Väitöskirjat: Recent submissions

Now showing items 1-20 of 7031
  • Spoljaric, Inkeri (Helsingin yliopisto, 2019)
    Spontaneously arising network events are a characteristic feature of all developing neural networks. This activity is crucial for normal neuronal development and the establishment of appropriate synaptic connectivity. In the developing hippocampus, depolarizing GABAergic drive is essential in generation of early network events, known as giant depolarizing potentials (GDPs). Blockade of GABAergic signaling leads to hypersynchronization of the network and emergence of ictal-like events, pointing to dual, both excitatory and inhibitory roles for GABA, in regulation of these events. In Studies I-III of this thesis, we examined the role of GABAA receptor (GABAAR) -mediated neurotransmission with some parallel work on glycinergic signaling as well as neuronal Cl- regulation in modulation of GDPs in the developing rodent hippocampus. In Study I, we demonstrate that low levels of GABA and glycine suppress GDPs by activating extrasynaptic receptors. This implies that regardless of the depolarizing drive for Cl- currents at this developmental stage, a low conductance via Cl- -permeable GABAARs and glycine receptors (GlyRs) can cause efficient shunting and inhibition of the network events. In Study II, we discovered that sustained activation of a subset of hippocampal interneurons, caused by the neuropeptide arginine vasopressin (AVP), silences the network events in the perinatal hippocampus, regardless of the maturational level of the GABAergic system as compared across species. This is attributed to decreased synchronous interneuronal input that is essential for the GDP generation. In Study III, we demonstrate that transport-functional K-Cl cotransporter 2 (KCC2) is present in the CA3 pyramidal neurons already in the perinatal stages in mice and rats. Cl- extrusion by KCC2 counteracts the dominant Na-K-2Cl cotransporter 1 (NKCC1) -mediated Cl- uptake and restrains the depolarizing GABAergic drive onto the CA3 pyramidal cells. Thereby, function of KCC2 limits pyramidal neuron spiking and synchronization during GDPs and participates in the modulation of GDPs from their developmental onset. This work describes novel physiological GABAergic mechanisms that control GDPs in the perinatal rodents and establishes a role for KCC2 in regulation of pyramidal neuron excitability and synchronization during GDPs starting from their developmental onset.
  • White, Joanne (Helsingin yliopisto, 2019)
    Information needs associated with forest monitoring have become increasingly complex. Data to support these information needs are required to be systematically generated, spatially exhaustive, spatially explicit, and to capture changes at a spatial and temporal resolution that is commensurate with both natural and anthropogenic impacts. Moreover, reporting obligations impose additional expectations of transparency, repeatability, and data provenance. The overall objective of this dissertation was to address these needs and improve capacity for large-area monitoring of forest disturbance and subsequent recovery. Landsat time series (LTS) enhance opportunities for forest monitoring, particularly for post-disturbance recovery assessments, while best-available pixel (BAP) compositing approaches allow LTS approaches to be applied over large forest extents. In substudies I and IV, forest monitoring information needs were identified and linked to image compositing criteria and data availability in Canada and Finland. In substudy II, methods were developed and demonstrated for generating large-area, gap-filled Landsat BAP image composites that preserve detected changes, generate continuous change metrics, and provide foundational, annual data to support forest monitoring. In substudy III a national monitoring framework was prototyped at scale over the 650 Mha of Canada’s forest ecosystems, providing a detailed analysis of areas disturbed by wildfire and harvest for a 25-year period (1985–2010), as well as characterizing short- and long-term recovery. New insights on spectral recovery metrics were provided by substudies V and VI. In substudies V, the utility of spectral measures of recovery were evaluated and confirmed against benchmarks of forest cover and height derived from airborne laser scanning data. In substudy VI the influence of field-measured structure and composition on spectral recovery were examined and quantified. By focusing on four key aspects of forest monitoring systems: information needs, data availability, methods development, and information outcomes, the component studies demonstrated that combining BAP compositing and LTS analysis approaches provides data with the requisite characteristics to support large-area forest monitoring, while also enabling a more comprehensive assessment of forest disturbance and recovery.
  • Haltia, Ulla-Maija (Helsingin yliopisto, 2019)
    Adult-type granulosa cell tumor (AGCT) is a unique subtype of ovarian cancer, accounting for 5% of all ovarian malignancies. The prognosis of AGCTs is often favorable, however these tumors have a tendency for late relapse. Eventually AGCT recurs in every third patient, and half of them succumb to the disease. Surgery is the mainstay of treatment. Platinum-based chemotherapy is used in advanced and inoperable AGCTs, although its efficacy is only modest. The objectives of this study were to improve the preoperative diagnostics of AGCTs and to uncover targeted treatments for AGCT. Serum markers HE4 and CA125 are commonly used in the preoperative evaluation of unknown ovarian masses, but their roles in AGCTs are unknown. Based on our results, HE4 levels are not elevated in AGCTs. We detected increased CA125 levels in a subset of AGCTs; however, the marker had no prognostic significance. These results underline the possibility of malignant ovarian tumor even in situations where CA125 and HE4 are both normal. Based on our and previous findings, inhibin B and AMH are the most specific markers in distinguishing AGCT from other malignant or benign ovarian tumors. The equilibrium between proliferation and apoptosis is crucial in the physiology of normal granulosa cells and it has been proposed to be disturbed in AGCTs. We evaluated the role of TNF-related apoptosis inducing ligand (TRAIL) in clinical AGCT samples and detected a significant correlation of TRAIL to its receptors (DR4 and DR5) in AGCT tissue samples, indicating active TRAIL signaling in AGCTs. Furthermore, both circulating and tissue TRAIL expressions were decreased in patients with large AGCTs, implying a tumor suppressive role for TRAIL in AGCTs. Our results suggest a potential role for TRAIL in AGCT treatment. We characterized the hormonal milieu of AGCTs in a vast collection of AGCT samples and studied the functional effects of follicle-stimulating hormone (FSH) and estradiol (E2) in tumor proliferation by using cell culture assays. FSH receptor and estrogen receptor beta were found to be expressed in the majority of tumors whereas the expression of aromatase, a crucial enzyme in estrogen synthesis, varied significantly among the studied tumors. In functional assays, FSH increased the viable cell number in subset of AGCTs, whereas E2 increased the cell number only at high concentrations. The aromatase inhibitor letrozole was able to block E2 synthesis in AGCTs but had no effect on cell viability. To systematically screen for new targeted therapies for AGCTs, we performed drug sensitivity and resistance testing and transcriptomic profiling. Seven AGCT primary cell cultures were exposed to a collection of 230 oncologic regimens. Among these compounds, a multi tyrosine kinase inhibitor dasatinib emerged as the most effective targeted treatment. Furthermore, dasatinib in combination with the traditional chemotherapeutic paclitaxel showed a synergistic effect, suggesting clinical testing of these regimens in patients with advanced AGCT. In conclusion, we verified that inhibin B and AMH are the most specific serum markers in AGCT preoperative diagnostics. Even though aromatase inhibitors showed no efficacy in inhibition of AGCT cell growth, further clinical studies are needed to verify the role of hormonal treatments in AGCTs. Importantly, our results suggest a role for TRAIL and dasatinib in AGCT treatment and encourage clinical testing of these regimens.
