water. The financial attractiveness of coatings is considered for HEX subject to linearly and asymptotically increasing fouling resistance and using a spatially resolved fouling model. An explicit solution to the cleaning-scheduling problem is presented for the case of equal heat capacity flow rates in a counter-current HEX. Scenarios where the use of coatings may be attractive or where there is no financial benefit in cleaning a fouled exchanger are identified. Finally, experimental data are used to estimate the economic potential of fluoropolymer coated HEXs in the ultra-high-temperature treatment of milk. In the considered case, the value of a fluoropolymer coating inferred from the reduction in fouling is estimated to be around 2000 US$/m².

La modélisation numérique des structures composites à renfort fibreux de géométrie complexe constitue un axe de recherche majeur afin de prédire correctement leur comportement mécanique. Dans ce contexte, l’étude menée dans ce travail de thèse porte sur le développement de nouveaux éléments finis basés sur une approche numérique multi-échelle, appelée Approche de la Fibre Projetée (AFP). Cette approche a l’avantage de tenir compte de la présence des fibres au sein d’un espace matrice sans les discrétiser, ce qui limite considérablement la taille du système à résoudre. Pour analyser le comportement des structures composites, plusieurs éléments finis 2D et 3D ont été développés et implémentés dans le code ABAQUS via la routine UEL. Plusieurs cas tests de validation sont considérés pour tester la précision et l’efficacité des éléments finis proposés et les résultats obtenus sont globalement en bon accord avec les solutions de référence. De plus, l’intérêt de la nouvelle approche (AFP) est particulièrement mis en exergue en étudiant des structures composites complexe à renfort 3D : une plaque sandwich cousue et une plaque sandwich à âme creuse renforcée par des fibres en forme de « 8 ». / Numerical modeling of composite materials and structures with complex geometry of fiber reinforcement, such as stitched composites, constitutes a major research axis in order to correctly predict their mechanical behavior. Within this context, this study focuses on the development of new linear and nonlinear specific finite elements based on a multiscale numerical approach, called the Projected Fiber Approach (PFA). This numerical approach has the advantage of taking into account the presence of fi bers, long or short and distributed randomly or specifically, within a matrix space without discretizing them. Consequently, the obtained system of equations size is equivalent to that without reinforcement (matrix), which considerably reduces the computational cost. To analyze the linear and geometrically nonlinear behaviors of composite structures, two membrane finite elements, named PFT3 and PFQ4, and a 3D solid finite element, named PFH8, were developed and implemented into the commercial finite element code ABAQUS via the user element subroutine (UEL). Several numerical linear and nonlinear tests are considered to assess the accuracy and efficiency of the proposed composite finite elements, and the obtained results are globally in good agreement with the reference solutions. Moreover, the major interest of the PFA approach is particularly emphasized by studying two 3D complex reinforced composite structures: a stitched sandwich plate and a hollow core sandwich plate reinforced by "8" shape fibers.

