Opinnäytteet ja väitöskirjat: Recent submissions

Now showing items 1-20 of 45942
  • Oliveira da Silva, Filipe (Helsingin yliopisto, 2021)
    Snakes are intriguing organisms, yet their ancestral ecology and evolutionary history remained uncertain for centuries. This debate received renewed attention due to controversies about the interpretations of fossils, ecologies, and evolutionary relationships. Thus, new approaches were needed to investigate the early evolution of snakes. It is well-known that biological shape can be linked with certain functions and that the skull is an important ecological structure. So, it is relevant to investigate the skull shape to understand more details about the evolution and ecology of early snakes. In this dissertation, I investigated hundreds of skulls of lizards, snakes, and tuatara to address the ecological origin and radiation of snakes from lizards. I used cutting-edge geometric morphometrics (investigates the form of biological structures), comparative (uses phylogenetic trees), and multivariate analyses (takes higher biological complexity into consideration). I evaluated four hypotheses. i: skulls of lizards and snakes that dig in the soil and mostly live underground (fossorial) are more similar than expected under a neutral model of evolution; ii: skull shapes and ecologies are correlated, meaning that certain shapes are commonly associated with certain ecologies, which also allows us to predict the ecology of fossils and estimated ancestors based on the skull shape; iii: snakes evolved from either a fossorial, marine, or terrestrial ancestor; and iv: heterochrony - evolutionary changes due to changes in the rate and length of development - underlies the skull shape development and morphological innovation within and among snakes. I found that the skull shape of fossorial lizards and snakes are convergent, indicating that natural selection played an important role. I found a significant correlation between form and function or skull shape and ecology. In an analogy, this is like thinking about the different kinds of pans you have in your kitchen. The frying pan has a different shape in comparison to the boiling pot and you recognize their use based on their shape. I then estimate the shape of the ancestors and with high statistical confidence the ancestral ecology of snakes. Surprisingly, snakes most likely evolved from a terrestrial lizard-like ancestor. The earliest snake ancestor was most likely small and fossorial. Finally, heterochrony through acceleration in the skull shape development was detected in alethinophidian snakes, likely underlying the rise of evolutionary innovation and ecological radiation. All that said, this dissertation opened new avenues and approaches to investigate snake and vertebrate evolution in innovative ways that led to intelligible, plausible, and fruitful outcomes.
  • Kemppinen, Heikki (Suomalainen lakimiesyhdistys, 2021)
    This study focuses on why a judge should provide reasoning for a decision of criminal sentencing and how the reasons should be written in different circum- stances. While answering said questions, the aim of the study is to create a com- prehensive picture of sentencing and the various separate decisions a judge may have to deliberate on before arriving at the final length and form of the sentence. The preliminary chapters of the study provide a foundation for the discussion of reasoning by focusing on the legal sources of sentencing. When dealing with the question ”why reason”, the study applies theories about legal reasoning of judicial decisions to the area of sentencing. A central focus is on the so-called functions of judicial reasoning. On the other hand, the analysis is enriched by factors dealing namely with sentencing, such as the demands of equality and uniform sentencing practice. The question “how to reason” is handled both as a general matter and through an examination of different situations most commonly faced by judges. The aim is not to present models of optimal reasoning but to examine how different situ- ations and contexts of decision-making and the norms related thereto affect the content of reasoning. Theoretical discussion of the subject is paired with an empirical portion, in which a sample of judicial decisions in criminal cases is analyzed in terms of the reasoning of sentencing contained therein. The aim of the theoretical part of the study is to systematize and interpret the legal norms dealing with sentencing and reasoning, while also keeping an eye on the somewhat unique sources of law regarding sentencing practice. The em- pirical analysis has features of both qualitative and quantitative research. As for point of view, the reasoning of sentencing decisions is approached from the judge’s perspective. In other words, the research questions concerning the factors to be taken into account in the reasoning of sentencing decisions are combined with the actual deliberation of sentencing carried out by the judge.
  • Salovaara, Veronica (Helsingin yliopisto, 2021)
    This study examines students’ scope of action in the transition phase from basic education to further education and training. The focus in this research is on how inequality is reproduced in the transition phase from basic education to upper secondary education, as well as the role of family, school and other social networks in contesting inequality. The analysis shows the complexity on how students navigate in the transition phase from basic education to further education and training. A student’s scope of action in this study is understood as the scope in which students make their decisions and reflect on their options, whether it is a more agency reflected process, or a process steered by the capitalistic power mechanisms or habitus. Young peoples’ agency is therefore understood as structured by the interplay between students own choices and wishes, social background and habitus, situated in a sociopolitical and education policy context. The data set has been derived from the three-year (2010–2012) comparative European project GOETE - Governance of Educational Trajectories in Europe. The data set is a multifaceted qualitative data set comprehending interviews and focus groups with 101 people from three local schools in Finland, social and youth work as well as education policy; students, parents, teachers, guidance counselors, principals and other experts at school, such as school social workers, school nurses and school psychologists. In addition, the data consists of interviews with experts in education and social work, e.g., education policy experts, social and youth workers and guidance counselors from the upper secondary level as well as relevant policy documents. The results showed a paradox in the discourses: students are responsible for their own educational trajectory, however the trajectory is predetermined. Throughout the analysis, there is a discourse emphasizing students’ agency, or a discourse emphasizing responsibility, that students should choose their educational trajectory by themselves without interference from others. Students used various modes of reflectivity when choosing their educational trajectory. A discourse on accepting predetermined educational trajectories was present among school professionals, either by accepting predetermined educational trajectories as something static that is difficult to change, or by fighting against these predetermined educational trajectories. Family background shapes the student’s decision-making process and therefore when students are using agency in the decision-making process, the agency is merely a reflection of the social structure as the social structure and the structural position of the individual is generating the individual’s agency. The responsibility that students are demanded to take, while making the decision within a certain context, or within ‘predetermined limits’, gives the students an illusion of choice. Structures of inequality and class casts a long shadow in education and is reproduced through the practices of accepting educational inequality by not contesting the role of the gatekeepers of equality and equity. At the national level, education is regarded as one of the more effective means to prevent the marginalization and social exclusion of young people.
