Testing demographic models of effective population size.

Due to practical difficulties in obtaining direct genetic estimates of effective sizes, conservation biologists have to rely on so-called 'demographic models' which combine life-history and mating-system parameters with F-statistics in order to produce indirect estimates of effective sizes. However, for the same practical reasons that prevent direct genetic estimates, the accuracy of demographic models is difficult to evaluate. Here we use individual-based, genetically explicit computer simulations in order to investigate the accuracy of two such demographic models aimed at investigating the hierarchical structure of populations. We show that, by and large, these models provide good estimates under a wide range of mating systems and dispersal patterns. However, one of the models should be avoided whenever the focal species' breeding system approaches monogamy with no sex bias in dispersal or when a substructure within social groups is suspected because effective sizes may then be strongly overestimated. The timing during the life cycle at which F-statistics are evaluated is also of crucial importance and attention should be paid to it when designing field sampling since different demographic models assume different timings. Our study shows that individual-based, genetically explicit models provide a promising way of evaluating the accuracy of demographic models of effective size and delineate their field of applicability.

An estimate of the potential number of mayfly species (Ephemeroptera, Insecta) still to be described in Brazil

ABSTRACTThis study reviewed the data on the Brazilian Ephemeroptera, based on the studies published before July, 2013, estimated the number of species still to be described, and identified which regions of the country have been the subject of least research. More than half the species are known from the description of only one developmental stage, with imagoes being described more frequently than nymphs. The Brazilian Northeast is the region with the weakest database. Body size affected description rates, with a strong tendency for the larger species to be described first. The estimated number of unknown Brazilian species was accentuated by the fact that so few species have been described so far. The steep slope of the asymptote and the considerable confidence interval of the estimate reinforce the conclusion that a large number of species are still to be described. This emphasizes the need for investments in the training of specialists in systematics and ecology for all regions of Brazil to correct these deficiencies, given the role of published papers as a primary source of information, and the fundamental importance of taxonomic knowledge for the development of effective measures for the conservation of ephemeropteran and the aquatic ecosystems they depend on.

Activation mechanisms of the protease MALT1 and cleavage of one of its targets - the ribonuclease Regnase-1- in lymphocytes and lymphoma cell lines

