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  • Tuomisto, Maiju (Helsingin yliopisto, 2018)
    The rationale for this thesis was grounded on the general importance of finding novel, research-based chemistry teaching approaches to engage students in learning, because lower secondary students are commonly not interested in chemistry and their attitudes toward this subject are often negative. Educational games have been noted to promote motivation, interest and enjoyment in learning, but the research in the field has focused more on digital games than card and board games. There is also a need to develop quality evaluation criteria for educational games. Evaluation frameworks have been developed for digital games, but not for card and board games, and particularly not to support the use of educational games in chemistry education. In-game learning is the main purpose of educational games. Therefore learning with an educational game should be connected to a definition that explains how learning principles are tied to playing that game. In previous research, this line of reasoning has not been presented in studies concerning educational chemistry games. The main research problem in this thesis was: how do we support the design and evaluation of educational chemistry card and board games and in-game learning using them? From the research problem, three aims for the study have been derived: 1) to develop a practical and high-quality tool for designing and evaluating educational card and board games for chemistry education; 2) to design research-based educational games for chemistry education in order to support both the learning of central chemistry concepts and the use of this knowledge and related skills in different daily life situations; 3) to achieve understanding of the relationship between educational games and students’ concept development and transfer of knowledge in context-based learning. In order to achieve the aims, design challenges 1, 2 and 3 were executed in this study. This thesis followed the research-based principles of design-based research (DBR) and was based on a qualitative approach; hence qualitative research methods were executed in the problem analyses and game testing sessions of three design challenges (1–3) and their cyclic structures. Small-scale questionnaires, diaries, literature review, observations and video recordings were used as data collection methods. Data was analysed using content analyses and conversation analysis. Chemistry teacher educators, chemistry teachers, chemistry and home economics pre-service teachers, and students at upper and lower secondary levels participated in the six case studies of this study. Design challenge 1 aimed to answer research question 2: which features of an educational game may support the development of lower secondary students’ skills to learn and use a piece of information included in the periodic table? Two educational card games, Periodical Domino and Collect a Triplet, were designed to promote the development of lower secondary students’ ability to learn and use information included in the periodic table. Argumentation and construction of students’ own models of the periodic table were the two specific features in these games. In the first design cycle, the games were developed based on theoretical frameworks about games and educational games, and the results of empirical problem analysis, in which Finnish lower secondary students’ (n = 38, 8th grade) understanding of the periodic table and related topics, and their skills in using it, were studied using two small-scale questionnaires. As a result, information about specific difficulties among students in understanding the concepts related to the periodic table was discovered. The first versions of the games were tested on chemistry teachers (n = 22), on whom a small-scale questionnaire was used. As a result, feedback and suggestions for improving the games were achieved. In the second design cycle, the games were developed further based on the results. According to CHEDU Game design Tool, the games were found to satisfyingly fulfill the quality criteria for educational chemistry card games, and consistency between the evaluators was substantial (Periodical Domino κ = 0.756; Collect a Triplet κ = 0.718). According to evaluators, in these games in-game chemistry learning is supported by making thinking visible, application of knowledge and with suitable challenges in the zone of students’ proximal development. But improvements should be made at least in the categories of pre- and postgame evaluation and connection to the macroscopic level and daily life. Even though Periodical Domino and Collect a Triplet card games were research-based and based on theoretical frameworks developed to support learning, they have not yet been tested with students. Therefore, in this research, it was not possible to present evidence about their actual ability to support lower secondary students’ learning and use of skills regarding the periodic table. Design challenge 2 aimed to answer research question 1: what kind of game design and evaluation tool for educational card and board games supports both teaching and learning in chemistry education? The educational card and board game design and evaluation tool for lower secondary education (CHEDU Game Design Tool) was designed to support game developers and teachers in designing and evaluating quality educational games particularly for chemistry education purposes. In the first cycle of the design process, a theoretical problem analysis with integrative literature review was implemented. As a result, the elements of high-quality digital and non-digital games and educational games were uncovered. The tool was developed based on these features and the current Finnish national core curriculum for basic chemistry education. In the second design cycle, the tool was tested on chemistry and home economics pre-service teachers (n = 25), while game design diaries were kept and the tool supported the design process. As a result, information about pre-service teachers’ ability to benefit from the game design tool in their game design processes were achieved. The tool was further developed based on the results. The first version of the educational game design and evaluation tool was used in evaluation of the games developed in design challenge 1, and the second version was used in designing an educational board game in design challenge 3. Design challenge 3 aimed to answer research question 3: how does an educational game in a food and cooking context help students with development and transfer of knowledge between theory, everyday life contexts and hands-on activity? The Proteins in Backyard board game was designed to support lower secondary students in learning about protein chemistry, and in enhancing transfer of knowledge in daily life contexts and in hands-on activity. The theoretical framework about context-based learning, criteria in the CHEDU Game Design Tool and the results of two empirical problem analyses were exploited in the first cycle of the design process. In the first empirical problem analysis, pre-service teachers’ (n = 25) game design processes were analysed and as a result, information about specific quality game elements in their games was collected. In the second empirical problem analysis, upper secondary students’ (n = 22) interest and attitudes toward chemistry, food and cooking, and molecular gastronomy were studied using a small-scale questionnaire. As a result, information about their cooking