535 resultados para Jo


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Länsimaat ovat rahoittaneet kehitysyhteistyöhankkeita jo lähes kuuden vuosikymmenen ajan, mutta kehitysavun tehokkuudesta ei olla edelleenkään päästy yksimielisyyteen. Yksi avunantajamaiden tapa vaikuttaa kehitysavun tehokkuuteen, eli avun vaikutukseen vastaanottajamaan taloudellisen kasvun kiihdyttäjänä, on sitoa ne julkisen sektorin infrastruktuurihankkeisiin. Joissain tapauksissa tämä vaikuttaa avun vastaanottajan käytökseen ja asenteisiin kehitysapua kohtaan. Tutkielmassa käsitellään kehitysavun tehokkuutta tilanteessa, jossa se on sidottu julkisen sektorin investointeihin kehitysmaassa. Tutkimus pohjaa Kalaitzidakisin ja Kalyvitisin (2008) malliin, jossa osa kehitysmaan julkisen talouden investoinneista rahoitetaan kehitysavulla. Seuraavaksi tarkastellaan ylijäämää tavoittelevan käyttäytymisen (rent- seeking) vaikutusta kehitysavun tehokkuuteen pohjaten Economidesin, Kalyvitisin ja Philippopoulosin (2008) malliin. Tutkielmassa referoidaan lisäksi tutkimuskysymystä sivuavia empiirisiä tutkimuksia, esitellään aluksi tavallisimmat kehitysyhteistyön muodot, sekä esitellään talousteoreettisia näkökulmia kehitysyhteistyön tehokkuuden määrittelylle. Tutkielma perustuu puhtaasti teoreettisiin malleihin ja niissä sovelletut menetelmät ovat matemaattisia. Tutkielmassa käsitellään ensin tapaus, jossa kehitysyhteistyöllä rahoitetaan julkisen sektorin investointihankkeita. Jossain tapauksissa kehitysavun kasvu lasku siirtää vastaanottajamaan kulutusta julkisista investoinneista kulutukseen, jolloin kehitysyhteistyövaroin osittain rahoitettujen hankkeiden koko pienenee, ja suhteellinen tehokkuus laskee. Seuraavaksi tarkastellaan tilannetta, jossa kehitysyhteistyövaroista vain osa päätyy hankkeen rahoittamiseen, ja todetaan, että kehitysavun tehokkuus ja vaikutus maan kansantulon kasvuun vähenee talouden toimijoiden ylijäämää tavoittelevan käyttäytymisen (mukaan lukien korruptio) myötä entisestään. Tämän tutkimuksen perusteella voidaan todeta, että kehitysapu vaikuttaa kehittyvän maan talouden kasvuun tapauksessa, jossa julkisia infrastruktuurihankkeita rahoitetaan osittain maan omin verovaroin ja osittain kehitysyhteistyövaroin. Ylijäämää tavoitteleva käyttäytyminen vaikuttaa kehitysavun tehokkuuteen negatiivistesti vähentäen kehitysavun positiivisia kasvuvaikutuksia.

