Erythrocyte phosphoglucomutase activity of bipolar I patients currently using lithium or carbamazepine

Lithium has been used for the last five decades to treat bipolar disorder, but the molecular basis of its therapeutic effect is unknown. Phosphoglucomutase is a key enzyme in the metabolism of glycogen. In yeast, rabbit and human HEK293 cells, it is inhibited by lithium in the therapeutic concentration range. We measured the phosphoglucomutase activity in erythrocytes and the inhibitor constant for lithium in a population of healthy subjects and compared them to those of bipolar patients treated with lithium or carbamazepine. The specific activity of phosphoglucomutase measured in vitro in erythrocytes from control subjects presented a normal distribution, with the difference between the lowest and the highest activity being approximately 2-fold (0.53-1.10 nmol mg Hb-1 min-1). Comparison of phosphoglucomutase activity in untreated bipolar patients and control subjects showed no significant difference, whereas comparison between bipolar patients treated with carbamazepine or lithium revealed significantly lower mean values in patients treated with carbamazepine (747.3 ± 27.6 vs 879.5 ± 35.9 pmol mg Hb-1 min-1, respectively). When we studied the concentration of lithium needed to inhibit phosphoglucomutase activity by 50%, a bimodal distribution among the population tested was obtained. The concentration of LiCl needed to inhibit phosphoglucomutase activity by 50% was 0.35 to 1.8 mM in one group of subjects and in the other it was 3 to 4 mM. These results suggest that phosphoglucomutase activity may be significant in patients with bipolar disorder treated with lithium and carbamazepine.

User Experience of Geocaching and Its Application to Tourism and Education

Advances in technology have provided new ways of using entertainment and game technology to foster human interaction. Games and playing with games have always been an important part of people’s everyday lives. Traditionally, human-computer interaction (HCI) research was seen as a psychological cognitive science focused on human factors, with engineering sciences as the computer science part of it. Although cognitive science has made significant progress over the past decade, the influence of people’s emotions on design networks is increasingly important, especially when the primary goal is to challenge and entertain users (Norman 2002). Game developers have explored the key issues in game design and identified that the driving force in the success of games is user experience. User-centered design integrates knowledge of users’ activity practices, needs, and preferences into the design process. Geocaching is a location-based treasure hunt game created by a community of players. Players use GPS (Global Position System) technology to find “treasures” and create their own geocaches; the game can be developed when the players invent caches and used more imagination to creations the caches. This doctoral dissertation explores user experience of geocaching and its applications in tourism and education. Globally, based on the Geocaching.com webpage, geocaching has been played about 180 countries and there are more than 10 million registered geocachers worldwide (Geocaching.com, 25.11.2014). This dissertation develops and presents an interaction model called the GameFlow Experience model that can be used to support the design of treasure hunt applications in tourism and education contexts. The GameFlow Model presents and clarifies various experiences; it provides such experiences in a real-life context, offers desirable design targets to be utilized in service design, and offers a perspective to consider when evaluating the success of adventure game concepts. User-centered game designs have adapted to human factor research in mainstream computing science. For many years, the user-centered design approach has been the most important research field in software development. Research has been focusing on user-centered design in software development such as office programs, but the same ideas and theories that will reflect the needs of a user-centered research are now also being applied to game design (Charles et al. 2005.) For several years, we have seen a growing interest in user experience design. Digital games are experience providers, and game developers need tools to better understand the user experience related to products and services they have created. This thesis aims to present what the user experience is in geocaching and treasure hunt games and how it can be used to develop new concepts for the treasure hunt. Engineers, designers, and researchers should have a clear understanding of what user experience is, what its parts are, and most importantly, how we can influence user satisfaction. In addition, we need to understand how users interact with electronic products and people, and how different elements synergize their experiences. This doctoral dissertation represents pioneering work on the user experience of geocaching and treasure hunt games in the context of tourism and education. The research also provides a model for game developers who are planning treasure hunt concepts.

