Familjära förmaksflimrets karaktär i långtids EKG registrering

Målsättningen med denna studie var att karaktärisera familjära fall av förmaksflimmer (FA) och bestämma förekomsten av fokalt fött FA i detta material. Undersökningsmaterialet bestod av FA patienter på Mejlans rytmkardiologiska klinik, samt familjemedlemmar till dessa. För detta arbete analyserades 24 eller 48 timmars ambulatoriskt EKG på 42 personer. Bland dessa fanns 17 familjer av flera generationer vilka studerades närmare, främst med avseende på förekomsten av fokala triggrar. 40% av FA fallen uppfyllde de uppställda kriterierna för fokalt FA. Denna siffra är signifikant lägre än de ca 80% som tidigare rapporterats vid non-familjärt enskilt FA. Detta kunde tyda på en vid familjärt FA ökad känslighet i förmaken för ändå förekommande men lågfrekventa fokala triggrar. Undersökningen visade att en detaljanalys av 24 timmars Holter registrering är ett användbart sätt att kartlägga förmaksflimrets bakgrund.

The Networks of Learning in Technological Innovation : The Emergence of Collaboration Across Fields of Expertise

This study addresses four issues concerning technological product innovations. First, the nature of the very early phases or "embryonic stages" of technological innovation is addressed. Second, this study analyzes why and by what means people initiate innovation processes outside the technological community and the field of expertise of the established industry. In other words, this study addresses the initiation of innovation that occurs without the expertise of established organizations, such as technology firms, professional societies and research institutes operating in the technological field under consideration. Third, the significance of interorganizational learning processes for technological innovation is dealt with. Fourth, this consideration is supplemented by considering how network collaboration and learning change when formalized product development work and the commercialization of innovation advance. These issues are addressed through the empirical analysis of the following three product innovations: Benecol margarine, the Nordic Mobile Telephone system (NMT) and the ProWellness Diabetes Management System (PDMS). This study utilizes the theoretical insights of cultural-historical activity theory on the development of human activities and learning. Activity-theoretical conceptualizations are used in the critical assessment and advancement of the concept of networks of learning. This concept was originally proposed by the research group of organizational scientist Walter Powell. A network of learning refers to the interorganizational collaboration that pools resources, ideas and know-how without market-based or hierarchical relations. The concept of an activity system is used in defining the nodes of the networks of learning. Network collaboration and learning are analyzed with regard to the shared object of development work. According to this study, enduring dilemmas and tensions in activity explain the participants' motives for carrying out actions that lead to novel product concepts in the early phases of technological innovation. These actions comprise the initiation of development work outside the relevant fields of expertise and collaboration and learning across fields of expertise in the absence of market-based or hierarchical relations. These networks of learning are fragile and impermanent. This study suggests that the significance of networks of learning across fields of expertise becomes more and more crucial for innovation activities.

Neuronal oscillations in gamma- and alpha-frequency bands: from object representations to sensory awareness

The synchronization of neuronal activity, especially in the beta- (14-30 Hz) /gamma- (30 80 Hz) frequency bands, is thought to provide a means for the integration of anatomically distributed processing and for the formation of transient neuronal assemblies. Thus non-stimulus locked (i.e. induced) gamma-band oscillations are believed to underlie feature binding and the formation of neuronal object representations. On the other hand, the functional roles of neuronal oscillations in slower theta- (4 8 Hz) and alpha- (8 14 Hz) frequency bands remain controversial. In addition, early stimulus-locked activity has been largely ignored, as it is believed to reflect merely the physical properties of sensory stimuli. With human neuromagnetic recordings, both the functional roles of gamma- and alpha-band oscillations and the significance of early stimulus-locked activity in neuronal processing were examined in this thesis. Study I of this thesis shows that even the stimulus-locked (evoked) gamma oscillations were sensitive to high-level stimulus features for speech and non-speech sounds, suggesting that they may underlie the formation of early neuronal object representations for stimuli with a behavioural relevance. Study II shows that neuronal processing for consciously perceived and unperceived stimuli differed as early as 30 ms after stimulus onset. This study also showed that the alpha band oscillations selectively correlated with conscious perception. Study III, in turn, shows that prestimulus alpha-band oscillations influence the subsequent detection and processing of sensory stimuli. Further, in Study IV, we asked whether phase synchronization between distinct frequency bands is present in cortical circuits. This study revealed prominent task-sensitive phase synchrony between alpha and beta/gamma oscillations. Finally, the implications of Studies II, III, and IV to the broader scientific context are analysed in the last study of this thesis (V). I suggest, in this thesis that neuronal processing may be extremely fast and that the evoked response is important for cognitive processes. I also propose that alpha oscillations define the global neuronal workspace of perception, action, and consciousness and, further, that cross-frequency synchronization is required for the integration of neuronal object representations into global neuronal workspace.

