Bunch frequency multiplication by RF injection into an isochronous ring

La collaboration CLIC (Compact LInear Collider, collisionneur linéaire compact) étudie la possibilité de réaliser un collisionneur électron-positon linéaire à haute énergie (3 TeV dans le centre de masse) et haute luminosité (1034 cm-2s-1), pour la recherche en physique des particules. Le projet CLIC se fonde sur l'utilisation de cavités accélératrices à haute fréquence (30 GHz). La puissance nécessaire à ces cavités est fournie par un faisceau d'électrons de basse énergie et de haute intensité, appelé faisceau de puissance, circulant parallèlement à l'accélérateur linéaire principal (procédé appelé « Accélération à Double Faisceau »). Dans ce schéma, un des principaux défis est la réalisation du faisceau de puissance, qui est d'abord généré dans un complexe accélérateur à basse fréquence, puis transformé pour obtenir une structure temporelle à haute fréquence nécessaire à l'alimentation des cavités accélératrices de l'accélérateur linéaire principal. La structure temporelle à haute fréquence des paquets d'électrons est obtenue par le procédé de multiplication de fréquence, dont la manipulation principale consiste à faire circuler le faisceau d'électrons dans un anneau isochrone en utilisant des déflecteurs radio-fréquence (déflecteurs RF) pour injecter et combiner les paquets d'électrons. Cependant, ce type de manipulation n'a jamais été réalisé auparavant et la première phase de la troisième installation de test pour CLIC (CLIC Test Facility 3 ou CTF3) a pour but la démonstration à faible charge du procédé de multiplication de fréquence par injection RF dans un anneau isochrone. Cette expérience, qui a été réalisée avec succès au CERN au cours de l'année 2002 en utilisant une version modifiée du pré-injecteur du grand collisionneur électron-positon LEP (Large Electron Positron), est le sujet central de ce rapport. L'expérience de combinaison des paquets d'électrons consiste à accélérer cinq impulsions dont les paquets d'électrons sont espacés de 10 cm, puis à les combiner dans un anneau isochrone pour obtenir une seule impulsion dont les paquets d'électrons sont espacés de 2 cm, multipliant ainsi la fréquence des paquets d'électrons, ainsi que la charge par impulsion, par cinq. Cette combinaison est réalisée au moyen de structures RF résonnantes sur un mode déflecteur, qui créent dans l'anneau une déformation locale et dépendante du temps de l'orbite du faisceau. Ce mécanisme impose plusieurs contraintes de dynamique de faisceau comme l'isochronicité, ainsi que des tolérances spécifiques sur les paquets d'électrons, qui sont définies dans ce rapport. Les études pour la conception de la Phase Préliminaire du CTF3 sont détaillées, en particulier le nouveau procédé d'injection avec les déflecteurs RF. Les tests de haute puissance réalisés sur ces cavités déflectrices avant leur installation dans l'anneau sont également décrits. L'activité de mise en fonctionnement de l'expérience est présentée en comparant les mesures faites avec le faisceau aux simulations et calculs théoriques. Finalement, les expériences de multiplication de fréquence des paquets d'électrons sont décrites et analysées. On montre qu'une très bonne efficacité de combinaison est possible après optimisation des paramètres de l'injection et des déflecteurs RF. En plus de l'expérience acquise sur l'utilisation de ces déflecteurs, des conclusions importantes pour les futures activités CTF3 et CLIC sont tirées de cette première démonstration de la multiplication de fréquence des paquets d'électrons par injection RF dans un anneau isochrone.<br/><br/>The Compact LInear Collider (CLIC) collaboration studies the possibility of building a multi-TeV (3 TeV centre-of-mass), high-luminosity (1034 cm-2s-1) electron-positron collider for particle physics. The CLIC scheme is based on high-frequency (30 GHz) linear accelerators powered by a low-energy, high-intensity drive beam running parallel to the main linear accelerators (Two-Beam Acceleration concept). One of the main challenges to realize this scheme is to generate the drive beam in a low-frequency accelerator and to achieve the required high-frequency bunch structure needed for the final acceleration. In order to provide bunch frequency multiplication, the main manipulation consists in sending