Dissertations and theses


Digital dissertations and theses from the University of Helsinki. Contains both open access theses as well as metadata records.

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  • Ehlers, Pauliina (2022)
    Research around food-derived compounds possessing pharmacological effects and potentially also affecting health status beneficially has during the recent years increased. At the same time, new regulations have been put in place to direct the use of different claims on food products. Distinction between food and drugs needs to be clear and consumers and patients cannot be misled. One of the focus areas in research has been products affecting cardiovascular function. The aim of this licentiate thesis was to find out if already developed high blood pressure can be decreased and endothelial dysfunction improved by bioactive milk-derived tripeptides isoleucine-prolineproline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) and plant sterols in an experimental animal model (spontaneously hypertensive rats, SHR). In addition, one of the aims was to investigate if combining tripeptides and plant sterols could have positive, synergistic effects on the development of hypertension and endothelial dysfunction. As pre-clinical studies precede extensive clinical studies in humans also during the drug development process, some comparison between food-derived substances and blood pressure-lowering drugs was made and interfaces between functional foods and drugs was discussed. This licentiate thesis showed that long-term treatment with fermented milk enriched with tripeptides and plant sterols decreased systolic blood pressure, improved endothelial dysfunction and affected signaling pathways related to inflammatory responses in SHR with already established hypertension. Long-term treatment with plant sterols had only a slight but not significant effect for the development of hypertension. Plant sterols did not provide any beneficial effects on endothelial function in hypertensive rats; however, treatment with both plant sterols and tripeptides showed mild anti-inflammatory effects. To get a better picture of the magnitude of the effect of the studied food-derived substances on blood pressure and vascular function, further studies (either with animals or humans) would benefit from including both food-derived substances and drugs as different treatment arms in the same study. Taken together, there are some similarities between functional foods and drugs what comes to product approval processes or claims made on the products, research and effects on blood pressure, for example, but studying food-derived substances brings several challenges compared to drugs what comes to study set-up and interpretation of the results. However, reflecting on the results of the present studies and available literature, food-derived substances such as tripeptides from milk could be a good alternative for subjects with increased blood pressure who do not yet implicitly need drug treatment and can still try to improve their health status with lifestyle changes, such as nutrition.
  • Piela, Emma (Helsingin yliopisto, 2022)
    Organized sports for children provide important health benefits continuing also later in life and are highly segregated based on gender. Having opportunities of organized physical activities within reasonable travel times has been shown to have an effect in participation of sports. In this thesis few of the most popular sports for each gender; dance, horse riding, floorball and football were chosen and the service level of the facilities providing organized sport activities in the age group of 7- to 12-year-olds were analysed in the Helsinki Metropolitan Area. Special interest lied in how equally these services can be reached with different travel modes in reasonable travel times also in relation to spatial socioeconomic differences. As the research on the topic has been inconsistent and sparse, this thesis contributes to the research field with comprehensive outlook on equality considerations and a seldomly used perspective of children’s sports facility accessibility focused on provided services. The methods used included identifying locations used by children in the chosen sports, analysing travel times to these locations with the Helsinki Region Travel Time Matrix and comparing the resulting spatial accessibility conditions to a sum index of disadvantage calculated from a population grid database. This comparison was done through a Student’s t-test and testing of local bivariate relationships. Generally, the results indicated quite similar spatial patterns and good spatial accessibility conditions in floorball, football and dance when it comes to travel times to closest facilities. The horse riding facilities were located in more remote areas and were significantly fewer which resulted in longer travel times. Overall, most children reached their closest floorball, football or dance facilities within 15 minutes of biking, public transport or car travel times. Biking travel times were found to be shorter than public transportation travel times while private car provided the shortest travel times. The t-test revealed many statistically significant relationships indicating difference in travel times in the most and least disadvantaged quintile areas of the sum index of disadvantage. In these results, travel times especially in football were found to be shorter in more disadvantaged areas. This was the direction of the findings also in floorball and dance. Horse riding travel times were longer in most disadvantaged areas. The bivariate relationship tools revealed variation in the local relationships between the travel times and the sum index. In conclusion, due to travel times being of reasonable length considerable inequalities in the spatial accessibility conditions were not found, although horse riding facilities indicated some inequalities.
  • Karila, Kristiina (Helsingin yliopisto, 2022)
    Background. Among the gastrointestinal diseases of preterm infants, necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) cause the highest morbidity and mortality rates. Aim of the study. Retrospective assessment of outcome in NEC and SIP of morbidity, mortality, intestinal failure associated cholestasis (IFAC), late abdominal surgical interventions, and the effects of patients´ characteristics. Patients and methods. Data was obtained by review of hospital records with institutional ethical consent. The setting was Finnish university hospital centres: two in studies I-II and one in studies III-IV. Included were 225 surgical NEC and SIP patients from 1986 to 2014 (I-II), 93 surgical NEC and SIP patients and 20 medical NEC patients from 2002 to 2019 (III), and 165 surgical NEC and SIP patients from 1986 to 2019 (IV). The main outcome measures were mortality (I, II, III), development of IFAC (II), and late reoperations (IV). Secondary outcome measures were loss of small intestine and duration of parenteral nutrition (PN) (III). Survival statistics were assessed with LogRank (Mantel-Cox) test and risk levels with logistic regression analysis. Results. Overall three-month survival in surgical NEC and SIP was 74 %. From 1986-2000 to 2001-2014, overall three-month survival improved from 69% to 81 % (p=0.04), in NEC from 69% to 77% (p=0.30) and in SIP from 69% to 89% (p=0.04). Independent risk factors of overall three-month survival (1986-2014) were admittance to the newborn intensive care unit (NICU), birth weight (BW), gestational age (GA), respiratory distress syndrome (RDS), and septicaemias: RR=1.6-3.3 (95%CI= 1.1-8.6), p=0.005-0.01. The strongest overall predictor was the admittance to the NICU: RR=2.8 (95% CI = 1.4-5.3), p=0.003 (I). IFAC developed in 41% of patients (NEC 48%, SIP 31%, p=0.04) and was predicted by septicaemias (p=0.001) and abdominal reoperations (p<0.001). All patients with unresolved IFAC died (II). Preoperative transfusions predicted the two-week mortality in surgical NEC, although weakly: RR=1.1-1.2 (95%CI= 1.0-1.5), p= 0.03-0.04 (III). The major cause of late abdominal reoperations was small bowel obstruction with a cumulative risk 8.7% at ten years and 16% at 20 (IV). Conclusions. Overall three-month survival in NEC and SIP patients increased significantly from 69% in 1986-2000 to 81% in 2001-2014. Admission to NICU was the strongest predictor of mortality. IFAC developed in 42% of surgical patients. Unresolved IFAC was lethal. Preoperative transfusion increased two-week mortality in NEC. Small bowel obstruction was the most common late reoperation with 16% risk at two years.
