Väitöskirjat

Recent Submissions

  • Teirilä, Laura (Helsingin yliopisto, 2017)
    Fungi are associated with a wide range of diseases from superficial skin syndromes to invasive life-threating conditions. Furthermore, exposure to non-infectious fungal components in the context of agricultural work or in water-damaged houses has been associated to illnesses in the respiratory tract. The inadequate knowledge of the immune mechanisms behind these illnesses has triggered an intense research effort attempting to understand how fungi can activate the defense mechanisms of immune system. This thesis focused on the inflammation triggered by the fungal components. The inflammatory response and related mechanisms were studied in vitro in the key defense cell of innate immunity, the macrophage, which were treated with a central cell wall component of fungi, (1,3)- β-glucan. One major outcome of this thesis was the finding that β-glucan evokes a strong pro-inflammatory response via the IL-1 family cytokines in human macrophages. These cytokines are crucial mediators of inflammation, thus their secretion is highly regulated. Our study showed that β-glucan, on its own, could cause the efficient secretion of functional IL-1β and other mediators of inflammation via unconventional secretion pathways by activating both dectin-1 signaling pathway and NLRP3 inflammasome. This β-glucan-induced protein secretion via unconventional pathways was suppressed by inhibition of inflammasome activity or by preventing the process of autophagy. Furthermore, the well-known myeloid cell growth factor, granulocyte-macrophage colony-stimulating factor seems to be one of the factors boosting the β-glucan-triggered inflammatory response of macrophages. In an attempt to obtain direct information about conditions caused by the exposure to fungal and other microbial particles, we characterized the proteomic changes present in the bronchoalveolar lavage obtained from patients suffering illnesses associated with exposure to inhaled microbial particles. The proteomic profiles of hypersensitivity pneumonitis (HP) were different from the profile of damp building-related illness (DBRI), indicating that these conditions are not closely associated. However, the increase in the levels of two well-known markers of inflammation was observed in both HP and DBRI, evidence for the activation of inflammatory mechanisms in both of these conditions. This thesis provides novel knowledge concerning the inflammatory response and related mechanisms triggered by fungal components. These results may help to clarify the mechanisms behind the inflammatory symptoms experienced by individuals with fungal infections or exposure to fungal particles and will provide future tools for the treatment of fungal-related disorders.
  • Vanonen, Hanna (Helsingin yliopisto, 2017)
    This study focuses on the Qumran War Text manuscripts, especially those found in Cave 4 (4Q471, 4Q491a, 4Q491b, 4Q492 4Q497). There has been a clear need to study these Cave 4 manuscripts in detail and in their own right, not just as additional evidence of the large and well-preserved War Scroll (1QM) from Cave 1. The study produces a thorough close-reading analysis of these fragments and manuscripts, with a critical evaluation of existing editions, paying attention not only to their contents but also to manuscripts as material artifacts. Consequently, three different types of relationships between the manuscripts are distinguished. First, it can be said that some manuscripts are literarily dependent on each other. When comparing 1QM 14 17 and 4Q491a, it is demonstrated that the author/compiler of 1QM has used the text known in 4Q491a, modified it (in the case of battle instructions) and sometimes largely reworked it (in the case of encouragement speeches). It is not clear whether the author/compiler of 1QM actually had the exact manuscript 4Q491a in front of him but he clearly knew its text and used it, aiming at preserving its style and its main content. Second, it is discovered in the analysis that there are manuscripts that were produced in the process of producing another manuscript. When comparing 4Q492, 1QM 12 and 1QM 19, it is demonstrated that 4Q492 probably is a draft version used in order to modify the text of 1QM 19 to fit in 1QM 12. Third, there are manuscripts that are not copied from each other but that yet have much in common and have probably been somehow related, at least on the level of common themes. For example, 4Q493 and 1QM may have been developed without any direct literary dependence but similar themes interested the authors of both texts and the author/compiler of 1QM probably knew a text or texts that at least resembled that of 4Q493. The titles given to the texts indicate that both authors clearly thought to represent one Milhamah-tradition, but they also felt free to modify it for their own purposes, their own audiences which probably were different. After that, the manuscripts are discussed together, focusing particularly on similarities between them and asking which subgenres of the War Texts were actively transmitted and to what extent it was possible to change them. Battle instructions and encouragement speeches are shown to be the two main subgenres. The battle instructions were carefully transmitted whereas speeches offered a place for literary creativity and provided an opportunity to add new elements to the text. The study demonstrates that in addition to a traditional chronological literary-critical model, other models to explain the relationships and meanings of the manuscripts are needed. In the case of the War Texts, at least liturgical use and study purposes may have created needs for producing different manuscripts that were simultaneously important. Also, through a constant writing of structured war visions, their main message everything is in God s hands was made real and more convincing to new audiences.
