Väitöstiivistelmät

Recent Submissions

  • Koskinen, Hanna (Kela, 2018)
    This study examines the impact of the implementation of a generic reference price system on pharmaceutical prices and competition within the market. The focus is particularly on antipsychotic medications. Furthermore, the impact of reference pricing on previously implemented generic substitution is assessed. Antipsychotics and antidepressants were, in terms of value, among the fastest growing pharmaceutical groups in Finland at the turn of the 21st century. For antipsychotics, most of the cost growth resulted from the rise in the mean daily cost of treatment, whereas the main reason for antidepressant cost growth was the increased number of patients. The implementation of reference pricing decreased the daily cost of the studied antipsychotics. The decreases ranged from 30% to 66% in the short term and from 25% to 51% in the medium-to-long term. When the study was extended to other pharmaceutical groups, the average decrease was 35% at the end of the first year, 56% at the end of the second year and 60% at the end of the third year. However, there were large differences in the size of the decrease between groups. Being included in the reference price system had the largest decreasing impact on prices. However, the reference price system’s impact on prices appeared to be waning; the later an active substance was included in the system, the higher the price level remained. In addition, the impact of the reference price system on previously implemented generic substitution remained low, and 2.5 years after the implementation of the reference price system it was almost non-existent. Generic pharmaceutical markets are highly concentrated in Finland. In addition, there is an overall lack of transparency in the pharmaceutical distribution chain. Further research is needed on the barriers of entry and on the role different operators of the pharmaceutical distribution chain have in promoting price competition in the generic market sector.
  • Jansson, Julia (Unigrafia, 2018)
    Most past definitions of terrorism have included a political element. What would terrorist acts be without the political/ideological element? Mass killings, hijackings, bombings... 'Common' crimes, combined with often uncommonly destructive elements. Regardless of this inherent political element, the last decades have seen a global trend of depoliticising terrorism for the purpose of international collaboration. My thesis describes and discusses this trend and the reasons behind it. Following a thorough analysis of international conventions and treaties as well as bilateral extradition treaties from the 1800s until the early 2000s, it suggests that terrorism has been depoliticised due to the existence of the so-called political offence exception to extradition that emerged in extradition treaties in 1834. Because of the exemption, a widely accepted spawn of the revolutionary era, political offenders, in some cases including terrorists, were for a long time protected from extradition. The aim of the depoliticisation formula was to protect ‘legitimate’ political offenders, but exclude terrorists from the protection of the political offence exemption. Alongside the depoliticisation of terrorism, the political offence exemption was growingly limited since the emergence of the modern terrorist threat in the 1970s. In addition to the depoliticisation of terrorism, we have witnessed a contradicting trend of what I call repoliticisation, where special laws and tribunals have been set to deal with the terrorist threat. The new laws, contrary to the depoliticisation strategy, underline the political nature of terrorism by criminalising acts such as the glorification of terrorism. My thesis examines these contrasting trends and takes a critical look at the various implications of both the depoliticisation of terrorism and underlining the political element of it. One of these implications is the decreasing global protection for non-violent political offenders.