  • Baddam, Vikram (Helsingin yliopisto, 2022)
    Solution properties and self-assembling of three polycations have been studied. The main emphasis was on poly((vinylbenzyl) trimethylammonium triflate) (PVBTMA-OTf), synthesized via RAFT polymerization. The PVBTMA-OTf is soluble in water, however, the presence of triflate ions turned it thermoresponsive. Both PVBTMA-OTf and its counterpart with a chloride counterion (PVBTMAC) underwent an UCST type phase transition in aqueous triflate solutions. With increasing the molar mass the cloud point shifted to higher temperatures. The behavior was different in two less hydrophobic polycations, poly((2-(methacryloyloxy)ethyl) trimethylammonium chloride) (PMOTAC) and poly (3-(acrylamidopropyl)trimethylammonium chloride) (PAMPTMAC). Higher amounts of hydrophobic ions were needed to induce the UCST behavior. Diblock copolymers comprised of a poly(ethylene glycol) (PEG) block and PVBTMA-OTf with different block lengths were synthesized via controlled RAFT polymerizations. The block copolymers underwent stepwise phase separation when the polycation blocks were kept short. During cooling, the polymers first phase separated below cloud point temperature (TcU), but solutions became clear (at TcL) upon further cooling. The stepwise phase separation was dependent on the LiOTf concentration and molar mass of the polymers. The copolymers with longer cationic blocks phase separated in a single step similarly to the phase separation of the homopolymer PVBTMA-OTf. The block copolymers formed core-shell particles below TcL. Copolymers with short cationic blocks built up PEG-stabilized particles, however, when the positively charged blocks were long, PEG was buried inside the particles. Due to the complex interactions between two blocks and as well as the interactions mediated by the counterions, the segregation of the blocks is difficult. As a result, with increasing the cationic block length the copolymers phase separated into complex aggregates. Styrenic polycations PVBTMAC were chain extended with diacetone acrylamide (DAAM) via RAFT in aqueous solutions. Only spherical particles were obtained in pure water. However, by increasing the ionic ratio [NaCl]/[Cp] (where [Cp] is the concentration of cationic repeating unit), the particle morphology changed from spheres to fused aggregates or worms, even to vesicles when short styrenic macroCTAs were used. The final morphology depended on the second block length and the solids content. Copolymers with either long styrenic stabilizers or with other macroCTAs, PMOTAC and PAMPTMAC formed spheres, cloudberries, or raspberries with increasing the salt concentration or the solids content. Cationic particles from PVBTMAC prepared in salt-free dispersions phase separated in aqueous triflate solutions at a critical temperature. In some cases, the phase separation occurred in two steps. When the PISA reactions were conducted in triflate solutions, fused spheres were obtained. Increasing the solids content, particle morphologies evolved to vesicles with small lumens. The particles prepared at 70° C in aqueous LiOTf changed from spheres or fused spheres to wormlike networks/ fused aggregates when cooled to room temperature. On the other hand, the morphologies of the particles prepared with PMOTAC or PAMPTMAC macroCTAs were not affected by triflate ions. To sum up, this work presents the use of triflate ions to induce thermoresponsive behavior in polycations and their diblock copolymers. Covalent linkage of hydrophilic PEG blocks to the responsive polycation PVBTMA-OTf enhances the stability of the particles, and the behavior is dependent on molar mass and LiOTf concentration. Using styrenic polycations as sole steric stabilizers in PISA, a full morphological window of particles can be obtained simply by adjusting the ionic strength. The particles made with styrene based cationic stabilizers also show UCST behavior. This study demonstrates the use of triflate ions in PISA to induce order-order or morphological transitions.
