Thrombophilia and direct thrombin inhibitor lepirudin clinical and monitoring aspects

Thrombophilia (TF) predisposes both to venous and arterial thrombosis at a young age. TF may also impact the thrombosis or stenosis of hemodialysis (HD) vascular access in patients with end-stage renal disease (ESRD). When involved in severe thrombosis TF may associate with inappropriate response to anticoagulation. Lepirudin, a potent direct thrombin inhibitor (DTI), indicated for heparin-induced thrombocytopenia-related thrombosis, could offer a treatment alternative in TF. Monitoring of narrow-ranged lepirudin demands new insights also in laboratory. The above issues constitute the targets in this thesis. We evaluated the prevalence of TF in patients with ESRD and its impact upon thrombosis- or stenosis-free survival of the vascular access. Altogether 237 ESRD patients were prospectively screened for TF and thrombogenic risk factors prior to HD access surgery in 2002-2004 (mean follow-up of 3.6 years). TF was evident in 43 (18%) of the ESRD patients, more often in males (23 vs. 9%, p=0.009). Known gene mutations of FV Leiden and FII G20210A occurred in 4%. Vascular access sufficiently matured in 226 (95%). The 1-year thrombosis- and stenosis-free access survival was 72%. Female gender (hazards ratio, HR, 2.5; 95% CI 1.6-3.9) and TF (HR 1.9, 95% CI 1.1-3.3) were independent risk factors for the shortened thrombosis- and stenosis-free survival. Additionally, TF or thrombogenic background was found in relatively young patients having severe thrombosis either in hepatic veins (Budd-Chiari syndrome, BCS, one patient) or inoperable critical limb ischemia (CLI, six patients). Lepirudin was evaluated in an off-label setting in the severe thrombosis after inefficacious traditional anticoagulation without other treatment options except severe invasive procedures, such as lower extremity amputation. Lepirudin treatments were repeatedly monitored clinically and with laboratory assessments (e.g. activated partial thromboplastin time, APTT). Our preliminary studies with lepirudin in thrombotic calamities appeared safe, and no bleeds occurred. An effective DTI lepirudin calmed thrombosis as all patients gradually recovered. Only one limb amputation was performed 3 years later during the follow-up (mean 4 years). Furthermore, we aimed to overcome the limitations of APTT and confounding effects of warfarin (INR of 1.5-3.9) and lupus anticoagulant (LA). Lepirudin responses were assessed in vitro by five specific laboratory methods. Ecarin chromogenic assay (ECA) or anti-Factor IIa (anti-FIIa) correlated precisely (r=0.99) with each other and with spiked lepirudin in all plasma pools: normal, warfarin, and LA-containing plasma. In contrast, in the presence of warfarin and LA both APTT and prothrombinase-induced clotting time (PiCT®) were limited by non-linear and imprecise dose responses. As a global coagulation test APTT is useful in parallel to the precise chromogenic methods ECA or Anti-FIIa in challenging clinical situations. Lepirudin treatment requires multidisciplinary approach to ensure appropriate patient selection, interpretation of laboratory monitoring, and treatment safety. TF seemed to be associated with complicated thrombotic events, in venous (BCS), arterial (CLI), and vascular access systems. TF screening should be aimed to patients with repeated access complications or prior unprovoked thromboembolic events. Lepirudin inhibits free and clot-bound thrombin which heparin fails to inhibit. Lepirudin seems to offer a potent and safe option for treatment of severe thrombosis. Multi-centered randomized trials are necessary to assess the possible management of complicated thrombotic events with DTIs like lepirudin and seek prevention options against access complications.

Aspects of Inflationary Models at Low Energy Scales

Cosmological inflation is the dominant paradigm in explaining the origin of structure in the universe. According to the inflationary scenario, there has been a period of nearly exponential expansion in the very early universe, long before the nucleosynthesis. Inflation is commonly considered as a consequence of some scalar field or fields whose energy density starts to dominate the universe. The inflationary expansion converts the quantum fluctuations of the fields into classical perturbations on superhorizon scales and these primordial perturbations are the seeds of the structure in the universe. Moreover, inflation also naturally explains the high degree of homogeneity and spatial flatness of the early universe. The real challenge of the inflationary cosmology lies in trying to establish a connection between the fields driving inflation and theories of particle physics. In this thesis we concentrate on inflationary models at scales well below the Planck scale. The low scale allows us to seek for candidates for the inflationary matter within extensions of the Standard Model but typically also implies fine-tuning problems. We discuss a low scale model where inflation is driven by a flat direction of the Minimally Supersymmetric Standard Model. The relation between the potential along the flat direction and the underlying supergravity model is studied. The low inflationary scale requires an extremely flat potential but we find that in this particular model the associated fine-tuning problems can be solved in a rather natural fashion in a class of supergravity models. For this class of models, the flatness is a consequence of the structure of the supergravity model and is insensitive to the vacuum expectation values of the fields that break supersymmetry. Another low scale model considered in the thesis is the curvaton scenario where the primordial perturbations originate from quantum fluctuations of a curvaton field, which is different from the fields driving inflation. The curvaton gives a negligible contribution to the total energy density during inflation but its perturbations become significant in the post-inflationary epoch. The separation between the fields driving inflation and the fields giving rise to primordial perturbations opens up new possibilities to lower the inflationary scale without introducing fine-tuning problems. The curvaton model typically gives rise to relatively large level of non-gaussian features in the statistics of primordial perturbations. We find that the level of non-gaussian effects is heavily dependent on the form of the curvaton potential. Future observations that provide more accurate information of the non-gaussian statistics can therefore place constraining bounds on the curvaton interactions.