  • Hirvonen, Elina (Helsingin yliopisto, 2019)
    Familial clustering in hematological malignancies is well known. Although many factors have been identified as predisposing to acute myeloid leukemia (AML) and other myeloid disorders, there are still clinical challenges in the recognition. Identification of inherited mutations is important for the screening of family members and other individuals at higher risk of developing a myeloid malignancy. The aim of this thesis was to study germline alterations in myeloid disorders. The first aim was to discover the germline mutations in genes associated with AML pathogenesis and DNA repair in an unselected series of adult AML patients. We identified 34 variants of uncertain significance (VUS) or mutations in 42/68 (62%) patients with exomes available. Most of the identified gene alterations were found in DNA repair genes. The fraction of potentially pathogenic mutations was 9%. This study implicates that germline defects possibly associated with AML can also be identified in older cases without a known family history of cancer. The second aim of this study was to identify novel candidate predisposition genes to a myeloproliferative neoplasm named polycythemia vera (PV) by conducting an exome sequencing analysis in a family with four PV patients. Three variants shared by all the patients were identified in the genes ZXDC, ATN1, and LRRC3. The variants were screened in six other families with PV clustering, but those patients did not carry the variants. However, exome sequencing is very feasible in identifying new candidate variants. The third aim of this study was to investigate an X-chromosome-linked telomere biology disorder in three female siblings with a heterozygous germline DKC1 mutation. Two brothers in the family were diagnosed with dyskeratosis congenita (DC), which predisposes to e.g. AML. All three female mutation carriers showed DC-like manifestations; usually, X-chromosome inactivation (XCI) silences the defective X-chromosome in females, protecting them from symptoms. We examined the XCI status and mutant allele expression in different tissue samples. The results showed expression of both alleles in e.g. blood in two out of three females. Further, two of the females showed shortened telomere length. Recognition and follow-up of the females carrying mutations is important.
  • Melin, Johanna (Helsingin yliopisto, 2019)
    The development of modern cancer therapies has led to increased survival in most early onset cancer patients. As more patients experience long-term survival, the late effects of cancer and its treatments affecting both the health and quality of life of survivors have become evident. Female cancer survivors are concerned about the possible adverse effects of cancer on their reproductive health. The aim of this study was to evaluate use of fertility treatments, as well as adverse pregnancy-related conditions and obstetric outcomes in female cancer survivors. In this thesis, Finnish population-based registers were used to compare female cancer survivors to female siblings (Studies I, II and IV) and age-matched female comparison subjects (Study III). The study cohort, which was identified from the Finnish Cancer Register, comprised female cancer survivors diagnosed with cancer between 1953 and 2004 at the age of 0-34 years (N=13,799) and between 1953-2012 at the age of 0-39 years (N=24,610). Female siblings and age-matched comparison subjects were identified by linkage to the Central Population Register. Information on the use of fertility drugs (Study I) was obtained from the Reimbursement Register of Prescribed Medicines. Information on fertility treatments in women giving birth (Study II), as well as information on pregnancy-related conditions (Study III) and obstetric outcomes (Study IV), was retrieved from the Medical Birth Register. Female cancer survivors have an increased use of fertility drugs compared to siblings, explained by the increased use of assisted reproductive technology (ART). Time period played a key role, with increased use of ART in cancer survivors from 2003 onwards (Study I). In cancer survivors giving birth, time elapsed from cancer treatment increased the use of fertility treatments over time, suggesting that cancer treatments lead to a diminished ovarian reserve and a narrowed fertile window (Study II). The risk for preterm deliveries is increased in cancer survivors but the underlying reasons behind them have been unclear. Our results showed that certain pregnancy related conditions (vaginal bleeding and pre-eclampsia) tend to be more severe in cancer survivors, as these conditions more often lead to preterm delivery in cancer survivors compared to comparison subjects with the same condition (Study III). In addition, cancer survivors have an increased risk for hospitalization during pregnancy, intrahepatic cholestasis, fear of childbirth and mental disorders and diseases of the nervous system (Study III). Cancer survivors also have an increased risk for induction of labor and elective cesarean sections compared to siblings. The risk of adverse delivery outcomes were most increased in childhood cancer survivors, aged 0-14 years at diagnosis (Study IV). The increased use of fertility treatments in female cancer survivors emphasizes the need for collaboration between oncologists and gynecologists in order to identify those cancer survivors at risk for subfertility or infertility. Our results show an increased use of fertility treatments during recent years, indicating a more active approach towards treating cancer survivors with fertility issues. Our results further indicate that once pregnant, though most cancer survivors have uncomplicated deliveries, some are at an elevated risk for complications, that place them at risk of preterm delivery and adverse obstetric outcomes. Health-care providers should be aware of these risks, attempt to identify these women and provide adequate follow up for this subgroup.
  • Erpyleva, Svetlana (Helsingin yliopisto, 2019)
    In this monograph, the author analyzes a new type of politicized local activism that emerged as an outcome of the nationwide post-election 2011-12 protests in Russia, while these protests have been widely criticized for their political vagueness. Outwardly, new local groups resembled numerous activist groups that were active before the post-election mobilization. However, the pre-protest local activism was deliberately “apolitical” and focused on concrete and small problem-solving, while the post-protest local activism combined oppositional politics and “real deeds” tactics. This integration of opposite practices and meanings led to the emergence of the new politicized civic culture. The question the author answers is how the event of the protest mobilization could lead to the long-term changes in activist political culture. Considering this political evolution, she focuses on activists’ biographical trajectories. Basing on qualitative data (interviews, focus-groups, and observations of local activists groups organized in Moscow and St. Petersburg) and the existing theories of social movement studies, social events, and political socialization, the monograph proposes a new approach to the analysis of social and cultural changes through an event. The results show that patterns of activists’ socialization highly influenced the types of their future political involvement. Moreover, the post-election protest as an event (in terms of W. Sewell, 1996) helped people with different experiences who would never meet and act together before (e.g., apolitical volunteering and oppositional struggle) suddenly find themselves together and pushed them to continue their activity. Meanings and know-how that ordinarily are at odds (apolitical ideology of “helping people” and politics) met in post-protest local activism, thus creating new hybrid forms of civic participation and negotiating the opposition between the apolitical and the political. In the scholarly literature on an event and a biography, biographies are considered usually among the things an event can influence on, together with social structure, cultural meanings, etc. In the monograph, it is argued that the biography can be considered as an important tool, helping scholars to understand how exactly an event influence on structure or culture. The socialization taken in interactionist perspective, i.e., as the careers and not as the set of more or less stable dispositions, is a necessary tool to study how different experiences, visions, and know-how are accumulated, transferred from one place to another, find each others in the same groups or even the same lives, and how all these processes finally contribute to the creation of new elements of political culture. In this monograph thus, the author claims that in order to explain social movement transformations and changes produced by an event, people’s biographies should be brought back into the analysis.