the beam through an isochronous combiner ring using radio-frequency (RF) deflectors to inject and combine electron bunches. However, such a scheme has never been used before, and the first stage of the CLIC Test Facility 3 (CTF3) project aims at a low-charge demonstration of the bunch frequency multiplication by RF injection into an isochronous ring. This proof-of-principle experiment, which was successfully performed at CERN in 2002 using a modified version of the LEP (Large Electron Positron) pre-injector complex, is the central subject of this report. The bunch combination experiment consists in accelerating in a linear accelerator five pulses in which the electron bunches are spaced by 10 cm, and combining them in an isochronous ring to obtain one pulse in which the electron bunches are spaced by 2 cm, thus achieving a bunch frequency multiplication of a factor five, and increasing the charge per pulse by a factor five. The combination is done by means of RF deflecting cavities that create a time-dependent bump inside the ring, thus allowing the interleaving of the bunches of the five pulses. This process imposes several beam dynamics constraints, such as isochronicity, and specific tolerances on the electron bunches that are defined in this report. The design studies of the CTF3 Preliminary Phase are detailed, with emphasis on the novel injection process using RF deflectors. The high power tests performed on the RF deflectors prior to their installation in the ring are also reported. The commissioning activity is presented by comparing beam measurements to model simulations and theoretical expectations. Eventually, the bunch frequency multiplication experiments are described and analysed. It is shown that the process of bunch frequency multiplication is feasible with a very good efficiency after a careful optimisation of the injection and RF deflector parameters. In addition to the experience acquired in the operation of these RF deflectors, important conclusions for future CTF3 and CLIC activities are drawn from this first demonstration of the bunch frequency multiplication by RF injection into an isochronous ring.<br/><br/>La collaboration CLIC (Compact LInear Collider, collisionneur linéaire compact) étudie la possibilité de réaliser un collisionneur électron-positon linéaire à haute énergie (3 TeV) pour la recherche en physique des particules. Le projet CLIC se fonde sur l'utilisation de cavités accélératrices à haute fréquence (30 GHz). La puissance nécessaire à ces cavités est fournie par un faisceau d'électrons de basse énergie et de haut courant, appelé faisceau de puissance, circulant parallèlement à l'accélérateur linéaire principal (procédé appelé « Accélération à Double Faisceau »). Dans ce schéma, un des principaux défis est la réalisation du faisceau de puissance, qui est d'abord généré dans un complexe accélérateur à basse fréquence, puis transformé pour obtenir une structure temporelle à haute fréquence nécessaire à l'alimentation des cavités accélératrices de l'accélérateur linéaire principal. La structure temporelle à haute fréquence des paquets d'électrons est obtenue par le procédé de multiplication de fréquence, dont la manipulation principale consiste à faire circuler le faisceau d'électrons dans un anneau isochrone en utilisant des déflecteurs radio-fréquence (déflecteurs RF) pour injecter et combiner les paquets d'électrons. Cependant, ce type de manipulation n'a jamais été réalisé auparavant et la première phase de la troisième installation de test pour CLIC (CLIC Test Facility 3 ou CTF3) a pour but la démonstration à faible charge du procédé de multiplication de fréquence par injection RF dans un anneau isochrone. L'expérience consiste à accélérer cinq impulsions, puis à les combiner dans un anneau isochrone pour obtenir une seule impulsion dans laquelle la fréquence des paquets d'électrons et le courant sont multipliés par cinq. Cette combinaison est réalisée au moyen de structures déflectrices RF qui créent dans l'anneau une déformation locale et dépendante du temps de la trajectoire du faisceau. Les résultats de cette expérience, qui a été réalisée avec succès au CERN au cours de l?année 2002 en utilisant une version modifiée du pré-injecteur du grand collisionneur électron-positon LEP (Large Electron Positon), sont présentés en détail.

