Väitöskirjat

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  • Hotta, Jaakko (Helsingin yliopisto, 2017)
    Complex regional pain syndrome (CRPS) causes disabling and severe limb pain that is difficult to treat. The pain typically increases during motor actions, but is present also at rest. The pathophysiology of CRPS is incompletely understood. Some of the symptoms suggest involvement of the central nervous system, and accordingly, patients have been shown to display alterations in, for instance, the primary sensorimotor cortex (SM1) and indications of neuroinflammation. More thorough pathophysiological knowledge of CRPS would help to develop better treatments and diagnostics. My thesis includes four studies exploring the cerebral basis of CRPS. All patients participating in these studies suffered from unilateral upper-limb CRPS. Studies I and II explored the complex couplings between pain, motor actions and visual information in CRPS. In healthy persons, observation and imagery of motor actions are known to elicit brain activation in similar brain areas as does action execution. CRPS patients experience pain while they execute or imagine actions and at the same time their brain activity is abnormal. However, these phenomena have not previously been studied for action observation in CRPS. In Study I, ratings of subjective experiences (e.g. pain) during observation of others’ actions were compared between 19 CRPS patients and 19 healthy control subjects. We found that CRPS patients experienced observation of motor actions as unpleasant and painful, and they overestimated the force applied in the observed actions. In Study II, the brain responses to action observation, measured with functional magnetic resonance imaging (fMRI), were compared between 13 CRPS patients and 13 healthy control subjects using multivariate pattern analysis (MVPA). During painful action-observation, the patients displayed abnormal activity in, for example, the representation area of the painful limb in the SM1 as well as in other brain areas important for pain experience and motor actions. With MVPA, these abnormal activations reliably discriminated CRPS patients from healthy subjects, indicating potential of fMRI responses as biomarkers for CRPS. Together Studies I and II build the grounds for future studies on using action observation as an add-on treatment for CRPS. Study III elucidated alterations of brain functioning during spontaneous pain in CRPS. Comparison of resting-state fMRI between 12 CRPS patients and 17 healthy control subjects showed disrupted functional connectivity of the SM1 in CRPS, especially for the representation areas of the painful and contralateral non-painful limb. These results suggest that pain alters SM1 functions even during rest, disrupting normal brain processes that could e.g. support motor learning. In Study IV, volumes of brain structures, measured with magnetic resonance imaging, were compared between 12 CRPS patients, 8 non-CRPS pain patients and 12 healthy control subjects. In the CRPS patients, the right-ventricle choroid plexus was about one-fifth larger than in healthy subjects and about one-eight larger than in non-CRPS patients. Choroid plexus is important in e.g. neuroinflammation and this finding may open new lines in research for the pathogenesis and treatment of CRPS. In conclusion, these studies revealed novel brain-derived symptoms and signs of CRPS. Brain changes involved especially areas that have already previously been studied in CRPS (e.g. the representation areas of the painful and contralateral non-painful limb in the SM1) but also other areas, such as choroid plexus. The findings further corroborate central nervous system involvement in CRPS.
  • Regina, Sirpa (Helsingin yliopisto, 2017)
    The objective of this doctoral dissertation is to present views, experiences and practices mainly related to the working-age insomniac, insomnia, and the treatment of it, as expressed by pharmacists working in Finnish community pharmacies. The specific aim is to investigate whether pharmacists see the pharmacy as having an important role in the initial stages of treating those who experience insomnia and are seeking to cure it. With regard to the self-treatment of insomnia, the study examines the kind of non-pharmacological advice offered by pharmacists when recommending self-care products and whether or not any underlying causes are being discussed with the customer. A further aim is to investigate what kind of pharmaceutical advice pharmacists provide on hypnotics and the kind of practices they employ in dispensing medicine to individual customers. Pharmacists’ views on working-age people who use hypnotics are also explored. The study was conducted as a qualitative cross-sectional study. The participants were pharmacists working at community pharmacies in mainland Finland (n = 188–277). The data was collected from five online surveys carried out in the spring of 2013. The participants were contacted using the mailing lists of the Finnish Pharmacists’ Association’s member organisations. The surveys could be accessed via a link sent by e-mail. The key questions were open-ended so as to obtain in-depth information on the pharmacists’ views, experiences and practices related to the research topic. The data was analysed mainly by using thematic analysis and both deductive and inductive content analysis. SPSS statistical software was also utilised in the analysis process. According to the study, pharmacists did not consider the pharmacy to be an obvious first choice for providing help to those with insomnia. Determining the cause of insomnia was not considered by all pharmacists to be part of their remit, nor did they necessarily even think it was their job to find out why the customer used hypnotics. Pharmacists did not always automatically provide non-pharmacological advice on insomnia in connection with self-care products, and the treatment instructions they provided differed in both quantity and quality. Even for customers buying hypnotics for the first time, the advice related to the possible side effect, addiction, varied greatly from one pharmacist to the another. Customers whose use of hypnotics exceeded the recommended dose also received very different