Väitöskirjat: Recent submissions

Now showing items 1-20 of 7995
  • Laiho, Leena (Helsingin yliopisto, 2021)
    This study is about ‘literary translation’, and the nature of its being. The notion of literary translation is here understood as a translation of a literary work of art. The doctoral thesis focuses on the relationship between a work of literature as an original and its translation. The research aims to answer the question of whether a literary translation is the same work as the original literary work. This question of identity is an ontological issue. The research question can also be expressed as a question about the ‘translatability’ of a literary work of art. Accordingly, if a work is translatable, it can survive translation and remain the same. What kind of an entity is a literary translation? We know that a literary translation is a new cultural entity that has never existed before, and yet some literary practices, especially the culture of reviewing, seem to approach translations of literature as identical with their originals. The relationship between original and identity appears unclear. Obviously, there are several ways to understand the key notions of translation, original, and identity. This doctoral thesis focuses on exploring the notional complexity of the issue of translatability, and further, on answering the question of ‘being the same’. The research method for investigating the identity issue is qualitative analysis, more exactly, a conceptual analysis. The key notions are examined in two theoretical frameworks, Translation Studies and the Philosophy of Art. To be analysed, there are different scholarly approaches from both academic fields. The doctoral dissertation consists of five sub-studies and a summary. It includes four published original articles. In this study, the ontological peculiarity of a literary translation is clarified. I argue that a literary translation is not the same as the original; it is a work that should be considered as a version. I propose that a literary translation as an ontological derivative is a presented work of art. As a presentation, it can be regarded as a performed work of art. Key notions: literary work of art, translation, original, identity, translatability, ontology, presentation
  • Sakaya, Joseph Hosanna (Helsingin yliopisto, 2021)
    Bayesian models capture the intrinsic variability of a data-generating process as a posterior distribution over the parameters of the model for the process. Decisions that are optimal for a user-defined loss are obtained by minimizing expectation of the loss over the posterior. Because posterior inference is often intractable approximations of the posterior are obtained either via sampling with Monte Carlo Markov chain methods or through variational methods which minimize a discrepancy measure between an approximation and the true posterior. Probabilistic programming offers practitioners tools that combine easy model specification with automatic approximate inference techniques. However, these techniques do not yet accommodate posterior calibrations that yield decisions that are optimal for the expected posterior loss. This thesis develops efficient and flexible variational approximations as well as density function transformations for flexible modeling of skewed data for use in probabilistic programs. It also proposes extensions to the Bayesian decision framework and a suite of automatic loss-sensitive inference techniques for decision-making under posterior approximations. Briefly, we make four concrete contributions: First, we exploit importance sampling to approximate the objective gradient and show how to speed up convergence in stochastic gradient and stochastic average gradient descent for variational inference. Next, we propose a new way to model skewed data in probabilistic programs by prescribing an improved version of the Lambert W distribution amenable to gradient-based inference. Lastly, we propose two new techniques to better integrate decision-making into probabilistic programs - a gradient-based optimization routine for the loss-calibrated variational objective, specifically for the challenging case of continuous losses, and an amalgamation of learning theory and Bayesian decision theory that utilizes a separate decision-making module to map the posterior to decisions minimizing the empirical risk.
  • Wardi, Eva Elisa (Helsingin yliopisto, 2021)
    Väitöskirjatutkimuksen kolmen empiirisen osatutkimuksen tutkimuskohde on moraalin, oikeudenmukaisuuden ja eettisten ristiriitojen tutkiminen työelämän vuorovaikutussuhteissa suhteessa huolenpidon ammattilaisten omiin elämän arvoihin. Tutkimukset suoritettiin sosiaalikasvattajien lastensuojelun nuorisotyön avohoidon piirissä, sosionomien ja geronomien vanhustyössä valtion ja yksityisissä hoivakodeissa ja historiallisessa tapaustutkimuksessa kasvattajien (myöhemmin sosiaalikasvattajien) sotaorpojen orpokotien kasvatuksen tutkimuksena vuoden 1918 Suomessa. Tavoitteena ja kohteena ovat näin olleet lapset, nuoret ja yhä kasvava vanhusväestö sekä hoivakulttuurin inhimillisyyden ja oikeudenmukaisuuden ristiriidat ja kehitys maassamme. Ensimmäisen osatutkimuksen aineisto kerättiin Helsingin Diakonissalaitoksen sosiaalialan oppilaitoksessa sosiaalikasvattajaopiskelijoiden piiristä kehittävän työntutkimuksen innoittamana koulutusinterventiona. Tutkimus suoritettiin opetuskokeiluna, joka koostui neljästä orientoivan opetuksen opetusjaksosta. Niissä opeteltiin käyttämään kehittävän työntutkimuksen kolmiomallia, jonka tarkoituksena oli orientoida käsittelemään omakohtaisia työn sisällön ongelmia osana lastensuojelutyön työyhteisön työnjakoa ja muita reunaehtoja. Tutkimukseen osallistui 18 sosiaalikasvattajaopiskelijaa. Aineisto, joka koostui työhön liittyvien dilemmojen kuvauksista, tuotettiin ½ vuoden välein kahdella lastensuojelun avohuollon kenttätyöjaksolla. Omakohtaisia dilemmojen ratkaisumalleja verrattiin toisiinsa ja käytettiin työn sisällön kehittämisen välineenä koulutusten jälkeen tapahtuvan palautteen muodossa. Lastensuojelulaitosta pidettiin tutkimuksessa toimintajärjestelmänä, jonka piirissä pienetkin vuorovaikutuksen ristiriidat vaikuttavat koko toimintajärjestelmään sen jollakin tasolla. Työhön liittyvät esseemuotoiset raportit pisteitettiin Kohlbergin oikeudenmukaisuustasoille. Lisäksi tutkittiin Warkin ja Krebsin typologiaa soveltaen aineistossa esiintyneet dilemmatyypit. Tarkastelu toi dilemmakuvauksissa esiin vuorovaikutuksen ristiriidan kohteena olleet vanhemmat työntekijät, myös muut tahot kuten perhe saatettiin mainita. Tulokseksi saatiin havainto, että koulutusintervention vaikutuksesta vastaajat käyttivät useammin ylempää moraalikehityksen oikeudenmukaisuusajattelua sekä toiminnanteorian käsitteellistä kolmiota työnsä mallintamisen ja vuorovaikutuksen kehittämisen välineenä. Toisen tutkimuksen aineisto kerättiin kahdesta aikuiskoulutusoppilaitoksesta. Tutkimukseen valikoitui 14 vanhustyöntekijää, jotka