  • Väätäinen, Matti (Helsingin yliopisto, 2019)
    Ecclesiology has been one of the rising areas in systematic theology in the recent decades. The leading, paradigmatic theme has been communion ecclesiology: the unity of the church and the fellowship of Christians have been understood generally as communion, meaning shared life (koinonia). This kind of koinonia or communion of the church is justified by a trinitarian way on the basis of the unity and distinction of the Father, the Son, and the Spirit. The unity of the church is manifested in its sacramental life in different local churches. The purpose of this study was to investigate Wolfhart Pannenberg’s (1928-2014) undestanding of the unity of the church as communion. The task of the study included an analysis of the systematic theological prerequisities for the unity of the chuch as communion in Pannenberg’s thinking. It was assumed – as the central hypothesis – that the whole of Pannenberg’s ecclesiological scheme is focused on and structured around the theme of the unity of the church. It was also presumed that the theme of unity is central in his mind-set not only because of his ecumenical activity but also because of the contents, main questions, and inner logic of his own comprehensive theological system. Pannenberg’s insights were thus to analyse in the overall context of this theology. The method used was systematic immanent by nature. The results of the study proved that the hypothesis was correct: Pannenberg’s view on the unity of the church as communion with the specific internal dimensions and solutions is connected with the general guiding principles of his theology – specifically with its foundational question concerning the unity of trinitarian God. Pannenberg offers a carefully structured systematic theological basis for striving for the unity of the church. At the same time he shows by a theologically justified way why the unity of the church is important in the first place: it is connected with the appearance or coming of the eschatological kingdom of God – that is: the manifestation of the one final truth about God, salvation, and the whole existence. Pannenberg sees the church as an anticipating sign of the kingdom of God in history. According to him, the church can credibly be this kind of a sign only if it’s one. That is: when it’s one communion comprising all Christian churches. Thus, the unity it not just an additional value but an important value in itself. According to Pannenberg, the unity of the church comprises both spiritual and visible aspects. He refers to this by describing the unity of the church primarily in terms of the body of Christ (sacramental communion), but also by the terms of the people of God (the concrete, living fellowship of the church). In this way, Pannenberg’s model is characterized by a nuanced ontology of communion. At the same time he offers some remarkable solutions to the central challenges to the unity of the church – such as questions concerning the ordained ministry.
  • Haaramo, Anu (Helsingin yliopisto, 2019)
    Crohn´s disease (CD) is a chronic inflammatory disease that can affect any part of the digestive tract, including the mouth. The reported prevalence of oral manifestations in CD varies widely and ranges from 0.5% to 80%. Orofacial granulomatosis (OFG) is a rare chronic inflammation presenting in the oral cavity and around the mouth without intestinal involvement. Typical is labial or facial oedema and ulceration in the oral mucosa. Melkersson-Rosenthal syndrome (MRS) is considered to be one manifestation of OFG, where granulomatous inflammation and oedema is accompanied by recurrent facial palsy and fissured tongue. Oral lesions in CD, OFG, and MRS cannot be clinically or histologically distinguished. Patients with OFG may develop CD and it is debated whether OFG is an oral manifestation of CD, or a separate inflammatory disorder. In addition, it is unknown whether patients with MRS are prone to develop CD in follow-up. The aim of this thesis was to investigate and compare conditions presenting with orofacial symptoms —OFG, CD, and MRS— and study the connection between these entities. This thesis consists of studies on patients with pediatric-onset OFG, patients with pediatric-onset CD who had reached adulthood and patients with triad or oligosymptomatic MRS or its monosymptomatic form cheilitis granulomatosa (CG). Otorhinolaryngological and dental examinations, evaluation of nutrition from food records, and laboratory tests were included. Orofacial findings were photographed and recorded using a structural schema. Possible factors predicting bowel disease in orofacial patients were of special interest. In patients with CD, health-related quality of life (HRQoL) was evaluated. Blood samples were collected to investigate inflammatory markers and anti-Saccharomyces cerevisiae antibodies A (ASCAbA) and G (ASCAbG). In patients with OFG, the HLA-haplotypes (Human leucocyte antigen) were also examined to evaluate the role of HLA in the pathogenesis of OFG. Stool samples were collected to evaluate faecal calprotectin, a surrogate marker for intestinal inflammation. We found that prognosis for OFG is good. Symptoms tend to diminish during the course of the disease. Of the patients with pediatric-onset OFG, 72% developed CD. Elevated ASCAbA may serve as a factor predicting the underlying or developing CD in patients with OFG. Examination of HLA-haplotypes showed that tissue antigen HLA-B*44 might be a marker for OFG, but further studies are needed. In patients with CD the oral symptoms seem to be inactive when the gut disease is under good therapeutic control. However, patients with CD and a history of perianal abscessing disease seem to be prone to oral manifestations. Of the patients with MRS or CG, in total 11.1% had a diagnosis of inflammatory bowel disease (IBD) which suggests a link between MRS and IBD, not only CD but ulcerative colitis as well. None of the nutritional factors or dental findings correlated to oral findings in patients with OFG or pediatric-onset CD. Otorhinolaryngological findings were minor in both groups. Thus, OFG and CD do not seem to increase otorhinolaryngological comorbidity.