  • He, Xu-Cheng (Helsingin yliopisto, 2021)
    New particle formation is estimated to contribute to around half of the cloud condensation nuclei (CCN) in the atmosphere which in turn have a cooling effect on Earth’s surface. Only a few gas species, including sulfuric acid, oxidized organic vapors and iodine species, are confirmed to contribute to new particle formation, which converts gases to aerosol particles. While new particle formation from sulfuric acid (with water or bases, such as ammonia and amines) is recognized globally, new particle formation solely induced by pure organic vapors only occurs under special conditions. Least is known about the coverage of iodine particle formation processes in the atmosphere. Iodine species have widely been measured in marine and polar environments. However, most ambient measurements concentrated on molecular iodine (I2 ), iodine monoxide (IO), iodine dioxide (OIO) and organic iodine precursors. These measurements constrained the effect of iodine species in catalytic ozone loss processes, but far from enough to understand the particle formation processes. In this thesis, I utilized a bromide chemical ionization method to nearly comprehensively measure inorganic iodine species, including I2 , iodine oxides and oxoacids. An unprecedented performance both in coverage and sensitivity is achieved. We further deployed the bromide chemical ionization method for ambient observations at the Mace Head observatory on the Atlantic coast of Ireland. First successful online measurements of hypoiodous acid (HOI), bromoiodide (IBr) and chloroiodide (ICl) confirmed the heterogeneous uptake of HOI at ambient conditions which enhanced iodine atom production rate by 32% and accelerated ozone (O3 ) loss by 12%. Comprehensive experiments were further carried out at the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber to understand the iodine particle formation mechanisms. We found that the ion-induced (charged) and neutral nucleation proceed via distinct mechanisms. The ion-induced nucleation proceeds primarily by sequential addition of iodic acid (HIO3 ) which was measured to proceed at the kinetic limit. However, in contrast to earlier expectations, neutral nucleation additionally involves iodous acid (HIO2 ) to stabilize HIO3 , replacing the role of the negative charge in the ion-induced nucleation. After passing the critical size of nucleation, the growth of iodine particles is essentially sustained by HIO3 , with minor contributions from other species, which are present at much lower concentrations. Additionally, iodine oxoacids have much faster particle formation rates than the sulfuric acid – ammonia mixture at the same acid concentrations (when the ammonia mixing ratio is 100 parts per trillion by volume). While sulfuric acid – ammonia new particle formation has been confirmed to be an important mechanism in polar regions, the role of iodine new particle formation is usually considered to have a limited global reach. We carried out iodic acid measurements at ten boundary layer sites, ranging from the cleanest polar regions to polluted urban environments. The existence of iodic acid is ubiquitously confirmed, with concentrations comparable to sulfuric acid. This indicates a greater importance of iodine oxoacid particle formation processes than just a coastal phenomenon.
  • Hannikainen, Pietari (Helsingin yliopisto, 2021)
    This study examines the worship community movement in the Evangelical Lutheran Church of Finland, by using the methods of quantitative participant research. The movement consists of about 40 worship communities that build alternative, communal congregational life and worship in and around local parishes. It connects to a broader paradigm shift in Protestant churches that have faced the challenges of pluralistic and secularized societies. As the movement is growing and attracts participants of all ages, the research focused on determining what factors of the movement explain its expansion at a time when the cultural position of the Evangelical Lutheran Church in Finland is breaking down and its membership is sharply declining. This question was addressed, first, by determining what the religiosity of the worship community participants is like. In addition, efforts were made to find out how the cultural changes associated with modernization are reflected in the values, communality and religiosity of community participants. The data was collected by two-level cluster sampling from ten communities representing the community movement. The result was 529 acceptably completed forms. The results of the data analysis were published in three scientific articles that make up the material of the summary article of this dissertation. Three types of participants were discovered with regard to patterns of participation, which were termed as traditional, community-oriented, and experiential. The traditional type represented culturally declining models of collective cultural forms, while other types appeared more culturally modern. The values and participation of the community-oriented type were characterized by openness to change, a desire to learn new things and a commitment to the opportunities of active participation offered by the communities. Consequently, they experienced the strongest sense of belonging to the community. The experiential type of participation was the least committed and appeared to be the most self-centered in terms of values. These traits were explained in some measure by difficulties in their personal and social lives. According to the study, the new communities of worship have emerged as a culturally innovative movement whose religiosity emphasizes the transcendent core of Christianity. Also the study indicates that they are theologically inclusive and do not place particular emphasis on the doctrinal and normative aspects of Christianity. Thus, they can be seen to represent a broader shift in religiosity that reflects a response to the broad “subjective turn” in values that is taking place in the postindustrial West. On the other hand, the movement can also be seen as a reaction to the secularization of the church and of society as well as to individualism, which tends to exclude individuals from social safety nets. Communities for the New Generation provides comparable and generalizable empirical information on a little-studied, emerging phenomenon that reflects wider developments within protestant churches as well as people’s changing expectations of parish-life, church, and spiritual life in our time.
  • Facciotto, Chiara (Helsingin yliopisto, 2021)
    Overcoming drug resistance in cancer is one of the most pressing issues in oncology. The last century saw a dramatic increase in the discovery of new cancer therapies, so much so that chemotherapeutic agents and immunotherapies are now, alone or in combination, the backbone of treatment for many cancers. Despite the increased rate of treatment success brought by these regimens, cancer patients can become resistant to these drugs. This leads to disease relapse, hindering patient survival. Drug resistance remains the primary cause of death in most advanced-stage cancer patients. The molecular mechanisms responsible for the development of a resistance phenotype in cancer cells are complex and include both genetic and epigenetic alterations. Since drug resistance is a multifactorial phenomenon, we used a systems biology approach to investigate it on different fronts. Specifically, we developed a high-throughput drug screening method to test new drug combinations, identifying epigenetic inhibitors able to sensitize lymphoma cells to doxorubicin. We also implemented a bioinformatic pipeline which combines multiple omics data to identify genes and pathways driving platinum response across multiple cancers. We then developed a method to compute differential methylation between cancer samples with varying and unknown tumor purity, which we used to investigate DNA methylation changes linked to drug resistance in ovarian cancer and lymphoma. Finally, we created a workflow management system to build complex bioinformatic pipelines and aid researchers in the analysis of high-throughput biomedical data. By combining laboratory biology experiments and computational analyses, we gained a broader understanding of the cellular mechanisms behind immunochemotherapy failure. Moreover, we were able to identify novel biomarkers associated with platinum response in multiple cancers, as well as new drug combinations able to overcome immunochemotherapy resistance in lymphoma cells. The in vitro and in silico methods presented in this thesis can not only assist researchers in the cancer field, but are broadly applicable to other fields of biomedical research. Overall, this work is an important stepping stone in both understanding and overcoming drug resistance in cancer, and has great potential to improve outcomes for cancer patients in the future.