  • Tuulasvaara, Anni (Helsingin yliopisto, 2017)
    The immune system should react effectively towards harmful pathogens but tolerate own tissues. The tolerance comprises central and peripheral tolerance. Negative selection, where cells reacting harmfully towards own tissues are eliminated, is part of central tolerance. One part of peripheral tolerance is the regulatory T cell population. Errors in tolerance cause autoimmune diseases, an example of which is APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. The basis of tolerance is the development of T lymphocytes in the thymus. During this process most of the developing thymocytes die. To survive, thymocytes have to recognize peptides presented in the major histocompatibility complex (MHC) with proper affinity with their αβ T cell receptor (TCR). TCRs have a huge variation in sequence in their complementarity determining region 3 (CDR3), due to somatic recombination and additional editing. In this thesis I have studied this development of T cells in the human thymus, and then more specifically the regulatory CD4+ FOXP3+ T cell population. The effect of positive and negative selection on the TCR repertoire of developing thymocytes was analyzed. Very few shared sequences were found between different populations, showing the huge diversity of the TCR repertoire. In physicochemical analysis the basic TCR structure remained the same from already the most immature population before selections. A reduction in the average CDR3 length was seen between the CD4+CD8+ double-positive (DP) and CD4+ populations, probably reflecting the effect of thymic selections. To study thymic selection in APECED patients, the observed reduction in the length of CDR3 was used as an indicator of selection. The average CDR3 length of the peripheral CD4+ and CD8+ T cell populations of APECED patients was compared with healthy controls. No significant differences in CDR3 lengths between the patients and healthy controls were found, not even in the CD8+RA+ population that is abnormal in APECED patients. As most studies have been done in mouse models, the precise steps of regulatory T cell development are poorly known in human. DP thymocytes are thought to be the precursors of CD4 FOXP3+ regulatory T cells. After an overnight culture and flow cytometry analysis more apoptotic DP thymocytes than CD4+ thymocyte were found, showing their precursor cell characteristics. Furthermore, the effect of interleukin 7 (IL-7) on developing thymocytes was studied. Mature regulatory T cells express the IL-7 receptor α chain CD127 at low levels. However, stimulation with IL-7 in culture increased the percentage of FOXP3+ DP and CD4 single-positive thymocytes. The mechanism behind this seemed to be an inhibition of apoptosis and possibly also increased FOXP3 expression. These results increase the knowledge on T cell development in human but many details are yet to be revealed.
  • Timko, Krisztina (Helsingin yliopisto, 2017)
    Whenever a common goal requires coordinated action of a team, leadership facilitates the endeavor. Historically, men have held most of the leadership positions, and up to date, women are still a minority in top‐level business positions. Using the turnaround game in controlled laboratory experiments and varying treatment conditions, we investigate whether men and women are equally effective leaders. The first chapter reviews research from three different perspectives: coordination games in economic laboratory experiments and their real‐world implications, gender studies in relation to leadership and ongoing trends, and studies of the democracy effect related to leader effectiveness and gender equality. The second chapter shows with a basic experiment using the weak‐link game that men and women are equally effective leaders, no matter if gender is revealed or not. The third chapter considers communication styles of leaders and finds that despite the different paths in communication, men and women are equally effective leaders. The fourth chapter varies the selection process and presents a replication of the democracy effect on leader effectiveness in a laboratory experiment using the turnaround game as studied earlier by Brandts et al. (2015). The fifth chapter finds that women are elected at a similar rate than men and elected women are marginally less effective leaders than elected men, although the gender difference disappears with repeated interaction. The broad conclusion is that organizations can benefit from both employee participation in choosing group leaders and reconsidering gender imbalance in top‐level positions.
