Doctoral dissertations

Recent Submissions

  • Mesihää, Samuel (Helsingin yliopisto, 2021)
    Legal medicines and illegal drugs play a significant role in today’s society. The laboratory analysis of these substances is central not only in therapeutic monitoring but also in clinical and forensic toxicology, which aims to provide evidence-based information on the abuse and harmful effects of these substances. The rapid emergence of newly abused drugs known as new psychoactive substances (NPS) has challenged the conventional drug testing concept. On the European illicit drug market, approximately fifty new substances are identified each year, many of which are poorly characterized for their pharmacological effects or toxicity. Moreover, the lack of authentic primary reference standards (PRS) bottlenecks the development of analytical assays for NPS, which hinders both detection and toxicological evaluation of these drugs. High-resolution mass spectrometry (HRMS) has recently been applied to tentative identification of unknown compounds by targeting the precursor ions with high mass accuracy, resolution and speed. This capability has permitted a breakthrough in facile screening for suspected NPS, but until now, no practical method has been described for quantitative bioanalysis of NPS in the absence of PRS. In this thesis, a new analytical platform was developed and exploited for the simultaneous qualitative and quantitative analysis of NPS and metabolites without using PRS. In this platform, the gas chromatographic (GC) flow was divided between an atmospheric pressure chemical ionization - quadrupole time-of-flight mass spectrometer (APCI-QTOFMS) for tentative identification and a nitrogen chemiluminescence detector (NCD) for quantitative estimation based on the detector’s equimolar response to nitrogen-containing substances. Replacement of the ordinary electron ionization (EI) source with APCI was proven to be useful in substance identification by QTOFMS because it allowed the preservation of the precursor ion for tentative identification. The GC-APCI-QTOFMS tandem mass spectrometry (MS/MS) experiments using 29 NPS showed that all substances shared the same major fragments as in the commercial spectral library created by using liquid chromatography (LC) electrospray (ESI) MS/MS instrumentation. Consequently, these findings promote the usability of external soft-ionization compound libraries with the new GC-APCI-QTOFMS platform. The accuracy and precision of the N-equimolar quantification by GC-NCD were tested using several NPS in four separate studies using post-spiked sheep blood (n = 5), post-mortem blood (n = 38) and urine (n = 3), and in seized powdery material (n = 28). The combined results from these studies, excluding the post-spiked samples, showed that NPS could be quantified with a grand mean accuracy of 91.7% and with a grand mean imprecision (CV) of 9.5% in the absence of PRS for compensating sample preparation and analysis. In conclusion, the GC-NCD-APCI-QTOFMS platform proved feasible for analyzing suspected nitrogen-containing drugs, such as stimulant-type NPS and metabolites, in situations where appropriate reference standards are not readily accessible. Simultaneous tentative identification by HRMS and quantitative estimation by NCD has unparalleled potential for fast preliminary analysis until a certified PRS becomes available. The possibility for high-throughput retrospective identification and quantification is an additional advantage of this platform, providing a means for further research on emerging NPS.
  • Pospelov, Alexey (Helsingin yliopisto, 2021)
    Treatment of birth asphyxia (BA) is a challenging problem – this condition is common and often leads to severe life-long neurological dysfunction. The pathophysiology of BA is complex and not fully understood, and the existing therapeutic approaches are not effective. Animal models are the main source of knowledge about the pathophysiology of BA, but many of the existing models have little relevance to the defining features of BA – the co-occurring hypoxia and hypercapnia – making the results obtained from such models, which concentrate on hypoxia in isolation, difficult to apply in clinical practice. This Dissertation consists of three studies (Studies I–III), which address the above shortcomings and suggest alternative approaches. Study I characterizes the pH-dependent vasomotor responses in a novel, physiologically-validated model of BA. The key advantage of this model is that it reproduces not only the hypoxic but also the hypercapnic component of asphyxia. The importance of the co-occurrence of these two components is directly demonstrated in experiments showing that in the absence of hypercapnia, shifts in brain pH and in partial pressure of oxygen (Po2) during and after hypoxia are qualitatively different from those during asphyxia proper. The respiratory acidosis, associated with the latter, triggers protective mechanisms that have emerged during mammalian evolution to ameliorate brain damage during asphyxia. In Study II, we investigated the therapeutic potential of carbon dioxide (CO2) supplemented in ambient air for the treatment of BA-seizures. Seizures are a common acute consequence of BA and they exacerbate the brain damage caused by asphyxia itself. We found that supplementing the inhaled air with 5% CO2 immediately after the asphyxia period prevents seizures, presumably by slowing down the brain pH recovery from acidosis caused by asphyxia. Study III focuses on carbonic anhydrase inhibitors (CAIs), drugs that cause respiratory acidosis by retention of metabolically-generated CO2. These drugs produced brain pH and Po2 responses similar to the responses to CO2 supplementation and similarly suppressed seizures triggered by BA. As first shown in this study, the most widely used CAI, acetazolamide (AZA) is therefore a candidate drug for the treatment of BA seizures. In sum, this doctoral thesis work developed and characterized a novel rodent model of BA and used this model for testing a novel treatment strategy for BA and post-asphyxia seizures.
  • Chen, Liangzhi (Helsingin yliopisto, 2021)
    Soil is one of the most critical components in Earth systems in connecting the lithosphere, hydrosphere, atmosphere, and biosphere. The responsiveness of soil temperature to climatic changes has been tackled in a number of studies. However, a timely understanding of the recent shallow–depth soil temperature evolution in response to changing climate and environment at inter-annual time scale over northern Eurasia is inadequate and needed for assessing the land–atmosphere thermal interactions and consequences at a broad spatiotemporal scale. This thesis backs up the aforementioned knowledge gaps by 1) quantifying and contrasting soil temperature changes in northern Eurasia and subregions; 2) investigating discordant changes in soil and air temperatures and their links with environmental changes; 3) assessing and examining the stability of soil–air temperature coupling at an inter-annual time scale and the underlying mechanisms. This thesis demonstrated that shallow–depth soil temperature significantly increased over the region since the 1970s in terms of the annual mean, maximum, and minimum soil temperatures. However, the warming rates were spatially heterogenous at different depths and over the subregions divided by the extent of frozen ground. In the region as a whole, the average increases in the annual mean, maximum and minimum temperatures ranged between 0.30–0.31, 0.33–0.44, and 0.24–0.25 °C/decade, respectively, at multiple depths. As such, the overall faster increase in the annual maximum temperature than minimum temperature led to an increase in intra-annual variability of soil temperature over the years. The soil temperature changes were consistently smaller than the air temperature changes except in the seasonal frost area at a depth of 0.2 m. Such discordant changes in soil and air temperatures led to inter-annual variations of soil–air temperature difference over the period. Furthermore, the environmental changes essentially explained the variability of temperature difference. Among the examined variables, changes in the snow cover characters showed overriding effects. Other environmental changes such as surface net solar radiation, liquid precipitation, and soil moisture had comparatively smaller impacts but still significant, which cannot be ignored at some ground depths. It is also revealed that coupling, which is defined as the linear regression slope between the mean annual soil and air temperatures, was not a stable property and significantly decreased from 1984 to 2013. The declined coupling was likely due to the compound effects of changing thawing/freezing-degree days of air temperature and snow cover characteristics. The findings further question the rationality of using air temperature to proxy soil temperature (or vice versa) at inter-annual and long-term time scales. This thesis provides a thorough picture of the recent shallow–depth soil temperature evolution in response to climate changes and related consequences over northern Eurasia. The findings will help understand land–atmosphere thermal interactions and the role of environmental components at inter-annual and long-term time scales. Considering soil temperature as a critical parameter for Earth systems research, the findings can be referred¬¬ to and implemented for various aims, such as climate projection, land–surface model development, and agricultural management.
