There has been an increasing demand for commercial organisations to foster real-time interaction with customers, because harnessing customer competencies has been shown to be a major contributor towards various benefits, such as growth, innovation and competition. This may drive organisations to embrace the development of multimodal interaction and complement Electronic Customer Knowledge Management Systems (E-CKMS) with metaphors of audio-visual nature. Although the implementation of E-CKMS encounters several challenges, such as lack of trust and information overload, few empirical studies were devoted to assess the role of audio-visual metaphors, and investigate whether these technologies can be put into practice. Therefore, this thesis describes a comparative evaluation study carried out to examine the implication of incorporating multimodal metaphors into E-CKMS interfaces on not only usability of E-CKMS, but also the user¿s trust, knowledge and acceptance. An experimental E-CKMS platform was implemented with three different modes of interaction: Visual-only E-CKMS (VCKMS) with text and graphics, Multimodal E-CKMS (MCKMS) with speech, earcons and auditory icons and Avatar-enhanced multimodal E-CKMS (ACKMS). The three platforms were evaluated by three independent groups of twenty participants each (total=60) who carried out eight common tasks of increasing complexity and design based on three different styles. Another dependent group of forty-eight participants (n=48) was instructed to interact with the systems under similar usability conditions by performing six common tasks of two styles, and fill a questionnaire devised to measure the aspects of user acceptance. The results therein revealed that ACKMS was more usable and acceptable than both MCKMS and VCKMS, whereas MCKMS was more usable than VCKMS, but less acceptable. Inferential Statistics indicated that these results were statistically significant.

Detta arbete undersöker temperaturdynamiken och sluttemperaturen hos ledare iinstallationskablar för olika fall av belastningsström. En laborativ model och entidsstegande numerisk modell har skapats och jämförts. Resultaten jämförs med denmärkström som ges i installationsstandarder, och även med de överlastnivåer somkan tolereras av säkringar och strömbrytare enlig Europeiska standarder.Exempel på användningsområden för studiens resultat är kabelklassificeringar medtillfälliga laster, och potentiell överlast på grund av tung belastning kombineratmed extra matningar till en krets (t.ex. inkopplad solkraft). De studerade kablarnavar fyllda och ofyllda 3-ledarkablar (varav 2 belastade) med PEX-isolering, allamed 1,5 mm2 kopparledare (EQLQ 3G 1,5 mm2). De testades fritt i luft och i ensektion av värmeisolerad vägg. Strömmar applicerades från en styrbar likströmskälla.Ledarens temperatur mättes genom att logga spänningsfallet över en cirka 10 cmlång ledarsektion, med tanke på resistansens temperaturkoefficient. Denna metodverifierades genom tester i ett värmeskåp.Resultaten visade att ledarna maximalt nådde 92 % av den tillåtna drifttemperaturen(90 ◦C) vid 150 % belastning av typisk säkringsstorlek. Kombinerat med extramatningar nådde den maximala temperaturen 118 % av drifttemperaturen vid 170 %belastning av typisk säkringsstorlek. Resultaten visade också en temperaturskillnadmellan horisontella och vertikala förläggningar, som varierade från 3-10 ◦C högre idet vertikala fallet, beroende på belastning och kabel. / This work examines the temperature dynamics and final temperature of conductorsin electrical installation cables, for various cases of load current. A laboratory modeland a time-stepping numerical model have been made and compared. Results arecompared with the ampacity given in installation standards, and also with theoverload levels that could be sustained by fuses and circuit breakers, followingEuropean standards.Examples of use-cases for the study’s results are cable ratings with intermittentloads, and potential overload due to heavy load combined with extra infeeds intoa circuit (e.g. plug-in solar power). The studied cables were filled and non filled 3-conductor (of which 2 loaded) PEX insulated installation cables, all with 1.5 mm2copper conductors (EQLQ 3G 1.5mm2). They were tested in open air and in a sectionof insulated cavity wall. Currents were applied from a controlled dc current source.The conductor temperature was measured by logging the voltage drop across a 10 cmlength of conductor, bearing in mind the temperature coefficient of resistance. Thismethod was verified by tests in a heating chamber.Results showed that conductors reached a maximum of 92 % of the permissibleoperating temperature (90 ◦C) at 150 % load of typical fuse-size. Combined withextra infeeds the maximum temperature reached 118 % of operating temperatureat 170 % load of typical fuse-size. The results also showed a temperature differencebetween horizontal and vertical orientations, varying from 3-10 ◦C higher in thevertical scenario, depending on load and cable