Combined transcriptomic and proteomic studies reveal non-canonical signaling functions in the jasmonate pathway

Abstract Lipid derived signals mediate many stress and defense responses in multicellular eukaryotes. Among these are the jasmonates, potently active signaling compounds in plants. Jasmonic acid (JA) and 12-oxo-phytodienoic acid (OPDA) are the two best known members of the large jasmonate family. This thesis further investigates their roles as signals using genomic and proteomic approaches. The study is based on a simple genetic model involving two key genes. The first is ALLENE OXIDE SYNTHASE (AOS), encoding the most important enzyme in generating jasmonates. The second is CORONATINE INSENSITIVE 1 (COI1), a gene involved in all currently documented canonical signaling responses. We asked the simple question: do null mutations in AOS and COI1 have analogous effects on the transcriptome ? We found that they do not. If most COI1-dependent genes were also AOS-dependent, the expression of a zinc-finger protein was AOS-dependent but was unaffected by the coi1-1 mutation. We thus supposed that a jasmonate member, most probably OPDA, can alter gene expression partially independently of COI1. Conversely, the expression of at least three genes, one of these is a protein kinase, was shown to be COI1-dependent but did not require a functional AOS protein. We conclude that a non-jasmonate signal might alter gene expression through COIL Proteomic comparison of coi1-1 and aos plants confirmed these observations and highlighted probable protein degradation processes controlled by jasmonates and COI1 in the wounded leaf. This thesis revealed new functions for COI1 and for AOS-generated oxylipins in the jasmonate signaling pathway. Résumé Les signaux dérivés d'acides gras sont des médiateurs de réponses aux stress et de la défense des eucaryotes multicellulaires. Parmi eux, les jasmonates sont de puissants composés de sig¬nalisation chez les plantes. L'acide jasmonique (JA) et l'acide 12-oxo-phytodienoïc (OPDA) sont les deux membres les mieux caractérisés de la grande famille des jasmonates. Cette thèse étudie plus profondément leurs rôles de signalisation en utilisant des approches génomique et protéomique. Cette étude est basée sur un modèle génétique simple n'impliquant que deux gènes. Le premier est PALLENE OXYDE SYNTHASE (AOS) qui encode l'enzyme la plus importante pour la fabrication des jasmonates. Le deuxième est CORONATINE INSENSITIVE 1 (COI1) qui est impliqué dans la totalité des réponses aux jasmonates connues à ce jour. Nous avons posé la question suivante : est-ce que les mutations nulles dans les gènes AOS et COI1 ont des effets analogues sur le transcriptome ? Nous avons trouvé que ce n'était pas le cas. Si la majorité des gènes dépendants de COI1 sont également dépendants d'AOS, l'expression d'un gène codant pour une protéine formée de doigts de zinc n'est pas affectée par la mutation de COI1 tout en étant dépendante d'AOS. Nous avons donc supposé qu'un membre de la famille des jasmonates, probablement OPDA, pouvait modifier l'expression de certains gènes indépendamment de COI1. Inversement, nous avons montré que, tout en étant dépendante de COI1, l'expression d'au moins trois gènes, dont un codant pour une protéine kinase, n'était pas affectée par l'absence d'une protéine AOS fonctionnelle. Nous en avons conclu qu'un signal autre qu'un jasmonate devait modifier l'expression de certains gènes à travers COI1. La comparaison par protéomique de plantes aos et coi1-1 a confirmé ces observations et a mis en évidence un probable processus de dégradation de protéines contrôlé par les jasmonates et COU_ Cette thèse a mis en avant de nouvelles fonctions pour COI1 et pour des oxylipines générées par AOS dans le cadre de la signalisation par les jasmonates.