  • Simola, Anna (Helsingin yliopisto, 2021)
    This dissertation is an investigation of young European Union (EU) citizens’ experiences of free mobility in precarious labour conditions. It seeks to understand situations in which young, university-educated Europeans move in search of work opportunities that would allow them to exploit their education, their skills and their passions, but who end up experiencing precarity. The research is located in a context in which young, educated workers across Europe face persistent difficulties in the labour markets and are disproportionately exposed to unemployment and precarious types of work. Meanwhile, various EU Member States have adopted policies that render EU migrants’ access to rights associated with EU citizenship increasingly conditional on their ability to demonstrate employment, self- sufficiency or ‘genuine’ employability. These policies resonate with workfarist welfare policies that stress the responsibility of individuals in managing the social and economic risks they confront in the labour market. However, they are in sharp conflict with the EU’s official discourse and policies, which seek to encourage mobility among young people by depicting it as a means to enhance their ‘employability’, while primarily focusing on unpaid labour options, such as internships and volunteering. The three articles that form the empirical foundation of the dissertation build on data obtained through narrative interviews in 2014-2015. Additionally, one of the articles also draws on a complimentary dataset based on answers to written questions the same participants were asked to respond to in 2018. The study is qualitatively comparative in a multi-contextual setting that includes one country of destination (Belgium) and four countries of origin, in which the institutional and economic conditions vary significantly. The empirical sample consists of 27 university-educated young adults originating from Italy (10), Spain (eight), Finland (seven) and Denmark (two). In order to maximise the study’s capacity to capture the effects of labour market precarity on mobility, the study focuses on the experiences of persons who had moved to Brussels to work but had subsequently experienced unemployment and worked under precarious arrangements. In the study, I adopt a cross-disciplinary approach in order to capture different dimensions of precarity in this specific context. The study combines theoretical insights from the fields of sociology of work, critical migration research, comparative welfare state research and governmentality studies, while also contributing to these fields of research. Whilst the articles draw on different theoretical discussions, they are interconnected, and all address the influence of neoliberal governance on precarity as experienced by young EU migrants. All three articles aim, from their distinct perspectives, to understand: (1) The reasons for which highly educated young EU migrants accept their precarious working and living conditions, and the implications of this acceptance. (2) The role of institutions in conditioning young EU migrants’ autonomy, independence and room for manoeuvre in precarious labour market conditions, and the possible inequalities emerging in this respect. A thorough contextualisation (i.e. a parallel reading of the legal and policy documents and the existing research addressing the legal-institutional environment etc.) formed an integral part of the analysis of the participants’ personal narratives. In Article I, I analyse the interplay of precarious employment, social and legal norms regulating EU citizens’ free movement, and the local bureaucratic implementation of these norms. The results point to a consequential role for administrations in producing precarious citizenship status for EU migrants in precarious work arrangements. Furthermore, in Article II, written jointly with Sirpa Wrede, we show how migration puts young EU citizens under the influence of several welfare models at the same time, making their access to social entitlements contingent not only on the conditionality of welfare and residence rights in their destination country, but also on the policies in their country of origin. Together, Articles I and II demonstrate how institutionally enforced barriers to rights and the uncertainty and temporariness of status often negatively impacted the participants’ room for manoeuvre in the labour market, thus further exposing them to precarious work. Finally, in Article III, I analyse the participants’ migration as an expression of self-developing, self- entrepreneurial subjectivity, showing how this neoliberal mode is encouraged by EU mobility policies. In this context, the article demonstrates that, while young migrants very often perceived their migration as a means to, or even as the prerequisite for, finding work corresponding to their passion, they could be compelled to tolerate highly precarious and even injurious working and living conditions. All in all, the dissertation is an illustration of the ambivalence of autonomy and compulsion in the context of presumably ‘free’ mobility. It shows how the participants’ room for making choices regarding mobility and for acting upon their precarious conditions is bound to hegemonic discourses and policies informed by neoliberalism. The study also identifies institutional drivers of inequality emerging between young EU migrants from different national and social origins, affecting their financial security and access to independence, their exposure to precarity, and their ability to use mobility to pursue their passion. By acknowledging the implications of precarity in this context, the study advances new conceptual tools and approaches for future critical research on EU migration.
  • Tavakoli, Shirin (Helsingin yliopisto, 2021)
    The prevalence of vision-threatening diseases of the posterior eye segment, such as age-related macular degeneration (AMD), diabetic retinopathy, diabetic macular edema and glaucoma, is increasing worldwide. This is a major burden to patients and health care systems. Current therapy includes intravitreal injections of anti-angiogenic agents against vascular endothelial growth factor (VEGF), because drug delivery to the back of the eye is hampered by anatomical and physiological barriers. Intravitreal injections are uncomfortable, may cause adverse reactions and reduced compliance leading to suboptimal treatment outcomes. Furthermore, current anti-VEGF drugs are not effective in all patients. Therefore, new drugs and delivery systems for targeted and prolonged action are needed for posterior segment eye treatment. Nanoparticles have been investigated as a long-acting and targeted ocular drug delivery systems that may prolong actions of small molecule drugs (e.g. corticosteroids and tyrosine kinase inhibitors) with short vitreal half-lives. Nanoparticles are also important for delivery of labile therapeutics with intracellular targets, including some proteins, neuroprotective peptides and nucleic acids (RNA, DNA). However, several barriers hamper retinal delivery of intravitreal nanoparticles and interspecies differences may lead to poor clinical translation. Hence, the overall objective of this study was to generate improved understanding of ocular barriers to retinal delivery of nanoparticles by using translationally valid preclinical models. We systematically studied vitreal diffusion of various liposomes and other lipid-based nanoparticles by analyzing the mobility of the nanoparticles with single particle tracking in intact porcine central vitreous with similar structure to human vitreous. We evaluated the physicochemical features of nanoparticles affecting their vitreal mobility (e.g. particle size, surface change, surface coating with polyethylene glycol or hyaluronic acid). Neutral and anionic liposomes showed faster diffusion than cationic liposomes. Small size and polymer coating modestly facilitated vitreal mobility of liposomes. Kinetic analysis demonstrated that nanoparticles’ distribution in the human vitreous is controlled by convection rather than diffusion, while vitreous liquefaction may increase the role of nanoparticle diffusion. We also studied protein corona formation on liposomes’ surface, since it may affect the hydrodynamic diameter and cellular interactions. In this regard, surface plasmon resonance analysis was performed to monitor the protein corona formation in the presence of porcine vitreous. Insignificant size change was seen indicating that vitreal diffusion is not influenced by protein corona. In addition, high-resolution proteomics confirmed identity of the proteins on liposomal surface that may change the biological interactions of the liposomes. Next, retinal permeation of liposomes was studied systematically using ex vivo analyses and bovine retinal explants. Neutral and anionic liposomes with high vitreal mobility were studied for their potential in overcoming the ILM barrier. Liposomes with diameters over 100 nm fail in retinal entry irrespective of their surface charge, while small anionic PEG-coated liposomes (<50 nm) distributed into the retina. Lastly, a liposomal formulation was developed to encapsulate sunitinib, a small molecule anti-neovascular drug for VEGF suppression. Unlike sunitinib solution, the liposomal formulation showed anti-neovascular effect in laser induced mouse choroidal neovascularization model. In summary, this study extended understanding of the retinal drug delivery barriers related to the intravitreal injections. It also informed about the role of nanoparticles’ characteristics on their interactions with ocular barriers. These findings can be leveraged in understanding pharmacokinetics and design of retinal drug delivery systems.