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Tutkimuksessa tarkastellaan dementiakuolleisuutta sekä siihen vaikuttavia sosiaalisia tekijöitä. Dementia on oireyhtymä, jota pääasiassa sairastavat yli 65 -vuotiaat henkilöt. Väestön ikääntyessä sekä elinajanodotteen kasvaessa on odotettavissa, että dementiaa sairastavien määrä tulee kasvamaan merkittävästi lähivuosina. On viitteitä siitä, että dementiaan sairastumisen riskiin vaikuttavat erilaiset sosiaaliset tekijät kuten koulutus, mutta varsinkin dementiakuolleisuudesta tiedetään vähän. Tutkielman aineistona käytettiin Tilastokeskuksen muodostamaa Elinolot ja kuolinsyyt -rekisteriaineistoa, joka koostuu väestölaskentatiedoista sekä työssäkäyntitilaston pitkittäisaineistosta, johon on liitetty kuolinsyytietoja. Peruskuolinsyyn lisäksi aineistossa oli tieto korkeintaan kolmesta myötävaikuttavasta syystä. Dementiakuolleisuuden on esitetty aliarvioituvan peruskuolinsyynä, joten dementiakuolleisuuden määrittelyssä käytettiin myös tietoa myötävaikuttavista syistä. Rajausten jälkeen aineistossa on 317 944 henkilöä, joista 128 562 on miehiä ja 189 382 naisia. Pääanalyysimenetelmänä on käytetty elinaikamalleihin kuuluvaa Coxin regressiota. Dementiakuolleisuudessa oli vaihtelua kaikkien tutkimuksessa käytettyjen muuttujien, eli koulutuksen, sosiaaliluokan, tulojen, siviilisäädyn sekä perhemuodon mukaan. Koulutuksen vaikutus välittyi osin ammattiasemaan perustuvan sosiaaliluokan kautta. Suurimpia ryhmien väliset suhteelliset erot olivat nuoremmissa ikäryhmissä sekä sosiaaliluokan ja siviilisäädyn kohdalla. Eronneilla ja naimattomilla oli selvästi kohonnut riski suhteessa naimisissa oleviin. Myös työntekijöillä havaittiin kohonnut riski suhteessa ylempiin toimihenkilöihin. Siviilisääty vaikutti olevan merkittävä tekijä siinä mielessä, että koulutuksen, sosiaaliluokan ja tulojen tuominen malliin ei juuri vaikuttanut siviilisäätyryhmien välillä havaittuun vaihteluun. Dementiakuolleisuudessa havaitut ryhmien väliset suhteelliset erot olivat hieman pienempiä kuin muissa syissä, mutta kuitenkin hyvin samaa suuruusluokkaa. Tulosten perusteella on identifioitavissa tekijöitä, jotka suojaavat dementialta. Erityisesti avioliitto, korkea koulutus sekä ylemmät toimihenkilöammatit vaikuttavat olevan dementialta suojaavia tekijöitä. Avioliiton suojaavan vaikutuksen voidaan tulkita liittyvän sosiaaliseen kanssakäymiseen sekä puolison tukeen ja läsnäoloon. Korkea koulutus sekä toimihenkilöammatit indikoivat virikkeellisempää työympäristöä, mutta niiden vaikutus voi myös kulkea ylipäänsä aktiivisemman ja kognitiivisesti virikkeellisemmän elämäntavan kautta. Aktiivisen ja kognitiivisesti haastavan elämäntavan on esitetty suojaavan dementiaan sairastumiselta. Tuloksia voidaan tulkita elämänkaarinäkökulman kautta. Jo nuoruudessa vaikuttavilla tekijöillä, kuten koulutuksella, on vaikutusta. Tämän lisäksi elämänkaaren aikana myöhemmin vaikuttavat tekijät ovat merkityksellisiä. Näiden tekijöiden on esitetty vaikuttavan aivojen hermoverkostoon ja -yhteyksiin ja luovan kognitiivista reserviä, minkä on esitetty ehkäisevän tai lykkäävän dementiaan sairastumista.

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The modern food system and sustainable development form a conceptual combination that suggests sustainability deficits in environmental impacts and nutritional status of western populations. This study explores actors orientations towards sustainability by probing into social dynamics for sustainability within primary production and public consumption. If actors within these two worlds were to express converging orientations for sustainability, the system dynamics of the market would enable more sustainable growth in terms of production dictated by consumption. The study is based on a constructivist research approach with qualitative text analyses. The findings were validated by internal and external food system actors and are suggested to represent current social dynamics within Finnish food system. The key findings included primary producers social skilfulness, which enabled networking with other actors in very different paths of life, learning in order to promote one s trade, and trusting reflectively in partners in order to expand business. These activities extended the supply chain in a spiral fashion by horizontal and vertical forward integration, until large retailers were met for negotiations on a more equal basis. This mode of chain level coordination, typically building around the core of social and partnership relations, was coined as a socially overlaid network, and seen as sustainable coordination mode for endogenous growth. The caterers exhibited more or less committed professional identity for sustainability within their reach. The facilitating approaches for professional identities dealt successfully with local and organic food in addition to domestic food, and also imported food. The co-operation with supply chains created innovative solutions and savings for the business parties to be shared. There were also more complicated identities as juggling, critical and delimited approaches for sustainability, with less productive efforts due to restrictions such as absence of organisational sustainability strategy, weak presence of local and organic suppliers, limited understanding about sustainability and no organisational resources for informed choices for sustainability. The convergence between producers and caterers existed to an extent allowing suggestion that increased clarity about sustainable consumption and production by actors could be constructed using advanced tools. The study looks for introduction of more profound environmental and socio-economic knowledge through participatory research with supply chain actors. Learning in the workplace about food system reality in terms of supply chain co-operation may prove to be a change engine that leads to advanced network operations and a more sustainable food system.