Oppimisen kohteen ja oppijan vastavuoroinen kehitys : Teleyrityksen asiakaspalvelun työyhteisöjen oppimiskäytäntöjen uudistaminen osana teknologis-taloudellista kumousta

Reciprocal development of the object and subject of learning. The renewal of the learning practices of front-line communities in a telecommunications company as part of the techno-economical paradigm change. Current changes in production have been seen as an indication of a shift from the techno-economical paradigm of a mass-production era to a new paradigm of the information and communication technological era. The rise of knowledge management in the late 1990s can be seen as one aspect of this paradigm shift, as knowledge creation and customer responsiveness were recognized as the prime factors in business competition. However, paradoxical conceptions concerning learning and agency have been presented in the discussion of knowledge management. One prevalent notion in the literature is that learning is based on individuals’ voluntary actions and this has now become incompatible with the growing interest in knowledge-management systems. Furthermore, commonly held view of learning as a general process that is independent of the object of learning contradicts the observation that the current need for new knowledge and new competences are caused by ongoing techno-economic changes. Even though the current view acknowledges that individuals and communities have key roles in knowledge creation, this conception defies the idea of the individuals’ and communities’ agency in developing the practices through which they learn. This research therefore presents a new theoretical interpretation of learning and agency based on Cultural-Historical Activity Theory. This approach overcomes the paradoxes in knowledge-management theory and offers means for understanding and analyzing changes in the ways of learning within work communities. This research is also an evaluation of the Competence-Laboratory method which was developed as part of the study as a special application of Developmental Work Research methodology. The research data comprises the videotaped competence-laboratory processes of four front-line work communities in a telecommunications company. The findings reported in the five articles included in this thesis are based on the analyses of this data. The new theoretical interpretation offered here is based on the assessment that the findings reported in the articles represent one of the front lines of the ongoing historical transformation of work-related learning since the research site represents one of the key industries of the new “knowledge society”. The research can be characterized as elaboration of a hypothesis concerning the development of work related learning. According to the new theoretical interpretation, the object of activity is also the object of distributed learning in work communities. The historical socialization of production has increased the number of actors involved in an activity, which has also increased the number of mutual interdependencies as well as the need for communication. Learning practices and organizational systems of learning are historically developed forms of distributed learning mediated by specific forms of division of labor, specific tools, and specific rules. However, the learning practices of the mass production era become increasingly inadequate to accommodate the conditions in the new economy. This was manifested in the front-line work communities in the research site as an aggravating contradiction between the new objects of learning and the prevailing learning practices. The constituent element of this new theoretical interpretation is the idea of a work community’s learning as part of its collaborative mastery of the developing business activity. The development of the business activity is at the same time a practical and an epistemic object for the community. This kind of changing object cannot be mastered by using learning practices designed for the stable conditions of mass production, because learning has to change along the changes in business. According to the model introduced in this thesis, the transformation of learning proceeds through specific stages: predefined learning tasks are first transformed into learning through re-conceptualizing the object of the activity and of the joint learning and then, as the new object becomes stabilized, into the creation of new kinds of learning practices to master the re-defined object of the activity. This transformation of the form of learning is realized through a stepwise expansion of the work community’s agency. To summarize, the conceptual model developed in this study sets the tool-mediated co-development of the subject and the object of learning as the theoretical starting point for developing new, second-generation knowledge management methods. Key words: knowledge management, learning practice, organizational system of learning, agency