  • Amara, Edward (Helsingin yliopisto, 2022)
    A heterogeneous landscape with different land uses or a cluster of several ecosystems is known as a mosaic landscape. In the African savannas, such landscapes comprise, for example, agricultural fields, patches of forest, fallow fields, and wooded and open grasslands. Woody plants play important role in ecosystem services in the African savanna biome. Woody aboveground biomass (AGB) is a critical Earth’s terrestrial carbon sink and exerts a strong control on the evolution of atmospheric CO2 concentration. Mapping and monitoring carbon stocks in the tropical African region has attracted a great deal of attention in recent years. Deforestation and land degradation account for large amounts of anthropogenic carbon emissions and are now included in climate change negotiations. Therefore, quantification of woody AGB and understanding its drivers are significant in the implementation of climate change mitigation strategies in tropical savanna regions. Also, considering the growing impact of climate change and anthropogenic consequences on savanna land cover, understanding of the AGB and land use and land cover (LULC) dynamics in this region is important. The main goal of this thesis was to examine woody AGB and its drivers in mosaic landscapes of West and East Africa, namely in Sierra Leone and Kenya. More specific objectives were to study 1) the relationships among aboveground carbon stock, soil organic carbon stock and tree species diversity, 2) the impact of conservation and fences on density and distribution of woody AGB, and 3) the effect of tree size and species composition on AGB across LULC types. To accomplish these objectives, field inventory data and remote sensing data were used. The field data were collected from northern Sierra Leone and southeastern Kenya. In Sierra Leone, field data were collected from 160 plots of 1000m2 while 224 plots of the same size and airborne laser scanning (ALS) data were used in Kenya. Acquiring field data is arduous, expensive, and sometimes challenging, especially in remote areas. Remote sensing data (e.g., ALS and Sentinel-2 satellite images) data complement field-based inventories to produce LULC and AGB maps. The results emphasized that forests and woodlands in mosaic savannas have high carbon stocks and tree species diversity. The results also showed how agroforestry contributes in retaining carbon in African mosaic landscapes. Remote sensing data in combination with field inventory data provided a spatial analysis of vegetation and AGB distribution Wildlife conservation and management practices, separated by fences, significantly affect AGB and carbon stocks in tropical savannas. Overgrazing and browsing of wildlife in the conservation areas contribute to the sharp AGB transitions that lead to reduced AGB stocks. Exotic tree species, even though invasive, can have a large contribution to carbon stocks. Good management of plantation forest and conservation of forest patches especially on isolated highlands contribute largely to carbon pools. Furthermore, large trees contribute disproportionately to AGB stock. Normally these trees are harvested for different purposes, for example, for timber and fuelwood. In addition, the AGB distribution is influenced by LULC type in mosaic savannas. In conclusion, the results of this thesis highlight the importance of species composition, and large trees in AGB dynamics in African savanna landscapes. The result also revealed the variability of AGB density among LULC types and its significance in carbon storage. Laser scanning data were combined with other data to observe how conservation of megafaunas converts dense vegetation into treeless savanna grassland and results into a decline in AGB density. Therefore, keeping large trees and conserving trees with high carbon stocks in LULC types (croplands, pastures, and forests) is necessary. Moreover, the material, method, and results of this thesis are useful for national and global policy formulation on climate change mitigation and other climate change initiatives, especially those for savanna regions of tropical Africa. Keywords: Aboveground biomass; carbon; biodiversity; land use land cover types; wildlife conservation; fence; tree species composition; diameter at breast height; field inventory; mosaic savanna biome
  • Robinson-Lehtinen, Rachel Kristin (Helsingin yliopisto, 2022)
    Preterm birth (<37 gestational weeks) increases the risk for mental health problems in childhood. However, the negative mental health and the positive developmental outcomes in adulthood remain unclear. As well as, whether the increased parental stress following preterm birth (e.g. maternal postpartum depression(PPD)) impacts the relationship between preterm birth and childhood mental disorders is not known. Systematic review found consistent, moderate to high quality evidence that Very preterm / Very Low Birth weight born individuals have an increased risk for psychotropic medication use compared to term born individuals, but the evidence for specific mental health problems was inconclusive(Study I). Similarly, moderate to high quality studies of ADHD symptoms and diagnoses in adulthood revealed conflicting findings(Study II). IPD meta-analysis showed that preterm and term born adults self-reported similar levels of ADHD symptoms. However, a Finnish population-based-register study found that preterm borns had a higher risk for ADHD diagnosis at ≥18 years compared to term borns(Study II). Regarding positive developmental outcomes, systematic review found no studies on optimism among preterm born adults and IPD meta-analysis indicated preterm and term borns adults report similar levels of optimism (Study III). Finally, overall, low to moderate quality existing evidence on preterm birth and maternal PPD disorders is inconclusive(Study IV). Here, preterm birth was associated with higher maternal PPD symptoms, and higher odds of the mother having had consistently high depressive symptoms across the prenatal and postpartum period. Maternal PPD symptoms partially mediated and aggravated the association between preterm birth and child mental disorders(Study IV). The evidence on mental health in adults born preterm largely remains inconclusive, but preterm borns are more likely than term borns to be prescribed psychotropic medications and more likely to be diagnosed with ADHD in adulthood. However, preterm born adults themselves report similar levels of ADHD symptoms and describe themselves with the same level of optimism as term borns. Overall, large-scale, high-quality studies which can account for both maternal and individual level factors are needed for both negative mental health and positive developmental outcomes. The latter of which is almost entirely non-existent. Lastly, mothers experiencing PPD following preterm birth and their preterm born children may benefit from early interventions to decrease the risk of later life mental disorders.
  • Lappas, Stefanos (Helsingin yliopisto, 2022)
    Rubio de Francia’s extrapolation theorem constitutes a powerful result in the theory of weighted norm inequalities, which is a subarea of Harmonic Analysis. It allows one to deduce an inequality (often but not necessarily: the boundedness of an operator) on all weighted Lp spaces with a range of p, by checking it just for one exponent p (but all relevant weights). The main goal of this dissertation is to show analogous methods for extrapolation of compactness. The dissertation consists of an introductory part and three research articles. Our frameworks are the weighted Lebesgue and weighted Morrey spaces. In the first article we provide extrapolation of compactness for linear operators on weighted Lebesgue spaces. Several generalizations of this result such as off-diagonal and limited range extrapolation of compactness are proved as well. In the second article a bilinear extension of the main result of the first article is considered. In addition, we discuss more general results which deal with multilinear operators. The final article extends the first one to the setting of weighted Morrey spaces. Regarding the applications of all articles, in a relatively soft way, our methods recover several recent results and also give some new ones about compactness of commutators of linear and bilinear singular integrals, fractional integrals and multipliers on weighted spaces.