Survey of management of first-ever seizures in a hospital based community

Résumé Contexte: Bon nombre d'études épidémiologiques concernant les premières crises comitiales ont été effectuées principalement sur des populations générales. Cependant, les patients admis dans un hôpital peuvent présenter des éléments cliniques différents. Nous avons donc mené une étude prospective auprès de sujets dans une population hospitalière ayant subi une première crise d'épilepsie, afin d'étudier leur pronostic et le rôle des examens complémentaires (examen neurologique, imagerie cérébrale, examens sanguins, EEG) dans le choix de l'administration d'une médication antiépileptique. Méthodes : Sur une période d'une année, nous avons suivi 177 patients adultes, admis consécutivement, ayant présenté une crise d'épilepsie dont l'évaluation aiguë a été effectuée dans notre hôpital. Pendant 6 mois, nous avons pratiqué pour chaque patient un suivi du traitement antiépileptique, des récidives de crises et d'un éventuel décès. Résultats : L'examen neurologique était anormal dans 72.3% des cas, l'imagerie cérébrale dans 54.8% et les examens sanguins dans 57.1%. L'EEG a montré des éléments épileptiformes dans 33.9% des cas. L'étiologie la plus fréquemment représentée était constituée par des intoxications. Un traitement antiépileptique a été prescrit chez 51% des patients. 31.6% des sujets suivis à six mois ont subi une récidive ; la mortalité s'est élevée à 17.8%. Statistiquement, l'imagerie cérébrale, l'EEG et l'examen neurologique étaient des facteurs prédictifs indépendants pour l'administration d'antiépileptiques, et l'imagerie cérébrale le seul facteur associé au pronostic. Conclusions : Les patients évalués en aigu dans un hôpital pour une première crise comitiale présentent un profil médical sous-jacent, qui explique probablement leur mauvais pronostic. L'imagerie cérébrale s'est avérée être le test paraclinique le plus important dans la prévention du traitement et du pronostic. Mots-clés : première crise d'épilepsie, étiologie, pronostic, récidive, médication antiépileptique, population hospitalière Summary Background: Epidemiological studies focusing on first-ever seizures have been carried out mainly on community based populations. However, since hospital populations may display varying clinical features, we prospectively analysed patients with first-ever seizure in a hospital based community to evaluate prognosis and the role of complementary investigations in the decision to administer antiepileptic drugs (AED). Methods: Over one year, we recruited 177 consecutive adult patients with a first seizure acutely evaluated in our hospital. During six months' follow-up data relating to AED treatment, recurrence of seizures and death were collected for each patient. Results:. Neurological examination was abnormal in 72.3%, neuroimaging in 54.8% and biochemical tests in 57.1%. Electroencephalogram (EEG) showed epileptiform features in 33.9%. Toxicity represented the most common aetiology. AED was prescribed in 51% of patients. Seizure recurrence at six months involved 31.6% of patients completing the follow-up; mortality was 17.8%. Statistical analysis showed that brain CT, EEG and neurological examination are independent predictive factors for AED administration, but only CT scan is associated with outcome. Conclusions: Patients evaluated acutely for first- ever seizure in a hospital setting have severe underlying clinical conditions apparently related to their relatively poor prognosis. Neuroimaging represents the most important paraclinical test in predicting both treatment administration and outcome.

Glutathione deficit in schizophrenia: strategies to increase glutathione levels in " in vitro " and clinical studies