kuvasivat henkilökohtaisen vanhustyöhön liittyvän ongelman ja vastasivat moraalisia skeemoja kartoittavaan Restin DIT-testiin ja Schwartzin PVQ42 -arvomittariin. Tutkittavien raportoimat ongelmat sijoittuivat pääosin Warkin ja Krebsin typologian sosiaalinen paine ja lojaalisuus -luokkiin. Niissä tuli esiin ristipaine omien ja työyhteisön asettamien arvojen välillä sekä ristiriita organisaation vaatimusten ja vanhuksen itsemäärämisoikeuden toteutumisen välillä. Työntekijöiden arvot ja moraaliset ajattelumallit näkyivät myös kuvattujen ongelmatilanteiden sisällössä, sillä universalismia ja itseohjautuvuutta arvostavat kiinnittivät useammin huomiota vanhusten autonomian toteutumiseen. Niin ikään tulokset antoivat viitteitä siitä, että vallitsevaa moraalisten ongelmien luokittelujärjestelmää pitäisi tarkentaa, koska monia dilemmoja oli vaikeata luokitella yhteen dilemmatyyppiin. Kolmas tutkimus käsitteli vuoden 1918 sisällissodan punaorpokysymyksen ratkaisua, jossa päätettiin sulauttaa punaisten lapset valkoiseen nationalistiseen kasvatusihanteeseen kasvattajakoulukunnan kasvattajien toimesta. Tapausta ja sen oikeudenmukaisuusajattelua tarkasteltiin toiminnanteorian, Kohlbergin moraaliteorian sekä Leyensin infrahumanisaatioteorian näkökulmasta. Historiallinen tapaustutkimus kohdistui kasvattajakoulutuksen opetusmateriaalin saksalaiseen aatehistorialliseen taustaan ja nationalistisen etiikan luonteen normatiiviseen tarkasteluun. Tarkastelun kohteena oli myös kaksi aikalaista: Sisälähetysseuran Kasvattajaopiston rehtori Ruusu Heinisen (1876-1962), joka valtion ja kirkon välisissä neuvotteluissa oli katsottu poliittisesti sitoutuneena valkoisena sopivaksi kouluttamaan sosiaalihallituksen ohjeen mukaan oikeaoppisia sijaisäitejä sisällissodan köyhille punaorvoille ja Sortavalan Diakonissalaitoksen sitoutumaton johtaja Jenny Ivalo (1854-1921). Heidän oikeudenmukaisuusajatteluaan ja toimintaansa tutkittiin kirjallisiin dokumentteihin tukeutuen, Kohlbergin heteronomisen A- ja universalistisen B-tyypin avulla. Laajemmin valkoista Suomea koskien tutkimus toi esiin vuoden 1918 samantapaisen jyrkän moraalisen kahtiajaon, sotaorpolainsäädännössä, kasvatusfilosofiassa ja opetuskirjallisuudessa, joissa A- tyyppi ja valkoinen sisäryhmäajattelu oli hallitsevaa ja B-tyyppi ja toisenlaisen, omasta sisäryhmäajattelusta poikkeavan ajattelun hyväksyminen kovin harvinaista. Tuloksia havainnollistava historiallinen aineisto kertoo Suomen oloissa harvinaisesta lasten indoktrinaatiosta ja toisaalta siirtymästä oikeudenmukaisempaan ajatteluun 1918 jälkeen niin lainsäädännön kuin sen hallinnon alaisuudessa olevan koulutuksen osalta. Myöhemmät vuosikymmenet ovat osoittaneet, että oikeudenmukaisuusajattelu on muuttunut ratkaisevasti demokraattisempaan suuntaan, mutta lasten tasa-arvoon liittyvät kysymykset muodostavat edelleen jossakin määrin haasteen. Avainsanat: moraalin kehitys, oikeudenmukaisuusajattelu, oman elämän moraalikonfliktit, roolinotto, kehittävä työntutkimus, arvo, arvoristiriidat, skeemat
  • Hassan, Ghada (Helsingin yliopisto, 2021)
    Antibiotic resistance is a current threat to modern medicine. Not only is it challenging to treat but it also adds considerable costs to the healthcare systems. At the current rate of rising drug resistance, approximately 10 million people will die annually by 2050. The World Health Organization (WHO) has listed the six most threatening pathogens for which new antibiotics and approaches are urgently needed. One of the fastest evolving and most notorious Gram-positive bacteria in the list is Staphylococcus aureus. In addition to developing resistance to a vast number of antibiotics, this bacterium can attach to surfaces and form biofilms. This lifestyle allows bacteria to protect themselves from the immune system and impairs treatment. Thus, new innovative approaches and antibacterial agents are needed to fight bacterial resistance. As microbial adhesion is the first step of biofilm formation, the first aim of this study was to develop novel antibacterial surfaces to hamper the accumulation of antibiotic-resistant microbes. Cellulose is the most abundant natural polymer with various appealing characteristics. It is renewable, biocompatible, biodegradable, and possesses excellent mechanical properties. Cellulose nanofibers are prepared by mechanical disintegration of cellulose. Thin films of cellulose nanofiber can be prepared, and their surface can be modified to provide cellulose with new properties. Terpenoids such as abietic acid and dehydroabietic acid originating from conifer resin possess antibacterial and antifungal activities. We have previously shown that the amino acid-bearing derivatives of dehydroabietic acid possess antimicrobial properties. Herein, I report the design and the synthesis of new wide-spectrum contact-active non-leaching antibacterial cellulose nanofiber films by coupling the films with dehydroabietylamine, dehydroabietic acid and their derivatives. Different techniques and measurements were used to study the new biomaterials including contact angle (CA), streaming current measurements, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), oxygen transmission rate (OTR), water vapor transmission rate (WVTR), scanning electron microscope (SEM), tensile strength, and Young’s modulus. Our unique design rendered four anionic surfaces highly active against the Gram-positive S. aureus, including the drug resistant methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative Escherichia coli. The proposed modes of action and the fact that the compounds are based on a new chemical class account for a low potential to spread resistance. Our most active material 87 was tested against bacterial colonization in both biofilm and artificial dermis models. The bacterial colonization was efficiently prevented in both models. Material 87 proved to be biocompatible as it nurtured fibroblast growth at its surface without causing significant hemolysis. Our originally designed surfaces represent a new class of renewable biomaterials suitable for biomedical applications. The second aim of this thesis was to develop a new class of pyrimidine derivatives against S. aureus biofilms. From our novel set of pyrimidines, compounds 89, 99e, and 100e displayed potent activities. They inhibited biofilm formation and were active against pre-formed biofilms of S. aureus ATCC 25923 and Newman strains with IC50 values ranging between 11.6 to 62.0 μM. The compounds were also effective against planktonic cells with minimum inhibitory concentration (MIC) values lower than 60 μM. Only marginal cytotoxicity was revealed against human Hep2 cells at concentrations comparable to their pre-exposure IC50 values. Overall, this study resulted in the synthesis of four new antibacterial biomaterials and 26 new pyrimidine derivatives. This thesis offers novel approaches to target one of the most dangerous antibiotic-resistant bacteria S. aureus and efficiently limit its proliferation.
