E-thesis - dissertations and theses

Recent Submissions

  • Mauranen, Aleksanteri (Helsingin yliopisto, 2019)
    Tässä maisterintutkielmassa tutkin romanialaisen taloustieteilijän Nicholas Georgescu-Roegenin (1904–1994) vaikutusta ekologisen taloustieteen koulukunnan muodostumiseen. Laadullisen sisällönanalyysin keinoin tutkin Georgescu-Roegenin avainajatuksia kahdeksan tekstin (artikkeleita, luentoja ja postuumisti julkaistu käsikirjoitus vuosilta 1970–1989) valossa ja vertaan niitä ekologisen taloustieteen ominaispiirteisiin. Teen myös katsauksen Georgescu-Roegenia käsittelevään kirjallisuuteen ekologisen taloustieteen kentällä. Näin saan kaksi näkökulmaa hänen intellektuaaliseen vaikutukseensa. Kirjallisuuskatsauksen perusteella arvioin myös Georgescu-Roegenin sosiaalista vaikutusta ekologisen taloustieteen syntyvaiheilla. Kaiken kaikkiaan selvitän Georgescu-Roegenin avainajatuksia ekologisen taloustieteen kannalta ja hänen roolejaan koulukunnan varhaisessa kehityksessä. Georgescu-Roegenin keskeiset ajatukset jäsentyvät työssäni 24 teeman alle, jotka vuorostaan muodostavat viisi kattoteemaa. Ensimmäinen kattoteema, entropia ja luonnontieteet, kuvaa Georgescu-Roegenin ajattelun läpäisevää biofyysistä maailmankuvaa, jota ilman hänen johtopäätöksiään ei voi syvällisesti ymmärtää. Toinen kattoteema, ihmiskunnan historia ja tulevaisuus, kattaa hänen käsityksensä ihmisestä ja ihmiskunnasta sekä erityisesti siitä auttamattoman kestämättömästä tilanteesta, johon entropian laki hänen mukaansa ihmiskunnan sitoo. Kolmas kattoteema, varsinainen taloustiede, käsittelee Georgescu-Roegenin käsityksiä taloustieteen filosofisesta perustasta, sen teoreettisista ja käsitteellisistä ongelmista sekä eräitä teknisempiä ja matemaattisempia erityiskysymyksiä. Neljäs ja viides kattoteema muodostuvat pääasiassa jo aiemmissa kattoteemoissa esiin tuoduista ajatuksista uudelleen järjesteltyinä: kritiikki kokoaa Georgescu-Roegenin kritiikkiä erityisesti muita tutkimussuuntauksia kohtaan sen kohteen mukaan järjestettynä, ja ratkaisut puolestaan esittelee hänen ratkaisuehdotuksiaan niin taloustieteen kuin koko ihmiskunnankin tasolla. Ekologisen taloustieteen kannalta Georgescu-Roegenin keskeisimmät ajatukset koskevat erityisesti ensimmäistä ja kolmatta kattoteemaa. Aineen, energian ja entropian lain suuri merkitys taloudellisessa prosessissa sekä Georgescu-Roegenin uudelta taloustieteeltä edellyttämät eettinen normatiivisuus ja poikkitieteellisyys ovat ekologisen taloustieteen peruspilareita. Ekologinen taloustiede vastaa monilta osin niihin kritiikkeihin, joita Georgescu-Roegen oman aikansa taloustieteen suuntauksiin kohdisti. Hänen sosiaalis-intellektuaalinen merkityksensä voidaan tiivistää viiteen rooliin: varhainen tiennäyttäjä ja kriitikko; varhainen kokoaja ja teoreetikko; vaikuttava, mutta hankala mentori; kuuseen kurkottava erakko ja kiistelty klassikko. Mahdollisia jatkokysymyksiä samalta suunnalta voisivat olla esimerkiksi Georgescu-Roegenin pääteoksen, The Entropy Law and the Economic Processin (1971), klassikkoaseman tarkastelu tai samantyyppinen vaikutusanalyysi muista ekologisen taloustieteen varhaisista uranuurtajista. Myös ekologisen taloustieteen käytännön tutkimustodellisuuden suhde sen ääneenlausuttuihin periaatteisiin ansaitsisi lähempää tarkastelua. Entropian lakia olisi kiinnostavaa tutkia taloustieteen näkökulmasta joko analysoimalla aiheesta käytyä runsasta keskustelua tai pureutumalla entropian käsitteen antroposentrisyyden ja objektiivisuuden väliseen jännitteeseen.
  • Särkkä, Iro (Helsingin yliopisto, 2019)
    The objective of this study is to analyse NATO as portrayed in Finland’s foreign and security policy, by focusing on the study of policy discourses and rhetoric. The main research question is the following: how have conceptions of NATO changed in the Finnish foreign and security policy debate during the post-Cold War period? As a theoretical framework of the study, a constructivist approach to foreign policy analysis was applied, with the aim of accounting for the significance of political language, policy discourses and rhetoric in defining the Finnish security policy. Within this paradigmatic approach, my aim was to identify and explain for the long-term discursive changes in the Finnish foreign and security policy as well as the policy positions of the key foreign and security policy actors. Empirical and inductive qualitative content analysis (QCA) was applied as methodological approach in analysing the three primary research sources: 1) NATO’s official summit declarations (1990–2016), 2) Finnish foreign, security and defence policy reports (1995–2017) and 3) the corresponding speeches held by the members of the parliament addressing NATO (N=915 speeches addressing NATO). Within the constructivist approach of foreign policy analysis, dominant discourses play an important role in defining the foreign and security policy outcomes. Foreign policy discourses are used as means to legitimize foreign policy action and goal formation; however, they also direct foreign policy debates in domestic policy forums. In this study, my aim was to analyse, the extent to which government led foreign policy transmits to the corresponding foreign policy in the national parliament. I studied the speeches held by members of the Finnish Parliament in the corresponding timeframe in relation to four attributes: 1) the content of the speech and the policy discourses, 2) the rhetorical means employed by the speaker (Aristotles’s ethos, pathos and logos), 3) the formal roles that the speakers held (ministers, group leaders, members of the parliament) as well as 4) the NATO-related rhetorician types (pro-NATO, pragmatics, skeptics and anti-NATO -speakers). In addition to these four parameters, my aim was to synthetize the change in the foreign policy rhetoric of eight major political parties present at the Finnish parliament as well as the movement between the rhetorician types. This doctoral thesis has provided new, previously undiscovered empirical knowledge about the content and the use of different rhetorical means in relation to NATO in the post-Cold War Finnish foreign and security policy debate. Furthermore, it has sought to outline differences in the contextual interpretation of NATO, between the Finnish government and the parliament. Above all the study has shown, how complex foreign and security policy issue NATO is and how many different types of interpretations it may evoke in the Finnish security policy debate.