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This doctoral thesis is about the solar wind influence on the atmosphere of the planet Venus. A numerical plasma simulation model was developed for the interaction between Venus and the solar wind to study the erosion of charged particles from the Venus upper atmosphere. The developed model is a hybrid simulation where ions are treated as particles and electrons are modelled as a fluid. The simulation was used to study the solar wind induced ion escape from Venus as observed by the European Space Agency's Venus Express and NASA's Pioneer Venus Orbiter spacecraft. Especially, observations made by the ASPERA-4 particle instrument onboard Venus Express were studied. The thesis consists of an introductory part and four peer-reviewed articles published in scientific journals. In the introduction Venus is presented as one of the terrestrial planets in the Solar System and the main findings of the work are discussed within the wider context of planetary physics. Venus is the closest neighbouring planet to the Earth and the most earthlike planet in its size and mass orbiting the Sun. Whereas the atmosphere of the Earth consists mainly of nitrogen and oxygen, Venus has a hot carbon dioxide atmosphere, which is dominated by the greenhouse effect. Venus has all of its water in the atmosphere, which is only a fraction of the Earth's total water supply. Since planets developed presumably in similar conditions in the young Solar System, why Venus and Earth became so different in many respects? One important feature of Venus is that the planet does not have an intrinsic magnetic field. This makes it possible for the solar wind, a continuous stream of charged particles from the Sun, to flow close to Venus and to pick up ions from the planet's upper atmosphere. The strong intrinsic magnetic field of the Earth dominates the terrestrial magnetosphere and deflects the solar wind flow far away from the atmosphere. The region around Venus where the planet's atmosphere interacts with the solar wind is called the plasma environment or the induced magnetosphere. Main findings of the work include new knowledge about the movement of escaping planetary ions in the Venusian induced magnetosphere. Further, the developed simulation model was used to study how the solar wind conditions affect the ion escape from Venus. Especially, the global three-dimensional structure of the Venusian particle and magnetic environment was studied. The results help to interpret spacecraft observations around the planet. Finally, several remaining questions were identified, which could potentially improve our knowledge of the Venus ion escape and guide the future development of planetary plasma simulations.

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Africa is threatened by climate change. The adaptive capacity of local communities continues to be weakened by ineffective and inefficient livelihood strategies and inappropriate development interventions. One of the greatest challenges for climate change adaptation in Africa is related to the governance of natural resources used by vulnerable poor groups as assets for adaptation. Practical and good governance activities for adaptation in Africa is urgently and much needed to support adaptation actions, interventions and planning. The adaptation role of forests has not been as prominent in the international discourse and actions as their mitigation role. This study therefore focused on the forest as one of the natural resources used for adaptation. The general objective of this research was to assess the extent to which cases of current forest governance practices in four African countries Burkina Faso, The Democratic Republic of Congo (DRC), Ghana and Sudan are supportive to the adaptation of vulnerable societies and ecosystems to impacts of climate change. Qualitative and quantitative analyses from surveys, expert consultations and group discussions were used in analysing the case studies. The entire research was guided by three conceptual sets of thinking forest governance, climate change vulnerability and ecosystem services. Data for the research were collected from selected ongoing forestry activities and programmes. The study mainly dealt with forest management policies and practices that can improve the adaptation of forest ecosystems (Study I) and the adaptive capacity through the management of forest resources by vulnerable farmers (Studies II, III, IV and V). It was found that adaptation is not part of current forest policies, but, instead, policies contain elements of risk management practices, which are also relevant to the adaptation of forest ecosystems. These practices include, among others, the management of forest fires, forest genetic resources, non-timber resources and silvicultural practices. Better livelihood opportunities emerged as the priority for the farmers. These vulnerable farmers had different forms of forest management. They have a wide range of experience and practical knowledge relevant to ensure and achieve livelihood improvement alongside sustainable management and good governance of natural resources. The contributions of traded non-timber forest products to climate change adaptation appear limited for local communities, based on their distribution among the stakeholders in the market chain. Plantation (agro)forestry, if well implemented and managed by communities, has a high potential in reducing socio-ecological vulnerability by increasing the food production and restocking degraded forest lands. Integration of legal arrangements with continuous monitoring, evaluation and improvement may drive this activity to support short, medium and long term expectations related to adaptation processes. The study concludes that effective forest governance initiatives led by vulnerable poor groups represent one practical way to improve the adaptive capacities of socio-ecological systems against the impacts of climate change in Africa.

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In Finland, specialized studies in social work (professional licentiate education) were begun in the year 2000. The education is targeted at experienced social workers and leads to a licentiate degree (a degree between master s and doctorate). In this study, the experiences of members of the first study cohort, specializing in social work with children and young people, are examined. The study s theoretical frame of reference is based on the morphogenetic approach, developed by British sociologist Margaret Archer. In it, the potential powers of both an agent as well as social and cultural structures are considered important and worth taking into account. Archer sees reflexivity, a person s ability to analyze herself/himself, as an essential starting point for agency. Thanks to reflexivity, people are able to engage in internal conversations , discuss the concerns that are important to them and form agential projects . In Archer s theory, the social structures and traits of the cultural system are seen as having potential power in relation to people s agential projects; these powers can enable but also restrain the realization of the projects. On the other hand, individuals can try to review the factors affecting their agential projects and find ways of action that facilitate them. The research task is to study the self-understanding of social work professionals in the 21st century, the issues and goals professionally important for them, as well as the contexts framing the realization of these goals. The research questions are as follows: 1) What kind of internal conversations, concerns and agential projects related to their work did the professionals taking part in licentiate education bring to light? 2) What kind of enabling and restraining factors can be identified in their situations? And 3) What kind of social structures and traits related to the cultural system are connected to these factors? The research material was collected by interviewing the students in different phases of their education. In 2001 and 2004 all members of the study group (n = 25) were interviewed. In 2007, 13 students took part. The themes of the internal conversations brought to light in the interviews were divided into four broad thematic categories: professional development, the position of children in social work, multiprofessional work and structural social work. In relation to these themes the students formed different kinds of agential projects. In addition, the study reveals several cultural and social structures that have enabled but also restrained the realization of the agential projects. These structures are linked, for example, to the relations between employees and employers, students and teachers, children and adults as well as between the representatives of different professions. Working conditions which social workers often consider weak are discussed as a focal issue related to many themes. These working conditions become evident, for example, in the great imbalance which exists between the professional tasks and the amount of time that social workers have for them. Difficult situations arise when social workers feel they cannot reach the goals that are professionally important to them because of the strict external conditions of the work.

