Väitöskirjat

Recent Submissions

  • Rozov, Stanislav (Helsingin yliopisto, 2016)
    The histaminergic neurons of the hypothalamus in conjunction with hypocretinergic cells, monoaminergic nuclei of the brainstem and basal forebrain centers, constitute the ascending arousal system that plays a pivotal role in maintenance of wakefulness state. It has predominantly inhibitory reciprocal connections to their sleep-active counterparts, which enables an efficient transition between wakefulness and sleep. In combination with the circadian clock and homeostatic regulation of sleep its forms a network that regulate the sleep-wakefulness cycle. Because of the complex organization, it becomes difficult to estimate the significance of the crosstalk between the individual components of this regulatory network. Therefore, we focused on examination of interactions between the histaminergic system, the circadian and homeostatic components. We used electroencephalography in combination with behavioral analysis to quantify changes in spontaneous locomotion, wakefulness, non-rapid eye movement sleep and rapid eye movement sleep stages in response to an alterations of pacemaker rhythm. The shortening of the light-dark cycle led to re-distribution of these parameters towards aperiodicity, as well as increased sleep propensity, diminished daily rhythms of power of high θ-, and γ-waves, which are characteristic of an active wakefulness state as well as strengthened the phase-amplitude coupling between these frequencies. We used in vivo microdialysis in combination with sleep deprivation to understand the histaminergic regulation of homeostatic sleep propensity. During 6-hours of sleep deprivation, the histamine release was upregulated and comparable to its level during wakefulness, whereas when the sleep deprivation ceased, the release of histamine immediately dropped to the baseline level. To assess the effects of circadian regulation on histaminergic neurons, we estimated the daily changes of activities of the key enzymes involved in the histamine metabolism, histidine decarboxylase and histamine-N-methyltransferase as well as diurnal profile of histamine release. The 24-hour rhythms of production and release of histamine and its metabolite, 1-methylhistamine were detected, whereas activities of the enzymes had no detectable diurnal rhythm. Histamine release was highly positively correlated with changes in the power of the θ-frequency range. In order to understand the possible role of the histaminergic regulation of circadian system functioning we utilized mouse strains that constitutively lack histamine 1 and 3 receptors. The lack of histamine 1 receptor had no effects on the circadian rhythm of spontaneous locomotion, but the knockout of the histamine 3 receptor resulted in a substantial reduction of free-running activity rhythm amplitude. The expressions of the core clock genes, Per1, Per2 and Bmal1, in the suprachiasmatic nuclei of the hypothalamus, the cerebral cortex and the striatum were not affected in these knockout models. Based on the acquired results we concluded that the circadian process may affect homeostatic regulation, thus indicating an interaction of these processes. The circadian regulation of the histaminergic neurons takes place mainly at the level of histamine accumulation and release. In contrast, alterations in histamine-mediated signal transduction caused only minor alterations in examined circadian rhythms. Finally, we could not find evidence of an involvement of the histamine in homeostatic regulation of sleep-wakefulness cycle.
  • Vaahersalo, Jukka (Helsingin yliopisto, 2016)
    Aims The objectives of this study were to evaluate the incidence and neurological outcomes of out-of-hospital cardiac arrest (OHCA) patients in Finnish intensive care units (ICU). This study also investigated the use of therapeutic hypothermia (TH), arterial blood gas (ABG) pressures and different biomarkers association with one-year neurological outcome after OHCA. Materials and methods The FINNRESUSCI study was conducted in 21 out of 22 ICUs in Finland during a one-year study period. All adult patients after OHCA who were treated in ICU were included. Blood samples for biomarker evaluation were collected and neurological outcomes were determined 12 months after CA. All patients were included when evaluated the incidence, the implementation of TH and outcomes. In Study II, all ABG samples obtained from mechanically ventilated patients during the first 24h from ICU admission. In Study III and IV, biomarkers were measured from patients resuscitated from VF/VT. Main results FINNRESUSCI study included 548 patients, of whom 311 (56.8%) had shockable (VF/VT) and 237 (43.2%) non-shockable (PEA or asystole) as an initial rhythm. TH was induced totally in 311 unconscious patients 85.8% in VF/VT and 31.4% in PEA or asystole group. Good neurologic outcome was achieved in 58.0% patients with shockable rhythms and in 19.4% with non-shockable rhythms after TH treatment. The mean PaCO2 tension during the first 24-hour in ICU was an independent predictor of a good outcome with an odds ratio (OR) of 1.054, but the mean PaO2 tension was not. The time spent above PaCO2 45 mmHg was associated with good neurologic outcome and patients with the highest mean PaCO2 and PaO2 values had better neurologic outcome than predicted with an OR of 3.2 (95% CI 1.1-9.2). IL-6 and S-100B was associated with time to ROSC and poor neurological outcome (p less than 0.001). Admission IL-6 was associated with extra-cerebral organ dysfunction (p less than 0.001) and was an independent predictor of poor neurological outcome with an OR of 1.006 (95% CI 1.000-1.011). Hs-TnT levels were elevated in all of the patients, higher in patients with poor vs. good neurological outcome 739 vs. 334 ng/l (p=0.028), but there was no statistical difference in mortality. Conclusions TH is well implemented in clinical practice in Finnish ICUs. The majority of OHCA patients with shockable rhythms survive with good neurology, while the outcome of patients with non-shockable rhythms is poorer despite the TH treatment. There was no harmful association between hyperoxia and outcome, but instead mild hypercapnia combined with mild hyperoxia might be beneficial during the first 24 hours. IL-6 was associated with extra-cerebral organ dysfunction and predicted neurological outcome after OHCA-VF/VT, while hs-TnT does not give any additional prognostic information.
  • Kuhlefelt, Marina (Helsingin yliopisto, 2016)
    Smoking cessation and surgical planning decrease complications and compromised healing in patients undergoing orthognatic surgery Orthognatic surgery is surgery for the correction of discrepancies in the facial skeleton. The main aim of the thesis was to identify factors that increase complications and compromised healing in these patients. Medical records of orthognatic patients treated at the Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland were retrieved retrospectively for the first two studies. For the last two studies patients planned for bilateral sagittal split osteotomy (BSSO) were recruited at the Department before surgery and followed up for one year. The outcome variable in the first study was the removal of one symptomatic titanium miniplate, whereas in the second study it was a surgical site infection. The predictor variables were age, gender, smoking status, duration of operation, general diseases, dimensions of mandibular movement and osteosynthesis supporting material. The main outcome variable in the third study was neurosensory disturbance, whereas in the last study it was temporomandibular disorders at one year post-operative. The main predictor variable in the third study was the degree of manipulation of the mandibular nerve and in the last study TMD before surgery, evaluated by the Helkimo Dysfunction index. Explanatory variables age, gender, smoking status, mandibular advancement and duration of operation were also recorded for the statistical analyses. 19.0% of the inserted miniplates were removed in 153 BSSO patients. Plate-related reasons for removal were infection and screw-loosening. 9.1% of the patients (n= 286) in the second study had a surgical site infection. Smoking was the only significant predictor for infections or removal of osteosynthesis material. 90.2% BSSO patients (n= 41) reported altered sensations in the lower lip one year after surgery. The disturbance tended to increase the more the mandibular nerve was manipulated during surgery. Four patients had a visible nerve laceration and all of them experienced a major burden of the altered sensation. Two of these patients (4.9%) had neuropathic pain. Most patients were satisfied with the treatment, but the four patients with visible nerve lacerations were not. A substantial proportion (42.5%) of the patients in the last study had TMD as one of the reasons for seeking treatment. The TMD did not change after treatment in the majority of patients (60%), 30% improved and for 10% the situation impaired. The main finding was that smoking cessation will reduce infections and the need for removal of osteosynthesis material. Regarding neurosensory complications, the surgical technique does matter, and nerve manipulation and lacerations should be avoided at all costs. TMD symptoms improved for only 30% of patients undergoing BSSO. Thus BSSO is not a predictable treatment for TMD patients.