Kaveriporukasta liiketoiminnaksi : Tuotannon häiriöt ja organisaation oppiminen nopeasti muuttuvassa yrityksessä

In the 1990 s the companies utilizing and producing new information technology, especially so-called new media, were also expected to be forerunners in new forms of work and organization. Researchers anticipated that new, more creative forms of work and the changing content of working life were about to replace old industrial and standardized ways of working. However, research on actual companies in the IT sector revealed a situation where only minor changes to existing organizational forms were seen .Many of the independent companies faced great difficulties trying to survive the rapid changes in the products and production forms in the emerging field. Most of the research on the new media field has been conducted as surveys, and an understanding of the actual everyday work process has remained thin. My research is a longitudinal study of the early phases of one new media company in Finland. The study is an analysis of the challenges the company faced in a rapidly changing business field and the attempts to overcome these challenges. The two main analyses in the study focus on the developmental phases of the company and the disturbances in the production process. Based on these analyses, I study changes and learning at work using the methodological framework of developmental work research. Developmental work research is a Finnish variant of the cultural-historical activity theory applied to the study of learning and transformations at work. The data was gathered over a three-year period of ethnographic fieldwork. I documented the production processes and everyday life in the company as a participant observer. I interviewed key persons, video and audio-taped meetings, followed e-mail correspondence and collected various documents, such as agreements and memos. I developed a systematic method for analyzing the disturbances in the production process by combining the various data sources. The systematic analysis of the disturbances depicted a very complex and only partly managed production process. The production process had a long duration, and no single actor had an understanding of it as a whole. Most of the disturbances had to do with the customer relationships. The nature of the disturbances was latent; they were recognized but not addressed. In the particular production processes that I analyzed, the ending life span of a particular product, a CD-ROM, became obvious. This finding can be interpreted in relation to the developmental phase of the production and the transformation of the field as a whole. Based on the analysis of the developmental phases and the disturbances, I formulate a hypothesis of the contradictions and developmental potentials of the activity studied. The conclusions of the study challenge the existing understanding of how to conceptualize and study organizational learning in production work. Most theories of organizational learning do not address qualitative changes in production nor historical challenges of organizational learning itself. My study opens up a new horizon in understanding organizational learning in a rapidly changing field where a learning culture based on craft or mass production work is insufficient. There is a need for anticipatory and proactive organizational learning. Proactive learning is needed to anticipate the changes in production type, and the life cycles of products.

Gone with the Wind? : Immigrant Women and Transnational Everyday Life in Finland

Increased mass migration, as a result of economic hardship, natural disasters and wars, forces many people to arrive on the shores of cultures very different from those they left. How do they manage the legacy of the past and the challenges of their new everyday life? This is a study of immigrant women living in transnational families that act and communicate across national borders on a near-daily basis. The research was carried out amongst immigrant women who were currently living in Finland. The research asks how transnational everyday life is constructed. As everyday life, due to its mundane nature, is difficult to operationalise for research purposes, mixed data collection methods were needed to capture the passing moments that easily become invisible. Thus, the data were obtained from photographic diaries (459 photographs) taken by the research participants themselves. Additionally, stimulated recall discussions, structured questionnaires and participant observation notes were used to complement the photographic data. A tool for analysing the activities devealed in the data was created on the assumption that a family is an active unit that accommodates the current situation in which it is embedded. Everyday life activities were analysed emphasizing social, modal and spatial dimensions. Important daily moments were placed on a continuum: for me , for immediate others and with immediate others . They portrayed everyday routines and exceptions to it. The data matrix was developed as part of this study. The spatial dimensions formed seven units of activity settings: space for friendship, food, resting, childhood, caring, space to learn and an orderly space. Attention was also paid to the accommodative nature of activities; how women maintain traditions and adapt to Finnish life or re-create new activity patterns. Women s narrations revealed the importance of everyday life. The transnational chain of women across generations and countries, comprised of the daughters, mothers and grandmothers was important. The women showed the need for information technology in their transnational lives. They had an active relationship to religion; the denial or importance of it was obvious. Also arranging one s life in Finnish society was central to their narrations. The analysis exposed everyday activities, showed the importance of social networks and the uniqueness of each woman and family. It revealed everyday life in a structured way. The method of analysis that evolved in this study together with the research findings are of potential use to professionals, allowing the targeting of interventions to improve the everyday lives of immigrants.