Persistent infection induces an adaptive immune response that is mediated by T and B lymphocytes. Upon triggering with an antigen, these cells become activated and turn into fast expanding cells able to efficiently defend the host. Lymphocyte activation is controlled by a complex composed of CARMA1, BCL10 and MALT1 which regulates the NF-KB signaling pathway upon antigen triggering. Abnormally high expression or activity of either one of these three proteins can favor the development of lymphomas, while genetic defects in the pathway are associated with immunodeficiency. MALT1 was identified as a paracaspase sharing homology with other cysteine proteases, namely caspases and metacaspases. In order to be active, caspases need to dimerize. Based on their sequence similarity with MALT1, we hypothesized that dimerization might also be a mechanism of activation employed by MALT1. To address this assumption, we performed a bioinformatics modelling based on the crystal structures of several caspases. Our model suggested that the MALT1 caspase-like domain can indeed form dimers. This finding was later confirmed by several published crystal structures of MALT1. In the dimer interface of our model, we noticed the presence of charged amino acids that could potentially form salt bridges and thereby hold both monomers together. Mutation of one of these residues, E549, into alanine completely blocked the catalytic activity of MALT1. Additionally, we provided evidence for a role of E549 in promoting the MALTl-dependent growth of cells derived from diffuse large B cell lymphoma (DLBCL) of the aggressive B cell-like type (ABC). To our initial surprise, the E549A mutation showed only a partial defect in dimerization, indicating that additional residues are essential to form a stable dimer. The MALT1 crystal structures revealed a key function for E549 in stabilizing the catalytic site of the protease via its interaction with an arginine which is located next to the catalytic active cysteine. In an additional study, we discovered that MALT1 monoubiquitination is required for the catalytic activity of the protease. Interestingly, we found that the MALT1 dimer interface mutant E549A could not be monoubiquitinated. Based on these findings, we suggest that correct formation of the dimer interface is a prerequisite for monoubiquitination. In a second project, we discovered a novel target of the protease MALT1, the ribonuclease Regnase¬la It was described that the RNase activity of Regnase-1 negatively regulates immune responses. We could show that in ABC DLBCL cell lines, Regnase-1 is not only cleaved by MALT1 but also phosphorylated, at least in part, by the inhibitor of KB kinase (IKK). Both regulations appear to restrain the RNase function of Regnase-1 and thereby allow the production of pro-survival proteins. In conclusion, our studies further highlight and explain the importance of the catalytic activity of MALT1 for the activation of lymphocytes and provide additional knowledge for the development of specific drugs targeting the catalytic activity of MALT1 for immunomodulation and treatment of lymphomas.  SUMMARY IN FRENCH PhD Thesis Katrin Cabalzar 2 SUMMARY IN FRENCH Une infection persistante induit une réponse immunitaire adaptative par l'intermédiaire des lymphocytes T et B. Quand elles reconnaissent l'antigène, ces cellules sont activées et se multiplient très rapidement pour défendre efficacement l'hôte. L'activation des lymphocytes est transmise par un complexe composé de trois protéines, CARMA1, BCL10 et MALT1, qui régule la voie de signalisation NF-KB lorsque l'antigène est reconnu. L'expression ou l'activité anormalement élevée de l'une de ces trois protéines peut favoriser le développement de lymphomes, tandis que des défauts génétiques de cette voie de signalisation sont associés à l'immunodéficience. MALT1 a été identifiée comme étant une paracaspase qui partage des séquences homologues avec d'autres protéases à cystéine, comme les caspases et les métacaspases. Pour être actives, les caspases ont besoin de dimériser. Etant donné leur similarité de séquence avec MALT1, nous avons supposé que la dimérisation pouvait aussi être un mécanisme d'activation utilisé par MALT1. Pour vérifier cette hypothèse, nous avons conçu un modèle bioinformatique à partir des structures cristallographiques de plusieurs caspases. Et notre modèle a suggéré que le domaine catalytique de MALT1 était effectivement capable de former des dimères. Cette découverte a été confirmée plus tard par des publications qui montrent des structures cristallographiques dimériques de MALT1. Dans l'interface du dimère de notre modèle, nous avons remarqué la présence d'acides aminés chargés qui pouvaient former des liaisons ioniques et ainsi réunir les deux monomères. La mutation de l'un de ces résidus, E549, pour une alanine, a complètement inhibé l'activité catalytique de MALT1. De plus, nous avons mis en évidence un rôle d'E549 dans la croissance dépendante de MALT1, des cellules dérivées de lymphomes B diffus à grandes cellules (DLBCL) de sous-type cellules B actives (ABC). Dans un premier temps nous avons été surpris de constater que cette mutation révélait seulement un défaut partiel de dimérisation, ce qui indique que des acides aminés supplémentaires sont indispensables pour former un dimère stable. Les structures cristallographiques de MALT1 ont révélé un rôle primordial d'E549 dans la stabilisation du site catalytique de la protéase via son interaction avec une arginine qui se trouve à côté de la cystéine du site actif. Dans une autre étude, nous avons découvert que la monoubiquitination de MALT1 est requise pour l'activité catalytique de la protéase. A remarquer que nous avons trouvé que le mutant E549A de l'interface dimère de MALT1 n'a pas pu être monoubiquitiné. Sur la base de ces résultats, nous suggérons que la formation correcte de l'interface du dimère est une condition préalable pour la monoubiquitination. Dans un second projet, nous avons découvert une nouvelle cible de la protéase MALT1, la ribonucléase Regnase-1. Il a été décrit que l'activité RNase de Regnase-1 régulait négativement les réponses immunitaires. Nous avons pu montrer que dans les lignées cellulaires ABC DLBCL, la Regnase-1 n'était pas seulement clivée par MALT1 mais également phosphorylée, au moins en partie, par la kinase de l'inhibiteur de KB (IKK). Les deux régulations semblent supprimer la fonction RNase de Regnase-1 et permettre ainsi la stabilisation de certains ARN messagers et la production de protéines favorisant la survie. En conclusion, nos études mettent en évidence le rôle-clé de la dimérisation de MALT1 et expliquent l'importance de l'activité catalytique de MALT1 pour l'activation des lymphocytes. Ainsi, nos résultats apportent des connaissances supplémentaires pour le développement de médicaments spécifiques ciblant l'activité catalytique de MALT1, qui pourraient être utiles pour modifier les réponses immunitaires et traiter des lymphomes.

