Un projet multicentrique suisse pour améliorer la prévention et la récidive après un syndrome coronarien aigu [A Swiss multicentric project to improve the prevention of cardiovascular event recurrence after acute coronary syndromes].

Recurrence of cardiovascular events and mortality remain high after acute coronary syndromes. A Swiss multicentric study, "Inflammation and acute coronary syndromes (ACS)--Novel strategies for prevention and clinical managements", is currently underway with the support of the Swiss National Science Foundation. The study includes a clinical research subproject of which the aim is to assess the impact of the ELIPS program (multi-dimEnsionaL prevention Program after acute coronary Syndrome) on the recurrence of cardiovascular events after an ACS. The basic research sub-projects aim to investigate novel cardiovascular risk biomarkers and genetic determinants of recurrence and to study the role of stem cells after an ACS. Another sub-project will evaluate intracoronary imaging techniques and the efficacy of different types of stents.

Population based screening - the difficulty of how to do more good than harm and how to achieve it.

Screening people without symptoms of disease is an attractive idea. Screening allows early detection of disease or elevated risk of disease, and has the potential for improved treatment and reduction of mortality. The list of future screening opportunities is set to grow because of the refinement of screening techniques, the increasing frequency of degenerative and chronic diseases, and the steadily growing body of evidence on genetic predispositions for various diseases. But how should we decide on the diseases for which screening should be done and on recommendations for how it should be implemented? We use the examples of prostate cancer and genetic screening to show the importance of considering screening as an ongoing population-based intervention with beneficial and harmful effects, and not simply the use of a test. Assessing whether screening should be recommended and implemented for any named disease is therefore a multi-dimensional task in health technology assessment. There are several countries that already use established processes and criteria to assess the appropriateness of screening. We argue that the Swiss healthcare system needs a nationwide screening commission mandated to conduct appropriate evidence-based evaluation of the impact of proposed screening interventions, to issue evidence-based recommendations, and to monitor the performance of screening programmes introduced. Without explicit processes there is a danger that beneficial screening programmes could be neglected and that ineffective, and potentially harmful, screening procedures could be introduced.

Social inequalities of functioning and perceived health in Switzerland: a representative cross-sectional analysis.

Many people worldwide live with a disability, i.e. limitations in functioning. The prevalence is expected to increase due to demographic change and the growing importance of non-communicable disease and injury. To date, many epidemiological studies have used simple dichotomous measures of disability, even though the WHO's International Classification of Functioning, Disability, and Health (ICF) provides a multi-dimensional framework of functioning. We aimed to examine associations of socio-economic status (SES) and social integration in 3 core domains of functioning (impairment, pain, limitations in activity and participation) and perceived health. We conducted a secondary analysis of representative cross-sectional data of the Swiss Health Survey 2007 including 10,336 female and 8,424 male Swiss residents aged 15 or more. Guided by a theoretical ICF-based model, 4 mixed effects Poisson regressions were fitted in order to explain functioning and perceived health by indicators of SES and social integration. Analyses were stratified by age groups (15-30, 31-54, ≥55 years). In all age groups, SES and social integration were significantly associated with functional and perceived health. Among the functional domains, impairment and pain were closely related, and both were associated with limitations in activity and participation. SES, social integration and functioning were related to perceived health. We found pronounced social inequalities in functioning and perceived health, supporting our theoretical model. Social factors play a significant role in the experience of health, even in a wealthy country such as Switzerland. These findings await confirmation in other, particularly lower resourced settings.

New directions in Stochastic Multicriteria Acceptability Analysis

Decisions taken in modern organizations are often multi-dimensional, involving multiple decision makers and several criteria measured on different scales. Multiple Criteria Decision Making (MCDM) methods are designed to analyze and to give recommendations in this kind of situations. Among the numerous MCDM methods, two large families of methods are the multi-attribute utility theory based methods and the outranking methods. Traditionally both method families require exact values for technical parameters and criteria measurements, as well as for preferences expressed as weights. Often it is hard, if not impossible, to obtain exact values. Stochastic Multicriteria Acceptability Analysis (SMAA) is a family of methods designed to help in this type of situations where exact values are not available. Different variants of SMAA allow handling all types of MCDM problems. They support defining the model through uncertain, imprecise, or completely missing values. The methods are based on simulation that is applied to obtain descriptive indices characterizing the problem. In this thesis we present new advances in the SMAA methodology. We present and analyze algorithms for the SMAA-2 method and its extension to handle ordinal preferences. We then present an application of SMAA-2 to an area where MCDM models have not been applied before: planning elevator groups for high-rise buildings. Following this, we introduce two new methods to the family: SMAA-TRI that extends ELECTRE TRI for sorting problems with uncertain parameter values, and SMAA-III that extends ELECTRE III in a similar way. An efficient software implementing these two methods has been developed in conjunction with this work, and is briefly presented in this thesis. The thesis is closed with a comprehensive survey of SMAA methodology including a definition of a unified framework.