behaviors, discussions related to chemistry and cooking, as well as their favourite topics in the field of molecular gastronomy were collected. The top three among these students were: fudges, cream foam and meringues. The board game was first tested on chemistry educators (n = 3) and, based on observation, feedback and video recording, important information concerning the game’s playability and video recording settings was collected. In the second cycle, the game was further developed and tested on 9th grade students (n = 6) using video recording, observation and a small-scale questionnaire. As a result, information about in-game activities, such as engagement, in-game learning and transfer of knowledge was collected. Based on the results, development and transfer of knowledge, as well as engaging game elements were noted to be apparent during play, but bridging them to hands-on activity was not observed. Based on the results, the game mechanics and difficulty level of missions in the playing cards in particular were further developed in the third design cycle for the game. This board game was found to fulfill the quality criteria for educational chemistry board games laudably, although there was still room for improvement – for example, increasing difficulty during play was missing. In general, in this thesis different design solutions were developed to draw on the research on educational games and chemistry education. The Periodical Domino and Collect a Triplet card games, the Proteins in Backyard board game and the CHEDU Game Design Tool are four guiding development models which follow the research-based design processes described in this thesis. Hence, in this study, four prescriptions for successful design processes were developed. During the design processes, descriptive and guiding theories were also developed. The results of this research suggested new theories about quality educational card and board games by revealing elements that play important roles in increasing the quality of non-digital educational games, and particularly in chemistry education. Simultaneously, the need to develop tools to systematically assess quality of educational games was answered. A theory about using educational game design as a part of chemistry teacher education was developed, and it was observed not just to support previous studies, but also to give new information about the quality game elements in the games designed by pre-service teachers. Also, a new theory about developing educational games to support chemistry learning and about in-game chemistry learning was developed. Theoretical bases for developing research-based quality educational chemistry games were presented so that design decisions concerning both game mechanics, game dynamics and game material were justified in a transparent manner, showing how they are designed to support possible in-game learning. These processes and embedding a hands-on activity into the board game make this study unique compared to previous research in the field. According to this study, when using quality educational games, in-game engagement and learning is possible at least via in-game transfer of knowledge in daily life contexts. This kind of research concerning in-game learning and in-game engagement has not been reported in the previous studies of educational games in chemistry education. However, due to the qualitative nature of this design research, these results are not generalizable, only indicative. This study presents theory and tools to use quality educational card and board games as an effective teaching approach in chemistry education, as well as providing ideas about how to carry out studies in the field of in-game learning research. It also offers ready-made tools, such as game materials, for chemistry teachers and teacher educators to apply in their teaching. KEYWORDS: chemistry education, context-based learning, educational game design, transfer of knowledge
  • Pekkala, Johanna (Helsingin yliopisto, 2018)
    Sickness absence indicates ill-health among working populations and gives rise to notable costs due to lost working days. Employees in lower occupational classes have more sickness absence compared to those in higher classes. Extending working careers by reducing sickness absence has been a target at the national level in many Western countries due to ageing workforce and weakening economic dependency ratio. Socioeconomic differences in health, in turn, have remained significant over time. However, less is known about changes in occupational class differences in sickness absence over time in nationwide populations. The aim of this study was to examine occupational class differences in long-term sickness absence and underlying diagnostic causes of the class differences over time in the Finnish employed population. The study was based on data obtained from national registers. A 70% random sample of working-age Finnish residents was linked to data on medically certified sickness absence of over 10 working days based on paid sickness allowances retrieved from the Social Insurance Institution of Finland. Data on occupational class was obtained from Statistics Finland. The study focused on upper non-manual employees, lower non-manual employees and manual workers. The study covered the years from 1996 to 2014, the diagnosis-specific examination spanning from 2005 to 2014. Statistical methods included a direct age-standardisation method, the Slope Index of Inequality (SII), the Relative Index of Inequality (RII) and a negative binomial hurdle model. The results showed that, despite modest annual variations, occupational class differences in all-cause sickness absence were clear and persistent among both genders over time. Lower occupational class was consistently associated with higher all-cause sickness absence, both in absolute and relative terms, with men having larger differences than women. The most prominent class differences were detected in sickness absence due to musculoskeletal diseases throughout, with men having very large relative differences. With regard to specific musculoskeletal diagnoses, the class differences in the occurrence of absence were by far the largest in shoulder disorders and back pain. Chronic musculoskeletal diseases, namely rheumatoid arthritis, disc disorders and, among men, also hip osteoarthritis, caused the largest class differences in the length of absence. During the study period, large occupational class differences were also detected in sickness absence due to home and leisure injuries, particularly among men. In contrast, modest occupational class differences were found in sickness absence due to mental disorders among both genders. Among women, a divergent pattern was found in sickness absence due to breast cancer: the higher the class, the greater the cumulative incidence but the shorter the duration of absence throughout. Health inequalities have remained prominent over time in the Finnish working population. No major progress has taken place, despite several health policy programs aiming at reducing socioeconomic health differences over time. Future actions should have a specific emphasis on employees in lower occupational classes and on manual workers in particular in order to tackle the class differences in sickness absence effectively. The study further highlights that sickness absence due to musculoskeletal diseases, especially prevention of sickness absence due to back pain and shoulder disorders, and home and leisure injuries should be paid attention in the future.