  • Martikainen, Julia (Helsingin yliopisto, 2021)
    Physical characterization of asteroid surfaces by studying the scattered light is challenging as the light-scattering processes are affected by the particle sizes, shapes, and materials, which in most cases are unknown. When interpreting remote-sensing observations, it is important to choose the correct methods for realistic analyses. In the past decades, several extensive studies have been carried out to understand asteroid surfaces, however, none of the previously used models are able to interpret spectroscopy, photometry, and polarimetry at the same time with sufficient precision. In the thesis, light-scattering methods were developed and utilized together with laboratory measurements to characterize asteroid regoliths and meteorite surfaces. The light-scattering methods presented in the thesis take into account both wavelength-scale particles and particles larger than the wavelength of the incident light, which is important as the models used for each wavelength domain are different, and the resonance region is difficult to account for. First, the reflectance spectra of three meteorite samples are simulated using a model combining olivine, pyroxene, and iron. The results are promising as we are able to match the simulated spectra fairly well with the measured spectra. Second, spectroscopic, photometric, and polarimetric modeling of asteroid (4) Vesta shows good results as the reflectance spectra can be modeled with reasonable precision, and the modeled photometry and polarimetry produce non-linear brightening and negative degree of linear polarization in the backscattering direction that is also seen in the observations. Finally, asteroid taxonomic classification is analysed by performing lightcurve inversion for 491 asteroids using convex and ellipsoid shapes. We retrieve phase curve slope parameters, rotation periods, pole orientations, shapes, reference phase curves, and absolute magnitudes in the G band of the ESA Gaia space telescope. Our analysis indicates that there can be mis-classifications in the current taxonomic systems. Asteroid photometry complements the existing classifications based on spectroscopy and provides us with a way to find the correct taxonomy. The forward methods of modeling the scattering properties of surfaces used in the thesis are vital in future studies as they can be applied to other Solar System objects, such as comets and satellite surfaces. Furthermore, retrieving the scattering properties of asteroid surfaces plays a vital role in the future space missions, including asteroid mining. Asteroid lightcurve inversion is useful especially when carrying out taxonomic classification as it provides additional information on the physical properties of the surface. The upcoming Gaia Data Release 3 will be extensive enough for rotational pole retrievals and will improve our current knowledge of the asteroids' physical properties.
  • Malani, Disha (Helsingin yliopisto, 2021)
    Acute myeloid leukemia (AML) is an aggressive and heterogeneous malignancy of the hematopoietic system. This thesis explores functional precision medicine approaches to target subsets of AML, in vitro, ex vivo and in the clinic. The experimental strategies focused on high-throughput drug sensitivity and resistance testing (DSRT), exome and RNA-sequencing. The real-time implementation of molecular and functional data for relapsed and refractory patients highlighted the opportunities of future individually tailored therapies in AML. We investigated the functional and molecular basis of cytarabine resistance to identify the molecular mechanisms of resistance and drugs that overcome the resistance. Cytarabine resistant AML cell lines MOLM-13 and SHI-1 variants were generated by long-term culturing. The cells were subjected to genomic sequencing, gene expression profiling and DSRT along with AML patient samples. We found a marked increase in glucocorticoid sensitivity in SHI-1 cytarabine resistant variants and in two AML patients treated with cytarabine-based regimens. Analysis of a larger set of relapsed or refractory AML patient samples revealed wild type FLT3 was significantly associated with sensitivity to glucocorticoids. The finding suggests glucocorticoids could be an effective class of drugs for a subset of cytarabine resistant AML patients with wild type FLT3 gene. We sought to identify drugs showing the discrepancy in responses between cell lines and patient samples, and potential drug sensitivity biomarkers. The drug responses, exome and RNA sequencing data were analyzed from 45 AML patient samples and 28 AML cell lines. Dasatinib, a multi tyrosine kinase inhibitor, was observed as one of the drugs with remarkably high sensitivity in the patient samples compared to the established cell lines. The upregulation of the KIT pathway was significantly associated with ex vivo dasatinib efficacy. The KIT pathway upregulation and ex vivo dasatinib sensitivity were found to be correlated with clinical response to dasatinib in three AML patients. Our results warrant testing dasatinib in a clinical trial for the AML patients with ex vivo dasatinib sensitivity and gene expression-based KIT pathway upregulation. A real-time precision systems medicine strategy was applied to identify targeted therapeutic options and biomarker associations in 252 samples from 186 AML patients. The integration of molecular profiling and DSRT data revealed ex vivo drug efficacies and underlying mutations and gene expression biomarkers for the subsets of AML patient samples. We developed a multidisciplinary functional precision medicine tumor board (FPMTB) to guide clinical therapy decisions for chemorefractory and recurrent (R/R) AML patients in a prospective real-time non-randomized clinical study. Our data suggest that functional precision medicine could have clinical utility, although it needs supportive evidence from formal prospective clinical trials. This thesis highlights novel avenues to define therapeutic opportunities for specific molecular subgroups of adult AML. The strategies described here could be useful for prioritizing drug development, identifying molecular subsets and drug response biomarkers, defining ideas for clinical trials, as well as the direct implementation of the therapies in individual AML patients in the FPMTB system.