Summary: Decrease in glutathione (GSH) levels was observed in cerebrospinal fluid, prefrontal cortex and post-mortem striatum of schizophrenia patients. Evidences suggest a defect in GSH synthesis at the levels of the rate-limiting synthesizing enzyme, glutamate cysteine ligase (GCL). Indeed, polymorphisms in the gene of the modifier subunit of GCL (GCLM) was shown to be associated with the disease in three different populations, GCLM gene expression is decreaséd in fibroblasts from patients and the increase in GCL activity induced by an oxidative stress is lower in patients' fibroblasts compared to controls. GSH being a major antioxydant and redox regulator, its presence is of high importance for protecting cells against oxidative stress. The aim of the present work was to use various substances to increase GSH levels by diverse strategies. Since the synthesizing enzyme GCL is defective, bypassing this enzyme was the first strategy we used. GSH ethyl ester (GSHEE), a membrane permeable analog of GSH, succeeded in replenishing GSH levels in cultured neurons and astrocytes previously depleted in GSH by L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of GCL. GSHEE also abolished dopamine-induced decrease of NMDA-mediated calcium response observed in BSO-treated neurons. y-Glutamylcysteine ethyl ester (GCSE), a membrane permeable analog of the product of GCL, increased GSH levels only in astrocytes. The second strategy was to boost the defective enzyme GCL. While quercetin (flavonoid) could increase GSH levels only in astrocytes, curcumin (polyphenol) and tertbutylhydroquinone (quinone) were successful in both neurons and astrocytes, via an increase in the gene expression of the two subunits of GCL and, consequently, an increase in the activity of the enzyme. However, FK506, an immunosupressant, was unefficient. Treating astrocytes from GCLM KO mice showed that the modulatory subunit is necessary for the action of the substances. Finally, since cysteine is the limiting precursor in the synthesis of GSH, we hypothesized that we could increase GSH levels by providing more of this precursor. N-acetyl-cysteine (NAC), a cysteine donor, was administered to schizophrenia patients, using adouble-blind and cross-over protocol. NAC significantly improved the mismatch negativity (MMN), a component of the auditory evoked potentials, thought to reflect selective current flowing through open, unblocked NMDA channels. Considering that NMDA function is reduced when GSH levels are low, increasing these levels with NAC could improve NMDA function as reflected by the improvement in the generation of the MMN. Résumé: Les taux de glutathion (GSH) dans le liquide céphalo-rachidien, le cortex préfrontal ainsi que le striatum post-mortem de patients schizophrènes, sont diminués. L'enzyme limitante dans la synthèse du GSH, la glutamyl-cysteine ligase (GCL), est défectueuse. En effet, des polymorphismes dans le gène de la sous-unité modulatrice de GCL (GCLM) sont associés à la maladie, l'expression du gène GCLM est diminuée dans les fibroblastes de patients et, lors d'un stress oxidative, l'augmentation de l'activité de GCL est plus faible chez les patients que chez les contrôles. Le GSH étant un important antioxydant et régulateur du status redox, sa présence est primordiale afin de protéger les cellules contre les stress oxydatifs. Au cours du présent travail, une variété de substances ont été utilisées dans le but d'augmenter les taux de GSH. Passer outre l'enzyme de synthèse GCL qui est défectueuse fut la première stratégie utilisée. L'éthylester de GSH (GSHEE), un analogue du GSH qui pénètre la membrane cellulaire, a augmenté les taux de GSH dans des neurones et des astrocytes déficitaires en GSH dû au L-buthionine-(S,R)-sulfoximine (BSO), un inhibiteur du GCL. Dans ces neurones, le GSHEE a aussi aboli la diminution de la réponse NMDA, induite parla dopamine. L'éthyl-ester de y-glutamylcysteine (GCEE), un analogue du produit de la GCL qui pénètre la membrane cellulaire, a augmenté les taux de GSH seulement dans les astrocytes. La seconde stratégie était d'augmenter l'activité de l'enzyme GCL. Tandis que la quercétine (flavonoïde) n'a pu augmenter les taux de GSH que dans les astrocytes, la curcumin (polyphénol) et le tert-butylhydroquinone (quinone) furent efficaces dans les deux types de cellules, via une augmentation de l'expression des gènes des deux sous-unités de GCL et de l'activité de l'enzyme. Le FK506 (immunosupresseur) n' a démontré aucune efficacité. Traiter des astrocytes provenant de souris GCLM KO a permis d'observer que la sous-unité modulatoire est nécessaire à l'action des substances. Enfin, puisque la cysteine est le substrat limitant dans la synthèse du GSH, fournir plus de ce présurseur pourrait augmenter les taux de GSH. Nacétyl-cystéine (NAC), un donneur de cystéine, a été administrée à des schizophrènes, lors d'une étude en double-aveugle et cross-over. NAC a amélioré le mismatch negativity (MMN), un composant des potentials évoqués auditifs, qui reflète le courant circulant via les canaux NMDA. Puisque la fonctionnalité des R-NMDA est diminuée lorsque les taux de GSH sont bas, augmenter ces taux avec NAC pourrait améliorer la fonction des R-NMDA, réflété par une augmentation de l'amplitude du MMN.

Exploring the strategic impact of technological change - Studies on the role of Internet in magazine publishing

Over the past few decades, turbulent change has characterized the situation in the media industry. It has been noted that digitalization and new media are strongly influencing the industry: it is changing the existing market dynamics and requires new strategies. Prior research on the impact of digitalization and the Internet has emphasized news-focused media such as newspaper publishing and broadcasting, yet magazine publishing is very seldom the focus of the research. This study examines how the Internetimpacts magazine publishing. The work presents a multi-level analysis on the role and impact of the Internet on magazine products, companies and industry. The study is founded on strategic management, technology management and media economics literature. This study consists of two parts. The first part introduces the research topic and discusses the overall results of the study. The second part comprises five research publications. Qualitative research methods are used throughout. The results of the study indicate that the Internet has not had a disruptive effect on magazine publishing, and that its strategic implications could rather be considered complementary to the print magazine and the business as a whole. It seems that the co-specialized assets, together with market-related competencies and unchanged core competence have protected established firms from the disruptive effect of the new technology in magazine publishing. In addition, it seems that the Internet offers a valuable possibility to build and nourish customer relationships. The study contributes tomedia management and economics research by moving from product- or industry-level investigations towards a strategic-management perspective.