The Finnish Competition State and Entrepreneurial Policies in the Helsinki Region

The thesis examines the intensification and characteristics of a policy that emphasises economic competitiveness in Finland during the 1990s and early 2000s. This accentuation of economic objectives is studied at the level of national policy-making as well as at the regional level through the policies and strategies of cities and three universities in the Helsinki region. By combining the analysis of state policies, urban strategies and university activities, the study illustrates the pervasiveness of the objective of economic competitiveness and growth across these levels and sheds light on the features and contradictions of these policies on a broad scale. The thesis is composed of five research articles and a summary article. At the level of national policies, the central focus of the thesis is on the growing role of science and technology policy as a state means to promote structural economic change and its transformation towards a broader, yet ambivalent concept of innovation policy. This shift brings forward a tension between an increasing emphasis on economic aspects – innovations and competitiveness – as well as the expanding scope of issues across a wide range of policy sectors that are being subsumed under this market- and economy oriented framework. Related to science and technology policy, attention is paid to adjustments in university policy in which there has been increasing pressure for efficiency, rationalisation and commercialisation of academic activities. Furthermore, political efforts to build an information society through the application of information and communication technologies are analysed with particular attention to the balance between economic and social objectives. Finally, changes in state regional policy priorities and the tendency towards competitiveness are addressed. At the regional level, the focus of the thesis is on the policies of the cities in Finland’s capital region as well as strategies of three universities operating in the region, namely the University of Helsinki, Helsinki University of technology and Helsinki School of Economics. As regards the urban level, the main focus is on the changes and characteristics of the urban economic development policy of the City of Helsinki. With respect to the universities, the thesis examines their attempts to commercialise research and thus bring academic research closer to economic interests, and pays particular attention to the contradictions of commercialisation. Related to the universities, the activities of three intermediary organisations that the universities have established in order to increase cooperation with industry are analysed. These organisations are the Helsinki Science Park, Otaniemi International Innovation Centre and LTT Research Ltd. The summary article provides a synthesis of the material presented in the five original articles and relates the results of the articles to a broader discussion concerning the emergence of competition states and entrepreneurial cities and regions. The main points of reference are Bob Jessop’s and Neil Brenner’s theses on state and urban-regional restructuring. The empirical results and considerations from Finland and the Helsinki region are used to comment on, specify and criticise specific parts of the two theses.

Uuden median murros Alma Mediassa, Sanoma Oy:ssä ja Yleisradiossa 1994-2004

This is a qualitative and multimethodological comparative study, which consists of two main parts: examining the development of new media and analysing and comparing the new media strategies of the three companies studied (Alma Media, Sanoma and the Finnish Broadcasting Company Yleisradio). The study includes the first large-scale review in Finnish of the development of new media, paying attention to the birth of the Internet as well as to mobile media, web TV and any other element of new media. It also concentrates on the function of electronic distribution channels before the age of the Internet, e.g. cable text and videotext. Answers about how the three traditional Finnish media houses began spreading their content to the Internet and wireless applications in 1994–2004 are also given. In researching the new media strategies the study pays special attention to the attitudes that the three media companies adopted towards the Internet and other forms of new media in their strategies during the years in question. By analysing and comparing, e.g., the companies’ strategies and their investments, the study ascertains whether the companies had a joint functional model in adopting new media or acted totally on their own without taking too much notice of the media field overall. The study makes extensive use of previously published material. The researcher has also interviewed almost twenty people who were involved in getting the companies’ new media functions under way. The methods for the interviews were dialogue and snowball sampling. The researcher has created a classification in which he divides the business strategies into four different categories: active strategy, careful strategy, permissive strategy, and passive strategy. In comparing and analysing the companies the researcher has used the classification devised by Allan Afuah & Christopher L. Tucci. The seven element classification consists of dominant managerial logic, competency trap, fear of cannibalisation and loss of revenue, channel conflict, political power, co-opetitor power and emotional attachment. In analysing the company strategies the researcher has also noted the classifications of convergence made by Everette E. Dennis and Graham Murdock as well as the aspects formulated by Sylvia Chan-Olmsted and Louisa Ha concerning the success of the companies in adopting the Internet into their functions. Based on all these classifications and by further developing them the researcher analyses and compares the success of the new media strategies of the three Finnish companies. The outcome of the study is a conclusion as to what kind of strategies the companies have carried out their new media functions and how they have succeeded in it.