  • Sandberg, Erja (Helsingin yliopisto, 2016)
    ADHD in the family - The support provided by the educational, social and health sectors, and the experienced impact The aim of this study was to collect and describe the experiences of families with family members who have ADHD and are in need of support from different bodies such as educational, social and health services. The study also collected and described the co-operation between such bodies over the last six decades. With the assistance of netnography, the research data was collected in 2012 to 2014 from a social network group a nationwide ADHD peer support group. The material includes both questionnaires and interviews. The interviews were used to complement the results of the questionnaires. The main unit of analysis was the family (N = 208), and in each family, one or more members had been diagnosed with or showed symptoms of ADHD. The entire family was included in the study because ADHD affects more than just the individual him/herself. ADHD is often familial, and therefore some of the families in this study had over sixty years experience of ADHD, even though the definitions have changed over the years. Despite the increase in and specification of supportive services, the participants saw the different bodies as too bureaucratic, splintered and regionally differentiated. People showing symptoms of ADHD who had notable functional impairments were not able to find the supportive measures they needed and were not able to endure long wait times due to their worsening situation. Co-operation between the different bodies was seen as a necessity. In the research material, three out of five families described such co-operation as not being realised as it is meant to be according to the law. The difficult situations of the families were demonstrated in the research material in that every third family participating in this study included a socially excluded person or someone at risk of social exclusion. In general, a lack of education, fewer chances of finding a job and associated symptoms of ADHD all contributed to social exclusion. Becoming socially excluded is a long process and not a conscious choice. The participants stated that social exclusion is a vicious circle from which escape is difficult when no support is available. After examining the family types, it can be stated that socio-demographic background variables, particularly educational capital, and the latest information on ADHD, along with support found within the family, were seen as protective factors allowing highly educated families with ADHD a greater chance to better function in Finnish society. Keywords: ADHD, family, netnography, support services, service system, social exclusion
  • Anyan, James (Helsingin yliopisto, 2016)
    This study explores how opportunities for higher education (HE) are distributed in Ghana s public universities to students; and particularly, how those from the disadvantaged sections of the Ghanaian society fare in that regard. It was approached as a multi-level (integrating elements of micro, meso and macro) and multi-perspective dual transformative case study. Drawing mainly upon data collected from semi-structured interviews with students, graduates, university officials and policy-makers, as well as secondary data archived by the relevant institutions; it examines the processes and patterns in the distribution of admission slots to students. It engages with the tensions and dilemmas confronting the universities in such allocations, and debates same, in the context of procedural justice and meritocracy on the one hand, and distributive justice and affirmative action on the other. The interactions and intersections of socio-economic and other significant variables parental education, family income, geographical location, gender and disability are discussed, principally, in the framework of effectively maintained inequality (EMI), to understand the factors influencing the patterns of distribution observed. The data were thematically analysed using both sensitising concepts from the literature review, the conceptual frameworks as well as the indigenous concepts that emerged from the data. The findings indicate that the distribution of HE seats in the two public universities selected for the study is highly inequitable with students who graduated from the few urban-based and elite upper secondary schools overrepresented while graduates from the majority rural-based and resource-poor schools are underrepresented. Although there was unanimity among the different groups of participants about the existence and persistence of the problem, their approaches to dealing with the problem proved dichotomous. While students from the rural schools, for instance, exposed their status frustration and assumed a reformist stance on the issue of remodelling the current grade-based admission system to one cognisant of the difficult circumstances under which rural students pursue their upper secondary education, their counterparts from the elite schools essentially defended the maintenance of the status quo. The majority of female participants, contrary to the views of policy-makers, strongly objected to affirmative action for the admission of females; arguing that the policy reinforces the notion that they are inferior to their male counterparts. The results further reveal a multi-layered social stratification in access to, and equity in HE in Ghana. Almost all the students and graduates who were admitted into the universities on affirmative action basis identified themselves as rural people from low-income families, with little or no parental education, and poor parental occupations. Such students, though in dire financial straits, were contrary to expectations, found to be very resilient and highly motivated to complete their studies; posting excellent academic performance. Students with disabilities were also found to be internally excluded, facing life and academic threatening challenges, whereas female students reported entrenched socio-cultural norms impeding the education and aspirations of women in the Ghanaian society. Against these backdrops, the study calls for a rethink of the current overly meritocratic admission procedures in Ghana s public universities that do harm to access and equity for the majority rural students. It further recommends financial support from government to support the affirmative action initiatives of the public universities; an improvement in the conditions of students with disability, and multi-sectoral interventions to ameliorate the barriers impeding the education of females. The successful completion of HE holding all things constant by these disadvantaged groups, with its attendant better educated citizenry, enhanced civic consciousness, empowerment and participation, in addition to other socio-economic benefits, make such investments worthwhile. Keywords: distributive justice, procedural justice, affirmative action, gender, disability, stratification.