levels of support when collecting their next batch of hypnotics, since the pharmacists had different ways of dealing with this kind of situation. Pharmacists criticised medical doctors for their treatment practices regarding insomnia. The issue generating the most criticism was deviation from the clinical guidelines for treating insomnia. According to this doctoral dissertation, those with insomnia are far from receiving equal treatment when seeking help at a pharmacy. The quality of service received by customers with sleep problems depends on the pharmacist serving them, on the pharmacist’s competence, and on their motivation to collaborate with the customer. On the other hand, the pharmacists’ positive attitude towards non-pharmacological self-care for insomnia creates opportunities for expanding the range of services provided by pharmacies. More and more frequently, the care pathway for those experiencing insomnia could thus start at the pharmacy. This does, however, require that pharmacists receive further training. Some pharmacists also need to obtain a basic knowledge of insomnia treatment as well as information on doctors’ treatment practices for insomnia.
  • Kilasi, Doward (Helsingin yliopisto, 2017)
    Students’ mathematical identity, referring to students’ context-based narratives about their mathematical self-perceptions, has recently received researchers’ increased attention in mathematics education because, as a construct, it offers a broader socially engaging perspective for analysing the role of these perceptions and socio-cultural factors that shape them. While previous studies have mostly examined students in ‘Western’ schools who do not vary greatly in their mathematical and socio-economic backgrounds compared to students in Tanzanian schools, this study focused on a Tanzanian mathematics classroom whose students varied greatly in these backgrounds. The study applied socio-cultural and socio-psychological perspectives to examine the features and development of these students’ mathematical identity. An ethnographic approach was used to collect and analyse data on the students’ mathematical identity and conditions affecting its development at home, in school, and in the classroom. Students’ narratives provided insights into context-specific features of mathematical identity and patterns of identity development. Also, observations of the school and mathematics classroom, review of official documents, and open-ended questionnaires generated data for contextualising students’ identity narratives.Data analysis resulted in multiple mathematical identities. While positive identities of Innate ability, Persistent effort, and Image-maintenance characterised students’ engagement in mathematical activities, the negative mathematical identity of Oppositional identity was accompanied by the students’ tendency to refrain from these activities. The study further showed that each type of mathematical identity had a distinct pattern of mathematical experiences. Overall, positive mathematical identities were associated with more supportive previous mathematical experiences compared to the negative identity. Contextual factors such as teachers and parents positively or negatively shaped these experiences. The study suggests that teaching strategies that enable students to exercise their agency may not be enough to promote students’ mathematical identities. It is also important to understand how students have experienced mathematics and how they perceive their future relationship with mathematics, and support them accordingly. ________________________________________ Keywords: mathematical identity, positive mathematical identity, negative mathematical identity, mathematical experiencing, contextual factors
  • Keskitalo, Salla (Helsingin yliopisto, 2017)
    A decade after identification of the human kinome, only a fraction of the kinome has been systematically studied. This clearly illustrates the lack of knowledge regarding the functions and cellular effects that these proteins have in the establishment of cellular phenotypes. Surprisingly, recent evidence suggests that approximately 23% of all kinase genes were estimated to function as cancer genes. The overall aim of this thesis project was to shed light on the mechanisms controlling protein kinase activity and function, particularly in human cancers. A global and comprehensive interactomics analysis of the signaling networks of the evolutionarily conserved CMGC-protein kinase family, consisting of cyclin-dependent kinases [CDK], mitogen-activated protein kinases [MAPK], glycogen synthase kinases [GSK3] and CDC-like kinases [CLK]) was performed. From this physical and functional interaction analysis, hundreds of novel interactions, kinase-substrate relationships and previously unknown links to human diseases, such as cancer were identified. The unprecedented sensitivity and specificity of this approach was also illustrated, and highlighted, for example, by the purification and identification of the complete translational co-activator complex (the Mediator complex) with two of the CMGC kinases (CDK8 and CDK19). At the same time, the Mediator complex was identified mutated in benign uterine human tumors (uterine leiomyomas). To further deepen the understanding of the role of CDK8 and CDK19 kinases in controlling human disease pathways, we studied the functional role of two MED12 mutations in uterine leiomyoma and prostate cancer. Based on these studies, MED12 was found essential for the kinase activity of CDK8 in the context of the Mediator kinase module. Furthermore, disruption of the Mediator kinase module subunit interactions was shown as a common mechanism contributing to the formation of uterine leiomyoma. The MED12 mutants in leiomyoma and prostate cancer were shown functionally different. Finally, a novel MED12 nuclear localization signal was identified, and its importance in the correct nuclear localization of MED12 and subsequent proper assembly and function of the Mediator kinase module was experimentally proven. The described results from the multidisciplinary studies clarify the cellular roles of CMGC kinases and Mediator subunits, facilitating the design of targeted future therapies/therapeutics against human diseases.