Putative adverse outcome pathways relevant to neurotoxicity.

The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways.

Insights into the Design and Characteristics of the Sedimentation Process at Multi-Barrel Culverts in Iowa, TR-596, 2010

The present study is an integral part of a broader study focused on the design and implementation of self-cleaning culverts, i.e., configurations that prevent the formation of sediment deposits after culvert construction or cleaning. Sediment deposition at culverts is influenced by many factors, including the size and characteristics of material of which the channel is composed, the hydraulic characteristics generated under different hydrology events, the culvert geometry design, channel transition design, and the vegetation around the channel. The multitude of combinations produced by this set of variables makes the investigation of practical situations a complex undertaking. In addition to the considerations above, the field and analytical observations have revealed flow complexities affecting the flow and sediment transport through culverts that further increase the dimensions of the investigation. The flow complexities investigated in this study entail: flow non-uniformity in the areas of transition to and from the culvert, flow unsteadiness due to the flood wave propagation through the channel, and the asynchronous correlation between the flow and sediment hydrographs resulting from storm events. To date, the literature contains no systematic studies on sediment transport through multi-box culverts or investigations on the adverse effects of sediment deposition at culverts. Moreover, there is limited knowledge about the non-uniform, unsteady sediment transport in channels of variable geometry. Furthermore, there are few readily useable (inexpensive and practical) numerical models that can reliably simulate flow and sediment transport in such complex situations. Given the current state of knowledge, the main goal of the present study is to investigate the above flow complexities in order to provide the needed insights for a series of ongoing culvert studies. The research was phased so that field observations were conducted first to understand the culvert behavior in Iowa landscape. Modeling through complementary hydraulic model and numerical experiments was subsequently carried out to gain the practical knowledge for the development of the self-cleaning culvert designs.

Information and Communication Society's Impact on Global Paper Consumption

Tämän tutkielman tavoitteena on selvittää informaatio- ja kommunikaatioyhteiskunnan vaikutusta paperin kulutukseen maailmanlaajuisesti. Tarkoituksena on löytää informaatio- ja kommunikaatioyhteiskuntaa kuvaavia mittareita, joiden avulla voidaan vertailla kehittyneitä ja kehittyviä markkina-alueita keskenään. Tutkimusongelmaan haetaan ratkaisua tutkimalla sekä kirjallisuutta että tilastoja, ja vertaamalla niitä esitettyihin teorioihin informaatio- ja kommunikaatioyhteiskunnan kehityksestä. Tutkielman avulla pyritään arvioimaan ja kuvaamaantoimintaympäristön muutoksia paperin kulutuksen suhteen pitkällä aikavälillä informaatio- ja kommunikaatioyhteiskunnan näkökulmasta.