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Suomen kylmän sodan aikaisesta kaupankäynnistä sosialististen maiden kanssa poliittisesti ja taloudellisesti merkittävintä oli kahdenvälinen kauppasuhde Neuvostoliiton kanssa. Tässä tutkielmassa määrittelen idänkaupan Suomen ja Neuvostoliiton väliseksi erityissuhteeksi, jota luonnehti käsitys molempien toisilleen myöntämästä erityisasemasta, kaupan tason poliittinen merkitys, jatkuvuuden korostaminen sekä clearing-järjestelmä. Neuvostoliiton hajotessa vuonna 1991 myös idänkauppa loppui. Tässä tutkielmassa argumentoin kuitenkin, ettei idänkaupan loppuminen ollut suoranaisesti seurausta Neuvostoliiton hajoamisesta. Kehityskulut, jotka johtivat idänkaupan loppumiseen, olivat murtaneet perustan kahdenvälisen kaupan erityissuhteelta jo ennen kuin Neuvostoliitto lopetti olemassaolonsa. Tarkastelen kaupan erityissuhteen purkautumista vuosina 1988–1991. Keskeisiä tapahtumia idänkaupan loppuvaiheessa oli clearing-järjestelmän uudistaminen vuonna 1988, viimeisen clearingpohjaisen runkosopimuksen allekirjoittaminen 1989, clearing-järjestelmän lopettaminen vuonna 1990 sekä Neuvostoliiton hajoaminen 1991. Keskityn kauppapolitiikan valmistelutason toimintaan. Tärkeimmän lähdeaineiston muodostavat ulkoministeriön kauppapoliittisen osaston ja Suomen Pankin idänkaupan osaston arkistoaineisto. Tutkimuskysymys on kaksiosainen. Ensinnäkin tutkin Suomen kauppapolitiikan toimijoiden näkemyksiä idänkaupan tulevaisuudesta. Käsittelen sitä, miltä idänkaupan tulevaisuus näytti silloin, kun se oli loppumassa. Vaikka idänkaupan loppuminen näyttää jälkikäteen suoraviivaiselta, se ei ollut sitä tapahtumahetkellä. Käytän apunani Reinhart Koselleckin käsitteitä odotushorisontista (horizon of expectations) ja kokemusavaruudesta (space of experience). Toiseksi pyrin piirtämään kuvan siitä idänkaupasta, joka loppui. Tarkastelen idänkauppaa sille ominaisten piirteiden kautta selvittääkseni, mitkä idänkaupan ominaisuudet vaikuttivat sen loppumiseen. Tutkielman perusteella Suomen ja Neuvostoliiton välinen kauppasuhteen erityisyyden purkaantuminen johtui ensisijaisesti muutoksista Neuvostoliitossa, mutta myös Suomen ja kansainvälisen ympäristön poliittisilla ja taloudellisilla muutoksilla oli merkitystä. Idänkaupan järjestelmä loppui, koska se ei sopeutunut muuttuvaan maailmaan. Idänkaupan ilmiöön liittyneiden vahvojen epämuodollisten instituutioiden ansiota oli, että erityissuhde jatkui niin pitkään.