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.

Project Success through Effective Decisions: Case Studies on Project Goal Setting, Success Evaluation and Managerial Decision Making

The objective of the thesis is to structure and model the factors that contribute to and can be used in evaluating project success. The purpose of this thesis is to enhance the understanding of three research topics. The goal setting process, success evaluation and decision-making process are studied in the context of a project, business unitand its business environment. To achieve the objective three research questionsare posed. These are 1) how to set measurable project goals, 2) how to evaluateproject success and 3) how to affect project success with managerial decisions.The main theoretical contribution comes from deriving a synthesis of these research topics which have mostly been discussed apart from each other in prior research. The research strategy of the study has features from at least the constructive, nomothetical, and decision-oriented research approaches. This strategy guides the theoretical and empirical part of the study. Relevant concepts and a framework are composed on the basis of the prior research contributions within the problem area. A literature review is used to derive constructs of factors withinthe framework. They are related to project goal setting, success evaluation, and decision making. On the basis of this, the case study method is applied to complement the framework. The empirical data includes one product development program, three construction projects, as well as one organization development, hardware/software, and marketing project in their contexts. In two of the case studiesthe analytic hierarchy process is used to formulate a hierarchical model that returns a numerical evaluation of the degree of project success. It has its origin in the solution idea which in turn has its foundation in the notion of projectsuccess. The achieved results are condensed in the form of a process model thatintegrates project goal setting, success evaluation and decision making. The process of project goal setting is analysed as a part of an open system that includes a project, the business unit and its competitive environment. Four main constructs of factors are suggested. First, the project characteristics and requirements are clarified. The second and the third construct comprise the components of client/market segment attractiveness and sources of competitive advantage. Together they determine the competitive position of a business unit. Fourth, the relevant goals and the situation of a business unit are clarified to stress their contribution to the project goals. Empirical evidence is gained on the exploitation of increased knowledge and on the reaction to changes in the business environment during a project to ensure project success. The relevance of a successful project to a company or a business unit tends to increase the higher the reference level of project goals is set. However, normal performance or sometimes performance below this normal level is intentionally accepted. Success measures make project success quantifiable. There are result-oriented, process-oriented and resource-oriented success measures. The study also links result measurements to enablers that portray the key processes. The success measures can be classified into success domains determining the areas on which success is assessed. Empiricalevidence is gained on six success domains: strategy, project implementation, product, stakeholder relationships, learning situation and company functions. However, some project goals, like safety, can be assessed using success measures that belong to two success domains. For example a safety index is used for assessing occupational safety during a project, which is related to project implementation. Product safety requirements, in turn, are connected to the product characteristics and thus to the product-related success domain. Strategic success measures can be used to weave the project phases together. Empirical evidence on their static nature is gained. In order-oriented projects the project phases are oftencontractually divided into different suppliers or contractors. A project from the supplier's perspective can represent only a part of the ¿whole project¿ viewed from the client's perspective. Therefore static success measures are mostly used within the contractually agreed project scope and duration. Proof is also acquired on the dynamic use of operational success measures. They help to focus on the key issues during each project phase. Furthermore, it is shown that the original success domains and success measures, their weights and target values can change dynamically. New success measures can replace the old ones to correspond better with the emphasis of the particular project phase. This adjustment concentrates on the key decision milestones. As a conclusion, the study suggests a combination of static and dynamic success measures. Their linkage to an incentive system can make the project management proactive, enable fast feedback and enhancethe motivation of the personnel. It is argued that the sequence of effective decisions is closely linked to the dynamic control of project success. According to the used definition, effective decisions aim at adequate decision quality and decision implementation. The findings support that project managers construct and use a chain of key decision milestones to evaluate and affect success during aproject. These milestones can be seen as a part of the business processes. Different managers prioritise the key decision milestones to a varying degree. Divergent managerial perspectives, power, responsibilities and involvement during a project offer some explanation for this. Finally, the study introduces the use ofHard Gate and Soft Gate decision milestones. The managers may use the former milestones to provide decision support on result measurements and ad hoc critical conditions. In the latter milestones they may make intermediate success evaluation also on the basis of other types of success measures, like process and resource measures.