Kuvausmenetelmänvalinta ja käyttöönotto ohjelmistotuoteorganisaatiossa

Useiden pitkän kehityskaaren ohjelmistojen ylläpitäminen ja kehittäminen on vaikeaa, sillä niiden dokumentaatio on vajaata tai vanhentunutta. Tässä diplomityössä etsitään ratkaisua tällaisen ohjelmiston ja sen taustalla olevan järjestelmän kuvaukseen. Tavoitteina on tukea nykyisen ohjelmiston ylläpitoa ja uuden työvoiman perehdyttämistä. Tavoitteena on myös pohjustaa uuden korvaavan ohjelmiston suunnittelua kuvaamalla nykyiseen järjestelmään sitoutunutta sovellusalueosaamista. Työssä kehitetään kuvausmenetelmä järjestelmän kuvaamiseen hierarkkisesti laitteistotason yleiskuvauksesta ohjelmiston luokkarakenteeseen sekä toiminnallisuuteen asti. Laite- ja luokkarakennekuvaukset ovat rakenteellisia kuvauksia, joiden tehtävänä on selittää järjestelmän ja sen osien kokoonpano. Toiminnallisuudesta kertovat kuvaukset on toteutettu käyttötapauskuvauksina. Työssä keskityttiin erityisesti kohdejärjestelmän keskeisen ohjelmiston ja tietokannan kuvaamiseen. Ohjelmistosta valittiin tärkeimmät ja eniten sovellusalueen tietotaitoa sisältävät osat, joista työssä luotiin esimerkkikuvaukset. Kuvauksia on kehitettyä menetelmää hyödyntäen helppo laajentaa tarpeiden mukaan paitsi ohjelmiston muihin osiin, myös laitteiston ja järjestelmän kuvaamiseen kokonaisuudessaan syvemmin.

Siltanosturin teräsrakenteen suunnittelun avuksi luodun ohjelman jatkokehitys

Diplomityössä tehdään jatkokehitystä KCI Konecranes yrityksen siltanosturin laskentaohjelmaan. Ohjelman tärkeimmät jatkokehityskohteet kartoitettiin käyttäjäkyselyn avulla ja niistä valittiin toivotuimmat, sekä diplomityön lujuusopilliseen aihepiiriin parhaiten soveltuvat. Työhön valitut kaksi aihetta ovat koteloprofiilin kaksiosaisen uuman lujuuslaskennan selvittäminen ja siltanosturin kahdeksanpyöräisenpäätykannattajan elementtimallin suunnittelu. Diplomityössä selvitetään jatkokehityskohteisiin liittyvä teoria, mutta varsinainen ohjelmointi jätetään työn ulkopuolelle. Kaksiosaisella uumalla varustetussa koteloprofiilissa nostovaunun kulkukiskon alla olevan uuman yläosa tehdään paksummaksi, jotta uuma kestäisi nostovaunun pyöräkuormasta aiheutuvan paikallisen jännityksen, eliniin sanotun rusennusjännityksen. Rusennusjännityksen määrittäminen uumalevyissä on kaksiosaisen uuman lujuuslaskennan tärkein tehtävä. Rusennuksen aiheuttamankalvojännityksen ja jännityskeskittymien määrittämiseen erilaisissa konstruktioissa etsittiin sopivimmat menetelmät kirjallisuudesta ja standardeista. Kalvojännitys voidaan määrittää luotettavasti käyttäen joko 45 asteen sääntöä tai standardin mukaista menetelmää ja jännityskonsentraatioiden suuruus saadaan kertomallakalvojännitys jännityskonsentraatiokertoimilla. Menetelmien toimivuus verifioitiin tekemällä kymmeniä uuman elementtimalleja erilaisin dimensioin ja reunaehdoin ja vertaamalla elementtimallien tuloksia käsin laskettuihin. Käsin lasketut jännitykset saatiin vastaamaan tarkasti elementtimallien tuloksia. Kaksiosaisen uuman lommahdus- ja väsymislaskentaa tutkittiin alustavasti. Kahdeksanpyöräisiä päätykannattajia käytetään suurissa siltanostureissa pienentämään pyöräkuormia ja radan rusennusjännityksiä. Kahdeksanpyöräiselle siltanosturin päätykannattajalle suunniteltiin elementtimallit molempiin rakenteesta käytettyihin konstruktioihin: nivelöityyn ja jäykkäkehäiseen malliin. Elementtimallien rakentamisessa hyödynnettiin jo olemassa olevia malleja, jolloin niiden lisääminen ohjelmakoodiin nopeutuu ja ne ovat varmasti yhteensopivia muiden laskentamoduuleiden kanssa. Elementtimallien värähtelyanalyysin reunaehtoja tarkasteltiin. Värähtelyanalyysin reunaehtoihin ei tutkimuksen perusteella tarvitse tehdä muutoksia, mutta staattisen analyysin reunaehdot kaipaavat vielä lisätutkimusta.