  • Mäkelä, Johanna (Helsingin yliopisto, 2016)
    Neurodegenerative diseases are characterized by the progressive loss of structure and function of neurons, but the underlying mechanisms for this are largely unknown. Disturbed cell signaling and protein metabolism as well as mitochondrial dysfunctions are thought to be involved in several neurodegenerative diseases. Mitochondria are the major source of energy in the cell, and they also regulate cell death. In brain, neurons are highly dependent on oxidative energy metabolism. Mitochondrial dysfunctions cause oxidative stress with an excess production of reactive oxygen species (ROS). In neurodegenerative diseases such as Parkinson s disease (PD), ROS are thought to contribute to the loss of dopaminergic neurons in substantia nigra pars compacta (SNpc), which leads to dopamine depletion in striatum. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a transcriptional co-activator that regulates mitochondrial biogenesis, ROS defense and respiration. The lack of PGC-1α has been shown to increase the sensitivity of neurons to oxidative stress and brain injuries. In this study we show that increasing the expression of PGC-1α protects against toxin-induced oxidative stress in dopaminergic neurons. We show that PGC-1α expression in dopaminergic neurons can be modulated by resveratrol (RSV), fibroblast growth factor 21 (FGF21) and peroxisome proliferator-activated receptor γ (PPARγ) that are known to regulate metabolism in other tissues. The increase in PGC-1α expression and activation was linked to metabolic changes mimicing low energy levels in the cell, and an increase in SIRT1, a metabolic regulator sensing changes in energy levels. PGC-1α activation was further associated with an increase in mitochondrial respiration and antioxidant levels suggesting that the neuroprotective effect of PGC-1α was due to an improved capacity to combat oxidative stress. These results show that regulation of metabolism by PGC-1α activators could be a useful tool to prevent neurodegeneration in PD. In addition to modulating PGC-1α, RSV was also found to increase the expression of dopamine transporter (DAT) in dopaminergic neurons of female mice. The increase in the level of DAT increases the uptake of dopamine, further indicating that RSV has beneficial effects in dopaminergic neurons. By affecting DAT, RSV also contributes to maintaining functional neurons, as a decline in DAT has been associated with degeneration of dopaminergic neurons. This effect on DAT expression was mediated by estrogen receptors, indicating that the effect of RSV differs between genders that should be considered if RSV is used as therapy for patients with PD.
  • Godenhjelm, Sebastian (Helsingin yliopisto, 2016)
    Over the past few decades, contemporary public policy and governance systems have been transformed in response to both local and supra-national societal problems and demands. Clear-cut means of tackling these problems and demands are rare. Public policy problems seldom fall neatly within specific jurisdictions or agencies. The state has become increasingly dependent on a wide range of policies and arrangements that produce public services, provide rapid results and facilitate timely interventions. As a response, the choice of governance mechanisms and organizational forms that enable collaborative, dynamic and flexible arrangements in the implementation of public policy becomes highly relevant. This study analyses the increasing use of temporary project organisations as new governance mechanisms in contemporary policy implementation and the prospects for action that this entails. The main argument is that project organisations could yield significant benefits and can play a vital role as horizontal as well as vertical interlinking mechanisms between various administrative levels. They could also include challenges that have not yet been fully understood. The overarching aim of the study is to conceptualise and understand the benefits and challenges related to the increasing number of temporary governance mechanisms in the form of project organisations in the public sector context. The study analyses the potential consequences and advantages of public sector projectification in four research articles and this summary article, focusing on how projectification is driven forward, as well as what the consequences of projectification are in the European Union (EU) context and the public sector in general. It considers the long-term effects of project organisations and the extent to which the added value they produce can be utilized. Who are the beneficial social partners and what types of collaborative procedures and actions are needed to achieve innovation in EU structural fund projects? The multifaceted and ambiguous nature of public sector project research, the uniqueness associated with the various actor objectives, interests and participatory procedures regarding projects, as well as their management requires a broad theoretical view and a variety of methods. Three interrelated strands of research in this respect are particularly relevant: the New Public Management (NPM) discourse, theories of Governance, and project management ideals and Governance of Projects (GoP). They represent a mixture of old and new, which is necessary in order to understand the functioning of