  • Karhunmaa, Kamilla (Helsingin yliopisto, 2021)
    In this dissertation, I examine how societal debates on energy policy and the necessity of energy transitions unfold in Finland. Transforming energy systems is acknowledged as one of the most important areas for action on climate change and numerous voices across the globe have called for radical shifts in current energy policies and practices. Simultaneously, discussions on energy policy revolve around futures – both expected and feared – and the measures required to attain them. Finland is an interesting context to study claims about change and transitions as it has both commitments to action on climate change as well as stable institutional structures that have been described as resistant to change. My perspective on energy policy and governance is broad and I analyse various arenas where energy issues are debated. These include the Finnish Parliament and Helsinki City Council, the media and discussions amongst various actors attempting to influence energy policy and working at the science-policy interface. In my analysis, I show how Finnish energy policy actors are broadly committed to a sociotechnical imaginary of carbon neutrality, or a collectively held and publicly performed vision of a desirable future. In the imaginary, Finland is envisioned as a prosperous welfare society that has addressed climate change by attaining a balance between greenhouse gas emissions and removals. The imaginary of carbon neutrality is broad and interpretatively flexible, thus accommodating diverse views on what carbon neutrality can entail. In the articles that comprise this dissertation, I engage with a wide range of literature from science and technology studies, sociotechnical transitions studies, social scientific studies on energy, institutional theory and analyses on science-society relations. Specifically in the thesis summary, I address a research gap within the literature on sociotechnical imaginaries, by examining how questions regarding scale, heterogeneity and mobility shape the co-production of imaginaries as well as enable and curtail the scope of agency. I build on a constructivist and interpretative approach to research and use a range of materials, such as interviews, documents, news articles, Parliamentary and City Council transcripts, press releases and participant observation. Empirically, I focus on the 2010s as the decade when a sociotechnical imaginary of carbon neutrality emerged and became consolidated in Finland. In this thesis, I argue that sociotechnical imaginaries, in this case carbon neutrality, form the imaginative foundations of national policy debates that motivate and justify action, while simultaneously retaining space for negotiation on how to attain those futures. The empirical analysis demonstrates that there is no overarching consensus in Finland over what carbon neutrality means and what practices it allows for. I demonstrate that the context where an imaginary is co-produced both enables and constrains the scope of possible political debate and action by requiring actors to formulate their views through interpretations of desirable pathways towards carbon neutrality. I conclude that carbon neutrality is likely to persist as a widely shared sociotechnical imaginary in Finland due to the political possibilities for debate and compromise that it offers. At the same time, I propose that the concept of carbon neutrality will be increasingly challenged by questioning whose imaginary is it, what type of practices does it enable and how are different actions evaluated as carbon neutral. Likewise new concepts, such as climate emergency, are likely to challenge the imaginary of carbon neutrality. I conclude that such debates are both necessary and desirable as we collectively face, address and learn to live with climate change.
  • Ignatenko, Olesia (Helsingin yliopisto, 2021)
    Mitochondria are organelles critical for cellular energy metabolism and homeostasis. Pathogenic DNA variants that disrupt organelle function manifest as a heterogeneous group of diseases. These include severe brain encephalopathies that lack curative treatments, leading to early childhood lethality. Typical findings in brain samples of patients with mitochondrial encephalopathies include neuronal degeneration and histopathological changes of non-neuronal cells, referred to as reactive gliosis. The severe manifestations of mitochondrial encephalopathies have thus far been explained by the vulnerability of neurons to mitochondrial dysfunction, while reactive gliosis is considered a secondary response to the neuronal pathology. In my thesis research, I used genetically modified mouse models to investigate the cell-specific contribution to the pathogenesis of mitochondrial dysfunction in the central nervous system. Using Cre-Lox recombination, the gene encoding the mitochondrial DNA helicase Twinkle was conditionally disrupted in postnatal astrocytes or neurons. In neurons, we observed the well-established vulnerability to mitochondrial dysfunction. Whereas in astrocytes, our data show reactive astrogliosis as a cell-autonomous response to mitochondrial dysfunction. Furthermore, the formation of microscopic vacuoles in the brain characteristic of spongiotic encephalopathies was only observed upon mitochondrial dysfunction in astrocytes. Collectively, these findings shift the paradigm on the contribution of individual cell types to the brain pathology of mitochondrial disorders. Next, I used these mouse models to test two therapeutic approaches that act to remodel cellular metabolism for modulating mitochondrial dysfunction. The first intervention used rapamycin to inhibit activity of the key nutrient sensor mTORC1; while the second used dietary intervention by shifting the carbon source to generate ketone bodies as an alternative energy source for the brain. Neither of the treatments improved the spongiotic pathology or attenuated reactive astrogliosis, and moreover the ketogenic diet exacerbated these phenotypes. Since rapamycin and ketogenic diet have been used successfully in treating other mouse models of mitochondrial dysfunction, it emphasizes the importance of using disease-specific models in preclinical studies. In the final part of my thesis, astrocyte responses to mitochondrial dysfunction were investigated. We found that lipid biosynthesis was downregulated in astrocytes, which was paralleled by changes in brain lipid composition and accumulation of lipid droplets. We also discovered an induction of a motile ciliogenesis program as an astrocyte response to pathological stimuli. Mitochondrial dysfunction resulted in anomalous expression of motile cilia components and abnormal morphology of cilia in astrocytes. Astrocytes are normally devoid of motile cilia but possess a primary cilium, which has signalling functions. Our findings raise the possibility of the remodelling of cilia function in astrocytes in response to mitochondrial dysfunction, which may contribute to pathogenesis. Altogether, the research presented in this thesis has implicated astrocytes as a critical contributor to mitochondrial disease manifestations, and provided a solid base for the future efforts to target astrocyte responses to mitochondrial dysfunction.
  • Dang, Kien (Helsingin yliopisto, 2021)
    The aim of this doctoral thesis was to utilize molecular biology techniques to detect expressed KRAS and BRAF mutations in samples at high sensitivity and specificity and evaluate the clinical role of the RNA expression of these mutations in certain MAPK/ERK-driven cancers. In the early phase of the study, we developed a novel method named extendable blocking probe reverse transcription (ExBP-RT) for detecting expressed mutations at the mRNA level. With this method we were able to detect mutations expressed in mRNA with a very high sensitivity and specificity. The ExBP-RT assay was optimized to detect expressed BRAF and KRAS mutations in a 1000-fold – 6000-fold excess of wild-type mRNA. A further improvement of the method allowed detection of expressed BRAF mutations, in thyroid cancer (TC) tissue, in a 10000-fold excess of wildtype mRNA. This novel strategy not only reveals the presence or absence of low-abundance mutations with an exceptionally high selectivity, but also provides a convenient tool for accurate determination of the mRNA levels of the mutated genes in different settings, such as quantification of allele-specific expression. We used the ExBP-RT technique to measure the mRNA levels of all seven KRAS mutations at codon 12 and 13 in primary tumour tissue samples of 571 patients with colorectal cancer (CRC). Survival data was analysed to determine the prognostic potential of this novel mRNA-based biomarker. A high level of mutated KRAS mRNA was associated with an inferior 5-year diseasespecific survival (DSS). This association was highly significant, but only in left-sided CRC (P < 0.001). Thus, the mRNA level of the mutated KRAS allele in primary tumour tissue was found to be highly prognostic in left-sided CRC, but not in right-sided disease. To study the RNA expression of BRAF mutations as a diagnostic marker in thyroid cancer (TC), we analysed 62 formalin fixed paraffin embedded (FFPE) samples from TC patients. We detected BRAF V600E mutations at the mRNA level in 56,3% (18/32) and on the DNA level in 40,6% (13/32) of thyroid cancer patients, which is in concordance with the reported prevalence of these mutations. In order to evaluate whether sensitive detection of KRAS and BRAF mutations in mRNA could serve as a biomarker for early detection of malignant transformation in patients at risk of developing colorectal cancer, we analysed esophageal atresia (EA) patient cohorts. The ExBP-RT technique was used to evaluate tissue expression of KRAS and BRAF mutations in endoscopic biopsies from 61 adults, who had been surgically treated for EA in infancy. Despite the presence of histological findings indicating an increased risk of developing cancer, we found no detectable tissue expression of KRAS or BRAF mutations in this cohort. In conclusion, we successfully established a novel technique – ExBP-RT to detect KRAS and BRAF mutations at the mRNA level with very high sensitivity and selectivity. We found a strong association between the tumour tissue expression of KRAS mutations and prognosis in left-sided, stage III CRC. We also successfully detected and quantified the level of BRAF V600E mRNA in FFPE tissue from thyroid cancer. We could not, however, detect neither KRAS nor BRAF mutations in either of the cohorts of EA patients representing potential pre-malignant conditions.