Studies on coordination of systems development process

This thesis examines coordination of systems development process in a contemporary software producing organization. The thesis consists of a series of empirical studies in which the actions, conceptions and artifacts of practitioners are analyzed using a theory-building case study research approach. The three phases of the thesis provide empirical observations on different aspects of systemsdevelopment. In the first phase is examined the role of architecture in coordination and cost estimation in multi-site environment. The second phase involves two studies on the evolving requirement understanding process and how to measure this process. The third phase summarizes the first two phases and concentrates on the role of methods and how practitioners work with them. All the phases provide evidence that current systems development method approaches are too naïve in looking at the complexity of the real world. In practice, development is influenced by opportunity and other contingent factors. The systems development processis not coordinated using phases and tasks defined in methods providing universal mechanism for managing this process like most of the method approaches assume.Instead, the studies suggest that managing systems development process happens through coordinating development activities using methods as tools. These studies contribute to the systems development methods by emphasizing the support of communication and collaboration between systems development participants. Methods should not describe the development activities and phases in a detail level, butshould include the higher level guidance for practitioners on how to act in different systems development environments.

Cannabis use and other illicit drug use: Do subjective experiences during first cannabis use increase the probability of using illicit drug use?

Background and aims: Few studies have examined whether subjective experiences during first cannabis use are related to other illicit drug (OID) use. This study investigated this topic. Methods: Baseline data from a representative sample of young Swiss men was obtained from an ongoing Cohort Study on Substance Use Risk Factors (N ¼ 5753). Logistic regressions were performed to examine the relationships between cannabis use and of subjective experiences during first cannabis use with 15 OID. Results: Positive experiences increased the likelihood of using hallucinogens (hallucinogens, salvia divinorum, spice; p50.015), stimulants (speed, ecstasy, cocaine, amphetamines/methamphetamines; p50.006) and also poppers, research chemicals, GHB/GBL, and crystal meth (p50.049). Sniffed drugs (poppers, solvents for sniffing) and ''hard'' drugs (heroin, ketamine, research chemicals, GHB/GBL and crystal meth) were more likely to be used by participants who experienced negative feelings on first use of cannabis (p50.034). Conclusion: Subjective feelings seemed to amplify the association of cannabis with OID. The risk increased for drugs with effects resembling feelings experienced on first cannabis use. Negative experiences should also be a concern, as they were associated with increased risk of using the ''hardest'' illicit drugs.

The REporting of Studies Conducted Using Observational Routinely-Collected Health Data (RECORD) Statement: Methods for Arriving at Consensus and Developing Reporting Guidelines.

OBJECTIVE: Routinely collected health data, collected for administrative and clinical purposes, without specific a priori research questions, are increasingly used for observational, comparative effectiveness, health services research, and clinical trials. The rapid evolution and availability of routinely collected data for research has brought to light specific issues not addressed by existing reporting guidelines. The aim of the present project was to determine the priorities of stakeholders in order to guide the development of the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. METHODS: Two modified electronic Delphi surveys were sent to stakeholders. The first determined themes deemed important to include in the RECORD statement, and was analyzed using qualitative methods. The second determined quantitative prioritization of the themes based on categorization of manuscript headings. The surveys were followed by a meeting of RECORD working committee, and re-engagement with stakeholders via an online commentary period. RESULTS: The qualitative survey (76 responses of 123 surveys sent) generated 10 overarching themes and 13 themes derived from existing STROBE categories. Highest-rated overall items for inclusion were: Disease/exposure identification algorithms; Characteristics of the population included in databases; and Characteristics of the data. In the quantitative survey (71 responses of 135 sent), the importance assigned to each of the compiled themes varied depending on the manuscript section to which they were assigned. Following the working committee meeting, online ranking by stakeholders provided feedback and resulted in revision of the final checklist. CONCLUSIONS: The RECORD statement incorporated the suggestions provided by a large, diverse group of stakeholders to create a reporting checklist specific to observational research using routinely collected health data. Our findings point to unique aspects of studies conducted with routinely collected health data and the perceived need for better reporting of methodological issues.