  • Antin, Katri (Helsingin yliopisto, 2019)
    This thesis examines how divine knowledge is understood to be transmitted from God to human beings in the seven sapiential Thanksgiving Psalms (1QHa 5:12‒6:33; 7:21‒8:41; 9:1‒10:4; 15:29‒36; 17:38‒19:5; 19:6–20:6; 20:7–22:42). A modern scholarly definition of divination is used as an aid to analysis, and how the transmission of divine knowledge is understood in the sapiential Thanksgiving Psalms is discussed in relation to previous theories about the divinatory practices of the Second Temple period. The demarcations and structure of each Thanksgiving Psalm are discussed by noting scribal practices. The sapiential Thanksgiving Psalms can be grouped together by their inclusion of various sapiential themes, forms, and vocabulary, but when it comes to the transmission of divine knowledge, they form a heterogenous group. Four sapiential out of the seven Thanksgiving Psalms (1QHa 5:12‒6:33; 7:21‒8:41; 9:1‒10:4; 20:7–22:42) depict a teacher of wisdom as the mediator of divine knowledge, the divine knowledge itself described as a mystery (רז) that concerns God’s deterministic plan for his creation. In 1QHa 5:12‒6:33 and 7:21‒8:41, God’s deterministic plan are described in terms of two diverse ways. Previously, several sapiential Thanksgiving Psalms have been studied in relation to either sapiential divination or inspired interpretation of earlier traditions; thus far, however, it has gone unnoticed that same psalms include features of both phenomena. In 1QHa 5:12‒6:33, 7:21‒8:41, and 9:1‒10:4, divine knowledge is acquired and transmitted through the implicit interpretation of earlier traditions, but, instead of making this process visible, the transmission of divine knowledge is described as a sapiential revelatory process. These earlier traditions concern especially the creation. Both “biblical” and “non-biblical” compositions are interpreted in the same psalms, indicating that the division to “biblical” and “non-biblical” arises more from modern conceptions of the Bible than from that of the late Second Temple sources themselves. Transmission of divine knowledge includes both inductive and intuitive aspects. The sapiential Thanksgiving Psalms relate similar intuitive elements of the transmission of divine knowledge as the classical prophetic books of the Hebrew Bible. Nonetheless, the transmission of divine knowledge requires also elements that are more at home with inductive than with intuitive divination. According to 1QHa 15:29‒36, 17:38‒19:5, and 19:6–20:6, no mediator is needed to have access to divine knowledge.One possible explanation for why these psalms do not depict any human mediator is that they lack didactic elements, unlike 1QHa 5:12‒6:33, 7:21‒8:41, and 9:1‒10:4. The psalms 1QHa 9:1‒10:4, 15:29‒36, 17:38‒19:5, and 19:6–20:6 contribute to our understanding of the role divine knowledge played in praising God as well as in eschatological beliefs. On the other hand, 1QHa 5:12‒6:33, 7:21‒8:41, and 9:1‒10:4 not only describe the transmission of divine knowledge; these psalms could themselves have functioned as vehicles in that transmission. The process of transmitting divine knowledge can be examined as part of the literary and oral transmission of these psalms.
  • Kousa, Päivi (Helsingin yliopisto, 2019)
    Classrooms are becoming more diverse and the number of low achieving students is continuously increasing. About 20% of European 15-year-old-children are not at the required educational levels. There are many reasons for students’ low achievement such as negative attitudes, immigrant or low socio-economic backgrounds, learning difficulties etc. Furthermore, students find that science and especially chemistry is boring, uninteresting, irrelevant and difficult. Nevertheless, low achievement can have critical consequences for the entire society, if students are unable to participate in it as equal citizens, make rational and sustainable decisions or be sufficiently qualified for working life demands. Accordingly, more research is needed, how low achieving students could be supported in diverse classrooms. Science teachers tend have more negative beliefs towards student diversity and teaching practices in diverse classrooms compared to subject teachers. That is crucial, because teachers' beliefs and practices can affect students' achievement. The aim of this thesis is to understand, how science, and especially chemistry teachers could be better supported and prepared for diversity and better student achievement during their entire careers. The main research question is: What is the relationship between student achievement and teachers' beliefs about diversity and science teaching practices for diverse students? In order to answer to the main research question, three subquestions are asked. Firstly, low achieving students' thoughts about chemistry and chemistry teaching practices compared to other students is analyzed. The second question clarifies, how does the STSE-based school-industry collaboration affect to pre-service science teachers' beliefs about their future practices. The third question is about pre- and in-service teachers' beliefs about teaching chemistry in diverse classrooms. This thesis consists of three interconnected studies and one descriptive report (I-IV). Study I describe what is the connection between students' low achievement and most preferred teaching practices compared to other students. Since there was a clear evidence of the fact, that all students in spite of their achievement levels preferred industry visits, it was chosen to be a main topic in study II. In that study, the connection between pre-service teachers' beliefs and STSE-based teaching practices were examined in a context of school-company collaboration and visits. Since pre-service teachers' beliefs were significantly improved after the STSE-based course, the following descriptive report III concentrated on science teacher education and how it could be developed in order to prepare future chemistry teachers for diversity. Furthermore, the last study IV is about the in-service chemistry teachers' beliefs about their work in diverse classrooms. The mixed methods approach which includes survey and case-study is used in order to answer the research questions. Data for the survey was collected from 2949 secondary school students with the help of the Finnish National Board of Education (study I). Secondly, the effects of STSE-based teaching practices were carried out in Finland and Slovenia with 42 pre-service chemistry and science teachers (study II). The presented teaching model for teaching diverse students (report III) was based on German and Finnish chemistry teacher education programs. Furthermore, the beliefs of eight in-service science teachers were examined by case-study (study IV). There is not much national or international research about the topic of this thesis. This thesis presents prominent insights and ideas, how especially low achieving students could be supported by developing science and chemistry teacher education. Accordingly, following suggestions are made: (i) Practices for teaching diverse students have an influence on students' achievement. Therefore, it is beneficial to take students' thoughts into account when activities are planned and implemented. It is worth noticing, that students prefer similar practices in spite of their achievement levels: company visits, using digital implementations and working in groups. (ii) STSE-based teaching practices such as company visits are preferred by diverse students and they also have a positive effect on teachers' beliefs. For that reason, teachers should have regular opportunities to practice those skills in authentic environments. STSE-based teaching material can be also beneficial for diverse students. (iii) In-service teachers do have basic knowledge about diversity, and they use a considerable amount of effort in order to take their students' needs into account. However, they need more support and resources. In conclusion, pre-and in-service teachers' concerns, needs and beliefs should be taken into account, when support for them is planned during their entire career. Teacher support for diversity and better student achievement need both national and international collaboration among teacher educators, pre- and in-service teachers, special education teachers, students, parents and other community members. This has a significant effect on student achievement and the entire society in turn.