  • Holm, Matilda (Helsingin yliopisto, 2021)
    Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for around 10% of the global cancer burden, and is second only to lung cancer in terms of cancer death. For patients with CRC, the overall 5-year survival rate is around 65%, although it is highly dependent on stage at diagnosis. Biomarkers are molecules that can be used for the detection of a disease, follow-up after radical surgery, monitoring of progression, detecting or assessing the risk of recurrence, and predicting prognosis. Glycans are carbohydrates that play important physiological roles in processes such as cell signaling, growth, and motility. Changes in glycans are seen during cancer and glycans are directly involved in different aspects of cancer such as proliferation, invasion, and metastasis. The proteome, which consists of all the proteins expressed in a cell, tissue, or organism, is dynamic due to factors such as posttranslational modifications, regulation of gene expression, and differential splicing of mRNAs. Changes in the proteome are also seen during cancer. The plasma proteome is a good candidate for studies due to the multitude of proteins it contains, the ease of obtaining samples, and the way it reflects the condition of the host. Mass spectrometry is often used to study the glycome and proteome in order to discover candidates for new biomarkers and to obtain new knowledge of how the levels of glycans and proteins change during cancer. The aim of this study was the glycomic and proteomic profiling of CRC with a focus on studying differences in glycan and protein levels depending on factors such as tumor location, stage, and patient outcome. Glycans were isolated from CRC tissue samples and healthy colonic tissue and analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Separately, preoperative plasma samples were processed and analyzed using Ultra Performance Liquid Chromatography-Ultra Definition Mass Spectrometry. All samples were obtained from patients who underwent surgery at Helsinki University Hospital. The results were analyzed using methods including principal component analysis, Mann-Whitney U and ANOVA tests, hierarchical clustering, pathway analysis, the Kaplan-Meier method, log-rank tests, and Cox proportional hazards regression analysis. The main differences in glycan levels seen were between acidic glycans, several of which had significantly different levels between stage II and III CRC. Surprisingly, the only significant differences in glycan levels between samples from patients with cancer in the right and left colon were seen when samples were divided according to both tumor location and stage. Many significant differences were seen in the levels of glycans when compared between healthy colon and tumor tissue samples. Multiple plasma proteins were identified whose levels differed significantly between stage II and III CRC. The levels of 13 proteins were found to differ between stage II and III CRC regardless of primary tumor location. Significant differences in plasma protein levels were also observed depending on primary tumor location. Samples from patients with rectal cancer separated from samples from patients with colon cancer solely on the basis of plasma protein expression when analyzed using principal component analysis and hierarchical clustering. Several plasma proteins were identified of which altered levels were independently linked to significant differences in long-term outcome. Higher plasma levels of proteins such as ceruloplasmin and fetuin-B were linked to significantly improved long-term survival rates for stage II CRC patients, while higher plasma levels of signal-induced proliferation-associated 1-like protein 1 and the CNK3/IPCEF1 fusion protein were linked to significantly poorer long-term survival rates for stage III CRC patients. In conclusion, these glycomic and proteomic studies provide new knowledge of CRC at the molecular level and show that significant differences can be seen in the levels of specific glycans and plasma proteins depending on factors such as tumor stage, location, and patient outcome. These results lend further support to the notion that it may be important to consider colon and rectal cancer as separate entities. While multiple plasma proteins that could be of value for predicting cancer progression and, separately, patient outcome were identified, validation of their clinical utility is still needed. Further studies to investigate why the levels of certain glycans and plasma proteins differ depending on CRC stage, tumor location, or patient outcome are also warranted.
  • Toppinen, Mari (Helsingin yliopisto, 2021)
    Some viruses can establish life-long persistence in their hosts after primary infection. The main aims of this thesis were to investigate the persistence, molecular epidemiology, and evolution of human parvovirus B19 (B19V). B19V is a small single-stranded DNA virus that has been shown to persist in various human soft tissues. The disease associations or mechanisms of this persistence, both at the cellular and molecular level, have remained unknown. At the beginning of this thesis work, we developed a quantitative PCR (qPCR) method for the detection, quantification, and differentiation of all three B19V genotypes. The method was shown to be suitable for B19V diagnosis and research both in human body fluids and solid tissue samples. Measurement of the B19V load is essential in i) timing of the primary infection, ii) investigation of the persistence mechanisms, and iii) plasma pool screening in blood product manufacturing. Next, we performed in-depth studies on the B19V persistence in tonsil, bone marrow, and bone. B19V-DNA tissue prevalences were high (35-74 %). Our results were in line with previous publications (tonsils), showed a higher prevalence than earlier detected (bone marrow), and described an entirely new tissue harboring B19V DNA (bone). We described, for the first time, the cell type accounting for the lifelong B19V-DNA tissue persistence in tonsils. Our results showed that B19V persists preferentially in B cells and that the entry mechanism into these cells is antibody-mediated. Antibody-dependent enhancement (ADE) may account for the B19V symptoms during primary infection or play a role in the establishment of persistence. In B cells of four individuals over 45 years, we detected a B19V genotype 2 that had disappeared from circulation before the 1970s. As B19V does not evolve or reactivate within human tissues, these individuals must have carried the genotype 2 virus in their B cells for over 40 years, suggesting a survival time of several decades for these B cells. Indeed, immunological memory may be, in addition to antigen re-exposure, due to a decades-long survival of the original B cell clones. In addition to persistence, we investigated in this thesis B19V molecular epidemiology and evolution. We constructed several full-length genomic sequences of B19V genotypes 1 and 2. By combining our bone marrow and bone data, we observed that within an individual, a single B19V genotype is present. We found that the inverted terminal repeat (ITR) sequences, crucial for B19V replication, are similar in both genotypes, and thus, do not explain the disappearance of genotype 2. We searched B19V DNA from long bones of World War II (WWII) casualties and found an astonishingly high prevalence (45 %). This work, for the first time, shed light on the epidemiological occurrence of B19V in Northern Europe between ~1923 and 1944 and laid the foundation for a new research approach: archeovirology, i.e., the study of virus occurrence and evolution via ancient relics. Indeed, we describe in this thesis – first in the world – persistent viral genomes in human bone. In addition to B19V, we investigated the prevalences of altogether 37 human DNA viruses in contemporary femoral bones via qPCR and next-generation sequencing (NGS). We discovered several members of the parvo-, herpes-, papilloma- and polyomavirus families, as well as hepatitis B virus and torque teno virus. Thus, our findings revealed bone to be a much richer source of persistent DNA viruses than ever perceived. Our results show that human skeletal remains – both contemporary and ancient – are suitable material for the investigation of epidemiologies and evolutionary histories of DNA viruses. After our work on WWII bones, archeovirology has expanded: other groups have described B19V, hepatitis B virus, and variola virus sequences in thousands of years old dental and skeletal human remains. Ancient specimens will provide an unforeseen historical perspective on viruses and infectious diseases.
  • Tiira, Jussi (Helsingin yliopisto, 2021)
    Snow has an important impact on hydrology, agriculture, climate and weather, infrastructure and different forms of both aerial and land transportation. The accumulation and properties of snow are inherently connected to the microphysical processes through which the falling ice particles grow. Furthermore, snow processes affect rainfall as well, since the vast majority of rain events originate as melted snow. For monitoring precipitation, the spatial coverage and resolution of radar instrumentation are unmatched. The quality of quantitative precipitation estimation using radars depends on our ability to establish meaningful relations between microphysical and electromagnetic scattering properties of hydrometeors. Especially for snow particles, these properties are diverse and the relations between them complex involving prominent uncertainties and knowledge gaps. Furthermore, the properties are constantly evolving as the falling particles undergo series of microphysical processes including growth from vapour, aggregation and riming. This dissertation work addresses these knowledge gaps by parametrizing microphysical properties of falling snow using ground based measurements, investigating the links between the properties and ice processes, and further studying their manifestations in collocated and off-site radar observations. A novel method is introduced for retrieving ensemble mean density of falling snow using a video disdrometer and a precipitation gauge. These retrievals are used in identifying triple frequency radar signatures of rimed particles and low density aggregates, and to develop a method for retrieving rime mass fraction. Based on the rime mass fraction retrievals, the effect of riming to snowfall is quantified. Using multifrequency Doppler radar and scanning C band radar observations we show that the downward streching of melting layer is linked primarily to precipitation intensity and secondarily to riming. Machine learning methods are employed in objectively documenting and automatically detecting known polarimetric fingerprints of ice microphysical processes in vertical profiles of radar variables. Automated ice process detection is anticipated to open the door for adaptive radar retrieval methods of snowfall rate.