  • Hafez, Ahmad (2018)
    Background: Management strategies for brain arteriovenous malformation (AVM) remain controversial. AVM resection is the optimal, definitive treatment, if performed with little risk of consequences and complications. The aim is to evaluate the features, surgical treatment, results, and outcomes of AVMs. Patients and methods: Six operative cases from the University of California, San Francisco, were selected to demonstrate the surgical technique used in and results of a contralateral anterior interhemispheric approach (CAIA) to medial frontal AVMs. We also analyzed the clinical and radiological data from a database of 805 consecutive patients. They were treated between 1942- 2014” and diagnosed with AVM at the Department of Neurosurgery of the Helsinki University Hospital, which served Southern Finland. We focused a defined subgroup of the whole study in each part of this study. A detailed analysis of 59 surgically-treated ruptured supratentorial AVMs was conducted, focusing on the time elapsed before surgery as a unique factor for the outcome. A novel Supplementary Spetzler-Martin Grading System (also known as Lawton-Young Grading Scale) was applied to predict outcomes of AVM surgery on 200 patients admitted between 2000- 2014; results were then compared to the more classical Spetzler-Martin scale. Results: A CAIA to access medial frontal AVMs is a safe alternative to the ipsilateral approach, in certain circumstances. Elapsed time (as a sole factor) between rupture and surgery did not affect early or final outcomes. Many other factors played more significant roles than timing in long-term outcomes for surgically-treated, ruptured supratentorial AVMs. For cases with poor final outcomes, associated aneurysms, high Hunt and Hess (H&H) grades, and more than 400cc of bleeding during surgery were significant factors. For predicting surgical outcome for AVMs, performance of the Supplementary Spetzler-Martin Grading System was superior to original Spetzler-Martin Grading Scale in short- and long-term follow-ups. Deep perforator supply, which is not part of either the scale, proved to be an important factor influencing outcomes. Conclusions: Microsurgery is the treatment of choice for a considerable number of brain AVMs. Certain locations and vascular features of brain AVMs could necessitate contralateral approaches. For ruptured AVMs, the elapsed time before surgery has no significant influence on the outcome. Application of the Supplementary Spetzler-Martin Grading System in patients with brain AVMs improves prediction of surgical outcomes better than the original Spetzler-Martin grading system.
  • Yan, Yan (Hansaprint, 2018)
    The LKB1-AMPK signaling pathway is critical in cell growth control and energy metabolism homeostasis. As a energy sensor, AMPK regulates numerous downstream pathways to reprogram cellular energy metabolism, thereby restoring energy balance via direct phosphorylation of downstream substrates or indirect modulation of metabolic transcription programs. While the discoveries of AMPK-regulated pathways have been crucial in understanding how AMPK restores energy homeostasis, evidence of modulating AMPK activity in a substrate specific manner is lacking. The first study of this thesis provided the first evidence that AMPKα1, the catalytic subunit of the AMPK, is SUMOylated and that the activity of AMPKα1 towards mTORC1, a downstream pathway of AMPK and a central regulator of cell growth, is specifically regulated. SUMOylation of AMPKα1 is induced upon AMPK activation, and PIAS4 was identified as the E3 ligase catalyzing the AMPKα1 SUMOylation. Cells depleted of either the sole E2 enzyme Ubc9, or E3 ligase PIAS4, or that harbor only SUMOylation-defective AMPKα1 mutant, all exhibit significantly higher AMPKα1 activity specifically towards mTORC1. Taken together, these data suggest that SUMOylation of AMPKα1 by PIAS4 upon AMPK activation serves as a “braking system” to prevent over-repression of mTORC1. Importantly, depleting PIAS4 potentiates the ability of AMPK to suppress mTORC1 and cell proliferation of breast cancer cells, implying that inhibition of AMPK SUMOylation may provide a novel strategy to inhibit cancers with hyperactive mTORC1.  In contrast to well-established roles in maintaining cellular energy homeostasis, the functions of AMPK in non-metabolic cellular processes have been less investigated. The second study of this thesis examined the role of AMPK in cell adhesion and mechanotransduction, and identified AMPK as a negative regulator of integrin, a key mediator of cell-matrix interactions. AMPKα1 and AMPKα2 redundantly repress ß1-integrin activity, integrin-dependent fibrillar adhesion formation, cell spreading and traction stress. Mechanistically, AMPKα inhibits integrin activity by repressing the expression of integrin-binding proteins, Tensin1/3. The study demonstrated that repression of Tensin by the energy sensor AMPK is a novel mechanism that regulates the activity of integrin, an essential membrane receptor that mediates extracellular matrix (ECM)-cytoskeleton interactions.  While the primary function of Lkb1, the major upstream kinase of AMPK in response to energy stress, is to restrict cell division and thereby suppress neoplastic growth of many tissues, it has also been reported to play critical roles in tissue homeostasis, such as hematopoietic stem cells (HSCs) homeostasis where Lkb1 is essential for maintaining stem cell quiescence. The critical role of Lkb1 in HSCs raised an intriguing question: does Lkb1 play a similar role in all stem cell populations or is it restricted to stem cells that are predominantly quiescent? The third study of this thesis investigated the role of Lkb1 in actively cycling intestinal stem cells (ISCs) and identified Lkb1 as a critical factor for maintaining ISCs. Mechanistically, Lkb1 represses the secretory cell gatekeeper, Atoh1, to restrict ISCs and intestinal progenitors from differentiating into secretory cell lineages. Importantly, both the repression of Atoh1 and the maintenance of ISCs by Lkb1 are independent of the classic Dll-Notch mediated cell extrinsic mechanism, thus establishing Lkb1as a cell intrinsic regulator of Atoh1 and ISCs.