  • Akenji, Lewis (Helsingin yliopisto, 2019)
    Transitioning to sustainable living is a complex, conflicting, and highly contested issue. As part of this push, governments and businesses have focused on promoting green consumerism - framing people as primarily consumers with “a utility function” and seeking to solve the consumerism problem by paradoxically building consumer capacity to purchase more energy and material efficient products. The now-debunked assumption is that a critical mass of informed, ecologically conscious consumers can, through the market mechanism, apply pressure on producers and thus transform the economic system into a sustainable one. In this thesis I argue that this approach, which is driven by economistic thinking, is consumer scapegoatism, and is both simplistic and flawed. In light of the magnitude and urgency of the unsustainability problem, green consumerism could even be dangerous as it delays deployment of effective solutions. Consumer scapegoatism occurs when ecological imbalance is examined primarily through an economic-growth lens, and the critical role of addressing these systemic flaws is ascribed to the consumer without proper regard for whether he or she has the power to influence other more salient actors in the system. This thesis argues for the need to develop an explicit political economy approach to sustainable living research, policy and practice. Political economy asks questions about power, institutions and agency. For sustainable living, these would be questions such as: who benefits or loses from current patterns of consumption, what are the drivers and structures that propagate unsustainable consumption, where are the meaningful points of intervention that can have desired effects. Critical to finding solutions is in understanding the power dynamics around the issue. I analyse sustainable living as an issue of heterogeneous claims and conflicting interests. The means and practical implications of achieving sustainable living threaten the interests of powerful actors such as national governments, large transnational corporations, and institutions that together shape contemporary politics, policy, and markets. Such actors are also responsible for the systems of provisioning and choice architecture that largely predetermine how individuals and communities pursue and meet their needs. As heterogeneity and conflict of interests are essential to political economy, this approach is well situated as the organizing frame of the field of sustainable living. I discuss the main tensions embodied in the pursuit of sustainable living, and juxtapose these with characteristics of the political economy approach that make it a suitable research framing. Political economy characteristics include: understanding of social transition; interdisciplinarity in research design; use of a moral perspective; and praxis, or practice orientation. I emphasize the element of power as vital in the articulation of social transformation, and highlight the need for sustainable living research to undertake a systemic analysis of power. To apply this, I develop the In-Power framework for analysing power dynamics within a system. The in-power framework has four components: institutions, interests, instruments, and influence. Institutions set the conditions or “rules of the game” for how actors operate in the production-consumption system; Interests identify stakes, showing heterogeneity or homogeneity of those interests in the sustainable living issue; Instruments refer to sources of power and tools available to each stakeholder to support its objectives; and Influence refers to activities stakeholders undertake and reflects agency. I use the framework to analyse the global value chain of consumer goods with a view to understanding drivers of consumption, how power is wielded by stakeholders, and potential points of effective intervention that can enable sustainable living. Dismantling the architecture of unsustainability would invariably call for a questioning of corporate architechture, not only due to the environmental impact resulting from its mode of operation, but also its lock-in effect on institutions and other actors of society. By extension, understanding unsustainable consumption and approaching sustainable living has at its core the need to address the balance – or imbalance – in power dynamics between consumption patterns and corporate power. Using the in-power framework to analyse power flows in a value chain leads to identifying the nexus of influence and the lead actor. The nexus of influece is the concentration of stakeholders who act interdependently and who have a combined decisive influence on the final product and also on the eco-system around it. The lead actor is the main actor in the system with a critical marketing, technological, or financial edge that permits it to set the standards or specifications for other actors in the value chain, and the characteristics that determine its production and use. Thus I argue that consumer scapegoatism, assigning full responsibility to the consumer, is ineffective; a more effective approach to addressing the systemic flaws causing or caused by unsustainable consumption is to target the nexus of influence and the lead actors in order to reform the choice architecture and systems of provision upon which people depend for meeting their needs and wants. Finally, I discuss two points not addressed in this thesis but which are essential to the political economy of sustainable living. They are: the need to define parameters for a sustainable consumption space; and to move research on sustainable living out of the shadows of economics.
  • Summa, Maija (Helsingin yliopisto, 2019)
    Human noroviruses (HuNoVs) are yearly responsible for a large number of acute human gastroenteritis cases globally in all age groups. Typically, the virus transmits via the fecal-oral route from person to person, causing strong symptoms such as nausea, vomiting, and diarrhea, which usually disappear in a few days. However, HuNoVs cause also numerous food-related illnesses in developed countries, including Finland, inducing gastroenteritis outbreaks through contaminated water and foodstuffs. According to the reports of the European Commission, both in Europe and in Finland the most common foods causing HuNoV outbreaks are shellfish, berries (especially frozen raspberries), vegetables, and mixed foods, which most likely became contaminated by a sick food handler. Noroviruses belong to the Caliciviridae family and are classified into seven genogroups. HuNoVs belong to genogroups I (GI), II (GII), and IV (GIV). Other genogroups contain only animal noroviruses. Noroviruses are generally regarded as host-species-specific, but the possibility of zoonotic transmission and infections has been discussed for over a decade for several genotypes. The purpose of this study was to develop a simple and rapid method for detection of HuNoVs in food. The potential zoonotic nature of HuNoVs, particularly whether animals can serve as transmitters for these viruses, was also investigated. In the past two decades, numerous methods for detecting HuNoVs in food have been developed. However, many of these are time-consuming and the sensitivity of the methods has been highly variable. In this work, four published extraction methods for detection of HuNoV in food (lettuce, ham, and frozen berries) were compared. The method based on alkaline elution and polyethylene glycol (PEG) precipitation was found to be the most reliable detection method for all three food matrices tested. The recovery efficiency of the method with frozen raspberries was on average 28%. Two rapid methods for detection of HuNoV in frozen raspberries were also presented. The rapid method based on direct RNA extraction yielded the same recovery levels (32%) as the PEG precipitation method. The method proved to be sensitive because it detected HuNoV also with a virus level of 100 genome copies in a 25 g sample. Moreover, the method detected HuNoV in naturally contaminated berry samples that were linked to outbreaks of disease. A treatment with either a chloroform-butanol mixture or dilution of the food samples for the RT-PCR reaction was efficient in reducing the effect of PCR inhibitors. The same effect was achieved with PEG as a supplement in the food samples. Thirty-nine frozen berry samples purchased from local stores in 2010, 2014, and 2017 were screened. All berries tested negative for HuNoVs GI and GII. HuNoV genome was detected in the feces of 31 birds, two rats, and four pet dogs. The genotypes found in six bird samples and all dog samples were the same as those commonly found in human samples at the time of sampling. HuNoVs can be detected in food samples also in small numbers using the rapid method presented in this study. The use of PEG as a supplement was found to reduce inhibition of the RT-PCR reaction in the two rapid methods, and therefore, the commonly used chloroform-butanol treatment, which easily loses viruses during processing, could be omitted. The results of animal samples strongly indicate that wild birds, pet dogs, and possibly also rats may be involved in the transmission of HuNoVs to food, water, and surfaces
  • Salonen, Antti P (Helsingin yliopisto, 2019)
    The emergence and rapid evolution of the over-the-counter (OTC) derivatives market in the early 1980s revolutionized the whole landscape of finance. OTC derivatives are financial products that are transnational in their nature. These products do not follow any jurisdictional lines nor theoretical boundaries focusing on state-made law. They transcend them. The central argument of this research is that legal scholarship requires a legal theoretical approach capable of recognizing private normativity and that accepts that it is not only nation states and organizations that derive their powers from states that can produce law. Transnational method allows the observer to acknowledge the transnational elements of finance and then set them into a legal theoretical structure. This research retells the evolution of the OTC derivatives market through the application of transnational method. Instead of building a narrative emphasizing the de- and reregulation policies and politics, the research focuses on early beginnings of the largest capital market in the world, the so-called eurobond market of the 1960s. Through legal innovation, this market developed its own transnational rules. In the 1980s, this market became integrated with the rapidly growing market for swaps, a type of OTC derivative. Seeing the demand for contractual standardization,a handful of financial institutions became organized through a trade organization today known as the International Swaps and Derivatives Association, Inc. (ISDA). The main product of ISDA, the ISDA Master Agreement architecture, had become by far the most used standard agreement in the OTC derivatives market already before the 1990s. Post financial crisis of 2008, this transnational contract still holds a central position in a very different regulatory environment than that of the 1980s. Transnational method identifies the supply and demand for financial and legal innovation, and the facilitative role that nation states and international organizations can play in enhancing private normativity and the transnationalisation of law. The results that transnational method tells are first and foremost descriptive. The application of transnational method requires a functional, rather than formal, understanding of ‘law’ because this allows private normativity to be recognized and its ontology properly understood.