  • Kyrö, Kukka (Helsingin yliopisto, 2021)
    Urbanisation drives drastic changes in land cover and land use with multiple environmental impacts. A compact city structure, e.g., helps to reduce energy consumption and fossil fuel emissions. Yet, the increase in urbanized land cover has become a major cause of habitat loss and fragmentation – factors that are rated among the greatest threats to the variety of life on earth. Thus, there is an urgent call to search for tools that mitigate and, eventually, halt the decline of wildlife and plants with urbanization. In this thesis, I study vegetated roofs as tools for arthropod conservation in urban environments. Vegetated roofs, also known as green roofs, are purposely covered with substrate or soil and plants. They avert a multitude of environmental problems caused by the replacement of natural habitats with anthropogenic land use. They can be used, e.g., for stormwater retention and carbon sequestration. In addition, they turn building tops into habitat for plants and mobile animals. Thus, they are assumed to mitigate the loss of habitat and biodiversity due to urban development, but knowledge from vegetated roofs as habitat patches has not been sufficient to evaluate this assumption. I use arthropod data from vegetated roofs with low-growing, drought tolerant vegetation dominated either by forbs and/or grasses or succulents and mosses. I describe arthropod assemblages (beetles in Chapter I and multi taxa assemblages in Chapters II & III) using taxonomic and trait data and apply island biogeography theory and community ecology as frameworks to study the effects of biophysical roof characteristics, roof age and the landscape on arthropod abundance, richness and community composition. I found vegetated roofs to host arthropods with active and passive aerial dispersal strategies and either tolerating a wide range of habitats or associated with dry habitats. Most species were common generalists, but a few rare and endangered species also occurred on roofs. In addition, I found indication that vegetated roofs may sometimes serve as platforms for introductions of exotic arthropod species. Both local roof characteristics and the landscape shaped arthropod community composition on vegetated roofs. Roof characteristics, particularly vegetation, but also roof height and age, shaped arthropod abundance with taxon-specific effects. Most taxa responded positively to forb cover or to a combined cover of forbs and grasses, and some phytophagous groups were rare on roofs that had vegetation consisting almost exclusively of succulents and mosses. The vertical isolation of roof habitats is an effective filter that excludes less mobile species, but species that were able to colonize the roofs responded even positively to roof height, possibly because of decreased competition and/or predation. Roof age had a variable effect on arthropod abundance and richness, which are likely connected to variation in the vegetation and changes in biotic interactions. In this thesis, I have shown that urban vegetated roofs with shallow substrate benefit native arthropods associated with dry habitats and open vegetation, but do not automatically provide high biodiversity values and may sometimes serve as agents for exotic species. The ecological value of roofs can be improved by designing them from a habitat provision perspective and as part of the habitat network existing at ground level. My results point to the benefits of planting roofs with diverse vegetation instead of using only a few succulent species, when designing vegetated roofs to support a rich arthropod fauna.
  • Schön, Esa (Helsingin yliopisto, 2021)
    The study examines the player contract models of professional and amateur athletes commonly used in Finland from the perspective of the law in force. The study seeks to determine how the specific features of the contractual relationship affect the determination of the legal effects of a professional athlete's contract as an employment contract, and how the legal status of professionals and amateurs differs from each other. A player contract can be defined as a contract of employment, which establishes an obligation for the athlete to contribute to the sporting success of the club by working in accordance with the provisions of its coaching staff in the team assigned to him at any given time. The characteristics of a player contract involve certain legal effects, the most important of which is probably that the player contracts are without exception fixed-term contracts. Competitive sport is a struggle between participants for mutual superiority according to the rules. It is characterized by rule-specificity, as sports are in practice sets of rules, and competition requires that all participants commit to the rules. The pursuit of victory is at the heart of competitive sport and a central part of the principle of fair play. Deliberately impairing the performance of the game or playing in pursuit of a pre-agreed outcome is therefore contrary to the player's contractual obligations. On the other hand, competitive sports by their nature are also characterized by the possibility of failure. A player cannot be considered in breach of his obligations, even if the sporting objectives have not been achieved, unless can be shown to have intentionally played below his ability, neglected training or by his conduct impaired his ability to play. Nor can a player be required to precisely follow the orders of the coaching staff in an everchanging game situation. The most important feature of player contracts is their emphasized personal nature. It is particularly relevant to the athlete's obligation to work and to the application of the provisions of the Employment Contracts Act, which restrict the use of fixed-term contracts, but also to the termination of a player's contract, for example. It also requires that the club allows players to play the sport and take into account the athlete's legitimate interests in deciding, for example, team composition and player training, although the athlete does not have a subjective right to be part of a team even when, for their sporting merits, this could objectively be considered to fit into it. Professional and amateur player contracts are essentially similar in content and legal effect. However, there are also some differences between them, which are the result of mandatory labour law that applies predominantly to professional athletes.
  • Pärnänen, Katariina (Helsingin yliopisto, 2021)
    Antibiotics were once miracle cures, but because of the spread of antibiotic resistance in bacteria, their effectiveness is threatened. Although antibiotics have only been produced industrially for 70 years, antibiotic-resistant bacteria are a threat to human health. The effects of antibiotic use pass on over generations, and resistance kills an estimated 214,000 infants a year. Antibiotic-resistant bacteria have also become widespread in the environment. In my dissertation, I used a microbial ecology perspective to study how the antibiotic resistance crisis manifests itself in humans (with a focus on mothers and infants) and in the environment. My main lines of research focused on selection pressures that shape bacterial communities and the effects of the spread of resistant bacteria. I studied the amounts of antibiotic resistance genes in different environments, utilizing methods based mainly on metagenomics. Mothers pass on antibiotic-resistant bacteria to their children. However, in my study, the resistance load of infants’ intestines was most affected by infant formula use. Infants who received formula had a significantly higher proportion of bacteria carrying resistance genes than exclusively breastfed infants. Surprisingly, formula use increased the intestinal resistance load more than the antibiotic regimens given to babies, which could not be shown to have an effect in my dissertation. Antibiotic selection pressure did not explain the number of resistance genes in the environmental samples I studied either. The results suggested that fecal contamination is almost always behind the resistance load observed in the environment. It was therefore interesting that the treated wastewater discharged from European wastewater treatment plants into the environment corresponded to the types of resistance of bacterial strains isolated from infected patients. The result suggests that inadequate wastewater treatment is part of the resistance problem in Europe as well, and not just in developing countries, and potentially increases the spread of antibiotic-resistant bacteria to humans. My work shows that the most effective ways to reduce resistance may not be intuitive. Bacterial spread may play a larger role than previously thought. Efficient waste treatment and exclusive breastfeeding may reduce the number of resistant bacteria in society, the environment, and young children more effectively than reducing the use of antibiotics.