  • Xavier, Carlton (Helsingin yliopisto, 2022)
    Atmospheric aerosols are small, solid, or liquid particles suspended in the air surrounding us. Although small in size, aerosol particles significantly influence human life, by deteriorating the health, air quality in urban centers and influencing climate both directly and indirectly by scattering and absorption of solar radiation and modifying cloud properties. Atmospheric new particle formation (NPF) contributes the major fraction of atmospheric total particle number concentrations. NPF proceeds via the formation of nanometer-sized molecular clusters followed by the subsequent growth to larger sizes, when they can act as cloud condensation nuclei (CCN) and thus potentially affect the climate. The growth of the aerosols in the atmosphere is driven primarily by the condensation of organics or heterogeneous and multi-phase chemistry and is termed as secondary aerosol formation. In this thesis we elucidated the role of secondary aerosol formation and its impact in continental and remote Arctic regions. Additionally, we attempted at quantifying the long-term trends of important atmospheric oxidants (OH and NO3) which potentially impact both NPF and secondary aerosol formation. In spring-time boreal forest (SMEAR II) ion-mediated H2SO4-NH3 clustering could explain 91% of NPF while organics-H2SO4 clustering played a minor role according to our model simulations. Depending on the volatility, highly oxidized organic molecules (HOM), which are formed from the oxidation of volatile organic compounds (VOCs), can contribute to the growth of aerosol particles. Results from simulations performed at SMEAR II indicate that HOM contributes almost 18% to total secondary organic aerosol (SOA) mass concentration. The results further show that HOM SOA can result in a net negative radiative forcing. This negative radiative forcing by HOM SOA is offset by a net positive forcing caused by NPF under certain meteorological conditions. In remote marine environments compounds such as methane sulfonic acid (MSA), which are aqueous-phase DMS oxidation products contribute substantially to the growth of secondary aerosol particles. The long-term trends of OH and NO3 radicals show an opposite trend over the boreal forest. The OH concentrations show an increasing trend of 2.39 % annually, while NO3 decreases at a rate of -3.4 % annually. The contrasting trend of these important atmospheric oxidants, coupled with a decreasing trend in H2SO4 can have substantial climatic impacts in relation to NPF and CCN concentrations and needs to be considered in future climate predictions. Furthermore, we performed detailed process-model simulations to study the SOA mass yields from selected biogenic volatile organic compounds (BVOCs). Our results indicate that HOM dimers contribute comparatively less to SOA mass concentrations in an oxidative flow tube (OFR) when compared to smog chamber simulations. Since this directly impacts SOA mass concentrations, a cautious approach should be taken when implementing SOA mass yield parameterization from either OFR or smog chambers into global CTMs. Additionally, we developed a detailed process model ARCA-Box a flexible and easy-to-use 0-D model, which is freely available on our group website and is already used by more than 30 international researchers. This thesis attempts to improve our understanding of secondary aerosol formation using detailed process modeling and the results obtained have the potential to be applied to large-scale models.
  • Niemelä, Mikko (Helsingin yliopisto, 2022)
    Curriculum integration refers to the integration of educational knowledge or to the building of an interdisciplinary curriculum with the objective of making learning more holistic. Key questions pertaining to curriculum integration include how to differentiate between and integrate knowledge within and across the boundaries of school subjects. However, school subjects often contradict curriculum integration because the subjects seemingly fragment the curriculum. This thesis explores what it means to adopt a knowledge-based approach to curriculum integration and examines the kinds of conditions set by knowledge integration with respect to teaching and curriculum design. This article-based thesis includes three studies. Two of the studies are theoretical, while the other applies quantitative empirical methods. The studies identify three major conditions affecting curriculum integration. The first study presents curriculum integration as a challenge for teachers precisely because it expands the demands of teacher knowledge. The second study points to the subject-matter specific character of curriculum integration, meaning that not all subjects can be equally integrated with one another. Given that curriculum integration creates challenges for teachers and is subject-matter specific, the third study suggests that it needs to be addressed more clearly as an issue concerning the organisation of educational knowledge in the written curriculum. To study the requirements of teacher knowledge and how they change when curriculum is integrated, the thesis applies Lee Shulman’s construct of pedagogical content knowledge. Then, to examine why knowledge matters at the level of written curriculum, it draws on discussions about powerful knowledge in education initiated by Michael F.D. Young and Johan Muller. These two frameworks serve in a mutually complementary way to assess both the level of teaching and that of curriculum design. The knowledge-based approach reveals that integrating educational knowledge is essential to the formation of school subjects and to the design of the curriculum as a coherent whole. The major claim of this thesis is that separate school subjects and curriculum integration are not opposing poles, but rather comprise the basic elements of teaching and curriculum design.
  • Kavlak, Alper Tuna (Helsingin yliopisto, 2022)
    A major proportion of the costs of pork production is related to feed; thus, improving feed efficiency is one of the most important breeding goals in pig breeding programs. Feed efficiency measurements are based on the performance of pigs in a controlled test station environment with an automatic feeding system. During the test period, a large amount of feeding-related information, including time entering the feeder, time leaving the feeder and amount of feed consumed, are gathered. These data can be used to form different feeding behaviour traits (FBT) such as daily feed intake (DFI) or feed intake per visit (FPV). During the test period, pigs are group housed. Therefore, social behaviour between pen mates may affect feeding behaviour, production traits (PT) and welfare of other pen mates. Furthermore, unusual or radical changes in pigs’ behaviour can be a sign of diseases or discomfort and can be used for the detection of diseases for timely intervention. The thesis has three objectives. The first objective was to estimate the heritability of FBT and their correlation with PT in the Finnish Yorkshire pig population (I). The second objective was to estimate genetic parameters of feeding behaviour and PT in Finnish pig breeds using a model with a social genetic effect (SGE; study II). The third objective was to develop machine learning methods for detection of pigs that may need medical treatment or extra management based on changes in their feeding behaviour patterns (III). The data consisted of purebred Finnish Yorkshire and Finnish Landrace pigs and their F1-crosses. Pigs were raised in a controlled test station environment located in Längelmäki, Finland (Figen Oy). Pigs arrived at the test station at an average age of 89 ± 10 days (mean ± standard deviation) and an average weight of 34.7 ± 6.4 kg. The slaughter age was 186 ± 10 days, and the