  • Kukkoaho, Silja (Helsingin yliopisto, 2017)
    KOHTAAMISTAVALLA ON VAIKUTUSTA YLÄKOULUOPPILAAN UJOUTEEN Koulun kiireisessä arjessa ujo oppilas saattaa saada toisia oppilaita vähemmän huomiota ja ohjausta opettajalta. Tutkimukseen osallistuneet yläkoulun opettajat kuvailivat ujon oppilaan olevan erilainen olemukseltaan ja vuorovaikutussuhteiltaan kuin muut oppilaat.Toiset oppilaat voivat vierastaa ujoa tämän hiljaisuuden ja vetäytyvyyden takia.Kielteiset kokemukset muista muuttivat ujon aikaisempaa vetäytyvämmäksi toisia kohtaan.Myönteiset kokemukset toisista ja turvallisesta ympäristöstä lisäsivät ujon kontaktinottoa muihin oppilaisiin. Tutkimukseen osallistuneiden opettajien taitavaan ujon oppilaan kohtaamiseen liittyi voimakas eettinen näkökulma. Ujoa autettiin kiusallisissa tilanteissa suhtautumalla häneen sensitiivisesti.Ujon näkökulmasta kirjoittaneet oppilaat kertoivat voimakkaasta pelosta uudessa tilanteessa. Oppilaiden välinen vieraus,ujon puhumattomuus ja vetäytyvyys työskentelytilanteessa rakensivat toiseutta oppilaiden välille.Jos ei-ujot oppilaat kohtasivat ujon empaattisesti tai jos ujo voitti ujoutensa, työskentely rakensi keskinäistä hyväksyntää, hyvää ilmapiiriä ja jopa ystävyyttä. Ujouden ymmärtäminen lisää tasa-arvoa oppilaiden välillä ja opettajan taitoa kohdata erilainen oppija erilaisin pedagogisin teoin ja toimintavoin.Tieto ujoudesta voi kehittää myös opettajan kykyä ohjata toisia oppilaita erilaisuutta salliviksi ja tukea opiskelua sekä kouluhyvinvointia. Tutkimus on laadullista tapaustutkimusta, ja se toteutettiin yläkoulussa.Aineisto kerättiin aineenopettajia ryhmähaastattelemalla ja oppilailta eläytymiskertomuksia kirjoituttamalla.Lähestymistapa aineiston keruussa ja analyysissä oli narratiivinen.Ryhmähaastatteluaineisto analysoitiin sisällönanalyysillä. AVAINSANAT: ujous,välittävä kohtaaminen, oppilaiden vuorovaikutus, pedagogiset teot, narratiivinen ryhmähaastattelu, eläytymismenetelmä, kotitalousopetus HÖGSTADIEELEVENS BLYGSEL PÅVERKAS AV BEMÖTANDET I den hektiska skolvardagen kan en blyg elev få mindre uppmärksamhet och handledning av läraren än andra elever. Enligt de högstadielärare som deltog i undersökningen är en blyg elev annorlunda till sitt väsen och i sin interaktion jämfört med andra elever. De andra eleverna kan känna sig främmande för en blyg elev som är tystlåten och inåtvänd. Negativa erfarenheter av andra gjorde den blyga mer tillbakadragen än tidigare gentemot andra. Positiva erfarenheter av andra och av en trygg miljö gjorde den blyga mer benägen att ta kontakt med andra. För de lärare som deltog i undersökningen var ett skickligt bemötande av en blyg elev förknippat med en tydlig etisk aspekt. I plågsamma situationer hjälpte man den blyga genom ett sensitivt förhållningssätt. De elever som skrev utifrån en blyg elevs synvinkel vittnade om en stark rädsla i nya situationer. När eleverna i en arbetssituation var främmande för varandra och den blyga var tystlåten och tillbakadragen uppstod utanförskap eleverna emellan. Samarbetet fungerade om de icke-blyga bemötte den blyga empatiskt eller om den blyga deltog. Arbetssituationen lade då grunden för en inbördes acceptans, skapade en god atmosfär och utmynnade till och med i vänskap. Förståelse för blygsel ger ökad jämlikhet eleverna emellan och förbättrar lärarens förmåga att bemöta en annorlunda elev med hjälp av särskilda pedagogiska handlingar och tillvägagångssätt. Dessa kan också utveckla lärarens förmåga att handleda de andra eleverna till tolerans inför det som är annorlunda, stöda lärandet och välmågan i skolan. Undersökningen är en kvalitativ fallstudie i högstadiet. Materialet insamlades genom gruppintervjuer av ämneslärare och inlevelseberättelser av elever. Greppet vid både insamlandet och analysen av materialet var narrativt. Materialet från gruppintervjun analyserades med hjälp av innehållsanalys. NYCKELORD: blygsel, hänsynsfullt bemötande, elevinteraktion, pedagogiska handlingar, narrativ gruppintervju, inlevelsemetod, undervisning i hushållslära