Nutritional aspects of nile tilapia (Oreochromis niloticus) silage

One third of the world's fishing produce is not directly used for human consumption. Instead, it is used for making animal food or is wasted as residue. It would be ideal to use the raw material thoroughly and to recover by-products, preventing the generation of residues. With the objectives of increasing the income and the production of the industry, as well as minimizing environmental and health problems from fish residue, chemical silage from Tilapia (Oreochromis niloticus) processing residues was developed after homogenization and acidification of the biomass with 3% formic acid: propionic, 1:1, addition of antioxidant BHT and maintenance of pH at approximately 4.0. Analyses to determine the moisture, protein, lipids and ash were carried out. The amino acids were examined in an auto analyzer after acid hydrolysis, except for the tryptophan which was determined through colorimetry. The tilapia silage presented contents that were similar to or higher than the FAO standards for all essential amino acids, except for the tryptophan. The highest values found were for glutamic acid, lysine and leucine. The results indicate a potential use of the silage prepared from the Nile tilapia processing residue as a protein source in the manufacturing of fish food.

Investigating the Existence of Business-IT Alignment Trap in Finnish IT Organizations

The overall purpose of this master's thesis is to investigate the existence of business-IT alignment trap in Finnish IT organizations. The alignment trap refers to the inability of IT investments to deliver the expected business benefits. The basis for this investigation is due to the previous knowledge that high level of IT alignment practice with very low efficacy in an organization can lead to alignment trap. The theory which was established on the dimensions of IT-alignment and efficacy of IT as a whole with considerations for cost reduction and revenue growth benefits. This study explored the same dimensions with the previous study but identified additional benefit (profitability). The study was conducted using the Finnish IT barometer data from different IT organizations. A quantitative research method was used in conducting this study which was built on positivist philosophical stance. The empirical data is based on survey data, an excerpt from the Finnish IT barometer data that captured the annual survey results of IT significance to Finnish organizations as evaluated by business and IT professionals. The survey data comprised of 249 respondents and their responses were categorized into high and low IT intensive which form the basis of the statistical analysis conducted. Overall, five analyses were conducted using the variables of cost reductions, revenue growth and profitability in the 2x2 matrix dimensions of IT alignment and efficacy of IT, grouped into alignment trap, maintenance zone, well-oiled IT and IT-enabled growth. The empirical results, revealed a partial existence of alignment trap in Finnish IT organizations. This is due to a very minute number of organizations that were ensnared in the alignment trap zone on the analyses conducted. Although they recorded considerable high performances in terms of revenue growth rate with IT spending below the average companies, their profitability was considered very low. Generally it was observed that Finnish IT organizations with high efficacy of IT practices had good performances, while those with low efficacy of IT experienced low performances, especially in the aspect of profitability, regardless of the degree of IT alignment. The study proposes that organizations should improve on practices that enhance effectiveness of IT more in order for them to realize the full benefits of IT and to avoid alignment trap.

Form(s)-of-life: agamben's reading of Wittgenstein and the potential uses of a notion

Giorgio Agamben and Ludwig Wittgenstein seem to have very little in common: the former is concerned with traditional ontological issues while the latter was interested in logics and ordinary language, avoiding metaphysical issues as something we cannot speak about. However, both share a crucial notion for their philosophical projects: form of life. In this paper, I try to show that, despite their different approaches and goals, form of life is for both a crucial notion for thinking ethics and life in-common. Addressing human existence in its constitutive relation to language, this notion deconstructs traditional dichotomies like bios and zoé, the cultural and the biological, enabling both authors to think of a life which cannot be separated from its forms, recognizing the commonality of logos as the specific trait of human existence. Through an analogical reading between both theoretical frameworks, I suggest that the notion of form-of-life, elaborated by Wittgenstein to address human production of meaning, becomes the key notion in Agamben's affirmative thinking since it enables us to consider the common ontologically in its relation to Human potentialities and to foresee a new, common use of the world and ourselves.

