Safety and outcome of coronary interventions with special reference to anticoagulation and stent type

University of Turku, Faculty of Medicine, Department of Cardiology and Cardiovascular Medicine, Doctoral Programme of Clinical Investigation, Heart Center, Turku University Hospital, Turku, Finland Division of Internal Medicine, Department of Cardiology, Seinäjoki Central Hospital, Seinäjoki, Finland Heart Center, Satakunta Central Hospital, Pori, Finland Annales Universitatis Turkuensis Painosalama Oy, Turku, Finland 2015 Antithrombotic therapy during and after coronary procedures always entails the challenging establishment of a balance between bleeding and thrombotic complications. It has been generally recommended to patients on long-term warfarin therapy to discontinue warfarin a few days prior to elective coronary angiography or intervention to prevent bleeding complications. Bridging therapy with heparin is recommended for patients at an increased risk of thromboembolism who require the interruption of anticoagulation for elective surgery or an invasive procedure. In study I, consecutive patients on warfarin therapy referred for diagnostic coronary angiography were compared to control patients with a similar disease presentation without warfarin. The strategy of performing coronary angiography during uninterrupted therapeutic warfarin anticoagulation appeared to be a relatively safe alternative to bridging therapy, if the international normalized ratio level was not on a supratherapeutic level. In-stent restenosis remains an important reason for failure of long-term success after a percutaneous coronary intervention (PCI). Drug-eluting stents (DES) reduce the problem of restenosis inherent to bare metal stents (BMS). However, a longer delay in arterial healing may extend the risk of stent thrombosis (ST) far beyond 30 days after the DES implantation. Early discontinuation of antiplatelet therapy has been the most important predisposing factor for ST. In study II, patients on long-term oral anticoagulant (OAC) underwent DES or BMS stenting with a median of 3.5 years’follow-up. The selective use of DESs with a short triple therapy seemed to be safe in OAC patients, since late STs were rare even without long clopidogrel treatment. Major bleeding and cardiac events were common in this patient group irrespective of stent type. In order to help to predict the bleeding risk in patients on OAC, several different bleeding risk scorings have been developed. Risk scoring systems have also been used also in the setting of patients undergoing a PCI. In study III, the predictive value of an outpatient bleeding risk index (OBRI) to identify patients at high risk of bleeding was analysed. The bleeding risk seemed not to modify periprocedural or long-term treatment choices in patients on OAC after a percutaneous coronary intervention. Patients with a high OBRI often had major bleeding episodes, and the OBRI may be suitable for risk evaluation in this patient group. Optical coherence tomography (OCT) is a novel technology for imaging intravascular coronary arteries. OCT is a light-based imaging modality that enables a 12–18 µm tissue axial resolution to visualize plaques in the vessel, possible dissections and thrombi as well as, stent strut appositions and coverage, and to measure the vessel lumen and lesions. In study IV, 30 days after titanium-nitride-oxide (TITANOX)-coated stent implantation, the binary stent strut coverage was satisfactory and the prevalence of malapposed struts was low as evaluated by OCT. Long-term clinical events in patients treated with (TITANOX)-coated bio-active stents (BAS) and paclitaxel-eluting stents (PES) in routine clinical practice were examined in study V. At the 3-year follow-up, BAS resulted in better long-term outcome when compared with PES with an infrequent need for target vessel revascularization. Keywords: anticoagulation, restenosis, thrombosis, bleeding, optical coherence tomography, titanium

Toisen jäte on toisen raaka-aine – Kierrätys ja uudelleenvalmistus taloudellisesti ja ekologisesti kestävänä liiketoimintamahdollisuutena