  • Väärikkälä, Sofia (Helsingin yliopisto, 2021)
    The European Union (EU) began to provide legislation on farm animal welfare four decades ago. Farmers working in the EU are required to comply with standards to ensure that the welfare of animals is managed, and no unnecessary pain, suffering or injury is inflicted on the animals. EU member states (MS), on the other hand, are obligated to control the compliance of the farmers. The competent authorities of the MS must conduct on-farm controls regularly, on a risk basis and with appropriate frequency, and apply appropriate enforcement measures to secure the rectification of non-compliance. Since official animal welfare control plays a pivotal role in the enforcement of animal welfare legislation, it is of the utmost importance that the control functions in practice. This research investigated how Finnish official animal welfare control appears at the farm level. Official veterinarians as enforcers and farmers as targets of the controls were surveyed to examine their views on the matter, and the reports from animal welfare inspections and court decisions regarding animal welfare crimes were analysed to explore the outcomes of the controls. Animal welfare control work caused stress to official veterinarians. High levels of stress were associated with threatening situations at work, the inconvenience of working alone, disrupted work–life balance, and a large amount of overtime work. The more stress the official veterinarians experienced, the more poorly they perceived their job satisfaction. Nevertheless, the job satisfaction was positively influenced by the provision of support and sufficient resources, an opportunity to work in pairs and well-functioning collaboration with other officials. Farmers experienced animal welfare inspections on their own farms negatively. Over half of the responding farmers saw the inspection as unnecessary and one in three considered it as violating their legal protection. Easy interaction with the visiting official veterinarian and the comprehensibility of inspection documents improved the attitude of the farmers towards the inspection. The farmers reported appreciating explicit reasons for the inspections, adequate reasoning for non-compliance detected, and the provision of appeal directions. Our results show that a quarter of cattle and pig farms inspected based on sampling was non-compliant during 2010-2015. The most frequently reported non-compliance on cattle farms included wet and dirty lying areas, inadequate weather protection and the deficient housing conditions of calves, while on pig farms they included the insufficient provision of enrichment material and incomplete records of medical treatments. Non-compliance was reported more frequently on cattle farms with small herds, tie-stall housing or outdoor rearing, and on pig farms with a farrow-to-finish unit. Our investigation identified slowness in criminal procedures and illogicality in penalties regarding animal welfare crimes during 2011-2016. In most cases, animal welfare violations had continued for a long time before the case was heard in court. The median span was nearly two years from the beginning of an offense to a conviction. Of the accused individuals, 96% were found guilty and punished for an animal welfare crime. The court frequently applied the lower end of penal scale; however, they still imposed a ban on animal keeping for every second perpetrator. Our research uncovered certain weaknesses in Finnish official animal welfare control, including unsuccessful targeting of animal welfare inspections, inadequate guidelines for ambiguous animal welfare standards, official veterinarians’ high workload and insufficient safety at work, limited collaboration between official veterinarians and officials for social and health welfare, and inefficiency in criminal procedure regarding animal welfare matters. The findings yield the following recommendations: i) Inspections should be more accurately targeted. ii) Official veterinarians should aim at a constructive dialogue with a farmer and ensure that they understand the outcome of an animal welfare inspection and the progress of the matter. iii) Guidelines for implementing ambiguous animal welfare standards should be improved. iv) Official veterinarians should be offered the opportunity to conduct controls with a partner, be strongly supported by their supervisors, and receive training in communication skills. v) Collaboration between official veterinarians and other officials, such as the police and social welfare and health officials, should be consolidated. vi) The official veterinarians’ role as an expert during criminal procedures should be strengthened.
  • Ruohtula, Terhi (Helsingin yliopisto, 2021)
    Type 1 diabetes (T1D) and allergies are considered autoimmune diseases. The exact mechanisms leading to these diseases are mostly unknown, but genetic and environmental factors are involved. Regulatory T cells (Tregs) have a crucial role in initiating and maintaining tolerance, limiting harmful autoantigen-specific inflammation processes. This doctoral thesis explores the effect of environmental factors on the development of the immune system by studying peripheral immunological responses in healthy infants at genetic risk of T1D in two follow-up studies. The first study investigated the development of peripheral Treg cells in infants from Estonia and Finland, neighboring countries with differing living standards, and the incidence of T1D and allergies. We demonstrated a two-step maturation process in the circulating Treg cell population in the first two years of life. First, a decrease in the proportion of Treg cells followed by an increase in the highly activated Treg cells (TregFOXP3high), with enhanced suppressive activity. The Treg cell maturation process coincided with the microbiota composition development from a Bifidobacteria dominated to one dominated by butyrate-producing species by 36 months. The abundance of Bifidobacteria and the relative abundance of B.longum alone at three months showed an inverse association with atopic sensitization. The switch in the microbiota happened earlier in Estonia and was associated with more highly activated TregFOXP3high cells with FOXP3 and CTLA-4 expression. This earlier maturation of the circulating Treg population is associated with a lower risk of allergic diseases in Estonian children. Additionally, we analyzed the common enteral virus infections in the first year of life. We observed a temporal association of virus infection with the expression of FOXP3 in regulatory T cells. Infants with enterovirus infection during the preceding 30 or 60 days had a significantly decreased FOXP3 expression in TregFOXP3high cells. In addition, we observed upregulation of Th1- and Th17 -related cytokines and a decreased activation of CCL22, associating with activation of proinflammatory pathways and reduced immune regulation. In the second study, we examined whether exposure to bovine insulin is a trigger of autoimmunity