  • Punger, Tatjana (Helsingin yliopisto, 2017)
    Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. It arises from skeletal muscle stem cells, which fail to differentiate. Multimodal treatment approach has improved the outcome of RMS during the recent years. However, in case of relapsed or metastatic disease, the prognosis is still very poor. This indicates a high demand for novel targeted therapy approach for RMS. Prox1 transcription factor has been shown to regulate myoblast differentiation into skeletal muscle fibers. Our unpublished observations indicate that Prox1 is highly expressed in RMS tumors and that it is essential for RMS cell growth. The aim of this study was to find novel drug candidates for RMS treatment depending on Prox1 and/or its downstream signaling. High-throughput drug screening with 528 oncology compounds was tested on wild-type and Prox1 silenced rhabdomyosarcoma cells (RD cell line). Gene silencing was performed via lentiviral vectors encoding shRNA for Prox1. In the screening results, we focused on the drugs, which were more potent in Prox1 silenced cells with nano- or micromolar concentrations compared to the wild-type cells. The results revealed 7 potential groups of inhibitors, which had superior suppressive effect on RMS cell viability specifically when Prox1 was silenced. In vitro validation of high-throughput screening results by MTT and luciferase assays confirmed the results. Based on the magnitude of their inhibitory effect and information available on these compounds, three drugs were chosen for further investigation. Two of these compounds also potently inhibited the growth of patient-derived primary RMS cells, which we obtained from the Helsinki University Hospital and named KLHEL1. These drugs were also less toxic to healthy myoblasts. In addition, these two compounds significantly decreased Prox1 mRNA and protein levels in wild-type cells, and completely inhibited the ability of both RD and KLHEL1 cells to form colonies. Combinational exposure to these inhibitors further enhanced the effect compared to a single agent treatment. The present findings demonstrate a potential for repurposing of these drugs for targeted treatment in rhabdomyosarcoma expressing high Prox1 levels.
  • Hlushchenko, Iryna (Helsingin yliopisto, 2019)
    This thesis explores the role of several actin-binding proteins in the regulation of brain physiology with a focus on dendritic spines. Dendritic spines are considered the plausible physical substrate for learning and memory, as their morphology allows for modulating incoming signals. Disruptions in spine density and morphology are also often associated with neuropsychiatric disorders. The two cellular processes representing neuronal learning are long-term potentiation (LTP) and long-term depression (LTD). Here, I show that the actin-severing protein gelsolin transiently relocates to dendritic spines upon LTD induction, but not LTP induction or spontaneous neuronal activity. It is plausible that the modest – but relatively long-lasting – LTD-induced elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin, thus inducing the relocalization of gelsolin to dendritic spines. Proper spine regulation is crucial for learning in live animals. MIM is an I-BAR containing membrane curving protein, shown to be involved in dendritic spine initiation and dendritic branching in Purkinje cells in the cerebellum. Behavioral analysis of MIM knock-out (KO) mice revealed defects in both learning and reverse-learning, alterations in anxiety levels and reduced dominant behavior, and confirmed the previously described deficiency in motor coordination and pre-pulse inhibition. Anatomically, we observed a decreased density of thin dendritic protrusions, enlarged brain ventricles and decreased cortical volume. Genetic studies have pointed out that genes often disturbed in neuropsychiatric disorders encode synaptic actin regulators. We selected five genes encoding different actin-regulating proteins and induced ASD-associated de novo missense mutations in these proteins. These mutations induced changes in the localization of α-actinin-4, which localized less to dendritic spines, and for SWAP-70 and SrGAP3, which localized more to dendritic spines. Among the wild-type proteins studied, only α-actinin-4 expression caused a significant change in dendritic spine morphology by increasing mushroom spine density and decreasing thin spine density. We hypothesized that mutations associated with ASD shift dendritic spine morphology from mushroom to thin spines. An M554V mutation in α-actinin-4 (ACTN4) resulted in the expected shift in dendritic spine morphology by increasing the density of thin spines. In addition, we observed a trend toward higher thin spine density with mutations in myosin IXb and SWAP-70. Myosin IIb and myosin IXb expression increased the proportion of inhibitory synapses in spines. The expression of mutated myosin IIb (Y265C), SrGAP3 (E469K), and SWAP-70 (L544F) induced variable changes in inhibitory synapses.