Deviations of Governance In IT Multi-Sourcing: A Case Study

IT outsourcing (ITO) refers to the shift of IT/IS activities from internal to external of an organization. In prior research, the governance of ITO is recognized with persistent strategic importance for practice, because it is tightly related to ITO success. Under the rapid transformation of global market, the evolving practice of ITO requires updated knowledge on effective governance. However, research on ITO governance is still under developed due to the lack of integrated theoretical frameworks and the variety of empirical settings besides dyadic client-vendor relationships. Especially, as multi-sourcing has become an increasingly common practice in ITO, its new governance challenges must be attended by both ITO researchers and practitioners. To address this research gap, this study aims to understand multi-sourcing governance with an integrated theoretical framework incorporating both governance structure and governance mechanisms. The focus is on the emerging deviations among formal, perceived and practiced governance. With an interpretive perspective, a single case study is conducted with mixed methods of Social Network Analysis (SNA) and qualitative inquiries. The empirical setting embraces one client firm and its two IT suppliers for IT infrastructure services. The empirical material is analyzed at three levels: within one supplier firm, between the client and one supplier, and among all three firms. Empirical evidences, at all levels, illustrate various deviations in governance mechanisms, with which emerging governance structures are shaped. This dissertation contributes to the understanding of ITO governance in three domains: the governance of ITO in general, the governance of multi-sourcing in particular, and research methodology. For ITO governance in general, this study has identified two research strands of governance structure and governance mechanisms, and integrated both concepts under a unified framework. The composition of four research papers contributes to multi-sourcing research by illustrating the benefits of zooming in and out across the multilateral relationships with different aspects and scopes. Methodologically, the viability and benefit of mixed-method is illustrated and confirmed for both researchers and practitioners.

Out of the darkness and into the light : a study of inauthentic and authentic speech

Introduction Man can be described as the being who shows himself in speech, and from birth to death is continually speaking. Communication is so close to us, so woven into our very being, that we have little understanding of the way it is constituted; for it is as hard to obtain distance from communication as it is to obtain distance from ourselves. All communication is not alike. There are two basic modesl of communication, the inauthentic and the authentic, between which there occurs a constant tension. It is in the inauthentic mode, points out Heidegger, that we find ourselves "proximately and for the most part"; 1. Being and Time, pg. 68 Dasein decides as to the way it will comport itself in taking up its task of having being as an issue for it. " •.• it~, in its very being 'choose' itself and win itself; it can also lose itself and never win itself or only "seem" to do so. But only in so far as it is essentially something which can be authentic--that is, something of its own--can it have lost itself and not yet won itself." 2. therefore Heidegger also terms it "everydayness".2 Caught up in the world of everydayness, our speaking covers over and conceals3 our rootedness in being, leaving us in the darkness of untruth. The image of darkness may be inferred from Heidegger's use of the image of "clearing,,4 to depict being as 2. ibid. pg. 69 "Dasein's average everydayness, however, is not to be taken as a mere 'aspect'. Here too, and even in the mode of inauthenticity, the structure of existentiality lies ~ priori and here too Dasein's being is an issue for it in a definite way; and Dasein comports itself towards it the mode of average everydayness, even if this is only the mode of fleeing in the face of it and forgetfulness thereof." 3. ibid. pg. 59 "covering over" and "concealing" are 1;yays Dasein tries to flee its task of having being as an issue for itself. " ••• This being can be covered up so extensively that it becomes forgotten and no question arises about it or its meaning ••• n How everyday speaking accomplishes this will be taken up in detail in the second chapter which explores Dasein's everyday speech. 4. ibid, pg. 171 lI ••• we have in mind nothing other than the Existential - ontological structure of this entity (Dasein), that it is in such a way as to be its 'there'. To say that it is -' illuminated' [tlerleuchtet"] means that as Being-in-theworld it is cleared [gelichtetJ in itself7 not through any other entity, but in such a way that it is itself the clearing. Only for an entity which is eXistentially cleared in this way does what is present-at-hand become accessible in the light or hidden in the dark •••• " 3 dis-coveredness and truth. Our first task will be to explore the nature of communication in general and then to explore each of the modes manifested in turn. The structure of the inauthentic mode of communication can be explored by asking the following questions: What is this speaking about? Who is it that is speaking and who is spoken to? Does this speaking show man in his speech? The authentic mode is distinguished by the rarity with which we encounter it; as the inauthentic conceals, so the authentic reveals our rootedness in being. Yet this rarity makes it difficult to delineate its elusive structure clearly. Its constituent elements can be brought into focus by asking the same questions of this mode that we previously asked of the inauthentic mode. Our initial response to the disclosure of the authentic mode is to attempt to abandon the inauthentic mode and leave the darkness behind dwelling only in the "lighted place". All through the ages, some men pushing this to extreme, have, upon uncovering their relatedness to being, experienced a deep longing to dwell in such a "place" of pure truth and oft times denigrated or attempted to exclude the everyday world. Such 4. flight is twice mistaken: first it atbempts to fix truth as unchanging and static and secondly, it opposes this to untruth which it seeks to abolish. This is both the wrong view of truth and the wrong view of untruth as Heidegger points out in The Origin of The-Work of Art: The Way-to-be of truth, i.e., of discoveredness, is under the sway of refusal. But this refusal is no lack or privation, as if truth could be simply discoveredness rid of all covers. If it could be that, it would no longer be itself . ••• Truth in its way-to-be is untruth.5 Pure light is not the nature of Being nor is pure unconcealedness possible for man. Failure to remember this is the failure to realize that communication destroys itself in such flight because it no longer maintains the contingency of its task, i.e., the dis-closedness of being. We are reminded of the strong attraction this flight from darkness held for Plato. Light, truth and Being are all beyond the darkness and have nothing to do with it. In Book VII of the R~public, Socrates' explanation of the Allegory of the Cave to Glaucon points to a decided preference men have for the "lighted place". 5. The Origin Of The Work Of Art, pg. 42 5. Come then, I said, and join me in this further thought, and do not be surprised that those who attained to this height are not willing to occupy themselves with the affairs of men, but their souls ever feel the upward urge and yearning for that sojourn above. For this, I take it, is likely if in this point too the likeliness of our image holds. 6 Despite the attraction to pure truth, human communication is more complex than putting down one mode of communication and picking up another. Due to the fact that we are always on the way, the title of my thesis will have to be amended: OUT OF THE DARKNESS AND INTO THE LIGHT--AGAIN AND AGAIN. It must be this way because this is what it means to be human. This is the point made by Mephisto to Faust in pointing out that man, standing between God and the devil, needs both darkness and light: Er findet sich in einem ewigen Gl~t Uns hat er in die Finsternis gebracht, Und euch taugt einzig Tag und Nacht. 7 6. Republic z (517 c & d) It should be noted however, that while the philosopherking must be compelled to return to the cave for purely political reasons, once he has taken adequate view of the "brightest region of being" he has the full truth and his return to darkness adds nothing to the truth. 7. Faust, pg. 188 6. This thesis proposes to examine the grounds that give rise to communication, uncovering the structure of its inauthentic and authentic modes and paying close attention to tpeir interrelationship and to their relationship to language as "the house of Being": language that both covers and opens up man's rootedness in Being, transforming him as he moves along his way, taking up his "ownmost task" of becoming who he is. roots. He is the being who shows himself inn that reflects his forgetfulness or remembrance of his rootedness in being. Man comes into an already existent world and is addressedl through things in the world which are c