  • Lagerblom, Kalle (Helsingin yliopisto, 2018)
    The selective oxidation of alcohols to aldehydes, ketones and carboxylic acids is among the pivotal reactions in organic chemistry. Traditionally, the transformation is conducted using stoichiometric amounts of heavy metal oxidants, which are costly and their use produces large amounts of hazardous waste. In this respect, the development of catalytic methods, which use oxygen as the oxidant and produce water as sole by-product, is crucial from the sustainable point of view. Recently, aerobic oxidation catalysts based on the combined used nitroxyl radicals and different co-catalysts have gained considerable amount of research interest due to their excellent performance in selective oxidation of alcohols under very mild conditions. The literature section of this thesis covers the selective aerobic oxidation of alcohols to carbonyl and carboxylic compounds with homogeneous catalysts based on the use of nitroxyl radicals together with different oxygen-activating co-catalysts. The experimental section presents the central findings and discussions from the author’s peer reviewed publications. In the first part, a catalytic oxidation method based on the combined use of nitroxyl radicals with Fe-based co-catalyst system is described. The method enables the oxidation of primary alcohols selectively either to aldehydes or carboxylic acids under mild conditions. The second part focuses on a catalyst system that is based on combined use of nitroxyl radicals and a Mn-based co-catalyst system. This catalytic method provides a highly practical way to selectively oxidize primary and secondary alcohols to aldehydes and ketones using simple reaction setup and workup procedures. The third section presents a further improved version of the aforementioned nitroxyl radical/Mn catalyst, which allows the oxidation of alcohols to be performed with very high efficiency using a small amount of catalyst.
  • Paukkonen, Heli (Helsingin yliopisto, 2018)
    The main role of excipients is to ensure the safety and efficacy of the whole pharmaceutical formulation throughout its shelf-life and administration. Formulation design and development as well as material testing are the key components for successful drug delivery. This is becoming increasingly complicated as new active pharmaceutical ingredients typically have poor solubility and/or bioavailability. Due to this, there is an ever increasing need to explore new excipients and material combinations as innovative formulation solutions are required. Furthermore, modified release formulations are needed to control the release rates and to adjust the desired therapeutic effects, raising even more demand for effective formulations. The main aim of this thesis was to evaluate the performance of plant based materials nanofibrillar cellulose (NFC) and anionic carboxylated nanofibrillar cellulose (ANFC) as pharmaceutical excipients for modified release formulations and bioadhesive films. These materials are widely available from renewable sources; biocompatible with relatively low toxicity combined with high mechanical strength and large surface area available for encapsulation. NFC and ANFC, together with HFBII protein, were used as emulsion stabilizers for encapsulation and release of poorly water-soluble drugs. The synergistic stabilization mechanism achieved with these biopolymers improved emulsions stability with extremely low concentrations. In another study, ANFC hydrogels were evaluated as matrix reservoirs for diffusion controlled drug release. Their rheological and drug release properties were shown to be preserved after freeze-drying and reconstruction. The ANFC hydrogels controlled the release kinetics of small molecular weight drugs moderately, whereas significant control was obtained in the case of large proteins. In a comparative study, three new grades of microcrystalline cellulose (MCC) hydrogels were evaluated for diffusion controlled drug release. MCC matrices efficiently controlled the release of both large and small compounds, indicating great potential for drug release applications in a similar manner to the ANFC hydrogels. Bioadhesive NFC and ANFC based films were prepared by incorporating bioadhesive polymers mucin, pectin and chitosan into the film structure. The bioadhesive properties of the films combined with good mechanical and hydration properties, together with low toxicity makes them a feasible option for buccal drug delivery applications. In conclusion, NFC and ANFC were shown to be versatile excipients applicable for several types of dosage forms. In the future, it is seen that these materials may be used systematically as functional excipients for modified release dosage form.
  • Laurén, Patrick (Helsingin yliopisto, 2018)
    Hydrogels are emerging as an important source for current biomaterial design, as they often possess intrinsic physical and mechanical similarities with soft tissue, are non-toxic and biocompatible. However, many hydrogel-based biomimetic materials are either derived from limited sources, or require external activators to achieve functionality, such as chemical crosslinking or environmental cues. Furthermore, many cross-linkers used with hydrogels are toxic, and environmental cues invoke slow responses. Therefore, to function as a rational biomaterial design for a biomedical application, these properties are preferably avoided, or improved with a composite system containing two or more polymer components to overcome these limitations. Plant-derived nanofibrillar cellulose (NFC) possesses the same intrinsic properties as many other hydrogels derived from the components of extracellular matrices (ECM). Therefore, NFC shares the biocompatibility and non-toxicity aspects of biomimetic materials. However, additional features of NFC can be exploited, such as shear-thinning properties, spontaneous self-gelation and chemical modification capabilities. Additionally, the source of NFC is practically inexhaustible, and is environmentally biodegradable, bearing no ecological burden. Therefore, when designing hydrogel-based biomaterials, NFC offers versatility, which enables the fabrication of potential biomedical applications for various purposes in an environmentally safe way. In this thesis, a wide range of potential applications of NFC-based hydrogels were investigated. These include 3D cell culturing, in vivo implantation and coating systems for drug and cell delivery, controlled drug delivery and local delivery as a bioadhesive system. These methods offer insight into the versatility of NFC-based hydrogels, which could improve the future design of biomaterials, for a safer and more efficient use in biomedical applications.