  • Köykkä, Arto (Helsingin yliopisto, 2017)
    This thesis studies how Pentti Saarikoski has chosen and used religious language and what this language tells about his thoughts related to his worldview and religion. My point of view is not restricted to Christianity, although Saarikoski emphasized the importance of the church Bible from 1938 for his work. I analyze books that Saarikoski meant to be published during his lifetime. Diaries are not part of my essential source material, but I use them when they contribute toward understanding my actual research material. Of the diaries examined, the most meaningful are those of adolescence, which illustrate his religious period and the literary favorites of his adolescence. Various interpretative methods need to be applied to my heterogeneous and multigenre source material, depending on the text being studied. Religious allusions in the texts are sorted in accordance with the strategies of comparative literature, especially an intertextual approach. Furthermore, I analyze this material using methods of systematic analysis. I look for permanent thought structures and study how they are related to religious and even philosophical paradigms. Linguistics and exegetics are used when needed. At the same time I take into account that everything said by Saarikoski does not need to be understood as his own thoughts. Two kinds of religious language are perceived in his works: on the one hand, there is language that originates from religion, but does not editorialize the content of the language; in other words, language whose religious origin is seen only etymologically. On the other hand, there is religious language proper that has an existential and subjective dimension. Manifestations of religious allusions were investigated in Saarikoski s works of different periods. In the first three poem collections Runoja, Toisia runoja and Runot ja Hipponaksin runot there are only a few religious allusions. In these collections, Saarikoski is consciously building his image and parting from his adolescent religiosity. In the collection Mitä tapahtuu todella? expressions drawn from the church Bible show up visibly in his text, and after that they are strongly present in all of his works. During his period in Sweden, poems become more abstract. On the other hand, his description of religious experience becomes more concrete in the radio drama series Köyhyyden filosofia that is set at the end of the 19th and the beginning of the 20th centuries. People living frugally do not just use a language of religious origin etymologically, but they express their life experience through religious language, existentially. Allusions of religious language are grouped in the study, according to their reference texts and how the allusions are used. From the books of the Bible, Saarikoski is especially interested in the Book of Genesis and the Gospels. Theology and the doctrines of Paul are more unfamiliar to him. While making allusions to the Gospels, he avoids narrations that are scientifically suspicious. I also show texts in the works of Saarikoski, where he refers to the Book of Psalms , to adolescent language of the congregation, or to non-Christian religious material. Mostly he enriches his writing with a language of religious origin , but within his works there is also an abundance of texts where he modifies his thoughts and comments on the religious world and its phenomena. In an excursus on the Gospel of Matthew that Saarikoski translated I make comparisons to allusions in his texts drawn from the church Bible. Here I shows comprehensively that, even after translating the Gospel, the allusions Saarikoski uses are always to the church Bible, and not to his translation. Analysis of Saarikoski s political texts showed that communism was a structure good to think with that mostly substituted his religious ways of thinking. Saarikoski elevates the historical person of Jesus among the greats of humanity, but in his works he is not especially interested in the significance of the teachings of Christ, only in his rebellion and humanity. Saarikoski depicts the members of his personal communistic person-gallery with means of religious language. He especially admires Lenin in this sense. The naming of things and phenomena is important to Saarikoski. This shows, for instance, in how he speaks about God. When he refers to God in the upper case initial, he is always referring to the Christian God. The lower case initial shows that the text refers to a false god, or to a degenerated Christian god that does not deserve the name of God. I also show that Saarikoski sometimes uses religious expressions in a way that resembles performatives. For example , when his literary self blesses everything he sees on a sea shore. My analysis shows that the antipathy Saarikoski feels towards the Church and its clergy is based primarily on the thought that one should not speak about things that cannot be spoken about. Saarikoski has thoroughly absorbed the final sentence of Wittgenstein s Tractatus Logico-Philosophicus: Whereof one cannot speak, thereof one must be silent. It reflects Saarikoski s own thoughts about the limits of language. He veils his God-related thoughts to concepts like dark and fog used in Apophatic theology. It cannot be proven that he was really familiar with Apophatic theology. But both his residence at the Greek Orthodox monastery of Valamo in central Finland and his translations of J. D. Salinger s Franny and Zooey, related to the prayer of Jesus, have undoubtedly influenced his orientation toward theology.