  • Latva-Mäenpää, Harri (Helsingin yliopisto, 2017)
    The current era of bioeconomy strives to develop new, innovative products from natural raw materials in a sustainable way. In this PhD thesis, we have searched potential bioactive compounds from different parts of the neglected roots and stumps of conifer trees for high value products. Our aim was to establish deeper knowledge concerning chemical compositions of specified and defined biomass sources (roots and stumps of conifer trees) as well as the chemistry of certain natural polyphenolic compounds in different conditions. Using methods of natural products chemistry, such as solvent extraction and chromatographic separation and analysis techniques (GC-MS, HPLC-DAD/MS), we found that the root bark of Norway spruce is a rich source of stilbenoid glucosides (astringin, isorhapontin and piceid). These have structural similarities with the most studied stilbenoid, resveratrol. We also found that the stumps of Scots pine are a source of stilbenoids, pinosylvin and its derivatives. Stilbenoids are bioactive compounds and they have shown a variety of beneficial activities in studies related for example to human health. They have also shown antimicrobial and protective properties in trees and also in tests against micro-organisms. The highest concentrations of stilbenoid glucosides were found from the inner bark of the root zones closest to the stem of Norway spruce. This study also revealed that the root neck of Norway spruce is a new source of the bioactive lignan hydroxymatairesinol (HMR). Chromatographic and spectroscopic methods were developed to isolate pure stilbenoids from the bark of Norway spruce roots for further experiments. The complete structural elucidation of stilbenoids from Norway spruce was performed by HPLC-DAD-NMR. The HPLC-DAD method was further optimized to isolate stilbenoids in a semipreparative scale. The invividual stilbenoid molecules were isolated from the extracts and their photochemical stabilities (under fluorescent and UV light) were studied by HPLC-DAD, MS and NMR. Naturally-occurring trans stilbenoids undergo photochemical transformations to cis forms. However, the extended UV irradiation caused stilbenoids to form phenanthrene structures by intramolecular cyclisation. This is the first time that these new phenanthrene structures are reported to be derived from stilbenoids of spruce bark. Our results show that that the roots and stumps of conifer trees contain bioactive polyphenolic compounds, such as stilbenoids and lignans. These molecules and the compounds formed thereof may have commercial value and the information gained would offer a base platform for the possible new commercial high-value products developed from forest biomass. Our study has also provided new scientific knowledge of natural compounds and their properties that may lead to new findings and deeper understanding of the physiology and internal protection processes of plants by their bioactive secondary metabolites. Roots and stumps of conifer trees (Norway spruce and Scots pine) are a vast source of biomass containing potentially bioactive polyphenolic extractives as shown in this work, but this biomass is currently used for low-value energy production only. With already existing harvesting techniques, roots and stumps of conifer trees could be used as a source of commercially valuable biochemicals.