  • Rantala, Teija (Unigrafia, 2018)
    This study examines women’s aspirations within the Conservative Laestadian movement. The Conservative Laestadian movement is a religious revival movement that is part of the Lutheran Church in Finland. Women in this religious movement have recently been at the centre of both scholarly and media discourse due mostly to the movement’s negative attitude towards birth control and female priesthood. In their avoidance of contraceptive use, Laestadian women go through childbirth repeatedly, often risking their health in the process. Consequently, these women’s participation in the movement and obedience to the laws of the doctrine, especially on the issue of contraceptive use, is widely considered to be a human rights issue. In this regard, the women are oppositionally positioned depending on whether they either resist or support changes in the movement: those women who advocate changes are presented as modern and independent, on the contrast, those women who resist changes are presented as subjugated victims of the patriarchal movement. My task has been to illuminate and even complicate this binary by examining the differing aspirations of Laestadian women with regard to their identities in the Laestadian movement. As a non-Laestadian researcher with a family background in the movement, I was able to produce data with the women within this exclusive movement. The main data consist of thirteen pieces of autobiographical writing but also include collaborative pieces and data produced before, during and after memory work sessions with four women. Memory work data was produced also with members of my own family. All the data were produced between 2012 and 2016 at various locations in Finland. The task of exploring the diversity of these women’s aspirations concerning their subjectivity formation required the employment of feminist and experimental poststructuralist analysis. To provide a depiction of the women’s aspirations outside normative and victimizing inquiry, I examined them using Gilles Deleuze’s and Félix Guattari’s schizoanalysis. With schizoanalysis, I asked what kinds of formations of subjectivity the women’s aspirations produce and how they intertwine with and differ in relation to faith, motherhood and womanhood. Schizoanalysis served in analysing these processes through complex and stratified examination. It also involved understanding of the various connections the aspirations are able to produce. This approach enabled the women’s desired subjectivities to be read beyond being oppressed, but neither as ready-formed and defined parts of the religious community or as fractional or self-contradictory. Rather, the formations were understood as changing, complex and shared. With the Laestadian women’s contributions to the data and with the assistance of feminist poststructuralist theory and methods, I argue that the Laestadian women’s desired formations of subjectivity are complex in the sense that they vary in their connectedness and separation to the community, but also always function both within and beyond the given positions of a sister and a mother.