by studying the appearance of diabetes autoantibodies. We studied exclusively breastfed infants or infants after exposure to different infant formulas; cow-milk formula (CMF) with bovine insulin, whey-based hydrolyzed formula, or a virtually bovine insulin-free whey-based hydrolyzed FINDIA formula during the first six months of life, whenever breast milk was not available. The follow-up was up to at least three years of age. We showed that weaning to the FINDIA formula reduced the incidence of autoantibody positivity when compared with CMF-formula. This result might reflect a dysfunctional immune system. Bovine insulin peptides from the infant formula may activate autoreactivity against the primary autoantigen, i.e., human insulin, resulting in non-tolerogenic T cells. To conclude, the study shows that environmental factors may influence regulatory T cells and immunotolerance. Also, nutrition may influence the development of the immune system or autoantibodies to T1D in infants genetically at risk. Keywords: type 1 diabetes, allergy, regulatory T cells, autoantibodies, viruses, diet
  • Rawlings, Anna (Helsingin yliopisto, 2021)
    The aim of the thesis was to examine how temperamental reward and punishment sensitivities guide motivation in different learning contexts. Motivation was approached as students' relatively stable motivational tendencies (i.e., achievement goal orientations), and appraisals of domain- and course-specific interest, strain, and effort. The thesis comprises three articles. In Article I, the dimensional structure of temperamental sensitivities was studied in two data sets (Study 1; N = 157; Study 2; N = 506), and the predictions of temperamental sensitivities on university students’ achievement goal orientations were also examined. In Article II, the relationships between temperamental sensitivities and achievement goal orientations were followed over the first three school years (N = 212). In Article III, the impact of temperamental sensitivities on interest, strain, and effort was investigated in the domain of mathematics among eighth-graders (Study 1; N = 268), and course-specifically in four different subjects among general upper-secondary students (Study 2; N = 155). Reward sensitivity separated into two main dimensions, defined by the source of reward. Interindividual reward is dependent on the attitudes and actions of others (e.g., attention, praise), whereas intraindividual reward is derived from the individual’s own inner states and actions (e.g., positive responsiveness to novelty, enthusiasm and excitement over successes). Temperament was consistently associated with motivation, regardless of the age of the participants. Interindividual reward sensitivity appears motivationally problematic, given its negative links with mastery strivings, and positive with concerns over one’s performance relative others, work avoidance, and psychological strain. Punishment sensitivity was also linked with higher performance concerns and strain. In contrast, intraindividual reward sensitivity was associated with higher mastery strivings, interest appraisals, and willingness to exert effort, and may hence be more beneficial motivationally and for well-being. The findings indicate that temperamental sensitivities guide motivation in adaptive and maladaptive ways, both academically and as regards well-being more generally. Also notable for research and educational practice are the differential linkages between sensitivity to qualitatively different rewards and motivation.
  • Åberg, Annika (Helsingin yliopisto, 2021)
    A proper risk assessment is part of mining projects from early stages to mine closure. Publicly companies present these assessments for example, in their Environmental Impact Assessment (EIA) reports. Potential risks related to water circulation can be investigated using groundwater flow modelling. In the present study, series of simple to more complex 3D geological models (GMs) were constructed from a Sakatti Ni-Cu-PGE deposit area in Sodankylä, northern Finnish Lapland to produce a numerical groundwater model. The 3D GMs were constructed utilizing data from outcrop investigations, various types of drillings and data obtained from non-destructive ground penetrating radar (GPR) soundings. In order to shed light on regional glacial history of central Finnish Lapland, outcrop studies, the existing till stratigraphy (GTK database) and LiDAR DEM imageries were used to investigate the sedimentary succession, interpret the depositional environments and reconstruct the Weichselian glacial flow patterns. The results of this study indicate that complex and detailed geological models are beneficial, especially in areas with a high hydraulic gradient, multiple units with differing hydraulic conductivity, and altered upper bedrock zone with variable degrees of weathering. Furthermore, it is essential to identify low conductive units, such as interbedded fine-grained till units, as well as high conductivity units such as fractures and faults, since they affect the location of recharge and discharge areas in hydrostratigraphic flow models. The 3D GMs constructed for the Sodankylä study area illustrate that altered bedrock, including fractured bedrock as well as grus- and clay-type weathered bedrock, is a prominent feature of the study area. The results of this study for example, indicate that fractured bedrock is more than 50 metres thick at the bend of the River Kitinen, while the grus-type weathered unit is on average 6 metres thick and the clay-type weathered unit 2.5 metres thick. Weak glacial erosion in the study area has enabled the preservation of Quaternary sediments spanning from pre-Weichselian, (most likely Saalian), to the Holocene. The thickness of the Quaternary deposits is variable, with an average thickness of approximately 8 metres. The Quaternary deposits consist of at least three separate till units and four interbedded sorted units. The Early Weichselian (MIS 5b) till unit is the most widespread and laterally continuous till unit in the area. The glacial lineations reflect pre-Late Weichselian glacial flow directions rather than rather than subglacially formed ice flow lineations formed during the Late Weichselian. During the Middle Weichselian stadial (MIS 4), the glacier flowed from N/NNE and had an overall weak impact on sedimentation, leaving sparse and thin remains of glacial till. The Late Weichselian glaciation (MIS 2) deposited a thin till cover, which was partly eroded by fluvial processes during the last deglaciation. Flow direction analysis of the till clast fabric suggests a northern location for the ice-divide zone during the Early and Middle Weichselian, and a more W/SW ice-divide position during the Late Weichselian. The optically stimulated luminescence (OSL) age determination suggests ice-free areas in the vicinity of the River Kitinen valley already during the Bølling–Allerød warm period, indicating that ice had retreated from the area at that time patchy ice cover or rapid deglaciation.