Although disaster risk reduction is still not considered a priority by many countries and organisations, there is significant progress made towards the reduction of disaster risk. The experience of the International Decade for Natural Disaster Reduction (IDNDR, 1990–1999) prompted a major conceptual shift from disaster response to disaster reduction underscoring the crucial role of human action (UNISDR, 2001:03). This circumstance led to the adoption of an International Strategy for Disaster Risk Reduction (ISDR) in 1999 by the participants of the IDNDR Programme Forum. The adoption gave emphasis to the importance of a global strategy that encourages and facilitates concerted action to reduce risk and vulnerability to natural and related technological and environmental hazards. This research then focuses on the disaster risk reduction phenomenon and major or international initiatives and forums aimed at improving or raising the disaster risk reduction profile. It also focuses on disaster risk management in the South African context. In recent years, disaster risk reduction has grown in importance on the international agenda. This followed the prevalence of natural hazards such as floods, drought, earthquakes, tsunamis, as well as epidemics, which have had an increasing impact on humans, due to population growth, urbanization, rising poverty and the onset of global environmental changes. Aspects of environmental change include climate change, land degradation and deforestation. Practitioners and researchers widely acknowledge that poor planning, poverty and a range of other underlying factors create conditions of vulnerability that result in insufficient capacity or measures to reduce hazards‘ potentially negative consequences (IISD/UN/ISDR, 2007:01). It is in this light that in 2005 many governments around the world committed themselves to take action to reduce disaster risk, and thereby adopted a guiding document to reduce vulnerabilities to natural hazards, called the Hyogo Framework for Action (HFA). The HFA was adopted in January 2005 at the World Conference on Disaster Reduction, in Kobe Hyogo, Japan by 168 States. The aim of the HFA is to assist the efforts of nations and communities to become more resilient to, and cope better, with the hazards that threaten their development gains with the overriding goal of achieving a substantial reduction in global disaster risk. It also emphasizes that disaster risk reduction is a central issue for development policies, in addition to being of interest to various science, humanitarian and environmental fields. To help attain the expected outcome, the HFA identified five specific priorities for action (PFAs) which are: (i) making disaster risk reduction a priority; (ii) improving risk information and early warning; (iii) building a culture of safety and resilience; (iv) reducing the risks in key sectors; and (v) strengthening preparedness for response. The Global Network of Civil Society Organisation for Disaster Risk Reduction (GNDR) which was launched in 2007 in Geneva, is a major international network of civil society organisations working to influence and implement disaster risk reduction policies and practice around the world. The major programme of the global network is to collect perspective for the local level as to how the HFA is progressing. The Views from the Frontline (VFL) is the first independent assessment project undertaken towards the implementation of the HFA at the local level and is led by the Global Network. The aim of this project is to measure the gap between policy formulation at international level with the realities of policy execution at local level and to deepen the communication and coordination between different stakeholders on disaster risk reduction by involving government organisation and communities at the local level. The VFL perspective is that nationally formulated policies are not generating widespread systematic changes in local practices. There is a concern that the current approach is top–down and engages minimally with affected communities and fails to address their needs and capacities (GNDR, 2008:01). The main objective of this research was to provide an overview of progress made in the implementation of the HFA at local level particularly in the Kabokweni Location. The approach adopted in this study is called 'the Views from the Frontline', and explores the extent of the actual progress made toward the implementation and impact of the HFA priorities at local level, namely the Kabokweni community in the Mbombela Local Municipality (MLM) situated in the Mpumalanga Province of South Africa. / Thesis (M. Development and management)--North-West University, Potchefstroom Campus, 2011.