projects and projectification as well as their embeddedness in the public sector environment. The study follows an empirically informed interpretive approach, which emphasises the intentionality of actions, practices, and social life. It uses a mixed-methods approach and advocates multi-perspectivism and paradigm interplay. It also combines different interpretations of the existing governance frameworks and public sector projects, thus acknowledging that alternative views might exist. The methods used in the individual articles represent metaevaluation, qualitative content analysis, logistic regression analysis and social network analysis (SNA). The findings highlight the lack of conceptualizations concerning the relationship between temporary and permanent structures, and suggest that an increasing temporality in public decision-making may challenge fundamental administrative values such as transparency and democratic accountability. The findings question the often over-emphasised value of using projects as opposed to other more permanent mechanisms in the public sector environment and suggest that there is a potential mismatch between the operational logic of projects and the prevailing project and program evaluation system in the public sector. Projects can act as hubs where valuable information is produced, and project stakeholder networks and various collaborative efforts can play a role in predicting project innovations. There is, however, an overly optimistic view of collaborative efforts in achieving project innovations, calling collaboration in projects into question as a direct remedy for a lack of innovation. The study concludes that an increasing use of project organisations in the public sector may have significant consequences, as well as showing that the expected advantages of project organisations are related to the rationalistic ideals, but also that temporality as such poses challenges to permanent administrative structures. Although projects might be superior to permanent structures in producing quick outputs, too much focus on the rational logic of project organisations means that their added value remains underutilized in a public sector context. The study contributes to a theoretical understanding of projectification, what the key drivers of projectification are, as well as specific public sector features that need to be accounted for in a projectified public sector. The study concludes that contextually sensitive interlinking mechanisms between temporary and permanent organizations are vital in explaining the outcome of temporary organizations in a politico-administrative context.
  • Toivonen, Marjaana (Helsingin yliopisto, 2016)
    Environmental fallows are fields that aim to produce environmental benefits instead of agricultural products. In many European countries, the establishment and management of fallows is funded via agri-environmental programmes. This thesis focuses on the biodiversity benefits of environmental fallows in boreal farmland. I examined the impacts of different fallow types and landscape structure on the diversity and species composition of multiple taxa in fallows. I also aimed to evaluate what fallow types, and in what landscape context, are needed to contribute to different biodiversity objectives: the promotion of conservation concern species, overall species diversity or ecosystem services. Species richness and composition of the studied species groups differed substantially between fallow types, and landscape context further modified the value of fallows. Perennial fallows sown with meadow plants supported high plant species richness and bumblebee abundance. Old grassland fallows benefitted both butterflies in general, and butterflies and bumblebees with narrow niches and low dispersal capacities. The positive impacts were emphasized when long-term fallows were located in complex landscapes. High forest cover in the surrounding landscape increased plant species richness in perennial fallows. The breeding density of open farmland birds was highest in short-term meadow fallows in landscapes rich in perennial grasslands. Foraging edge birds preferred short-term meadow fallows in open landscapes and long-term grassland fallows in forested landscapes. Vegetation of annual fallow types game fields and landscape fields differed considerably from perennial fallows and other non-crop biotopes, thus enhancing landscape heterogeneity. My results show that the biodiversity benefits of fallows can be enhanced by adapting fallows to the landscape context and to specific conservation objectives. If the objective is to support species of conservation concern, managing long-term fallows in complex landscapes rich in perennial grasslands is probably the best strategy. Overall biodiversity can also be enhanced in short-term fallows, especially if they are sown with diverse seed mixtures of species that are not too competitive in field conditions. Depending on the sown species, short-term fallows provide good possibilities to enhance landscape heterogeneity and promote ecosystem services. Future studies should consider the specific roles of forest and perennial grasslands in driving the effectiveness of agri-environment schemes. In addition, the impacts of agri-environment schemes, including fallows, on realized ecosystem services should be investigated.