Toisen jäte on toisen raaka-aine – Kierrätys ja uudelleenvalmistus taloudellisesti ja ekologisesti kestävänä liiketoimintamahdollisuutena Väitöskirjatutkimus tarkastelee kierrätystä ja uudelleenvalmistusta sekä siihen perustuvaa kierrätysliiketoimintaa taloudellisesti ja ekologisesti kestävänä liiketoimintamahdollisuutena. Tässä kestävyys tarkoittaa jätekysymysten ratkaisemista tavalla, joka mahdollistaa kestävän kehityksen periaatteiden mukaisen yhteiskunnan kehittymisen. Jätteisiin liittyvät taloudelliset ja ekolo- giset kysymykset ovat merkittävä yhteiskunnallinen haaste. Tämä luo tarpeen tutkimukselle, jonka lähtökohtana on jätekysymysten moniulotteinen tarkas- telu ja yksittäisen yrityksen toiminnan suhteuttaminen osaksi laajempaa kokonaisuutta. Tässä tutkimuksessa jätteen hyödyntämistä materiaalina lähestytään sekä empiirisesti yrityksen näkökulmasta että teoreettisesti systeemiajattelun tarjoamasta laajemmasta perspektiivistä. Tutkimuksen tavoitteena on ymmär- tää kierrätystä ja uudelleenvalmistusta liiketoimintamahdollisuutena, niiden merkitystä yrityksessä, alueella ja kierrätystaloudessa sekä näiden vuorovai- kutteista suhdetta taloudelliseen ja ekologiseen kestävyyteen nähden. Tutki- muskysymys on tärkeä, koska siihen vastaamalla syvennetään ymmärrystä yrityksissä tapahtuvan kierrätyksen ja uudelleenvalmistuksen merkityksestä kestävämmän yhteiskunnan rakentumisessa. Tutkimuksen teoriaperusta pohjautuu teollisen ekologian kirjallisuuteen ja ekoteollisen kehityksen tutkimukseen. Kierrätysliiketoiminnan kestävyyden tarkastelu rakentuu tutkimuksessa teollisen ekologian ja ekoteollisen kehityk- sen lähtökohtana olevaan win-win-ajatteluun, jonka mukaan hyvä ympäristö- suorituskyky ja hyvä taloudellinen suorituskyky voivat vahvistaa toisiaan. Kierrätysliiketoiminnan teoreettisessa tarkastelussa keskeisiä elementtejä ovat kierrätystalouden malli, teollisen ekologian alueelliset systeemit, ekoteolliset verkostot ja yrityksen rooli teollista ekologiaa soveltavana toimijana. Tutki- muksen keskeisenä kontribuutiona on yritysnäkökulman integroiminen aiem- paa vahvemmin osaksi teollisen ekologian diskursseja. Kierrätysliiketoiminnan taloudelliseen ja ekologiseen kannattavuuteen ja sen myötä kestävyyteen liittyviä kysymyksiä on lähestytty tekemällä yritys- haastatteluja ja hyödyntämällä valmista haastatteluaineistoa. Tutkimusta varten haastattelin 10 kierrätysliiketoimintaa harjoittavaa yritystä vuosina 2007 ja 2008. Tämän lisäksi tutkimuksessa on hyödynnetty Turun ammatti- korkeakoulun ja Turku Science Parkin toteuttamassa RESU-hankkeessa (Kierrätysliiketoiminta ja resurssitehokkuus Varsinais-Suomen vahvuudeksi – RESU) vuosina 2013 ja 2014 kerättyä aineistoa. Hankkeessa haastateltiin yhteensä 25 jätemateriaalia hyödyntävää ja/tai tuottavaa yritystä. Aineistojen analysointimenetelmänä on sisällönanalyysi. Analyysin tulok- sena muodostettiin yhteensä viisi pääteemaa ja 12 alateemaa. Teemat kuvaavat kierrätysliiketoimintaa aiempaa moniulotteisemmin ja näin syventävät ymmär- rystä ilmiön merkityksestä kestävämmän yhteiskunnan rakentumisessa. Teolli- sen ekologian alaan kuuluvat kvalitatiiviset tutkimukset ovat melko harvinai- sia, joten tämän väitöstutkimuksen ilmeisenä vahvuutena on laadullisen tutkimusmenetelmän hyödyntäminen. Tutkimuksen tuloksena voidaan todeta, että kierrätystalouden kehittymistä edistävä kierrätysliiketoiminta on monimuotoista ja sisältää erilaisia liiketoi- mintamahdollisuuksia sekä arvoketjuja. Paikallistuntemus ja keskeinen sijainti jätemateriaalien tuottajien suhteen on tärkeä kriteeri kierrätysliiketoiminnassa, mutta jätemateriaaleja myös kuljetetaan pitkiä matkoja. Paikallisia tai alueelli- sia jätevirtoja hyödyntävä kierrätysliiketoiminta voi tukea alueellista kestä- vyyttä, mutta toisinaan myös keskitetty hyödyntäminen voi olla kestävä vaih- toehto. Yhteistyöverkostot ovat tärkeitä jätemateriaalin laadun ja saatavuuden näkökulmasta. Tutkimus osoittaa, että kierrätysliiketoimintaa harjoittavat yritykset ovat samalla sekä kierrätystalouden käytännön toimeenpanijoita että uuden toimintakulttuurin luojia. Tutkimuksen tulosten perusteella voidaan esittää johtopäätös, että kierrä- tysliiketoiminta on taloudellisesti ja ekologisesti kannattava liiketoimintamah- dollisuus. Win-win-ratkaisut eivät kuitenkaan takaa kierrätysliiketoiminnan kestävyyttä. Kierrätysliiketoiminnan kestävyyden arvioiminen edellyttää laajaa perspektiiviä ja toiminnan vaikutusten suhteuttamista mittakaavaan, ajalliseen ulottuvuuteen, interventioon ja sosiaalisiin kysymyksiin. Teolliseen ekologiaan perustuva kierrätysliiketoiminta luo mahdollisuuksia edistää kestävyyttä, joten tällä perusteella kierrätystä ja uudelleenvalmistusta voidaan pitää kestävänä liiketoimintamahdollisuutena. Avainsanat: kierrätysliiketoiminta, kierrätys, uudelleenvalmistus, systeemiajattelu, teollinen ekologia, ekoteollinen kehitys, kierrätystalous, win-win-ajattelu, kestävyys One company's waste is another's raw material –Recycling and remanufacturing as an economically and environmentally sustainable business opportunity The thesis investigates whether product recycling and remanufacturing can serve as a business opportunity that is economically and ecologically sustaina- ble. In this effort, my idea is to contribute to solving the waste issue in a manner that makes it possible to strive toward sustainable societal develop- ment. The economic and ecological questions associated with waste flows are a significant challenge. The complexity of the issue requires a multidimen- sional approach in which the operation of an individual company is viewed in the context of the larger societal system. In this thesis waste utilization as a resource with value is considered both from an empirical perspective on the firm as well as from a more general viewpoint offered by systems analysis. The objective of the thesis is to under- stand recycling and remanufacturing as a business opportunity. The thesis considers the meaning of recycling and remanufacturing for a single company, for the region the company is located and for the recycling economy. The objective of this study is important for it enhances the understanding of the product recycling and remanufacturing processes that take place within busi- ness organizations and how these processes affect societal sustainable development. The theoretical basis arises from industrial ecology and from the literature on eco-industrial development. The business-economic win-win situation and this vision serve as the basic position from which recycling business is inves- tigated in the thesis. In the theoretical discussion, key elements are recycling economy model, regional and local industrial ecosystems, eco-industrial networks and the role of a company as an actor that applies industrial ecology in practice. The main contribution of this study lies in integrating the company perspective more strongly into the industrial ecology discourses. The recycling business has been studied by conducting interviews in companies and by secondary analysis of an existing interview material. During 2007 and 2008 I made 10 interviews in companies that are active in recycling business. In addition, I used interview material gathered for the project “Recycling business and resource efficiency as the strength of Southwest Finland” (RESU) by Turku University of Applied Sciences and Turku Science Park during the period 2013–2014. This data covers altogether 25 businesses that either utilize and/or produce waste materials. The data has been analyzed using the content analysis method. This process led to the development of 5 main themes and 12 sub-themes. These themes describe the recycling business multi-dimensionally and thus understanding of the phenomenon and its role in building a sustainable society are substantially deepened in this research. In the field of industrial ecology qualitative studies are relatively rare and therefore the qualitative research approach is an evident strength of the thesis. The results show that the recycling business activity supporting recycling economy has diverse dimensions including various business opportunities and diverse value chains. The results show that for waste producers it is important to know the local situational factors and to have a central geographical location. Waste materials are, however, transported over long distances as well. The study indicates that local waste flow utilization can support regional sustainability, while occasionally a more centralized utilization can be sustain- able. Collaboration networks are important to secure the quality and availabil- ity of utilizable waste materials. The thesis demonstrates that the companies practicing recycling business serve simultaneously as actors that implement recycling economy and enhance a new operation culture within the business community. The overall conclusion of the thesis argues that recycling business is a business opportunity that can support both an economically and environmen- tally viable business operation. However, win-win solutions do not secure the sustainability of recycling business. The sustainability evaluation of recycling business requires a holistic systems perspective. The actions undertaken need to be considered with changing spatial and temporal system boundaries, societal intervention and placed in the context of relevant societal issues. Industrial ecology -based recycling business creates opportunities for sustain- ability and thus recycling and remanufacturing present an opportunity for sustainable business. Keywords: Recycling business; Recycling; Remanufacturing, Systems thinking; Industrial ecology; Eco-industrial development; Recycling Economy; Win-Win thinking; Sustainability