  • Metsäniitty, Mari (Helsingin yliopisto, 2019)
    Assessment of an individual’s age has important applications in forensics. From developing countries, the possibility to gather reliable reference data for forensic age estimation may be difficult. The aim was 1) to analyse the validity of the Greulich and Pyle method (1959), and other skeletal and dental methods; 2) to analyse forensic age assessments of asylum seekers in Finland, and the Finnish legislation; 3) to compare a created Somali dental development model (SM) on lower left permanent teeth (PT) from 31 to 37 with the Willems et al. model (WM; 2001); and 4) to study whether the addition of information on the development of third molars (TM) with PT increases the accuracy of age assessment of young Somalis. Dental and skeletal radiographic age-assessment methods were compared using Finnish child victim data (N=47). Information on forensic age assessment was collected from Finnish legislation texts, EU statistics, and public statistics by Immigration Authorities on asylum seekers in Finland. Analysis was made of forensic age assessments in Finland in 2015. The dental development of Somalis, born and living in Finland, was analysed, staging the PT according to Demirjian et al. (1973) and TM according to Köhler et al. (1994). First, both SM and WM on PT were validated on 635 Somalis, aged 4–18 years. Secondly, the age prediction performances of PT and TM development were tested separately and combined on 803 Somalis, aged 3–23 years, using a Bayesian approach. Of the compared dental and skeletal methods, development of PT showed the smallest deviation from the chronological age. In 2015, 149 asylum seekers, originating most often from Afghanistan, Iraq, and Somalia, were assessed for age using methods authorised by the Finnish legislation. Comparing the performances of the WM and SM, small but statistically significant differences in mean error were detected: -0.07 years in males and 0.16 years in females. The approach combining PT and TM predicted the age with the highest accuracy. In conclusion, dental methods, except using only TM, override skeletal methods in accuracy. The current Finnish legislation on forensic age assessment has been successfully implemented in Finland. In age assessment, the WM performs well for Somali children. The age prediction performance improves by combining the information of PT and TM, especially in 12- to 15-year-olds, when both PT and TM are still developing.
  • Adam, Magdy (Helsingin yliopisto, 2019)
    The impact of the peripherally selective α2-adrenoceptor antagonist, vatinoxan, on selected pharmacodynamic and pharmacokinetic properties of two selective α2-adrenoceptor agonists, medetomidine and dexmedetomidine, were investigated in sheep. Moreover, certain interactions between vatinoxan and atipamezole, a specific α2-adrenoceptor antagonist, were evaluated. The initial objective of this study was to identify a dose of vatinoxan that would best mitigate the undesirable cardiopulmonary changes produced by intramuscular (IM) medetomidine-ketamine in sheep. Specifically, three doses of vatinoxan (150, 300 and 600 µg/kg) or saline were combined in the same syringe with medetomidine (30 µg/kg) and ketamine (1 mg/kg) and given IM. Systemic hemodynamics, arterial blood gas tensions, clinical sedation and plasma drug concentrations were compared, both before and after reversal with IM atipamezole (150 µg/kg). The middle dose of vatinoxan (300 µg/kg), which appeared to be optimal among the other doses, was then added to medetomidine (30 µg/kg) and co-administered IM, followed by atipamezole for reversal. Last, the influence of intravenous pre-treatment with vatinoxan on dexmedetomidine-induced cardiopulmonary alterations was investigated in sevoflurane-anesthetized sheep. Following concomitant IM administration, vatinoxan dose-dependently attenuated some of medetomidine’s cardiopulmonary side effects. Vatinoxan did not significantly affect the level of sedation or the plasma concentrations of drugs when ketamine was included in the same syringe. Conversely, vatinoxan significantly increased the plasma concentrations of medetomidine, and accelerated the onset and intensified the degree of sedation when compared with the agonist alone. Moreover, recoveries after atipamezole-reversal were more complete in the presence of vatinoxan. No deleterious effects were noted between vatinoxan and atipamezole. Pre-treatment with vatinoxan prevented all dexmedetomidine-induced pulmonary alterations in sheep anesthetized with sevoflurane. In conclusion, vatinoxan alleviated or prevented the unwanted cardiopulmonary effects of (dex-) medetomidine by blocking the peripheral α2-adrenoceptors. Presumably, when co-administered IM in the same syringe, vatinoxan accelerated the absorption of medetomidine and increased its concentration in blood, which resulted in a faster and more intense sedation than when the agonist was used alone. Vatinoxan also decreased later exposure to dexmedetomidine, which appeared to improve atipamezole’s efficacy to reverse both the central and peripheral effect of the agonist.
  • Kantosalo, Anna (Helsingin yliopisto, 2019)
    Human-computer co-creativity examines creative collaboration between humans and artificially intelligent computational agents. Human-computer co-creativity researchers assume that instead of using computational systems to merely automate creative tasks, computational creativity methods can be leveraged to design computational collaborators capable of sharing creative responsibility with a human collaborator. This has potential for extending both human and computational creative capability. This thesis focuses on the case of one human and one computational collaborator. More specifically this thesis studies how children collaborate with a computational collaborator called the Poetry Machine in the linguistically creative task of writing poems. This thesis investigates three topics related to human-computer co-creativity: The design of human-computer co-creative systems, their evaluation and the modelling of human-computer co-creative processes. These topics are approached from two perspectives: an interaction design perspective and a computational creativity perspective. The interaction design perspective provides practical methods for the design and evaluation of interactive systems as well as methodological frameworks for analysing design practices in the field. The computational creativity perspective then again provides a theoretical view to the evaluation and modelling of human-computer co-creativity. The thesis itself consists of five papers. This thesis starts with an analysis of the interaction design process for computational collaborators. The design process is examined through a review of case studies, and a thorough description of the design process of the Poetry Machine system described in Paper I. The review shows that several researchers in the field have assumed a user-centered design approach, but some good design practices, including the reporting of design decisions, iterative design and early testing with users are not yet fulfilled according to the best standards. After illustrating the general design process, this thesis examines different approaches to the evaluation of human-computer co-creativity. Two case studies are conducted to evaluate the usability of and user experiences with the Poetry Machine system. The first evaluations are described in Paper II. They produced useful feedback for developing the system further. The second evaluation, described in Papers III and IV, investigates specific metrics for evaluating the co-creative writing experience in more detail. To promote the accumulation of design knowledge, special care is taken to report practical issues related to evaluating co-creative systems. These include, for example, issues related to formulating suitable evaluation tasks. Finally the thesis considers modelling human-computer co-creativity. Paper V approaches modelling from a computationally creative perspective, by extending the creativity-as-a-search paradigm into co-creative systems. The new model highlights specific issues for interaction designers to be aware of when designing new computational collaborators.