  • Weigel, Anna Lena (not decided yet, 2018)
    The starting point of this study is the thesis that the Internet has not only altered the way we live, communicate, and think, but that it (along with other new media) has also breathed new life into the contemporary book market. We are in the midst of a paradigm shift in writing and reading novels, which has been triggered by medialization and digitalization processes. More and more 21st-century writers invoke new media in their literary texts and explore the limits of the novel as a medium by using intermedial and transmedial storytelling techniques. Because the media landscape and the book market are changing rapidly, new literary experiments are cropping up nearly every day. One primary goal of this study was to give a broad and extensive overview of the manifold tendencies in contemporary writings that are influenced by the Internet and new media on a thematic, structural, and transmedial level. This study therefore contributes to the ongoing debates on intermediality studies, transmedia storytelling, and genre theory, filling the gap in the area of intermedial and transmedial relations between 21st-century novels and new media. To contextualize this interdisciplinary study with regard to contemporary scholarship, I have combined text-centered with transgeneric, transmedial, and cultural-oriented approaches from literary, cultural, and media studies, and have focused on three main concepts—namely, ‘intermediality’, ‘transmedia storytelling’, and ‘genre/generic change’. In the theoretical section, I develop intermedial, transmedial, and genre-based frameworks and propose analytical catego¬ries which not only help to systematize the manifold new tendencies in contemporary writings, but also serve as useful tools for the analysis of ‘fictions of the Internet’. In this study, I use the label ‘fictions of the Internet’ in three ways: first, to describe cultural, medial, and ideological fictions and myths surrounding the Internet that masquerade as truth while actually being false; second, to refer to literary fictions that thematize and critically reflect on such fictions of the Internet age; and finally, I use the term as a generic label to subsume all the innovative 21st-century novels that deal with the Internet and new media on a thematic, structural, and trans¬medial level. By looking at seven in-depth case studies and considering 150 primary works that fall under the category of ‘fictions of the Internet’, it becomes clear that intermedial and transmedial storytelling techniques are not isolated phenomena—rather, they form an integral part of contemporary fiction. Based on the findings in the analysis chapters, ‘fictions of the Internet’ have creatively responded to the changing media landscape with regard to their content, form, materiality, technological support, and interactive and participatory features. The generic field of ‘fictions of the Internet’ is still in the process of development and could potentially change with new technological advances and with each new literary experiment. Although the designation of new genres is a difficult endeavor, I suggest new generic terms for literary innovations that are related to the Internet and new media: ‘psychological Internet thriller’, ‘Facebook novel’, ‘Internet satire’, ‘multimedia Internet novel’, ‘Internet-enhanced detective, thriller, and mystery novel’. Admittedly, all these labels are preliminary, but there are encouraging signs that they might have the potential to achieve acceptance in literary scholarship and develop into full-fledged genres in the years to come.
  • Dahlberg, Julia (Helsingin yliopisto, 2018)
    The intellectual culture in Finland during most of the 19th century was strongly influenced by philosophical idealism, Christian ethics and political nationalism. The self-understanding of the educated elite revolved around the German concept of 'Bildung', as translated into the Swedish concept of 'bildning' and the equivalent in Finnish ('sivistys'). As a concept, 'bildning' was understood as a moral obligation to promote the general well-being of the collective society, as defined through the national culture. Although this demand was extended to all social classes, it became particularly important for the self-understanding of the educated elite, which was expected to selflessly devote both time and effort to the Finnish nation and its people, language and culture. With special attention to the role of female artists, the aim of this study is to discuss how this understanding of the educated elite’s responsibilities within this “culture of bildung” was challenged among the Swedish-speaking educated elite in Finland during the late 19th century. Focusing on the artist, writer and public intellectual Helena Westermarck (1857–1938), the thesis discusses the public self of the female artist as a performance following the lines of the "artistic persona", or the culturally defined pattern for what is expected of an artist. Focusing on three lines of enquiry, the study analyses what kind of personal capacities, practical skills and virtues Westermarck associated with an artist, how she fashioned her public self as an artist, and how this performance was affected by different ideals associated on the one hand with the Finnish culture of 'bildung' and on the other hand with European liberalism, the cultural radicalism of the 1880s and what was called the Modern Breakthrough in Scandinavian cultural field. Using a broad range of published and unpublished texts such as letters, diaries, memoirs, novels, articles and other written and painted works by Westermarck as source materials, the study shows how the expectations placed on the artistic persona changed during the period 1880–1910 and how Westermarck gradually came to think of artists, writers and other public thinkers as a creative and intellectual elite within the educated elite. Arguing that this new identity helped Westermarck to distinguish herself from the larger mass of liberal professions and to promote her own position as a female artist, the study shows how Westermarck fashioned herself into a public intellectual with a self-conscious intellectual persona.