  • Nieminen, Emmi (Helsingin yliopisto, 2017)
    This thesis examines the optimal economic management of the Baltic Sea fisheries and contributes to the existing literature with its novel bioeconomic and game theoretic applications enhancing more holistic fisheries management than traditionally, and thus taking a step towards ecosystem-based management. Such management can be interpreted as integrated management of the ecosystem instead of concentrating on a single issue in isolation. This approach is fulfilled in four separate dimensions: Firstly, the thesis studies the optimal management of several species instead of focusing on only one species. Secondly, the focus is not only on management in a single country; instead, the thesis has a wider scope and analyse the prospects of cooperation among several countries. Thirdly, the problems are modelled by taking into account the long-term perspective, i.e., by maximising the resource rent over a long time period and by analysing the possible effects of climate change. Fourthly, this thesis applies a cross-sectoral approach and examines several sectors affecting the ecosystem (fisheries and energy sectors) instead of only focusing on one. This thesis highlights the importance of linking economics to biology and its significance to fisheries management. In fact, fisheries management based on society s profit maximising bioeconomic objectives with biologic constraints are often more conservative for a fish stock than management relying solely on biologic advice. The increased profitability of the fisheries industry could furthermore be improved by international coordination among fishing nations. The positive effects of bioeconomic management would be even greater when the fish stocks are weak, which may be the future in the Baltic Sea with the continuing effects of climate change. Additionally, this thesis takes into consideration the positive value of migratory fish for the recreational river anglers. When those values are included, it is often profitable from the society's point of view to enable the upstream migration even in regulated rivers producing hydropower. The optimal measures targeted to enhance the migration depend on the number of the dams in the river: the more dams, the more profitable to trap and transport fish over the dam instead of constructing fishways.
  • Salo, Heini (Helsingin yliopisto, 2017)
    This study presents the materials, methods, and results of the economic evaluations of 7-valent pneumococcal conjugate vaccination (PCV7) programme, influenza vaccination programme and human papillomavirus (HPV)-associated cost of illness study, all of which were used in the vaccine adoption decision-making process in Finland in 2001 2011. Vaccinations of all children aged 6 36 months with influenza vaccine were accepted into the NVP in 2007, infant pneumococcal vaccinations in 2010 and HPV vaccinations of all girls in 2013. When a new vaccine is considered for inclusion into the NVP in Finland the expected public health benefit, the safety of the vaccine for an individual, the safety of the vaccination programme at the population level, and the cost-effectiveness of the vaccination programme are evaluated. An economic evaluation is needed to support the decision-making process. The decision-makers have not specified an explicit range of cost-effectiveness threshold values below which an intervention would automatically be accepted and lead to funding. In the first economic evaluation of the infant PCV7 vaccination programme (excluding indirect herd effects) the cost per QALY gained was EUR 54 600. In the economic re-evaluation, including the indirect herd effects of the vaccination programme in older age groups reduced the cost per QALY gained to EUR 20 600. The influenza vaccination programme of healthy children was found to yield cost savings from the health care provider perspective even though the indirect herd effects and influenza-associated deaths were excluded. The vaccination programme was estimated to save annually EUR 7.6 per vaccinated child aged 0.5 4 years when the assumed vaccine efficacy was 60%. In Finland, there is a considerable annual disease burden of HPV-related genital disease in the female population. Most of it is detected by the 446 000 annual screening tests, 55% of which are carried out as opportunistic tests. The opportunistic tests account for 71% of the total of EUR 22.4 million screening costs. Further diagnostics, management and treatment of HPV-related genital disease resulted in an additional cost of EUR 22.3 million, of which the costs of less severe HPV-related disease manifestations were EUR 15.5 million. Considering all tests taken both within and outside the organised programme, the 5-year coverage of Pap testing in Finland was 87% among women aged 25 69 years. At present, the successful reduction in the cervical cancer incidence and mortality is due to tests taken both within and outside organised screening. Opportunistic Pap testing both substitutes and overlaps with the tests taken within the organised programme. Overlapping tests stem from the lack of coordination and result in over-management of reversible lesions. In order to be able to coordinate organised and opportunistic Pap testing without losing the high coverage, it is essential to establish a nationwide Pap test register. Furthermore, such a register is necessary for the effective and cost-effective secondary prevention of cervical cancer, which will be needed in both unvaccinated and vaccinated populations.