From absolutes to aesthetics : John Dewey and the art of experience /

In this thesis I sought to capture something of the integrity of John Dewey's larger vision. While recognizing this to be a difficult challenge, I needed to clear some of the debris of an overly narrow reading of Dewey's works by students of education. The tendency of reducing Dewey's larger philosophical vision down to neat theoretical snap shots in order to prop up their particular social scientific research, was in my estimation slowly damaging the larger integrity of Dewey's vast body of work. It was, in short, killing off the desire to read big works, because doing so was not necessary to satisfying the specialized interests of social scientific research. In this thesis then I made a plea for returning the Humanities to the center of higher education. It is there that students learn how to read and to think—skills required to take on someone of Dewey's stature. I set out in this thesis to do just that. I took Dewey's notion of experience as the main thread connecting all of his philosophy, and focused on two large areas of inquiry, science and its relation to philosophy, and aesthetic experience. By exploring in depth Dewey's understanding of human experience as it pertains to day-to-day living, my call was for a heightened mode of artful conduct within our living contexts. By calling on the necessity of appreciating the more qualitative dimensions of lived experience, I was hoping that students engaged in the Social Sciences might begin to bolster their research interests with more breadth and depth of reading and critical insight. I expressed this as being important to the survival and intelligent flourishing of democratic conduct.

Transmission of West Nile virus in the Niagara Region among a population at risk for exposure