Although disaster risk reduction is still not considered a priority by many countries and organisations, there is significant progress made towards the reduction of disaster risk. The experience of the International Decade for Natural Disaster Reduction (IDNDR, 1990–1999) prompted a major conceptual shift from disaster response to disaster reduction underscoring the crucial role of human action (UNISDR, 2001:03). This circumstance led to the adoption of an International Strategy for Disaster Risk Reduction (ISDR) in 1999 by the participants of the IDNDR Programme Forum. The adoption gave emphasis to the importance of a global strategy that encourages and facilitates concerted action to reduce risk and vulnerability to natural and related technological and environmental hazards. This research then focuses on the disaster risk reduction phenomenon and major or international initiatives and forums aimed at improving or raising the disaster risk reduction profile. It also focuses on disaster risk management in the South African context. In recent years, disaster risk reduction has grown in importance on the international agenda. This followed the prevalence of natural hazards such as floods, drought, earthquakes, tsunamis, as well as epidemics, which have had an increasing impact on humans, due to population growth, urbanization, rising poverty and the onset of global environmental changes. Aspects of environmental change include climate change, land degradation and deforestation. Practitioners and researchers widely acknowledge that poor planning, poverty and a range of other underlying factors create conditions of vulnerability that result in insufficient capacity or measures to reduce hazards‘ potentially negative consequences (IISD/UN/ISDR, 2007:01). It is in this light that in 2005 many governments around the world committed themselves to take action to reduce disaster risk, and thereby adopted a guiding document to reduce vulnerabilities to natural hazards, called the Hyogo Framework for Action (HFA). The HFA was adopted in January 2005 at the World Conference on Disaster Reduction, in Kobe Hyogo, Japan by 168 States. The aim of the HFA is to assist the efforts of nations and communities to become more resilient to, and cope better, with the hazards that threaten their development gains with the overriding goal of achieving a substantial reduction in global disaster risk. It also emphasizes that disaster risk reduction is a central issue for development policies, in addition to being of interest to various science, humanitarian and environmental fields. To help attain the expected outcome, the HFA identified five specific priorities for action (PFAs) which are: (i) making disaster risk reduction a priority; (ii) improving risk information and early warning; (iii) building a culture of safety and resilience; (iv) reducing the risks in key sectors; and (v) strengthening preparedness for response. The Global Network of Civil Society Organisation for Disaster Risk Reduction (GNDR) which was launched in 2007 in Geneva, is a major international network of civil society organisations working to influence and implement disaster risk reduction policies and practice around the world. The major programme of the global network is to collect perspective for the local level as to how the HFA is progressing. The Views from the Frontline (VFL) is the first independent assessment project undertaken towards the implementation of the HFA at the local level and is led by the Global Network. The aim of this project is to measure the gap between policy formulation at international level with the realities of policy execution at local level and to deepen the communication and coordination between different stakeholders on disaster risk reduction by involving government organisation and communities at the local level. The VFL perspective is that nationally formulated policies are not generating widespread systematic changes in local practices. There is a concern that the current approach is top–down and engages minimally with affected communities and fails to address their needs and capacities (GNDR, 2008:01). The main objective of this research was to provide an overview of progress made in the implementation of the HFA at local level particularly in the Kabokweni Location. The approach adopted in this study is called 'the Views from the Frontline', and explores the extent of the actual progress made toward the implementation and impact of the HFA priorities at local level, namely the Kabokweni community in the Mbombela Local Municipality (MLM) situated in the Mpumalanga Province of South Africa. / Thesis (M. Development and management)--North-West University, Potchefstroom Campus, 2011.

Thèse de doctorat présenté en vue de l'obtention du doctorat en psychologie - recherche intervention, option psychologie clinique (Ph.D) / La gestion des réactions de stress post-traumatique dans les premiers jours suivant l’exposition à un événement traumatique (ÉT) au travail reste un défi pour les organisations de premiers répondants et répondantes d’urgence tels que les services médicaux d’urgence (SMU) dans lesquels travaillent les paramédics et les répartitrices et répartiteurs médicaux d’urgence (RMU). Ces travailleurs et travailleuses sont particulièrement exposés à des situations traumatiques imprévisibles et récurrentes, qui les rendent plus à risque de vivre de la détresse et des difficultés d’adaptation. Les recherches doivent se poursuivre pour savoir comment intervenir auprès de ces personnes, car à l’heure actuelle aucune intervention n’a démontré une efficacité suffisante. L’approche des Premiers Soins Psychologiques (PSP), informée par les données probantes, vise à réduire la détresse initiale et promouvoir des stratégies d’adaptation chez les individus exposés à un ÉT. Elle peut être délivrée par des paires aidantes et pairs aidants précocement, en accord avec des directives internationales. Cette approche est encore peu étudiée par la recherche scientifique. L’objectif de cette thèse est d’identifier comment l’approche des PSP peut s’intégrer auprès de paramédics et RMU. Une première étude a été menée auprès de 11 paires aidantes et pairs aidants afin d’explorer qualitativement les facteurs qui peuvent influencer l’adhésion dans le temps des bénéficiaires et des paires aidantes et pairs aidants dans leur participation