Roles of keratins in intestinal health and disease

Intermediate filament keratins (K) play a pivotal role in protein targeting and epithelialcytoprotection from stress as evidenced by keratin mutations predisposing to human liver and skin diseases and possibly inflammatory bowel disease (IBD). The K8-null (K8-/-) mice exhibit colonic phenotype similar to IBD and marked spontaneous colitis, epithelial hyperproliferation, decreased apoptosis, mistargeting of proteins leading to defective ion transport and diarrhea. The K8-heterozygote (K8+/-) mouse colon appears normal but displays a defective sodium (Na+) and chloride (Cl-) transport similar to, but milder than K8-/-. Characterization of K8+/- colon revealed ~50% less keratins (K7, K8, K19, K20) compared to K8 wild type (K8+/+). A similar ~50% decrease was seen in K8+/- mRNA levels as compared to K8+/+, while the mRNA levels for the other keratins were unaltered. K8+/- keratins were arranged in a normal colonic crypt expression pattern, except K7 which was expressed at the top of crypts in contrast to K8+/+. The K8+/- colon showed mild hyperplasia but no signs of inflammation and no resistance to apoptosis. Experimental colitis induced by using different concentrations of dextran sulphate sodium (DSS) showed that K8+/- mice are slightly more sensitive to induced colitis and showed a delayed recovery compared to K8+/+. Hence, the K8+/- mouse with less keratins and without inflammation, provided a novel model to study direct molecular mechanisms of keratins in intestinal homeostasis and ion transport. Different candidate ion transporters for a possible role in altered ion transport seen in the K8-/- and K8+/- mouse colon were evaluated. Besides normal levels of CFTR, PAT-1 and NHE-3, DRA mRNA levels were decreased 3-4-fold and DRA protein nearly entirely lost in K8-/- caecum, distal and proximal colon compared to K8+/+. In K8+/- mice, DRA mRNA levels were unaltered while decreased DRA protein level and patchy distribution was detected particularly in the proximal colon and as compared to K8+/+. DRA was similarly decreased when K8 was knocked-down in Caco-2 cells, confirming that K8 levels modulate DRA levels in an inflammation-independent manner. The dramatic loss of DRA in colon and caecum of K8-/- mice was responsible for the chloride transport defect. The milder ion transport in K8+/- colon might be related to DRA suggesting a role for K8 in regulation of DRA expression and targeting. The current study demonstrates the importance of keratins in stress protection and cell signaling. Furthermore, we have also successfully developed a novel, simple, fast, cost effective, non-invasive in vivo imaging method for the early diagnosis of murine colitis with specificity for both genetic and experimental colitis. The said modality provides continuous measurements of reactive oxygen and nitrogen species (RONS) and minimizes the use of an increased number of experimental animals by using a luminal derivative chemiluminescent probe, L-012 which provides a cost-effective tool to study the level and longitudinal progression of colitis.