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This study identified the molecular defects underlying three lethal fetal syndromes. Lethal Congenital Contracture Syndrome 1 (LCCS1, MIM 253310) and Lethal Arthrogryposis with Anterior Horn Cell Disease (LAAHD, MIM 611890) are fetal motor neuron diseases. They affect the nerve cells that control voluntary muscle movement, and eventually result in severe atrophy of spinal cord motor neurons and fetal immobility. Both LCCS1 and LAAHD are caused by mutations in the GLE1 gene, which encodes for a multifunctional protein involved in posttranscriptional mRNA processing. LCCS2 and LCCS3, two syndromes that are clinically similar to LCCS1, are caused by defective proteins involved in the synthesis of inositol hexakisphosphate (IP6), an essential cofactor of GLE1. This suggests a common mechanism behind these fetal motor neuron diseases, and along with accumulating evidence from genetic studies of more late-onset motor neuron diseases such as Spinal muscular atrophy (SMA) and Amyotrophic lateral sclerosis (ALS), implicates mRNA processing as a common mechanism in motor neuron disease pathogenesis. We also studied gle1-/- zebrafish in order to investigate whether they would be a good model for studying the pathogenesis of LCCS1 and LAAHD. Mutant zebrafish exhibit cell death in their central nervous system at two days post fertilization, and the distribution of mRNA within the cells of mutant zebrafish differs from controls, encouraging further studies. The third lethal fetal syndrome is described in this study for the first time. Cocoon syndrome (MIM 613630) was discovered in a Finnish family with two affected individuals. Its hallmarks are the encasement of the limbs under the skin, and severe craniofacial abnormalities, including the lack of skull bones. We showed that Cocoon syndrome is caused by a mutation in the gene encoding the conserved helix-loop-helix ubiquitous kinase CHUK, also known as IκB kinase α (IKKα). The mutation results in the complete lack of CHUK protein expression. CHUK is a subunit of the IκB kinase enzyme that inhibits NF-κB transcription factors, but in addition, it has an essential, independent role in controlling keratinocyte differentiation, as well as informing morphogenetic events such as limb and skeletal patterning. CHUK also acts as a tumor suppressor, and is frequently inactivated in cancer. This study has brought significant new information about the molecular background of these three lethal fetal syndromes, as well as provided knowledge about the prerequisites of normal human development.

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Continuing urbanization is a crucial driver of land transformation, having widespread impacts on virtually all ecosystems. Terrestrial ecosystems, including disturbed ones, are dependent on soils, which provide a multitude of ecosystem services. As soils are always directly and/or indirectly impacted through land transformation, land cover change causes soil change. Knowledge of ecosystem properties and functions in soils is increasing in importance as humans continue to concentrate into already densely-populated areas. Urban soils often have hampered functioning due to various disturbances resulting from human activity. Innovative solutions are needed to bring the lacking ecosystem services and quality of life to these urban environments. For instance, the ecosystem services of the urban green infrastructure may be substantially improved through knowledge of their functional properties. In the research forming this thesis, the impacts of four plant species (Picea abies, Calluna vulgaris, Lotus corniculatus and Holcus lanatus) on belowground biota and regulatory ecosystem services were investigated in two different urban soil types. The retention of inorganic nitrogen and phosphorus in the plant-soil system, decomposition of plant litter, primary production, and the degradation of polycyclic aromatic hydrocarbons (PAHs) were examined in the field and under laboratory conditions. The main objective of the research was to determine whether the different plant species (representing traits with varying litter decomposability) will give rise to dissimilar urban belowground communities with differing ecological functions. Microbial activity as well as the abundance of nematodes and enchytraeid worm biomass was highest below the legume L. corniculatus. L. corniculatus and the grass H. lanatus, producing labile or intermediate quality litter, enhanced the proportion of bacteria in the soil rhizosphere, while the recalcitrant litter-producing shrub C. vulgaris and the conifer P. abies stimulated the growth of fungi. The loss of nitrogen from the plant-soil system was small for H. lanatus and the combination of C. vulgaris + P. abies, irrespective of their energy channel composition. These presumably nitrogen-conservative plant species effectively diminished the leaching losses from the plant-soil systems with all the plant traits present. The laboratory experiment revealed a difference in N allocation between the plant traits: C. vulgaris and P. abies sequestered significantly more N in aboveground shoots in comparison to L. corniculatus and H. Lanatus. Plant rhizosphere effects were less clear for phosphorus retention, litter decomposition and the degradation of PAH compounds. This may be due to the relatively short experimental durations, as the maturation of the plant-soil system is likely to take a considerably longer time. The empirical studies of this thesis demonstrated that the soil communities rapidly reflect changes in plant coverage, and this has consequences for the functionality of soils. The energy channel composition of soils can be manipulated through plants, which was also supported by the results of the separate meta-analysis conducted in this thesis. However, further research is needed to understand the linkages between the biological community properties and ecosystem services in strongly human-modified systems.