  • Juvonen, Teo (Helsingin yliopisto, 2021)
    The doctoral thesis "The language of possession: Genitive variation in Late Middle and Early Modern English" examines the English possessive (e.g. “John’s son”) and its variation with the of-construction (e.g. “the son of John”) in Late Middle and Early Modern English, from about the middle of the 15th century to the middle of the 17th century. The thesis is comprised of four articles and an introduction that discusses the theoretical and methodological foundations for these articles. The first article studies genitive variation (i.e. the variation between the English possessive and the of-construction) in the private correspondence genre. The second article looks at genitive variation in three different genres, sermons, history writing and private correspondence. The third article examines the evidence available in this period for the analysis of the morpho-syntactic nature of the English possessive. The fourth article is a micro-historical study from a linguistic point of view on the use of various linguistic constructions available to express possessive meaning in the letters of John Paston, the eldest son of a rising gentry family in late middle England. One of the main findings of the articles contradicts previous research which argued that the English possessive had almost died out by the Late Middle English period, but recovered over the course of the Late Middle and Early Modern English periods. The results from the articles show rather that the English possessive was an integral part of the language system throughout this period, and that no patterned change over time can be detected despite significant variation in the use of the possessive. Further important findings include the significance of accounting for genre in the analysis of genitive variation, and some of the complexities having to do with the use of genre as a factor in quantitative studies. The minutiae and context of the historical material used to study genitive variation is also examined in a more philological fashion to illustrate the importance of historical detail and background in the research on genitive variation.
  • Cervera-Carrascón, Víctor (Helsingin yliopisto, 2021)
    Over the last ten years, the use of immunotherapeutic treatments for cancer has exponentially increased due to the promising responses across different tumour types. One of the particularities of the approach is that patients can develop long lasting curative responses. Unfortunately, those encouraging complete responses happen only in a minority of patients (< 10%). Immune checkpoint inhibitors, like anti-PD-1 or anti-PD-L1, are embodiments of that kind of therapy, whose concept revolves around the concept of stopping inhibitory signals that limit the development of antitumour responses. Results obtained from clinical experiences showed that patients responding better to immune checkpoint inhibitors tend to have “hot tumours”, meaning that there are effector components (such as T cells) and the microenvironment supports their function. To make immune checkpoint inhibitors work in those patients with cold tumours, the use of oncolytic adenoviruses could provide the spark to warm them. Viruses are able to trigger the immune alarm and thus, make tumours hot when their replication is restricted to the tumour. To study the potential of oncolytic viruses to increase the efficacy of immune checkpoint inhibitors, an array of preclinical models that allowed to study the matter from different angles were used. While in vivo murine and hamster models provided the basis for direct antitumour effect and survival assessments, other studies including human tumour sample histocultures and other in vitro experiments were performed to understand the subjacent cellular and molecular mechanisms involved. Due to the critical role of the T-cell compartment surrounding the activity of immune checkpoint inhibitors, different virus families were studied in terms of their ability to trigger T-cell responses. The best T-cell engagement was provided by the adenovirus candidate. An adenovirus engineered to support further antitumour immune responses was used to enable anti-PD-1 and anti-PD-L1 therapies. In both cases, the proposed strategy was able to cure all the animals. Additionally, tumours that were already refractory to anti-PD-1 still respond to virotherapy and the virus resets the tumour microenvironment sensitizing those tumours respond to anti-PD-1. Overall, this work revealed the potential of using engineered adenoviruses to repolarize the tumour microenvironment in general and the T-cell compartment in particular to a point that complement the mechanism of action of PD-1 and PD-L1 inhibitory antibodies. That synergistic combination rendered an increased percentage of responses even in tumours previously resistant or refractory to immune checkpoint inhibitors.
  • Vuorela, Miikka (Helsingin yliopisto, 2021)
    The purpose of this study is to form an overall view of the development of recorded crime, sentencing practices and incarceration rates in Finland during the period of autonomy. Additionally, Finland is systematically compared to the other Nordic countries. A collection of statistics depicting convictions, sanctions and imprisonment in Finland, Denmark, Norway and Sweden in 1809–1917 is also constructed in the study. With the new statistics, incarceration statistics now begin in 1810 and conviction and sanction statistics in 1842. These time series are analysed using quantitative methods in this study. The study consists of three main parts discussing respectively criminality, sentencing practice and the prison system. In the early 19th century crime and its control were concentrated in rural areas and the most common types of convictions were illicit intercourse and timber theft. During the century, convictions were starting to consist more and more of urban misdemeanours such as public intoxications. In the meantime, offences related to the protection of communal moral values, such as illicit intercourse, breach of the sabbath and slander were slowly disappearing from the court agendas. The most important single event affecting the development of criminality in the 19th century was the Finnish famine of 1866–1868 which launched the first recorded crime wave in the history of Finland, causing theft convictions to quadruple in just two years. The chapter on sentencing practices examines the criminal law reforms of the 19th century and the forms of punishment in legislature and court practice. The draconic penal system of the Swedish Civil Code of 1734 faded away during the century and the law was not enacted according to its letter. Executions demanded by the statute were converted to deportations to Siberia, and most corporal punishments were converted in the courts of appeal. The period of autonomy denoted the disappearance of the old forms of punishment and their replacement by the current system of incarceration and fines. This development culminated in Finland in the enactment of the new Criminal Code of 1889. The new law was significantly delayed due to the so-called state night and Finland was left decades behind the other Nordic countries in terms of the criminal justice system. The chapter on incarceration examines the structure and development of the prison system. The Finnish incarceration statistics are also built to their maximum length. Using the new data, it is for the first time possible to study how the imprisonment rates in Finland developed during the 19th century compared to the other Nordic countries. Incarceration rates began to differ in 1867. The number of prisoners decreased in Denmark, Norway and Sweden but remained stable in Finland. By the end of the century, the Finnish incarceration rate was significantly higher than in the other Nordic countries. The effects of the deportations from Finland to Siberia on the Finnish imprisonment rates and the severity of the criminal justice system is analysed for the first time in the study. The effects of the deporations may perhaps best be demonstrated by noting that during the 1870s Finland had in Siberia a second incarceration system which was as large as the one in Finland. The inclusion of the deported in the analysis of incarceration rates shows that the Finnish criminal justice system at the end of the 19th century was significantly more severe than in the other Nordic countries.