  • Wahlman, Lumi-Pyry (Helsingin yliopisto, 2019)
    Among all models of inflation, Higgs inflation stands out in its minimalistic approach. In Higgs inflation, the Standard Model Higgs boson drives the expansion of the spacetime. The properties of the Higgs boson are known from collider experiments, and the only new ingredient is a non-minimal coupling of the Higgs boson to gravity. There is no need to add any new particles, and the non-minimal coupling is the only free parameter of the model. While the predictions of Higgs inflation agree with observations at classical level, loop corrections to the Higgs self-potential and gravitational action complicate the picture. From the renormalisation group equations of the Standard Model it is known that the Higgs self-coupling decreases when the energy scale increases. Significant running at the scale of inflation can foil the flat plateau of tree-level inflation. It is also known that loop corrections to gravity will destabilise pure Higgs inflation. There is also another fundamental source of uncertainty: the gravitational degrees of freedom. In Higgs inflation, the spacetime metric is usually taken to be the only gravitational degree of freedom, but this need not be the case. In the Palatini formulation of General Relativity both the metric and the connection are independent degrees of freedom. In the case of Higgs inflation, these two approaches lead to physically inequivalent theories. This thesis focuses on the differences of Higgs inflation in metric and the Palatini formulation. First we show that the metric perturbations must be quantised, if the Higgs boson is the inflaton. Then we consider loop corrections to the Higgs self-coupling, and find that the tensor-to-scalar ratio is smaller in the Palatini formulation. We also consider dimension four correction terms in the gravitational action and find a similar effect on the tensor-to-scalar ratio. There is no clear theoretical indication of how to choose the gravitational degrees of freedom. Hence it is important to be able to differentiate between different choices by observations. We find that the metric and Palatini formulation of General Relativity have distinct cosmological signatures, which can be tested with next generation experiments. If a non-zero tensor-to-scalar ratio is detected, we can rule out Higgs inflation in the Palatini formulation.
  • Kanerva, Meeri (Helsingin yliopisto, 2019)
    Breast cancer is the most common cancer among women world wide and it´s incidence is constantly growing. The prognosis of local breast cancer is good and patients with metastatic breast cancer are living longer with their disease. The growing survivorship and population of chronically ill breast cancer patients has made quality of life one of the most important aspects in the treatment of breast cancer. Cytotoxic chemotherapy is a widely used treatment for breast cancer. Chemotherapy can cause difficult adverse events, which can affect the patients’ quality of life. Chemotherapy can also relieve the symptoms caused by cancer when used to treat metastatic breast cancer. The aim of this systematic review was to collect the currently available literature about breast cancer patients´ health related quality of life as comprehensively as possible, review the quality of the literature and the effects of chemotherapy on breast cancer patients ‘quality of life. The literature search produced 1666 references. According to the inclusion and exclusion criteria, 107 full text articles were accepted to the final systematic review, 53 of which reported the health related quality of life during adjuvant treatment of breast cancer, and 51 of which reported it during the treatment of advanced or metastatic breast cancer. In addition 3 previous systematic reviews were found. The basic information about the articles was extracted into a table. Articles were heterogeneous regarding their study settings, used quality of life instruments and reporting. Most studies used a disease specific quality of life instrument. The collected literature gave a strong indication of quality of life worsening during adjuvant chemotherapy of breast cancer. This observation was further supported by the previous systematic reviews. Most of the studies reporting the quality of life during chemotherapy for metastatic breast cancer, reported less than clinically important changes during the treatment. A few studies reported clinically important worsening or improvement in quality of life. 11 studies, which were made during or after 21: st century, which reported numerical data from quality of life, which reported predominantly quality of life and which had sample size of at least 100 patients in baseline, were accepted to further assessment of quality of the studies and closer observation. The quality of the studies was assessed with STROBE and CONSORT checklists. The quality of studies was heterogeneous as the studies fulfilled 44.8 % to 86.1 % of the scoring items. Only one randomized controlled trial reported quality of life as their primary end point. The data from these studies supported the previous observation of quality of life worsening during adjuvant chemotherapy of breast cancer. The effect of chemotherapy during metastatic breast cancer on quality of life was not unambiguous. Both clinically meaningful worsening and improvement of quality of life was reported. Breast cancer patients´ health related quality of life has been assessed in multiple publications, but the existing literature is heterogeneous and it´s use in decision making and economic evaluation is not easily feasible. Breast cancer patients´ health related quality of life worsened during adjuvant chemotherapy. Significant improvement in breast cancer patients´ health related quality of life was not observed during chemotherapy for metastatic breast cancer.
  • Karasti, Eveliina (Helsingin yliopisto, 2019)
    The amount of informal caregiving has increased in Finland, with a growing emphasis on the older adults. Although the medication management process in informal caregiving has been studied and is known to have significant risks, research data focusing on the older adults is still limited. The aim of this study was to describe the medication management process of informal carers and care recipients of at least 65 years old. The aim was to identify medication errors and medication risks in the medication management process and to find out how the caregivers manage them. In addition, the study examined the informal carers and care recipients own development proposals to improve medication management process. A total of 21 volunteer informal carers and care recipients living in the Helsinki metropolitan area were recruited to this study. The study was conducted as a qualitative interview survey in the homes of the participants. The interviews were a combination of semi-structured interviews and narrative approach. The material to this study was collected during spring and summer 2018. The study was analysed with abductive content analysis combining both deductive and inductive approach. The aim was to find repetitive elements by encoding and grouping expressions. The results of this study were compared with previous theory and the results were supplemented with a picture of the medication management process and a fishbone diagram was drawn from the risk factors and contributing factors of the medication management process. The families had medication errors in all stages of the medication management process. The most frequent medication errors were found in counselling, medication administration and in medication treatment monitoring. As a contributing factor, the healthcare professionals’ haste and the responsibility of the caregiver recurred in the background of the medication errors. Family caregivers and care recipients wish to have more counselling, more monitoring of medication and better interaction with health care. Carers often felt left alone to take care of another person's medications and felt they lack support from healthcare. By facilitating access to a physician, improving the availability of a physician, increasing the amount of counseling and support provided by healthcare, including pharmacies, could the safety of medication management at home be improved.
  • Äijö, Nelli (Helsingin yliopisto, 2019)
    As the population becomes older and the amount of multimorbid patients increases, also health care spending increases. New care models are needed where patients’ needs are taken into consideration by providing preventive and patient-centred care. In Finland and internationally, new ways to treat elderly, chronically ill patients have been developed. One of the new models is the health and care plan model. This longitudinal, randomised, controlled trial studied the health and care plan model’s impact on healthcare costs, patients’ physical functioning and patients’ quality of life. The aim of the study was to study the cost-effectiveness of the health and care plan model compared to standard care practice. The goal of this study was to study if rational pharmacotherapy and self-management support can prevent the decline in physical functioning, the decline in quality of life and the increase in health service use and costs among elderly population. This study was conducted between 2014-2018 as a multi-disciplinary cooperation between Tornio health station, University of Helsinki Faculty of Pharmacy and Alatornio pharmacy. The patients in this study were over 75-year old, multimorbid, community dwelling, polypharmacy patients. The patients in the intervention group received an interview based clinical medication review and were formed a medication plan. Furthermore, the patients in the intervention group were planned a health and care plan that was combined with the medication plan into a comprehensive self-management plan in a multi-disciplinary meeting. A case manager was appointed for the patients in the intervention group and the case manager could be contacted by the patients in the intervention group at any point of the study if there arose a non-acute concern with the patient’s health. The patients in the control group were conducted a prescription review based on the information available in the electronic health records system and continued receiving the standard care practice. Cost and effectiveness data were gathered from the patients over the period of two years. The effectiveness data were gathered at Tornio health station where the intervention and control group’s quality of life was measured with the SF-36 generic quality of life measure and physical functioning was measured with Short Physical Performance Battery (SPPB). The quality of life data gathered with SF-36 were transformed into one preference based single index score SF-6D to calculate the quality of life and quality adjusted life years (QALY). Data about the use of health services were extracted from the electronic health records system and transformed into costs by using the national reference costs. At the beginning of the study, the intervention and control group were statistically significantly similar. During the two-year follow-up, no statistically or clinically significant differences were observed between the intervention and control group in their quality of life, in their physical functioning or in the costs of used health services. However, in the intervention group, the cost of used health services was on average 2 406 euros smaller than those of the control group’s during the two-year follow-up. The health and care plan model was cost-effective compared to standard care practice. The incremental cost-effectiveness ratio was -64 504 € per one QALY. Based on this study, it is recommended to support the self-management and physical functioning of the elderly with an intervention like health and care plan model to decrease the health care spending. The results of this study can be applied to Finnish healthcare system to decrease the health care spending of multimorbid, community dwelling and polypharmacy elderly patients. The use of real-world evidence increases the reliability of this study.