  • Rajala, Pauliina (Helsingin yliopisto, 2017)
    Low- and intermediate-level radioactive waste (LLW/ILW) is produced during the operation and decommission of nuclear power plants. At the Olkiluoto power plant, LLW/ILW is disposed of in an underground repository excavated into the bedrock 60–100 m below sea level. The metallic portion of this waste is typically made of carbon steel and stainless steels. In anoxic conditions, such as the groundwater at the Olkiluoto repository site, carbon steel corrosion rate is very slow unless the groundwater is highly acidic or microbial activity is high, altering local conditions to corrosion inducing direction. Microorganisms are able to accelerate general corrosion as well as induce localized corrosion forms and stress corrosion cracking as conditions under the biofilm can differ markedly from those in the adjacent environment. Critically, corrosion of metallic waste can release radioactive nuclides into the groundwater and threaten the long-term integrity of the storage site. The objective of this research was to determine the importance of microbially- induced corrosion (MIC) of carbon steel placed in deep geological repository containing LLW/ILW. The structure and function of microbial communities in the deep biosphere are still poorly understood but could have important consequences for the long-term storage of radioactive waste in underground repositories. MIC of carbon steel in anoxic groundwater was studied in the laboratory and in situ in experiments with exposure time ranging from 3 months to 15 years. MIC was examined using gravimetric and electrochemical techniques complemented by molecular biology and surface characterization methods. It was shown that conditions beneath the microbial biofilm accelerated corrosion rate of carbon steel, especially localized corrosion, and that microbial activity in deep groundwater is enhanced by the presence of carbon steel. Naturally- occurring microorganisms in deep groundwater environments have a great affinity for the surface of carbon steel and rapidly form a biofilm. Phylum proteobacteria, beta- or deltaproteobacteria depending on the experiment, were in the majority in the biofilm forming bacterial community. Archaeal biofilm was formed by phylas Euryarchaeota (DHVE) and Thaumarcheota (MBGB). However, corrosion was inhibited in concrete-encased environments, due to high alkalinity and calcium carbonate concentration in the environment. In many cases, LLW/ILW repositories contain concrete materials, which according to the present results hinders the corrosion at least in the beginning of repository time scale.
  • Sjöstedt, Noora (Helsingin yliopisto, 2017)
    Transport proteins embedded in the cell membranes of many organs can affect the absorption, distribution and elimination of numerous drugs. This can lead to the enhanced or restricted uptake or distribution of the drugs, nonlinear pharmacokinetics, transporter-mediated drug-drug interactions (DDIs) and inter-individual variability. Transporters may therefore alter the safety and efficacy of drugs, thus it is important to study drug-transporter interactions in drug development. The breast cancer resistance protein (BCRP, ABCG2) is one of the transporters involved in drug disposition. It belongs to the ATP-binding cassette (ABC) transporter family and uses ATP to expel drugs and other substrates out from cells. BCRP was initially found to cause drug resistance in cancer cell lines, but it is also expressed in healthy tissues such as the intestine, liver and blood-brain barrier, where it is one of the transporters limiting the uptake of many structurally diverse compounds. Despite interest in BCRP and other ABC transporters, it remains poorly understood how they recognize their substrates and which chemical structures are liable to interaction. In this thesis, a vesicle-based in vitro method was used to study the ligand preferences of BCRP. The results were compared to those obtained for the multidrug resistance associated protein 2 (MRP2, ABCC2), which is also implicated in drug transport. The results show that a range of natural compounds and their derivatives are able to inhibit BCRP transport and among these, flavonoids were identified as the most important group for inhibition. Conversely, MRP2 transport was affected by only few of the tested compounds. However, a more similar pattern of inhibition was seen for the two transporters when selected food additives were studied, where several food colourants were identified as inhibitors. In addition, the effect of one assay component (bovine serum albumin, BSA) on the in vitro transport kinetics of BCRP and MRP2 was evaluated. The inclusion of BSA in the vesicle assay lead to moderate changes (up to 2-fold) in transport activity, but the effects on in vitro − in vivo extrapolation are expected to be minor, at least based on the tested compounds. Finally, the vesicle assay was used to study the functionality of selected BCRP variants with polymorphisms in the transmembrane helices and they were found to have significantly impaired transport activity and expression compared to wild type BCRP. In summary, the vesicle-based transport assay was successfully applied to identify and evaluate the effects that BCRP interactions may have on the pharmacokinetics of BCRP substrates.