  • Äyräs, Outi (Helsingin yliopisto, 2016)
    Background: Increased nuchal translucency (NT) has been used as a screening method for fetal aneuploidies since 1990s. It is also known to be associated with a wide variety of structural defects and genetic syndromes. Long-term studies with a large cohort about the neurodevelopmental outcome of euploid children with increased fetal NT are sparse and the neurodevelopment is worth further study. Aim: The primary aim of this study was to collect data on the pregnancy outcomes, long-term neurodevelopmental and overall outcomes in a large cohort of fetuses with increased NT from singleton pregnancies in order to improve parental counselling. Material: All singleton pregnancies referred to the Department of Fetal Medicine at the Helsinki University Hospital due to increased NT in the first-trimester screening during 2002 2007 were studied. The outcome data were retrieved from hospital databases and national registers. Results: There were 1063 fetuses with increased NT in the first-trimester screening. Abnormal karyotype was observed in 224 fetuses (21%) and adverse pregnancy outcome occurred in 322 (30%). Termination of pregnancy was performed in 209 (20%) and there were 43 (4%) miscarriages and perinatal deaths. Of the 834 euploid fetuses 74 (9%) had structural defects or genetic disorders. Favourable pregnancy outcome became less likely by increasing NT: favourable outcome occurred in 92% in the lowest NT group (95th percentile 3.4 mm) and in 18% in the highest NT group (≥ 6.5 mm). Of the euploid fetuses with normal second-trimester ultrasound examination 96% were healthy at the discharge from the delivery hospital. During the follow-up (mean 6.5 years) neurodevelopmental impairment was detected in 29 (4.2%) and it was severe in 12 (1.7%). Major structural defects, severe neurodevelopmental impairment, or genetic disorders were detected in 54 cases (7%). Conclusion: One in five fetuses with increased NT (≥ 95th percentile) has chromosomal abnormalities and one in ten of the euploid fetuses has structural defects or genetic syndromes. Major health impairment (major structural defect, severe neurodevelopmental impairment, or genetic syndrome) is likely to be detected in 7% of euploid children with increased NT in the first-trimester screening but normal findings in the second-trimester screening. These results are helpful in counselling the parents when increased NT is detected.
  • Buysse, Manon (Helsingin yliopisto, 2016)
    Clause linking, or the incorporation of multiple predications within a complex linguistic unit, is an essential component of efficient language use, but also a major hurdle in the language learning process. Although discrete aspects of clause linking and its development in second language acquisition (SLA) have been studied before, a comprehensive and theoretically unified approach to the phenomenon in SLA is still lacking. To redress this gap, the study presented in this doctoral dissertation proposes a model of clause linking and its development in SLA based on the theoretical framework of Role and Reference Grammar (RRG; Van Valin and LaPolla 1997, Van Valin 2005) and its application to first language acquisition (Van Valin 2001). It provides a detailed account of clause linking, formalized in the Interclausal Relations Hierarchy (IRH; Van Valin 2005), which takes into account various structural levels of language and considers both the syntactic and the semantic aspects of clause linking. Oral narratives in L2 French and English were transcribed and divided into four groups based on their overall proficiency level in the L2, resulting in a total of 100 (4 x 25) samples per L2. Matched narrative production data from 25 native speakers of each target language served as a benchmark for our analyses. Results provide evidence for the universality of RRG s hypotheses in the sense that L2 learners seem to be guided by the same principles as L1 acquirers; forms of linkage characterized by similar syntactic and semantic strength are acquired more easily (as predicted by the IRH), and syntactic junctures at particular structural levels are associated with particular semantic relations between events. However, our L2 productions were also found to develop differently from those of Van Valin s (2001) young L1 acquirers in various respects: our L2 learners produce complex clauses from early stages of development onwards, as the hurdles they encounter in mastering the various L2 linking devices are unrelated to the development of their cognitive abilities or discourse organization capacities. In addition, we observed that the learners of L2 French and those of L2 English behave rather similarly in how they establish clause linking at various stages of development, but also deviate from one another in non-trivial ways which merit further research.
  • Ilander, Mette (Helsingin yliopisto, 2016)
    Chronic myeloid leukaemia (CML) is caused by a translocation between chromosomes 9 and 22. As a result of the translocation Philadelphia chromosome that contains a malignant oncogene is born. Tyrosine kinase inhibitors (TKIs) target the malignant oncokinase that is produced from the oncogene and drives the development of CML. The prognosis of CML patients has improved significantly after the emergence of the TKIs. Some patients can even stop the treatment without imminent disease relapse. However, it has been shown that patients who stay in remission without any treatment still have leukemic cells left. We hypothesized that the immune system is able to keep these cells under control and studied the mechanisms behind immune surveillance by analysing the immune cell phenotype and function in CML patients. The results of this thesis show that the immune system plays a role in the successful discontinuation of the treatment. The results from 3 separate studies suggested that natural killer cells are important in successful treatment discontinuation in CML, and that they might be capable of activating T cells and adaptive immunity to keep leukaemia under control. We further studied the effects of 2nd generation TKI dasatinib, known to have immunomodulatory effects. We observed that dasatinib treatment increased the number of Granzyme B expressing memory CD4+ helper and CD8+ cytotoxic T-cells, which were highly active by secreting interferon γ (IFN-γ). We hypothesized that these cells may have a role in the anti-leukaemia activity, as IFN-γ is known to be important in tumour control. The dasatinib induced antitumour immune effects were confirmed in a B16.OVA mouse melanoma model. We were able to demonstrate that dasatinib treatment increases the amount of tumour-infiltrating CD8+ cytotoxic T cells and induces a tumour size reduction dependent on the presence of functional T cells. Taken together, this thesis work illustrates the significance of an active immune system in successful treatment discontinuation in CML. Based on our results it would be important to combine immune activating agents in the future treatment strategies of CML in order to increase the number of patients who are able to successfully discontinue the treatment and be cured.