à l’intervention des PSP, grâce à des entretiens semi-structurés individuels. Quatre thèmes et 11 sous- thèmes influençant l’adhésion ont été identifiés : (1) perceptions et attitudes individuelles des paires aidantes et pairs aidants et des bénéficiaires à l’égard des PSP ; (2) impacts perçus sur les paires aidantes et pairs aidants et les bénéficiaires ; (3) soutien organisationnel aux PSP et (4) congruence avec la culture professionnelle. Les résultats de cette étude suggèrent qu’il est possible d’agir sur divers facteurs au niveau individuel, organisationnel et culturel pour améliorer l’adhésion et qu’il faut surveiller les facteurs pouvant nuire à l’intervention des PSP dans le temps. Une seconde étude qualitative a exploré la perception des bénéficiaires (n=13) de l’intervention des PSP. Les résultats semblent indiquer que l’intervention des PSP permet de répondre aux besoins immédiats des travailleurs et travailleuses en accord avec les cinq principes essentiels d’une intervention précoce de Hobfoll (Hobfoll et al., 2007). L’intervention des PSP favoriserait également l’adaptation et le rétablissement après un ÉT, en contribuant à réduire la stigmatisation de la santé mentale, à augmenter les comportements de recherche d’aide et à diminuer les impacts négatifs organisationnels. Enfin, des éléments spécifiques à l’intervention ont été identifiés comme favorisant l’appréciation de l’intervention. L’identification de ces composantes nous donne des pistes d’amélioration de l’intervention afin de guider au mieux les organisations dans l’implantation et la mise en œuvre des PSP. Ces résultats qualitatifs peuvent également contribuer à informer de futures études quantitatives quant aux directions à prendre pour tester l’efficacité des PSP. Les résultats issus de ces deux articles ont permis de contribuer au développement de la littérature scientifique sur la pertinence et la façon dont peut s’intégrer l’intervention des PSP dans les organisations de premiers répondants et répondantes d’urgence en agissant sur divers facteurs au niveau individuel, organisationnel et culturel et ainsi améliorer l’adhésion dans le temps. Ils mettent aussi en lumière les bénéfices possibles des PSP et offrent des pistes concrètes d’amélioration pour les organisations qui souhaitent implanter ou bonifier la mise en œuvre des PSP comme intervention post-traumatique précoce auprès de leur personnel. / Managing post-traumatic stress reactions during the first days following exposure to a traumatic event (TE) at work remains a challenge for first responder organizations such as emergency medical services (EMS) (p.ex. paramedics and emergency medical dispatchers). These workers are particularly exposed to unpredictable and recurring traumatic situations, which puts them at increased risk for distress and adjustment difficulties. More research is needed to determine how to intervene with these people as no intervention has yet been shown to be sufficiently effective. The evidence informed Psychological First Aid (PFA) approach aims to reduce initial distress and promote coping strategies in individuals exposed to a TE. It can be early delivered by peer helpers, congruently with international guidelines. This approach is still largely unexplored in the scientific literature. The purpose of this thesis is to identify how the PFA approach can be integrated among paramedics and emergency medical dispatchers. The first paper was conducted with 11 peer helpers to qualitatively explore factors that may influence adherence over time of recipients and peer helpers in their participation in the PFA intervention, through individual semi-structured interviews. Four themes and 11 subthemes influencing adherence were identified: (1) individual perceptions and attitudes of peer helpers and recipients about PFA intervention; (2) perceived impacts on peer helpers and recipients; (3) organizational support to PFA intervention; and (4) congruence with the occupational culture. The results of this study suggest that a variety of factors can be acted upon to improve adherence and that factors that may interfere with PFA involvement over time should be monitored. A second paper explored recipients’ (n=13) perceptions of the PFA intervention. The results of the thematic analysis suggest that the PFA intervention addresses the immediate needs of workers in accordance with Hobfoll’s five essential principles of early intervention (Hobfoll et al., 2007). This intervention would also promote adjustment and recovery after a TE, regarding the reduction of stigma, the increase of help-seeking behaviours, and the decrease of organizational difficulties. Finally, specific components regarding the intervention or the provider were identified as promoting appreciation of the PFA intervention. The identification of these components provides us with avenues for intervention improvement to best guide first responder organizations in the implementation and delivery of PFA. These qualitative findings also help to inform future quantitative studies as to which directions to take to test the effectiveness of this intervention. The results of these two articles have contributed to the development of the scientific literature on whether and how to integrate the PFA intervention in first responder organizations. They highlighted the possible benefits of such an intervention and offered concrete avenues for improvement for organizations wishing to implement or improve the implementation of PFA as an early post-traumatic intervention for their personnel.