Palladin, a novel microfilament protein

Palladin is a novel actin microfilament associated protein, which together with myotilin and myopalladin forms a novel cytoskeletal IgC2 domain protein family. Whereas the expression of myotilin and myopalladin is limited mainly to striated muscle, palladin is widely expressed in both epithelial and mesenchymal tissues, including heart and the nervous system. Palladin has a complex genetic structure and it is expressed as several different sized and structured splice variants, which also display differences in their expression pattern and interactions. In muscle cells, all the family members localize to the sarcomeric Z-disc, and in non-muscle cells palladin also localizes to the stress-fiber-dense regions, lamellipodia, podosomes and focal adhesions. A common feature of this protein family is the binding to α-actinin, but other interactions are mostly unique to each member. Palladin has been shown to interact with several proteins, including VASP, profilin, Eps8, LASP-1 and LPP. Its domain structure, lack of enzymatic activity and multiple interactions define it as a molecular scaffolding protein, which links together proteins with different functional modalities into large complexes. Palladin has an important role in cytoskeletal regulation, particularly in stress fiber formation and stabilization. This assumption is supported by several experimental results. First, over-expression of palladin in non-muscle cells results in rapid reorganization of the actin cytoskeleton and formation of thick actin bundles. Second, the knock-down of palladin with anti-sense and siRNA techniques or knock-out by genetic methods leads to defective stress fiber formation. Furthermore, palladin is usually up-regulated in situations requiring a highly organized cytoskeleton, such as differentiation of dendritic cells, trophoblasts and myofibroblasts, and activation of astrocytes during glial scar formation. The protein family members have also direct disease linkages; myotilin missense mutations are the cause of LGMD1A and myofibrillar myopathy. Palladin mutations and polymorphisms, on the other hand, have been linked to hereditary pancreatic cancer and myocardial infarction, respectively. In this study we set out to characterize human palladin. We identified several palladin isoforms, studied their tissue distribution and sub-cellular localization. Four novel interaction partners were identified; ezrin, ArgBP2, SPIN90 and Src-kinase.The previously identified interaction between palladin and α-actinin was also characterized in detail. All the identified new binding partners are actin cytoskeleton associated proteins; ezrin links the plasma membrane to the cytoskeleton, ArgBP2 and SPIN90 localize, among other structures, to the lamellipodia and in cardiomyocytes to the Z-disc. Src is a transforming tyrosine kinase, which besides its role in oncogenesis has also important cytoskeletal associations. We also studied palladin in myofibroblasts, which are specialized cells involved in diverse physiological and pathological processes, such as wound healing and tissue fibrosis. We demonstrated that palladin is up-regulated during the differentiation of myofibroblasts in an isoform specific manner, and that this up-regulation is induced by TGF-β via activation of both the SMAD and MAPK signalling cascades. In summary, the results presented here describe the initial characterization of human palladin and offer a basis for further studies.

Soil hydrological properties and conditions, site preparation, and the long-term performance of planted Scots pine (Pinus sylvestris L.) on upland forest sites in Finnish Lapland

Scots pine (Pinus sylvestris L.) and Norway spruce (Picea abies (L.) Karst.) forests dominate in Finnish Lapland. The need to study the effect of both soil factors and site preparation on the performance of planted Scots pine has increased due to the problems encountered in reforestation, especially on mesic and moist, formerly spruce-dominated sites. The present thesis examines soil hydrological properties and conditions, and effect of site preparation on them on 10 pine- and 10 spruce-dominated upland forest sites. Finally, the effects of both the site preparation and reforestation methods, and soil hydrology on the long-term performance of planted Scots pine are summarized. The results showed that pine and spruce sites differ significantly in their soil physical properties. Under field capacity or wetter soil moisture conditions, planted pines presumably suffer from excessive soil water and poor soil aeration on most of the originally spruce sites, but not on the pine sites. The results also suggested that site preparation affects the soil-water regime and thus prerequisites for forest growth over two decades after site preparation. High variation in the survival and mean height of planted pine was found. The study suggested that on spruce sites, pine survival is the lowest on sites that dry out slowly after rainfall events, and that height growth is the fastest on soils that reach favourable aeration conditions for root growth soon after saturation, and/or where the average air-filled porosity near field capacity is large enough for good root growth. Survival, but not mean height can be enhanced by employing intensive site preparation methods on spruce sites. On coarser-textured pine sites, site preparation methods don t affect survival, but methods affecting soil fertility, such as prescribed burning and ploughing, seem to enhance the height growth of planted Scots pines over several decades. The use of soil water content in situ as the sole criterion for sites suitable for pine reforestation was tested and found to be a relatively uncertain parameter. The thesis identified new potential soil variables, which should be tested using other data in the future.