Towards a contextual understanding of B2B salespeople's selling competencies – An exploratory study among purchasing decision-makers of internationally-oriented technology firms

ABSTRACT Towards a contextual understanding of B2B salespeople’s selling competencies − an exploratory study among purchasing decision-makers of internationally-oriented technology firms The characteristics of modern selling can be classified as follows: customer retention and loyalty targets, database and knowledge management, customer relationship management, marketing activities, problem solving and system selling, and satisfying needs and creating value. For salespeople to be successful in this environment, they need a wide range of competencies. Salespeople’s selling skills are well documented in seller side literature through quantitative methods, but the knowledge, skills and competencies from the buyer’s perspective are under-researched. The existing research on selling competencies should be broadened and updated through a qualitative research perspective due to the dynamic nature and the contextual dependence of selling competencies. The purpose of the study is to increase understanding of the professional salesperson’s selling competencies from the industrial purchasing decision- makers’ viewpoint within the relationship selling context. In this study, competencies are defined as sales-related knowledge and skills. The scope of the study includes goods, materials and services managed by a company’s purchasing function and used by an organization on a daily basis. The abductive approach and ‘systematic combining’ have been applied as a research strategy. In this research, data were generated through semi- structured, person-to-person interviews and open-ended questions. The study was conducted among purchasing decision-makers in the technology industry in Finland. The branches consisted of the electronics and electro-technical industries and the mechanical engineering and metals industries. A total of 30 companies and one purchasing decision-maker from each company were purposively chosen for the sampling. The sample covers different company sizes based on their revenues, their differing structures – varying from public to family companies –that represent domestic and international ownerships. Before analyzing the data, they were organized by the purchasing orientations of the buyers: the buying, procurement or supply management orientation. Thematic analysis was chosen as the analysis method. After analyzing the data, the results were contrasted with the theory. There was a continuous interaction between the empirical data and the theory. Based on the findings, a total of 19 major knowledge and skills were identified from the buyers’ perspective. The specific knowledge and skills from the viewpoint of customers’ prevalent purchasing orientations were divided into two categories, generic and contextual. The generic knowledge and skills apply to all purchasing orientations, and the contextual knowledge and skills depend on customers’ prevalent purchasing orientations. Generic knowledge and skills relate to price setting, negotiation, communication and interaction skills, while contextual ones relate to knowledge brokering, ability to present solutions and relationship skills. Buying-oriented buyers value salespeople who are ‘action oriented experts, however at a bit of an arm’s length’, procurement buyers value salespeople who are ‘experts deeply dedicated to the customer and fostering the relationship’ and supply management buyers value salespeople who are ‘corporate-oriented experts’. In addition, the buyer’s perceptions on knowledge and selling skills differ from the seller’s ones. The buyer side emphasizes managing the subject matter, consisting of the expertise, understanding the customers’ business and needs, creating a customized solution and creating value, reliability and an ability to build long-term relationships, while the seller side emphasizes communica- tion, interaction and salesmanship skills. The study integrates the selling skills of the current three-component model− technical knowledge, salesmanship skills, interpersonal skills− and relationship skills and purchasing orientations, into a selling competency model. The findings deepen and update the content of these knowledges and skills in the B2B setting and create new insights into them from the buyer’s perspective, and thus the study increases contextual understanding of selling competencies. It generates new knowledge of the salesperson’s competencies for the relationship selling and personal selling and sales management literature. It also adds knowledge of the buying orientations to the buying behavior literature. The findings challenge sales management to perceive salespeople’s selling skills both from a contingency and competence perspective. The study has several managerial implications: it increases understanding of what the critical selling knowledge and skills from the buyer’s point of view are, understanding of how salespeople effectively implement the relationship marketing concept, sales management’s knowledge of how to manage the sales process more effectively and efficiently, and the knowledge of how sales management should develop a salesperson’s selling competencies when managing and developing the sales force. Keywords: selling competencies, knowledge, selling skills, relationship skills, purchasing orientations, B2B selling, abductive approach, technology firms