  • Nieminen, Anna (Helsingin yliopisto, 2021)
    Gastric cancer (GC) is the fifth most common cancer worldwide and third most common cause of cancer-related deaths. In low-risk countries, such as Finland, most GCs are diagnosed at an advanced stage, which decreases the prognosis. This thesis consists of four studies. In two studies, the aim was to evaluate GC risk in elderly male smokers with atrophic corpus gastritis. The prognostic staging systems Operative Link for Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) were assessed in these patients. We also created a new staging system, Topography, Atrophy, and Intestinal Metaplasia (TAIM), which combines atrophy and IM into one staging. In the third study the aim was to investigate the results of surgical treatment in patients with early gastric cancer (EGC) and to elucidate the extent of lymphadenectomy (D1 vs D2) on morbidity and survival. The aim of the fourth study was to investigate the cyclooxygenase (COX) profile of GC cell lines and the effect of two probiotic bacteria, Lactobacillus acidophilus and Bifidobacterium lactis, on COX expression profile. The patient materials of studies I-II were based on the previous Helsinki Gastritis Study, where 22 346 male smokers were screened for serum pepsinogen I (PGI). 1344 men with low PGI participated. The third study consisted of 94 patients with EGC operated at Helsinki University Hospital between the years 1983 and 2007. The fourth study was performed on primary and metastatic GC cell lines. COX expression profiles were determined by real-time PCR. In study I, 35 (2.6%) men were diagnosed with GC during the follow-up with incidence rate 1.94/1000 patient-years. The standardized incidence rates (SIRs) were calculated for male smokers with low and normal PGI and results were compared to an age-matched general male population (SIR 1.00). Male smokers with normal PGI had SIR 1.13; those with low PGI had SIR 2.43. In study II, OLGIM and TAIM stagings showed prognostic value in evaluating GC risk in men with atrophic corpus gastritis. In the EGC study, the extent of lymphadenectomy did not affect survival, but the risk of complications was higher in D2 operated patients and those with total gastrectomy or pancreatic resection. In the COX study, probiotic bacteria L. acidophilus and B. lactis did not affect COX-2 expression profile. Instead, L. acidophilus upregulated cytoprotective COX-1. Male smokers with atrophic corpus gastritis had an over 2-fold increased GC risk than the general male population. The staging methods OLGIM and TAIM can stratify patients with highest GC risk. Extent of lymphadenectomy did not influence on survival of the patients with EGC. Probiotic bacterium L. acidophilus may possess cytoprotective properties in the gastric mucosa.
  • Kiiski, Iiro (Helsingin yliopisto, 2021)
    Drug metabolism is an enzyme-catalyzed process that has major implications for a drug’s safety and efficacy. Consequently, evaluating the metabolic properties of a new drug candidate is of paramount importance already in the preclinical phase of drug development. Although the available in vitro techniques for drug metabolism research have improved over recent years, the state-of-the-art methodology relies on enzyme assays conducted in static conditions, with limited spatiotemporal control of assay variables. Conducting metabolic assays under flow-through conditions could pave the way for more in-depth understanding of the mechanistic basis underlying drug-enzyme and drug-drug interactions. This, however, requires that drug-metabolizing enzymes be immobilized onto a solid support material without compromising protein folding or enzyme function. Although a wealth of different enzyme immobilization strategies are currently available, most of them are not amenable to immobilization of the microsomal, drug-metabolizing enzymes. The aim of this thesis was to establish immobilized enzyme microreactor (IMER) platforms for studying drug metabolism under flow conditions, thereby improving the in vitro-in vivo prediction of the metabolic fate of new drug candidates. The use of microfluidics and microfabrication technology facilitated the straightforward implementation of flow-through assays and furthermore allows their multiplexing (parallelism) and integration with other operational units on a single platform, minimizing both reagent consumption and dead volumes. In the first sub-project (publication I), a novel strategy for the immobilization of the membrane-bound enzymes cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) was designed and implemented on microreactors fabricated from off-stoichiometric thiol-enes (OSTE). The strategy was based on biotinylation of human liver microsomes via biotin-tagged fusogenic liposomes, and utilized the tunable surface chemistry of OSTEs to allow easy functionalization of the microreactor surface. The IMER platform was preliminarily characterized to ascertain enzyme stability and preservation of key enzyme kinetic parameters, with an emphasis on CYP-mediated (phase I) oxidoreductive reactions. In the second sub-project (publication II), the feasibility of the IMER platform for studying the kinetics of UGT-mediated drug conjugation (phase II) was assessed, with an emphasis on the mechanistic basis for the pronounced underestimation of in vivo clearance kinetics by the currently available static in vitro techniques. In particular, the effect of membrane disruption and fatty-acid inhibition on UGT-kinetics in vitro was studied in detail. The kinetics of zidovudine glucuronidation (the model reaction used in this study) under flow-through conditions was shown to be in good agreement with that obtained using microsomal incubations in static conditions without the need for added pore-forming agents such as alamethicin. In the third sub-project (publication III), the technology was further developed by incorporating a highly overlooked dimension in the assay design: the impact of oxygen partial pressure on the metabolic fate of drug candidates. This was achieved by exploiting the unique material-induced oxygen scavenging property of thiol-ene polymers. The developed chip design allowed the rapid and simple control of oxygen concentration in enzymatic assays, which is difficult to achieve with conventional static assay methods. Overall, the developed methodology was shown to retain enzyme activity and native enzyme kinetic parameters of both CYP and UGT enzymes, an unconditional prerequisite for drug metabolism assays. With the immobilization method utilizing membrane biotinylation via liposome fusion, common problems (such as diffusion-limited kinetics and enzyme inactivation) associated with conventional immobilization approaches were circumvented. Furthermore, the universal applicability of the immobilization method for all membrane-bound enzymes was preliminarily demonstrated with recombinant CYP enzymes in sub-project/publication I. The methodology developed here also enabled mechanistic studies focused on the alamethicin-induced membrane disruption (commonly used in UGT assays to overcome mass transfer limitations) and the proposed inhibitory effects of fatty acids, which may shed light on the foundations behind the poor in vivo correlation associated with UGT reactions in vitro. The material-induced oxygen scavenging facilitated by OSTE polymers, together with microfluidic actuation, was shown to be an easily controllable approach for adjusting the oxygen partial pressure on demand. The advantage of this approach is that, unlike in typical approaches, complex chip designs or pressurized compartments are not needed. Beyond the demonstrated feasibility of the IMER platform for studying the impact of NADPH-cytochrome P450 oxidoreductase (POR)-mediated metabolism, the theoretical framework established here for OSTE-enabled oxygen control in microfluidic assays is likely to find many applications, particularly in organ-on-a-chip research. In conclusion, the microreactor platform developed in this thesis offers an enabling toolbox for conducting in vitro drug metabolism assays under flow conditions that circumvents many of the key shortcomings of current state-of-the-art (static) in vitro enzyme assay methodology, as well as those of previously reported IMER platforms. At the time of publication, the methodology developed herein has already been utilized in several follow-up studies and has shown utility in diverse applications beyond this work.