Thesis (MSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Computer-based virtual worlds are increasingly used for activities which previously required physical environments. However, in its mainstream form, such a virtual world provides output on a graphical display and is thus inaccessible to a blind user. To achieve accessibility for blind users, an alternative to graphical output must be used. Audio and text are two output methods that can be considered. However, when using audio, care must be taken not to overload the audio channel. Channel overloading is possible with audio since it is not a selective output medium like the visual channel, that is, the user cannot choose what he/she wants to hear. Text should also be treated as audio, since a blind user consumes textual information as synthesized speech. In this research we discuss one possible solution to the problem of channel overloading, by the use of multiple exploration and navigation tools. These tools should allow the user to shape the information provided as audio output. Specially, we discuss the development of a virtual world client called Perspective, enabling non-visual access to virtual worlds by the use of multiple navigation and exploration tools. Perspective also serves as a framework for tool implementation and evaluation. Finally we give recommendations for improvements to current virtual world building practices and protocols, as to work toward an accessibility standard. / AFRIKAANSE OPSOMMING: Rekenaargebaseerde virtuele wêrelde word toenemend gebruik vir aktiwiteite wat voorheen fiesiese omgewings benodig het. Tog verskaf so 'n virtuele wêreld, in sy standaard vorm, afvoer as 'n grafiese beeld en is dus ontoeganklik vir 'n blinde gebruiker. Om toeganklikheid vir blinde gebruikers te bewerkstellig, moet 'n alternatief vir die grafiese beeld gebruik word. Klank en teks is twee alternatiewe wat beskou kan word. Tog moet klank versigtig gebruik word, aangesien die klankkanaal oorlaai kan word. Die klankkanaal kan oorlaai word aangesien dit nie 'n selektiewe kanaal soos die visuele kanaal is nie, met ander woorde, die gebruiker kan nie kies wat hy/sy wil hoor nie. Teks moet ook as klank beskou word, aangesien 'n blinde gebruiker teks in die vorm van gesintetiseerde spraak inneem. Met hierdie navorsing bespreek ons een oplossing vir die probleem van kanaaloorlading, deur die gebruik van verskeie navigasie- en verkenningsgereedskapstukke. Hierdie gereedskapstukke behoort die gebruiker in staat te stel om die inligting wat as klank oorgedra word, te bepaal. Ons bespreek spesi ek die ontwikkeling van 'n virtuele wêreld-kliënt genaamd Perspective, wat nie-visuele toegang tot virtuele wêrelde bewerkstellig deur die gebruik van meervoudige navigasie- en verkenningsgereedskapstukke. Perspective dien ook as 'n raamwerk vir die ontwikkeling en evaluering van gereedskapstukke. Laastens verskaf ons voorstelle vir verbeteringe van die boutegnieke en protokolle van huidige virtuele wêrelde, as eerste stap na 'n toeganklikheidsstandaard vir virtuele wêrelde.

Thesis (MMed)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: There is growing interest in how genetic and environmental risk factors interact to confer risk for dysregulated iron homeostasis, which is considered a possible pathogenic mechanism in multiple sclerosis (MS). While iron deficiency has been associated with greater disability and disease progression, cerebral accumulation and overload of insoluble iron has also been reported in MS patients. Variation in the matriptase-2 (TMPRSS6) gene has recently been described that may lead to reduced iron levels, which raised the question of whether it may be involved in dysfunctional iron regulation as a pathogenic mechanism in MS. The aims of the study were as follows: 1)) comparison of the allele frequencies and genotype distribution for TMPRSS6 A736V (rs855791, c.2207C>T) and HFE C282Y (rs1800562, c.845G>A) between patients diagnosed with MS and unaffected controls; 2) determination of the effects of clinical characteristics, relevant lifestyle factors and genotype on serum iron parameters in MS patients compared to population matched controls; and 3) determination of clinical outcome in relation to age of onset and degree of disability in MS patients. The study population included 121 Caucasian MS patients and 286 population-matched controls. Serum iron, transferrin, ferritin and transferrin saturation levels were available from previous studies and lifestyle factors were subsequently documented in a subgroup of 68 MS patients and 143 controls using the study questionnaire. Genotyping of TMPRSS6 A736V and HFE C282Y were performed using allele-specific TaqMan technology. The genotype distribution and allele frequencies of TMPRSS6 A736V and HFE C282Y did not differ between MS patients and controls. MS patients homozygous for the iron-lowering minor T-allele of TMPRSS6 A736V had significantly lower serum iron levels (p=0.03) and transferrin saturation levels (p=0.03) compared to CC homozygotes. In MS patients the iron-loading minor A-allele of HFE C282Y was also associated with a paradoxical decrease in serum ferritin (p<0.01) compared to GG homozygotes. When considering the combined effect of the minor alleles of TMPRSS6 A736V and HFE C282Y with opposite effects on iron levels, we found a significant reduction in serum ferritin levels (p<0.05), independent of age, sex, body mass index (BMI) or dietary red meat intake in MS patients. A similar effect was not observed in the population- and age-matched controls. Higher dietary red meat intake correlated significantly with increased ferritin only in controls (p=0.01 vs. 0.21 for MS patients). In the presence of the minor allele of HFE C282Y, the TMPRSS6 A736V CT and TT genotypes were associated with a significantly earlier age of onset of MS when the post hoc test was applied (p=0.04). All the study aims were successfully accomplished. Our results support the possibility of an epistatic effect between TMPRSS6 A736V and HFE C282Y associated with reduced ferritin levels in MS patients. Pathology-supported genetic testing (PSGT) applied in this study as a new concept for analysis of complex diseases with a genetic component, is well placed to optimise clinical management in patients with MS. / AFRIKAANSE OPSOMMING: Daar heers toenemende belangstelling in hoe die wisselwerking tussen genetiese en omgewingsfaktore die risiko tot wanregulering van yster-homeostase beïnvloed. Laasgenoemde is ‘n moontlike patogeniese meganisme vir meervoudige sklerose (MS). Alhoewel verhoogde gestremdheid en siekteprogressie met ystertekort geassosieer is, is ysterophoping in die serebrum asook ‘n oormaat onoplosbare yster al by MS-pasiënte gevind. Variasie in die matriptase-2 (TMPRSS6) geen wat tot verlaging in ystervlakke kan lei, is onlangs beskryf en laat die vraag ontstaan of dit betrokke is by wanregulering van yster-homeostase as patogeniese meganisme in MS. Die doelwitte van die studie was as volg: 1) vergelyking van alleelfrekwensies en genotipeverspreiding vir TMPRSS6 A736V (rs855791, c.2207C>T) en HFE C282Y (rs1800562, c.845G>A) tussen MS-pasiënte en ongeaffekteerde kontroles; 3) bepaling van die effekte van kliniese indikators, relevante leefstylfaktore en genotipe op serum yster parameters in MS-pasiënte in vergelyking met populasie-ooreenstemmende kontroles; en 4) bepaling van kliniese uitkoms ten opsigte van aanvangsouderdom en graad van MS-aantasting. Die studiepopulasie het uit 121 kaukasiese MS-pasiënte en 286 kontroles van dieselfde populasie, wat nie die siekte het nie, bestaan. Serum yster, transferrin, ferritien en transferrien-versadigingsvlakke was beskikbaar vanaf vorige studies. Leefstylfaktore is in ‘n subgroep van 68 MS-pasiënte en 143 kontroles gedokumenteer met behulp van die studie-vraelys. TMPRSS6 A736V en HFE C282Y genotipering is met alleel-spesifieke TaqMan-tegnologie uitgevoer. Beide pasiënte en kontroles het dieselfde genotipeverspreiding en alleelfrekwensies getoon. Die A-alleel van HFE C282Y is met ‘n paradoksale verlaging in serum ferritien geassosieer (p<0.01) in MS-pasiënte met TMPRSS6 A736V, moontlik weens geen-geen interaksie wat nie deur ouderdom, liggaamsmassa-indeks of inname van rooivleis in die dieet beïnvloed is nie (p<0.05) en nie by kontroles gevind is nie. MS-pasiënte wat homosigoties is vir die T-alleel van TMPRSS6 A736V, het statisties betekenisvolle laer serum ystervlakke (p=0.03) en transferrienversadiging (p=0.03) getoon in vergelyking met CC-homosigote. In MS-pasiënte was die yster-oorlading A-alleel van HFE C282Y ook geassosieer met ‘n paradoksale afname in serum ferritien (p<0.01) in vergelyking met GG-homosigote. Wanneer die gekombineerde effek van die risiko-geassosieerde allele van TMPRSS6 A736V en HFE C282Y met teenoorgestelde effekte op ystervlakke geanaliseer word, is daar ‘n statisties beteknisvolle afname in serum ferritienvlakke (p<0.05), onafhanklik van ouderdom, geslag, liggaamsmassa-indeks of rooivleisinname in MS-pasiënte. ‘n Soortgelyke effek is nie waargeneem in populasie- en geslag-gelyke kontroles nie. Die inname van rooivleis in die dieet was betekenisvol minder by MS-pasiënte teenoor kontroles (p=0.03) en dit het slegs betekenisvol met verhoogde ferritien by kontroles gekorreleer (p=0.01 teenoor 0.21 by MS-pasiënte). In die teenwoordigheid van die risiko-geassosieerde alleel van HFE C282Y, is die TMPRSS6 A736V CT en TT genotipes geassosieer met ‘n statisties-betekenisvolle vroeër aanvangsouderdom van MS soos bepaal met die post hoc-toets (p=0.04). Al die doelwitte van die studie is suksesvol uitgevoer. Die resultate ondersteun die moontlikheid van ‘n epistatiese effek tussen TMPRSS6 A736V en HFE C282Y wat geassosieer is met ‘n verlaging in ferritienvlakke in MS-pasiënte. Patologie-gesteunde genetiese toetsing soos toegepas in hierdie studie as ‘n nuwe konsep vir analise van komplekse siektes met ‘n genetiese komponent, is goed geplaas om kliniese hantering van MS-pasiënte te optimaliseer.