Asumisstrategian täytäntöönpano, prosessi ja kehittäminen Imatran kaupungissa

Asumisstrategia muodostaa kiinteän osan Imatran kaupungin kokonaisstrategiaa. Se laaditaan myös erillisenä strategia-asiakirjana. Tutkimuksen tavoitteena oli selvittää miten asumisstrategia toteutuu Imatran kaupungissa, mitkä tekijät tukevat asumisstrategian toteuttamista ja mitkä tekijät toimivat toteuttamisen esteinä sekämillainen asumisstrategiaprosessi on ja miten sitä voitaisiin kehittää. Tutkimus toteutettiin kvalitatiivisena tutkimuksena, jonka aineisto muodostuu asumisstrategiatyöryhmälle suunnatuista teemahaastatteluista ja käytössä olleista kaupungin strategia-asiakirjoista. Tutkimus toi esiin sen, kuinka vaikea ja monimuotoinen asumisstrategiaprosessi on sekä sen, kuinka monin eri tavoin asumisstrategiaa toteutetaan Imatran kaupungissa. Tutkimus toi esiin myös asumisstrategiaprosessiin liittyviä vahvuuksia ja heikkouksia sekä näiden, lähinnä hidasteiksi katsottavien tekijöiden poistamiseen käytettäviä kehittämiskeinoja. Tutkimuksen perusteella onnistunut strategian toteuttaminen edellyttää toimeenpanijoiden ymmärtävän strategian sisällön ja merkityksen omalle työlleen.

Divergent and narrower climatic niches characterize polyploid species of European primroses in Primula sect. Aleuritia

Aim It is hypothesized that the ecological niches of polyploids should be both distinct and broader than those of diploids - characteristics that might have allowed the successful colonization of open habitats by polyploids during the Pleistocene glacial cycles. Here, we test these hypotheses by quantifying and comparing the ecological niches and niche breadths of a group of European primroses. Location Europe. Methods We gathered georeferenced data of four related species in Primula sect. Aleuritia at different ploidy levels (diploid, tetraploid, hexaploid and octoploid) and used seven bioclimatic variables to quantify niche overlap between species by applying a series of univariate and multivariate analyses combined with modelling techniques. We also employed permutation-based tests to evaluate niche similarity between the four species. Niche breadth for each species was evaluated both in the multivariate environmental space and in geographical space. Results The four species differed significantly from each other in mono-dimensional comparisons of climatological variables and occupied distinct habitats in the multi-dimensional environmental space. The majority of the permutation-based tests either indicated that the four species differed significantly in their habitat preferences and ecological niches or did not support significant niche similarity. Furthermore, our results revealed narrower niche breadths and geographical ranges in species of P. sect. Aleuritia at higher ploidy levels. Main conclusions The detected ecological differentiation between the four species of P. sect. Aleuritia at different ploidy levels is consistent with the hypothesis that polyploids occupy distinct ecological niches that differ from those of their diploid relative. Contrary to expectations, we find that polyploid species of P. sect. Aleuritia occupy narrower environmental and geographical spaces than their diploid relative. These results on the ecological niches of closely related polyploid and diploid species highlight factors that potentially contribute to the evolution and distribution of polyploid species.

Natural aphrodisiacs: studies of commercially-available herbal recipes, and phytochemical investigation of "Erythroxylum vacciniifolium" Mart. (Erythroxylaceae) from Brazil