Vulnerability as a heuristic for interdisciplinary research: Assessing the thematic and methodological structure of empirical life-course studies

Changes in human lives are studied in psychology, sociology, and adjacent fields as outcomes of developmental processes, institutional regulations and policies, culturally and normatively structured life courses, or empirical accounts. However, such studies have used a wide range of complementary, but often divergent, concepts. This review has two aims. First, we report on the structure that has emerged from scientific life course research by focusing on abstracts from longitudinal and life course studies beginning with the year 2000. Second, we provide a sense of the disciplinary diversity of the field and assess the value of the concept of 'vulnerability' as a heuristic tool for studying human lives. Applying correspondence analysis to 10,632 scientific abstracts, we find a disciplinary divide between psychology and sociology, and observe indications of both similarities of-and differences between-studies, driven at least partly by the data and methods employed. We also find that vulnerability takes a central position in this scientific field, which leads us to suggest several reasons to see value in pursuing theory development for longitudinal and life course studies in this direction.

The rare cancer network: ongoing studies and future strategy.

The Rare Cancer Network (RCN) was formed in the early 1990's to create a global network that could pool knowledge and resources in the studies of rare malignancies whose infrequency prevented both their study with prospective clinical trials. To date, the RCN has initiated 74 studies resulting in 46 peer reviewed publications. The First International Symposium of the Rare Cancer Network took place in Nice in March of 2014. Status updates and proposals for new studies were heard for fifteen topics. Ongoing studies continue for cardiac sarcomas, thyroid cancers, glomus tumors, and adult medulloblastomas. New proposals were presented at the symposium for primary hepatic lymphoma, solitary fibrous tumors, Rosai-Dorfman disease, tumors of the ampulla of Vater, salivary gland tumors, anorectal melanoma, midline nuclear protein in testes carcinoma, pulmonary lymphoepithelioma-like carcinoma, adenoid cystic carcinoma of the trachea, osteosarcomas of the mandible, and extra-cranial hemangiopericytoma. This manuscript presents the abstracts of those proposals and updates on ongoing studies, as well a brief summary of the vision and future of the RCN.

Bilateral deep brain stimulation: the placement of the second electrode is not necessarily less accurate than that of the first one.

BACKGROUND: Deep brain stimulation (DBS) is recognized as an effective treatment for movement disorders. We recently changed our technique, limiting the number of brain penetrations to three per side. OBJECTIVES: The first aim was to evaluate the electrode precision on both sides of surgery since we implemented this surgical technique. The second aim was to analyse whether or not the electrode placement was improved with microrecording and macrostimulation. METHODS: We retrospectively reviewed operation protocols and MRIs of 30 patients who underwent bilateral DBS. For microrecording and macrostimulation, we used three parallel channels of the 'Ben Gun' centred on the MRI-planned target. Pre- and post-operative MRIs were merged. The distance between the planned target and the centre of the implanted electrode artefact was measured. RESULTS: There was no significant difference in targeting precision on both sides of surgery. There was more intra-operative adjustment of the second electrode positioning based on microrecording and macrostimulation, which allowed to significantly approach the MRI-planned target on the medial-lateral axis. CONCLUSION: There was more electrode adjustment needed on the second side, possibly in relation with brain shift. We thus suggest performing a single central track with electrophysiological and clinical assessment, with multidirectional exploration on demand for suboptimal clinical responses.

The swiss transplant cohort study: lessons from the first 6 years.

Prospective cohort studies significantly contribute to answering specific research questions in a defined population. Since 2008, the Swiss Transplant Cohort Study (STCS) systematically enrolled >95 % of all transplant recipients in Switzerland, collecting predefined data at determined time points. Designed as an open cohort, the STCS has included >3900 patients to date, with a median follow-up of 2.96 years (IQR 1.44-4.73). This review highlights some relevant findings in the field of transplant-associated infections gained by the STCS so far. Three key general aspects have crystallized: (i) Well-run cohort studies are a powerful tool to conduct genetic studies, which are crucially dependent on a meticulously described phenotype. (ii) Long-term real-life observations are adding a distinct layer of information that cannot be obtained during randomized studies. (iii) The systemic collection of data, close interdisciplinary collaboration, and continuous analysis of some key outcome data such as infectious diseases endpoints can improve patient care.