  • Vainio, Sanna (Helsingin yliopisto, 2019)
    Despite the long history of skin grafting, there is no standardized treatment for split-thickness skin graft donor sites. These sites cause a notable amount of pain and discomfort to the patients and open wounds also introduce a risk for infection. There is an extensive need for treatment options promoting the fastest and least painful healing possible while also being infection-free. The treatment of split-thickness skin graft donor sites is constantly studied and there is plenty of scientific literature available about this topic. In the theory section of this Master’s thesis, the structure of skin, the process of wound healing, skin grafting surgery and wound care products for split-thickness skin graft donor sites are briefly introduced. Additionally, the method of systematic review is described. In the empirical section, a systematic review is performed to compare animal- and non-animal-based wound care products in the treatment of split skin graft donor sites. The methodological quality of the included studies is reviewed. In the literature search, 3552 references were found. In this systematic review a total of 23 articles were included comprising of 21 comparative clinical studies and two previous literature reviews. Of the original studies, 20 reviewed healing, 14 infection and 17 pain of the split-thickness skin graft donor sites. Based on the results of the systematic review, animal-based wound care products might promote healing and reduce pain experienced by patients in the treatment of split-thickness skin graft donor sites when compared with non-animal-based wound care products. The results concerning infection were inconsistent. Generally, the reporting of the clinical original studies was not comprehensive enough for proper evaluation of methodological quality. Some defects, mostly in the blinding of the patients, study personnel and the assessors of outcomes, were also found. Moreover, the studies were heterogeneous in their definitions and measuring of the reported outcomes. Therefore, there is substantial uncertainty in the results of this systematic review. The systematic and transparent way of conducting the literature search, the review of the methodological quality and the reporting of the outcomes can be considered as a strength of this thesis. The main weakness is, that only one person performed the critical steps of this study, which might increase the risk of bias and reduce the repeatability of the study.
  • Aalto, Aura (Helsingin yliopisto, 2019)
    Lääkevalmisteiden, lääkinnällisten laitteiden ja sekä lääke- että laiteosan sisältävien yhdistelmätuotteiden tulee täyttää niiden tehoa, turvallisuutta ja laatua koskevat viranomaisvaatimukset ennen markkinoille tuloa. Lääkkeiden ja lääkinnällisten laitteiden rekisteröinnissä dokumentaatiovaatimukset, hakemusprosessit ja viranomaiskäsittelyt eroavat kuitenkin toisistaan. Yhdistelmätuotteet rekisteröidään Euroopan unionissa joko lääkkeinä tai laitteina niiden pääasiallisen vaikutusmekanismin mukaan. Laitteiden rekisteröintivaatimukset ovat parhaillaan muuttumassa, sillä uusi lääkinnällisiä laitteita koskeva EU-asetus 2017/745 (medical device regulation, MDR) astui voimaan toukokuussa 2017. Asetuksen käyttöönoton siirtymäkausi jatkuu toukokuulle 2020 asti. Tutkimus on jatkoa aiemmin toteutetulle tutkimukselle (Nuolimo 2016), jossa selvitettiin lääkkeiden ja lääkinnällisten laitteiden rekisteröintiprosessien eroja. Aiemman tutkimuksen johtopäätöksenä oli, että rekisteröintiprosessien erot vaikuttaisivat suosivan valmisteen rekisteröintiä CE-merkityksi terveydenhuollon laitteeksi sellaisissa rajatapaustilanteissa, joissa rekisteröinti sekä lääkevalmisteeksi että lääkinnälliseksi laitteeksi on mahdollista. Nyt tehdyn teemahaastattelututkimuksen tavoitteena oli edelleen selvittää rekisteröintiprosessien eroja ja erityisesti tuotteen rekisteröintistatuksen valintaan vaikuttavia taustatekijöitä. Tutkimuksen tavoitteina oli myös selvittää, miten yhdistelmätuotteiden rekisteröintiprosessi eroaa muista rekisteröintiprosesseista ja miten uusi lääkinnällisiä laitteita koskeva EU-asetus 2017/745 vaikuttaa käytännön rekisteröintityöhön. Teemahaastattelututkimuksessa haastateltiin kunkin tuoteryhmän rekisteröinnin asiantuntijoita. Tutkimukseen osallistui yhteensä kahdeksan haastateltavaa. Rekisteröinnin asiantuntijoiden työtoimenkuvat vaihtelivat niin paljon, että rekisteröintiprosessien vertailu oli vaikeaa. Tutkimuksessa todettiin, että laitteiden rekisteröintiprosessi on kevyempi kuin lääkkeiden. Rekisteröintistatus valitaan tuotekohtaisesti. Yhdistelmätuotteiden rekisteröintiprosessin raskaus riippuu siitä, onko tuote rekisteröity lääkkeeksi vai laitteeksi. Yhdistelmätuotteiden kohdalla rajanvetotilanteet, joissa täytyy määritellä, rekisteröidäänkö tuote lääkkeeksi vai laitteeksi, voivat olla haastavia. Uuden laiteasetuksen implementointi oli tutkimusajankohtana vielä kesken, mutta asetus oli jo lisännyt työtä laite- ja yhdistelmätuotteiden rekisteröinnissä ja tuonut uusia liiketoimintamahdollisuuksia CRO-yrityksille.