  • Rämö, Lasse (Helsingin yliopisto, 2021)
    Introduction Humeral shaft fractures account for 1–3% of all adult fractures. They are usually caused by simple falls, traffic accidents, and sports injuries. Historically, the treatment of these injuries has been mainly nonsurgical. However, there has been a marked increase in the rate of surgical treatment for humeral shaft fractures in recent years without high-quality evidence supporting this trend. Aim The Finnish Shaft of the Humerus (FISH) randomized clinical trial was planned to compare the effectiveness of surgery versus nonsurgical care in the treatment of humeral shaft fractures in patients traditionally deemed suitable for nonsurgical care with functional bracing (Study I). Patients and methods Patient recruitment was conducted at the Helsinki and Tampere University hospitals between November 2012 and January 2018. Consenting adult patients with displaced, closed, unilateral humeral shaft fractures were randomized to either surgical care using open reduction and plate fixation or nonsurgical care using functional bracing. Patients with a history or condition affecting the function of the injured upper limb, pathological fracture, other concomitant injury affecting the same upper limb, other trauma requiring surgery (e.g., fracture, internal organ, brachial plexus, or vascular injury), polytrauma, multimorbidity with high anesthesia risk, or inadequate cooperation for any reason were excluded. Altogether, 321 patients were assessed for eligibility and of these 140 were eligible for randomization. After informed consent, 82 were willing to undergo randomization. The primary outcome was the Disabilities of the Arm, Shoulder, and Hand (DASH) score (range, 0 to 100 points; 0 = no disability, 100 = extreme disability). In Study II, the patients were analyzed according to the initially allocated treatment method (surgery group and bracing group). In Study III, the patients were analyzed in three groups according to their final treatment method: 1) initial surgery group, 2) bracing group with successful healing, and 3) secondary surgery group including patients randomized to functional bracing but who underwent late surgery due to fracture healing problems. Results Study II. The mean DASH score was 8.9 (95% confidence interval [CI], 4.2 to 13.6) in the surgery group and 12.0 (95% CI, 7.7 to 16.4) in the bracing group at 12 months. The between-group difference was -3.1 (95% CI, -9.6 to 3.3). This difference was not statistically significant, and it was below the predefined minimal clinically important difference of 10 points. Of the patients allocated to functional bracing, 13/44 (30%) underwent late surgery due to healing problem during the 12-month follow-up. In the post hoc analysis, the results of those with initial surgery were superior to those with late surgery due to healing problem (between-group difference, -11.1; 95% CI, -20.1 to -2.1) at 12 months. Study III. The mean DASH score was 6.8 (95% CI, 2.3 to 11.4) in the initial surgery group (n=38), 6.0 (95% CI, 1.0 to 11.0) in the bracing group (n=30), and 17.5 (95% CI, 10.5 to 24.5) in the secondary surgery group (n=14) at the 2-year follow-up. The between-group difference was -10.7 (95% CI, -19.1 to -2.3) between the initial and secondary surgery groups and -11.5 (95% CI, -20.1 to -2.9) between the bracing and secondary surgery groups. Conclusions Study II. Surgery with plate fixation, compared with functional bracing in the treatment of adult patients with closed humeral shaft fractures, did not significantly improve functional outcomes at 12 months. However, 30% of the patients allocated to functional bracing underwent late surgery due to healing problem. Study III. Shared decision-making between the clinicians and patients with closed humeral shaft fractures should weigh the prospect that 2/3 of patients undergo successful healing and have good functional outcomes using functional bracing against the 1/3 risk of fracture healing problems leading to secondary surgery and inferior outcomes even at 2 years after the injury.
  • Abushahba, Ahmed (Helsingin yliopisto, 2021)
    Bone tissue engineering (BTE) has shown a great promise in providing the next generation medical bioimplants for treating bone defects. However, BTE faces many obstacles which need to be addressed for promoting translatability. The objective of this thesis work was to explore clinically translatable tissue engineering approaches for the management of craniomaxillofacial bone defects. The role of the employed cells has witnessed a critical turning point towards an increased appreciation of the cellular paracrine effects. This paracrine effect is mediated via secreted proteins and released membrane-bound vesicles called extracellular vesicles (EVs). For advancing our knowledge about the biological roles of EVs, we employed RNA sequencing to provide a comprehensive overview of the expression profiles of small non-coding transcripts carried by the EVs derived from human adipose tissue stromal/stem cells (AT-MSCs) and human pluripotent stem cells (hPSCs). Our findings revealed distinctive small non-coding RNA profiles from hPSCs and AT-MSCs EVs. The regulatory miRNAs of stem cells at cellular level are also present in their EVs, indicating an important regulatory role which is mediated via EVs. Vascularization is the key challenge for BTE applications in large bone defects. The local delivery of growth factors leads to short lived effects. Small molecule chemicals feature alternative cost-effective bioactive agents with better stability. We assessed the ability of two small molecules; DMOG and baicalein, in triggering the proangiogenic secretome of AT-MSCs in vitro. Additionally, other effects, such as proliferation and osteogenic differentiation of AT-MSCs were assessed. DMOG and baicalein efficiently stabilized the hypoxia-inducible factor (HIF-1α) and upregulated proangiogenic cytokines, e.g., vascular endothelial growth factor (VEGF) and platelet derived growth factor-BB (PDGF-BB) of AT-MSCs in normoxic conditions. These effects were further associated with upregulated stemness-related gene expression, slowed proliferation, and reduced osteogenic potential. Chemically-induced hypoxia maintained the stemness and self-renewal properties of AT-MSCs, while enhancing their proangiogenic potential. The in vivo bioreactor (IVB) concept combines the potential of BTE and reconstructive surgery by employing the patient body for prefabricating new prevascularized tissues. Ideally, IVB should minimize the need for exogenous growth factors or cells and harness the native regenerative potential of employed tissues. Using acellular alloplastic bone blocks, we compared muscle-IVB with and without periosteal/pericranial grafts and flaps for prefabricating tissue engineered bone (TEB) flaps. We also assessed their functional outcomes in reconstructing a mandibular defect in an ovine model. The employment of vascularized periosteal flaps did result in more robust vascularization as compared to other IVB techniques. Both the periosteal grafts and periosteal flaps enhanced the performance of the prefabricated TEB flaps after transplantation into a mechanically stimulated bony microenvironment. However, more new bone formation and biomaterial remodeling was associated with the vascularized periosteal flaps.