  • Leden, Laura (Helsingin yliopisto, 2021)
    This interdisciplinary thesis is the first more comprehensive study of girls’ book translations in Sweden and Finland. The study examines adaptation of the image of girlhood in girls’ books translated from English to Swedish and Finnish between 1945–1965. Girls’ literature and girls’ books are children’s literary genres about girlhood, about girls’ lives and what it means to be a girl in a certain historical context. Girlhood is depicted in relation to norms for how girls are expected to behave, which means that the girl protagonists often both confirm norms by adapting to the expectations of society and rebelliously challenge these norms. Translations of girls’ books are influenced by norms of girlhood, narrative norms, and translations norms. These result in adaptation, a translations practice where translations are adapted to the norms of the target context (the target culture and the publisher) and to the target audience, in this case young girls. The frame of reference is the polysystem theory, according to which all genres and literary works belong to the literary polysystem, a network of partly overlapping systems in which tensions arise between the center with higher prestige and the periphery with lower prestige. The objective of this study has been to analyze how the peripheral position of girls’ literature within the general literary polysystem and the internal relations between the center (Bildungsromane with higher status) and the periphery (series books with lower status) within the girls’ literary polysystem influences the amount and type of adaptation in girls’ books. The ways in which this peripheral position impacts the image of girlhood in the books is also examined. A further aim has been to analyze whether the Finnish girls’ book system has been influenced by the Swedish system due to Finland’s peripheral position in the Nordic translation system. The qualitative material consists of three Bildungsromane by L. M. Montgomery, Jean Webster, and Laura Ingalls Wilder, and three series books by Helen D. Boylston, Carolyn Keene (a pseudonym), and Helen Wells, as well as their Swedish and Finnish translations. These books represent the series that, according to my initial quantitative survey, were the most prominent among the girls’ books published in both Swedish and Finnish in 1945–1965 (52 books). To contextualize the material, a paratextual analysis of publisher correspondence and the covers and cover texts of the translations has been conducted. The analysis shows that the Nordic countries were a uniform system with Sweden and Norway at its center, as books and series came to Finland via these countries, and Swedish and Norwegian translations were used as source texts for three of the Finnish translations in my study. This interdisciplinary study has three methodological starting points for the analysis of the effects of adaptation on the image of girlhood. The primary descriptive translation studies method consists of a comparative and categorizing adaptation analysis, my linguistic method involves an analysis of semantic-pragmatic features and pragmatic language functions, and my literature studies method is a narrative analysis of character indictors in relation to gender stereotype schemata for masculine and feminine narration, which represent norm-confirming and norm-breaking narration. The results demonstrate that both target-oriented abridged translations and source-oriented faithful translations appear in both the Bildungsromane and series book material. Thus, the amount of adaptation does not correlate with the polysystemic position of the translation. This indicates that the polysystem hypothesis that translations with a peripheral status are likely to be target-oriented is not supported within the girls’ book genre. Instead, adaptation occurs according to commercial, didactic, and pedagogical norms regardless of the polysytemic position. In the adapted translations, the image of girlhood is influenced by downplaying of character traits associated with norm-breaking girlhood, and by an increase of plot-oriented narration, which is the norm within children’s literature.
  • Murtoniemi, Katja (Helsingin yliopisto, 2021)
    Pre-eclampsia is a placenta-driven pregnancy complication causing systemic inflammation and endothelial dysfunction. It is characterised by increased blood pressure and proteinuria and affects vital organs of the body. Therefore, without surveillance and treatment it threatens the health and life of the mother and the foetus. Every year approximately 70,000 mothers die due to pre-eclampsia and its complications globally. There is still no cure for pre-eclampsia other than delivery. The aim of this thesis was to investigate associations of biomarkers to pre-eclampsia, and to find better ways to predict the disease and its subtypes, and accordingly to also increase the understanding of the mechanisms and pathways of the pathophysiology of pre-eclampsia, which eventually may lead to innovations of new therapeutic targets. This thesis includes data from the multidisciplinary PREDO (Prediction and prevention of pre-eclampsia and fetal growth restriction) project, which consists of 988 pregnant women with and 117 without known risk factors for pre-eclampsia. These women were recruited between September 2005 and December 2009 in ten maternity clinics in Finland. The usefulness of serum hyperglycosylated human chorionic gonadotropin (hCG-h) or the proportion of hCG-h to hCG (%hCG-h) was assessed for the prediction of pre-eclampsia in the first trimester (Study I). These were combined with maternal risk factors, known biomarkers (placental growth factor (PlGF), free human chorionic gonadotropin beta (hCGβ) and pregnancy-associated plasma protein A (PAPP-A)), and biophysical measurements (mean arterial pressure and mean uterine artery pulsatility index). The study was conducted in a subcohort of 257 women with known risk factors for pre-eclampsia. We found that prior pre-eclampsia and low serum %hCG-h were associated with late-onset and non-severe pre-eclampsia, whereas low serum PlGF was associated with early-onset and severe pre-eclampsia. Free hCGβ was higher in women who developed severe pre-eclampsia than in women who did not develop severe pre-eclampsia, whereas low serum PAPP-A was associated with non-severe pre-eclampsia. Multivariate models constructed with regularised logistic regression provided only modest prediction rates for all pre-eclampsia (36% sensitivity with 90% specificity) and its subtypes (20% sensitivity for early-onset pre-eclampsia and 32% sensitivity for late-onset pre-eclampsia with 90% specificity). The effect of low-dose aspirin (100mg/d) on maternal serum concentrations of PlGF during pregnancy from the first trimester to the late second trimester was investigated (Study II). Blood samples were collected at 12–14, 18–20 and 26–28 weeks of gestation. The main finding was that high-risk women who had low-dose aspirin treatment (N=61) started before 14 weeks of gestation for prevention of pre-eclampsia had higher concentrations of serum PlGF than high-risk women who had placebo treatment (N=62). The difference was evident from mid-gestation onwards. We investigated the differences of haemoglobin scavenger proteins haemopexin (Hpx) and alfa-1-microglobulin (A1M) in high risk women and low risk women at 26–28 weeks of gestation (Study III). It was a case–control study with high-risk women who subsequently developed pre-eclampsia (n=42), high-risk women who did not develop pre-eclampsia (n=49) and low-risk women (n=51). We found higher plasma Hpx concentration in high risk women, who developed pre-eclampsia compared to low risk women. Plasma A1M was higher in the group of high-risk women, who did not develop pre-eclampsia than in other groups. We investigated the changes in maternal plasma Hpx and A1M concentrations from the first trimester to late second trimester (blood sampling at 12–14, 18–20 and 26–28 weeks of gestation) (Study IV). We used the same study cohort than in the third study. It appeared that high-risk women, who did not develop pre-eclampsia had a unique profile of haemoglobin scavenger proteins during pregnancy. Firstly, unlike in other groups, plasma Hpx concentration did not change during the study period, and it was lower during the first half of the pregnancy than in other groups. Secondly, the A1M concentration increased during the first half of the pregnancy and stayed at the higher level compared to the other two study groups. During the first half of the pregnancy the change in A1M concentration in high-risk women who did not develop pre-eclampsia was opposite to the change seen in those women who developed pre-eclampsia, while there was no change of plasma A1M concentration in low-risk women. We also found that women who subsequently developed pre-eclampsia and gave birth to a small-for-gestational-age newborn had consistently higher plasma levels of A1M than women who developed pre-eclampsia and gave birth to an appropriate-for-gestational-age newborn. The difference was significant from mid-gestation onwards. In conclusion, the serum PlGF concentration of women who started low dose aspirin before 14 weeks of gestation was higher from mid-gestation onwards compared to the other groups. This may provide one mechanism by which low-dose aspirin prevents pre-eclampsia. This thesis sheds light on the serum haemoglobin scavenger protein dynamics during the first and second trimester of pregnancy in women who have low or high risk for pre-eclampsia, as it was found that higher plasma concentrations of A1M in high-risk women, who do not develop pre-eclampsia may be associated with a reduced risk of developing pre-eclampsia. Furthermore, high-risk women who do not develop pre-eclampsia may have unique, protective dynamics of serum haemoglobin scavenger proteins. These findings suggest that not only clarification of the pathophysiology of pre-eclampsia, but also protective factors should be a focus of future research. Additionally, it was shown that the change in plasma A1M concentration in women who subsequently develop pre-eclampsia may be inversely related with foetal growth from mid-gestation onwards until the late second trimester. Multivariate models constructed with regularised logistic regression provided only modest prediction rates for all pre-eclampsia and its subtypes. This thesis strengthens the theory that pre-eclampsia is a complex multi-factorial syndrome, in which many biochemical pathways are affected.