  • Paloniitty, Tiina (Juvenes Print Oy, 2018)
    The EU has taken a multi-faceted approach in addressing agricultural runoff, specifically with regards to the eutrophication of the Baltic Sea. The approaches are studied in this thesis resulting in the outcome that when the deliberate regulative attempts fail, the issue in all its complexity is left for the scientists to untangle. The work abides by Martin and Craig’s epistemology of environmental law, and consists of policy analysis, doctrinal research, and jurisprudential examination. When required, the administrative-legal system of Finland is used as an example. The first three instruments examined are the Common Agricultural Policy (the erratic regulator), the Nitrates Directive (the naïve regulator) and the EU Strategy for the Baltic Sea Region (the candid regulator). The closest examination is given to the ambitious regulator who takes the demands for adaptive and integrated water management seriously and issues the Water Framework Directive, which was vested with new normative clout by the CJEU in 2015 (the Weser ruling). The suggested reading of the post-Weserian Directive distinguishes between its internal and external influence, the latter extending to all undertakings with water impacts. The assessment of forbidden derogation partly draws on meticulous scientific analysis that encompasses axiological considerations. Thus in the absence of a determinate and efficient regulator the decision-making territory is conquered by the scientists, whose considerations shirk judicial review—even in the example country where the scope of review is otherwise broad and scientific expertise readily available. The example emphasizes the significance for the legal to properly understand the manner in which scientific knowledge of the environment is produced. When it comes to the predominant paradigm of environmental studies, adaptive management, what is legally speaking normative may have already been decided upon when the legal begins to examine the ‘facts‘ and ’norms’ of the matter. The thesis analyses the relevance and consequences of adaptive management’s socio-ecological aspects from the viewpoint of the regulator / the adjudicator after which the examination continues to the legal sphere, scrutinizing the requirements the scientific reality presents for the legal. The conclusion is that rational natural resources governance only begins when administrative-legal systems are considered contingent on the scientific examination: successful regulation is to be anticipated only when the legal acknowledges the socio-ecological management of complex systems as it is and understands itself as a part of the adaptive cycles, not as a separate decision-making entity.
  • Jousimo, Jussi (2018)
    Environmental and ecological processes drive interactions between organisms in space and time. Inferences from observations, that are dependent and measure the processes of interest indirectly, require an appropriate statistical approach that accounts for the processes' autocorrelation and stochasticity. While acknowledged by ecologists, the presence of spatial dependencies is often ignored. We developed a spatio-temporally explicit statistical framework and considered three case studies in spatial population ecology. In the first study, we conducted a simulation study by mimicking a large-scale and long-term survey of a sparsely populated hypothetic species. The spatio-temporal approach provided density estimates which were found to be unbiased and more precise compared to the baseline models. Furthermore, the model was able to uncover missing observations if there were nearby observations. In addition, we developed a method to estimate population densities for habitat types that were not covered in the study by utilizing individual-level GPS movements data. During winter, the Eurasian red squirrel (Sciurus vulgaris) depends on cone seeds as its main source of nutrition and it is preyed on by several predators. In the second case study, we combined data from surveys of almost 30 years of multiple species in Finland and applied the spatio-temporal framework to find the effect of adjacent trophic interactions on the population dynamics of the red squirrel. The results showed that the population fluctuations of the red squirrel appears to be mostly driven by bottom-up effects such as the cone yield. Positive association with the predator abudance likely results from a shared preference for the habitat rather than predation, but local variation may exists. Powdery mildew (Podosphaera plantaginis) is a fungal disease that infects the plant Plantago lanceolata. In the Åland island of Finland, the plantago is found in a network of meadows and occupancy of the mildew was observed by a ten-year survey. The pathogen follows metapopulation dynamics with occasional colonizations and extinctions of local populations in the host network. Ecological theory predicts that the more isolated populations of a host plant are less susceptible to an infection. On the other hand, higher rates of gene flow in more connected areas facilitate the evolution of resistance. In the last study, by applying the spatio-temporal approach, we found the spatial connectivity to correlate negatively with the occupancies and colonizations and positively with the extinctions. A laboratory experiment confirmed that the plantago is more resistant in more dense sub-networks. We hypothesize this to be a result of a higher gene flow in more dense sub-networks and/or an ability to invest in resistance more in nutritionally rich areas.