  • Kaskinen, Anu (Helsingin yliopisto, 2017)
    Congenital heart defects (CHD) are classified as acyanotic and cyanotic. In cyanotic CHD, a mixing of deoxygenated in oxygenated blood reduces arterial oxygenation and the child may be cyanotic, i.e., bluish. Many children with CHD need cardiac surgery. Congenital cardiac surgery often aims to restore normal circulation and correct the defect as seen in vast majority of pulmonary atresia with ventricular septal defect (PA+VSD), but palliative surgery may also be needed or may be the only possible treatment strategy. After congenital cardiac surgery excessive extravascular lung water (EVLW) may appear and impair optimal gas exchange. Effective clearance of EVLW and lung edema rests on active airway epithelial Na+ transport. Postoperative lung edema after congenital cardiac surgery has principally been assessed by chest radiography (CXR), which may be inaccurate and causes irradiation. Excessive EVLW promotes appearance of artifacts called B-lines in lung ultrasound (US), whereas lung compliance associates negatively with increased EVLW. In this thesis the effect of chronic hypoxemia on lung liquid transport was studied in children with CHD. Second, feasibility of lung US and lung compliance in assessment of EVLW and in predicting short-term clinical outcome was tested after congenital cardiac surgery. Third, the long-term survival of a cyanotic CHD was retrospectively evaluated in patients with PA+VSD. According to our findings, the airway epithelial Na+ transport was impaired in profoundly hypoxemic children with cyanotic CHD. After congenital cardiac surgery, lung US B-line score and static lung compliance correlated with CXR lung edema assessment. However, ventilator-derived dynamic lung compliance may not reflect the state of lung parenchyma similar to static compliance. Furthermore, both early postoperative lung US B-line and CXR lung edema scorings predicted short-term outcome interpreted as length of postoperative mechanical ventilation and intensive care. Among factors affecting the long-term survival of PA+VSD the primary anatomy of pulmonary circulation and achievement of repair were most important. In summary, our results emphasize the effect of postoperative pulmonary complications on short-term outcome after congenital cardiac surgery. Our data suggests that hypoxemia may attenuate the constitutional mechanism of the lung to prevent excessive lung liquid accumulation. To detect this, lung US can be used to complement CXR when assessing EVLW in children undergoing cardiac surgery. This may be particularly useful in profoundly hypoxemic children with cyanotic CHD and may promote early recognition of postoperative pulmonary complications. Although primary anatomical factors affect long-term outcome of PA+VSD, an important form of cyanotic heart disease, the treatment should aim for corrective surgery in all PA+VSD patients.
  • Smeds, Eero (Helsingin yliopisto, 2017)
    Accurate control of motor performance requires close co-operation between the motor and sensory functions of the human nervous system. Proprioceptive information about the positions and movements of one s own body parts needs to be carefully monitored to allow fine-tuning of motor output. At the same time, the brain needs to block the influence of distracting external stimuli, such as movements of other persons and various sounds, on the ongoing movements. My thesis focuses on the cortical processes related to these phenomena. In the first studies of this thesis, we explored motor stability by recording brain and muscle activity with magnetoencephalography (MEG) and electromyography, respectively, from healthy adults who were maintaining a steady finger pinch. We analyzed the effects of simple auditory and visual distractors as well as observed movements of another person on the functional state of the primary motor (MI) cortex. All studied stimuli caused transient enhancement of the coupling between cortical and muscular activity at ~20 Hz, reflecting the maintenance of stable motor output. As expected based on earlier studies, movement observation also caused mirror activation in the MI cortex of the viewer, demonstrated by MEG-power suppression at ~7 and ~15 Hz. Importantly, these two simultaneous but opposite processes occurred at distinct frequency bands, suggesting that they were mediated by different populations of MI neurons. The results might explain how the human brain blocks the effects of external distractors on motor behavior and prevents unintentional imitation of observed movements. The latter part of my thesis focuses on cortical activity evoked by proprioceptive afference in adults and newborns. In adults, we recorded MEG responses to proprioceptive input elicited by passive finger extensions and flexions. The amplitudes of the ~70-ms (extension) and ~90-ms (flexion) responses in the primary somatosensory cortex increased by a factor of ~3 and ~6, respectively, when the interstimulus interval was prolonged from 0.5 to 8 s. These findings suggest an optimum interstimulus interval of 1.5 3.0 s for future applications in research and in the clinic. Finally, we showed using electroencephalography that proprioceptive stimulation with continuous passive hand movements elicits a prominent cortical response already at the neonatal phase. Such a passive-movement-based stimulation method could help assess the integrity of somatosensory pathways in neurologically impaired newborns. This thesis improves understanding of the cortical mechanisms essential for proper motor control. The gained knowledge can ultimately benefit diagnostics, treatment, and follow-up of motor-system impairments ranging from movement disorders to neonatal cerebrovascular problems.