  • Warpenius, Katariina (Helsingin yliopisto, 2019)
    Local alcohol policy as moral governance – Methodical and ethical questions raised by quasi-experimental effectiveness research The research analyses the effects of a local alcohol policy and discusses the problematics related to methods and ethics in quasi-experimental research into the effectiveness of an intervention programme. The first part of the research assess the effects of a local alcohol policy programme (PAKKA) on the frequency of alcohol served to intoxicated clients and the occurrence of violent assaults in licensed premises. The second part of the research discusses how effectiveness research per se can be used in the decentralised governing of local alcohol markets and communities. PAKKA was a community-based programme combining law enforcement, responsible beverage service-training (RBS), information and media campaigns and local structures for co-operation in two areas of Finland carried out in 2004–2007. The research design was a controlled quasi-experimental pre- and post-intervention study. In the field work, a male actor pretended to be clearly under the influence of alcohol and attempted to purchase a pint of beer from licensed premises in the study area. For the baseline measurement, every bar and night club was visited in the intervention and the control areas (94 licensed premises in total). Post-intervention data was gathered using the same method (100 licensed premises in total). The results were reported in terms of the service refusal rates. Logistic regression analyses were conducted to study the statistical significance of the results. In the post-intervention study there was a statistically significant increase in service denials to the actor in the intervention area (from 23% to 42% of the licensed premises) compared to the control area (OR = 3.7; p < 0.05). The refusal rates increased statistically significantly among the young servers. The findings demonstrate that multi-component community-based interventions can have a significant impact on over-serving alcohol to intoxicated customers. The most crucial element of the interventions seemed to be effective law enforcement. The local alcohol policy interventions had no scientifically demonstratable effects on the frequency of police-reported violent assaults in licensed premises. Quasi-experiments based on test purchases are open to criticism on methodological and ethical grounds. It is a challenge to control for methodical problems such as the validity of the comparative experimental setting, the standardisation of research assistants’ performances and the disclosure of covert field work. Ethical concerns relate to the fact that covert research is not declared to the research participants especially if the object of the study is an illegal action (i.e. selling and serving alcohol to intoxicated clients or minors). In this research, the concept of moral governance was developed as a theoretical perspective based on two traditions: Foucauldian analytics of government and theories of moral regulation. Local alcohol policy was viewed as a practice of moral governance, in which the responsibility for the regulation of lifestyle-related harm is decentralised from the central state to other actors. Confusion in terms of moral governance arises when market actors deploy the test purchasing method in order to highlight their own social responsibility and to promote private business interests in alcohol policy debates. Keywords: local alcohol policy, analytics of government, moral regulation, test purchase experiment, covert research
  • Lahti, Jaana (Helsingin yliopisto, 2019)
    The experience of working within a school community not only fosters the de-velopment of key knowledge-related skills, but it also develops important social and emotional skills, which are in turn important for, and when, working within other communities. When studying to become a teacher, students have the op-portunity to reflect on the nature and significance of socioemotional interaction skills and their own understandings in respect of these skills, as well as the chance to explore the co-regulation of collective activity when studying in a long-term communal small group. Contemporary society and the perspectives, values and current concerns of science also challenge the students to reflect not only the collaborative insights they achieve but also the flexible and creative application of them. As teachers they will also need skills that will help to secure pupils’ psychological well-being. Ethics, values and morality are concretized and consolidated in collaborative reflection. Such reflection shows the morality of behaviour as a reality that reflects the theoretical, tense principles of ethical views. Furthermore, teacher identity work challenges the students' ability to know, attend to, and negotiate conflicts and contradictions such that the emotional blocking and insecurity that can slow down effective reflection may be reduced. This study examines both challenging and supportive perspectives in the context of a long-term student teacher community-based small group. At the theoretical core of the study is an attentiveness to: the socioconstructivist notion that one of the benefits collaboration affords is the potential for reflection; the need for pedagogical support, scaffolding, and the elements of co-regulation. This is a case study. The data were collected through interviews and also by utilizing the students' reflection on video and audio materials, as well as their readings and a stimulated recall questionnaire. The material has been analysed through qualita-tive content analysis. The results show that the realization of a space for a meaningful negotiation of identity in a group requires both confidence and agency and a capacity to listen to others, especially in conflictual situations, including those situations where there is the threat of a suppressive or reductive consensus. In this study, the contextual supports that enabled student teachers to benefit from conflicts when reflecting were: emotional safety, the lengthy duration of the group process and time for reflection. The processes implicated in the development of a positive communication culture, one that encourages and supports reflection and interthinking, became a central focus for the study. Where there was not evidence of a positive culture of communication, there was evidence of an emotionally disruptive atmosphere and a threatened sense of security. With respect to the scaffolding of the group, an emotionally safe atmosphere was seen to be a pre-requisite for fostering a sense of creativity in within the collaborative community was implicated in the quality of collaboration. In this case, the fading of fear and insecurity made solidarity and mutual recognition of each other's often divergent views possible to accept. Pedagogical conclusions were drawn from the results of the study: intentionality as a space of free will that under-stands the well-being of psychic activity arises as a telos of pedagogical support. Scaffolding metacognitive and metacompetences may open up onward possibilities for supporting group reflection and co-regulation.
  • Felin, Elina (Helsingin yliopisto, 2019)
    Salmonella spp., Yersinia enterocolitica, Toxoplasma gondii and Trichinella spp. are the most relevant biological hazards in the context of meat inspection of pigs in the European Union (EU). These zoonotic pathogens show no clinical symptoms or gross pathological lesions in pigs, and thus are not detectable with current meat inspection procedures, except Trichinella spp. by laboratory analysis. In this study, we analysed the serological prevalence of these pathogens in Finnish fattening pigs and evaluated serological monitoring as a control method. In total, we studied 1353 meat juice samples and 1793 serum samples of fattening pigs using commercial ELISA kits. The seroprevalence of pathogenic Yersinia spp. was the highest of the studied pathogens, and Yersinia antibodies were detected in 57% and 66% of the meat juice and serum samples at the end of the fattening period, respectively. The seroprevalences of Salmonella spp. and T. gondii were low. Salmonella antibodies were detected in 3% of the meat juice samples and in 18% of the serum samples at the end of fattening. T. gondii antibodies were detected in 3% of meat juice samples and 1% of serum samples. Trichinella spp. antibodies were not detected. The seroprevalences at the end of the fattening or at slaughter were not associated with post-mortem findings of the current batch, which was expected. This indicates that we need new tools to control these public health hazards in pork. Meat juice serology at slaughter was feasible and easy to perform. We observed huge differences between farms considering Salmonella spp., Yersinia spp. and T. gondii seroprevalences. This shows that farm-level serological data could be used as part of the food chain information (FCI) for risk-based decisions to improve food safety. Risk-based decisions include slaughtering arrangements, additional carcass processing, targeted sampling at the slaughterhouse and improved biosecurity measures at the farm. However, risk mitigation targets and procedures must be carefully adjusted for each pathogen. With targeted serological monitoring of T. gondii we could effectively target control measures and diminish the pathogen in pork. Serological monitoring of pathogenic Yersinia spp. could be the first step in the huge challenge of Y. enterocolitica in pigs, allowing for the possibility of slaughtering pigs from high-risk farms at the end of the day. Serological monitoring of Salmonella spp. would be beneficial, but would only have a limited positive impact on food safety, because the current situation is already excellent. Serosurveillance of Trichinella spp. would become meaningful, if current testing is to be diminished. In addition to food safety issues, FCI could be useful for visual-only inspection, which should be the most common inspection method. We analysed authentic FCIs and meat inspection findings of 85 slaughter batches of fattening pigs. In addition, we analysed on-farm health status indicators, assessed by a veterinarian, and the meat inspection findings of another 57 slaughter batches. The partial carcass condemnation rate of the current batch was best predicted by the partial carcass condemnation rate of the pigs from the same farm within one year. Constant coughing and tail biting at a farm were associated with partial carcass condemnations. On-farm health indicators (such as the healed tail biting rate at the end of fattening and constant coughing during fattening) together with previous meat inspection results could be used as part of the FCI to make decisions regarding the meat inspection procedure: visual-only or additional inspections. However, farmers must be properly advised to carefully report this information.