  • Alves Antunes Soares, Joana Soares (2016)
    Atmospheric aerosols are subject to extensive research, due to their effect on air quality, human health and ecosystems, and hold a pivotal role in the Earth s climate. The first focus of this study is to improve the modelling of aerosol emissions and its dispersion in the atmosphere in both spatial and temporal scales and secondly, to integrate the dispersion modelling with population activity data that leads to exposure metrics. The mathematical models used in this study are fully or partially developed by the Finnish Meteorological Institute: a global-to -mesoscale chemical transport model, SILAM; a local-scale point/line-source dispersion model, UDM/CAR-FMI; and a human exposure and intake fraction assessment model, EXPAND. One of the outcomes of this work was the refinement of the emissions modelling for global-to-mesoscale dispersion model. Firstly, a new parameterisation for bubble-mediated sea salt emissions has been developed by combining and re-assessing widely used formulations and datasets. This parameterisation takes into account the effects of wind speed and seawater salinity and temperature, and can be applicable to particles with dry diameters raging between 0.01 and 10 µm. The parameterization is valid for low-to-moderate wind speed, seawater salinity ranging between 0 and 33 and seawater temperature ranging between -2 and 25 °C. Secondly, the near-real time fire estimation system, IS4FIRES, based on Fire Radiative Power (FRP) data from MODIS, was refined to reduce the overestimation of particulate matter (PM) emissions by including more vegetation types, improving the diurnal variation, removing highly-energetic sources and recalibrating the emission factors. Applying dynamic emission modelling brought more insight to the spatial distribution of these emissions, their contribution to the atmospheric budget, and possible impact on air quality and climate. The modelling shows that sea salt aerosol (SSA) can be transported far over land and contribute up to 6 µg m-3 to PM10 (at annual level), and indicate that the Mediterranean has sharp gradients of concentrations, becoming an interesting area to analyse for climate considerations. For fire, the simulations show the importance of meteorology and vegetation type for the intensity of the emissions. The simulations also show that MODIS FRP is accounting for highly energetic sources as a wildland fire, bringing up to an 80% overestimation in AOD, close to the misattributed sources. The second outcome is related to urban-scale modelling. The emissions for Helsinki Metropolitan Area (HMA) were revised to bring up-to-date the emissions for traffic and energy sectors in use for urban-scale modelling. The EXPAND model was revised to combine concentrations and activity data in order to compute parameters such as population exposure or intake fraction. EXPAND includes improvements of the associated urban emission and dispersion modelling system, time use of population, and infiltration coefficients from outdoor to indoor air. This refinement showed that PM2.5 in HMA is mainly originated from long-range transport, with the largest local contributors being vehicular emissions and shipping (at harbours and its vicinity). At annual level, the population living mostly indoors (home and work) is mainly exposed to PM2.5 with an acutely increased exposure while commuting.
  • Korhonen, Jaana (2016)
    International industrial competitiveness depends on many aspects. It can be based on cost advantages over international competitors, which are realized as higher market shares and increased trade flows in global markets. Competitiveness can also be improved by creating higher value through increased product quality and by means of sustainability. This places increasing strategic importance on scarcening natural resources and on how proactively environmental responsibility is perceived in the international forest sector in the future; as an additional cost or more as an opportunity of a high road to competitiveness? The goal of this dissertation is to analyze international competitiveness and its drivers from five different perspectives at the regional, country, and firm levels, with an emphasis on the pulp and paper industry. The empirical research problems of five individual research articles are approached by combining quantitative and qualitative data analyses. The time period from 1990 to 2030 was covered in the analyses. The results highlight the importance of forests, markets, and regulation in creating competitive advantages at different levels in the sector. The traditional forest sector factors such as resource availability and traditional economic factors such price competitiveness are going to play an important role also in the future. However, sustainability will become increasingly important for the value creation opportunities of industries. It is an opportunity for companies in their global value chains if the global environmental awareness and societal demand for sustainability continue to increase. Therefore, more responsible use of global forest resources can offer solutions to global sustainability challenges, and in the transition to a bioeconomy in which the forest industry plays a key role.