Bacillus cereus spores and cereulide in food-borne illness

B. cereus is a gram-positive bacterium that possesses two different forms of life:the large, rod-shaped cells (ca. 0.002 mm by 0.004 mm) that are able to propagate and the small (0.001 mm), oval shaped spores. The spores can survive in almost any environment for up to centuries without nourishment or water. They are insensitive towards most agents that normally kill bacteria: heating up to several hours at 90 ºC, radiation, disinfectants and extreme alkaline (≥ pH 13) and acid (≤ pH 1) environment. The spores are highly hydrophobic and therefore make them tend to stick to all kinds of surfaces, steel, plastics and live cells. In favorable conditions the spores of B. cereus may germinate into vegetative cells capable of producing food poisoning toxins. The toxins can be heat-labile protein formed after ingestion of the contaminated food, inside the gastrointestinal tract (diarrhoeal toxins), or heat stable peptides formed in the food (emesis causing toxin, cereulide). Cereulide cannot be inactivated in foods by cooking or any other procedure applicable on food. Cereulide in consumed food causes serious illness in human, even fatalities. In this thesis, B. cereus strains originating from different kinds of foods and environments and 8 different countries were inspected for their capability of forming cereulide. Of the 1041 isolates from soil, animal feed, water, air, used bedding, grass, dung and equipment only 1.2 % were capable of producing cereulide, whereas of the 144 isolates originating from foods 24 % were cereulide producers. Cereulide was detected by two methods: by its toxicity towards mammalian cells (sperm assay) and by its peculiar chemical structure using liquid-chromatograph-mass spectrometry equipment. B. cereus is known as one of the most frequent bacteria occurring in food. Most foods contain more than one kind of B. cereus. When randomly selected 100 isolates of B. cereus from commercial infant foods (dry formulas) were tested, 11% of these produced cereulide. Considering a frequent content of 103 to 104 cfu (colony forming units) of B. cereus per gram of infant food formula (dry), it appears likely that most servings (200 ml, 30 g of the powder reconstituted with water) may contain cereulide producers. When a reconstituted infant formula was inoculated with >105 cfu of cereulide producing B. cereus per ml and left at room temperature, cereulide accumulated to food poisoning levels (> 0.1 mg of cereulide per serving) within 24 hours. Paradoxically, the amount of cereulide (per g of food) increased 10 to 50 fold when the food was diluted 4 - 15 fold with water. The amount of the produced cereulide strongly depended on the composition of the formula: most toxin was formed in formulas with cereals mixed with milk, and least toxin in formulas based on milk only. In spite of the aggressive cleaning practices executed by the modern dairy industry, certain genotypes of B. cereus appear to colonise the silos tanks. In this thesis four strategies to explain their survival of their spores in dairy silos were identified. First, high survival (log 15 min kill ≤ 1.5) in the hot alkaline (pH >13) wash liquid, used at the dairies for cleaning-in-place. Second, efficient adherence of the spores to stainless steel from cold water. Third, a cereulide producing group with spores characterized by slow germination in rich medium and well preserved viability when exposed to heating at 90 ºC. Fourth, spores capable of germinating at 8 ºC and possessing the psychrotolerance gene, cspA. There were indications that spores highly resistant to hot 1% sodium hydroxide may be effectively inactivated by hot 0.9% nitric acid. Eight out of the 14 dairy silo tank isolates possessing hot alkali resistant spores were capable of germinating and forming biofilm in whole milk, not previously reported for B. cereus. In this thesis it was shown that cereulide producing B. cereus was capable of inhibiting the growth of cereulide non-producing B. cereus occurring in the same food. This phenomenon, called antagonism, has long been known to exist between B. cereus and other microbial species, e.g. various species of Bacillus, gram-negative bacteria and plant pathogenic fungi. In this thesis intra-species antagonism of B. cereus was shown for the first time. This brother-killing did not depend on the cereulide molecule, also some of the cereulide non-producers were potent antagonists. Interestingly, the antagonistic clades were most frequently found in isolates from food implicated with human illness. The antagonistic property was therefore proposed in this thesis as a novel virulence factor that increases the human morbidity of the species B. cereus, in particular of the cereulide producers.