  • Björkman, Johanna (Helsingin yliopisto, 2019)
    This doctoral thesis discusses the architecture of industrial communities constructed by forest industry companies from the perspective of cooperation and social networks of an architect and his clients between the two World Wars. The forest industry was the forefront of Finland’s rapid industrialization in the 1920s and 1930s. Success was manifested in the built environment. The main actor of this research is architect Wäinö Gustaf (W. G.) Palmqvist (1882–1964), who designed a considerable number of projects for Finnish industrial companies. In addition to the architect, the study also includes clients: G.A. Serlachius Oy and Yhtyneet Paperitehtaat Oy. The architect-client relationship was emphasized in the 1920s and 1930s as a personal relationship between Gösta Serlachius and Rudolf Walden. Serlachius and Walden are, along with Palmqvist, the ones I look at from the close range. More detailed research is focused on the Mänttä and Myllykoski mills. In both of these, the success of the forest industry's economic growth was – and still is – visible in the built structure and architecture of the entire community. Both are now valued as nationally significant built cultural environments mostly through their industrial history. In addition to economic growth, there were sociopolitical reasons behind building up the industrial communities. Forest industry companies struggled to restore peace after the Finnish civil war and to continue their production. I have described building the industrial communities as work where concepts of corporate social responsibility and welfare capitalism were connected. Besides the factories, the companies built housing, schools, churches and other social welfare amenities for the workers. It was a goal-oriented and guided construction where the idea behind the assignments given to the architect was to get the right, aesthetically high quality and beautiful community. In the study, architecture is linked to the political, economic and cultural contexts of time. This research connects Finnish industrial communities to the international models that first appeared in the United Kingdom, Germany and France and the United States. In this study, I refer in particular to the examples known as model communities. The communities have been designed with the ideas of urban design of the early 20th century, such as a garden city and the ideals of aesthetics. The research complements the art historical perspective in the history writing of forest industry.
  • Manninen, Antti (Helsingin yliopisto, 2019)
    Global and in-situ wind field observations are crucial for predicting weather and climate. Air motions within the atmospheric boundary layer (ABL) affect aerosol-cloud interactions and are essential in forecasting poor air quality episodes. During the last few decades remote sensing instruments, especially Doppler lidars, have been used to monitor the vertical profile of the ABL with high time and height resolution. Such lidars can measure the vertical velocity directly in vertical pointing mode and with a scanning capability also retrieve horizontal winds. From Doppler lidar measurements profiles of turbulent properties, wind shear, and higher order velocity statistics can be calculated – essential in revealing the vertical structure of the ABL. Pulsed Doppler lidar systems using heterodyne detection usually operate in the near-infrared spectral region. They transmit a laser pulse, which scatters from atmospheric particles, and record the backscattered part of the pulse. There are significant limitations in the sensitivity of such lidar systems in locations where aerosol load is low and hence the signal-to-noise ratio (SNR) is low. In theory, sensitivity of a pulsed Doppler lidar system can be improved by averaging the signal and thus increasing the SNR, assuming the noise is Gaussian. If not, the improvement in sensitivity is limited by the noise characteristics. Any bias in SNR is propagated into the velocity uncertainties and further to estimated turbulent properties. This thesis is comprised of research which aimed to fully characterise the noise in the backscatter signal of a pulsed Doppler lidar system, and to develop methods for correcting any bias detected in the noise. The instrument's sensitivity was improved significantly which increased data availability. Method for classifying ABL turbulent mixing was developed by combining several Doppler lidar quantities, which enables estimating the coupling of turbulence to the surface and/or clouds as well as identifying the sources causing turbulent mixing within the ABL. Data processing methods developed for the Doppler lidar system were applied to detect elevated aerosol layers from measurements of another lidar system. The developed methods were collected into a freely available software toolbox with the ultimate aim of generating harmonized Doppler lidar products across European Doppler lidar sites.
  • Kaltiainen, Hanna (Helsingin yliopisto, 2019)
    Mild traumatic brain injuries (mTBI) are common, and while most patients recover well, there is a minority of patients suffering from prolonged symptoms lasting over three months. Pathological processes provoke low-frequency (0.5 - 7 Hz) oscillatory brain activity, measurable with electroencephalography (EEG) and magnetoencephalography (MEG). After mTBI, low frequency activity (LFA) is hypothesized to arise from cortical neurons suffering from de-afferentation after traumatic axonal injury. The natural evolution and prognostic value of low-frequency activity (LFA) measured with MEG, however, is not yet firmly established and reliable biomarkers for cognitive complaints after mTBI are lacking. The aim of this thesis was to examine the occurrence and natural evolution of low frequency activity (LFA) after mild traumatic brain injury (mTBI), and to assess its prognostic value in predicting those with prolonged symptoms. Additionally, we wanted to examine the effect of mTBI to brain oscillatory activity during cognitive tasks and find indicators for altered processing. The existence of LFA in healthy subjects might, however, hamper its’ diagnostic value. Therefore, in Study I we created a reference database of resting-state oscillatory brain activity and observed LFA in only 1,4% of healthy subjects’ MEG recordings. The Study II assessed the occurrence and evolution of LFA in resting-state MEG recordings of mTBI patients. At a single-subject level, 7/26 patients presented aberrant 4–7 Hz (theta) band activity; 3/7 patients with abnormal theta activity were without any detectable lesions in MRI. Of the twelve patients with follow-up measurements, five showed abnormal theta activity in the first recording, but only two in the second measurement, implying the importance of early measurements in clinical settings. The presence of LFA was not, however, correlated with the prevalence of self-reported symptoms. The Study III concentrated on the modulation of oscillatory activity during cognitive tasks, Paced Auditory Serial Addition Test (PASAT) and a vigilance test. Attenuation of cortical activity at alpha band (8 – 14 Hz) during PASAT compared with rest was stronger in patients than in controls (p≤0.05, corrected). Furthermore, the patients presented significant attenuation of oscillatory activity also in the left superior frontal gyrus and right prefrontal cortices which was not detected in controls. Spectral peak amplitudes of areal mean oscillatory activity at the alpha band were negatively correlated with the patients’ neuropsychological performance (p<0.01, uncorrected). Areal alpha frequency modulation during PASAT compared with rest was altered in patients: While the alpha peak frequency increased occipitally and remained stable parietally in controls, it was stable occipitally and decreased parietally in mTBI patients (p=0.012). According to our studies, LFA, especially theta-band oscillatory activity can provide an early objective sign of brain dysfunction after mTBI, and cortical oscillatory activity during a demanding cognitive task (PASAT) is altered after mTBI. Our observations suggest that both aberrant theta-band activity and the altered alpha activity during cognitive tasks may offer clinically relevant indicators of changes in neural processing after mTBI.