Background. West Nile Virus (WNV), a mosquito-borne flavivirus, is one of an increasing number of infectious diseases that have been emerging or re-emerging in the last two decades. Since the arrival ofWNV to Canada to present date, the Niagara Region has only reported 30 clinical cases, a small number compared to the hundreds reported in other regions of similar conditions. Moreover, the last reported human case in Niagara was in 2006. As it has been demonstrated that the majority of WNV infections are asymptomatic, the question remains whether the lack of clinical cases in Niagara truly reflects the lack of transmission to humans or if infections are still occurring but are mostly asymptomatic. Objectives. The general objective of this study was to establish whether or not active WNV transmission could be detected in a human population residing in Niagara for the 2007 transmission season. To fullfil this objective, a cross-sectional seroprevalence study was designed to investigate for the presence of anti-WNV antibodies in a sample of Mexican migrant agricultural workers employed in farms registered with the Seasonal Agricultural Workers Program (SAWP). Due to the Mexican origin of the study participants, three specific research objectives were proposed: a) determine the seroprevalence ofanti-WNV antibodies as well as anti-Dengue virus antibodies (a closely related virus prevalent in Mexico and likely to confound WNV serology); b) analyze risk factors associated with WNV and Dengue virus seropositivity; and c) assess the awareness of study participants about WNV infection as well as their understanding of the mode of transmission and clinical importance of the infection. Methodology: After obtaining ethics clearance from Brock University, farms were visited and workers invited to participate. Due to time constraints, only a small number of farms were enrolled with a resulting convenience and non-randomized study sample. Workers' demographic and epidemiological data were collected using a standardized questionnaire and blood samples were drawn to determine serum anti-WNV and anti- Dengue antibodies with a commercial ELISA. All positive samples were sent to the National Microbiology Laboratory in Winnipeg, Manitoba for confirmation with the Plaque Reduction Neutralization Test (PRNT). Data was analyzed with Stata 10.0. Antibody determinations were reported as seroprevalence proportions for both WNV and Dengue. Logistic regression was used to analyze risk factors that may be associated with seropositivity and awareness was reported as a proportion of the number of individuals possessing awareness over the total number of participants. Results and Discussion. In total 92 participants working in 5 farms completed the study. Using the commercial ELISA, seropositivity was as follows: 2.2% for WNV IgM, 20.7% for WNV IgG, and 17.1 % for Dengue IgG. Possible cross-reactivity was demonstrated in 15/20 (75.0%) samples that were positive for both WNV IgG and Dengue IgG. Confirmatory testing with the PRNT demonstrated that none of the WNV ELISA positive samples had antibodies to WNV but 13 samples tested positive for anti-Dengue antibodies (14.1 % Dengue sereoprevalence). The findings showed that the ELISA performance was very poor for assessing anti-WNV antibodies in individuals previously exposed to Dengue virus. However, the ELISA had better sensitivity and specificity for assessing anti-Dengue antibodies. Whereas statistical analysis could not be done for WNV seropositivity, as all samples were PRNT negative, logistic regression demonstrated several risk factors for Dengue exposure_ The first year coming to Canada appeared to be significantly associated with increased exposure to Dengue while lower socio-economic housing and the presence of a water basin in the yard in Mexico appeared to be significantly associated with a decreased exposure to Dengue_ These seemingly contradictory results illustrate that in mobile populations such as migrant workers, risk factors for exposure to Dengue are not easily identified and more research is needed. Assessing the awareness of WNV and its clinical importance showed that only 23% of participants had some knowledge of WNV, of which 76% knew that the infection was mosquito-borne and 47% recognized fever as a symptom. The identified lack of understanding and awareness was not surprising since WNV is not a visible disease in Mexico. Since WNV persists in an enzootic cycle in Niagara and the occurrence of future outbreaks is unpredictable, the agricultural workers remain at risk for transmission. Therefore it important they receive sufficient health education regarding WNV before leaving Mexico and during their stay in Canada. Conclusions. Human transmission of WNV could not be proven among the study participants even when due to their occupation they are at high risk for mosquito bites. The limitations of the study sample do not permit generalizable conclusions, however, the study findings are consistent with the absence of clinical cases in the Niagara Region, so it is likely that human transmission is indeed neglible or absent. As evidenced by our WNV serology results, PRNT must be utilized as a confirmatory test since false positivity occurs frequently. This is especially true when previous exposure to Dengue virus is likely.

Aspects of spatial and habitat ecology of multiple Anopheles species (Diptera: Culicidae): malaria vectors in the highlands and foothills of Ecuador