Organizational creativity – Hegemonic and alternative discourses

SUMMARY Organizational creativity – hegemonic and alternative discourses Over the course of recent developments in the societal and business environment, the concept of creativity has been brought into new arenas. The rise of ‘creative industries’ and the idea of creativity as a form of capital have attracted the interests of business and management professionals – as well as academics. As the notion of creativity has been adopted in the organization studies literature, the concept of organizational creativity has been introduced to refer to creativity that takes place in an organizational context. This doctoral thesis focuses on organizational creativity, and its purpose is to explore and problematize the hegemonic organizational creativity discourse and to provide alternative viewpoints for theorizing about creativity in organizations. Taking a discourse theory approach, this thesis, first, provides an outline of the currently predominant, i.e. hegemonic, discourse on organizational creativity, which is explored regarding themes, perspectives, methods and paradigms. Second, this thesis consists of five studies that act as illustrations of certain alternative viewpoints. Through these exemplary studies, this thesis sheds light on the limitations and taken-for-granted aspects of the hegemonic discourse and discusses what these alternative viewpoints could offer for the understanding of and theorizing for organizational creativity. This study leans on an assumption that the development of organizational creativity knowledge and the related discourse is not inevitable or progressive but rather contingent. The organizational creativity discourse has developed in a certain direction, meaning that some themes, perspectives, and methods, as well as assumptions, values, and objectives, have gained a hegemonic position over others, and are therefore often taken for granted and considered valid and relevant. The hegemonization of certain aspects, however, contributes to the marginalization of others. The thesis concludes that the hegemonic discourse on organizational creativity is based on an extensive coverage of certain themes and perspectives, such as those focusing on individual cognitive processes, motivation, or organizational climate and their relation to creativity, to name a few. The limited focus on some themes and the confinement to certain prevalent perspectives, however, results in the marginalization of other themes and perspectives. The negative, often unintended, consequences, implications, and side effects of creativity, the factors that might hinder or prevent creativity, and a deeper inquiry into the ontology and epistemology of creativity have attracted relatively marginal interest. The material embeddedness of organizational creativity, in other words, the physical organizational environment as well as the human body and its non-cognitive resources, has largely been overlooked in the hegemonic discourse, although thereare studies in this area that give reason to believe that they might prove relevant for the understanding of creativity. The hegemonic discourse is based on an individual-centered understanding of creativity which overattributes creativity to an individual and his/her cognitive capabilities, while simultaneously neglecting how, for instance, the physical environment, artifacts, social dynamics and interactions condition organizational creativity. Due to historical reasons, quantitative as well as qualitative yet functionally- oriented studies have predominated the organizational creativity discourse, although studies falling into the interpretationist paradigm have gradually become more popular. The two radical paradigms, as well as methodological and analytical approaches typical of radical research, can be considered to hold a marginal position in the field of organizational creativity. The hegemonic organizational creativity discourse has provided extensive findings related to many aspects of organizational creativity, although the con- ceptualizations and understandings of organizational creativity in the hegemonic discourse are also in many respects limited and one-sided. The hegemonic discourse is based on an assumption that creativity is desirable, good, necessary, or even obligatory, and should be encouraged and nourished. The conceptualiza- tions of creativity favor the kind of creativity which is useful, valuable and can be harnessed for productivity. The current conceptualization is limited to the type of creativity that is acceptable and fits the managerial ideology, and washes out any risky, seemingly useless, or negative aspects of creativity. It also limits the possible meanings and representations that ‘creativity’ has in the respective discourse, excluding many meanings of creativity encountered in other discourses. The excessive focus on creativity that is good, positive, productive and fits the managerial agenda while ignoring other forms and aspects of creativity, however, contributes to the dilution of the notion. Practices aimed at encouraging the kind of creativity may actually entail a risk of fostering moderate alterations rather than more radical novelty, as well as management and organizational practices which limit creative endeavors, rather than increase their likelihood. The thesis concludes that although not often given the space and attention they deserve, there are alternative conceptualizations and understandings of organizational creativity which embrace a broader notion of creativity. The inability to accommodate the ‘other’ understandings and viewpoints within the organizational creativity discourse runs a risk of misrepresenting the complex and many-sided phenomenon of creativity in organizational context. Keywords: Organizational creativity, creativity, organization studies, discourse theory, hegemony

Tietohallinnon haasteet kasvavassa ja kehittyvässä toimintaympäristössä – Toimintatutkimus suomalaisen PK-yrityksen kasvusta globaaliksi toimijaksi

Tutkimuksen tavoitteena on kuvata suomalaisen PK-yrityksen kasvamista globaa- liksi toimijaksi. Tapahtunut kasvu on tarkoittanut case-yrityksen kohdalla liike- vaihdon ja henkilöstömäärän kasvun lisäksi myös toimipaikkojen määrän kasvua ja organisaatiorakenteen monimutkaistumista. Näiden muutosten perusteella ja ta- pahtuneiden muutoskohtien avulla on löydettävissä yrityksen toimintaa kuvaavia vaiheita, joita ovat alkuvaihe, kasvuvaihe ja kypsä vaihe. Näiden vaiheiden jälkeen tulee vielä neljäs vaihe, eli uusiutumisvaihe tai laskeva vaihe. Tämän neljännen vaiheen suunta riippuu yrityksen kyvystä uusiutua ja kehittyä vastaamaan uusiin tuleviin haasteisiin joita aikaisempaa globaalimpi toiminta tuo tullessaan. Tapahtuneilla muutoksilla on ollut myös vaikutusta tietohallintoon. Tämä tieto- hallinnossa tapahtunut muutos onkin tämän tutkimuksen ydin, eli mitä haasteita ja vaatimuksia Trafotekin tietohallinto on kohdannut toiminnan eri vaiheissa, ja onko tietohallinto pystynyt omalta osaltaan vastaamaan näihin vaatimuksiin. Toiminnan alkuvaiheessa tietotekniikalla ei ollut suurtakaan strategista ja liike- toimintaa tukevaa roolia, ja tietohallinto pystyikin vastaamaan liiketoiminnan vaa- timuksiin. Tässä vaiheessa Trafotekissa ei ollut erillistä tietohallintoa, vaan tieto- tekniset työt hoidettiin muiden työtehtävien ohessa. Tietotekniset tehtävät olivat lähinnä tukitoimintoihin liittyviä tehtäviä. Kasvuvaiheessa tietotekniikan merkitys kasvoi, ja Trafotekiin tuli tarvetta luoda erillinen tietotekninen työtehtävä. Tässä toiminnan vaiheessa kyvykkyydet ja kypsyys eivät kuitenkaan kehittyneet halu- tulla tavalla, sillä kaikki käytössä oleva resursointi käytettiin edelleen päivittäisiin tukitoimintoihin, kehittämisen sijaan. Sama kehittymättömyys vaivasi toiminnan kypsässä vaiheessa. Tässä vaiheessa toki alettiin jo ymmärtää, että tietohallinnolla on strateginen rooli, joka tukee liiketoimintaa sen tavoitteiden saavuttamisessa. Tehty tutkimus tukee näkemystä siitä, että myös tietohallinnon kehittäminen on kokonaisvaltaista kehittämistä, jossa pitää huomioida toimintaa tukevia kyvyk- kyyksiä kaikissa toiminnan vaiheissa. Yrityksen kasvaessa myös tietohallinnon tu- lee kasvaa ja kehittyä. Osa tämän tutkimuksen tapahtumista oli tapahtunut ennen tämän tutkimustyön varsinaista aloittamista, eli ne kuvataan ja selitetään jälkijättöisesti. Kyseessä on toimintatutkimus, joka ajoittuu vuosiin 1996–2014. Avainsanat: globalisaatio, kansainvälinen kasvu, tietohallinto, tietohallinnon joh- taminen ja kehitys, kasvu-, kehitys- ja kypsyysmalli