De tout temps, hommes et femmes ont cherché par tous les moyens à développer, préserver ou recouvrer leurs propres capacités sexuelles mais également à stimuler le désir du partenaire. L?utilisation d?aphrodisiaques naturels a été l?un des recours les plus répandus. De nos jours, la commercialisation de nouvelles "love drugs" de synthèse, e.g. Viagra®, Cialis®, Levitra®, a remis au goût du jour les aphrodisiaques classiques et à relancer la recherche sur des molécules nouvelles. La pratique croissante de l?automédication, le matraquage publicitaire sur les aphrodisiaques naturels, la prolifération sur le marché de compléments alimentaires non contrôlés et l?absence de véritable législation accroissent les risques qui pèsent sur la santé publique. Dans le but d?évaluer les risques potentiels sur le consommateur de produits aphrodisiaques commercialisés, le développement et la validation d?une méthode rapide d?analyse qualitative et quantitative de la yohimbine dans ces préparations du marché sont exposés dans la première partie de ce travail. La yohimbine est un antagoniste ?2-adrénocepteur du système nerveux central et périphérique, elle est employée depuis plus d?un siècle dans le traitement des dysfonctionnements érectiles. Cette méthode analytique utilise la chromatographie liquide couplée à l?ultraviolet et à la spectrométrie de masse (LC-UV-MS) et au total, vingt préparations aphrodisiaques ont été étudiées. La dose journalière de yohimbine mesurée s?est révélée très variable selon les produits puisqu?elle varie de 1.32 à 23.16 mg. La seconde partie de ce travail concerne l?étude phytochimique et pharmacologique d?Erythroxylum vacciniifolium Mart. (Erythroxylaceae), une plante, appelée localement catuaba, utilisée dans la médecine traditionnelle brésilienne comme tonique et aphrodisiaque. Dans un premier temps, l?extrait alcaloïdique a été analysé par chromatographie liquide haute performance (HPLC) couplée soit à un détecteur UV à barrette d?iode (LC-UV-DAD), soit à un spectromètre de masse (LC-MS), ou soit à un spectromètre de résonance magnétique nucléaire (LC-RMN). L?interprétation de ces données spectrales enregistrées en ligne a permis d?obtenir des informations structurales et d?identifier partiellement près de 24 alcaloïdes appartenant à la classe des tropanes et potentiellement originaux. Par des méthodes classiques de chromatographie liquide sur l?extrait alcaloïdique de la plante, dix sept tropanes nouveaux ont ensuite été isolés dont les catuabines et leurs dérivés, et les vaccinines. Tous ces composés sont des tropane-diols ou triols estérifiés par au moins un groupe acide 1-méthyl-1H-pyrrole-2-carboxylique. Un de ces composés a été identifié comme un tropane N-oxyde. Toutes les structures ont été déterminées par spectrométrie de masse haute résolution et spectroscopie RMN multi-dimensionnelle. Parmi les nombreux tests biologiques réalisés sur ces tropanes, seuls les tests de cytotoxicité se sont révélés faiblement positifs pour certains de ces composés.<br/><br/>Throughout the ages, men and women have incessantly pursued every means to increase, preserve or recapture their sexual capacity, or to stimulate the sexual desire of selected individuals. One of the most recurrent methods has been the use of natural aphrodisiacs. Nowadays, the commercialization of new synthetic "love drugs", e.g. Viagra®, Cialis® and Levitra®, has fascinated the public interest and has led to a reassessment of classical aphrodisiacs and to the search for new ones. The practice of self-medication by an increasing number of patients, the incessant aggressive advertising of these herbal aphrodisiacs, the invasion of the medicinal market with uncontrolled dietary supplements and the absence of real directives amplifies the potential health hazards to the community. In order to evaluate the possible risks of commercialized aphrodisiac products on consumer health, the development and validation of a rapid qualitative and quantitative method for the analysis of yohimbine in these products, is reported in the first part of the present work. Yohimbine, a pharmacologically well-characterized ?2-adrenoceptor antagonist with activity in the central and peripheral nervous system, has been used for over a century in the treatment of erectile dysfunction. The analytical method is based on liquid chromatography coupled with ultraviolet and mass spectrometry (LC-UV-MS) and in total, 20 commercially-available aphrodisiac preparations were analyzed. The amount of yohimbine measured and expressed as the maximal dose per day suggested on product labels ranged from 1.32 to 23.16 mg. The second part of this work involved the phytochemical and pharmacological investigation of Erythroxylum vacciniifolium Mart. (Erythroxylaceae), a plant used in Brazilian traditional medicine as an aphrodisiac and tonic, and locally known as catuaba. With the aim of obtaining preliminary structure information on-line, the alkaloid extract was analyzed by high performance liquid chromatography (HPLC) coupled to diode array UV detection (LC-UVDAD), to mass spectrometry (LC-MS) and to nuclear magnetic resonance spectroscopy (LCNMR). Interpretation of on-line spectroscopic data led to structure elucidation and partial identification of 24 potentially original alkaloids bearing the same tropane skeleton. Seventeen new tropane alkaloids were then isolated from the alkaloid extract of the plant, including catuabines D to I, their derivatives and vaccinines A and B. All compounds were elucidated as tropane-diol or -triol alkaloids esterified by at least one 1-methyl-1H-pyrrole-2-carboxylic acid. One of the isolated compounds was identified as a tropane alkaloid N-oxide. Their structures were determined by high resolution mass spectrometry and multi-dimensional NMR spectroscopy. Among the numerous bioassays undertaken, only the cytotoxicity tests exhibited a weak positive activity of certain compounds.