  • Koivuhovi, Satu (Helsingin yliopisto, 2021)
    The purpose of this dissertation was to examine whether studying in a selective class with a special emphasis influences children’s competence beliefs or mathematical thinking skills. The original idea was to explore empirically the commonly held assumption that studying in a class with a special emphasis improves motivation. This dissertation consists of four original empirical studies, all of which examined the research question from several perspectives. In this summary section, these perspectives were summarized into four research questions. The first overall aim was to examine how children’s competence beliefs and mathematical thinking skills develop during the comprehensive school years. The second overall aim was to examine, how pupils who study in classes with a special emphasis differ from pupils who study in classes without a special emphasis in terms of background factors. The third overall aim, focused on the differences between classes with and without a special emphasis in the development of competence beliefs and mathematical thinking skills. Finally, the last overall aim explored more specific peer effects (i.e., the Big-Fish-Little-Pond effect, the Reflected Glory effect and the Peer Spillover effect) related to selective classes and explored whether these effects were visible in the Finnish context. The data were drawn from a longitudinal learning-to-learn study in which the cognitive capabilities and motivational beliefs of 744 first graders were assessed and followed up throughout the comprehensive school years. Data consisted of several measurement points and tasks. The original sample size was increased during the follow up as children changed schools and new schools and classes were added to the sample. For the purpose of this thesis, data drawn predominantly from grades four to six (n=1025) and from seven to nine (n=2339) were used. Data were analyzed with statistical methods including single and multilevel structural equation models as well as repeated measures and analyses of variance. The first finding from this thesis considered the overall development of children’s competence beliefs and mathematical thinking skills and supported findings of prior research showing a decline in positive self-beliefs during the school years. Decline in the competence beliefs was detected at both primary school and lower secondary school but the trajectories of different belief types varied. Children’s mathematical thinking skills progressed, as expected, during the followed-up years. Additionally, the second finding from this thesis confirmed findings of prior research and showed that classes with a special emphasis clearly differed from classes without a special emphasis in terms of pupils’ background. Children who studied in classes with a special emphasis came from more highly educated families and had a higher grade point average (GPA) than pupils who studied in classes without a special emphasis. There were also detailed differences between classes with a special emphasis in terms of pupils’ background. The main results from this study considered the development of competence beliefs and mathematical thinking skills between classes with and without a special emphasis and showed interestingly, that there were no differences in the development. Even though pupils differed from each other initially due to the selective process of classes with a special emphasis, most of the differences in the development of competence beliefs and mathematical thinking skills were explained by these initial differences and the development was similar in different types of class after the background variables had been considered. Therefore, the results from this thesis gave no evidence of the assumed beneficial effects of emphasized teaching. On the contrary, findings regarding the peer effects explored showed that the Big-Fish-Little-Pond effect was visible in the Finnish context whereas other peer effects were not. In other words, the results showed that the average achievement level of class predicted individual pupil’s academic self-concept negatively. Therefore, these findings suggested that instead of the assumed beneficial motivational effects, studying in a highly selective class may have detrimental effects on individual pupil’s self-beliefs. ________________________________________ Keywords: Classes with a special emphasis, selective classes, competence beliefs, action-control-beliefs, academic self-concept, mathematical thinking skills, longitudinal study, class composition, Big-Fish-Little-Pond
  • Rouhikoski, Anu (Helsingin yliopisto, 2021)
    This dissertation examines the variation of directives (in the broad sense, including all kinds of control acts) in Finnish service encounters. Directives can be manifested as various grammatical constructions, e.g. imperative, interrogative, or a zero-person clause. The study is based on three major research questions: 1) Which contexts of use are typical for each grammatical construction? 2) Which factors contribute to the choice of a directive construction? 3) How can the variation of directives be studied from a sociolinguistic point of view? The data consist of 11.5 hours of video-taped service encounters in Finnish Social Insurance Institution (Kela) offices, 131 encounters in total. Focus lies on the employees' directives to their clients: 670 tokens of request, instructions, or advice. While the theoretical framework is interactional sociolinguistics, also conversation analysis is employed in the fine-grained analysis of the ongoing interaction. The analysis shows that each directive construction has a typical environment of use. Imperatives are usually found when the directed action is straightforward and unproblematic. Furthermore, they are often responsive to something that the client has said or inquired earlier. Zero person + modal verb constructions, in turn, are used in more contingent contexts. They typically involve disalignment, imposition, or an action that is previously undiscussed and therefore unprojectable. Once the variation in the local, interactional level has been examined, the analysis shifts to the macro-level, discussing the variation in relation to the macro-level sociolinguistic variables (e.g. age and gender). This analysis reveals some novel correlations: the use of imperative decreases while the client's age increases. 2nd person modal verb phrases, in turn, are mostly directed to the youngest clients who, based on the data, may not yet have very much practice in managing their social insurance matters. Therefore the employees have to highlight the client's own activity and involvement. Both local, situational factors (such as projectability and contingencies) and long-term, macro-level factors (e.g. age) prove to be meaningful in explaining the variation of directive constructions. As it turns out, the long-term factors are often intertwined with situational factors – for instance, the client's high age may indicate more contingencies with granting the directive. The dissertation provides new insights into the use of grammatical constructions as directives in Finnish. It brings together the sociolinguistic and the conversation-analytic perspectives by showing how the macro-level sociolinguistic variables can be integrated into the analysis of interaction. It also suggests that sociolinguistic factors have an impact on variation in the pragmatic level and broadens the scope of sociolinguistics towards syntactic and pragmatic variation.
  • Särkelä, Elina (Helsingin yliopisto, 2021)
    This dissertation is a qualitative study consisting of four sub-studies and this summary part. The task of my research is to describe and interpret life and future of the “global generation” in the light of qualitative materials produced by 14–19 year old young people, and to consider the development of school and especially geography teaching from the perspective of these materials. The aim of the study is to bring qualitative information about young people’s life and thoughts and about the use of the method of empathy-based stories and photography in geography teaching into the discussions about education. The research task is specified by the following research questions: 1a. How do young people describe the state and future of the world in their empathy-based stories? 1b. What do the issues raised by young people in their empathy-based stories mean for school and geography teaching? 2a. What picture of the global generation is based on empathy-based stories written by young people, photographs taken by young people and young people’s reflections on the Global South? 2b. How can the issues raised by young people in the materials they produced be considered in schools and in geography teaching? 3. What opportunities do the method of empathy-based stories and photography offer for geography teaching? The research was conducted from 2013 to 2020, in the context of geography teaching. The data used in the study were produced by young people born between 1995 and 2004 and living in the Helsinki Metropolitan Area (N = 169). At the time of the study, the participants were 14–19-year-old secondary and upper secondary school students. The material used in the study consisted of empathy-based stories (N = 110), photographs (N = 160) and their written interpretations (N = 160), written reflection tasks (N = 19), written evaluations of the use of photographs (N = 11) and writings on photography as a method (N = 20). In sub-studies 1 and 2, the material was produced by using the method of empathy-based stories that was developed by Antti Eskola (1988). In the first sub-study, young people were asked to empathize with utopia or dystopia and in the second sub-study, they were asked to reflect on the state of the world from an upper secondary school student’s point of view. The third sub-study was conducted in the context of global education as a part of geography and visual arts teaching. Young people were asked to photograph their lives and write interpretations of the photographs they took. In addition, participants wrote about their assumptions about the Global South, reflected on their assumptions using the photos they took and assessed whether the use of the photos supported this. In the fourth sub-study young people were asked to photograph inequality and write interpretations of the photographs they took, as well as write about photography as a process. When interpreting the meanings of photographs, the aim was to capture the meanings young people gave to the photographs they took – such as in photo-elicitation interviews in which participants’ interpretations are central and present to guide the researcher’s interpretations (Leonard & McKnight 2015; Pyyry, Hilander & Tani 2021). When analysing the empathy-based stories, the frame stories guided the formation of the first themes, and the analysis proceeded to form new themes from the data. The materials were analysed using qualitative content analysis and thematic analysis (Braun & Clarke 2006; Eskola 2001). In sub-study 1, thematic analysis was followed by constructing two different but typical stories from the material. Empathy-based stories written by young people were dominated by climate change and other people-caused risks. The world in which environmental problems, conflicts and individualism are present, and its dystopian future, were easier to imagine than a world in which everything is fine. Empathy-based stories made visible the risk awareness of young people and reflected the uncertainty and insecurity that shades the life of the global generation. The young people’s descriptions about risk society can work as a starting point for dialogue between the everyday geography of young people and the school geography. This could clarify the connections between different things, local and global, and support young people in managing uncertainty. Young