  • Muniandy, Maheswary (Helsingin yliopisto, 2018)
    Obesity remains a major health problem, partly due to our limited understanding of this complex disease. Obesity carries with it the risk of many other diseases including type 2 diabetes, cardiovascular disease, hyperlipidemia and some types of cancer. The variability in the disease as well as its related comorbidities makes it a complex, multi-factorial condition that is not easily categorised and treated. ‘Omics technologies and bioinformatics tools allow for the investigation of the complex biology behind obesity. These technologies enable production of complex multivariate datasets that can be investigated using bioinformatics tools to identify patterns in the data as well as associations between different features of the data. However, while advances in ‘omics technologies have allowed production of large amounts of data from biological samples, extraction of useful information from the data remains a huge challenge. Choosing the correct methodology and tools to transform heterogeneous data into biological knowledge is especially difficult when different methods on the same data may yield different results, requiring further statistical or biological validation. This thesis uses existing bioinformatics tools and methods to first combine and analyse transcriptomics and biochemical data and then, separately, metabolomics and biochemical data to gain an understanding of obesity. Body mass index (BMI)-discordant as well as BMI-concordant monozygotic (MZ) twin pairs were used to investigate the molecular effects of obesity by looking at gene expression and metabolite profiles in subcutaneous adipose tissue (SAT) and blood plasma, respectively, to gain biological insights into pathways that are associated with obesity and obesity-related clinical manifestations. The SAT was further interrogated using isolated adipocytes, to examine the transcriptomics patterns in obesity of this specific cell type. Using the blood plasma, metabolites associating with different cardiometabolic risk factors were also identified. Variations in the global profiles were also studied to assess if study participants form different subgroups of obesity according to their gene expression or metabolite profiles. Adiposity and blood biochemistry measure differences between these obesity subgroups were also examined.
  • Cañada, Jose A. (Helsingin yliopisto, 2018)
    In April 2009, the World Health Organization (WHO) declared influenza A H1N1 a public-health emergency of international concern. This event was especially significant for marking the first pandemic outbreak to fall under 2005’s new International Health Regulations, an ambitious binding agreement to regulate international health. Since then, other communicable diseases have provoked similar international responses, with Ebola and Zika among the latest examples. Each of them has occasioned scrutiny of the ability of national and international health organisations – the WHO among them – to handle health threats and emergencies situated at global level. Among the issues recurrently rearing their head amid controversy are uniformity in enforcement of international regulations across contexts, promotion of specific lines of research, rapid development of new drugs, the management of local and international health-care workers’ activities, and engagement with local populations. One of the main ways in which health organisations respond to the uncertainty generally associated with pandemic threats is through biopreparedness policies – policies that articulate response and resource management mechanisms before a pandemic event is declared or even before its characteristics are known. The thesis examines the discourses and practices of institutional and scientific actors, for greater understanding of how knowledge is constructed and later carried into implementation in such conditions of uncertainty. The focus is placed on processes of boundary-making, categorisation, and identification. The analysis of how health and scientific institutions identify, categorise, and describe the various human and nonhuman actors involved in pandemic events employs theoretical tools from science and technology studies, Foucauldian approaches, and understandings of the more-than-human in the social sciences. These shed light on the boundaries, categories, and identities at play during pandemic processes as shared among the many humans, animals, and molecular forms of life involved in pandemic events. The approach of assemblage ethnography is engaged with as an aid to navigating digital and material networks of public health from an empirical perspective. Public documents, interviews with public-health professionals, and field visits linked with diverse international organisations are used in combination with items of scientific news and articles from various journals to illuminate how pandemic threats and emergencies unfold. The empirical work suggests that knowledge-making in institutional and scientific settings always involves notions of threat and protection. In the material analysed, there is a tendency to identify and categorise a given actor as threatening, vulnerable (in need of protection), or expert (able to protect). This argument is unfolded in tandem with discussion of three, interconnected areas of focus in pandemic preparedness and response wherein boundaries are made: 1) the establishment of governmental stand-by networks, 2) knowledge-making and knowledge distribution practices, and 3) the conceptualisation and governance of threatening life. Each of these areas connects with one of the three main lines of analytically grounded argument. Firstly, institutional boundaries are challenged in efforts to construct more prepared governmental networks that are able to protect societies from pandemic threats and emergencies. As these networks emerge mostly in a context of uncertain and virtual threats, they impose a need for threats’ identification and characterisation. Secondly, practices of making and distributing knowledge are productive in that they determine the boundaries between expert, vulnerable, and threatening assemblages, creating differentiated communities by regulating who can produce knowledge and who may access it. The third main area of discussion involves how, from a governmental perspective, certain life forms (both human and nonhuman) come to be identified as hybrid threats because of its sociotechnical interactions. Such hybridity is a key element for the design of pandemic governance and response measures. Accordingly, the way in which actors are categorised in terms of threat, vulnerability, and expertise is defined with regard to their engagement with elements such as space, technology, nationality, and gender. The thesis concludes with discussion of three ways in which boundary-making, categorisation, and identification processes interact with pandemic preparedness and response: 1) by shedding light on the establishment of more-than-human modes of pandemic governance; 2) by drawing attention to the need for portable, permeable, and flexible boundaries between threat and protection; and 3) by considering how boundary-making reinforces intersectional inequalities in international health. These conclusions point to a need to incorporate, from both an academic and a policy perspective, alternative pandemic narratives that pay heed to the intersectional, changing, and situated definitions of threat and protection.