  • Hartoneva, Anne (Helsingin yliopisto, 2021)
    In this study, I examine the relationship between the Evangelical Lutheran Church of Finland and the State, especially from the perspective of the legal status of the Church as both a religious and a public community in Finnish society and legislation. In this regard, I examine the space given to the Church by the State through its legislation, as well as the views of the supreme overseers of legality, that is the Chancellor of Justice and the Parliamentary Ombudsman, on issues that may belong to the Church's autonomy or are close to that autonomy. It is a question of how much the State can limit the independence of the Church and how close it is legal and appropriate to come to the limit of the internal autonomy of the Church. In this study it is also a question of how the Church interprets the limits of its autonomy and the permanence of these limits. From this point of view, I examine how the General Synod making legislative proposals for the enactment of the Church Act and making other decisions, has taken a stand on the internal autonomy of the Church and its limits, and on the Church´s status under public law. Central to the study is how and on what grounds the area of the internal autonomy of the Church may have changed during the period between 1965 and 2019, which included significant social changes. This study belongs to the field of practical theology. The subject of this study is the tension between the internal autonomy of the Church and its status under public law. I examine three issues that are central to the activities of the Church. Each of them is opened up by three issues. The first question is the order and administration of the Church, the issues to be considered in this context are 1) the clergy representation structure and the lay repesentation structure in the administration of the Church, 2) the tasks and activity of the General Synod, and 3) the legal administrative activity of the Church. The second issue to be examined is doctrinal positions and religious practice. The issues that will be considered in this context are 1) the calendar location of the religious holidays, the days of prayer and the proclamation of the day of prayer, 2) the freedom of religion of the Church, and 3) the oath, promise, and affirmation as the form of commitment. The third issue to be examined is the Church's duty to protect fundamental and human rights. The issues to be considered in this context are 1) the interpretation of the priesthood as a question of office-holder´s freedom of religion and conscience, 2) marriage and its blessing as a question of office-holder´s freedom of religion and conscience, and 3) the freedom of religion and conscience in school teaching. It can be concluded from the research material that the special legislative procedure of the Church Act well safeguards the internal autonomy of the Church. However, the General Synod has not clearly expressed what issues are protected by the internal autonomy of the Church, where the limits of the internal autonomy of the Church are, and to what extent the border is absolutely inviolable. In many of its decisions which are important to the nature, unity, and mission of the Church, the General Synod came to solutions which were a compromise by nature, general, or half-way solutions that blurred the area and boundary of the Church's internal autonomy. The decisions of the General Synod have also not had some kind of legal force, because the same issue was brought to the General Synod soon after the previous decision and on several occasions. This has also blurred the area of the internal autonomy of the Church. It is also notable that as the study period proceeded, the General Synod increasingly based its decisions on general societal considerations, such as the requirements of fundamental and human rights, although decisions concerning the Church should be justified primarily on theological considerations. It can be concluded from the research material that in the legislation concerning the Church, the State largely took into account the position of the Church. The supreme overseers of legality approached the limit of the Church’s internal autonomy mainly in situations where an individual had felt the need for legal protection because of the Church measures. The overseers of legality based their decisions on general legislation, on which also the complainants had based their complaints in most cases. At the end of the study, I suggest that one solution to clarify the positions of the General Synod on the area of the internal autonomy of the Church could be to consider issues within the Church's autonomy in a similar way the Parliament´s Constitutional Law Committee have defined how the fundamental rights can be restricted. On the basis of such a consideration, pre-determined requirements would be set to the change of issues within the internal autonomy of the Church.
  • Huotari, Léa (Helsingin yliopisto, 2021)
    Prototype effect on subject change in translation A study in a French⇄Finnish bidirectional literary corpus This doctoral dissertation investigates the link between translation and prototype effect through the study of syntactic subject change in a French-Finnish literary bidirectional parallel corpus built specifically for the study. It examines the controversial topic of so-called translation universals and more widely the cognitive approach in the explanation of translation tendencies. More specifically, the study investigates the subject changes found in the corpus through six explanatory hypotheses proposed in translation studies to explain typical features of translations (translation universals, translational laws, translation figures, the gravitational pull hypothesis, orthonymy/prototipicality and anthropocentrism). The subject change is a particularly good candidate to test the explanatory power of the proposed hypotheses because the grammars of both Finnish and French describe the prototypical subject as being animate and cognitively more salient than an inanimate subject. The study found 320 relevant subject changes in the Finnish-->French and 408 in the French-->Finnish parallel corpora. These are categorized into four different types: 1. animation, 2. inanimation, 3. neutral animated change and 4. neutral inanimated change. The most frequent ones corresponded to animations of the subject, i.e. in most cases there occurred a humanisation of the subject in translation (60% in the French-->Finnish corpus and 49,5% in the Finnish-->French corpus). A thorough analysis of the relevant changes brought up five contextual factors that seemed to promote subject change in the corpus. Three factors are semantic (action, experience and possession) and two are pragmatic (particularization and homogenisation). The main contributions of the study are a methodology developed to analyse subject change between two languages from different language families, making use of the notion of shadow translation and a theoretical framework in the form of hypotheses built upon the five factors found. The hypotheses proposed make predictions about subject change that can be easily tested and further developed in other studies. Finally, the analysis shows that prototypicality is the most powerful explanation for the subject changes found in the corpus. This suggests that the most common way to say something and the anthropocentric conception of the world has an influence on the reading of the source text and thus also on the translation of the syntactic subject. Keywords: syntactic subject, French, Finnish, animacy, shadow translation, orthonymy, anthropocentrism, translation universals, translation laws, prototype.
