Väitöskirjat

Recent Submissions

  • 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.
  • Ylivinkka, Irene (Helsingin yliopisto, 2017)
    Glioblastoma is the most malignant brain cancer. Currently no cure has been established. The lethality of glioblastoma is a consequence of its extremely invasive nature: it rarely metastasizes outside the nervous system but effectively spreads throughout the brain parenchyma. This property, in addition to its challenging location makes it impossible to remove surgically. Furthermore, the tumors are heterogeneous and contain cells that are resistant to radiation therapy as well as to the only currently approved chemotherapy, temozolomide. Netrins are secreted extracellular matrix proteins. They were initially identified as proteins essential for the correct axonal wiring of both vertebrates and invertebrates. Later, they were observed to regulate the branching morphogenesis of various organs including mammary gland, lungs and pancreas. During recent years increasing number of studies have linked netrins to various forms of cancer. For example, netrin-1 induces the invasion of pancreatic, colorectal and hepatocytic cancers and medulloblastoma and promotes the survival of breast and lung cancer and neuroblastoma. Netrin-4 can modulate tumor growth, angiogenesis and metastasis. In the current work, we analyzed how netrins contribute to glioblastoma growth. We discovered that both netrin-1 and -4 regulate the malignancy of glioblastoma via independent pathways. Netrin-1 expression was upregulated in glioblastoma whereas netrin-4 was downregulated. However, both were associated with poor patient prognosis. The signaling pathways mediating the effects of these proteins were systematically explored. First, our results revealed a new mechanism where netrin-4 controls glioma cell proliferation via UNC5B and ITGB4 receptors. During normal cell culture conditions netrin-4 is abundantly expressed, and it binds to both UNC5B and ITGB4 receptors that counteract each other and keep glioma cell proliferation in balance. However, during glioma progression netrin-4 expression is decreased and the signaling is shifted towards ITGB4. This led to increased cell proliferation and tumor growth. Second, we discovered a mechanism through which netrin-1 promotes cell invasion. Netrin-1 expression associated with astrocytomas which are invasive glioma subtype. In glioblastoma cells it interacted with Notch2 and Jagged1 and facilitated the activation of the signaling. Subsequently, this led to an increase in cell invasion in vitro and in vivo. Furthermore, a unique invasion pattern was characterized where netrin-1 expressing cells were promoting the motility and stemness of the invasion leading stem-like cells. Third, we designed and engineered a recombinant peptide that had the capacity to inhibit netrin-1 signaling. This peptide was able to overcome the effects of the full-length netrin-1 and specifically inhibited the invasiveness of the stem-like glioblastoma cells in vitro and in vivo. This peptide may prove out to be of therapeutic value in GBM treatment.
  • Strien, Leena (Helsingin yliopisto, 2017)
    Sentinel node biopsy limits axillary lymph node resection to breast cancer (BC) patients with metastases in the sentinel node (SN). The reduced number of nodes allows detailed histopathologic assessment, followed by detection of foci < 2 mm size (micrometastases) or isolated tumor cells (ITC) ≤ 0.2 mm in size, with contradictory metastatic nature and prognostic significance. The aim was to investigate the malignant nature of smaller metastases by comparison analyses of altogether 1074 BC primary tumors (PT) and corresponding SN metastases, including macrometastases (≥ 2 mm in size), micrometastases and ITCs. This was performed by morphometry on 95 PTs and corresponding metastases and an analysis of MTA-1. Preoperative diagnostic needling as a possible cause for ITCs was investigated. HER-2 amplification analyzed by in situ hybridization was evaluated in 29 HER-2 amplified and 36 HER-2 non-amplified PTs and metastases, including ER and PR. Fifty-two BCs separated by Ki-67 ≤ 14% into luminal A and B subtypes for immunohistochemic CXCR4-, CCR7-, and Maspin-, and FOXP3-expression, all linked to more aggressive tumor behavior. Prevalence and risk factors for nonsentinel node (NSN) metastases in 484 patients with SN micrometastases and ITC were analysed. Statistical analyses were mostly descriptive. Factors between PTs and metastases were analysed by Chi square- and Mann-Whitney U -test and logistic regression analysis for NSN metastasis- associated factors as a nomogram. Morphometric analysis of ITCs showed similar atypia with the PTs. ITC prevalence was unrelated to PT biopsy methods. Concordance between PTs and ITCs in ER, PR, and HER-2 expression was high. HER-2 remained amplified in the metastases including the 3 cases with ITC. MTA-1, Maspin and CXCR4 expression pointed to more benign disease, no differences appeared between ITC and larger metastases. CCR7 expression and FOXP3-positive tumors showed some tendency toward more aggressive features; and combined CXCR4 and CCR7 seemed to suggest more aggressive disease. Factors associated with NSN metastases in patients with SN micrometastases an ITC were larger tumor size and multifocality. Only 7.2% had additional NSN metastases pointing to a low risk group. In the light of these studies, ITCs seem to represent malignant cells like micro- and macrometases, but their invasive character cannot be confirmed by these investigations. The expression of factors associated with invasion, metastasis, and poorer survival were expressed in ITCs as in their larger counterparts equally and seem to show connections with factors that may be associated with circulating tumor cells or tumor dormancy.
  • Ojanperä-Samulin, Helena (Helsingin yliopisto, 2017)
    The telephone counselling service Palveleva puhelin was founded to help people at risk for suicide. The purpose of this study is to find whether suicide prevention remained the main purpose of Palveleva puhelin or if changes took place during the years 1969-1995. The study is based on the assumption that if suicide prevention was a central part of Palveleva puhelin's service, this would have been reflected in the practical arrangements of the service, the distribution of information about the service, the training of the listeners and in the help provided. This study adopts historical and qualitative perspectives. I used Palveleva puhelin's documentation to identify who used the service and how the service and practices were developed. I used communication materials to find the nature of the help offered and the recipients of the service. The content of the training provided to the listeners was used to discover what sort of topics were expected to arise in the phone calls and how the listeners were trained. The norms of Palveleva puhelin and the training programmes and materials provided us with information on the nature of the help that was provided. The study shows that Palveleva puhelin s customer base changed over the years. During the first years, marriage and alcohol problems were prevalent topics in the conversations. However, in subsequent years, the most central topics included loneliness, religious questions, mental health issues and depression. Suicide came up as a topic in approximately five per cent of the telephone conversations during the period studied. The aim was to organise the practices of Palveleva puhelin in a manner that would make it easy for people to phone in and that enabled help to be available throughout the country to a similar extent. Suicide as a topic was permanently present on every level of listener training. However, in the communication and advertisements, the topic was not particularly prevalent. Advertisements were directed mainly to people experiencing loneliness, and the opportunity to talk to someone was emphasised. An interesting question is whether people who would have wanted to discuss suicide were able to find the Palveleva puhelin service. Palveleva puhelin was the first organised form of suicide prevention in Finland. Even though the topic did not arise in the phone calls very often, it is possible that the people who phoned Palveleva puhelin for help may later have found themselves at risk for suicide if they had continued to experience the issues they did for a longer period of time and had not sought help. During the period studied, Palveleva puhelin also received a number of calls from people in need of urgent care. In these cases, immediate help was sent to the callers.