  • Häggman, Verner (Helsingin yliopisto, 2019)
    If pharmaceutical quality system fails it causes a hazard to the patient’s health, but also to the manufacturer’s economy. For this reason, the manufacturer’s must make sure their products comply with the quality requirements placed by authorities. To ensure the compliance, the authorities perform inspections at the manufacturing sites. If the site does not comply with the quality requirements, the authority will take necessary measures. The goal of this study was to find what type of quality issues FDA and the authorities within EU have observed while inspecting manufacturing facilities, which of these issues are most common, in which countries the sites companies with issues have been located. The results were assessed from European pharmaceutical company’s point of view. The data for the study was collected from Eudra GMDP database and from FDA Warning letters sent by FDA headquarters from years 2015-2017. Qualitative analysis of content was chosen as the method of analysis. The collected data was classified into main classes and subclasses based on reoccurring topics. The classes were transferred in tables to compare how which of the classes were most common. Most often the facilities with quality issues were located in China and India. The authorities also perform a lot of quality inspections in these countries, but that alone doesn’t explain the large number of quality issues in these countries. The number of sites with quality issues per inspection was also high. Both the authorities of EU countries and FDA had mainly observed similar issues. Often quality issues were related to data integrity. Other common themes were quality management system, cleaning of equipment and facilities and analytical methods. There were also some differences in the observed issues. E.g. FDA had rarely observed issues related to personnel while EU authorities had observed such issues frequently. Quality issues which had led to measures by authorities were often related to larger problems with the quality management or to very basic quality actions. If company doesn’t have well-functioning quality organization, the quality system is often inadequate also in other ways. By comparing their own activities with the issues observed at other companies, it is easier for a company to improve their quality and avoid major quality issuer before they occur.
  • Takala, Sanni (Helsingin yliopisto, 2019)
    Tämä lisensiaatintutkielma on kirjallisuuskatsaus Cryptosporidium parvum -alkueläimestä vasikkaripulin aiheuttajana. Viime vuosina kryptosporidioosin esiintyvyys suomalaisilla nautatiloilla on kasvanut. Vaikka kryptosporidioosi aiheuttaa taloudellisia tappioita, ei aiemmin ole tiettävästi tehty kattavaa kirjallisuuskatsausta vasikoiden kryptosporidioosista. Kryptosporidioosi on C. parvum -alkueläimen aiheuttama sairaus. Tyypillisesti kryptosporidioosiin sairastuvat 1-2 viikon ikäiset vasikat. Vasikka saa tartunnan nieltyään keskimäärin 16,6 C. parvum -ookystaa, joita tartunnan saaneet vasikat erittävät ulosteeseensa. Kryptosporidioosin oireena on 1-2 viikkoa kestävä vetinen ripuli. Vakavimmiillaan kryptosporidioosin aiheuttama ripuli voi aiheuttaa vasikan kuoleman. Kryptosporidioosi voi olla vasikoilla myös oireeton, jolloin vasikalla ei ole ripulia, mutta se erittää ookystia ympäristöönsä. Ookystien eritys laskee iän myötä. Aikuiset naudat joko eivät eritä C. parvum -ookystia lainkaan tai ne erittävät ookystia hyvin vähän. C. parvum -tartunta leviää karjasta toiseen joko nautojen, muiden kotieläinten, villieläinten, vesistöjen tai ihmisten välityksellä. Ookystat säilyvät ympäristössä pitkään tartuntakykyisinä monenlaisissa olosuhteissa. Ympäristöolosuhteista ainoastaan korkeiden lämpötilojen, kuivumisen sekä UV-säteilyn on todettu tehokkaasti tuhoavan ookystia. Useat desinfektioaineet eivät tehoa C. parvum -ookystiin. Desinfioinnissa käytettävä sammutettu kalkki heikentää ookystien elinvoimaisuutta, myöhentää kliinisen kryptosporidioosin alkamisajankohtaa ja parantaa vasikoiden kuntoluokkaa. Kryptosporidioosiin tehoavaa lääkettä ei ole saatavilla useista tutkimuksista huolimatta. Kryptosporidioosin hoidossa keskeisintä on riittävä ja asianmukainen nesteytys. Kryptosporidioosin ehkäiseminen perustuu sairastuneiden yksilöiden hoitoon, hyvään hygieniaan sekä halofuginaatti-lääkitykseen. Halofuginaatti on lääke, jota käytetään kryptosporidioositiloilla kliinisen kryptosporidioosin ennaltaehkäisyyn. Myös riittävä ja oikea-aikainen ternimaidon saanti lieventää ripulioireita sekä vähentää eritettyjen ookystien määrää. Tämän kirjallisuuskatsauksen tarkoituksena on toimia tietolähteenä vasikoiden kryptosporidioosista. Katsaus käsittää C. parvumin elämänkierron, tartuntalähteet, diagnostiikan, hoidon sekä kryptosporidioosin ehkäisemisen. Kappaleet sisältävät tiivistettynä tämänhetkisen tutkimustiedon. Lisätietoa aihealueista voi etsiä kattavan lähdeluettelon avulla. Kirjallisuuskatsaus tuo esiin myös tarpeen kotimaiselle tutkimukselle vasikoiden kryptosporidioosista, sillä suomalaisia tutkimuksia aiheesta ei ole.