The role of keratin intermediate filaments in the colon epithelial cells

Keratins (K) are cytoskeletal proteins mainly expressed in the epithelium and constitute the largest subgroup of intermediate filaments (IFs). Simple epithelial keratins (SEKs) K7-K8 and K18-K20 are the major IF elements in the colon. SEK mutations are known to cause around 30 human diseases, mainly affecting liver and skin. However, so far no strong associations between K8 mutations and the development of human colitis have been found. The keratin contribution to colonic health comes from the K8 knock-out (K8-/-) mouse model, which develops an early chronic inflammation and hyperproliferation in the colon. The aim of this thesis was to investigate how keratins contribute to intestinal health and disease mainly by the experimental analysis using the K8-/- mouse colon and cell culture models. The work described here is divided into three studies. The first study revealed involvement of keratins in Notch1 signaling, which is the master regulator of cell fate in the colon. Immunoprecipitation and immunostaining, both in vitro and in vivo showed that K8 binds and co-localizes with Notch1. Interestingly, overexpression of keratins enhanced Notch1 levels and stabilized Notch intracellular domain (NICD), leading to higher activity of Notch signaling. The dramatic decrease in Notch activity in the K8-/- colon resulted in a differentiation shift towards goblet and enteroendocrine cells. The second study focused on the involvement of keratins in colitis-associated cancer (CAC). Although, the K8-/- inflamed colon did not develop colorectal cancer (CRC) spontaneously, it was dramatically more susceptible to induced CRC in two CRC models: azoxymethane (AOM) and multiple intestinal neoplasia (ApcMin/+). To understand how the loss of K8 contributes to CAC, the epithelial inflammasome signaling pathway was analyzed. The released component of active inflammasome, cleaved caspase-1 and its downstream protein, interleukin (IL)-18, were significantly increased in K8-/- and K8-/-ApcMin/+ colons. The inflammasome pathway has recently been suggested to control the levels of IL-22 binding protein (IL-22BP), which is a negative regulator of IL-22 activity. Interestingly, the activated inflammasome correlated with an upregulation of IL-22 and a complete loss of IL-22BP in the K8-null colons. The activation of IL-22 was confirmed by increased levels of downstream signaling, which is phosphorylated signal transducer and activator of transcription 3 (P-STAT3), a transcription factor promoting proliferation and tissue regeneration in the colon. The objective of the third study, was to examine the role of keratins in colon energy metabolism. A proteomic analysis identified mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) as the major ownregulated protein in the K8-/- colonocytes. HMGCS2 is the rate-limiting enzyme in ketogenesis, where energy from bacterially produced short chain fatty acids (SCFAs), mainly butyrate, is converted into ketone bodies in colonic epithelium. Lower levels and activity of HMGCS2 in the K8-/- colon resulted in a blunted ketogenesis. The studies upstream from HMGCS2, identified decreased levels of the SCFA-transporter monocarboxylate transporter 1 (MCT1), which led to increased SCFA content in the stool suggesting impaired butyrate transport through the colonic epithelium. Taken together, the results of the herein thesis indicate that keratins are essential regulators of colon homeostasis, in particular epithelial differentiation, tumorigenesis and energy metabolism.

Datenherrschaft – an Ethically Justified Solution to the Problem of Ownership of Patient Information