Äidinmaito - terveysjuomaa ja normaalibakteereita

The chemical composition of breast milk has been studied in detail in the past decades. Hundreds of new antibacterial and antiviral components have been found. Several molecules have been found to promote the proper function of neonatal intestine. However, microbiological studies of breast milk have been, until recently, focused mainly on detecting harmful and pathogenic bacteria and viruses. Natural microbial diversity of human milk has not been widely studied before the work reported in this thesis. This is mainly because breast milk has traditionally been thought to be sterile - even if a certain amount of commensal bacteria have usually been detected in milk samples. The first part of this licentiate thesis contains a short literature review about the anatomy and physiology of breast feeding, human milk chemical and microbiological composition, mastitis, intestinal flora and bacteriocins. The second part reports on the experiments of the licentiate work, concentrating on the microbial diversity in the milk of healthy breast-feeding mothers, and the ability of these bacteria to produce antibacterial substances against pathogenic bacteria. The results indicate that human milk is a source of commensal bacteria for infant intestine. 509 random isolates from 40 breast milk samples were isolated and identified by 16S rRNA sequencing. Median bacterial count was about 600 colony forming units per milliliter. Over half of the isolates were staphylococci, and almost one third streptococci. The most common species were skin bacteria Staphylococcus epidermidis and oral bacteria Streptococcus salivarius and Streptococcus mitis. Lactic acid bacteria, identified as members of Lactobacillus-, Lactococcus- and Leuconostoc -genera, were found in five milk samples. Enterococci were found in three samples. A novel finding in this study is the capability of these commensal bacteria to inhibit the growth of pathogens. In 90 precent of the milk samples commensal bacteria inhibiting the growth of Staphylococcus aureus were found. In 40 precent of samples the colonies could block the growth completely. One fifth of the isolated Staph. epidermidis strains, half of Str. salivarius strains, and all lactic acid bacteria and enterococci could inhibit or block the growth of Staph. aureus. In further study also Listeria innocua- and Micrococcus luteus active isolates were found in 33 and 11 precent of milk samples (out of 140). Furthermore, two Lactococcus lactis isolates from the breast milk were shown to produce bacteriocin nisin, which is an antimicrobial molecule used as a food preservative. The importance of these human milk commensal bacteria in the development of newborn intestinal flora and immune system, as well as in preventing maternal breast infections, should be further explored.