slaughter weight was 121.2 ± 12.9 kg. The feeding, production and sickness data were collected from 10,275 pigs that had entered the test station between 2011 and 2016 (October). From obtained feeding observation, daily values were calculated as the number of visits per day (NVD), time spent in feeding per day (TPD), DFI, time spent feeding per visit (TPV), FPV and feed intake rate (FR). The final records of FBT were calculated as averages of the daily records separately for the five testing time periods: 0 to 20 days (period 1), 21 to 40 days (period 2), 41 to 60 days (period 3), 61 to 80 days (period 4) and 81 to 93 days (period 5). The PT were average daily gain (ADG), feed conversion rate (FCR) and backfat thickness (BF) as well as residual feed intake (RFI), which was calculated as the difference between the observed and predicted DFIs. For the last objective, daily observations of the health status of pigs (794,509 daily observations) were used. The data included 13,018 observations of symptoms (cough, limp, loss of appetite, skin damage, bitten tail). Pigs with symptoms were classified as “sick” while the pigs with no symptoms were classified as “healthy”. For the first objective (I), a univariate animal model was applied for the estimation of heritability of FBT and PT and a bi-variate model for the estimation of genetic correlations between the traits. For the second objective, single-trait social genetic models were applied with two different group size parametrisations: a fixed group size with a random sampling of eight pigs for each pen and a variable group size model where the number of pen mates varied. The restricted maximum likelihood (REML) method and the DMU software were used for the variance component estimations (I and II). For the last objective, the machine learning algorithm (Xgboost) was designed with different window lengths (one-day, three-day and seven-day window lengths) using features calculated from the feeding data to predict the individual health status (sick or healthy). Heritability estimates for FBT and PT were moderate (around 0.3). Only the DFI had strong genetic correlations with PT (e.g., over 0.8 with RFI). Interestingly, the FR and FPV were associated with BF in early testing time (I). The SGE was significant for FBT and the FCR but not for the ADG and BF (II). For those traits, the total heritable variation was considerably higher than the pure classical heritability. The fixed and variable group size models produced very similar estimates (II). Using the Xgboost machine learning method, the best performance for predicting pigs’ daily health status was obtained with a seven-day window length (80% area under the Receiver Operator Characteristics (ROC) curve) [AUC], 7% F1-score, 67% sensitivity and 73% specificity). However, the precision was very low (0.04), possibly due to an imbalanced dataset (III). In conclusion, results indicate that the FBT are moderately inherited but their correlation with PT are weak; thus, FBT are not important in breeding programs. The social genetic component was important in FBT but also in the FCR; thus, applying SGEs in breeding value estimation would increase the accuracy of selection for the FCR. Predictions based on changes in feeding behaviour can help in the detection of sick pigs, leading to better pig welfare and increased sustainability of pork production.
  • Sarkia, Matti (Helsingin yliopisto, 2022)
    This dissertation deals with topics of interdisciplinary exchange and integration that arise at the intersection of analytic philosophy, behavioral and cognitive science, and the social sciences. Thematically, most of this dissertation is concerned with the phenomenon of social coordination, how it is studied in different scientific fields, and how their theoretical insights can be brought together and negotiated with one another. Methodologically, I draw on approaches in contemporary philosophy of science that are related to theoretical modeling and mechanistic explanation, understood as distinctive methodological strategies that scientists use to study complex phenomena. My focus is on studies of shared intentionality (which serves as a prerequisite for many central forms of social coordination) in analytic philosophy, and how philosophical studies of shared intentionality relate to studies of social coordination in other scientific disciplines, such as cognitive science, developmental psychology, evolutionary anthropology, and economics. In this respect, I compare the methodological status of philosophical studies of shared intentionality to the methodological status of theoretical models in science, and the activity of conceptual analysis to the activities of scientific modeling and model-construction (articles 1-3 of my dissertation). Moreover, I argue that the mechanistic approach to explanation can play an important role in bringing together different disciplinary perspectives on social coordination (articles 4-6 of my dissertation).
  • Villarreal, Sanna (Helsingin yliopisto, 2022)
    Stroke is among the most common causes of long-term disability, and cognitive symptoms especially affect patients’ recovery. Attention deficits are typical cognitive symptoms after stroke. Hemispatial neglect is a dramatic example of stroke disturbing attention as the patient’s attention is oriented toward the side of the brain lesion while the patient ignores the side opposite the brain lesion (i.e., the contralesional side). Severe neglect is associated with poor functional outcomes, but even milder deficits can cause significant real-life problems. Traditionally, neglect has been diagnosed with paper-and-pencil methods assessing visual attention. Severe neglect becomes easily evident with conventional methods, but milder deficits are more demanding to diagnose. The present set of studies aimed to examine whether visuoattentive deficits of stroke patients could sensitively be uncovered with computer-based methods. A novel large-screen method was developed, and another computer test battery was used. First, two large-screen dual tasks were compared, and their complexity was varied, in order to reveal subtle visual neglect (Study I). Then, two computer methods with different qualities were used to find out whether unilateral stroke patients show both contralesional and general deficits in visual attention (Study II). Lastly, a traditional cancellation task was converted into a digital large-screen format. The large-screen and the paper-and-pencil cancellation tasks were then compared with standard-screen dual tasks to find out which approach would be more sensitive in revealing signs of visual neglect (Study III). Forty patients with first-ever neuroradiologically verified stroke either in the left hemisphere (LHS patients, n = 20) or the right hemisphere (RHS patients, n = 20), and 20 healthy controls participated in the study. All participants underwent assessments with seven computer methods. The large-screen battery contained two visual dual tasks, a novel cancellation task, and a task with visual stimuli in fast downward motion. The standard-screen battery contained a visual single task in which brief unilateral and bilateral targets were presented, as well as two dual tasks analogous with the single task but with a visual or auditory secondary task. RHS patients showed contralesional visual inattention in all computer dual tasks, and in a standard-screen single task. Both patient groups showed general visual inattention for stimuli in fast downward motion. Neither paper-and-pencil nor the large-screen cancellation tasks were able to identify these deficits. In conclusion, computerized methods can offer sensitive assessment tools of visuoattentive deficits, which are subtle and remain undetected through traditional neuropsychological tests.