  • Mäkitie, Riikka (Helsingin yliopisto, 2018)
    Genetic factors are of key importance in governing bone health and usually determine an individual’s skeletal characteristics in a complex and polygenic manner. Recent research has, however, identified several monogenic forms of bone diseases where the deleterious molecular changes in one gene overrule and lead to a distinct skeletal pathology. In 2013, our research group showed that a heterozygous mutation in WNT1 leads to severe, early-onset dominantly inherited osteoporosis. Although many other families with WNT1-related skeletal fragility have since then been identified worldwide, much of the molecular and clinical features of WNT1 osteoporosis remain unclear. This study aimed to define the main clinical skeletal and extra-skeletal characteristics of WNT1 osteoporosis in children and adults. The cohort comprised affected individuals from two Finnish families with the same heterozygous missense mutation c.652T>G (p.Cys218Gly) in WNT1. As healthy controls, we recruited mutation-negative members from the same families. We evaluated their skeletal and extra-skeletal characteristics with biochemistry, radiography, magnetic resonance imaging (MRI), and dual-energy X-ray absorptiometry. Bone and bone marrow biopsies were further evaluated with histomorphometry, immunohistochemistry, and microscopy for detailed architectural, cellular, and molecular changes. We also evaluated serum concentrations of circulating microRNAs with qPCR. Clinical evaluation of mutation-positive individuals showed that mutated WNT1 leads to significant, early-onset and progressive skeletal pathology. Affected young individuals exhibited abnormal bone shaping, low bone mineral density and multiple peripheral fractures already in childhood. Vertebral compression fractures were apparent and prevalent in the over 50-year-old subjects, causing exaggerated kyphosis and loss in adult height. Bone biopsies showed inactive bone cells, low bone turnover and altered osteocyte protein expression. The mutated WNT1 also led to several extra-skeletal changes, such as deteriorated cartilaginous structures in spine and increased reticulin formation in bone marrow. Lastly, serum qPCR analysis revealed a unique microRNA profile in mutation-positive subjects. Although variable in its phenotypic features, individuals with a pathogenic, heterozygous WNT1 mutation are affected by severe skeletal morbidity. Based on our findings, WNT1 osteoporosis is characterized by multiple peripheral fractures and abnormalities in long bone shape already in childhood. Progressive loss in bone mineral leads to osteoporosis and prevalent thoracic compression fractures by early adulthood. The WNT1 mutation can also lead to various extra-skeletal changes and comorbidities such as in cartilaginous tissues and the bone marrow. The differentially expressed microRNAs could serve as potential new biomarkers in diagnosing and monitoring clinical course and treatment response in WNT1 mutation-positive subjects. Questions concerning effective treatment of WNT1 osteoporosis remain unanswered and warrant future studies.
  • Ahonen, Lauri (Helsingin yliopisto, 2018)
    The amount of information collected by personal health records, smartphone ecosystems, and other cloud services has increased enormously in recent years. This has, for instance, led to new ways of automated physical exercise assessment, but this also introduces the potential for novel methods and applications in the automated evaluation of various mental factors such as cognitive state and stress. Extracting such latent variables holds considerable promise, in particular in group-level analysis. Furthermore, the current initiatives and research programs collecting masses of health data from large cohorts create opportunities for developing the methodology. The lack of targeted research is partially hindering the development of the analysis of obscure factors, progress of machine learning and other algorithmic solutions, and the evolution of novel applications and technologies. As described in this introduction, various features inherent in biosignals increase the complexity in the research. In this thesis I provide an introduction to the emerging ubiquitous recording of physiological signals, its effects on the industry, opportunities for organizations and management, and data analytics and measurement techniques. The aim is to seek the future prospects of systemic scenarios and large-scale initiatives. The original publications reviewed in this thesis seek biosignals for features responsive for cognitive states such as stress and, more interestingly, second-order factors derived from inter-individual responses and activations. By introducing more complex features to psychophysiological research, group analytics can be further developed. Second-order analyses provide robust signal features and may lead to advanced applications in assessing well-being and performance. The original publications consist of three research articles and a primer review. The experiments include recordings of magnetoencephalography (MEG), heart rate variability (HRV), and electrodermal activity (EDA), and they exemplify systemic use cases of biosignals. The included primer review discusses general methods in psychophysiological research in human–computer interaction (HCI). Together with this introduction, my experimental results provide evidence that taking psychophysiological measurements from the laboratory to ecologically valid environments is plausible and effective. The literature suggests that consumer-grade devices and personal internet of things will revolutionize myriad sectors, e.g., organizational management. Together with an exponentially increasing data collection and novel applications, the industry will have large economical impacts.