  • Hsieh, Yi-Ta (Helsingin yliopisto, 2017)
    Visual attention is crucial in mobile environments, not only for staying aware of dynamic situations, but also for safety reasons. However, current mobile interaction design forces the user to focus on the visual interface of the handheld device, thus limiting the user's ability to process visual information from their environment. In response to these issues, a common solution is to encode information with on-device vibrotactile feedback. However, the vibration is transitory and is often difficult to perceive when mobile. Another approach is to make visual interfaces even more dominant with smart glasses, which enable head-up interaction on their see-through interface. Yet, their input methods raise many concerns regarding social acceptability, preventing them from being widely adopted. There is a need to derive feasible interaction techniques for mobile use while maintaining the user's situational awareness, and this thesis argues that solutions could be derived through the exploration of hand-based haptic interfaces. The objective of this research is to provide multimodal interaction for users to better interact with information while maintaining proper attention to the environment in mobile scenarios. Three research areas were identified. The first is developing expressive haptic stimuli, in which the research investigates how static haptic stimuli could be derived. The second is designing mobile spatial interaction with the user's surroundings as content, which manifests situations in which visual attention to the environment is most needed. The last is interacting with the always-on visual interface on smart glasses, the seemingly ideal solution for mobile applications. The three areas extend along the axis of the demand of visual attention on the interface, from non-visual to always-on visual interfaces. Interactive prototypes were constructed and deployed in studies for each research area, including two shape-changing mechanisms feasible for augmenting mobile devices and a spatial-sensing haptic glove featuring mid-air hand-gestural interaction with haptic support. The findings across the three research areas highlight the immediate benefits of incorporating hand-based haptic interfaces into applications. First, shape-changing interfaces can provide static and continuous haptic stimuli for mobile communication. Secondly, enabling direct interaction with real-world landmarks through a haptic glove and leaving visual attention on the surroundings could result in a higher level of immersed experience. Lastly, the users of smart glasses can benefit from the unobtrusive hand-gestural interaction enabled by the isolated tracking technique of a haptic glove. Overall, this work calls for mobile interaction design to consider haptic stimuli beyond on-device vibration, and mobile hardware solutions beyond the handheld form factor. It also invites designers to consider how to confront the competition of cognitive resources among multiple tasks from an interaction design perspective.
  • Kilpinen, Lotta (Helsingin yliopisto, 2017)
    Human mesenchymal stromal cells (hMSCs) are currently used in many advanced cellular therapies. The clinical use of hMSCs requires extensive cell expansion, but the consequences of expansion, especially at the molecular level, are not fully understood. The therapeutic effect of hMSCs is mediated paracrine interactions with immune cells modulating both innate and adaptive immune response. Membrane glycerophospholipids (GPLs) provide precursors for signaling lipids, which modulate cellular functions, including immunological effects. In this thesis, I investigated the effect of the donor’s age and cell doublings on the GPLs, gene expression and microRNA (miRNA) profiles of human bone marrow MSCs (hBM-MSCs). In order to gain more insight into the functional mechanisms of hMSCs, I investigated the extracellular vesicle secretion from human umbilical cord blood derived MSCs, and evaluated their immunosuppressive capacity in vitro as well as their possible immunomodulative and protective effect in kidney ischemia-reperfusion injury in vivo. In this study, I was able to demonstrate that the hBM-MSCs, harvested from 5 young adults and 5 old donors, showed clear compositional changes in their GPL profiles during expansion. Most strikingly, the molar ratio of arachidonic acid (20:4n-6) containing species of phosphatidylcholine and phosphatidylethanolamine accumulated, while the species containing monounsaturated fatty acids decreased during passaging. The lipid changes correlated with the decreased immunosuppressive capacity of hBM-MSCs suggesting a connection between lipid signaling and immunomodulatory functions. Although there were clear alterations in gene expression levels and lipid profiles, the miRNA expression levels were more stable. The expression levels of 37 miRNAs were changed in the old donors group and 36 miRNAs were changed in the young donors group. Of these, only 12 were differentially expressed in both young and old donor BM-MSCs and their predicted target mRNAs, the expression of which was changed, were mainly linked to cell proliferation and senescence. This thesis provides a detailed analysis of molecular changes during MSC expansion. The combination of in vitro and in vivo models accompanied with a detailed analysis of molecular characteristics is essential to understand the complexity of the MSC paracrine mechanisms and functionality.