  • Mäkelä, Mika (Helsingin yliopisto, 2022)
    The dissertation examines the urban renewal of Kallio district of Helsinki in 1933–1986. Kallio was originally a worker’s residence district situating next to Sörnäinen factory and harbour area. From the 1890 onwards, Kallio area (the sub-district known today as Linjat) was built with wooden houses typical Finnish housing style of the era and quickly became the most densely populated area in Helsinki. Urban renewal taken place in Kallio was part of the international phenomenon largely affected by the architectural ideology of modernism. It affected city centres or its surroundings – often particularly the traditional workers districts, such as Kallio. During the renewal period, extensive demolition of wooden houses and the construction of undeveloped plots in accordance with the new ideas of the time were carried out. As a result of the renewal, the western part of Kallio became an area reflecting the international modernism ideology of urban design, with its numerous new buildings. The research methods used in this research have included extensive archival material review, map analysis, literature review, and interviews. The key source material has included the material produced by the City of Helsinki's administration, such as the records of the City Board, the Real Estate Board, and the Town Planning Board with necessary appendixes, as well as the decisions of the City Council. Building permit applications, historiographies produced by different actors, minutes of general meetings, professional magazines and newspaper articles have also been some of the key source material. The aim of the map analyses is to show how the built environment of Kallio developed at different stages of the study period. I have illustrated this change in terms of planning, new construction, conversion into parks, the development of the street network and the key nomenclature. Scientific literature has been used as a background to describe the phenomena occurred and the general atmosphere of different periods. The interviewees have been city officials who have previously been responsible for Kallio's town planning, residents who have experienced the reform themselves, and researchers. The main result of the study has been the essential role of the City of Helsinki regarding the change of the built environment in Kallio district. Changes in building rights based on city’s decisions have significantly guided planning and construction. The city was also responsible for detail planning in the area and integrated the development of Kallio into the expanding centre of Helsinki by locating some of its key public buildings there. The city also provided plots of land in the area for many ac-tors for their construction projects and was actively involved in various types of real estate transactions. It is also noteworthy that, despite the city's strong role, the development in Kallio has been a coincidence in many aspects. It has been significantly affected by economic booms and busts, sudden phenomena such as the outbreak of the Winter War, the lack of funding for construction, and changes in legislation governing construction and finance. Despite the city's otherwise central role, the actual construction of housing was carried out mainly by private construction companies. Kallio’s renewal process was a “puzzle for decades”. From today's point of view, the renewal in Kallio can be seen partly successful but also partly a warning example of how the existing urban environment should be developed.
  • Norri, Tuukka (Helsingin yliopisto, 2022)
    Aligned texts, such as sequence alignments or multiple sequence alignments, are sets of two or more texts in which corresponding parts have been identified. Typically the corresponding parts are determined in such a way that the amount of changes needed to transform one text to another by using editing operations, such as replacements, insertions or deletions, is minimised. Such text alignments have a variety of uses when applied to biological sequences. In this dissertation, using a set of aligned texts as an input, we consider a set of related problems that have to do with finding segmentations, i.e. splitting the texts into shorter parts by some criteria. Our first aim is to identify equivalent parts of the texts for the purpose of data compression. From the resulting segmentation we would like to construct a smaller number of sequences. These are called founder sequences since they can theoretically be seen, considering DNA sequences, as those of the founding members of some population. We solve a variant of the problem where the maximum number of distinct segments over all groups of segments separated by segment boundaries is minimised, given that the segment boundaries occur in the same positions in all input texts. Our algorithm works in linear time and takes the minimum segment length as a parameter. We also adapt the algorithm to process a set of variant records directly, and use the resulting founder sequences to build an index for a genotyping workflow. Our second aim is to find a segmentation, in which the text segments are distinct by certain criteria. Consequently, a type of graph can be built in which solving the problem of offline string matching on a labelled graph can be done efficiently. The graphs in question are called founder graphs that have the property of being repeat-free or semi-repeat-free. We present algorithms for finding the required segmentation, constructing an index data structure and determining if a given pattern occurs in the built graph in either linear or near-linear time. The achieved time complexities make the algorithms relevant for practical purposes. The work is based on five published papers and previously unpublished research. In Paper I, we extend the positional Burrows-Wheeler transform to constant alphabets with more than two characters. The transform is used as an elementary part of the algorithm for segmenting a set of aligned texts for the purpose of generating founder sequences, presented in Paper II. These are incorporated into a genotyping workflow for short reads in Paper III, where we compare the variant calling accuracy to other workflows in experiments with both simulated and natural data. In particular, we show that utilising founder sequences this way results in good precision and recall especially in case of single-nucleotide variants. In Paper IV, we describe founder graphs and show how to construct them from a set of aligned texts, in which the unaligned texts are all of the same length. We also show that if the node labels are repeat-free, i.e. sufficiently unique, the graph admits efficient indexing. We extend the theory on founder graphs in Paper V by showing how to construct an indexable founder graph from a set of aligned texts that also contains insertions and deletions. In this case, we make use of semi-repeat-free founder graphs. Additionally, we show in this dissertation that semi-repeat-free founder graphs admit a type of prefix property. We make use of the property to augment the index generated from a founder graph to include path information for the purpose of identifying the path on which a given pattern occurs from a set of predefined paths. This part of the work has not been published earlier.