A Success Story or a Failure? : Representing the European Integration in the Curricula and Textbooks of Five Countries

The economic, political and social face of Europe has been changing rapidly in the past decades. These changes are unique in the history of Europe, but not without challenges for the nation states. The support for the European integration varies among the countries. In order to understand why certain developments or changes are perceived as threatening or as desired by different member countries, we must consider the social representations of the European integration on the national level: how the EU is represented to its citizens in media and in educational systems, particularly in the curricula and textbooks. The current study is concerned with the social representations of the European integration in the curricula and school textbooks in five European countries: France, Britain, Germany, Finland and Sweden. Besides that, the first volume of the common Franco-German history textbook was analyzed, since it has been seen as a model for a common European history textbook. As the collective representations, values and identities are dominantly mediated and imposed through media and educational systems, the national curricula and textbooks make an interesting starting point for the study of the European integration and of national and European identities. The social representations theory provides a comprehensive framework for the study of the European integration. By analyzing the curricula and history and civics textbooks of major educational publishers, the study aimed to demonstrate what is written on the European integration and how it is portrayed how the European integration is understood, made familiar and concretized in the educational context in the five European countries. To grasp the phenomenon of the European integration in the textbooks in its entirety, it was investigated from various perspectives. The two analysis methods of content analysis, the automatic analysis with ALCESTE and a more qualitative theory-driven content analysis, were carried out to give a more vivid and multifaceted picture of the object of the research. The analysis of the text was complemented with the analysis of visual material. Drawing on quantitative and qualitative methods, the contents, processes, visual images, transformations and structures of the social representations of European integration, as well as the communicative styles of the textbooks were examined. This study showed the divergent social representations of the European integration, anchored in the nation states, in the five member countries of the European Union. The social representations were constructed around different central core elements: French Europe in the French textbooks, Ambivalent Europe in the British textbooks, Influential and Unifying EU in the German textbooks, Enabling and Threatening EU in the Finnish textbooks, Sceptical EU in the Swedish textbooks and EU as a World Model in the Franco-German textbook. Some elements of the representations were shared by all countries such as peace and economic aspects of the European cooperation, whereas other elements of representations were found more frequently in some countries than in others, such as ideological, threatening or social components of the phenomenon European integration. The study also demonstrated the linkage between social representations of the EU and national and European identities. The findings of this study are applicable to the study of the European integration, to the study of education, as well as to the social representation theory.

Local Politicizations : A Comparison of Finns and French Practicing Democracy

This study examines how do the processes of politicization differ in the Finnish and the French local contexts, and what kinds of consequences do these processes have on the local civic practices, the definitions and redefinitions of democracy and citizenship, the dynamics of power and resistance, and the ways of solving controversies in the public sphere. By means of comparative anthropology of the state , focusing on how democracy actually is practiced in different contexts, politicizations the processes of opening political arenas and recognizing controversy are analyzed. The focus of the study is on local activists engaged in different struggles on various levels of the local public spheres, and local politicians and civil servants participating in these struggles from their respective positions, in two middle-size European cities, Helsinki and Lyon. The empirical analyses of the book compare different political actors and levels of practicing democracy simultaneously. The study is empirically based on four different bodies of material: Ethnographic notes taken during a fieldwork among the activities of several local activist groups; 47 interviews of local activists and politicians; images representing different levels of public portrayals from activist websites (Helsinki N=274, Lyon N=232) and from city information magazines (Helsinki-info N=208, Lyon Citoyen N= 357); and finally, newspaper articles concerning local conflict issues, and reporting on the encounters between local citizens and representatives of the cities (January-June in 2005; Helsingin Sanomat N=96 and Le Progrès N= 102). The study makes three distinctive contributions to the study of current democratic societies: (1) a conceptual one by bringing politicization at the center of a comparison of political cultures, and by considering in parallel the ethnographic group styles theory by Nina Eliasoph and Paul Lichterman, the theory on counter-democracy by Pierre Rosanvallon and the pragmatist justification theory by Luc Boltanski and Laurent Thévenot; (2) an empirical one through the triangulation of ethnographic, thematic interview, visual, and newspaper data through which the different aspects of democratic practices are examined; and (3) a methodological one by developing new ways of analyzing comparative cases an application of Frame Analysis to visual material and the creation of Public Justification Analysis for analyzing morally loaded claims in newspaper reports thus building bridges between cultural, political, and pragmatic sociology. The results of the study indicate that the cultural tools the Finnish civic actors had at their disposal were prone to hinder more than support politicization, whereas the tools the French actors mainly relied on were frequently apt for making politicization possible. This crystallization is defined and detailed in many ways in the analyses of the book. Its consequences to the understanding and future research on the current developments of democracy are multiple, as politicization, while not assuring good results as such, is central to a functioning and vibrant democracy in which injustices can be fixed and new directions and solutions sought collectively.