摘要 本研究從新奇追求動機探討遊客對旅遊產品的態度會被什麼因素所影響。許多學者提到，遊客對於新奇追求的差異，會影響他們選擇不同觀光活動及旅遊目的地的決策，因此旅遊行程有否提供遊客新奇的體驗（亦即新奇屬性）或是基於旅遊產品本身的新奇性，應能吸引不同新奇追求程度的遊客前往旅遊。然而以往關於新奇屬性的研究多針對實體產品，鮮少從服務性產品的面向做探討，文獻中對旅遊產品新奇性的描述亦甚少著墨，因此本研究藉由操弄新奇屬性和產品新奇性，從旅遊產品的角度觀察對於不同新奇追求程度的遊客之態度會產生什麼影響。 研究結果發現，旅遊行程加入新奇屬性或是產品新奇性較高的旅遊產品並不一定能讓遊客對有較好的印象。當面對無新奇屬性的旅遊行程或低新奇性產品（團體旅遊）時，低新奇追求的遊客相較於高新奇追求的遊客有更好的態度，但其同時對有新奇屬性的旅遊行程及高新奇性產品（自由行）也抱持同樣的好感；而面對有新奇屬性的旅遊行程或高新奇產品（自由行）時，高新奇追求的遊客則相對較有提升好感的趨勢。值得注意的是，當旅遊產品為高新奇性（自由行）並同時搭配具有新奇屬性的旅遊行程後，反而會使消費者發生資訊過載的情形進而提高學習成本，導致消費者對產品的評價混淆甚至產生負面態度。 因此，如果廠商想要在市場上推出新產品，以適度的新奇性做為產品設計的主軸是較為理想的選擇，例如自由行對於高、低新奇追求程度的消費者都具有一定的吸引力，或是團體旅遊搭配具有新奇屬性的旅遊行程亦是保險的組合方式。要注意的是，過多的新奇資訊同時也會增加消費者的學習成本，一旦造成消費者的資訊超載，反而會造成負面的效果。 / This research focuses on what factors based on novelty seeking will be influencing tourists’ attitude toward the tourism product. Many scholars have already mentioned that different degree of novelty seeking among tourists may influence their choices of different sightseeing activities and trip destination. Therefore, whether the travel programs provide novel experiences to the tourists(namely novel attributes) or any novelty of the product itself should be able to attract tourists with different degree of novelty seeking. However, researches on novel attributes in the past mostly put emphasis on substantial products and seldom discussed on service products. In addition, there is a lack of literature regarding product novelty as well. For these reasons, the purpose of this research is to observe the factors which influence attitudes of tourists with different degree of novelty seeking by means of manipulating novel attributes and product novelty. The result of this research shows that travel journey with novel attributes or just a tourism product with high degree of novelty don’t necessarily make better impressions on tourists. When facing travel journey with no novel attributes or just a product with low degree of novelty (package tour), tourists with low degree of novelty seeking show more favor towards the product than those with high degree of novelty seeking, but they as well have positive attitude when there is travel journey with novel attributes or just a product with high degree of novelty (semi-independent travel). On the other hand, the tourists with high degree of novelty seeking comparatively tend to show preference for the travel journey with novel attributes or just a product with high degree of novelty (semi-independent travel). Here what calls our attention is that, when the tourism product is with high degree of novelty (semi-independent travel) and is combined with the travel journey with novel attributes at the same time, it may cause information overload for consumers thus raise their learning cost instead. This even causes consumers to produce negative or confused attitude when evaluating the product. Hence, for the (tourism product) suppliers who want to release new products to the market, I suggest that product design should be emphasize on adding appropriate novelty. For example, semi-independent travel attracts consumers with both high and low degree of novelty seeking; tour package with novel attributes is also safe for tourists. What we should be aware of is that too much novel information increases consumer’s learning cost, and once it causes consumer’s information to overload, it may cause negative effect instead.