R&D Performance Analysis: Case Studies on the Challenges and Promotion of the Evaluation and Measurement of R&D

Due to the intense international competition, demanding, and sophisticated customers, and diverse transforming technological change, organizations need to renew their products and services by allocating resources on research and development (R&D). Managing R&D is complex, but vital for many organizations to survive in the dynamic, turbulent environment. Thus, the increased interest among decision-makers towards finding the right performance measures for R&D is understandable. The measures or evaluation methods of R&D performance can be utilized for multiple purposes; for strategic control, for justifying the existence of R&D, for providing information and improving activities, as well as for the purposes of motivating and benchmarking. The earlier research in the field of R&D performance analysis has generally focused on either the activities and considerable factors and dimensions - e.g. strategic perspectives, purposes of measurement, levels of analysis, types of R&D or phases of R&D process - prior to the selection of R&Dperformance measures, or on proposed principles or actual implementation of theselection or design processes of R&D performance measures or measurement systems. This study aims at integrating the consideration of essential factors anddimensions of R&D performance analysis to developed selection processes of R&D measures, which have been applied in real-world organizations. The earlier models for corporate performance measurement that can be found in the literature, are to some extent adaptable also to the development of measurement systemsand selecting the measures in R&D activities. However, it is necessary to emphasize the special aspects related to the measurement of R&D performance in a way that make the development of new approaches for especially R&D performance measure selection necessary: First, the special characteristics of R&D - such as the long time lag between the inputs and outcomes, as well as the overall complexity and difficult coordination of activities - influence the R&D performance analysis problems, such as the need for more systematic, objective, balanced and multi-dimensional approaches for R&D measure selection, as well as the incompatibility of R&D measurement systems to other corporate measurement systems and vice versa. Secondly, the above-mentioned characteristics and challenges bring forth the significance of the influencing factors and dimensions that need to be recognized in order to derive the selection criteria for measures and choose the right R&D metrics, which is the most crucial step in the measurement system development process. The main purpose of this study is to support the management and control of the research and development activities of organizations by increasing the understanding of R&D performance analysis, clarifying the main factors related to the selection of R&D measures and by providing novel types of approaches and methods for systematizing the whole strategy- and business-based selection and development process of R&D indicators.The final aim of the research is to support the management in their decision making of R&D with suitable, systematically chosen measures or evaluation methods of R&D performance. Thus, the emphasis in most sub-areas of the present research has been on the promotion of the selection and development process of R&D indicators with the help of the different tools and decision support systems, i.e. the research has normative features through providing guidelines by novel types of approaches. The gathering of data and conducting case studies in metal and electronic industry companies, in the information and communications technology (ICT) sector, and in non-profit organizations helped us to formulate a comprehensive picture of the main challenges of R&D performance analysis in different organizations, which is essential, as recognition of the most importantproblem areas is a very crucial element in the constructive research approach utilized in this study. Multiple practical benefits regarding the defined problemareas could be found in the various constructed approaches presented in this dissertation: 1) the selection of R&D measures became more systematic when compared to the empirical analysis, as it was common that there were no systematic approaches utilized in the studied organizations earlier; 2) the evaluation methods or measures of R&D chosen with the help of the developed approaches can be more directly utilized in the decision-making, because of the thorough consideration of the purpose of measurement, as well as other dimensions of measurement; 3) more balance to the set of R&D measures was desired and gained throughthe holistic approaches to the selection processes; and 4) more objectivity wasgained through organizing the selection processes, as the earlier systems were considered subjective in many organizations. Scientifically, this dissertation aims to make a contribution to the present body of knowledge of R&D performance analysis by facilitating dealing with the versatility and challenges of R&D performance analysis, as well as the factors and dimensions influencing the selection of R&D performance measures, and by integrating these aspects to the developed novel types of approaches, methods and tools in the selection processes of R&D measures, applied in real-world organizations. In the whole research, facilitation of dealing with the versatility and challenges in R&D performance analysis, as well as the factors and dimensions influencing the R&D performance measure selection are strongly integrated with the constructed approaches. Thus, the research meets the above-mentioned purposes and objectives of the dissertation from the scientific as well as from the practical point of view.

Sanomalehden lehtitilausprosessin kuvaus ja kehittäminen

Työn tavoitteena oli luoda selkeä kuvaus sanomalehden lehtitilausprosessin toiminnasta tilauksesta jakeluun sekä kartoittaa lehtitilausprosessiin liittyvät ongelmakohdat ja esittää alustavia parannus- ja kehittämisehdotuksia niiden ratkaisemiseksi. Kuvauksen rakenteen teoreettisen pohjan luo työn alussa esitetty strukturoitu analyysi eli SA-menetelmä (structured analysis), jota soveltaen varsinainen kuvaus pääosin henkilöhaastatteluista saatuihin tietoihin perustuen toteutettiin.Sanomalehden lehtitilausprosessi on hyvin laaja ja monivaiheinen prosessi. Työn yhtenä tarkoituksena olikin selventää henkilöstölle, mitä kyseisen prosessin sisällä oikein tapahtuu. Kuvausta tehtäessä havaittiin useita lehtitilausprosessiin liittyviä ongelma- ja kehittämiskohteita, joiden kuntoon saattamiseksi on työssä esitetty alustavia ratkaisuvaihtoehtoja. Diplomityön teettämisen perusteena oli halu kehittää lehtitilausprosessia tilauksesta jakeluun nykyprosessin laadun parantamiseksi.Toimenpide-ehdotuksena esitetään tutkimuksessa läpi käytyjen sekä sen pohjalta mahdollisesti ilmenevien uusien parannus- ja kehittämisehdotusten toteuttamista lähitulevaisuudessa. Näin kyetään takaamaan lehtitilausprosessin toimivuus sekä vastaamaan asiakkaiden kasvaviin tarpeisiin myös tulevaisuudessa.