  • Jurkiewicz-Rohrbacher, Edyta (Helsingin yliopisto, 2019)
    The objective of this contrastive research is (1) to determine the rules of correlation between the language-specific category Polish Verbal Aspect (PVA) and the elements of Finnish clause, whilst (2) re-examining the semantic scope of PVA, and (3) improving the definition of the cross-linguistically valid comparative concept of aspectuality. The investigation is empirical, and based on 900 Polish-Finnish clauses compiled in the form of a bidirectional parallel corpus stratified in three samples according to text types. The corpus is annotated on three levels, following the scalar model of temporality: the morphosyntactic and semantic clause-internal levels, as well as the clause-external level, including such elements as taxis and the quantificational-pragmatic context, temporally located (existentially quantified) situation, and generic or generalising interpretation (universal quantification). The reasoning in the study is mostly inductive. In contrast to the previous studies on aspect, the work is organised bottom-up. The data is approached quantitatively, using state-of-the-art methods. First, the descriptive statistics of temporal markers in the corpus are discussed. Afterwards, the data is summarised in a statistical model and visualised in a hierarchical cluster structure. Particularly interesting correlations (e.g. tense-aspect or case-aspect) are further validated with the random-forests method. The quantitative results yield a two-layered model of aspectuality, distinguishing between two levels: the outer, temporal-deictic level and the inner level related to the notion of change in time. Thus, the study confirms the validity of multi-layered concepts of aspectuality as previously postulated. As to language-specific results, PVA correlates with Polish and Finnish tenses within the outer, temporal-deictic layer. This interaction involves the third element – temporal quantification. The inner layer is realised in Finnish in the predicate-argument structure, and therefore, the Finnish argument case-marking is the closest correlate of PVA. Here the most important systematic opposition are between the lative and essive semantic cases (including Translative and Essive), and between the Total and Partitive type of object. The notion of change which is the semantically relevant factor is treated as gradable opposition (next to the traditionally used polar and equipollent oppositions), and therefore, the formal comparison between PVA and Finnish differential object marking is possible within the scalar description. The Finnish derivational valency modifiers (transtivisers and detransitivisers), however, do not seem to play any significant role in the marking of aspectual oppositions. Neither do lexical temporal expressions play much role here, as their generally low frequency does not deviate from the frequency of Polish expressions of that kind. In particular, the study shows that the measure adverbials in the object cases are quite infrequent in language use. Therefore, their contribution in expressing aspect is marginal.
  • Linnanmäki, Kirsikka (Alma Talent, 2019)
    My doctoral dissertation, titled The Best Interests of the Child in Child Custody Disputes in Court-connected Mediation, combines child law and mediation theories. I investigate how the best interests of the child and mediation are determined and how these two perspectives interact with each other, both in theory and in practice. In addition, needs for further development of the procedure are outlined. With child custody disputes, I refer to conflicts and disputes between the guardians (typically the parents) regarding their child, over custody, residence, right of access (contact, visitation) and child maintenance. Court-connected mediation in Finland is an in-court alternative process to court trial with one or more impartial, neutral mediator. In this interdisciplinary I have combined legal theory and doctrine, theories and methods from the social sciences and multidisciplinary mediation theories. First, I focused on the theories and principles of court-connected mediation through legal doctrine and mediation theories to outline the context for court-connected mediation. Secondly, I focused on the theories and principles of child law. The modern view of child law is based on the UN Convention on the rights of the child and its rights-based interpretations of the best interests of the child. In addition, national legislation is systemised and interpreted. Thirdly, I focused on the contents and definitions of custody disputes and court-connected mediation. In addition, I looked at access to justice. Fourthly, my research includes an empirical section with observations and interviews. No children were interviewed, since they did not participate in the mediations, which is customary in Finland. The data was analysed with content analysis. The main findings of the research are the following. First, the definitions of the best interests of the child are various and partly contradictory in the pluralistic legislation concerning court-connected mediation in custody disputes. Multiple interpretations of the best interests norm and principle are possible, but not all of them correspond to the modern child law perspective. Secondly, the court-connected mediation model in legislation is somewhat contradictory in child custody matters: the generally adopted dichotomy of facilitative and evaluative models seems to be insufficient to achieve a rights-based interpretation of the best interests of the child. Thirdly, I saw the best interests of the child as a multidisciplinary set of factors, including a child’s legal rights that need to be taken into account and evaluated individually on a case-by-case basis. The empirical data suggested that in practice the interpretations of mediation and of the best interests of the child were somewhat narrower compared to the theoretical options that are available. Consideration of the cross-effects of child law and mediation theory perspectives has thus unused potential. Court-connected mediation in child custody disputes in Finland could be improved both in theory and in practice by developing deeper understandings of child law and mediation theories as well as their interaction, by amendments to legislation and other regulations, by more training in mediation and child law, and by an altogether more systemic and reflexive approach. More attention could be paid to children’s human rights requirements and also to access to justice in its many dimensions in the context of mediation as an alternative process.