The resurgence of malaria in highland regions of Africa, Oceania and recently in South America underlines the importance of the study of the ecology of highland mosquito vectors of malaria. Since the incidence of malaria is limited by the distribution of its vectors, the purpose of this PhD thesis was to examine aspects of the ecology of Anopheles mosquitoes in the Andes of Ecuador, South America. A historical literature and archival data review (Chapter 2) indicated that Anopheles pseudopunctipennis transmitted malaria in highland valleys of Ecuador prior to 1950, although it was eliminated through habitat removal and the use of chemical insecticides. Other anopheline species were previously limited to low-altitude regions, except in a few unconfirmed cases. A thorough larval collection effort (n=438 attempted collection sites) in all road-accessible parts of Ecuador except for the lowland Amazon basin was undertaken between 2008 - 2010 (Chapter 3). Larvae were identified morphologically and using molecular techniques (mitochondrial COl gene), and distribution maps indicated that all five species collected (Anopheles albimanus, An. pseudopunctipennis, Anopheles punctimacula, Anopheles oswaldoi s.l. and Anopheles eiseni) were more widespread throughout highland regions than previously recorded during the 1940s, with higher maximum altitudes for all except An. pseudopunctipennis (1541 m, 1930 m, 1906 m, 1233 m and 1873 m, respectively). During larval collections, to characterize species-specific larval habitat, a variety of abiotic and biotic habitat parameters were measured and compared between species-present and species-absent sites using chi-square tests and stepwise binary logistic regression analyses (Chapter 4). An. albimanus was significantly associated with permanent pools with sand substrates and An. pseudopunctipennis with gravel and boulder substrates. Both species were significantly associated with floating cyanobacterial mats and warmer temperatures, which may limit their presence in cooler highland regions. Anopheles punctimacula was collected more often than expected from algae-free, shaded pools with higher-than-average calculated dissolved oxygen. Anopheles oswaldoi s.l., the species occurring on the Amazonian side of the Andes, was associated with permanent, anthropogenic habitats such as roadside ditches and ponds. To address the hypothesis that human land use change is responsible for the emergence of multiple highland Anopheles species by creating larval habitat, common land uses in the western Andes were surveyed for standing water and potential larval habitat suitability (Chapter 5). Rivers and road edges provided large amounts of potentially suitable anopheline habitat in the western Andes, while cattle pasture also created potentially suitable habitat in irrigation canals and watering ponds. Other common land uses surveyed (banana farms, sugarcane plantations, mixed tree plantations, and empty lots) were usually established on steep slopes and had very little standing water present. Using distribution and larval habitat data, a GIS-based larval habitat distribution model for the common western species was constructed in ArcGIS v.l 0 (ESRI 2010) using derived data layers from field measurements and other sources (Chapter 6). The additive model predicted 76.4 - 97.9% of the field-observed collection localities of An. albimanus, An. pseudopunctipennis and An. punctimacula, although it could not accurately distinguish between species-absent and speciespresent sites due to its coarse scale. The model predicted distributional expansion and/or shift of one or more anopheline species into the following highland valleys with climate warming: Mira/Chota, Imbabura province, Tumbaco, Pichincha province, Pallatanga and Sibambe, Chimborazo province, and Yungilla, Azuay province. These valleys may serve as targeted sites of future monitoring to prevent highland epidemics of malaria. The human perceptions of malaria and mosquitoes in relation to land management practices were assessed through an interview-based survey (n=262) in both highlands and lowlands, of male and female land owners and managers of five property types (Chapter 7). Although respondents had a strong understanding of where the disease occurs in their own country and of the basic relationship among standing water, mosquitoes and malaria, about half of respondents in potential risk areas denied the current possibility of malaria infection on their own property. As well, about half of respondents with potential anopheline larval habitat did not report its presence, likely due to a highly specific definition of suitable mosquito habitat. Most respondents who are considered at risk of malaria currently use at least one type of mosquito bite prevention, most commonly bed nets. In conclusion, this interdisciplinary thesis examines the occurrence of Anopheles species in the lowland transition area and highlands in Ecuador, from a historic, geographic, ecological and sociological perspective.

Evaluating perceptual maps of asymmetries for gait symmetry quantification and pathology detection

Le mouvement de la marche est un processus essentiel de l'activité humaine et aussi le résultat de nombreuses interactions collaboratives entre les systèmes neurologiques, articulaires et musculo-squelettiques fonctionnant ensemble efficacement. Ceci explique pourquoi une analyse de la marche est aujourd'hui de plus en plus utilisée pour le diagnostic (et aussi la prévention) de différents types de maladies (neurologiques, musculaires, orthopédique, etc.). Ce rapport présente une nouvelle méthode pour visualiser rapidement les différentes parties du corps humain liées à une possible asymétrie (temporellement invariante par translation) existant dans la démarche d'un patient pour une possible utilisation clinique quotidienne. L'objectif est de fournir une méthode à la fois facile et peu dispendieuse permettant la mesure et l'affichage visuel, d'une manière intuitive et perceptive, des différentes parties asymétriques d'une démarche. La méthode proposée repose sur l'utilisation d'un capteur de profondeur peu dispendieux (la Kinect) qui est très bien adaptée pour un diagnostique rapide effectué dans de petites salles médicales car ce capteur est d'une part facile à installer et ne nécessitant aucun marqueur. L'algorithme que nous allons présenter est basé sur le fait que la marche saine possède des propriétés de symétrie (relativement à une invariance temporelle) dans le plan coronal.