Syfte och frågeställning Syftet med denna studie är att identifiera effekten av svänghjulsträning på styrkerelaterade variabler som påverkar idrottslig prestation genom en sammanställning av befintlig vetenskaplig litteratur. Studiens frågeställning var: (1) Vilken effekt har svänghjulsträning på muskeltillväxt (hypertrofi)? (2) Vilken effekt har svänghjulsträning på utvecklingen av maximal styrka? (3) Vilken effekt har svänghjulsträning på utvecklingen av Power (effektutveckling)? (4) Vilken effekt har svänghjulsträning på horisontell förflyttning? (5) Vilken effekt har svänghjulsträning på vertikal förflyttning? Metod En metaanalys för 15 experimentella studier som uppfyllt urvalskriterierna genomfördes. De inkluderade studierna kvalitetsgranskades med Pedros skala. För att möjliggöra en sammanställning av samtliga resultat analyserades resultaten i dataprogrammet Review Manager version 5.3 med Random effekt modell och presenteras med Forest plots. Jämförelserna gjordes över en period på 4-24 veckor. Resultat Svänghjulsträning under en period av 4-24 veckor visar på en statistisk signifikant utveckling  av muskulär hypertrofi (effektstorlek 0,68), maximal styrka (1,40), Power (1,0), horisontell (0,54) och vertikal förflyttning (0,60). Slutsats Det finns stöd i litteraturen för att friska individer presterar bättre på så väl dynamiska styrketest som funktionella test efter svänghjulsträning. Evidensen är särskilt stark för att svänghjulsträning utvecklar maximal styrka och Power för tränade yngre individer samt i kortare mer intensiva block. Denna metaanalys har bara sammanställt skillnader i prestation före och efter svänghjulsträning och kan därför inte säga om effekten av svänghjulsträning är större än effekten av upprepade mätningar eller annan träning. / Aim The aim of this study was to identify the effect of the flywheel training on strength-related variables that affect athletic performance by compiling existing scientific literature. Research questions: (1) What effect does flywheel training have on muscle growth (hypertrophy)? (2) What effect does flywheel training have on the development of maximum strength? (3) What effect does flywheel training have on the development of Power (effect development)? (4) What effect does flywheel training have on the development of horizontal movement? (5) What effect does flywheel training have on the development of vertical movement? Method A meta-analysis was conducted from 15 experimental studies that met the selection criteria. The quality of included studies was reviewed by Pedro scale. In order to identify possible bias in the selection process a Funnel plot was carried out. To enable the compilation of all results an analyze with Random effect model was carried out with software Review Manager Version 5.3 and presented with Forest plots. Comparisons were made over a period of 4-24 weeks. Results Flywheel training for a period of 4-24 weeks show a statistically significant increase in effect size for muscular hypertrophy (0,49), maximum strength (1,40), Power (1,00), horizontal-(0,54) and vertical movement (0,60). Conclusions There's support in published studies that healthy individuals perform better on dynamic strength tests as wells as functional test after flywheel training. The evidence is particularly strong that flywheel training develops maximum strength and Power in trained younger individuals and in shorter more intensive blocks. This meta-analysis has just compiled the differences in performance before and after flywheel training and therefore cannot say if the effect of flywheel training is greater than the effect of repeated measurements or other exercise.

L’hémoglobine est une protéine contenue dans les globules rouges dont la principale fonction est le transport de l’oxygène. Chaque molécule d’hémoglobine est un tétramère constitué de deux paires de globines identiques de type α et β. La β-thalassémie est une maladie génétique hématopoïétique provenant de mutations du gène encodant l'hémoglobine. Ce désordre se caractérise par une diminution ou une absence totale de la synthèse de la chaîne β-globine résultant principalement en une anémie hémolytique sévère ainsi que des complications multisystémiques, telles que la splénomégalie, des déformations osseuses et une dysfonction hépatique et rénale. Actuellement, les transfusions sanguines chroniques représentent le traitement standard des patients β-thalassémiques. Cette thérapie nécessite l’administration conjointe d’un traitement chélateur de fer puisqu’elle entraîne une accumulation pathologique du fer, considéré à ce jour comme la source principale des complications cardiovasculaires de la β-thalassémie. Néanmoins, malgré le traitement efficace de la surcharge de fer transfusionnelle, l’insuffisance cardiaque demeure encore la principale cause de mortalité chez les patients atteints de β-thalassémie. Cette observation indique possiblement la présence d’un mécanisme complémentaire dans le développement de la physiopathologie cardiaque β-thalassémique. L’objectif du présent projet consistait donc à étudier les altérations cardiovasculaires de la β-thalassémie indépendamment de la surcharge de fer transfusionnelle. En utilisant un modèle murin non-transfusé de la β-thalassémie majeure, nous avons d’abord évalué in vivo, par méthode d’imagerie novatrice échographique à haute fréquence, les propriétés hémodynamiques vasculaires. Nos résultats d’index de Pourcelot ainsi que de résistance vasculaire périphérique totale