  • Panduru, Nicolae Mircea (Helsingin yliopisto, 2021)
    Introduction: Diabetic nephropathy (DN) is a devastating diabetes complication. DN is associated with a competitive risk of either progression to a worse stage of DN or premature mortality. Mortality is mainly due to cardiovascular events. Tubular dysfunction is involved in the loss of kidney function. Therefore, tubular biomarkers could add significant benefit to early identification of DN, prediction of DN progression and to screening for risk of cardiovascular events. Aims: The aims of this thesis were to investigate, in individuals with T1DM, if three urinary biomarkers [liver-type fatty acid binding protein (L-FABP), kidney injury molecule 1 (KIM-1) and urinary adiponectin (ADP)] could outperform the currently available biomarkers for the prediction of DN development and progression or even be causally related to the loss of kidney function. In addition, the thesis aimed to investigate if these biomarkers could predict cardiovascular disease (CVD) and premature mortality. Subjects and methods: All individuals with T1DM included in this thesis were enrolled between January 1998 and December 2002. The studies were part of the Finnish Diabetic Nephropathy Study (FinnDiane), a nationwide cohort of individuals with T1DM followed prospectively at more than 80 centres throughout Finland. The participants were followed for a median of 5.8 to 14.1 years, and clinical outcomes were prospectively evaluated. Results: In study I, L-FABP was shown to be an independent predictor of progression of DN irrespective of the disease stage and did not improve the risk prediction of DN progression. In study II, urinary ADP was an independent predictor of progression to end-stage renal disease (ESRD) and performed even better than AER and as good as eGFR. In study III, KIM-1 did not predict the progression to ESRD independently of AER. However, the Mendelian randomization (MR) analysis showed that KIM-1 is very likely to play a causal role in the loss of eGFR. In study IV, L-FABP was an independent predictor of stroke and premature mortality but did not add any predictive benefit on top of AER and eGFR. It is of note that urinary ADP and AER were common determinants of all tested biomarkers. Discussion and conclusions: By predicting the progression of DN, these biomarkers proved that tubular dysfunction is an important part of DN progression. However, judging by their baseline determinants, the studied tubular biomarkers represent much more than tubular injury, capturing also glomerular damage as well as systemic factors. L-FABP was an as good predictor as eGFR or AER of stroke or premature mortality, while the other biomarkers predicted various other cardiovascular outcomes. A causal relationship between these biomarkers and loss of kidney function could be demonstrated only for KIM-1, but this particular observation confirms a causal role of tubular dysfunction for the DN progression.
  • Wagner, Patrick (Helsingin yliopisto, 2021)
    The doctoral thesis examines the philosophical-historical interrelations between boredom and leisure. It follows the central hypothesis that both boredom and leisure express in a mirrored way a reflexive relationship of the human being to the self and the world, sharing a connecting element in their ontological reference to the absolute, i.e., God or the divine. The topics are presented in a threefold structure: Beginning with the modern position of Blaise Pascal and focusing on boredom (›ennui‹), followed by the early Christian and late ancient view of the neo-platonic theologian and philosopher Augustine of Hippo, dealing with curiosity (›curiositas‹) as the dialectical counterpart to boredom, and concluding with the ancient perspective of Aristotle, which has leisure (›scholē‹) as its subject. This inverted chronological arrangement of the three authors and the subject areas is methodologically justified, referring to the effective historical and hermeneutical perspective of the thesis: Starting from the most recent and best-known position of understanding boredom primarily as a psychological phenomenon, it is shown that even this seemingly purely psychological phenomenon has a historical dimension and is ontologically based. From there on, the historical and philosophical references to Augustine’s curiosity are presented, to finally juxtapose the dualism of ennui and curiositas with the psychological, historical, and ontological dimensions of leisure in Aristotle. Thus, the actual hermeneutic gain of the thesis consists in revealing the psychological, historical and, above all, ontological depth layers of boredom and leisure, which in particular broadens the view for the more recent philosophical discussions of the phenomena. Based on the three-stage structure of the thesis, several central results can be identified, which in turn stand in a holistic relationship to each other. Blaise Pascal’s Pensées, which contain the first philosophically profound examination of boredom, closely link ennui with the question of worldliness. Boredom in this specific context acts as mood-related evidence of an ontological dualism that draws a sharp distinction between the sensual world and the sphere of the divine. As a consequence of the apostasy of God, for Pascal boredom is precisely the expression of human worldly existence, even though this mode of being in most cases is suppressed by the means of distraction and diversion (›divertissement‹). In this sense, Pascal proposes an affirmation of boredom through which man orients himself towards the divine, creating ontological stability and establishing a relation to divine tranquility (›repos‹) without reaching it entirely. In this respect, boredom can be understood as a specifically transcendent mood that is essentially based on a dualistic conception of the world. The dialectical counterpart to this affirmation of boredom can be found in the phenomenon of curiosity (›curiositas‹), which is a central motif of the tenth book of the Augustinian Confessions and which can also be understood as an indicator of a dualistic division between the divine and the world. In the comparison of both positions, that of Pascal and that of Augustine, the philosophical-historical reference between a specific tendency of modern and early Christian late ancient thought emerges: The questioning and problematization of the human position within the world. The observed results lead to the conclusion that boredom in this specific context can be read as a form of unworldliness to which one can refer to as lingering in restlessness. It is therefore evident that boredom, in terms of the history of philosophy, has a genuine religious connotation and stems from the dualistic separation of man from God. In contrast to the interrelated perspectives of Pascal and Augustine, the Aristotelian position is characterized by fundamental ontological confidence towards nature, sensuality, and the world. This ontological trust subsequently has an impact on Aristotle’s assessment of the possibility of human tranquility and stability in the world itself. For Aristotle, leisure is a way of being that represents an ontological calmness in which something happens without something being intended. Leisure opens the space for theoretical life and, in doing so, it constitutes the relationship between man and the divine that is, concerning the aspect of worldliness, ontologically undivided. In contrast to the frozen restlessness of boredom, which exposes the ontologically absolute tranquility in its absence, Aristotelian leisure represents a resting in oneself, in which divine and human modes of being temporarily coincide. From an effective historical point of view, both boredom and leisure represent fundamental human forms of reference to the instance of the divine, aiming for some sort of rest and stability. The way they do this, however, is opposed to one another and depends on the ontological conception of the world they are embedded in. In this respect, it becomes clear that the two phenomena are closely intertwined with an ontological self-location of man within the world.