  • Ukkola, Markus (Helsingin yliopisto, 2018)
    The aim of the dissertation is to assess whether the jurisprudence of the Court has met the standards which secure the coherence and legal certainty and ultimately the acceptability of its rulings. The aim of the study is also to show how, by using systemic arguments, the Court could help to systematize this particular field of EU law and to improve legal certainty. In the study, legal reasoning and interpretation are assessed in the context of the European Court of Justice and the EU public procurement legislation. Using the terminology of MacCormick and Siltala, the approach utilized in the study is based on the Three C’s in Legal Reasoning: from linguistic consistency to the pursuit of principled, analogy-aligned coherence among legal principles and, ultimately, to the value-laden social consequences of law. Going through the academic work on the legal reasoning of the ECJ, it is suggested that there may not be a need for additional directives of preference, affecting the use of different legal arguments. It is also suggested that that numerous approaches to the legal reasoning of the ECJ support the sequential directive of interpretation. Especially in the context of EU public procurement legislation, which is a complex field of procedural legislation with risks of getting mixed with other EU legislation concerning the relationship between public authorities and the market, it is suggested that the essential elements of consistency, coherence and the formal side of legal certainty are hampered if there is an excessive emphasis on teleological or consequential arguments. The case law of the ECJ in cases concerning the scope of application of public procurement legislation and the requirement to tender out public contracts is evaluated through the normative viewpoint of sequential use of arguments It is shown how the consistency and coherence of the Court’s reasoning and justification is improved through focusing on the concept of a public contract and its elements such as consideration. Same positive effects are drawn from the conceptual analysis of cooperation between contracting authorities. On the other hand, it is argued that the excessive use of teleological and consequential arguments has had negative effects on the coherence of both the normative field of EU public procurement legislation and the reasoning itself. The excessive use of teleological or consequential arguments has led to the expansion of tendering requirements concerning concession contracts, the use of the procurement legislation to achieving objectives of EU competition law, the introduction of new objectives such as administrative efficiency, indeterminacy regarding the relationship and the division of tasks between free movement rules of the Treaty and the procurement directives, and the general uncertainty as to what types of arrangements of public authorities are covered by tendering rules. Through systemic reasoning it is argued that better cooperation with these institutional actors could have been achieved. In addition, the use of systemic arguments has been and could have been even more efficiently used as an essential tool in preventing the useless duplication of reasons and mixing together pieces of legislation which may be loosely connected in terms of their objectives but not in terms of their tasks.
  • Vepsäläinen, Henna (Helsingin yliopisto, 2018)
    Since food behaviors are learned during childhood and may also track into adulthood, promoting healthy food habits among children and families is of special importance. Health promotion has traditionally been focused on individuals, but during the recent decades, the attention has shifted more and more towards environments. The food environment – a concept that encompasses physical, social, cultural, economic and political environmental factors associated with food behavior – is especially important for children, who cannot be considered to be fully responsible for their food choices. Arguably, home, preschool and school are the most prominent food environments for children. It has been shown that parental food consumption and home food availability – the two most commonly used measures for food environment - are consistently associated with dietary behavior among children. However, most of the studies investigating parent-child dietary resemblance have focused on the consumption of single food groups, such as consumption of fruit and vegetables. Similarly, home food availability has mostly been measured unidimensionally: as the availability of a single food group or as healthy/unhealthy food availability. Additionally, the outcomes used in the studies have mostly been food groups or theory-based dietary indices. However, the use of data-driven dietary patterns may give a more realistic picture of the actual diets of the participants. Thus, this study aimed at investigating social and physical environmental factors associated with whole-diet among children. This thesis used data from two cross-sectional studies. Papers I and II were based on data from the DAGIS study, which was conducted in 66 Finnish preschools and investigated health behaviors and associated factors. The participants were 864 children from the groups of 3–6-year-olds. Food consumption among the children and both parents was measured using a food frequency questionnaire (FFQ) filled in by the parents. The parents also reported home food availability and sociodemographic factors of the family. Paper III used data from the ISCOLE study, which examined obesity-related lifestyle and environmental factors among 9–11-year-olds in 12 study sites worldwide. Altogether 6560 children (54% girls) were included in the current analyses. The children reported their own food consumption, whereas the parents of the participating children reported home food availability. Detailed school audits were performed in all participating schools (n=256) to measure school food availability. In paper I, parent-child dietary resemblance and associated sociodemographic factors were studied. A novel statistical method was used in order to compare food consumption of the parent and that of the child on a whole-diet level. Based on the consumption frequency, the food items were ranked separately in the child’s and the parents’ FFQs. A dietary resemblance measure was calculated for each parent-child pair: a similar ranking in both the child’s and the parent’s FFQ yielded a resemblance measure of +1, whereas no resemblance in ranking resulted in the resemblance measure of 0. Father-child resemblance was on average 0.50 (95% CI, confidence interval 0.48–0.52), whereas mother-child resemblance was 0.57 (95% CI 0.55–0.58). However, having mother as a respondent (providing food consumption information on behalf of the child) was inversely associated with father-child resemblance, and a tendency for similar reporter-bias was also seen in the mother-child resemblance. Additionally, the number of weekly family meals was positively associated with mother-child dietary resemblance. Parental educational level was not associated with parent-child dietary resemblance. In papers II and III, the availability of unhealthy foods in the home was positively associated with dietary patterns generally regarded as unhealthy. Although having healthy foods in the home was inversely associated with unhealthy dietary patterns, the abundance of unhealthy foods seemed to at least partly overrule this inverse relation. Respectively, the availability of healthy foods in the home was positively and that of unhealthy foods inversely associated with dietary patterns generally regarded as healthy. The results were similar both among preschoolers and school-aged children. School food availability was not associated with dietary patterns. In conclusion, parent-child dietary resemblance was moderate regardless of the socio-economic background of the family. In addition, an important observation was made: the diet of the child resembled more the diet of the parent providing food consumption data on behalf of the child. Since the possible reporter-bias can affect the interpretation of the results, it would be advisable for researchers to report who filled in food consumption information for the child and take this into account in further analyses. Furthermore, in order to capture the social food environment more comprehensively, fathers – not only mothers - should be involved as parents in family-based studies. Additionally, since the availability of unhealthy foods in the home was associated with unhealthy eating regardless of the availability of healthy foods, the results suggest that it is particularly important to limit the availability of unhealthy foods in the home. The results of this study can be used in planning and carrying out health promotion programs aiming at improving the diets of the families.