  • Tynjä, Tuula (Helsingin yliopisto, 2017)
    All research is bound to be selective about what to include in a study. The archaeological record is inherently only partially preserved due to the effects of ancient discard patterns and natural phenomena over time. These natural and anthropogeneous formation processes have been studied, but the consequences of research-based selections have been largely ignored. I investigated the impact of a deliberately designed archaeological retrieval strategy on the resultant artifact assemblage, both as to its size and quality. By retrieval strategy I mean the criteria that are used when deciding which material is to be kept from all the excavated material. The material that is discarded during fieldwork is typically dumped at the excavation site, and its contextual information is lost. Therefore, the discarded material is reduced in quality to that of stray finds. The recovered and kept material undergoes another selection process when only a part of this assemblage is selected for further, more detailed study. Even though archaeological reports only present a fraction of the recovered material, the criteria used in this material selection are constantly absent from archaeological reports. Ceramics typically constitute the majority of finds, and are usually reported as a typology. However, without knowing the selection process that the material went through to form the typological assemblage, our confidence in the final results is reduced. My typological analysis of the Tel Kinrot pottery attempts to overcome this challenge by presenting the selection process in detail. I have compared materials from two projects at Tel Kinrot, Israel. The first project took place in 1994 2001, and the later in 2003 2008. The excavated areas of the two projects are adjacent to each other, and the primary formation processes can be assumed to be very similar. This situation, combined with the introduction of changes in the retrieval strategy for the pottery from 2003 onwards, enabled me to assign the differences in the pottery assemblages to the research processes themselves with minimal confusing factors. As the result of my comparison, it is clear that the research-based differences in the materials are strong. Therefore, the retrieval strategies and other selection processes made by the researchers should be explicitly stated in their reports. The retrieval strategies at Tel Kinrot can be divided into two phases: the earlier strategy was used in 1994 2001, and can be described as intuitive selection. This meant keeping material that was considered diagnostic from loci that were considered important. Material was considered diagnostic if its chronological period or function could be identified. This resulted in an over-representation of small containers and lamps, and an under-representation of the most common vessel groups of bowls and cooking pots, in the pottery assemblage. During the later excavations by the Kinneret Regional Project in 2002 2008, an intensive retrieval and keeping strategy was conducted in two newly opened excavation areas. In these two areas, all rim fragments and an informal selection of body sherds were kept. In areas that had been excavated already in the 1990 s, the retrieval strategy followed the earlier practice of informal selection. However, the discarded material from these areas was documented in more detail than the discarded material was documented during the earlier excavations, providing the reader with an improved ability to evaluate the reliability of the results. As a result of the intensive retrieval practice, the pottery assemblage from the newly opened excavation areas is representative of all excavated pottery and therefore statistically sound. The assemblage is quantitatively larger than that from the other areas. Qualitatively, the intensive sub-assemblage in more varying: it includes well preserved vessels, but also a host of small rim shards that are hard to identify as to their function or chronology. Because the researcher-based bias is eliminated, the material of the intensive retrieval phase is better suited to assessing the pottery used and discarded by the ancient population. This constitutes a strong argument for the wide adoption of intensive retrieval strategies.
  • Myntti, Tarja (Helsingin yliopisto, 2017)
    Chorioamnionitis, the main single cause of preterm delivery, can be subdivided into clinical and subclinical forms. The latter is more common and includes intra-amniotic infection (IAI), inflammation, and histologic chorioamnionitis (HCA). Amniotic fluid (AF) biomarkers can help in diagnosing subclinical chorioamnionitis, which is necessary for optimal timing of delivery. The aim of the study was to evaluate AF biomarkers in the diagnosis of intra-amniotic infection. The study population comprised 155 cases with a suspicion of IAI or preterm prelabor rupture of the membranes (PPROM) and 46 controls. Amniocentesis was performed in 105 cases between 22+0 and 36+5 weeks of gestation and in 46 controls. AF was obtained vaginally from 53 cases. In such AF samples, AF-lactate dehydrogenase (AF-LD) and AF-Glucose concentrations were determined. Determination in amniocentesis samples was of AF-LD, AF-Glucose, AF-matrix metalloproteinase (MMP)-8, AF-cathelicidin, AF-MMP-9, AF-myeloperoxidase, AF-interleukin-6, AF-neutrophil elastase (HNE), AF-elafin, AF-MMP-2, AF- tissue inhibitor of matrix metalloproteinases -1 (TIMP-1), AF-MMP-8/TIMP-1 molar ratio, and AF-C-reactive protein (CRP) levels. AF-MMP-8 measurement was by an immunoenzymometric assay, AF-LD and AF-Glucose by immunochemiluminometric assays, and others by commercial ELISA. Microbiological analyses were based on molecular microbiology and culture techniques. Placental histopathologic examination was performed. The most optimal cut-off value based on the ROC-curve for AF-LD in vaginally obtained AF against HCA was 1029 IU/L with a sensitivity of 65% and specificity of 69%. In such samples, glucose concentrations did not differ between women with or without HCA. In amniocentesis samples, AF-LD and AF-Glucose correlated with HCA and MIAC, and the most optimal cut-off values for both end-points were a respective 429 IU/L and 0.7 mmol/L. When AF-LD and AF-Gluc concentrations were adjusted by gestational age at amniocentesis, the association disappeared. AF-MMP-8, AF-cathelicidin, AF-MMP-9, AF-MPO, AF-IL-6, AF-Elafin, AF-HNE, and AF-TIMP-1 were associated with MIAC, but AF-MMP-2 and AF-CRP were not. The results were similar also when adjusted by gestational age at amniocentesis. Neutrophil-produced biomarkers were associated with IAI. In conclusion, the accuracies of AF-LD and AF-Glucose were quite poor, and better biomarkers for IAI diagnostics are essential. None of the other biomarkers studied out-performed others. IAI seemed, however, to be associated with neutrophil activation. The usefulness of each biomarker for clinical purposes depends more on local circumstances and laboratory method availability than on exact differences in accuracy.