  • Cai, Yuhua (Helsingin yliopisto, 2021)
    This article-based dissertation aims to understand by means of mathematical models how organisms evolutionarily respond to fluctuations in the environment. It uses the approach of adaptive dynamics to study the long-term evolution of phenotypic strategies in an environment that fluctuates in time because of biotic interactions and/or external factors. The dissertation demonstrates how this approach can reveal clear-cut explanations for complex environment-phenotype relationships by one general method-oriented article and two case studies in two additional articles. In the first article, I show that under the standard assumptions of adaptive dynamics, in particular mutation-limited evolution and small mutation steps, the generic dynamics of the resident-invader population in fluctuating environments can be fully characterized in terms of the behaviour near the boundaries of population state space, which in turn can be determined by the invasion criteria. This generalizes previous results for unstructured populations in a constant environment, which is important because it justifies the use and interpretation of various methods in the theory of adaptive dynamics for a significantly larger class of ecological situations that include fluctuating environments and structured populations. The two case studies are applications of the classification of invasion outcomes to explore the long-term evolutionary consequences of many successive invasion events. In the first case study, I investigate the evolution of the irreversible transition from a free-swimming state to an immobile sessile state as seen in many aquatic invertebrates. To this end, I study the adaptive dynamics of the settling rate of a hypothetical microorganism onto the wall of a chemostat with a fluctuating nutrient availability. The results show that different dilution rates and spatial competition mechanisms, as well as different frequencies of the nutrient fluctuations, have qualitatively different effects on the evolution of the settling rate as well as on species diversity. The model generates several hypotheses for further empirical studies. In the second case study, I investigate the evolution of the colonization rate in an extended competition-colonization model with ownership effects and stochastically varying mortality rate. I find that the strength of the trade-off, ownership effect and fluctuation intensity all have a non-monotonic effect on the emergence of species diversity via evolutionary branching. In particular, intermediate disturbance---as measured by the fluctuation intensity of the mortality rate---promotes evolutionary branching and hence the emergence of polymorphisms. This provides new evidence for the intermediate disturbance hypothesis. I also find that there can be multiple evolutionary attractors for polymorphic populations, each with its own basin of attraction. Consequently, random mutation-induced transition of coevolutionary trajectories between neighbouring basins of attraction makes the long-term evolutionary outcome uncertain. By means of these examples, the dissertation demonstrates that the approach of adaptive dynamics is a powerful tool for untangling the connection between environmental changes and adaptive strategies.
  • Mesihää, Samuel (Helsingin yliopisto, 2021)
    Legal medicines and illegal drugs play a significant role in today’s society. The laboratory analysis of these substances is central not only in therapeutic monitoring but also in clinical and forensic toxicology, which aims to provide evidence-based information on the abuse and harmful effects of these substances. The rapid emergence of newly abused drugs known as new psychoactive substances (NPS) has challenged the conventional drug testing concept. On the European illicit drug market, approximately fifty new substances are identified each year, many of which are poorly characterized for their pharmacological effects or toxicity. Moreover, the lack of authentic primary reference standards (PRS) bottlenecks the development of analytical assays for NPS, which hinders both detection and toxicological evaluation of these drugs. High-resolution mass spectrometry (HRMS) has recently been applied to tentative identification of unknown compounds by targeting the precursor ions with high mass accuracy, resolution and speed. This capability has permitted a breakthrough in facile screening for suspected NPS, but until now, no practical method has been described for quantitative bioanalysis of NPS in the absence of PRS. In this thesis, a new analytical platform was developed and exploited for the simultaneous qualitative and quantitative analysis of NPS and metabolites without using PRS. In this platform, the gas chromatographic (GC) flow was divided between an atmospheric pressure chemical ionization - quadrupole time-of-flight mass spectrometer (APCI-QTOFMS) for tentative identification and a nitrogen chemiluminescence detector (NCD) for quantitative estimation based on the detector’s equimolar response to nitrogen-containing substances. Replacement of the ordinary electron ionization (EI) source with APCI was proven to be useful in substance identification by QTOFMS because it allowed the preservation of the precursor ion for tentative identification. The GC-APCI-QTOFMS tandem mass spectrometry (MS/MS) experiments using 29 NPS showed that all substances shared the same major fragments as in the commercial spectral library created by using liquid chromatography (LC) electrospray (ESI) MS/MS instrumentation. Consequently, these findings promote the usability of external soft-ionization compound libraries with the new GC-APCI-QTOFMS platform. The accuracy and precision of the N-equimolar quantification by GC-NCD were tested using several NPS in four separate studies using post-spiked sheep blood (n = 5), post-mortem blood (n = 38) and urine (n = 3), and in seized powdery material (n = 28). The combined results from these studies, excluding the post-spiked samples, showed that NPS could be quantified with a grand mean accuracy of 91.7% and with a grand mean imprecision (CV) of 9.5% in the absence of PRS for compensating sample preparation and analysis. In conclusion, the GC-NCD-APCI-QTOFMS platform proved feasible for analyzing suspected nitrogen-containing drugs, such as stimulant-type NPS and metabolites, in situations where appropriate reference standards are not readily accessible. Simultaneous tentative identification by HRMS and quantitative estimation by NCD has unparalleled potential for fast preliminary analysis until a certified PRS becomes available. The possibility for high-throughput retrospective identification and quantification is an additional advantage of this platform, providing a means for further research on emerging NPS.
  • Pospelov, Alexey (Helsingin yliopisto, 2021)
    Treatment of birth asphyxia (BA) is a challenging problem – this condition is common and often leads to severe life-long neurological dysfunction. The pathophysiology of BA is complex and not fully understood, and the existing therapeutic approaches are not effective. Animal models are the main source of knowledge about the pathophysiology of BA, but many of the existing models have little relevance to the defining features of BA – the co-occurring hypoxia and hypercapnia – making the results obtained from such models, which concentrate on hypoxia in isolation, difficult to apply in clinical practice. This Dissertation consists of three studies (Studies I–III), which address the above shortcomings and suggest alternative approaches. Study I characterizes the pH-dependent vasomotor responses in a novel, physiologically-validated model of BA. The key advantage of this model is that it reproduces not only the hypoxic but also the hypercapnic component of asphyxia. The importance of the co-occurrence of these two components is directly demonstrated in experiments showing that in the absence of hypercapnia, shifts in brain pH and in partial pressure of oxygen (Po2) during and after hypoxia are qualitatively different from those during asphyxia proper. The respiratory acidosis, associated with the latter, triggers protective mechanisms that have emerged during mammalian evolution to ameliorate brain damage during asphyxia. In Study II, we investigated the therapeutic potential of carbon dioxide (CO2) supplemented in ambient air for the treatment of BA-seizures. Seizures are a common acute consequence of BA and they exacerbate the brain damage caused by asphyxia itself. We found that supplementing the inhaled air with 5% CO2 immediately after the asphyxia period prevents seizures, presumably by slowing down the brain pH recovery from acidosis caused by asphyxia. Study III focuses on carbonic anhydrase inhibitors (CAIs), drugs that cause respiratory acidosis by retention of metabolically-generated CO2. These drugs produced brain pH and Po2 responses similar to the responses to CO2 supplementation and similarly suppressed seizures triggered by BA. As first shown in this study, the most widely used CAI, acetazolamide (AZA) is therefore a candidate drug for the treatment of BA seizures. In sum, this doctoral thesis work developed and characterized a novel rodent model of BA and used this model for testing a novel treatment strategy for BA and post-asphyxia seizures.