  • Räsänen, Pinja (Helsingin yliopisto, 2019)
    Ongelmakäyttäytyminen on eläimen käyttäytymistä, joka on haitallista eläimen omistajalle tai eläimelle itselleen. Ongelmakäyttäytyminen voidaan jakaa eläimelle normaaliin ja epänormaaliin käyttäytymiseen. Suurin osa kissojen ongelmalliseksi koetusta käyttäytymisestä on kissalle täysin luonnollista ja normaalia, mutta sen toteuttamistapa tai -ympäristö on omistajan mielestä sopimaton. Esimerkiksi kohteiden raapiminen on kissalle luontainen tapa, mutta monet omistajat pitävät sitä ongelmallisena. Kissat ovatkin usein hyvin väärinymmärrettyjä, kun ne toteuttavat luonnollisia tapojaan sisätiloissa. Kissan lajityypillisen käyttäytymisen ymmärtäminen auttaa ongelmakäyttäytymisen ehkäisemisessä ja hoidossa. Kissojen käyttäytymisongelmat ovat hyvin yleisiä ja niihin osataan harvoin puuttua. Kissan kouluttamisen sekä käyttäytymiseen liittyvien ongelmien ratkaisemisen ajatellaan olevan niin vaikeaa, etteivät omistajat usein koe sitä käytännössä mahdollisena. Käytösongelmien ratkaisemiseksi löytyy kuitenkin paljon erilaisia neuvoja, vaikka tieteellinen tutkimus niiden taustalla on monin paikoin vähäistä. Tässä kirjallisuuskatsauksessa käydään läpi kissojen yleisimpiä käyttäytymiseen liittyviä ongelmia, avataan niihin johtavia syitä ja annetaan ongelmiin hoitokeinoja. Kissojen yleisimmät käyttäytymisongelmat ovat aggressio ja tarpeiden tekeminen vääriin paikkoihin. Muita kissan käyttäytymiseen liittyviä ongelmia ovat muun muassa merkkailu, liiallinen ääntely ja pakko-oireinen käyttäytyminen. Ongelmakäyttäytymistä esiintyy enemmän puhdasrotuisilla kissoilla kuin kotikissoilla sekä kastroimattomilla ja steriloimattomilla kissoilla enemmän kuin leikatuilla kissoilla. Lisäksi ongelmakäyttäytyminen on yleisempää sisäkissoilla kuin vapaasti ulkoilevilla kissoilla. Sisäkissojen on havaittu olevan turhautuneempia ja nukkuvan enemmän kuin ulkoilevien kissojen. Liiallinen nukkuminen voi joissakin tapauksissa viitata masennukseen. On erittäin tärkeää selvittää, mitä kissan ongelmakäyttäytymisen taustalla on. Näin voidaan hoitaa syy käyttäytymisongelman taustalla ja päästään puuttumaan mahdollisesti vakaviinkin sairauksiin. Ongelmakäyttäytyminen voi lisäksi johtaa stressiin perheen sisällä, kissan sopimattomaan rankaisemiseen, kissan ja omistajan välisen suhteen heikkenemiseen, kissasta luopumiseen tai jopa kissan lopettamiseen. Stressi on yksi suurimmista syistä kissan ongelmakäyttäytymisen taustalla. Kontrollimahdollisuuksien puute, ympäristön ennakoimattomuus ja kissan ja omistajan välinen huono suhde ovat yleisiä syitä kissan stressiin. Lisäksi virikkeetön ympäristö voi aiheuttaa kissalle stressiä. Kissan stressin hoidossa ensiarvoisen tärkeää on stressitekijän poistaminen. Riittämätön henkinen stimulaatio ja liikunnan puute ovat myös usein kissan käyttäytymiseen liittyvien ongelmien taustalla. Tämän vuoksi kissan elinympäristön muokkaaminen kissalle sopivaksi muun muassa virikkeellistämällä auttaa moniin käytösongelmiin. Useita kissan käyttäytymisongelmia voidaan hoitaa opettamalla kissa toimimaan tietyllä tavalla tai siedättämällä sitä pikkuhiljaa pelottaviin tilanteisiin.
  • Keskitalo, Tiina (Helsingin yliopisto, 2019)
    Medetomidiini on α2-adrenoseptoriagonisti ja sen käyttö sedatiivina on kliinisessä eläinlääketieteessä hyvin yleistä. Medetomidiinilla saadaan aikaan sedaatio, joka annoksesta ja antoreitistä riippuen vaihtelee kevyestä uneliaisuudesta syvään sedaatioon, joka mahdollista pienet noninvasiiviset toimenpiteet. Medetomidiiniä käytetään usein yhdessä muiden lääkeaineiden kanssa, sillä esimerkiksi medetomidiini ja butorfanoli potentoivat toistensa vaikutuksia. Esilääkityksenä annettu medetomidiini vähentää myös yleisanesteettien tarvetta. α2-adrenoseptoriagonistien sedatiivinen vaikutus johtuu keskushermostossa tapahtuvaan presynaptisten α2-adrenoseptoreiden aktivaatiosta, mikä vähentää noradrenaliinin erittymistä synapsirakoon ja heikentää siten hermoimpulssien kulkua. α2-adrenoseptoreita on myös keskushermoston ulkopuolella esimerkiksi verisuonten sileän lihaksen pinnalla. Näiden perifeeristen α2-adrenoseptoreiden aktivaatio lisää verisuonten supistumista. Medetomidiini aiheuttaa haittavaikutuksina sykkeen ja sydämen minuuttitilavuuden laskua, verisuonten vastuksen nousua, muutoksia verenpaineeseen sekä erityisesti märehtijöillä hapen osapaineen laskua valtimoveressä. Verenpaineen muutos on kaksivaiheinen, sillä verenkierron vastuksen nousu perifeerisestä α2-adrenoseptoriaktivaatiosta johtuen nostaa verenpaineen ensin korkeaksi. Myöhemmin verenpaine laskee johtuen medetomidiinin sympatolyyttisistä keskushermostovaikutuksista. Verenkierron vastuksen noususta johtuva verenpaineen nousu käynnistää barorefleksin, jonka seurauksena syke laskee entisestään. Medetomidiinin aiheuttama sedaatio voidaan kumota ja haittavaikutuksia lievittää α2-adrenoseptoriantagonisti atipametsolilla. Vatinoksaani on toistaiseksi vain tutkimuskäytössä oleva α2-adrenoseptoriantagonisti, joka voidaan annostella yhdessä medetomidiinin kanssa samassa ruiskussa suonen- tai lihaksensisäisesti. Se ei juuri ylitä veriaivoestettä, eikä siten vaikuta medetomidiinin keskushermostovaikutuksiin, kuten sedaatioon. Se lievittää medetomidiinin aiheuttamia perifeerisestä α2-aktivaatiosta johtuvaa verenkierron vastuksen nousua ja vähentää siten verenpaineen nousua. Tämä vähentää barorefleksin aktivoitumista ja estää sykkeen ja sydämen minuuttitilavuuden laskua. Tämän tutkimuksen tavoitteena on selvittää vatinoksaanin, atipametsolin ja medetomidiinin yhteisvaikutuksia, kun vatinoksaani annostellaan lihaksen sisäisesti yhdessä medetomidiinin kanssa. Hypoteesi on, että vatinoksaani lievittää medetomidiinin haittavaikutuksia ilman, että se heikentää rauhoitusta tai heräämistä. Tutkimukseen käytettiin kahdeksaa lammasta, joista kukin sedatoitiin sekä pelkällä medetomidiiniä (30 μg/kg) tai medetomidiini-vatinoksaaniseoksella (30 μg/kg ja 300 μg/kg vastaavasti). 30 minuutin kuluttua annosteltiin atipametsoli (150 μg/kg).120 minuutin seurantajakson aikana kardiopulmonaarisia muuttujia mitattiin tietyin aikavälein. Sedaation tasoa seurattiin subjektiivisesti asteikolla 0-10. Vatinoksaani lievitti merkittävästi medetomidiinin aiheuttamia muutoksia sykkeeseen atipametsoli-injektion jälkeen ja verenkierron vastukseen jo ennen sitä. Vatinoksaani joudutti verenpaineen nousua ja hapen osapaineen laskua 10 minuuttia medetomidiinin annostelun jälkeen. Sekä sedatoituminen että herääminen oli varmempaa ja nopeampaa vatinoksaanin läsnä ollessa. Tuloksista voi päätellä, että vatinoksaanin käyttö saattaa parantaa sedaation kardiopulmonaarista laatua ja sen käyttö lampailla on turvallista myös siinä tapauksessa, että sedaatio kumotaan atipametsolilla.

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