The Role of ULK1 in the Pathophysiology of Osteoarthritis

L'arthrose est la maladie musculo-squelettique la plus commune dans le monde. Elle est l'une des principales causes de douleur et d’incapacité chez les adultes, et elle représente un fardeau considérable sur le système de soins de santé. L'arthrose est une maladie de l’articulation entière, impliquant non seulement le cartilage articulaire, mais aussi la synoviale, les ligaments et l’os sous-chondral. L’arthrose est caractérisée par la dégénérescence progressive du cartilage articulaire, la formation d’ostéophytes, le remodelage de l'os sous-chondral, la détérioration des tendons et des ligaments et l'inflammation de la membrane synoviale. Les traitements actuels aident seulement à soulager les symptômes précoces de la maladie, c’est pour cette raison que l'arthrose est caractérisée par une progression presque inévitable vers la phase terminale de la maladie. La pathogénie exacte de l'arthrose est encore inconnue, mais on sait que l'événement clé est la dégradation du cartilage articulaire. Le cartilage articulaire est composé uniquement des chondrocytes; les cellules responsables de la synthèse de la matrice extracellulaire et du maintien de l'homéostasie du cartilage articulaire. Les chondrocytes maintiennent la matrice du cartilage en remplaçant les macromolécules dégradées et en répondant aux lésions du cartilage et aux dégénérescences focales en augmentant l'activité de synthèse locale. Les chondrocytes ont un taux faible de renouvellement, c’est pour cette raison qu’ils utilisent des mécanismes endogènes tels que l'autophagie (un processus de survie cellulaire et d’adaptation) pour enlever les organelles et les macromolécules endommagés et pour maintenir l'homéostasie du cartilage articulaire. i L'autophagie est une voie de dégradation lysosomale qui est essentielle pour la survie, la différenciation, le développement et l’homéostasie. Elle régule la maturation et favorise la survie des chondrocytes matures sous le stress et des conditions hypoxiques. Des études effectuées par nous et d'autres ont montré qu’un dérèglement de l’autophagie est associé à une diminution de la chondroprotection, à l'augmentation de la mort cellulaire et à la dégénérescence du cartilage articulaire. Carames et al ont montré que l'autophagie est constitutivement exprimée dans le cartilage articulaire humain normal. Toutefois, l'expression des inducteurs principaux de l'autophagie est réduite dans le vieux cartilage. Nos études précédentes ont également identifié des principaux gènes de l’autophagie qui sont exprimés à des niveaux plus faibles dans le cartilage humain atteint de l'arthrose. Les mêmes résultats ont été montrés dans le cartilage articulaire provenant des modèles de l’arthrose expérimentaux chez la souris et le chien. Plus précisément, nous avons remarqué que l'expression d’Unc-51 like kinase-1 (ULK1) est faible dans cartilage humain atteint de l'arthrose et des modèles expérimentaux de l’arthrose. ULK1 est la sérine / thréonine protéine kinase et elle est l’inducteur principal de l’autophagie. La perte de l’expression de ULK1 se traduit par un niveau d’autophagie faible. Etant donné qu’une signalisation adéquate de l'autophagie est nécessaire pour maintenir la chondroprotection ainsi que l'homéostasie du cartilage articulaire, nous avons proposé l’hypothèse suivante : une expression adéquate de ULK1 est requise pour l’induction de l’autophagie dans le cartilage articulaire et une perte de cette expression se traduira par une diminution de la chondroprotection, et une augmentation de la mort des chondrocytes ce qui conduit à la dégénérescence du cartilage articulaire. Le rôle exact de ULK1 dans la pathogénie de l'arthrose est inconnue, j’ai alors créé pour la première fois, des souris KO ULK1spécifiquement dans le cartilage en utilisant la technologie Cre-Lox et j’ai ensuite soumis ces souris à la déstabilisation du ménisque médial (DMM), un modèle de l'arthrose de la souris pour élucider le rôle spécifique in vivo de ULK1 dans pathogenèse de l'arthrose. Mes résultats montrent que ULK1 est essentielle pour le maintien de l'homéostasie du cartilage articulaire. Plus précisément, je montre que la perte de ULK1 dans le cartilage articulaire a causé un phénotype de l’arthrose accéléré, associé à la dégénérescence accélérée du cartilage, l’augmentation de la mort cellulaire des chondrocytes, et l’augmentation de l'expression des facteurs cataboliques. En utilisant des chondrocytes provenant des patients atteints de l’arthrose et qui ont été transfectées avec le plasmide d'expression ULK1, je montre qu’ULK1 est capable de réduire l’expression de la protéine mTOR (principal régulateur négatif de l’autophagie) et de diminuer l’expression des facteurs cataboliques comme MMP-13 et ADAMTS-5 et COX-2. Mes résultats jusqu'à présent indiquent que ULK1 est une cible thérapeutique potentielle pour maintenir l'homéostasie du cartilage articulaire.