  • Ronkainen, Riitta (Helsingin yliopisto, 2017)
    Speech and language therapy for children with cochlear implants focuses on promoting the children's spoken language skills. In this dissertation, the professional practices of one speech and language therapist in promoting language learning are examined using a conversation analysis methodology. The research data consist of video recordings from speech and language therapy sessions, totalling approximately 36 hours. The total duration of analysed sequences is 3 hours, 52 minutes. The participants in the study are seven children with profound congenital hearing impairment who have received a cochlear implant and their speech and language therapist. The general aim of the dissertation is to increase knowledge of speech and language therapists' professional practices in supporting spoken language learning of children with cochlear implants. The therapist's practices are examined in both play and task interactions at three different stages of the therapy. First, the dissertation examines the ways in which the therapist enhances the children's listening and imitation skills in the early stages of therapy and cochlear implant use (Study I). Second, it analyses the therapist's professional practices of involving the parents in multiparty therapy interaction (Study II). Third, it demonstrates how the therapist promotes lexical learning in children with cochlear implants in the later stages of therapy (Study III). The dissertation offers new insights into the institutional nature of interaction in the speech and language therapy for children with cochlear implants. It demonstrates the therapist's professional practices and pinpoints techniques and strategies used in the intervention. Primarily, the children are provided with a repetitive and prosodically emphasised spoken language model to enhance their listening skills and spoken language learning. In addition multimodal elements such as gestures, signs and body movements are systematically used. The dissertation shows how the therapist supports the children's participation and fosters their competence, which is seen in the form of enhanced collaboration. Furthermore, the dissertation provides information about the ways in which the therapist involves parents in the therapy. The findings reported here contribute to research on speech and language therapy interaction, as well as more broadly to the study of institutional interaction. The findings expand and specify the professional stock of interactional knowledge about speech and language therapy. The dissertation provides detailed and concrete descriptions of therapeutic practices and suggests practical guidelines for supporting the spoken language learning of children with cochlear implants. These may be useful for clinicians and students working both with children with cochlear implants and children who have other communication disabilities.
  • Kemppainen, Teemu (Helsingin yliopisto, 2017)
    Insecure and restless neighbourhood conditions lower the quality of life, imply health risks and may accelerate segregation through selective migration. This study examined subjective insecurity and perceptions of social disorder—including public drunkenness, vandalism, threatening behaviour and the like—in different residential contexts. The focus was on Finnish post-WWII housing estates built in the 1960s and 1970s. Compared to other kinds of neighbourhoods, these areas often suffer from a negative reputation related to poverty, insecurity and disorder. However, the residents’ views are often at odds with the negative public image. There is a lack of reliable evidence on where estates stand in comparison to other kinds of neighbourhoods. Furthermore, the full diversity of estates has typically not been addressed in prior studies. Empirically, the study relied on three sets of survey data that were combined with contextual register data. The covered area varies from Helsinki to the entire country while the contextual units range from statistical grids to city districts. The key findings were the following: 1) The level of perceived social disorder was only slightly higher in the estates built in the 1960s and 1970s than in other multi-storey neighbourhoods. This small difference was due to socio-economic disadvantage. As expected, the low-rise neighbourhoods were considerably more peaceful than the multi-storey ones. 2) Rental-dominated tenure structure exposed the estate residents to higher levels of perceived disorder because rental estates are typically more disadvantaged. Social integration of the estate community played no role in terms of disorder. In contrast, the level of normative regulation partly explained why disadvantage is related to disorder. 3) At the district level, disadvantage, disorder (from police registers), residing in proximity to a metro or train station and living in a social housing flat exposed residents to subjective insecurity. Victimisation partly mediated the association between disadvantage and insecurity. The study shed light on the diversity of estates. From the point of view of social life, estates markedly differ from each other. Tenure structure has a decisive influence on the socio-economic structure, which implies differences in normative regulation and social order. This is an important finding in terms of tenure-mix policies. Compared to rental-dominated neighbourhoods, a more mixed tenure structure implies a less disadvantaged and more regulated local community, which paves way for a more peaceful local social life.
  • Koivisto, Jaana-Maija (Helsingin yliopisto, 2017)
    The aim of this study was to obtain knowledge about learning clinical reasoning through game-based simulation. This knowledge could be used in developing and embedding new learning methods for clinical reasoning in nursing education. Research has shown that nursing students lack knowledge and skills in detecting and managing changes in patients’ clinical conditions. This is often due to insufficient clinical reasoning, and thus, educational organisations need to more effectively enable the development of clinical reasoning during education. Digitalisation in higher education is increasing, and the use of virtual simulations and, recently, serious games to support professional learning and competence development is growing. The purpose of this research was to generate design principles for simulation games and to design and develop a simulation game for learning clinical reasoning. Furthermore, the purpose was to investigate nursing students learning through gaming. A design-based research methodology was used: iterative cycles of analysis, design, development, testing and refinement were conducted via collaboration among researchers, nurse educators, students, programmers, 3D artist and interface designers in a real-world setting. Mixed research methods were used. The results indicated that games used to provide significant learning experiences for nursing students need to share some of the characteristics of leisure games, especially visual authenticity, immersion, interactivity and feedback systems. In terms of the clinical reasoning process, students improved in their ability to take action and collect information. The findings showed that usability, application of nursing knowledge and exploration are the aspects of a simulation game that have the greatest impact on learning clinical reasoning. It was also revealed that authentic patient-related experiences, feedback and reflection have an indirect effect on learning clinical reasoning. This study provided opportunities to advance our knowledge of nursing students’ learning processes and experiences of learning clinical reasoning through game-based simulation. Its results add to the growing body of literature on game development in the field of nursing education by providing design principles for educational simulation games. The present study confirms previous findings and contributes additional evidence that suggests that game-based simulations are a valuable learning method for healthcare education. However, in order for serious games to add value to healthcare education, the essence of the profession needs to be built into the game, and here the contribution of healthcare professionals is priceless.