Alueellinen imago ja identiteetti liikkeessä

Regions are considered to be in competition for investments, industries, inhabitants and skilled labour nationally as well as internationally. In the context of tightening competition, more and more attention has been paid to regional attractors. A positive image is an important attractor in regional competition. In Finland, many towns and regions have either implemented or are planning to implement various image-enhancing campaigns or other measures aimed at improving their image. The role of identity is very important in developing a regional image. Good regional image should be based on a strong regional identity and awareness. Related to this is the perception of one's own region as separate from others and the familiarity of the region. If a region has no place in the awareness of its residents or if the inhabitants do not identify with it, its very existence as a social construct can be questioned. This means that building the regional image, which in this context is seen as social constructivism, is extremely difficult if the degree of regional awareness and identification is low. On the other hand, regional identity is being built also by developing the regional image. In a way, regional discourses have become more marketing-oriented in that instead of trying to create a regional esprit de corps there is now more image-oriented speech aimed at striving to improve the attractivity to outsiders of the region. Even though the goal is to bring the region to the attention of non-residents, a measure of construction of regional identity for the local population is automatically effected at the same time. Regional image and identity are consequences of linguistic producing and understanding of a region. It means that both image and identity are seen as language-created social constructions. The regional image is created through various discourses, but also the construction of a regional identity as regional consciousness and identification is largely a linguistic process. Essential in this context is perceiving the region as a discursive project characterized by its representation as texts, images and symbols. The linguistic production of a region is not a neutral description of "reality", but a representation based on interpretations, experiences and different motivations. Production and perceiving vary in time, so regional image and identity are on the move. This research is driven by the ongoing change of the regional system. The municipal and service structure reform is in progress and the number of municipalities seems to be on the decrease. At the same time, European Union s regional policy and regionalism on the whole are changing the status of sub-regions. At municipal level the crucial question is how the municipal structure reform will affect regional identity. This study points out that strong sense of municipal identity is a source of opposition to changes in municipal structure, but on the other hand the deinstitutionalization of the old municipality in municipal merger does not in itself mean the weakening of municipal identity.

The Human UDP-Glucuronosyltransferases: Studies on Substrate Binding and Catalytic Mechanism

PDF

Atrial remodeling in atrial fibrillation : Epidemiological, clinical and magnetocardiographic aspects

Atrial fibrillation is the most common arrhythmia requiring treatment. This Thesis investigated atrial fibrillation (AF) with a specific emphasis on atrial remodeling which was analysed from epidemiological, clinical and magnetocardiographic (MCG) perspectives. In the first study we evaluated in real-life clinical practice a population-based cohort of AF patients referred for their first elective cardioversion (CV). 183 consecutive patients were included of whom in 153 (84%) sinus rhythm (SR) was restored. Only 39 (25%) of those maintained SR for one year. Shorter duration of AF and the use of sotalol were the only characteristics associated with better restoration and maintenance of SR. During the one-year follow-up 40% of the patients ended up in permanent AF. Female gender and older age were associated with the acceptance of permanent AF. The LIFE-trial was a prospective, randomised, double-blinded study that evaluated losartan and atenolol in patients with hypertension and left ventricular hypertrophy (LVH). Of the 8,851 patients with SR at baseline and without a history of AF 371 patients developed new-onset AF during the study. Patients with new-onset AF had an increased risk of cardiac events, stroke, and increased rate of hospitalisation for heart failure. Younger age, female gender, lower systolic blood pressure, lesser LVH in ECG and randomisation to losartan therapy were independently associated with lower frequency of new-onset AF. The impact of AF on morbidity and mortality was evaluated in a post-hoc analysis of the OPTIMAAL trial that compared losartan with captopril in patients with acute myocardial infarction (AMI) and evidence of LV dysfunction. Of the 5,477 randomised patients 655 had AF at baseline, and 345 patients developed new AF during the follow-up period, median 3.0 years. Older patients and patients with signs of more serious heart disease had and developed AF more often. Patients with AF at baseline had an increased risk of mortality (hazard ratio (HR) of 1.32) and stroke (HR 1.77). New-onset AF was associated with increased mortality (HR 1.82) and stroke (HR of 2.29). In the fourth study we assessed the reproducibility of our MCG method. This method was used in the fifth study where 26 patients with persistent AF had immediately after the CV longer P-wave duration and higher energy of the last portion of atrial signal (RMS40) in MCG, increased P-wave dispersion in SAECG and decreased pump function of the atria as well as enlarged atrial diameter in echocardiography compared to age- and disease-matched controls. After one month in SR, P-wave duration in MCG still remained longer and left atrial (LA) diameter greater compared to the controls, while the other measurements had returned to the same level as in the control group. In conclusion is not a rare condition in either general population or patients with hypertension or AMI, and it is associated with increased risk of morbidity and mortality. Therefore, atrial remodeling that increases the likelihood of AF and also seems to be relatively stable has to be identified and prevented. MCG was found to be an encouraging new method to study electrical atrial remodeling and reverse remodeling. RAAS-suppressing medications appear to be the most promising method to prevent atrial remodeling and AF.