Development of cardiovascular magnetic resonance imaging techniques for improved characterization of atherosclerotic disease

Atherosclerosis is a chronic cardiovascular disease that involves the thicken¬ing of the artery walls as well as the formation of plaques (lesions) causing the narrowing of the lumens, in vessels such as the aorta, the coronary and the carotid arteries. Magnetic resonance imaging (MRI) is a promising modality for the assessment of atherosclerosis, as it is a non-invasive and patient-friendly procedure that does not use ionizing radiation. MRI offers high soft tissue con¬trast already without the need of intravenous contrast media; while modifica¬tion of the MR pulse sequences allows for further adjustment of the contrast for specific diagnostic needs. As such, MRI can create angiographic images of the vessel lumens to assess stenoses at the late stage of the disease, as well as blood flow-suppressed images for the early investigation of the vessel wall and the characterization of the atherosclerotic plaques. However, despite the great technical progress that occurred over the past two decades, MRI is intrinsically a low sensitive technique and some limitations still exist in terms of accuracy and performance. A major challenge for coronary artery imaging is respiratory motion. State- of-the-art diaphragmatic navigators rely on an indirect measure of motion, per¬form a ID correction, and have long and unpredictable scan time. In response, self-navigation (SM) strategies have recently been introduced that offer 100% scan efficiency and increased ease of use. SN detects respiratory motion di¬rectly from the image data obtained at the level of the heart, and retrospectively corrects the same data before final image reconstruction. Thus, SN holds po-tential for multi-dimensional motion compensation. To this regard, this thesis presents novel SN methods that estimate 2D and 3D motion parameters from aliased sub-images that are obtained from the same raw data composing the final image. Combination of all corrected sub-images produces a final image with reduced motion artifacts for the visualization of the coronaries. The first study (section 2.2, 2D Self-Navigation with Compressed Sensing) consists of a method for 2D translational motion compensation. Here, the use of com- pressed sensing (CS) reconstruction is proposed and investigated to support motion detection by reducing aliasing artifacts. In healthy human subjects, CS demonstrated an improvement in motion detection accuracy with simula¬tions on in vivo data, while improved coronary artery visualization was demon¬strated on in vivo free-breathing acquisitions. However, the motion of the heart induced by respiration has been shown to occur in three dimensions and to be more complex than a simple translation. Therefore, the second study (section 2.3,3D Self-Navigation) consists of a method for 3D affine motion correction rather than 2D only. Here, different techniques were adopted to reduce background signal contribution in respiratory motion tracking, as this can be adversely affected by the static tissue that surrounds the heart. The proposed method demonstrated to improve conspicuity and vi¬sualization of coronary arteries in healthy and cardiovascular disease patient cohorts in comparison to a conventional ID SN method. In the third study (section 2.4, 3D Self-Navigation with Compressed Sensing), the same tracking methods were used to obtain sub-images sorted according to the respiratory position. Then, instead of motion correction, a compressed sensing reconstruction was performed on all sorted sub-image data. This process ex¬ploits the consistency of the sorted data to reduce aliasing artifacts such that the sub-image corresponding to the end-expiratory phase can directly be used to visualize the coronaries. In a healthy volunteer cohort, this strategy improved conspicuity and visualization of the coronary arteries when compared to a con¬ventional ID SN method. For the visualization of the vessel wall and atherosclerotic plaques, the state- of-the-art dual inversion recovery (DIR) technique is able to suppress the signal coming from flowing blood and provide positive wall-lumen contrast. How¬ever, optimal contrast may be difficult to obtain and is subject to RR variability. Furthermore, DIR imaging is time-inefficient and multislice acquisitions may lead to prolonged scanning times. In response and as a fourth study of this thesis (chapter 3, Vessel Wall MRI of the Carotid Arteries), a phase-sensitive DIR method has been implemented and tested in the carotid arteries of a healthy volunteer cohort. By exploiting the phase information of images acquired after DIR, the proposed phase-sensitive method enhances wall-lumen contrast while widens the window of opportunity for image acquisition. As a result, a 3-fold increase in volumetric coverage is obtained at no extra cost in scanning time, while image quality is improved. In conclusion, this thesis presented novel methods to address some of the main challenges for MRI of atherosclerosis: the suppression of motion and flow artifacts for improved visualization of vessel lumens, walls and plaques. Such methods showed to significantly improve image quality in human healthy sub¬jects, as well as scan efficiency and ease-of-use of MRI. Extensive validation is now warranted