  • Capasso, Cristian (Helsingin yliopisto, 2018)
    With 1 685 210 new cases in 2016 in United States (American Cancer Society), cancer poses a serious challenge for the patients, the healthcare system and families of patients considering that 595 690 people will die from the disease. In the last decades, a new class of therapies raised particular interest thanks to the ability to promote long-lasting complete responses. Immune therapy exploits the patient´s own immune system to find and kill tumor cells. Once immunological memory is established, this can potentially grant long term protection. Nevertheless, the results of immunotherapies are often inconsistent as we observe a number of complete remissions together with patient that completely fail to respond to the therapy. Uncovering the mechanisms of such difference is the primary aim of researchers that try to optimize the strategies to ultimately increase the number of responders. In this thesis three main strategies will be reviewed, studied and finally combined: i) oncolytic adenoviruses; ii) cancer vaccines and iii) immune checkpoint inhibitors. In Study I, we developed an innovative cancer vaccine platform based on oncolytic adenoviruses. We used the adenovirus as a carrier able to deliver peptides to antigen presenting cells. The Virus-peptide complex (i.e. PeptiCRAd) was build with electrostatic interactions, thus preserving the virus ability to infect and kill tumors cells. In addition, we showed that PeptiCRAd was able to reduce the growth of B16OVA and B16F10 tumors by inducing antigen specific responses through the activation of dendritic cells. Ultimately, we showed its potential in humanized mice engrafted with both human melanomas and human peripheral blood mononuclear cells (PBMCs). In Study II we addressed the problem of optimizing the peptides formulations to be used in cancer vaccines. We set up an in silico framework that uses multiple in silico tools such as MHC-I affinity and immunogenicity predictions. This allowed us to directly compare how mutating specific residues would not only change the orientation of the peptide within the MHC-binding pocket, but it would re-shape the whole portion of the MHC molecule that is recognized by the TCRs. This gave us suggestions on the differences in anti-tumor efficacy observed when testing several several improved tumore-specific peptides against both B16OVA and B16F10 tumors. In Study III we used oncolytic vaccines to boost the response to PD-L1 blockade. The Combination proved to increase the survival of melanoma-bearing mice, promoting the presence of TILs with a non-exhausted state (PD-1+ TIM-3-). Hence checkpoint inhibition well synergized with the immune activating properties of the oncolytic vaccine. The findings described in this thesis highlight the necessity of combination therapies to increase the number of responders to immunotherapy. This is a critical aspect to enlarge the number of responding patients and to maximize the benefits of immunotherapies, considering that immunotherapeutic approaches are reaching the market with unprecedented speed.
  • Jääsaari, Jesse (Helsingin yliopisto, 2018)
    Fourier coefficients of cusp forms are interesting objects due to their arithmetic significance but we know very little about them in general. For instance, it is an interesting question, for a fixed form, to ask how these coefficients are distributed or how large their order of magnitude can be. Such coefficients are hard to study individually and therefore it is useful to have some other ways to study them. A classical theme in analytic number theory is to understand highly oscillatory objects, such as Fourier coefficients of cusp forms, by studying their sums and their correlations against other oscillating objects over certain intervals. Knowledge of sizes of above mentioned correlation sums can improve understanding of the nature of Fourier coefficients we are interested in. For example, if such a sum is large, this means that the Fourier coefficients and the test sequence oscillate similarly. This naturally leads to the exponential sums considered in this work. We study weighted sums of Fourier coefficients of Maass cusp forms against various oscillatory exponential phases. More specifically, we consider linear exponential phases. The sums over both long and short intervals are studied. The classical theory of Maass cusp forms (in which the underlying group is GL(2,R)) can be generalised to higher rank groups. In this thesis we consider both exponential sums involving Fourier coefficients of classical Maass cusp forms as well as Fourier coefficients of GL(n) Maass cusp forms with n>2. The thesis contains four scientific articles on the subject. The first and fourth article deal with short sums involving Fourier coefficients GL(n) Maass cusp forms. In the second article the size of rationally additively twisted sums involving Fourier coefficients of GL(3) Maass cusp forms is studied on average. To achieve this, a truncated Voronoi summation formula for such sums is established. In the third article various bounds for both long and short sums involving Fourier coefficients of GL(2) Maass cusp forms is proved.