  • Tapiola, Olli (Helsingin yliopisto, 2016)
    Different dyadic techniques are an inseparable part of modern-day harmonic analysis both in the Euclidean space and in metric spaces. In this dissertation, we improve adjacent and random dyadic techniques in metric spaces and apply these and previously known techniques for questions related to metric, Euclidean and vector-valued analysis. The dissertation consists of an introductory part and four research articles. In the first article, we present a general randomization procedure for dyadic systems in metric spaces which can be used for constructing both random and adjacent dyadic systems. As an application of the new random systems, we improve the continuity properties of metric wavelets of P. Auscher and T. Hytönen by exploiting the improved ``smallness of boundary'' property of our random cubes. In the third article, we prove some additional properties for our adjacent dyadic systems to prove a decomposition result for dyadic systems in metric spaces. With its help, we give an alternative proof for the quantitative bound of the Lp norm of shift operators acting on vector-valued functions in metric spaces. In the second article, we explore certain properties of the Muckenhoupt weight classes, the class of Reverse Hölder weights and their weakened versions in spaces of homogeneous type. In the Euclidean setting, the Muckenhoupt weight classes have numerous different equivalent definitions but in spaces of homogeneous type some of those equivalences break down. We show that although certain definitions are no longer equivalent in this context, their weakened versions still define the same weight classes. We also show that every weak Reverse Hölder weight has a self-improving property. In the literature, these types of weak weights appear especially in the theory of partial differential equations. In the fourth article, we prove quantitative weighted bounds for so called rough homogeneous singular integrals by combining older techniques with a quantitative version of M. Lacey's recent extension of the A2 theorem. The proof of this extension is based on a domination technique which provides a way to dominate Calderón-Zygmund operators pointwise with the help of a finite number of simple sparse operators associated with adjacent dyadic systems.
  • Vatanen, Anu (Helsingin yliopisto, 2016)
    Long-term ovarian function was retrospectively evaluated after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence. Cardiovascular risk factors, arterial morphology and stiffness, left ventricular (LV) mass and function, physical fitness and frailty were investigated in adult and adolescent survivors of high-risk neuroblastoma (HR NBL) after autologous HSCT in childhood. The first study population included a cohort of 92 female long-term survivors who were less than 20 years of age when treated at the Children s Hospital, Helsinki University Hospital, or Karolinska University Hospital, Huddinge, between 1978 and 2000. The follow-up data included signs of spontaneous puberty, age at menarche, the use of hormone replacement therapy, pregnancies, and information about pubertal or postpubertal serum FSH levels. The second study population included the Finnish national cohort of 19 long-term HR NBL survivors treated between 1980 and 2000, and 20 age- and sex-matched controls. Clinical examinations included 24h ambulatory blood pressure (BP), very-high-resolution vascular ultrasound, 3D echocardiography and Tissue Doppler Imaging ultrasounds, body composition, physical performance tests and interview. Older age at HSCT and total body irradiation and busulfan-based conditionings were risk factors for early ovarian aging. Leukemia survivors with previous cranial radiotherapy or transplanted after disease relapse were at high risk of premature ovarian failure. The HR NBL survivors showed increased carotid intima-media thickness, plaque formation and stiffness, increased radial artery intima thickness, and increased cardiovascular risk profile when compared to the controls. They had increased LV mass, decreased systolic and diastolic LV function when compared to the controls. Poor LV function associated with cardiac biomarkers, poor physical performance and increased BP. The survivors showed shorter telomere length and increased frequency of frailty phenotype when compared to the controls. The frailty phenotype associated with cardiovascular health and chronic inflammation. In conclusion, our study shows that the adult survivors after HSCT in young age are at risk of early reproductive and vascular aging and frailty. The survivors of pediatric HSCT require regular follow-up in adulthood and interventions for declining ovarian function, cardiovascular risk factors, high BP, subclinical signs of atherosclerosis and decreased cardiac function. Since lifestyle choices can influence cardiovascular health and frailty status, a healthy non-smoking lifestyle and physical activity should be advocated among all survivors who have received HSCT in childhood.