  • Lamminen, Marjukka (Helsingin yliopisto, 2019)
    The objective of the research described in this thesis was to evaluate the potential and sustainability of protein feed use of different non-defatted microalgae species in the nutrition of lactating dairy cows. Four physiological experiments (Publications I-III) were conducted with dairy cows to compare dry matter (DM) intake, milk production, energy metabolism, nitrogen (N) utilisation and amino acid (AA) metabolism using diets containing microalgae (Spirulina platensis, Chlorella vulgaris and Nannochloropsis gaditana) and conventional protein feeds (rapeseed meal, soya bean meal and faba beans). The microalgae diets constituted of S. platensis (Exp. 2, 3 and 4; I-III), C. vulgaris (Exp. 3; II), mixture of S. platensis and C. vulgaris (Exp. 1; I), and mixture of C. vulgaris and N. gaditana (Exp. 3; II). These microalgae substituted protein in rapeseed meal partially (Exp. 1, 2 and 4; I, III) or completely (Exp. 1 and 2; I), soybean meal completely (Exp. 3; II), and faba beans partially (Exp. 4; III). In addition, the effect of protein supplementation with rapeseed meal and microalgae in comparison to unsupplemented diet (Exp. 2; I) was studied. The crude protein (CP; Kjeldahl-N × 6.25) concentration of microalgae was on average 690 g/kg DM for S. platensis, 597 g/kg DM for C. vulgaris and 385 g/kg DM for N. gaditana. These microalgae were relatively low in crude fat, with highest concentration of 192 g/kg DM measured for N. gaditana. Compared to conventional protein feeds, all microalgae were lower in histidine, but higher in methionine. The DM intake (DMI) of microalgae containing feeds was lower than that of conventional protein feeds in three out of four experiments. When forage and concentrates were fed separately, cows compensated the decreased intake of microalgae containing concentrates by increasing silage intake (Exp. 2 and 3; I-II). Thus, total DMI remained unchanged (Exp. 2 and 3; I, II). This decreased the proportion of concentrate in the diet as much as 11.4 %-units. When all feed components were offered as total mixed ration (TMR), total DMI was decreased (on average 0.65 kg/d) as cows no longer were able to avoid microalgae (Exp. 4; III). The poor palatability of microalgae was not related to amount of microalgae in the diet, dietary crude fat concentration or stage of lactation. Milk yield was unaffected by microalgae inclusion in the diet in three out of four experiments. The partial substitution of rapeseed meal or faba beans with S. platensis decreased milk yield on rapeseed, but increased on faba bean supplemented diets (Exp. 4; III). The same was observed as a tendency for protein yield. Also in Experiment 2 (I), S. platensis tended to result in lower milk protein yield than rapeseed meal. Microalgae resulted in milk, energy corrected milk (ECM) and protein yields similar to soya bean meal (Exp. 3; II). S. platensis inclusion in the diet increased milk fat concentration on soya (Exp. 3; II) and rapeseed meal (Exp. 4; III) supplemented diets, which might have been caused by more acetate intensive ruminal fermentation, increased body mobilisation or higher methionine intake. Protein supplementation increased N excretion in urine and faeces, and decreased the conversion efficiency of dietary N into milk protein (milk N:N intake; NUE) (Exp. 2; I). The responses of microalgae inclusion in the diet depended on the source of protein in the basal diet. In Exp. 2 (I), the substitution of rapeseed meal with S. platensis decreased NUE and human-edible protein efficiency. The same was observed in Exp. 4 (III) on rapeseed meal supplemented diets, whereas on faba bean supplemented diets NUE was increased and human-edible protein efficiency was unaffected by S. platensis inclusion in the diet. In addition, the partial substitution of both rapeseed meal and faba beans resulted in increased urinary and total excretion of N (Exp. 4; III). The complete substitution of soya bean meal with different microalgae did not affect NUE, but decreased urinary N excretion and tended to increase human-edible protein efficiency. The substitution of all conventional protein feeds with microalgae decreased the intake of histidine and increased that of methionine. In two out of four experiments, these changes did not convert to major changes in arterial concentrations of these AA and their metabolites. The changes observed with S. platensis or mixture of S. platensis and C. vulgaris were decreased (Exp. 1; I) or tendency for decreased (Exp. 2; I) arterial histidine concentration, decreased arterial carnosine concentration in Exp. 1 and 2 (I), and decreased mammary uptake of histidine in Exp. 2 (I) and methionine in Exp. 4 (III). In conclusion, the results demonstrated no biological or physiological constraints for protein feed use of different microalgae. Moreover, microalgae seemed to be suitable substitute for soya bean meal and faba beans in dairy cow nutrition. However, microalgae are slightly inferior to rapeseed meal as indicated by results of milk production and N utilisation. The greatest challenge limiting the feed use of microalgae for lactating dairy cows is their poorer palatability relative to conventional feeds.
  • Haapanen, Markus (Helsingin yliopisto, 2019)
    The proportion of those aged 60 years and older is expected to double from 12 to 24 per cent by the year 2050. The prevalence of frailty increases rapidly with older age and is characterized by loss in biological reserve and resistance to stressors across several physiological systems. Frail people are at an increased risk of adverse health outcomes including hospitalization and premature mortality. Effective prevention of frailty requires knowledge on its risk factors across the life course. The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that early life influences may be important in determining disease risk in adulthood. There is evidence of early life influences in the pathogenesis of chronic diseases including cardiovascular disease and type 2 diabetes. The aim of the present study was to investigate early life exposures and frailty from a life-course perspective. The present study uses data from the Helsinki Birth Cohort Study that includes 8,760 individuals born in Helsinki in 1934-1944. A random subset of participants (n=2,902) was invited to participate in a baseline clinical examination; of those 2,003 participated in 2001-2004. Of these, 1,094 out of the invited 1,404 participated in a follow-up clinical examination in 2011-2013. Frailty was measured at the follow-up examination using the Fried phenotype model in participants with a mean age of 71 years. Data on infant and childhood development and exposures were extracted from healthcare records and national registers. Weight, length and body mass index (BMI) at birth were inversely associated with the presence of frailty in both sexes. Men who were frail in old age had experienced accelerated BMI gain from the age of 2 to 11 years compared to non-frail men. Similarly, men who as boys experienced wartime separation from both parents were at an increased risk of frailty compared to non-frailty. No similar associations were observed in women. Those who worked in manual labor occupations as adults were at an increased risk of frailty compared to those who worked as officials. Short leukocyte telomere length at the mean age of 61 years was associated with frailty at the mean age of 71 years. Furthermore, frail individuals had shorter telomeres at the mean age of 71 years compared to non-frail individuals. No association between telomere shortening and frailty was observed. Several life-course determinants of frailty were identified. Associations between factors taking place during gestation and early life suggest that susceptibility to frailty may be programmed early in life. Moreover, the association between BMI growth and wartime separation and frailty may vary by sex. Leukocyte telomere length may be a meaningful frailty biomarker in its ability to detect processes that are associated with frailty. The prevention of chronic disease and frailty should start already at a young age e.g. through the promotion of the health of mothers in childbearing age.