ont démontré une perturbation de l’écoulement microcirculatoire chez les souris β-thalassémiques non-transfusées. Subséquemment, nous avons étudié la fonction endothéliale de régulation du tonus vasculaire de vaisseaux mésentériques isolés. Nos résultats ont révélé un dysfonctionnement de la réponse vasodilatatrice dépendante de l’endothélium chez les souris β-thalassémiques malgré une augmentation de l’expression de l’enzyme de synthèse du monoxyde d’azote ainsi qu’un remodelage de la carotide commune caractérisé par un épaississement de la paroi vasculaire. Finalement, notre étude échocardiographique de la fonction et la morphologie cardiaque a montré, chez les souris β-thalassémiques, le développement d’une hypertrophie et une dysfonction ventriculaire gauche en l’absence de transfusions sanguines chroniques ou de dépôts directs de fer dans le myocarde. L’ensemble des résultats présentés dans le cadre de cette thèse indique la présence d’une pathologie cardiovasculaire chez les souris β-thalassémiques non-transfusés. Nos travaux permettent de proposer un mécanisme de la pathophysiologie cardiovasculaire β-thalassémique, indépendant de la charge de fer transfusionnelle, impliquant les effets compensatoires d’une anémie chronique combinés à une vasculopathie complexe initiée par les érythrocytes endommagés et l’hémolyse intravasculaire. / Hemoglobin is the major protein in red blood cells and is responsible of the oxygen transport. Each hemoglobin molecule is a tetramer consisting of two identical α- and β-globin subunits. β-thalassemia is a genetic hematopoietic disease caused by mutations in hemoglobin genes. This disorder is characterized by a decrease or absence of production of β-globin chain leading mainly to a severe hemolytic anemia and several systemic manifestations, including splenomegaly, skeletal deformities as well as hepatic and renal dysfunctions. Chronic blood transfusions remain the standard treatment for β-thalassemic patients. This therapy requires iron chelating management since it leads to pathological iron accumulation which is currently considered the main cause of cardiovascular complications of β-thalassemia. However, despite adequate control of transfusional iron loading, heart failure remains the leading cause of mortality in β-thalassemia. This issue is possibly indicative of additional pathogenic mechanisms underlying the development of the β-thalassemic cardiac pathology. The objective of the present research project was to study cardiovascular alterations of β-thalassemia independently of transfusional iron overloading. Using an untransfused murine model of β-thalassemia major, we have evaluated in vivo, by non-invasive high-frequency ultrasound imaging, vascular hemodynamic properties. Our results of Pourcelot indices and total peripheral vascular resistance have shown microcirculatory flow disturbances in untransfused β-thalassemic mice. Consequently, we have studied ex vivo the endothelial vasomotor function in isolated mesenteric arterioles. Our findings have pointed out endothelium-dependent vasodilator dysfunction in β-thalassemic mice despite increased expression of nitric oxide synthase, as well as remodeling of the common carotid artery wall. Lastly, our echocardiography studies of heart morphology and function in β-thalassemic mice have demonstrated the development of left ventricle hypertrophy and dysfunction in the absence of chronic blood transfusions or direct myocardial iron deposits. In conclusion, findings presented in this thesis have demonstrated for the first time development of severe cardiovascular complications in untransfused β-thalassemic mice. Based on our results, we have proposed a novel mechanism, independent of direct myocardial iron deposition, responsible for the cardiovascular complications in β-thalassemia. This model combines compensatory effects of chronic anemia with a complex vasculopathy initiated by abnormal erythrocytes and intravascular hemolysis.

La production de radicaux libres oxygénés (ROS), la surcharge calcique cytosolique et l’ouverture des pores de transition membranaires mitochondriales (mPTP) consécutives à l’ischémie myocardique (IM) sont aggravées lors de la reperfusion. Dans cette thèse, nous nous sommes intéressés : 1) à l’évaluation des effets de la trimétazidine sur le seuil électrique de fibrillation ventriculaire (VFT) et sur les lésions structurales et fonctionnelles des mitochondries lors de l’IM (étude 1, N=26 porcs); 2) à la détermination de la cinétique d’évolution des lésions d’ischémie/reperfusion (I/R) (étude 2a, N=30 porcs) ;3) à l’étude de l’impact de la ranolazine, du propranolol et de leur association dans la préventions des lésions d’I/R (étude 2b, N=30 porcs). Ces études qui ont été réalisées sur le cœur de porcs anesthésiés, ont permis de suivre l’évolution des paramètres électrophysiologiques et hémodynamiques cardiaques et, à l’échelle cellulaire, l’évolution de la structure et de la fonction des mitochondries. Les résultats montrent : 1) dans l’étude 1 : que la TMZ prévient la chute du VFT et l’ensemble des altérations structurales et fonctionnelles mitochondriales observées lors de l’IM ; 2) dans l’étude 2a : que les lésions observées durant l’IM sont significativement aggravées dans les premières dizaines de secondes de la reperfusion alors qu’une certaine amélioration est observée après 10 et surtout 45 min de reperfusion; 3) dans l’étude 2b : qu’un prétraitement par de la ranolazine, du propranolol et par leur