  • Hormio, Säde (Helsingin yliopisto, 2017)
    The topic of my thesis is individual and collective responsibility for collectively caused systemic harms, with climate change as the case study. Can an individual be responsible for these harms, and if so, how? Furthermore, what does it mean to say that a collective is responsible? A related question, and the second main theme, is how ignorance and knowledge affect our responsibility. My aim is to show that despite the various complexities involved, an individual can have responsibility to address climate change. I argue that climate change is not a problem just for states and international bodies, but also for individuals. There are three possible sources of moral responsibility for individuals in relation to climate change harms: direct responsibility (individuals qua individuals), shared responsibility as members (individuals qua members of collective agents), and shared responsibility as constituents (individuals qua constituents of unorganised collectives). Accounts that deny individual responsibility fail to either take our interdependent reality seriously or fail to understand marginal participation (or in the case direct responsibility, fail to appreciate the nature of the climate change phenomenon). Individuals can be complicit in climate change harms, either as members of collective agents (e.g. as citizens of states or employees of a corporation) or as constituents of unorganised collectives (e.g. as consumers or polluters). Although I focus on individual complicity, I do not deny the obligations of collective agents. However, nation-states, governments, and international bodies are not the only relevant collective agents in climate ethics: other collective agents, such as corporations, matter also and can have obligations concerning making sure that their activities are as carbon-neutral as possible. In addition, those corporations that have engaged in lobbying against climate regulation through creating and disseminating misleading information have acquired themselves additional obligations to mitigate climate change and compensate for the harm they have caused. Even so, the ethical claims can only be understood by individual members of these collective agents because only they can feel the pull of moral claims. I suggest that we could distinguish between what one must possess in order to be capable of making moral claims (i.e. moral agency conditions), and what it means to have the ability to exhibit such claims through one’s conduct. Individual direct responsibility is to not to increase the probable risk of serious harm to other people, at least as long as we can do so at a less than significant cost to ourselves. It is limited to relatively wealthy individuals. Offsetting is not a reliable way to meet this duty; we need to look at the emissions from our lifestyle choices (within the available infrastructure). Shared responsibility qua members of collective agents is the key individual responsibility, and it presses especially on those occupying key positions within key collective agents. Saying that, our shared responsibility qua constituents of unorganised collectives has the potential to be decisive in whether some action is taken or not, either through a set of actions that can signal certain acceptance or support, or as a form of political support from the grass roots.
  • Jokinen, Viljami (Viljami Jokinen, 2017)
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  • Gurkov, Aleksandr (Unigrafia, 2017)
    The dissertation is focused on the analysis of Russian regulations on arbitral awards deciding over relationships that are subject to competition law rules. This thesis investigates whether such relationships are arbitrable in Russia; in case these disputes can be resolved in arbitration, are there any additional requirements for arbitrators in such cases to secure state competition law policies; and finally, how can a public authority verify that antitrust policies were upheld in an arbitral award? To answer these questions, the research uses a doctrinal methodology, analyzing norms of Russian law. To support the study and make the answers more concrete, judicial practices of Russian courts are analyzed. The structure of this dissertation reflects the study’s set goals. After an introduction to the research, Chapter 2 provides a brief overview of some of the aspects of the Russian legal system that are relevant for the further study. Chapter 3 addresses arbitrability of disputes in question in Russia. Chapters 4, 5, and 6 deal with different aspects of public policy concept application in arbitration in Russia in the targeted group of cases. In particular, Chapter 4 focuses on the general characteristics of the public policy concept of arbitration in Russia, while Chapter 5 tackles more specifically a correlation between a prospective violation of competition law rules and public policy infringement in Russia. Finally, Chapter 6 addresses the extent of court review of arbitral awards and the possibility of such review in awards that could potentially violate Russian antitrust law provisions. Correspondingly, the study provides the following conclusions: 1) disputes involving competition law regulations are arbitrable in Russia, except for those disputes originating from public procurement contracts; 2) violation of Russian competition law can be considered as a violation of Russian public policy, if such violation evidently breaches the prohibition to engage in economic activity aimed at monopolisation and unfair competition; 3) Russian law does not allow substantive review of arbitral awards, even in cases where public policy could be at stake; at the same time, courts do not always follow this rule and sometimes take a closer look at the relations between parties and re-evaluate findings of arbitrators on matters of law.