  • Partanen, Lauri (Helsingin yliopisto, 2017)
    Sulfuric and hydrochloric acids participate in several important chemical processes occurring in the atmosphere. Due to its tendency to react with water molecules, sulfuric acid is an important factor in cloud formation and related phenomena. Hydrochloric acid is heavily implicated in stratospheric ozone depletion because of its role as a temporary reservoir for chlorine radicals. In this thesis, the thermodynamics and dynamics of these two acids are investigated. The dynamic part focuses on the chemical processes following collision of HCl on water and amorphous ice surfaces at different temperatures. By utilizing ab initio molecular dynamics, it is observed that the surface temperature and the initial kinetic energy of the HCl molecule have important and not wholly overlapping effects on its ionization behaviour. The results add to the understanding of hydrochloric acid dissociation on water surfaces in various parts of the atmosphere, potentially illuminating new pathways for related chemical reactions, such as the formation of ClNO on amorphous ice surfaces. The thermodynamic studies revolve around the impact of multiple low-lying stable conformers, or global anharmonicity, on the thermodynamic properties. The studies for this part focus on complexes of sulfuric acid, especially sulfuric acid monohydrate. Due to the relatively small size of the monohydrate, high-level ab initio methods can be employed to obtain accurate values for its thermodynamic properties, thus providing a reliable basis for comparison with less accurate approaches. New ways of accounting for global anharmonicity are developed both for small- and medium-sized clusters. For small clusters, an approximation is presented where the large amplitude motions connecting different conformers are treated separately from the rest of the vibrations, resulting in direct quantum mechanical accounting of the different conformers. In the case of medium-sized clusters, an equation based on statistical mechanics is derived to replace the erroneous Boltzmann averaging formula that has seen wide use in the literature.
  • Moisala, Mona (Helsingin yliopisto, 2017)
    Executive functions are pivotal in our everyday lives, as they form the basis for complex and goal-directed behavior. For example, the ability to maintain information in memory while making a decision requires executive processes. Whether or not executive functions can exhibit experience-dependent changes is still a topic of debate, but generally accepted principles of brain plasticity suggest that environmental factors can have an impact on cognitive processes and the activity and structure of their respective brain networks. One such environmental factor is the increasingly ubiquitous daily interaction with technology, which has been suggested to affect mental faculties such as the ability to maintain focus on a single task or to actively maintain information in short-term memory. The aim of the present thesis was to study activity in cortical networks of attention and working memory. In addition, we investigated whether any associations could be found between the recruitment of these networks or performance speed and accuracy in working memory and attention tasks, and the extent of daily technology-mediated activities reported by adolescent and young adult participants. In all studies, functional magnetic resonance imaging (fMRI) was used to record brain activity during task performance. By using novel experimental paradigms, the present results shed more light on the specific cortical networks recruited by different executive functions by showing that both common and specific brain regions are recruited by auditory and visual selective attention, divided attention and working memory processes. Furthermore, they demonstrate that during division of attention between two concurrent tasks (listening to speech and reading text), competition for neural resources in regions shared by the component tasks is a major contributor to performance limitations observed during multitasking. Importantly, the results of the present thesis also demonstrate that detectable associations exist between different types of daily technology use and cognitive functioning already in adolescence. More specifically, the results demonstrate that a tendency to use several media simultaneously (i.e., media multitasking) is related to increased distractibility. The extent of computer gaming in daily life, in turn, is associated with enhanced working memory functioning. These findings are of great importance, since it is vital to understand how the increasing amount of on-screen time might affect or interact with the cognitive and brain functioning of the current youth.