Patient information systems are crucial components for the modern healthcare and medicine. It is obvious that without them the healthcare cannot function properly – one can try to imagine how brain surgery could be done without using information systems to gather and show information needed for an operation. Thus, it can be stated that digital information is irremovable part of modern healthcare. However, the legal ownership of patient information lacks a coherent and justified basis. The whole issue itself is actually bypassed by controlling pa- tient information with different laws and regulations how patient information can be used and by whom. Nonetheless, the issue itself – who owns the patient in- formation – is commonly missed or bypassed. This dissertation show the problems if the legislation of patient information ownership is not clear. Without clear legislation, the outcome can be unexpected like it seems to be in Finland, Sweden and United Kingdom: the lack of clear regulation has come up with unwanted consequences because of problematic Eu- ropean Union database directive implementation in those countries. The legal ownership is actually granted to the creators of databases which contains the pa- tient information, and this is not a desirable situation. In healthcare and medicine, we are dealing with issues such as life, health and information which are very sensitive and in many cases very personal. Thus, this dissertation leans on four philosophical theories form Locke, Kant, Heidegger and Rawls to have an ethically justified basis for regulating the patient infor- mation in a proper way. Because of the problems of property and ownership in the context of information, a new concept is needed and presented to replace the concept of owning, that concept being Datenherrschaft (eng. mastery over in- formation). Datenherrschaft seems to be suitable for regulating patient infor- mation because its core is the protection of one’s right over information and this aligns with the work of the philosophers whose theories are used in the work. The philosophical argumentation of this study shows that Datenherrschaft granted to the patients is ethically acceptable. It supports the view that patient should be controlling the patient information about themselves unless there are such specific circumstance that justifies the authorities to use patient information to protect other people’s basic rights. Thus, if the patients would be legally grant- ed Datenherrschaft over patient information we would endorse patients as indi- viduals who have their own and personal experience of their own life and have a strong stance against any unjustified paternalism in healthcare. Keywords: patient information, ownership, Datenherrschaft, ethics, Locke, Kant, Heidegger, Rawls

Tehohoitopotilaan siirtotiedote hoitotyön päätöksenteon tukena - retrospektiivinen asiakirja-analyysi vuosilta 2001-2013

Tuija Lehtikunnas: Intensive care patient handover document in support of decision-making in nursing work - Retrospective document analysis for the period 2001–2013 University of Turku, Faculty of Medicine, Nursing Science Annales Universitatis Turkuensis Turku 2016 ABSTRACT The continuity of care and flow of information must be ensured when transferring the responsibility of care, whether this is done within an organisation or from one organisation to another. The purpose of this study was to describe and compare the nursing handover documents of long-term intensive care patients and changes to these documents during the years 2001–2013. Research data comprehended long-term intensive care patient handover documents (N = 250). Data was gathered from one university hospital intensive care unit and subjected to a content analysis of technical implementation, structure and content at five different time points. In addition to this, the nursing handover documents were analysed from a nursing decision-making standpoint. Sub-data (n = 5 x 50) from the years 2001, 2002, 2004, 2006 and 2013 was gathered. The first sub-data was manual, written on paper with a pen. The rest of the sub-data obtained was entered in a dedicated intensive care information system. The study developed an intensive care patient nursing handover document analysis framework, which was used to deductively analyse the research data. The results indicated that the transitioning to electronic records reinforced structure and identification improving the reusability of data was increased. Although intensive care nursing was recorded on nursing handover documents more comprehensively in more recent sub-data, it was done selectively with regard to overall patient care, e.g. there are no entries concerning the psychological support and counselling of patients or family members. Nursing handover documents do not contain a systematic description of the patient's communication and functional capacity at the moment of transfer. The patient's condition at the moment of transfer is not clearly indicated on the handover documents. Plans for follow-up treatment are not recorded at all. Nursing decision-making is difficult to find on the nursing handover documents used as research data. The study developed a handover document model for intensive care nursing that supports nursing decision-making and the continuity of care. Developmental recommendations focus on the management of co-operation within organisations for ensuring the continuity of care and enhancing each area of nursing in recording nursing handover documents by planning nursing for the patient, taking follow-up treatment resources into consideration. Keywords: Intensive care nursing, nursing decision-making, nursing records, information flow, nursing handover document, continuity of care

Collagen binding integrins and cancer testis antigens in prostate cancer and melanoma

Camilla Pelo Collagen Binding Integrins and Cancer Testis Antigens in Prostate Cancer and Melanoma Department of Biochemistry, MediCity Research Laboratory, University of Turku, Finland Annales Universitatis Turkuensis, Painosalama Oy, Turku, Finland 2016 ABSTRACT Prostate cancer is the second most common cancer in men worldwide. The incidence of melanoma, in turn, is increasing faster than any other cancer incidences. In Finland, more than 5000 prostate cancer and 1200 new melanoma cases are diagnosed each year. One approach to further understand the cellular processes involved in prostate cancer and melanoma is to gain better knowledge about alterations in gene expression and their potential impact on the progression of the diseases. This thesis is focused on expression studies in two gene families; integrins and cancer testis antigens (CT antigens), in human prostate adenocarcinoma and advanced human melanoma. Integrins are heterodimeric transmembrane receptors which regulate many important cellular processes such as cell proliferation, migration and survival. CT antigens are frequently expressed in different types of cancers, but are only expressed in testis in healthy individuals. CT antigens are also highly immunogenic proteins. Due to the properties mentioned above, integrins and CT antigens can function as target molecules for the development of cancer diagnostics and drugs. One of the main purposes of this thesis was to study the expression of the four collagen binding integrins α1β1, α2β1, α10β1, α11β1 and the cancer testis antigen 16 (CT16) in cancer cell lines and human tissues of prostate cancer and metastatic melanoma. Additional aims included studies on the biological role of CT16 and the abundance of CT16 in sera of advanced melanoma patients. The prognostic and diagnostic significance of CT16 and the collagen binding integrins were also evaluated. Expression studies on collagen binding integrins and the CT antigen CT16 in melanoma and prostate cancer were limited and the biological role of CT16 was unknown. In this thesis, the expression levels of α2β1 and α11β1 were found to be significantly altered in prostate cancer tissues. Integrin α2β1 decreased gradually during disease progression while α11 was elevated in prostate carcinoma compared to healthy tissues. In advanced melanoma, enhanced levels of α2 were associated with a significant shorter overall survival in advanced melanoma. In this thesis, CT16 was identified as a frequently expressed melanoma CT antigen with an anti-apoptotic function. To conclude, this thesis presents α2β1 and CT16, as potential and promising biomarkers for advanced melanoma. This thesis reports also the first functional study of CT16. Keywords: Collagen binding integrins, α1β1, α2β1, α10β1, α11β1, Cancer Testis antigens, CT16, melanoma, prostate cancer, expression