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Electric activity of the heart consists of repeated cardiomyocyte depolarizations and repolarizations. Abnormalities in repolarization predispose to ventricular arrhythmias. In body surface electrocardiogram, ventricular repolarization generates the T wave. Several electrocardiographic measures have been developed both for clinical and research purposes to detect repolarization abnormalities. The study aim was to investigate modifiers of ventricular repolarization with the focus on the relationship of the left ventricular mass, antihypertensive drugs, and common gene variants, to electrocardiographic repolarization parameters. The prognostic value of repolarization parameters was also assessed. The study subjects originated from a population of more than 200 middle-aged hypertensive men attending the GENRES hypertension study, and from an epidemiological survey, the Health 2000 Study, including more than 6000 participants. Ventricular repolarization was analysed from digital standard 12-lead resting electrocardiograms with two QT-interval based repolarization parameters (QT interval, T-wave peak to T-wave end interval) and with a set of four T-wave morphology parameters. The results showed that in hypertensive men, a linear change in repolarization parameters is present even in the normal range of left ventricular mass, and that even mild left ventricular hypertrophy is associated with potentially adverse electrocardiographic repolarization changes. In addition, treatments with losartan, bisoprolol, amlodipine, and hydrochlorothiazide have divergent short-term effects on repolarization parameters in hypertensive men. Analyses of the general population sample showed that single nucleotide polymorphisms in KCNH2, KCNE1, and NOS1AP genes are associated with changes in QT-interval based repolarization parameters but not consistently with T-wave morphology parameters. T-wave morphology parameters, but not QT interval or T-wave peak to T-wave end interval, provided independent prognostic information on mortality. The prognostic value was specifically related to cardiovascular mortality. The results indicate that, in hypertension, altered ventricular repolarization is already present in mild left ventricular mass increase, and that commonly used antihypertensive drugs may relatively rapidly and treatment-specifically modify electrocardiographic repolarization parameters. Common variants in cardiac ion channel genes and NOS1AP gene may also modify repolarization-related arrhythmia vulnerability. In the general population, T-wave morphology parameters may be useful in the risk assessment of cardiovascular mortality.

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This study discusses legal interpretation. The question is how legal texts, for instance laws, statutes and regulations, can and do have meaning. Language makes interpretation difficult as it holds no definite meanings. When the theoretical connection between semantics and legal meaning is loosened and we realise that language cannot be a means of justifying legal decisions, the responsibility inherent in legal interpretation can be seen in full. We are thus compelled to search for ways to analyse this responsibility. The main argument of the book is that the responsibility of legal interpretation contains a responsibility towards the text that is interpreted (and through the mediation of the text also towards the legal system), but not only this. It is not simply a responsibility to read and read well, but it transcends on a broader scale. It includes responsibility for the effects of the interpretation in a particular situation and with regard to the people whose case is decided. Ultimately, it is a responsibility to do justice. These two aspects of responsibility are conceptualised here as the two dimensions of the ethics of legal interpretation: the textual and the situational. The basic conception of language presented here is provided by Ludwig Wittgenstein s later philosophy, but the argument is not committed to only one philosophical tradition. Wittgenstein can be counterpointed in interesting ways by Jacques Derrida s ideas on language and meaning. Derrida s work also functions as a contrast to hermeneutic theories. It is argued that the seed to an answer to the question of meaning lies in the inter-personal and situated activity of interpretation and communication, an idea that can be discerned in different ways in the works of Wittgenstein, Derrida and Hans-Georg Gadamer. This way the question of meaning naturally leads us to think about ethics, which is approached here through the philosophy of Emmanuel Levinas. His thinking, focusing on topics such as otherness, friendship and hospitality, provides possibilities for answering some of the questions posed in this book. However, at the same time we move inside a normativity where ethics and politics come together in many ways. The responsibility of legal interpretation is connected to the political and this has to be acknowledged lest we forget that law always implies force. But it is argued here that the political can be explored in positive terms as it does not have to mean only power or violence.

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Bipolar I disorder is a severe psychiatric disorder characterized by episodic mood alterations that can be manic, depressive or mixed. Bipolar disorder seems to be highly genetic, but the etiology of this complex disorder has remained elusive. In recent years, studies have found that euthymic patients with bipolar disorder may have impairments particularly in executive functioning, verbal learning and memory. These impairments may be present also among some of the relatives of these patients, who may be vulnerable to the disorder. Using neuropsychological variables as endophenotypes, i.e. intermediate phenotypes between genes and the phenotypes, has been suggested to aid search for the etiological background of the disorder, but evidence is sparse on whether these variables fulfill the criteria for endophenotypes. The present thesis is part of the Genetic Epidemiology and Molecular Genetics of Severe Mental Disorders in Finland project. The specific aim was to investigate whether neuropsychological test variables would indicate genetic liability to the disorder and could therefore be regarded as endophenotypes. Thus, cognitive functions and their heritability were studied in bipolar I disorder patients and in their unaffected first-degree relatives from a population-based sample of families, comparing them to a population-based control group. In order to add homogeneity to the subgroups of bipolar disorder patients and their relatives, cognitive functions and their heritability were further studied in a group of families affected by bipolar I disorder only (bipolar families) and another group of families affected by both bipolar I disorder and schizophrenia or schizoaffective disorders (mixed families). Finally, the effect of processing speed on other cognitive functions was investigated. The study showed that especially executive functioning and processing speed fulfilled the endophenotype criteria. Impairments in these functions were found in bipolar patients and in their relatives irrespective of other severe psychopathology in the family. These functions were highly heritable in these families. Study also showed that generalized impairment in verbal memory may associate more with bipolar disorder than to vulnerability to other psychotic disorders, and be more related to fully developed disease; impairments in verbal learning and memory were found only in patients, and they were not found to be highly heritable. Finally, the most potential endophenotype, i.e. processing speed, seemed to contribute to a range of other cognitive dysfunctions seen in bipolar disorder patients. Processing speed, in particular, has also been shown to be a valid endophenotype in subsequent association analyses in psychiatric genetics in Finland and internationally. Information concerning cognitive impairments and their association with the psychosocial consequences of bipolar disorder is important in planning treatment. It is also important to understand and acknowledge that patients may have cognitive impairments that affect their everyday life. Psychosocial interventions and neuropsychological rehabilitation may supplement other conventional treatments for bipolar patients.