association réduit la sévérité de ces lésions d’I/R. Les mécanismes moléculaires et cellulaires d’action des produits utilisés dans cette étude seraient en rapport avec l’amélioration des lésions de l’I/R / The generation of reactive oxygen species (ROS), the cytosolic calcium overload and the opening of mitochondrial permeability transition pores (mPTP) resulting from myocardial ischemia (MI) are aggravated during reperfusion. In the present work, the following points have been addressed: 1) the evaluation of trimetazidine effects on the electrical threshold of ventricular fibrillation (VFT) and both structural and functional alterations of mitochondria during MI (study 1, N=26 pigs); 2) the determination of the kinetics of ischemia/reperfusion (I/R) lesions (study 2a, N=30 pigs); 3) the protective effects of ranolazine and propranolol, alone or combined on I/R lesions (study 2b, N=30 pigs). All studies were performed in anesthetized pigs. They allowed to follow changes in cardiac electrophysiological and hemodynamic parameters and, at the cellular level, changes in the structure and function of mitochondria. The obtained results show: 1) in study 1, that TMZ can prevent the drop in VFT and all structural and functional alterations of mitochondria noticed during MI; 2) in study 2a, that the lesions seen during MI are significantly aggravated within the first seconds of reperfusion whereas some improvement is observed after 10 minutes and more markedly after 45 minutes of reperfusion; 3) in study 2b, that pretreatment with ranolazine or propranolol, alone or combined can reduce the severity of I/R lesions. The molecular and cellular mechanisms of action of both agents are thought to be involved in this improvement of I/R lesions

Made available in DSpace on 2016-01-26T12:51:18Z (GMT). No. of bitstreams: 1 claudiathomebeletti_dissert.pdf: 580160 bytes, checksum: 663a2cdc74524cec05b176a5c247317d (MD5) Previous issue date: 2007-10-30 / Chronic daily headache (CDH) can be studied according to the psychosomatic perspective. Considering that CDH is a heterogeneous group of headaches and that some comorbidity and emotional factors can trigger the pain such as stress, anxiety and depression; a study that takes into account the emotional overload and its impact on the affected people's lives is very important. Objective: This research aims to investigate the presence of emotional overload in patients with CDH, and the possible reasons which may impair the symptoms as well as to know which are the psychological, social and existential aspects developed by these people. Casuistic and Method: The subjects of this study were 40 patients of both genders, over 18 years of age, who attended the headache clinic of Hospital de Base, Medical School of S?o Jos? do Rio Preto. A semi-structured interview as reference to the Psychosomatic Psychoanalytic Investigation was used. Results: The sample comprised 10% of males and 90% of females, the ages ranging from 24 to 64 years old. Since the majority of interviews were made up of open questions, it was decided to divide the answers into categories. The most frequent categories when they knew the meaning of getting sick were: psychical suffering (35.53%); physical suffering (23.68%); damage at work (19.74%) and social damage (10.52%). Regarding the question about factors related with pain, the main categories were: nervousness (23.16%); preoccupation (15.79%) and tension (11.58%). The question on how the pain was developed, the most frequent categories were: the attempt at self-cure (27.36%), different kinds of pain (16.98%) and affected by emotions (13.2%). The question on the consequences of the pain, the majority reported the interruption of their activities. The length-time of the disease varied between 2 and 40 years with headaches. It was also observed, if the patients with CDH had diagnosis hypotheses regarding their pains or a "personal insight" on the disease. Among them, psychical factors could trigger the pain with 48.84%, and 34.88% of them did not have hypothesis regarding their headaches. Conclusions: In conclusion, there is some emotional overload in patients with CDH, and the typical performance of the psychosomatic disorders and the operating mind control is directly related with the patient?s complaints. It was also observed aspects of depression associated with the emotional functioning of these people. / A cefal?ia cr?nica di?ria (CCD) pode ser estudada de acordo com a perspectiva psicossom?tica. Considerando-se que a CCD ? um grupo heterog?neo de cefal?ias e que algumas comorbidades e fatores emocionais est?o associados como precipitantes da dor, tais como o estresse, a ansiedade e a depress?o; um estudo que leve em conta a sobrecarga emocional e qual o impacto na vida das pessoas afetadas reveste-se de import?ncia. Objetivo: A presente pesquisa visa investigar presen?a de sobrecarga emocional de pacientes portadores de CCD, e os poss?veis motivos agravadores de sintomas, bem como conhecer quais os percursos psicol?gicos, sociais e existenciais desenvolvidos por esses indiv?duos. Casu?stica e M?todo: S?o sujeitos deste estudo 40 pacientes de ambos os sexos, maiores de 18 anos, atendidos no ambulat?rio de cefal?ias do Hospital de Base de S?o Jos? do Rio Preto. Foi utilizado um roteiro de entrevista semi-estruturada, tendo como refer?ncia a Investiga??o Psicossom?tica Psicanal?tica. Resultados: A amostra foi composta por 10% dos sujeitos do sexo masculino e 90% do sexo feminino, com idades