in patient populations to ascertain their diagnostic perfor¬mance. Eventually, these methods may bring the use of atherosclerosis MRI closer to the clinical practice. Résumé L'athérosclérose est une maladie cardiovasculaire chronique qui implique le épaississement de la paroi des artères, ainsi que la formation de plaques (lé¬sions) provoquant le rétrécissement des lumières, dans des vaisseaux tels que l'aorte, les coronaires et les artères carotides. L'imagerie par résonance magné¬tique (IRM) est une modalité prometteuse pour l'évaluation de l'athérosclérose, car il s'agit d'une procédure non-invasive et conviviale pour les patients, qui n'utilise pas des rayonnements ionisants. L'IRM offre un contraste des tissus mous très élevé sans avoir besoin de médias de contraste intraveineux, tan¬dis que la modification des séquences d'impulsions de RM permet en outre le réglage du contraste pour des besoins diagnostiques spécifiques. À ce titre, l'IRM peut créer des images angiographiques des lumières des vaisseaux pour évaluer les sténoses à la fin du stade de la maladie, ainsi que des images avec suppression du flux sanguin pour une première enquête des parois des vais¬seaux et une caractérisation des plaques d'athérosclérose. Cependant, malgré les grands progrès techniques qui ont eu lieu au cours des deux dernières dé¬cennies, l'IRM est une technique peu sensible et certaines limitations existent encore en termes de précision et de performance. Un des principaux défis pour l'imagerie de l'artère coronaire est le mou¬vement respiratoire. Les navigateurs diaphragmatiques de pointe comptent sur une mesure indirecte de mouvement, effectuent une correction 1D, et ont un temps d'acquisition long et imprévisible. En réponse, les stratégies d'auto- navigation (self-navigation: SN) ont été introduites récemment et offrent 100% d'efficacité d'acquisition et une meilleure facilité d'utilisation. Les SN détectent le mouvement respiratoire directement à partir des données brutes de l'image obtenue au niveau du coeur, et rétrospectivement corrigent ces mêmes données avant la reconstruction finale de l'image. Ainsi, les SN détiennent un poten¬tiel pour une compensation multidimensionnelle du mouvement. A cet égard, cette thèse présente de nouvelles méthodes SN qui estiment les paramètres de mouvement 2D et 3D à partir de sous-images qui sont obtenues à partir des mêmes données brutes qui composent l'image finale. La combinaison de toutes les sous-images corrigées produit une image finale pour la visualisation des coronaires ou les artefacts du mouvement sont réduits. La première étude (section 2.2,2D Self-Navigation with Compressed Sensing) traite d'une méthode pour une compensation 2D de mouvement de translation. Ici, on étudie l'utilisation de la reconstruction d'acquisition comprimée (compressed sensing: CS) pour soutenir la détection de mouvement en réduisant les artefacts de sous-échantillonnage. Chez des sujets humains sains, CS a démontré une amélioration de la précision de la détection de mouvement avec des simula¬tions sur des données in vivo, tandis que la visualisation de l'artère coronaire sur des acquisitions de respiration libre in vivo a aussi été améliorée. Pourtant, le mouvement du coeur induite par la respiration se produit en trois dimensions et il est plus complexe qu'un simple déplacement. Par conséquent, la deuxième étude (section 2.3, 3D Self-Navigation) traite d'une méthode de cor¬rection du mouvement 3D plutôt que 2D uniquement. Ici, différentes tech¬niques ont été adoptées pour réduire la contribution du signal du fond dans le suivi de mouvement respiratoire, qui peut être influencé négativement par le tissu statique qui entoure le coeur. La méthode proposée a démontré une amélioration, par rapport à la procédure classique SN de correction 1D, de la visualisation des artères coronaires dans le groupe de sujets sains et des pa¬tients avec maladies cardio-vasculaires. Dans la troisième étude (section 2.4,3D Self-Navigation with Compressed Sensing), les mêmes méthodes de suivi ont été utilisées pour obtenir des sous-images triées selon la position respiratoire. Au lieu de la correction du mouvement, une reconstruction de CS a été réalisée sur toutes les sous-images triées. Cette procédure exploite la cohérence des données pour réduire les artefacts de sous- échantillonnage de telle sorte que la sous-image correspondant à la phase de fin d'expiration peut directement être utilisée pour visualiser les coronaires. Dans un échantillon de volontaires en bonne santé, cette stratégie a amélioré la netteté et la visualisation des artères coronaires par rapport à une méthode classique SN ID. Pour la visualisation des parois des vaisseaux et de plaques d'athérosclérose, la technique de pointe avec double récupération d'inversion (DIR) est capa¬ble de supprimer le signal provenant du sang et de fournir un contraste posi¬tif entre la paroi et la lumière. Pourtant, il est difficile d'obtenir un contraste optimal car cela est soumis à la variabilité du rythme cardiaque. Par ailleurs, l'imagerie DIR est inefficace du point de vue du temps et les acquisitions "mul- tislice" peuvent conduire à des temps de scan prolongés. En réponse à ce prob¬lème et comme quatrième étude de cette thèse (chapitre 3, Vessel Wall MRI of the Carotid Arteries), une méthode de DIR phase-sensitive a été implémenté et testé