  • Valenzuela, Daniel (Helsingin yliopisto, 2017)
    This thesis is motivated by two important processes in bioinformatics, namely variation calling and haplotyping. The contributions range from basic algorithms for sequence analysis, to the implementation of pipelines to deal with real data. Variation calling characterizes an individual's genome by identifying how it differs from a reference genome. It uses reads -- small DNA fragments -- extracted from a biological sample, and aligns them to the reference to identify the genetic variants present in the donor's genome. A related procedure is haplotype phasing. Sexual organisms have their genome organized in two sets of chromosomes, with equivalent functions. Each set is inherited from the mother and the father respectively, and its elements are called haplotypes. The haplotype phasing problem is, once genetic variants are discovered, to attribute them to either of the haplotypes. The first problem we consider is to efficiently index large collections of genomes. The Lempel-Ziv compression algorithms is a useful tool for this. We focus on two of its exponents, namely the RLZ and LZ77 algorithms. We analyze the first, and propose some modifications to both, to finally develop a scalable index for large and repetitive collections. Then, using that index, we propose a novel pipeline for variation calling to replace the single reference by thousands of them. We test our variation calling pipeline on a mutation-rich subsequence of a Finnish population genome. Our approach consistently outperforms the single-reference approach to variation calling. The second part of this thesis revolves around the haplotype phasing problem. First, we propose a generalization of sequence alignment for diploid genomes. Next we extend this model to offer a solution for the haplotype phasing problem in the family-trio setting (that is, when we know the variants present in an individual and in her parents). Finally, in the context of an existing read-based approach to haplotyping, we go back to basic algorithms, where we model the problem of pruning a set of reads aligned to a reference as an interval scheduling problem. We propose a exact solution that runs in subquadratic time and a 2-approximation algorithm that runs in linearithmic time.
  • Laaksonen, Salla-Maaria (Helsingin yliopisto, 2017)
    This doctoral thesis investigates how the reputations of organizations are narrated in the hybrid media system, characterized by different media logics and technological principles, and the affective attunement of storytelling stakeholders. The research problem is two-fold: first, to study how the new communication landscape affects the formation of organizational reputation, and second, to investigate the cognitive and emotional influences of reputation in the hybrid media system. The dissertation sees organizational reputation as a communicative phenomenon, which exists both as individual beliefs and socially constructed narratives that are born and circulated in the hybrid media system. Hybrid stands for a combination of older and newer media forms, which are intertwined in complex and dynamic assemblages, formed by individuals, affects, social contexts, organizations, and technological platforms, who all mutually influence the process of storytelling. The dissertation is a compilation of five articles. It employs a parallel mixed methods approach by using four different data sets: interviews with communication professionals in organizations; social media discussions; Wikipedia data; and psychophysiological measurements. With a multimethodological approach the study builds a bridge between the different schools of reputation studies: reputations are constructed as narratives that also have measurable effects on the people who consume them. In light of the results, a hybrid reputation narrative is polyphonic, emotional, and is formed in a context characterized by relative power structures between human and non-human actors. It is a form of narrative, in which the story elements can be stored in databases, searched, and hyperlinked by various, interacting actors, who through their use of the technical platforms generate the reputation narrative from fragmentary story pieces by merging opinions and facts. This dissertation highlights two aspects: the interplay between the social and the technological, and the importance of affect. First, the technological affordances and the social practices together form the settings in which the narrating takes place in the hybrid media system. Second, affect emerges as an inherent property of reputation, as an important characteristic of the reputation narratives, and as a feature to evaluate different platforms.