people also wrote about different coping strategies, several of which were related to it how individuals can act. Related to this, they wondered if even adults know what is happening in the world. Among the despair young people also found hope. The hope was connected especially to their own generation, which respects other people and the environment. However, the role of hope was fragile, and action was not always connected to the notions about grievance. Therefore, it is important in geography teaching to build the hope and reflect the opportunities to take action. In this, the importance of cooperation should be empathized, as global problems cannot be solved individually. Based on the materials produced by the young people, the picture was drawn of the global generation, its life, and the future. The young people valued their identity, friends and family. School was important to some of them, but also a place where it was not possible for everyone to be themselves. The results show the importance of the assumption of the diversity of young people’s identities in all school activities. For young people it was obvious that people are equal, but they recognized that their generation’s starting points for life differ both near and far, and how they also have privileges. Young people’s assumptions about the Global South were partly stereotypical, but because this was recognized, it opens the opportunity to reflect to them and to deconstruct them. Based on the results, reflecting on one’s own assumptions and preconceptions is important in geography teaching, such as when studying issues related to different areas. The method of empathy-based stories proved to be a teaching method that makes it possible to spark the use of the imagination. The method enabled utopias that could be interpreted as ordinary, as well utopias for which realization does not seem possible so far, but within which the power of change may lie. In geography teaching, the method of empathy-based stories could be used when studying the opportunities to build a sustainable future. Photography directed young people’s gaze towards visually achievable things, but also made them reflect on the complexity of inequality. The photographs were personal and showed the diversity of young people’s appreciations. However, photography did not prove to be a shortcut to reach young people’s personal experiences. Some young people felt that the use of photographs made it easier to reflect on their own assumptions about the Global South, but it was not seen as a prerequisite for criticality. With the help of the method of empathy-based stories and photography in geography teaching, it was possible to build a dialogue between the young people’s lifeworld, everyday geographies and the academic geography of schools. The results of the study are not generalizable, but they provide insights into the debate on geography teaching and school. Keywords: everyday geographies, geography teaching, global generation, lifeworld, method of empathy-based stories, photography, risk society
  • Hiltunen, Riikka (Helsingin yliopisto, 2021)
    This thesis is about awareness of change in music, as well as future-oriented thinking, and their role in the creative actions and rationales of pop songwriters. My aim is to build an understanding of foresightfulness in the context of creating pop music. I analyse the ways in which pop songwriters relate to changes in music and music trends, and their attempts to foresee alternative musical futures or to influence them. In addition, I investigate the conceptions, values and beliefs of pop songwriters that relate to trend-spotting and future-oriented thinking. The research materials for the study consist of eight (8) interviews with Finnish professional songwriters in the field of pop music as well as three (3) field observations and the related documentation of songwriting sessions at international songwriting camps known as Song Castle and A-Pop Castle in 2015, 2017 and 2018. The resulting ethnographic research data are subjected to directed content analysis. The concepts directing the analysis derive from futures studies: foresight, future consciousness and attitudes towards the future, as well as from sociological concepts applied in studies of popular music, such as space of possibilities. On the theoretical level my study is built on systematic or confluential approaches to creativity. I investigate the creation of pop music as a psychological, social and cultural action, and domain-specific future consciousness as a component of creativity. More specifically, I bring popular music studies, futures studies and creativity studies together in the context of songwriting, examining foresightfulness as an ability, attitude or action that enhances or restricts creativity and thereby broadening current understanding of the concept. From this perspective, my study contributes to dismantling the opposition between creativity and commerce. My main finding is to show the significant role of future-oriented thinking and foresightfulness in pop songwriting, aspects that are scarcely recognised and explicated by the writers. The “targets” of foresight range from other songwriters and artists to expectations of the audience and of gatekeepers. Music trends are observed individually, but knowledge about them is shared with colleagues, and in this way emerging trends are strengthened collectively. Foreseeing and influencing the future are often inseparable. I also demonstrate how several contradictory conceptions, beliefs and values relate to, or influence foresightfulness among songwriters: their thoughts about the dynamics of change in music, audience expectations, individual abilities and being a songwriter, as well as being a pioneer or maintaining autonomy and honesty. The songwriters struggled with foresight, not least because of the new modes of consumption and fragmentism in musical trends. Some of them felt as if they were losing honesty in their creative process in attempting to follow trends, whereas for others, following and anticipating trends inspired them in their work.
  • Rico del Cerro, Daniel (Helsingin yliopisto, 2021)
    The overall aim of this thesis is to understand the chemistry of different types of ionic liquids (ILs) and their application in cellulose processing, as well as in the chemical analyses of pulp. ILs are applied either on their own or as electrolytes with dimethyl sulfoxide (DMSO) or gamma valerolactone (GVL) as co-solvents. All of the ILs utilised in this work were synthesised in our laboratory via Menshutkin reaction followed by metathesis to different counter anions or via acid-base chemistry. The beginning of our work focused on the investigation of the C2 chemistry of imidazolium ionic liquids (IMILs), one of the first class of ionic liquids utilised in biomass processing, resulting in the understanding of the C2 chemistry of IMILs under neutral and acidic conditions, which complete the comprehension on the mechanistic scenario of the C2 chemistry of IMILs. In this investigation, the importance of the quality of the ILs is remarked. The studies continued to investigate the activation of the chemical reactivity of pulps using tetrabutylphosphonium acetate ([P4444][OAc]), a more thermal stable ionic liquid. The non-dissolving pre-treatment of pulps by [P4444][OAc] demonstrated a reduction in the crystallinity of the pulp to be directly related to its chemical reactivity enhancement. Additionally, [P4444][OAc]:d6-DMSO (20:80 wt.%) was also investigated in both the regioselectivity studies of acetylation reactions and the oxidised nanocellulose nuclear magnetic resonance (NMR) analyses. Quantitative heteronuclear single quantum correlation (HSQC) NMR was a suitable experiment for the quantitation of the oxidation level achieved in the nanocellulose, demonstrating the potential of this method for cellulose analyses. Finally, the research concluded with the studies on other cellulose solvent systems, such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with dimethylsulphoxide (DMSO), which resulted on the discovery of the unexpected reactivity of 1,1,3,3-tetramethylguanidinium acetate ([TMG][OAc]). Furthermore, this investigation led us to the design and synthesis of a novel task-specific ionic liquid (TSIL), so called ‘TMG2SA’. This IL was investigated with regard to cellulose chemical modification, resulting in the high yield production of nanocellulose-type materials by a low demanding energy step, with a different approach than previously reported.
  • Berg, Mika (Helsingin yliopisto, 2021)
    The metabolic disorder type 2 diabetes characterized by insulin resistance and a reduced production of insulin is one of the fastest growing health and economic menaces for the society. Although, the increasing number of individuals suffering from type 2 diabetes and insulin resistance may have different diabetic characteristics and therefore a risk of severe diabetic complications such as diabetic kidney disease, most individuals still undergo the same forms of treatment and medication. Usually, the first line therapy option is the drug metformin. However, the use of metformin is contraindicated in many cases especially when kidney function declines. Apart from metformin the only insulin sensitizer available on the market is pioglitazone but its risks involving cardiovascular effects are highly debated. More recently, several alternative drugs with different drug targets have been introduced. However, they may possess poor efficiency or safety or are expensive. Consequently, new alternative and more individualized forms of treatment are desperately needed. The SH2-domain containing inositol 5´-phosphatase 2 (SHIP2) is a little studied target for the treatment of type 2 diabetes and insulin resistance. The study presented in this thesis mainly focuses on the design and synthesis of novel blood glucose lowering agents that potentially act as SHIP2 inhibitors and insulin sensitizers. In an in silico screening a group of compounds that bind to SHIP2 were found and were biologically validated in vitro by showing their inhibition of SHIP2. Interestingly, one of the compounds was the most widely used anti-diabetic drug metformin. Additionally, completely novel compounds that significantly inhibited SHIP2 were found. Based on these findings two sets of sulfonanilides were designed and synthesized and their biological efficacy was validated by a functionalized glucose uptake assay. Our best candidates were non-toxic and increased the glucose uptake into cells at lower concentrations than metformin. This indicates that our sulfonanilides can lower the blood glucose levels. We also provide insights into the protein-ligand interactions that may have some impact for future SHIP2 drug design. Large molecular libraries around the most promising candidate from the screening were designed and synthesized. In these sets of 181 molecules many compounds significantly increased the glucose uptake into cells. The druglike properties and in vitro efficacy of the top six compounds were investigated more closely. All compounds were non-toxic and soluble at the effective concentrations. However, some additional modifications and improvements are needed to optimize the metabolic stability of these compounds. Our aim in the future is also to show that these compounds protect podocytes from apoptosis which is an important factor considering the severe diabetic complication, diabetic kidney disease. In view of a huge unmet medical need, we aim to patent the specific new chemical entities after optimization of the metabolic stability properties. Our findings confirm that SHIP2 is an interesting alternative target that may be used for designing novel treatments for type 2 diabetes and insulin resistance. In addition, we have also shown the potential of our compounds for increasing the glucose uptake into cells thus lowering the blood glucose levels.