The ramp-up of new products in the outbound logistics

Tässä diplomityössä on perehdytty kaaoksen ja oppivan organisaation mekaniikkaan ja olemukseen. Niitä on sovellettu uuden tuotteen saattamiseen logistiikan toimitusketjuun Nokia Oyj:n Networks toimialaryhmässä. Samalla on pyritty löytämään ratkaisuja toiminnan parantamiseksi. Kaaosjohtaminen tarjoaa prosessijohtamista täydentävän tavan mallintaa muutosta ja selittää sen aikaansaamia ilmiöitä. Näiden kahden viitekehyksen avulla on pyritty pureutumaan laajaan ja moniulotteiseen ongelmakenttään. Muotoaan hakevassa organisaatiossa kaaoksen elementit ovat voimakkaasti läsnä. Kaaoksen hallintaan liittyy saumattomasti itseorganisoituminen ja oppiminen. Oppinen ei ole organisaatiolle yhtä luontainen kyky kuin se on yksilölle. Se vaatii organisaation jäseniltä oman roolinsa tiedostamista ja tiedon jakamista. Organisaation tavoitteet saattavat yksilön näkökulmasta tuntua joskus epäkonkreettisilta ja samalla muutokset hallitsemattomilta. Markkinoiden ja teknologian muuttuminen on ollut erityisen nopeaa telekommunikaatioalalla. Näissä olosuhteissa on tärkeää pyrkiä oppivaan organisaatioon, joka tukee organisaation toimintaa läpi muutoksen.

Laadun kehittämisen mahdollisuudet yliopistossa, tapaustutkimus Lappeenrannan teknillisestä korkeakoulusta

Tutkimuksen tarkoituksena on selvittää mitkä ovat Lappeenrannan teknillisen korkeakoulun laadun kehittämisen mahdollisuudet. Tutkimusongelmaa lähestytään selvittämällä kirjallisuudesta laadun kehittämisen yleisiä perusedellytyksiä ja miten toimiminen julkisesti rahoitetulla sektorilla vaikuttaa niihin. Teollisuudesta peräisin olevat laadun kehittämisen j a laatujohtamisen menetelmät eivät yksin sovellu tietointensiiviseen akateemiseen maailmaan. Tietojohtaminen tuo yliopistojen laadun kehittämiseen uuden ulottuvuuden. Organisaatiot on nähtävä moniulotteisina tietoyöparistoina, joissa on mekaanisia, orgaanisia ja dynaamisia piirteitä. Näissä tietoympäristöissä on omat periaatteensa, joiden mukaan niiden toimintaa tehokkaimmin johdetaan, ja kriteerinsä, joiden pohjalta laatu määräytyy. Tutkimus osoittaa, että LTKK:n johto suhtautuu myönteisesti laadun kehittämiseen ja LTKK:ssa on monia kohteita, joiden laatua voidaan kehittää. Vaikka LTKK:ssa arvostetaan innovatiivisuutta, joka on dynaamisen ympäristön laadun kriteeri, kehittämisehdotukset tukivat lähes kokonaan orgaanisen ympäristön laatua. jonka kriteerinä on hallittu kehittäminen. Suurimmat haasteet laadun kehittämisessä ovat kenties dynaamisen ympäristön tavoitteiden tunnistaminen, henkilöstön asenteiden muuttaminen ja yhteisöllisyyden lisääminen.