  • Salmiheimo, Aino (Helsingin yliopisto, 2017)
    Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer. Options for treatment are limited, and the only possibility of cure is radical surgery combined with chemotherapy. Inflammation and tumor stroma are important mediators in PDAC progression. Tumor-associated macrophages (TAMs), among other cells, create an immunosuppressive microenvironment and enhance tumor progression. Because they pivotally participate in tumorigenesis, TAMs are a potential target for therapeutic intervention. The aim of these studies was to explore inflammation and TAMs in PDAC. Three of the studies were conducted in cell cultures, and one was a retrospective clinical study. We polarized macrophages in cell cultures towards inflammatory M1 and anti-inflammatory M2 phenotypes and assessed the changes in the signaling pathways and the effect they had on pancreatic cancer cell migration. We studied the association of preoperative systemic inflammatory response (SIR), based on laboratory data, with the outcome of 265 patients with resectable PDAC. Tumor-associated anti-inflammatory M2 macrophages promoted pancreatic cancer cell migration in co-cultures by activating their MMP9 and ADAM8 expression. Support of the pro-inflammatory M1 phenotype causes these macrophages to inhibit cancer cell migration. Several intracellular STAT pathways and the NFkB pathway were activated by the interactions of cancer cells and macrophages. In preoperative laboratory data, patients elevated C-reactive protein (CRP), an indicator of SIR, predicted worse postoperative survival. Moreover, low levels of albumin, the most abundant protein in human blood circulation, as well as elevated tumor markers CA19-9 and CEA, were associated with worse survival. These studies provide novel insight into the interaction of TAMs and PDAC. The results encourage further research into TAMs and exploration of the possibilities of skewing macrophage polarization toward the inflammatory M1 phenotype. Development of SIR seems detrimental for patients with PDAC and predicts worse outcome. Preoperative CRP, in combination with albumin and tumor markers and clinical data, could prove useful when evaluating patients prognosis.
  • Nyberg, Solja (Helsingin yliopisto, 2017)
    Work is a common source of stress in modern societies. Job strain is the most widely used definition of work stress referring to a condition in which an employee has simultaneously high psychological job demands and a low level of work control. The aim of this study was to examine the extent to which job strain might increase the risk of incident type 2 diabetes and is associated with diabetes risk factors, such as obesity and physical inactivity. Data were obtained from the cohort studies participating in the European IPD Work Consortium. The analyses were based on individual-level data from 19 studies and up to 170 000 participants. Job strain and lifestyle factors were assessed by questionnaires and biological risk factors were measured in a biomedical examination in eight studies. Incident type 2 diabetes was ascertained from electronic health and mortality registers, repeated glucose-tolerance tests during the follow-up, or annual questionnaires. Operationalized definitions of job strain, lifestyle and covariate variables were harmonised before any analysis of the associations or linkage to outcome data. In harmonisation analyses, abbreviated scales, that were comparable to the complete scales, were developed. Job strain was associated with diabetes and its risk factors. After adjustment for age and sex, the odds ratio of having job strain was 1.19 (95% CI 1.13-1.25) times higher for class-I obese participants (BMI 30 to less than 35km/m2), and 1.30 (95% CI 1.16-1.46) times higher for the combined class II and III obesity groups (BMI at least 35 kg/m2), compared to normal-weight participants (BMI 18.5 to less than 25 kg/m2). Job strain was also associated with physical inactivity (odds ratio 1.36, 95% CI 1.25-1.48). The risk of incident diabetes was 1.15 (95% CI 1.06-1.25) times higher among the participants who reported job strain than among those who did not. This association was also observed in the subgroups, including those with and without lifestyle risk factors, and before and after adjustment for lifestyle factors including obesity and physical inactivity. According to cross-sectional analysis adjusted for age, sex and socioeconomic position, the odds for diabetes were 1.33 (95% CI 1.13-1.56) higher among participants with job strain as opposed to those without. In conclusion, these findings show a robust association between job strain, diabetes and its key risk factors. Nonetheless, the effect size was modest, suggesting that interventions to reduce job strain would not be very effective in combating diabetes on the population level.