  • Vulovic, Marina (Helsingin yliopisto, 2021)
    This thesis examines Serbia’s changing approach to dealing with the Kosovo question since 2012. The claim of Serbia that Kosovo is an indivisible part of its territory has been anchored in the institutional framework of the country ever since the Kosovo war (1998-1999). Serbia’s attachment to Kosovo is not only an institutional matter, but is also woven into the cultural fabric of the Serbian political collective. It resonates with the Kosovo myth, the main element of which is the physical and symbolic claim to Kosovo. Since Kosovo declared its independence in 2008, countering Serbia’s claim to Kosovo, the Serbian Government has struggled to accommodate this state of affairs with its EU integration process guided by the incentive of the Brussels dialogue for normalizing relations between the two entities. I study the Brussels dialogue between Serbia and Kosovo as a dynamic process of contestation of meaning. It is conceptualized as a contact zone that both enables and constrains the re-articulations of the constitutive Other, either as an enemy (through antagonism) or as an adversary (through agonism). The thesis particularly inquires how the Serbian Government led by the Serbian Progressive Party (SNS) since 2012 has re-articulated Kosovo within the Brussels dialogue. It locates two central moments in this process: adopting the Brussels agreement in 2013, and re-introducing the idea of partitioning Kosovo along ethnic lines as a solution to the Kosovo-Serbia dispute in 2018, both of which are understood as myths. The theoretical and methodological contribution of the thesis lies in the re-conceptualization of “myth”. While existing studies of myth in the context of Kosovo-Serbia relations have been focusing on the Kosovo myth, this thesis considers the Kosovo myth as a sedimented discourse, guided by a discourse theoretical lens. This discourse has turned into a social imaginary in Serbia, a horizon of meaning that defines and constrains what is said, felt, and otherwise practiced concerning Kosovo. The social imaginary structures the “Kosovo is Serbia” discourse based on Serbia’s physical and symbolic claim to Kosovo, which is deeply rooted in the political and cultural life in Serbia. In 2018, it was re-articulated into the idea of partition for Serbia to retain its claim to Kosovo. Making a claim to only a portion of the territory, Northern Kosovo, the partition leaves outside of contestation the “mythologically” laden central and Southern Kosovo where the sites that embody the Kosovo myth, the Serbian medieval monasteries, are located. A deconstructive reading of the Kosovo myth developed in this thesis reveals that the main discursive element that connects the Kosovo myth, the Kosovo social imaginary, and the idea of partition is territoriality. The thesis argues for a distinction between an ontological and empirical dimension of myths. As an ontological concept, myth specifically relates to an attempt to repair a dislocated discourse and potentially embodies an alternative political project that promises to fix what is broken. As such, myths do not only relate to past events, such as most of the scholarship on national myths would conceptualize it, but also to anchoring future but not yet realized political projects. Hence, the category of myth in this thesis is reserved for the Brussels agreement, and the idea of partition, since both emerged from dislocations as means to repair them. Developing a novel approach, the thesis highlights specifically temporal, material and affective dimensions of myth for discourse-theoretically inspired scholarly discussions to stress the necessity of myths for meaning-making. Myths are generated whenever we attempt to escape the constraints of a dislocated discourse by imagining alternative orders. Empirically, the thesis examines how the “Kosovo is Serbia” discourse becomes dislocated through Kosovo’s declaration of independence and is “repaired” by the two myths that resulted from the Brussels dialogue. Hence, this thesis also makes an empirical contribution to the field of Southeast European studies, by introducing a discourse-theoretical, performative/material, and affective dimension in mythmaking. Apart from operationalizing the elaborate theoretical framework I developed, the empirical aim of the thesis was to demonstrate that even the most entrenched discourses, such as the “Kosovo is Serbia” discourse, are not resistant to change under the right circumstances. In the empirical analysis, the thesis focuses on the various representations of Kosovo in Serbian political discourse and draws attention to the re-articulation of political frontiers. It argues that the main transformation relates to the question of who constitutes the political “us” and “them”, recognizing a clear shift from the agonistic discourse in 2013 (which emphasizes the “sharing” of Kosovo with Kosovo Albanians) to an antagonistic discourse in 2018 (which emphasizes a total separation between the two ethnic groups as the only solution). In this analysis, two central nodal points emerge: “territory” and “the people”. The thesis demonstrates how these elements have been reconstituted over time and how this process enabled the deepening of the divide between Serbia and Kosovo, which could have implications for the Brussels dialogue and for Serbia-Kosovo relations more broadly..
  • Kudinov, Andrei (Helsingin yliopisto, 2021)
    Implementation of genomic evaluation is challenging for populations with limited data. The main objective of this thesis was to identify an approach to implement single-step genomic best linear unbiased prediction (ssGBLUP) in a small-scale dairy cattle population. In particular, the aims were to predict GEBVs by ssGBLUP using local genotypes, enhance the reliability of prediction by incorporating data from an external breeding population, and implement the metafounder approach. The first objective of this study was to develop state-of-the-art BLUP Animal Model for Holstein (HOL) and Russian Black & White cattle of Leningrad region (LR, Russia). The traits of focus were milk, fat, and protein yield. The data used to develop the first (FLM) and multiple (MLM) lactation models included 320,633 repeated 305d records from 49 herds. The heritability estimates for milk, fat, and protein yield were 0.24, 0.20, and 0.20 for FLM and 0.18, 0.19, and 0.18 for MLM. For cows born between 2000 and 2016, MLM estimated an annual average genetic gain of 56 kg, 1.84 kg, and 1.62 kg for milk, fat, and protein yield, respectively. The second objective was to implement ssGBLUP for LR using a set of local genotyped animals. Genomic data were available from 1080 cows and 427 bulls. MLM was improved by adding a herd by sire interaction random effect. Milk yield cross-validation analysis showed a validation reliability (R^2) of 0.21 and 0.38 for bulls and cows, respectively. The R^2 values for fat yield for bulls and cows were 0.17 and 0.41. The third objective was to enhance the LR ssGBLUP prediction by using external DFS (Denmark, Finland, and Sweden) HOL genomic and pedigree information. The inclusion of DFS genotypes did not change the milk yield R^2 for bulls but slightly decreased it for cows (0.38 to 0.36). For fat yield, R^2 increased from 0.17 to 0.18 for bulls and decreased from 0.41 to 0.34 for cows. In analysis of milk yield, the highest R^2 was realized in the ssGBLUP model simultaneously using genomic and phenotypic data from both LR and DFS: 0.30 for bulls and 0.42 for cows. In fat yield, no improvement in R^2 was observed (0.18) for bulls and an unexpected decrease was observed for cows (0.21). The fourth objective was to implement the metafounder (MF) approach in ssGBLUP. The data were a subset of Finnish Red dairy cattle, including 112,479 cows with first lactation 305d milk records. Genomic data were obtained from 3,571 bulls and 16,186 cows. MF covariance matrix (Γ) was created using base population allele frequencies estimated using a one-generation pedigree for each animal. After the estimation, markers were filtered with a minor allele frequency criterion of 0.05. Diagonal elements of the genomic relationship matrix had a lower correlation with the regular pedigree relationship matrix (A; 0.66) than with the one using Γ (A^Γ; 0.76). Validation reliability of milk GEBVs in bulls increased by 0.04 (from 0.27 to 0.31) when using the MF approach. In cows the gain was 0.01 (from 0.36 to 0.37).