Characterization of Fas (Apo-1, CD95)-Fas ligand interaction.

The death-inducing receptor Fas is activated when cross-linked by the type II membrane protein Fas ligand (FasL). When human soluble FasL (sFasL, containing the extracellular portion) was expressed in human embryo kidney 293 cells, the three N-linked glycans of each FasL monomer were found to be essential for efficient secretion. Based on the structure of the closely related lymphotoxin alpha-tumor necrosis factor receptor I complex, a molecular model of the FasL homotrimer bound to three Fas molecules was generated using knowledge-based protein modeling methods. Point mutations of amino acid residues predicted to affect the receptor-ligand interaction were introduced at three sites. The F275L mutant, mimicking the loss of function murine gld mutation, exhibited a high propensity for aggregation and was unable to bind to Fas. Mutants P206R, P206D, and P206F displayed reduced cytotoxicity toward Fas-positive cells with a concomitant decrease in the binding affinity for the recombinant Fas-immunoglobulin Fc fusion proteins. Although the cytotoxic activity of mutant Y218D was unaltered, mutant Y218R was inactive, correlating with the prediction that Tyr-218 of FasL interacts with a cluster of three basic amino acid side chains of Fas. Interestingly, mutant Y218F could induce apoptosis in murine, but not human cells.

Tietointensiivisen palvelutuotannon kehittäminen: case televiestintäyrityksen vianhallinta

Tämän tutkimuksen tavoitteena oli luoda tavoitemalli TeliaSonera Finland Oyj:n vianhallintapalveluille. Tavoitemalli tuli muodostaa niin, että se tukee laadukasta ja tuottavaa teollista palvelutuotantoa. Tavoitemalli muodostettiin suhteellisen laajan teoriakatsauksen perusteella, joka tehtiin tiedon näkökulmasta. Palvelujen hallinnan viitekehyksessä tutkittiin palvelujen suorituskykyä, jossa erityisesti paneuduttiin laatuun, tuottavuuteen ja palvelutuotannon psykososiaaliseen työympäristöön. Tähän kokonaisuuteen yhdistettiin tutkimustietoa palvelujen teollistamisesta, sekä otettiin huomioon tietointensiivisen organisaation yleiset menestystekijät. Näin muodostettiin tietointensiivisen palvelutuotannon hallinnan ja kehittämisen viitekehys, jota sovellettiin vianhallintapalvelujen tavoitetilan muodostamiseen. Vianhallinnan tavoitetila testattiinosin empiirisesti, mutta lisätutkimusta tarvitaan työssä muodostetun teoreettisen viitekehyksen arviointiin.

Integration in strategic alliances : a conceptual framework of IT use in marketing as NPD key factor