  • Benkyi, Isaac (Helsingin yliopisto, 2022)
    Expanded porphyrins, porphyrinoids, porphycenes and N-doped nanographenes are multi- ring molecules whose aromaticity cannot be easily predicted based on NMR chemical shifts. The magnetically induced current-density susceptibility and the ring-current path- ways have been elucidated for these molecules at ab initio and density functional theory (DFT) levels using the gauge-including magnetically induced current (GIMIC) method. Calculations showed that the lowest electronic transition of the antiaromatic molecules are purely magnetic transitions which is also the main reason why these molecules sustain large net paratropic ring currents. The photophysical properties of expanded porphyrins, acenes and pyrene have also been studied using quantum mechanical methods. The absorption spectrum including vibrational bands of the acenes and pyrene were simulated and compared with those obtained in high-resolution measurements of the absorption spectra in the visible range. The vibra- tional contributions to the absorption spectra were obtained by using a time-generating function approach, which is computationally faster than alternative approaches. The 0-0 transition energies of acenes and pyrene are reported. Various vibrational modes contributing to the vibrational fine structure of these molecules have been identified. The quantum yield of luminescence was determined for the expanded porphyrins by calculating rate constants for radiative and non-radiative transitions between excited electronic states and the ground state
  • Saarikivi, Katri (Helsingin yliopisto, 2022)
    Musically trained individuals have been found to outperform untrained peers in various tasks specific to music performance. Interestingly, they have also been found to outperform their musically untrained peers in tasks not related to music-making, requiring a wide range of cognitive skills, such as executive functions. In a series of studies with the same participants, this thesis examines the developmental paths of different subcomponents of executive functions in a group of participants in their school years, from childhood until adolescence, while undergoing music training. Their neurocognitive development is compared with that of their musically untrained peers. The aim of the studies was to uncover whether music training is associated with improved executive functions and augmented functioning of the brain mechanisms of executive functions. Performance measures included various neuropsychological test measures and tasks created for neuroimaging experiments. Brain activation measures of executive functions were event-related potentials (ERPs) recorded with electroencephalography, and BOLD activation changes acquired with functional magnetic resonance imaging (fMRI). Differences in these measures between musically trained and untrained participants aged 9-21 were examined, as well as longitudinal change in test performance during six years. The results of the studies showed that music training is associated with the enhancement of various executive functions: working memory maintenance, inhibition, set shifting, and selective attention during childhood and adolescence. However, the improvement in set shifting diminishes with age being virtually nonexistent in early adulthood. Results also showed more efficient functioning of neural mechanisms related to executive functions. Musically trained participants exhibited lower distractibility and enhanced processing of targets during tasks for executive functions. Furthermore, still in late adolescence and early adulthood, musically trained participants had more adult-like responses and more efficient functioning of brain mechanisms for attention and executive control during tasks for executive functions than their untrained peers. Together, the results show that music training is associated with enhancement of brain mechanisms of executive functions and a passing advantage in tasks for executive functions, with the largest differences compared to untrained peers seen in school-age and early adolescence. In late adolescence, the advantage in tasks has disappeared but echoes of enhancement can be still seen in the more mature and more efficient functioning of neural mechanisms of executive functions.
  • Jansson Sigfrids, Fanny (Helsingin yliopisto, 2022)
    Despite improved treatment strategies during the past decades, individuals with type 1 diabetes remain burdened with an increased risk of premature mortality, especially due to cardiovascular causes of death. The presence and severity of diabetic kidney disease (DKD) is a main driver of the risk. DKD is predicted to affect every third individual with type 1 diabetes; however, the contemporary natural history of DKD has been poorly described. Therefore, the aim of this doctoral thesis was to obtain a holistic view of the incidence, progression, and regression of DKD. We studied incidence rate patterns, cumulative incidences, and time trends for moderate and severe albuminuria (the first clinical stages of DKD) using a population-based study design. The cohort encompassed a stratified random sample (n=1,500) of all individuals diagnosed with type 1 diabetes at the age of 0-14 years during 1970-99 in Finland. Differences between three cohorts defined by the calendar year of diabetes diagnosis (1970-79, 1980-89, 1990-99) were assessed. Progression and regression of albuminuria were studied in the nationwide, multicenter Finnish Diabetic Nephropathy (FinnDiane) Study. The DKD progression was assessed in light of remnant cholesterol and apolipoprotein C-III (apoC-III), both key components of the triglyceride-rich lipoprotein metabolism. Regression of albuminuria was defined as a change to a less advanced stage of albuminuria before the FinnDiane baseline visit. We investigated the association between regression and incident cardiovascular events and mortality. We found that the diabetes duration-specific incidence rate pattern of severe albuminuria had changed over time; the incidence peak noted at 15-19 years of diabetes duration in the 1970-79 diagnosis cohort was not replicated in those diagnosed later. The cumulative incidence of severe albuminuria had approximately halved between the 1970-79 and 1980-89 cohorts, but no further decrease was noticed between 1980-89 and 1990-99. The incidence rate of moderate albuminuria increased until 10 years after diabetes onset, then remained stable until starting to decrease at around 25 years of duration. No signs of a calendar effect for moderate albuminuria between 1980-89 and 1990-99 appeared. The albuminuria regression rate was 23%, independent of the initial DKD stage. Regression of albuminuria was associated with reduced risk of cardiovascular events and mortality to the same level of those who did not progress in the first place. Remnant cholesterol was robustly associated with DKD progression. ApoC-III was primarily associated with the progression from moderate to severe albuminuria; however, not independent of remnant cholesterol. This thesis concludes that the incidence of albuminuria has decreased over time but has plateaued after the 1980s; hence, a substantial residual burden of DKD in type 1 diabetes remains. Regression of albuminuria is a frequent phenomenon, and it is associated with an overall improved prognosis. The triglyceride-rich lipoprotein metabolism appears to be implicated in the development and progression of DKD, with remnant cholesterol possibly mediating the effects of apoC-III.
  • Saarukka, Laura (Helsingin yliopisto, 2022)
    Fluoroquinolones are a group of broad-spectrum antibacterial agents that are widely used and indicated for the treatment of genitourinary, respiratory, gastrointestinal, skin, and soft tissue infections. In Finland, fluoroquinolones comprise 5% of all systemic antimicrobial prescriptions. Fluoroquinolones are generally well tolerated and their common adverse reactions, such as nausea and headache, are mostly mild and resolve quickly. However, fluoroquinolones are also associated with more serious adverse reactions, including tendon injuries, Clostridioides difficile infections, and aortic ruptures, which can result in long-term impairment to patients and high healthcare costs. The aim of this study was to estimate the economic impact of fluoroquinolone-related adverse reactions in Finland. A systematic literature review (study I) was conducted to identify health service use and subsequent costs associated with ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin and ofloxacin -related adverse events. A retrospective observational cost of illness study (study II) was conducted to assess costs and health service use associated with tendon injuries after fluoroquinolone use in Finland during 2002-2012 with data from the Finnish Pharmaceutical Insurance Pool's pharmaceutical injury claims. Regression models were used to analyze the impact of patient characteristics on hospital days, as well as the relationship between patient characteristics and tendon ruptures. In study III, a cost of illness decision tree model was built to predict costs and mortality associated with serious adverse drug reactions. Severe Clostridioides difficile infections, severe cutaneous adverse reactions, tendon ruptures, aortic ruptures and liver injuries were included as serious adverse drug reactions in the model. In study I, 19 observational studies, including five case-control studies, fulfilled the inclusion criteria. Length of hospital stay associated with adverse events varied between <5 and 45 days. Clostridioides difficile infections were the adverse event type associated with the longest stays in hospital. The estimated cost of an adverse event treatment episode ranged between 140 € and 18,252 €. In study II, fifty-one percent of the claimants were hospitalized due to tendon injuries, with an average duration of 21 days and an average cost of 9,915 € per hospital episode. Hospital days and direct costs increased with the severity of the injury. Concurrent use of oral glucocorticoids and increasing age were associated with a higher likelihood of tendon ruptures. In study III, a total of 1,831,537 fluoroquinolone prescriptions were filled between 2008 and 2019 in Finland. Severe Clostridioides difficile infections were the most frequent, fatal, and costly serious adverse reactions associated with the use of fluoroquinolones. Because of the wide clinical use of fluoroquinolones, in particular serious fluoroquinolone-related adverse reactions can have substantial economic implications, in addition to imposing potential long-term disability for patients. Accordingly, the risks and benefits of fluoroquinolones should be weighed carefully in antibiotic prescription policies, and additional measures should be developed to prevent and reduce health service use and costs associated with fluoroquinolone-related adverse reactions.