  • Markkanen, Helene (Helsingin yliopisto, 2021)
    The measurement of serum growth hormone (GH) is the cornerstone of the diagnosis and management of GH-related disorders, acromegaly, and GH deficiency (GHD). GH secretion from the anterior pituitary gland is pulsatile and influenced by several factors (e.g. exercise, stress, glucose). Therefore, the GH result of a single blood sample is not diagnostic. Thus, the diagnosis is based on the suppression and stimulation tests of pituitary GH secretion. GH measurement is challenging due to the heterogenous structure and binding proteins of GH. The first assays for GH were based on radioimmunoassay (RIA) using polyclonal antibodies. The old International Standard (IS) reference preparations for GH assay calibration were of pituitary origin and contained a pooled cadaver-derived mixture of GH isoforms. During the 1990s, a significant methodological change in serum GH assays occurred, when RIAs were gradually replaced by more specific sandwich assays with monoclonal antibodies and highly sensitive labels. The use of monoclonal antibodies and IS preparations containing different GH isoforms caused significant between-assay and between-laboratory variation of GH levels. During the 1990s, the standard of recombinant 22-kDa GH became available. At the beginning of the 2000s, the WHO IS 98/574 (22 kDa) was established. During the last 10 years, GH immunoassay manufacturers have adopted this new standard for calibration of GH assays. Together with monoclonal antibodies, this has resulted in a significant reduction of GH concentrations obtained by recent GH assays. The aim of this study was to evaluate the interlaboratory variation of different GH assays used in Finland between 1998 to 2003 on the basis of an external quality assessment round of GH. Moreover, we wanted to compare the clinical use of two automated GH assays, AutoDELFIA and Immulite 2000 assays (calibrated against the same standard), with old polyclonal RIA with older standardization. The utility of consensus cut-offs of the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) in clinical practice was also studied by using those two automated assays. At the beginning of this study, the clinical use of a new GHRH+ARG test was assessed in control subjects and GHD patients by using the AutoDELFIA GH assay. Later, the cut-offs for the GHRH+ARG test were evaluated by using the Immulite 2000 XPi GH assay, which is calibrated against the current WHO IS 98/574. Our results showed that the international cut-off values for GH in consensus statements and guidelines cannot be directly adopted in diagnostic use without a clinical validation of the particular GH assay in use. We also showed that male control subjects in the OGTT and GHRH+ARG test had significantly lower GH values than women, suggesting that gender-specific cut-offs are needed. In our study, the ITT was an unreliable test for GHD. Almost half of apparently healthy adults have peak GH values <3 μg/L, which is the cut-off for GHD recommended in the consensus statement of 2011. Our present Immulite 2000 XPi assay yielded sufficiently similar GH results as the former AutoDELFIA assay. Thus, awareness of the differences between GH assays is important. It is crucial to use the same GH assay in the follow up of each patient with acromegaly or GHD.
  • Salo, Juho (Helsingin yliopisto, 2021)
    Chest wall resection and reconstruction pose unique surgical challenges given the complex anatomy and important functional role of the chest wall and its protective function for vitally important organs. Yet, a paucity of literature has reported large patient series, likely attributable to the rarity of cases and the challenges posed by this complex surgical procedure. This thesis summarises a retrospective analysis of chest wall resections and reconstructions resulting from malignant disease. Here, the focus lies on the surgical technique, short-term outcomes, survival and quality of life amongst patients. Study I consists of a retrospective review of patients who underwent oncological chest wall resection and reconstruction from 1997 through 2015 in the Department of Plastic Surgery at Töölö Hospital (Helsinki, Finland). The primary indications for resections were breast cancer, soft-tissue sarcoma and bone or chondrosarcoma. Amongst these resections, 53% were full- and 47% were partial-thickness resections, primarily located anterolaterally. Clear histological margins were reached in 82% of the resections. Reconstruction of the chest wall was warranted in 87% of cases and with 48% of cases involving stabilisation with a concurrent soft-tissue flap. The remaining patients underwent either chest wall stabilisation or soft-tissue flap coverage. This coverage most commonly consisted of pedicled or local flaps. Free flaps were necessary in 21% of cases, and no flaps were lost. Amongst 135 patients, 29 (21%) experienced complications. The most common complications included pneumonia and partial flap loss. We observed a 0% mortality rate. With a 4-year median follow-up, the 5-year overall survival rate reached 70%. Study II describes our surgical technique for diaphragm and thoracoabdominal wall reconstruction following oncological resection, focusing here on surgical outcomes. The most common indication for surgery was sarcoma. A thoracoabdominal wall reconstruction was performed using mesh in 14 cases and 7 cases relied on mesh and a flap. A diaphragm reconstruction with a second mesh was warranted in 6 cases. In 15 cases, the diaphragm was reattached using an acceptable tension. Our method of thoracoabdominal wall and diaphragm reconstruction proved safe without abdominal wall hernias or paradoxical chest wall movement. Study III evaluated the short-term outcomes, survival and tumour recurrence following chest wall resection amongst 49 soft-tissue sarcoma patients. Amongst these, 63% were high-grade and 37% were low-grade tumours. Surgery required 19 full- and 30 partial-thickness chest wall resections. The resection margins were wide or marginal in 86% of cases. The chest wall was stabilised and covered with soft tissue in 13 patients, reconstructed with a flap in 11, stabilised in 13and closed primarily in 12. In total, 11 patients experienced complications. During follow-up, local recurrence developed in 8 patients and 9 patients developed metastasis. The 1-, 5- and 10-year survival rates were 93.8%, 76.0% and 71.6%, respectively. Recurrence-free rates were 84.4%, 70.7% and 70.7%, respectively. Positive prognostic factors consisted of being under 50 years old (p = 0.01), a wide margin (p = 0.02) and radical treatment (p = 0.04) consisting of either resection with a wide margin or a marginal resection combined with adjuvant radiotherapy. Patients undergoing nonradical treatment experienced a 3.1-fold reduction in survival compared to patients who underwent radical treatment (95% confidence interval [CI] 0.96–10.12; p = 0.06). Cross-sectional study IV aimed to assess the long-term health-related quality of life (HRQoL) following chest wall reconstruction after oncological resection. In total, 78 patients who underwent surgery between 1997 and 2015 were invited to complete the 15D and Core Quality of Life for Cancer questionnaire (QLQ-C30) HRQoL instruments. Altogether, 55 patients (71%) completed the questionnaires, a median 66 ([IQR] 38–141) months after surgery. Indications for surgery included soft-tissue sarcoma (n = 16), advanced breast cancer (n = 15), bone or chondrosarcoma (n =14) or other tumour (n = 10). Following chest wall resection and reconstruction, the mean 15D score (0.878, standard deviation [SD] ±0.111) was comparable to that amongst the age- and gender-standardised general population (0.891, SD ±0.041). Patients were statistically significantly worse off on the dimensions of ‘breathing’ and ‘usual activities’. The QLQ-C30 cancer-specific HRQoL was 72 (maximum 100) and scores for the QLQ-C30 functional scales ranged from 78 (physical) to 91 (social). Within specific reconstruction subgroups, no statistically significant differences in HRQoL were detected after analyses were adjusted. In conclusion, chest wall resection and reconstruction represents a safe therapeutic modality when accompanied by careful patient selection, appropriate perioperative and postoperative care and selection of the proper surgical technique both in sarcoma and advanced breast cancer patients. Resection with wide margins remains the primary aim for treatment of chest wall soft-tissue sarcoma patients. If wide margins are not achieved, treatment should be combined with adjuvant radiotherapy. In locally advanced breast cancer, surgical chest wall resection and reconstruction play a role in the treatment of these patients. Following chest wall reconstruction after tumour resection, patients’ HRQoL is comparable to that amongst the age- and gender-standardised general population.

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