En una economia basada en el coneixement, la innovació del producte es considera un factor clau a l'hora de determinar la competitivitat, la productivitat i el creixement d'una companyia. No obstant això, l'experiència de les companyies demostra la necessitat d'un nou model de gestió de la innovació del producte: una gestió basada en el màrqueting, en què la cooperació i l'ús intensiu de les tecnologies de la informació i de la comunicació (TIC) són especialment importants. En els darrers anys, la bibliografia sobre màrqueting ha analitzat el paper de la cooperació en l'èxit del procés d'innovació. No obstant això, fins ara pocs treballs han estudiat el paper que té l'ús de les TIC en el màrqueting en l'èxit del desenvolupament de nous productes (NPD, New Product Development en anglès). És una omissió curiosa, tenint en compte que el nou entorn competitiu és definit per una economia i una societat basades principalment en l'ús intensiu de les TIC i del coneixement. L'objectiu d'aquest treball és investigar el paper que l'ús de les TIC en el màrqueting té en el procés de desenvolupament de nous productes, com a element que reforça la integració d'agents al projecte, afavorint l'establiment de relacions dirigides a la cooperació i l'adquisició d'intel·ligència de mercat útil en el procés de desenvolupament de nous productes. L'estudi d'una mostra de 2.038 companyies de tots els sectors de l'activitat econòmica a Catalunya ens permet contrastar hipòtesis inicials i establir un perfil de companyia innovadora basat en les importants relacions que hi ha entre la innovació, l'ús de TIC en el màrqueting i la integració. Sobresurten dues idees en la nostra anàlisi. En primer lloc, l'ús intensiu de les TIC en el màrqueting fa que la companyia sigui més innovadora, ja que percep que el seu ús ajuda a superar barreres a la innovació i accelera els processos, que es tornen més eficients. En segon lloc, incrementant l'ús de les TIC en el màrqueting es fa augmentar la predisposició de la companyia a integrar agents particulars en l'entorn de negoci en el desenvolupament del procés d'innovació i a col·laborar-hi, de manera que es millora el grau d'adaptació del nou producte a les demandes del mercat.

Osaaminen yrityksissä

Työn tavoitteena olitutkia osaamisen johtamista, kehittämistä ja hallintaa yrityksissä. Tutkimuksenpääkysymyksinä selvitettiin, kuinka tärkeänä yritykset pitävät osaamisen ja tietämyksen hallintaa, mitä ongelmia ja haasteita siinä koetaan sekä mitä työkalujayrityksissä käytetään osaamisen ja tietämyksen hallinnassa. Tutkimuksessa esitetään kirjallisuuden pohjalta, mitä on osaaminen sekä miten sitä voidaan kehittääja hallita. Aihepiiriin liittyen suoritettiin empiirinen tutkimus, jonka perusteella voidaan todeta, että osaamisen hallintaa pidetään yrityksissä erittäin tärkeänä asiana kilpailukyvyn kannalta vaikkakin se aiheuttaa paljon lisätyötä ja on aikaa vievää. Tutkimuksen tuloksen mukaan osaamisen kehittämisessä ja hallinnassa yrityksissä esiintyy paljon haasteita ja ongelmia.

Conflict-based Method for Conceptual Process Synthesis

The changing business environment demands that chemical industrial processes be designed such that they enable the attainment of multi-objective requirements and the enhancement of innovativedesign activities. The requirements and key issues for conceptual process synthesis have changed and are no longer those of conventional process design; there is an increased emphasis on innovative research to develop new concepts, novel techniques and processes. A central issue, how to enhance the creativity of the design process, requires further research into methodologies. The thesis presentsa conflict-based methodology for conceptual process synthesis. The motivation of the work is to support decision-making in design and synthesis and to enhance the creativity of design activities. It deals with the multi-objective requirements and combinatorially complex nature of process synthesis. The work is carriedout based on a new concept and design paradigm adapted from Theory of InventiveProblem Solving methodology (TRIZ). TRIZ is claimed to be a `systematic creativity' framework thanks to its knowledge based and evolutionary-directed nature. The conflict concept, when applied to process synthesis, throws new lights on design problems and activities. The conflict model is proposed as a way of describing design problems and handling design information. The design tasks are represented as groups of conflicts and conflict table is built as the design tool. The general design paradigm is formulated to handle conflicts in both the early and detailed design stages. The methodology developed reflects the conflict nature of process design and synthesis. The method is implemented and verified through case studies of distillation system design, reactor/separator network design and waste minimization. Handling the various levels of conflicts evolve possible design alternatives in a systematic procedure which consists of establishing an efficient and compact solution space for the detailed design stage. The approach also provides the information to bridge the gap between the application of qualitative knowledge in the early stage and quantitative techniques in the detailed design stage. Enhancement of creativity is realized through the better understanding of the design problems gained from the conflict concept and in the improvement in engineering design practice via the systematic nature of the approach.