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Cancer is becoming the leading cause of deaths in the world. As 90% of all deaths from cancer are caused by metastasis, discovery of the mechanisms behind cancer cell invasion and metastasis is of utmost importance. Only new effective therapies targeting cancer progression can reduce cancer mortality rates. The aim of this study was to identify molecules that are relevant for tumor cell invasion and spreading in fibrosarcomas and melanomas, and to analyze their potential for cancer biomarkers or therapeutic targets. First, the gene expression changes of normal cells and transformed cells showing high invasiveness, S-adenosylmethionine decarboxylase (AdoMetDC)-transfected murine fibroblasts and human melanoma cells, were studied by microarray analyses. The function of the identified candidate molecules were then studied in detail in these cell lines. Finally, the physiological relevance of the identified changes was studied by immunohistochemical analyses of human sarcoma and melanoma specimens or by a mouse xenograft model. In fibrosarcoma cells, the most remarkable change detected was a dramatic up-regulation of the actin-sequestering molecule thymosin beta 4 (TB4), which was shown to be important for the transformed phenotype of the AdoMetDC-transfected cells (Amdc-s and -as). A sponge toxin latrunculin A, inhibiting the binding of TB4 to actin, was found to selectively inhibit the migration and invasion of these cells. Further, Amdc-s-induced mouse tumors and human high-grade sarcomas were found to show intense TB4 immunostaining. In addition to TB4, integrin subunits alfa 6 and beta 7 (ItgA6 and ItgB7) were found to be up-regulated in Amdc-s and -as cells. ItgA6 was shown to dimerize mainly with ItgB1 in Amdc-s. Inhibition of ItgA6 or ItgB1 function with neutralizing antibodies fully blocked the invasiveness of Amdc-s cells, and importantly also human HT-1080 fibrosarcoma cells, in three-dimensional (3D)-Matrigel mimicking tumor extracellular matrix (ECM). By immunohistochemical analyses, strong staining for ITGA6 was detected in human high-grade fibrosarcomas and other sarcomas, especially at the invasion fronts of the tumors. In the studied melanoma cell lines, the expression levels of the adhesion-related ECM proteins tenascin-C (TN-C), fibronectin (FN), and transforming growth factor beta-induced (TGFBI) were found to be highly up-regulated. By immunohistochemistry, intense TN-C and FN staining was detected in invasive and metastatic melanoma tumors, showing co-localization (together with procollagen-I) in tubular meshworks and channels around the invading melanoma cells. In vitro, TN-C and FN were further found to directly stimulate the migration of melanoma cells in 3D-collagen-I matrix. The third candidate protein, TGFBI, was found to be an anti-adhesive molecule for melanoma cells, and knockdown of its expression in metastatic melanoma cells (TGFBI-KD cells) led to dramatically impaired tumor growth in immunocompromized mice. Interestingly, the control tumors showed intense TGFBI immunostaining in the invasion fronts, showing partial co-localization with the fibrillar FN staining, whereas the small TGFBI-KD cell-induced tumors displayed amorphous, non-fibrillar FN staining. These data suggest an important role for TGFBI in FN fibrillogenesis and melanoma progression. In conclusion, we have identified several invasion-related molecules, which show potential for cancer diagnostic or prognostic markers, or therapeutic targets. Based on our previous and present fibrosarcoma studies, we propose the possibility of using ITGA6 antagonists (affecting tumor cell adhesion) in combination with TB4 inhibitors (affecting tumor cell migration) and cathepsin L inhibitors (affecting the degradation of basement membrane and ECM proteins) for the treatment of fibrosarcomas and other tumors overexpressing these molecules. With melanoma cells, in turn, we point to the importance of three secreted ECM proteins, TN-C, FN, and TGFBI, in melanoma progression. Of these, especially the potential of TN-C as a prognostic melanoma biomarker and TGFBI as a promising therapeutic target molecule are clearly worth additional studies.