  • Katajisto, Milla (Unigrafia, 2017)
    Chronic obstructive pulmonary disease (COPD), mainly caused by inhaling tobacco smoke, is very common an the main symptom is slowly proceeding dyspnoea, which often reduces a patient’s physical activity. Physical inactivity in COPD relates to poor prognosis and lower quality of life. Pulmonary rehabilitation (PR), based on exercising, has been proven to be an effective intervention among COPD patients. One of the aims of this study was to evaluate physical activity among Finnish COPD patients, to better understand the reasons behind activity or inactivity and their interest in exercise-based PR, in order to improve their care in the future. The patient cohort of the Chronic Airway Disease (CAD) study made it possible to study physical activity in relation to quality of life and severity of disease, among other characteristics. A questionnaire asking about exercise habits, daily activities and patient history regarding sports and rehabilitation was sent to all COPD study patients in spring 2010. The main result was that dyspnoea was more severe among the inactive patients, even when adjusted to the forced expiratory capacity in one second (FEV1). Dyspnoea was also the main subjective obstacle to exercising. The study patients had given their consent to allow the study of their registries for medication purchases. The reimbursement registry of the National social insurance office made it possible to track the study patients' COPD drug medication in the same year that their physical activity status was evaluated. Episodes of severe exacerbation and pneumonia were also of interest, in relation to medication and physical activity. The result of this investigation was that the maintenance medication did not differ significantly among active and inactive patients; however, inactive patients suffered more from severe exacerbations and needed more rescue medication, antibiotics and oral steroids. Only half of the patients reached the daily defined dose (DDD), a dose considered relevant in care. During 2010 to 2013, PR was started with special funding available for workers of the Helsinki and Uusimaa (HUS) district, to development of new type of care for patients. Patients with COPD from Helsinki university hospital, who had severe disease, were included and the majority of them had a history of hospital admissions. The primary aim of the third study of this thesis, was to evaluate the short-term and long-term results and also to evaluate the cost effectiveness. The patients performed well in the PR programme, their test results improved as expected, and the hospitalisation days during the year after PR were less than half of the number of hospitalisation days during the year before.The secondary aim was to gather information, which so far had been lacking, about the occurrence of serious exacerbations in the Helsinki; in this district. Data for every hospital admission with the COPD ICD-code year 2014 were collected from eMr and the patient’s COPD diagnosis and the cause of hospital stay was evaluated. The data showed that there were 437 patients with severe exacerbations; 3 out of 4 of whom were treated in city hospitals and none of them was offered PR. The rate of readmissions due to exacerbations was 50% and total mortality during the year was 41%.Understanding of the importance of physical activity or exercise-based PR in treatment for COPD is not sufficient in health care. Access to PR should be made possible for all patients in need, inparticular for patients with severe COPD exacerbations.
  • Hasygar, Kiran (Painosalama Oy, 2017)
    The ability to dynamically adapt to fluctuating nutrient availability determines the survival of living organisms. While the capacity to grow rapidly and build energy stores on a nutritious diet can provide a selective advantage, being able to endure nutrient scarcity is also key to survival. Insulin/Insulin-like Signaling (IIS) is a conserved anabolic pathway which drives growth and energy storage during nutrient abundance. However, the IIS needs to be suppressed during starvation to readjust growth and energy homeostasis. The molecular factors which regulate the IIS to determine the optimal balance between anabolism and catabolism, aiding the survival of animals in a wide range of nutrient conditions remain poorly characterized. Using Drosophila melanogaster as a model organism, we aimed to identify novel nutrient responsive signaling pathways that coordinate animal growth and metabolic homeostasis. Conservation of the IIS pathway, availability of extensive genetic toolkit, and little genetic redundancy make Drosophila an attractive model to study growth and energy metabolism. Insulin secretion is dynamically regulated by nutrition in flies, and multiple nutrient sensing pathways converge on the Insulin Producing Cells (IPCs) to modulate Insulin secretion according to the nutrient status. Hence, we aimed to perform a tissue specific RNAi screen in the IPCs to identify novel regulators of the IIS