Organisaation sisäinen yhteistyökyvykkyys. Case: Metso Paper, Jyväskylä

Tutkielman tarkoituksena oli yleisesti ymmärtää sisäistä yhteistyökyvykkyyttä ja sen roolia yrityksen menestystekijänä. Empiirisesti sisäistä yhteistyökyvykkyyttä tarkasteltiin case-organisaation, Metso Paper Jyväskylän, avulla. Tavoitteena oli selvittää, mistä sisäinen yhteistyökyvykkyys koostuu sekä siihen vaikuttavia kriittisiä tekijöitä. Myös käytännön keinoja ja sovelluksia etsittiin edistämään sisäistä yhteistyötä. Tutkielmassa käytettiin kvalitatiivista tutkimusotetta. Tiedon hankinnan strategiana oli tapaustutkimus ja tutkimusaineisto kerättiin teemahaastattelujen avulla. Saatu aineisto analysoitiin teemoittelun avulla. Teemoja etsittiin tekstistä teoriasta johdettujen oletusten ja empiriasta löydettyjen tekijöiden perusteella. Tutkimuksen tuloksena oli, että yhteistyökyvykkyys koostuu sekä yksilöön että organisaatioon liittyvistä tekijöistä. Yhteistyökyvykkyyden kriittisiä ja sitä estäviä tekijöitä olivat toiminnan painottuminen ulkoisiin suhteisiin, muodollinen ja monitasoinen organisaatiorakenne, organisaatiorakenteiden nopea muutostahti, toimintamallin yksisuuntaisuus, organisaatio- ja johtamiskulttuuri, joka ei tue yhteistyötä, ylimmän johdon ja operatiivisten toimintojen välinen kuilu, tiedon painottuminen tietojärjestelmiin, dialogin puute, kommunikoinnin yksisuuntaisuus ja erilaisista työkulttuureista aiheutuvat kommunikaatioesteet, yhteistyösuhteiden puute ja transaktiosuhteiden painottuminen sekä ryhmien sisäisen yhtenäisyyden vahvuus. Näiden tekijöiden esiin tuominen tuo uusia näkökulmia organisaation sisäisen yhteistyökyvykkyyden ymmärtämiseen ja kehittämiseen.

Fusion weld metal solidification:Continuum from weld interface to centerline

We present a brief résumé of the history of solidification research and key factors affecting the solidification of fusion welds. There is a general agreement of the basic solidification theory, albeit differing - even confusing - nomenclatures do exist, and Cases 2 and 3 (the Chalmers' basic boundary conditions for solidification, categorized by Savage as Cases) are variably emphasized. Model Frame, a tool helping to model the continuum of fusion weld solidification from start to end, is proposed. It incorporates the general solidification models, of which the pertinent ones are selected for the actual modeling. The basic models are the main solidification Cases 1…4. These discrete Cases are joined with Sub-Cases: models of Pfann, Flemings and others, bringing needed Sub-Case variables into the model. Model Frame depicts a grain growing from the weld interface to its centerline. Besides modeling, the Model Frame supports education and academic debate. The new mathematical modeling techniques will extend its use into multi-dimensional modeling, introducing new variables and increasing the modeling accuracy. We propose a model: melting/solidification-model (M/S-model) - predicting the solute profile at the start of the solidification of a fusion weld. This Case 3-based Sub-Case takes into account the melting stage, the solute back-diffusion in the solid, and the growth rate acceleration typical to fusion welds. We propose - based on works of Rutter & Chalmers, David & Vitek and our experimental results on copper - that NEGS-EGS-transition is not associated only with cellular-dendritic-transition. Solidification is studied experimentally on pure and doped copper with welding speed range from 0 to 200 cm/min, with one test at 3000 cm/min. Found were only planar and cellular structures, no dendrites - columnar or equiaxed. Cell sub structures: rows of cubic elements we call "cubelettes", "cell-bands" and "micro-cells", as well as an anomalous crack morphology "crack-eye", were detected, as well as microscopic hot crack nucleus we call "grain-lag cracks", caused by a grain slightly lagging behind its neighbors in arrival to the weld centerline. Varestraint test and R-test revealed a change of crack morphologies from centerline cracks to grainand cell boundary cracks with an increasing welding speed. High speed made the cracks invisible to bare eye and hardly detectable with light microscope, while electron microscope often revealed networks of fine micro-cracks.

Identification and visualization of multidimensional antigen-specific T-cell populations in polychromatic cytometry data.

An important aspect of immune monitoring for vaccine development, clinical trials, and research is the detection, measurement, and comparison of antigen-specific T-cells from subject samples under different conditions. Antigen-specific T-cells compose a very small fraction of total T-cells. Developments in cytometry technology over the past five years have enabled the measurement of single-cells in a multivariate and high-throughput manner. This growth in both dimensionality and quantity of data continues to pose a challenge for effective identification and visualization of rare cell subsets, such as antigen-specific T-cells. Dimension reduction and feature extraction play pivotal role in both identifying and visualizing cell populations of interest in large, multi-dimensional cytometry datasets. However, the automated identification and visualization of rare, high-dimensional cell subsets remains challenging. Here we demonstrate how a systematic and integrated approach combining targeted feature extraction with dimension reduction can be used to identify and visualize biological differences in rare, antigen-specific cell populations. By using OpenCyto to perform semi-automated gating and features extraction of flow cytometry data, followed by dimensionality reduction with t-SNE we are able to identify polyfunctional subpopulations of antigen-specific T-cells and visualize treatment-specific differences between them.