Attitude in students of Health Sciences toward scientific knowledge

Educating health professionals implies the challenge of creating and developing an inquiring mind, ready to be in a state of permanent questioning. For this purpose, it is fundamental to generate a positive attitude toward the generation of knowledge and science. Objective: to determine the attitude toward science and the scientific method in undergraduate students of health sciences. Materials and methods: a cross-sectional study was made by applying a self-administered survey, excluding those who were transferred from other universities and repeated. The attitude toward science and the scientific method were valued using the scale validated and published by Hren, which contains three domains: value of scientific knowledge, value of scientific methodology, and value of science for health professions. Results: 362 students were included, 86,6% of them graded the attitude toward scientific knowledge above 135 points, neutral scale value. Similar scores were registered in the domains value of scientific knowlede for the human dimension of the students and value of science for health professions. 91,4% of the students graded the value of scientific methodology below 48 points. Conclusions: the favorable attitude of the students can be explained by the contact that they have with the scientific method since the beginning of their studies and its concordance with the evolution of science. The domain value of scientific methodology obtained the lowest grade on the part of the students, which could be related to the lack of knowledge about scientific methodology.

Definition of an it project portfolio management methodology for a pharmaceutical company

Con la creciente popularidad de las soluciones de IT como factor clave para aumentar la competitividad y la creación de valor para las empresas, la necesidad de invertir en proyectos de IT se incrementa considerablemente. La limitación de los recursos como un obstáculo para invertir ha obligado a las empresas a buscar metodologías para seleccionar y priorizar proyectos, asegurándose de que las decisiones que se toman son aquellas que van alineadas con las estrategias corporativas para asegurar la creación de valor y la maximización de los beneficios. Esta tesis proporciona los fundamentos para la implementación del Portafolio de dirección de Proyectos de IT (IT PPM) como una metodología eficaz para la gestión de proyectos basados en IT, y una herramienta para proporcionar criterios claros para los directores ejecutivos para la toma de decisiones. El documento proporciona la información acerca de cómo implementar el IT PPM en siete pasos, el análisis de los procesos y las funciones necesarias para su ejecución exitosa. Además, proporciona diferentes métodos y criterios para la selección y priorización de proyectos. Después de la parte teórica donde se describe el IT PPM, la tesis aporta un análisis del estudio de caso de una empresa farmacéutica. La empresa ya cuenta con un departamento de gestión de proyectos, pero se encontró la necesidad de implementar el IT PPM debido a su amplia cobertura de procesos End-to-End en Proyectos de IT, y la manera de asegurar la maximización de los beneficios. Con la investigación teórica y el análisis del estudio de caso, la tesis concluye con una definición práctica de un modelo aproximado IT PPM como una recomendación para su implementación en el Departamento de Gestión de Proyectos.

Is it always good to let universities select their students?

We undertake a first step to investigating a reform that has been applied in numerous universities across Europe: the right to select students. We ask to what extent this right will increase the efficiency of the university. While it seems evident that giving universities the right to select students that match best with the human capital of professors should increase efficiency measures in the productivities of students in the labor market, we point to a potentially negative efect. We argue that allowing universities to select the students they prefer can reduce the incentives of the universities to improve the human capital of their professors.