  • Rimpelä, Anna-Kaisa (Helsingin yliopisto, 2018)
    Diseases of the posterior segment of the eye, such as age-related macular degeneration and diabetic retinopathy, are the leading causes of blindness in the developed world. Drug delivery to the posterior eye tissues, including the retina and choroid, is accomplished by frequent intravitreal injections, which are expensive and burdensome to the health care providers and patients, and may cause harmful side effects. Therefore, sustained and less invasive delivery strategies are vitally needed to improve the treatment. Melanin pigment is found at high concentrations in ocular tissues, and many clinical drugs bind to it. Targeting the pigment to obtain sustained drug action in ocular tissues could be a feasible approach for improving ocular drug therapy. Therefore, this thesis project aimed to study the effects of pigment binding on pharmacokinetics in the eye with in vitro, in vivo and in silico methods. In addition, we investigated drug binding to the vitreous humor, as it may participate in modulating ocular pharmacokinetics and has been studied only scarcely. Melanin is a negatively charged, hydrophobic polymer, and it is expected to bind all basic and lipophilic drugs to some extent. Melanin is located in intracellular melanosomes, which are cell organelles surrounded by a lipid membrane, and are expected to have an acidic intraluminal pH. Due to the location of melanin, cellular and physiological factors act in concert with the binding to the melanin polymer, to impact ocular pharmacokinetics of melanin-binding drugs. We investigated pigment binding and related cellular and physiological factors with seven small molecule drug or drug-like compounds: chloroquine, timolol, nadolol, propranolol, methotrexate, 5(6)-carboxy-2′,7′-dichlorofluorescein (CDCF) and diclofenac. A pH-dependent binding (pH 5.0 vs. 7.4) to isolated porcine ocular melanin was observed, mainly with the acidic compounds that are less negatively charged and bind better at pH 5.0. Therefore, pH plays an important role in drug-melanin binding in the case of acidic drugs, but is less important in the case of basic drugs. The binding parameters, maximum binding capacity and affinity, were reliably calculated with the Sips binding isotherm instead of the commonly used Langmuir isotherms. The Sips isotherm is in line with the heterogeneous nature of the melanin surface to where the drugs bind, and, therefore, is better suitable for parameter analysis. Cellular uptake and intracellular binding in pigmented retinal pigment epithelial cells were shown to correlate with melanin binding, but other factors, such as lipophilicity of the drug, also need to be taken into account. Pharmacokinetic simulations of the retention of drugs in pigmented posterior segment tissues demonstrated that low drug permeability in the plasma and melanosomal membranes and the entrapment of positively charged drugs in the melanosome increases melanin binding related retention in these tissues. In addition, both the intracellular binding experiments with pigmented cells and the pharmacokinetic simulations showed that only a small fraction (~0.01%) of the highest binding drug of this study, chloroquine, is in the free form inside the cells. The free form of the drug elicits the drug action (beneficial or harmful), and it is, therefore, important to differentiate between the free and total drug inside the cells when assessing drug response. Furthermore, we demonstrated the distribution and retention of 123I-chloroquine in the eyes of pigmented but not albino rats after intravenous administration, establishing the use of single photon emission computed tomography/computed tomography imaging in monitoring melanin binding related kinetics in vivo. All in all, in the variety of experiments performed, melanin binding was shown to have a major impact on ocular pharmacokinetics in pigmented tissues. In addition to investigating melanin binding, drug binding to the vitreous humor was studied with a cassette of 35 clinical small molecule drugs. The binding was rather low and vitreal binding was concluded to have only a modest effect on ocular pharmacokinetics. In conclusion, this thesis project generated important information of the extensive pharmacokinetic impact of drug-melanin binding in ocular tissues. In addition, we demonstrated the moderate pharmacokinetic impact of vitreal drug binding, which is not comparable to melanin binding. The computational models developed on melanin binding and its pharmacokinetic implications can be used in drug discovery and development. The in vitro methods can also be implemented to the industry scale drug development process. The results obtained support the feasibility of using melanin targeting to attain sustained action in pigmented ocular tissues, but more research into the approach is needed before it can be employed in practice.
  • Kaartinen, Niina (Helsingin yliopisto, 2018)
    In the modern abundant food environment, the relationship between dietary carbohydrates and health outcomes is complex. The main aims of this thesis were to investigate the role of added sugar intake in the diet, and the relationship between dietary carbohydrates, the dietary glycaemic index (GI) and load (GL) and obesity. Another aim was to examine the dietary assessment methodology from the dietary carbohydrates perspective. This study was based on health examination surveys in the Finnish adult population conducted in 2000-2007: the DILGOM Study, the National FINRISK/FINDIET 2007 Study, the Health 2000 Survey and the Helsinki Birth Cohort Study (overall n=13 800, age 25+). The examinations included measured anthropometrics and questionnaires. The habitual diet was assessed with a food frequency questionnaire (FFQ). Food records served as a reference method in FFQ validation. Food GI values were based on a previous Finnish epidemiological GI database and were documented using international controlled vocabularies used in the Finnish national food composition database (Fineli). Intake of added sugars was estimated based on sucrose and fructose derived from foods other than fruits, berries, vegetables, and 100% fruit juices. On average, 40% of sucrose and fructose were from natural sources and the remaining 60% were added sugars. Subjects in the highest added sugar intake quartile were younger and had lower fibre, fruit, vegetable, rye, and fish intakes than subjects in the lowest added sugar intake quartile. Added sugar intake was associated positively with the intake of butter and butter mixtures. These results support the recommendation for the restriction of added sugars in the diet. In the meta-analysis of three cross-sectional studies (n=12 342), 23% of the subjects were classified as obese (body mass index, BMI ≥ 30 kg/m2). The likelihood of being obese was 35% lower in the highest quartile of total carbohydrate intake than in the lowest quartile. Total sucrose intake and dietary GL were also inversely associated with obesity. Dietary GI and fibre intake were not associated with obesity. Prospective cohort studies are needed to assess possible temporal relations. Instead of sucrose only, added sugars should be investigated. Between-method Spearman rank-correlation coefficients ranged from 0.27 (total sugars, men) to 0.70 (lactose, men). Based on the two methods, 73% of the subjects were correctly classified into the same or adjacent carbohydrate intake distribution quintile. Between-method agreement improved with decreasing age and with higher education, especially in women. The ability of the FFQ in ranking subjects according to most carbohydrate-related exposures is on the same level as in the international literature. However, sex, age and education represent important confounding factors. The origin and derivation methods of the GI values were successfully documented with the controlled vocabularies generally used in Fineli. This provides a foundation for the comparison of GI databases in international contexts.