Content-centered method for search engine optimization

Value of online business has grown to over one trillion USD. This thesis is about search engine optimization, which focus is to increase search engine rankings. Search engine optimization is an important branch of online marketing because the first page of search engine results is generating majority of the search traffic. Current articles about search engine optimization and Google are indicating that with the proper use of quality content, there is potential to improve search engine rankings. However, the existing search engine optimization literature is not noticing content at a sufficient level. To decrease that difference, the content-centered method for search engine optimization is constructed, and content in search engine optimization is studied. This content-centered method consists of three search engine optimization tactics: 1) content, 2) keywords, and 3) links. Two propositions were used for testing these tactics in a real business environment and results are suggesting that the content-centered method is improving search engine rankings. Search engine optimization is constantly changing because Google is adjusting its search algorithm regularly. Still, some long-term trends can be recognized. Google has said that content is growing its importance as a ranking factor in the future. The content-centered method is taking advance of this new trend in search engine optimization to be relevant for years to come.

How to reach more potential global b2b customers to Finnish high tech company websites

This thesis examines the optimization of a website in terms of creating website visibility and interesting and attractive online information, with the aim of finding ways how the case company can increase the number of online visitors for the websites, who would even-tually contact the case company, and become customers. The theoretical part concentrates on website visibility, academic knowledge about search engine optimization, integrated marketing communications, website effectiveness and influence tactics (mostly non-coercive) in an online b2b buying context. The empirical part included an experiment of two weeks on the case website. Search engine optimization requires the most relevant key terms and keywords to be selected and carefully implemented to meta descriptions of the most informational pages. The information visible to visitors on these pages was also opti-mized to make it interesting and purposeful for the targeted audience. The most suitable influence tactics were implemented to certain pages to attract the website visitors to con-tact the case company. The results suggest that relevant key terms in meta descriptions do improve, or maintain the same high, ranking a page has on search engine result pages, but this is not directly connected to the amount of visitors to the website. The number of visi-tors does not either affect the amount of customer contacts the company received during the experiment period.

Företagshälsovårdare

ÅBO AKADEMI UNIVERSITY Faculty of Education and Welfare Studies Author: Helena Nyman Supervisor: D.Sc. (Health Care), RN Jessica Hemberg Master´s Thesis The vision of caring – Occupational healthcare nurses experiences of fulfilling their ethical values CARING SCIENCE Keywords: Ethics, nursing, nursing ethics, healthcare, values April 2016 Number of pages: 53 Appendices: 5 The purpose of this study is to reach an understanding of what ethos is in an occupational healthcare context. The study seeks answer to the following questions: 1. What is ethos in an occupational healthcare context? 2. What does it mean for occupational healthcare nurses to fulfill their inner ethos in a healthcare context controlled by economic demands of gain and efficiency? The main concept in this study is ethos as Eriksson describes it in her caritative theory of caring. Ethos is associated with ethics and reflects the fundamental assumptions that we have about the human being´s holiness and dignity and about the inviolability of life. The empirical part of the study consists of focus interviews with four occupational healthcare nurses. The study uses hermeneutical reading as an interpretation method, and presents the results of the study in six theses reflecting these against both recent research and the theoretical background. The results of the study show that ethos in occupational healthcare has to do with justice, honesty and faithfulness. These concepts are common to nurses in different nursing contexts. Ethos is not primarily profession-bound but is something universal, and eternal in the human being´s way of being and becoming. The study shows that ethos is a way of being, openness and a way of existing in love. To fulfill ethos in an occupational health context means to choose ethos continuously and courageously for the sake of the patient and the good, even if it involves a struggle or a sacrifice.

Content-centered method for search engine optimization

Value of online business has grown to over one trillion USD. This thesis is about search engine optimization, which focus is to increase search engine rankings. Search engine optimization is an important branch of online marketing because the first page of search engine results is generating majority of the search traffic. Current articles about search engine optimization and Google are indicating that with the proper use of quality content, there is potential to improve search engine rankings. However, the existing search engine optimization literature is not noticing content at a sufficient level. To decrease that difference, the content-centered method for search engine optimization is constructed, and content in search engine optimization is studied. This content-centered method consists of three search engine optimization tactics: 1) content, 2) keywords, and 3) links. Two propositions were used for testing these tactics in a real business environment and results are suggesting that the content-centered method is improving search engine rankings. Search engine optimization is constantly changing because Google is adjusting its search algorithm regularly. Still, some long-term trends can be recognized. Google has said that content is growing its importance as a ranking factor in the future. The content-centered method is taking advance of this new trend in search engine optimization to be relevant for years to come.