Modeling and measuring organizational renewal capability

Globalization and new information technologies mean that organizations have to face world-wide competition in rapidly transforming, unpredictable environments, and thus the ability to constantly generate novel and improved products, services and processes has become quintessential for organizational success. Performance in turbulent environments is, above all, influenced by the organization's capability for renewal. Renewal capability consists of the ability of the organization to replicate, adapt, develop and change its assets, capabilities and strategies. An organization with a high renewal capability can sustain its current success factors while at the same time building new strengths for the future. This capability does not only mean that the organization is able to respond to today's challenges and to keep up with the changes in its environment, but also that it can actas a forerunner by creating innovations, both at the tactical and strategic levels of operation and thereby change the rules of the market. However, even though it is widely agreed that the dynamic capability for continuous learning, development and renewal is a major source of competitive advantage, there is no widely shared view on how organizational renewal capability should be defined, and the field is characterized by a plethora of concepts and definitions. Furthermore,there is a lack of methods for systematically assessing organizational renewal capability. The dissertation aims to bridge these gaps in the existing research by constructing an integrative theoretical framework for organizational renewal capability and by presenting a method for modeling and measuring this capability. The viability of the measurement tool is demonstrated in several contexts, andthe framework is also applied to assess renewal in inter-organizational networks. In this dissertation, organizational renewal capability is examined by drawing on three complimentary theoretical perspectives: knowledge management, strategic management and intellectual capital. The knowledge management perspective considers knowledge as inherently social and activity-based, and focuses on the organizational processes associated with its application and development. Within this framework, organizational renewal capability is understood as the capacity for flexible knowledge integration and creation. The strategic management perspective, on the other hand, approaches knowledge in organizations from the standpoint of its implications for the creation of competitive advantage. In this approach, organizational renewal is framed as the dynamic capability of firms. The intellectual capital perspective is focused on exploring how intangible assets can be measured, reported and communicated. From this vantage point, renewal capability is comprehended as the dynamic dimension of intellectual capital, which consists of the capability to maintain, modify and create knowledge assets. Each of the perspectives significantly contributes to the understanding of organizationalrenewal capability, and the integrative approach presented in this dissertationcontributes to the individual perspectives as well as to the understanding of organizational renewal capability as a whole.

Involvement of family physicians in structured programs for chronic diseases or multi-morbidity in Switzerland.

The increasing prevalence of chronic diseases and multi-morbidity represents challenges for health systems worldwide. In that perspective, the current organization of healthcare delivery, fragmentation of care, limited use of evidence-based guidelines and patients'insufficient empowerment are some reasons explaining the current limited effectiveness of the management of chronically ill patients. Based on theoretical models such as the Chronic Care Model (CCM), initiatives targeting improvements in the care of patients with chronic diseases have been implemented worldwide since more than a decade. Their development in Switzerland, a health system where more than half of practices are still single handed [6], is only recent and infrequent. Structured programs for patients with chronic diseases or multimorbidity usually propose patient-centered interventions and consider an integrative multidisciplinary approach. Currently, little is known on the existence of such programs and on the role of family physicians (FPs)within these programs, in Switzerland. The objective of this study was to identify and describe current structured programs targeting chronic diseases or multi-morbidity in Switzerland. This may help in examining innovative approaches that are only developed locally but would deserve wider interest for further implementation. We conducted a telephone-based survey between June and November 2013 and contacted systematically key institutions, informants and stakeholders nationwide and in the 26 cantons...