variando entre 24 e 64 anos. Por se tratar de entrevistas compostas, em sua maioria por quest?es abertas, optou-se por distribuir as respostas em categorias. Ao conhecer o significado de adoecer, as categorias que mais apareceram foram: sofrimento ps?quico (35,53%); sofrimento f?sico (23,68%); preju?zo no trabalho (19,74%) e preju?zo social (10,52%). Quanto ao questionamento com os fatores que relacionavam a dor, as principais categorias foram: o nervosismo (23,16%); preocupa??o (15,79%) e tens?o (11,58%). Na investiga??o de como se desenvolvia a dor, o que mais se verificou foram: tentativas de auto-cura (27,36%); diferentes tipos de dor (16,98%) e provocadas pelas emo??es (13,2%). A quest?o referente ?s conseq??ncias acarretadas pela dor mostrou que a grande maioria descreveu interromper as atividades. O tempo de doen?a variou entre dois e mais de quarenta anos de dores de cabe?a. Foi observado, ainda, se os portadores de CCD t?m hip?teses diagn?sticas a respeito das suas dores ou ?insight? pessoal sobre a doen?a. Entre elas, fatores ps?quicos poderiam desencadear a dor com 48,84% e 34,88% n?o t?m hip?tese a respeito das suas dores de cabe?a. Conclus?es: Pode-se concluir que existe sobrecarga emocional em pacientes portadores de CCD, e que o funcionamento caracter?stico dos transtornos psicossom?ticos e do pensamento operat?rio est? diretamente relacionado com suas queixas. Tamb?m foram observados aspectos de depress?o relacionados ao funcionamento emocional desses indiv?duos.

Resumo: Com a necessidade de atender com qualidade a crescente demanda por energia eletrica, com poucas interrupcoes e com níıveis de tensao satisfatorios, e tendo em vista as restricoes ambientais existentes, que dificultam a implantacao de novos recursos aos sistemas de transmissao, como linhas, usinas, subestacoes, etc., as empresas de transmissao tem buscado otimizar os recursos existentes, operando os sistemas com menos folga o que, em alguns casos, pode ocasionar pequenas sobrecargas nas linhas. Nas estruturas atuais de operacao, acoes corretivas usualmente aplicadas ao alıvio dos sistemas de transmissao, como alteracoes nos nıveis de geracao e corte de cargas, fazem parte das atribuicoes do operador do sistema e estao fora do escopo de acao das empresas transmissoras que podem, contudo, alterar as condicoes de operacao de seus dispositivos, como transformadores, compensadores, etc. Neste trabalho e apresentada uma proposta para o alıvio de pequenas sobrecargas em redes de transmissao com base no controle do fluxo reativo das linhas. As acoes corretivas sao determinadas com base na linearizacao dos parametros do sistema em torno de seu ponto de operacao inicial, solucionando-se um problema de programacao linear (PL) cuja funcao objetivo a ser minimizada e o produto entre o custo dos servicos de suporte de reativos prestados pelos dispositivos e o desvio do sistema de seu ponto de operacao inicial. Haja vista a grande quantidade de dispositivos instalados no sistema que podem fornecer servicos de suporte de reativos e que problemas relativos a potencia reativa sao solucionados localmente, e possıvel reduzir a quantidade de dispositivos "candidatos" a realizacao das acoes corretivas e, consequentemente, o numero de variaveis e restricoes no PL a ser solucionado... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The growing demand for electric power associated with the environmental limitations imposed to the expansion of power systems hamper the installation of new facilities, such as transmission lines, substations and power plants, and leads the transmission companies to optimize the existing resources. In consequence, transmission systems operate closer to their boundaries and small overloads may surge. In the deregulated operating environment, the standard overload relief procedures, based on generation redispatch and load shedding, are in charge of the system operator and cannot be performed by the transmission companies, which can, otherwise, modify the control parameters of the transmission system devices, such as transformers, shunt compensators, etc. An overload relief procedure based on reactive power control applicable to small disturbances is presented in this paper. The corrective actions are determined by linearizing the system parameters around the initial operating point and solving a linear problem (LP), that minimizes the product between the total cost of the reactive power support provided by the devices and the deviation of the system from its initial operating point. Considering that reactive sources are spread over the whole system and the solution for reactive power problems can be found locally, the set of devices to be applied for the corrective actions can be reduced and, consequently, the number of variables and constraints to be added to the LP problem. To accomplish that, linear sensitivity factors which relate the reactive flow variation in the overloaded line to the devices' control parameters are applied and the "n" most effective devices to mitigate the overloads can be determined. In many market structures reactive power support is a mandatory service and, in some cases, it is not remunerated. However, despite the low cost of production of reactive power... (Complete abstract click electronic access below) / Orientador: Antonio Padilha Feltrin / Coorientador: Javier Contreras Sanz / Banca: Percival Bueno Araújo / Banca: Dilson Amancio Alves / Banca: Eduardo Nobuhiro Asada / Banca: Madson Cortes de Almeida / Doutor