in vivo. In this thesis, we discover a novel role for a ribosome surveillance pathway in starvation response. We show that suppression of ribosome biogenesis in the IPCs leads to activation of a ribosome surveillance response, resulting in inhibition of Insulin secretion and animal growth. Also, we identify tumor suppressor p53 and an atypical MAP kinase ERK7 as essential components of this pathway. We demonstrate that ERK7 is expressed in the IPCs upon starvation, and its expression is sufficient and essential to inhibit Insulin secretion and growth. Moreover, inhibition of p53 or ERK7 in the IPCs results in a blunted starvation response, highlighting the importance of this cell intrinsic pathway. Further, we establish that another component of the secretory pathway, the Exocyst complex is essential for Insulin secretion in flies. In addition to its function in the IPCs, we show that ERK7 expression is elevated upon starvation in fat body, the fly counterpart of liver and adipose tissue, to regulate growth and metabolism. While ERK7 in the fat body limits animal growth through inhibiting the expression of an insulinotropic peptide, Stunted, it inhibits de novo lipogenesis and triacylglycerol (TAG) storage by suppressing the expression of a transcription factor, Sugarbabe. Also, we have generated ERK7 mutant flies, which display accelerated growth rate and store more TAG on a nutrient rich diet, consistent with ERK7 being an inhibitor of growth and lipid synthesis. However, ERK7 mutants fail to limit their growth, and sufficiently mobilize lipid stores during nutrient scarcity, and consequently survive poorly upon starvation. Further, we show that ERK7 regulates a majority of the starvation-induced gene expression on a genome wide scale, thus establishing ERK7 as a major determinant of systemic starvation response. Thus, we demonstrate that ERK7 is a starvation induced molecular factor regulating growth and metabolic homeostasis. Through inhibiting anabolic processes such as the Insulin signaling and lipid synthesis, and activating catabolic processes such as lipid breakdown, ERK7 facilitates survival of animals upon starvation.
  • Pipatti, Otto (2017)
    This study offers an overall interpretation of the sociologist and anthropologist Edward Westermarck’s (1862–1939) moral and social theory. It focuses on the key elements of Westermarck’s theory of moral emotions as presented in The Origin and Development of the Moral Ideas (1906-08) and summarized in Ethical Relativity (1932), and examines the importance of his work for understanding and explaining a wide range of social and moral phenomena that may be observed in all social environments. The study has two main aims. First, it lays out the key features of Westermarck’s theory of moral judgement, the nature of retributive emotions in which moral judgements are based, and the various psychological and social elements influencing them. At the same time, it shows that Westermarck’s account of morality is an ambitious and wide-ranging analysis of the fundamentals of human social behaviour and social reality. By combining the moral-psychological and sociological aspects of Westermarck’s work, the study reconstructs his understanding of emotions, and the different forms of emotional contagion in particular, as the fundamental elements of human sociality. What emerges is that at the heart of Westermarck’s theory-building is his neglected account of sympathy, proving to be crucial to his understanding of morality and human social life. The second aim of this study is to examine Westermarck’s thought in the context of his main sources of inspiration, enabling a better understanding of his work. In this regard, it highlights the importance of Darwinian evolutionism to the different aspects of Westermarck’s project, especially to his approach to the human mind. In addition, the study demonstrates how Westermarck’s theory of moral emotions developed out of, and in response to, David Hume’s and Adam Smith’s moral philosophy, combining their views on human nature, moral sentiments, and sympathy with Darwinian evolutionary thinking. The first part of this work focuses on the central elements in Westermarck’s moral and social theory, especially with respect to the nature of moral emotions, the role of sympathy and society, reciprocity, the emergence and maintenance of moral norms, and moral responsibility. The remaining part of the study expands upon and deepens these discussions by looking at Westermarck’s theory of moral emotions in relation to the sentimentalist tradition in British moral philosophy, whose importance Westermarck himself emphasised as the background for his thinking. Today, his legacy serves as an example of sociological theory-building that is not organized around the dualisms of nature/culture and animal/human which penetrate much of the social sciences. The study demonstrates Westermarck’s sociological relevance and broadens the view of Westermarck as the forerunner of modern evolutionary approaches to morality.