  • Kuisma, Heli (Helsingin yliopisto, 2022)
    Uterine leiomyomas (ULs) are extremely common, benign smooth muscle tumors. Their incidence is 70% in the Caucasian population by the age of fifty and even higher in black women. They cause symptoms such as pain and abnormal menstrual bleeding in 25% of the affected women. At present, surgery is still the only widely used curative treatment option. Taken together, ULs cause both significant morbidity and a huge economic burden. Based on driver alterations, ULs have been divided into three distinct subtypes: 70-80% of ULs have a MED12 mutation, 10-15% a HMGA2 overexpression, and 1% a biallelic FH inactivation. The driver event for the remaining 10-15% of ULs remains unknown. The subtypes have different molecular and clinical characteristics, but the tumorigenic mechanism of the driver events is elusive. Based on family studies, population disparity, and previous linkage- and association analyses, ULs have a hereditary component. The aim of this thesis was to characterize both the germline and somatic landscape of ULs utilizing various genome-wide methods and both biobank material and a large collection of over two thousand prospectively collected tumor samples. Previous studies on the heritable component of ULs have been limited by small sample sizes and have discovered only few significant loci. Furthermore, the role of these loci in myomagenesis remains unclear. In Study I, we performed the largest UL genome-wide association study (GWAS) to date revealing 22 significant loci. Most of the candidate genes could be categorized as either genitourinary development genes or genetic stability genes. Among the candidate genes were ESR1, MED12, TP53, and TERT. In Study II we scrutinized a set of tumors with an unknown driver event and discovered mutations in six of the nine SRCAP complex genes. Overall, these mutations were detected in 2% of all ULs. SRCAP complex loads variant histone H2A.Z into chromatin, mostly to active and bivalent transcription start sites and enhancers. We showed that this loading is defective in the SRCAP complex mutated lesions. By integrating data from various sources, we were also able to highlight the importance of bivalent regulation in all UL subtypes and pinpoint genes regulating development and differentiation, such as CBX2, CBX4, and CBX8, as potential players in UL genesis. In Study III we examined SNP-array data from 1,946 tumors and showed an association between parity and the total length of allelic imbalance, complex chromosomal rearrangements, and whole chromosome losses. Mechanical forces have been shown to be able to cause DNA damage; in pregnancy and parturition, the uterus undergoes major changes in size and is affected by large mechanical forces. Furthermore, we showed in vitro that stretching can cause damage and detected both increased DNA damage and repair in stretched myoma and myometrial cells. Taken together, we established mechanical stretching as a potential new mechanism for tumorigenesis. The differential diagnosis of uterine tumors is sometimes complicated. In Study IV we detected nine tumors initially diagnosed as ULs expressing tyrosine kinase fusion genes. Such fusions have not been described in ULs but are typical for inflammatory myofibroblastic tumors (IMTs). IMT is a rare tumor type with intermediate malignant potential. These tumors can have a fascicular growth pattern that closely resembles ULs. We discovered that the protein expression and morphological pattern of the tyrosine kinase fusion-positive samples were leiomyoma-like. In gene expression level, some differences to UL subtypes were detected. Among the pathways enriched in the tyrosine kinase fusion-positive lesions was epithelial-to-mesenchymal transformation. Our results raise the question on whether these tumors are UL-like IMTs or tyrosine kinase fusion-positive ULs and highlight the heterogeneity of uterine lesions.
  • Eklund, Andreas (Helsingin yliopisto, 2022)
    There has traditionally in political science research been a strong focus on democracy and how democratic countries function. In recent years there has also been a growing interest towards autocratic countries and their internal differences. The purpose of this dissertation is to study the impact of political structures on regime transitions in autocratic countries. The empirical investigation covers seventeen countries from the Middle East and North Africa and their political development from 2011 to 2019. The countries are compared on the basis of their differences in regime type, stateness and resources. The dependent variable is regime transitions and it is analyzed in two different phases and from two different perspectives. In the first phase, the countries are analyzed based on whether regime breakdown or regime survival took place after the large protests in 2011 that often are referred to as the Arab Spring. This analysis is conducted with qualitative comparative analysis (QCA). In the second phase, the results from the QCA analysis are placed within a longer timeframe from 2011 to 2019. To the extent that changes have occurred they are described as three different patterns: democratic transition, new autocratic regime type and state failure. The analysis shows that the countries with regime breakdown have developed in very different directions, where all of the previously mentioned patterns have occurred. The countries with regime survival have been less diverse in their development, although there also in the group are some deviating cases. The development over the period 2011 to 2019 is in all of the countries largely in line with the theoretical expectations concerning the impact of regime type, stateness and resources on regime transitions. There are however a few examples where deviating patterns concerning regime type and stateness occur. The dissertation provides a broader understanding of the link between regime breakdown and the subsequent political development. The dissertation further discuss the development in the Middle East and North Africa in the light of the global development of democracy.

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