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Merkel cell carcinoma (MCC) is a rare cutaneous malignancy that occurs predominantly on sun exposed skin areas. A new polyomavirus (MCPyV) was identified in MCC tumor tissues in 2008 suggesting that a viral infection might be an etiological factor. A typical MCC is a rapidly growing painless purple nodule. In its early stage it can be misjudged by its appearance as a cyst or abscess. Recurrences are common and approximately half of the patients will develop lymph node metastases and third of the patents will have distant metastases. It affects mostly elderly persons at an average age of 70 at the time of diagnosis. MCC was first described in 1972 and the first MCC patient in Finland was identified in 1983. MCC has been poorly recognized, but increased awareness and better diagnostic accuracy has increased the incidence since the early years. In this study, all cases with a notation of MCC during 1979 2008 were obtained from the Finnish Cancer Registry. Based on this data, the incidence is 0.11 for men and 0.12 for women. It is similar than that of other Nordic countries, but lower than in the USA. For clinical series, the files of patients diagnosed with MCC during 1983 2004 were reviewed, and the tissue samples were re-evaluated, if available (n=181). Third of the patients were men, and the most common site of the primary tumor was the head and neck (53%). The majority of the patients (86%) presented with a clinically node-negative (Stage I or II) disease, but the disease recurred in 38% of them. The treatment schemes were heterogeneous. No additional benefit from a wide margin (≥2 cm) was found compared to a margin of 0.1-1.9 cm, but intralesional excision was more often associated with local recurrence. None of the patients with Stage I-II disease who had received postoperative radiotherapy had local recurrence during the follow-up period. The 5-year relative survival ratio for Stage I disease was 68%, for Stage II 67%, for Stage III 16%, and for Stage IV 0%. The relative excess risk of death was significantly lower among women than among men. Some of these tissue samples were further analyzed for vascular invasion (n=126) by immunohistochemistry using vascular endothelial markers CD-31 and D2-40. Vascular invasion was seen in 93% of the samples and it was observed already in very small, <5mm tumors. The tissue samples were also analyzed for the presence of MCPyV by using a polymerase chain reaction (PCR) and quantitative PCR. MCPyV DNA was present in 80% of 114 samples studied. The patients with virus-positive tumors had better overall survival than patients with virus-negative tumors. Immunohistochemical analyses were performed for the expression of VEGFR-2 (n=21) and endostatin (n=19), but they had no prognostic value. Our results support the concept of treating MCC with margin-negative excision and radiotherapy to the tumor bed to reduce local recurrence. The finding of a high frequency of lymphovascular invasion reduces its value as a prognostic factor, but emphasizes the role of sentinel node biopsy even in very small primary MCC.

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The main aim of this work was to explore the use of Mao Zedong s (毛泽东, 1893—1976) visual image in contemporary Chinese art during the years 1976—2006. Chairman Mao is the most visually reproduced person in the People's Republic of China (PRC), and the presence of his image is still unquestionable at many levels. Although several scholars have provided insightful observations on this topic, research focusing on Mao's visual image has been neglected. Employing the interdisciplinary approach of visual studies and using image as the main concept, this research combines different theoretical frameworks, deriving from art history, image studies and social sciences, for each chapter in order to explain the origins, intentions and major strategies of the contemporary Chinese artists. The focus of this research was to elucidate how Mao's visual image, deriving from the Maoist era, is re-created and negotiated in contemporary Chinese art works. The material reproductions - the visual images in contemporary art - are created to be juxtaposed with the immaterial mental images of Mao that were created during the Maoist era through the original visual images of Mao. This complex interaction between visual and mental images is further exemplified by art works that do not include Mao's visual image, but still imply his mental image. The methods used derive from both sinology and art history. The research is based on extensive fieldwork in China, which was crucial for gathering new information and materials from this vigorous art scene. The topic is approached through a Chinese cultural, political and historical perspective that is necessary for a further understanding of how the original visual images of Mao obtained their omnipotent status and what kind of iconography was created. Close structural analysis, taking into account the format, style, techniques, composition, colors, materials and space used in the art works, is employed to demonstrate the great variety of visual images created. The analysis is further placed in a continuous dialogue both with the contemporary art works of Mao and with the original visual images of Mao from the past. In this study it is shown that contemporary Chinese art relating to Chairman Mao is a more versatile and multilayered phenomenon than is generally assumed. Although some of the art works seem to fit into the definition of superficial art, the study demonstrates that this reading of the art works is not adequate. The author argues that employing Mao's visual images in contemporary Chinese art is based on three main strategies used by artists: to create a visual dialogue with a traumatizing past, to employ transcontextual parody, and to explore the importance of Tian'anmen through site-dependent art. These strategies are not exclusionary, but instead interdependent and many art works employ more than one of them. In addition, these three main strategies include versatile methods used by artists that make the use of Mao's visual images even more multifaceted.