  • Martikainen, Joonas (Helsingin yliopisto, 2021)
    The purpose of this dissertation is to design a conception of political poverty that can address the loss of the experience of political freedom. This form of political poverty is described as separate from poverty of resources and opportunities, and poverty of capabilities required for participation. The study aims to make intelligible how a person or a group can suffer from a diminishing and fracturing of social experience, which can lead to the inability to experience oneself as a capable and credible political agent, political engagement as a meaningful field of action, and democratic politics as a meaningful avenue for changing things for the better. This is a phenomenon which has been heretofore neglected by political theorists. The study presents a heuristic diagnosis of political poverty as loss of experiential freedom that involves four aspects of experience that have specifically political relevance: loss of trust, loss of expressivity, loss of a sense of access to the public world, and the loss of future temporality in experience. Diminishing and fracturing of these aspects of social experience can lead to politically impoverished persons and groups to become complicit in their own marginalisation by remaining unmotivated to challenge it. These aspects of social experience are approached through phenomenological portraits, chosen from literature on social exclusion and poverty. The diagnosis remains open to further development through exploration of other aspects of experience. The study draws on the thinking of Maurice Merleau-Ponty and Hannah Arendt to present an account of political freedom as only experienced in co-existence with others. Through a critical discussion of their work, a more comprehensive account of political agency is developed. The experience of having political agency involves not just the cognitive and communicative capacities of the subject, but also the entire perceptual and motor intentionality of their lived body. The experience of meaningfulness is approached by exploring the intersubjective constitution of the self in a dialectical process with their social environment. This experience is described as a form of faith in oneself as an agent and in the meaningfulness of political engagement. Such faith is a practical, meaning-giving intentional relationship of a lived body to their social environment. This study emphasizes the experience of being a capable and credible political agent, and experiencing politics as a meaningful field for engagement, as important aspects of political freedom that should be considered alongside inclusivity of democratic processes, the equality of opportunity to participate, and the equality of the cognitive and communicative capabilities required for effective participation. In order to discuss political poverty as the loss of experiential freedom, we must go beyond objectivist models of social critique and approach the problem with the tools of existential phenomenology.
  • Kerminen, Sini (Helsingin yliopisto, 2021)
    Population genetics is today an essential part of the studies of human origin and history, as well as of the studies of disease genetics. Populations living apart from each other exhibit genetic variation and this variation between populations is called genetic structure. By studying the genetic structure around the world, it has become possible, for example, to elaborate on the migration patterns of modern humans from the African continent to the rest of the world during the last 100,000 years. In addition, the modern methods of population genetics have enabled a very detailed analysis of genetic structure and population history within single countries, but these methods have not yet been widely utilized in isolated populations such as in Finland. In medical genetics, the genetic background of diseases is routinely analyzed with a genome-wide association study (GWAS). In these studies, it is important to control for the genetic structure of the data appropriately, so that the genetic variation associated with the disease can be reliably distinguished from the general genetic variation associated with the genetic structure. The results of GWAS are used in research to predict the genetic disease risk of an individual using a polygenic score that summarizes the estimated genetic risk over multiple sites of the genome. Because of this summation, even a tiny bias in the GWAS results, due to the genetic structure, can lead to a significant bias in polygenic scores, which, in turn, can lead to incorrect conclusions especially in comparisons between populations. Therefore, understanding the genetic structure and its role in building polygenic scores is exceptionally important to properly understand both the benefits and limitations of polygenic scores in academic research and in future health-care applications. This doctoral thesis examined the fine-scale genetic structure and its role in the geographic distribution of polygenic scores in Finland. The first part of the thesis expanded the understanding of the genetic structure of Finland by determining the geographic border for the major genetic split between East and West Finland, and by identifying 17 previously unreported genetic fine-scale populations. The fine-scale populations were observed to be geographically clustered and to follow Finnish dialect regions. The second part of the thesis utilized the earlier results by building, based on the fine-scale genetic structure, reference groups to estimate the genetic ancestry profile of an individual within Finland. By estimating the genetic ancestry profiles for a set of individuals born between 1923 and 1987, this second study was able to map annual changes in the fine-scale genetic structure within 12 regions. The annual profiles matched well with the migration patterns of Karelian evacuees who were displaced by the war events between 1939 and 1945. The third part of the thesis assessed the role of the genetic split between East and West in the geographic distribution of the genetic risk of five complex diseases (coronary artery disease, rheumatoid arthritis, schizophrenia, ulcerative colitis, and Crohn’s disease) and three quantitative traits (height, body mass index, and waist-hip ratio) using polygenic scores. The third study demonstrated that most of the polygenic scores, that did show geographic variation, mirrored the genetic split between East and West Finland but also revealed bias associated with the genetic structure in Finland. This final study thus demonstrated two main points: first that polygenic scores are susceptible to genetic structure-related biases, even within a relatively homogeneous populations; and second that it is challenging to link population-genetic variation to geographic variation in disease incidence with the current methods. Overall, the results of this doctoral thesis update the current understanding of fine-scale genetic structure in Finland and its changes to meet the needs of modern genetics research. It also demonstrates, both for the scientific community and for the general public, the importance of understanding the genetic structure in the study of both population history and polygenic scores.
  • Haataja, Eeva (Helsingin yliopisto, 2021)
    Gaze is a crucial part of interaction. Teacher-student relationship is constructed on momentary classroom interactions. Recent eye-tracking research has charted some patterns of teacher gaze in classrooms, but the dynamics of the relation between teacher’s gaze and pedagogical intentions and teacher-student eye contact have remained unexplored. The aim of this dissertation was to explore how teachers’ momentary scaffolding intentions and interpersonal behaviors are manifested in their gaze behaviors and in momentary teacher-student eye-contact communication. The research setting included multiple mobile eye tracking in naturalistic classroom contexts. The studies combined data collected on three 9th-grade mathematics lessons: gaze data, video recordings, and an interview with one teacher. The students solved a problem collaboratively and the teachers guided the problem solving. This mixed method research combines theoretical and methodological traditions of psychology and education and creates new information on teacher-student interaction and analytical methods. To present the main findings, student faces and solution papers were the most significant gaze targets for the teacher. Student papers were the most significant target during teacher-led cognitive scaffolding interaction, and student faces during affective scaffolding. Students’ hands and bodies were a common target during metacognitive scaffolding. Teacher gazes at student gestures were few but very long and occurred often during cognitive scaffolding. The student-started eye contacts were significantly more frequent than teacher-started eye contacts. The occurrence and durations of the dyadic eye contacts were dependent on the teachers’ scaffolding intentions. The students tended to look their teacher in the eye during cognitive scaffolding. During affective scaffolding, the teacher-started eye contacts were relatively frequent. The students looked at their teacher during high teacher communion often and with long gazes. To conclude, during cognitive scaffolding interaction and teacher behaviors of high communion and agency, the student gazes focus on the teacher and teacher gazes on the learning content. During affective scaffolding, dyadic eye contacts often formed between the teacher and students. The between-individual and even within-individual variation of attentional behaviors underline using situational data collection methods and continuous coding and developing theories on scaffolding intentions and interpersonal behaviors toward the inclusion of the momentary variation in instructive interaction.
  • Peña, Sebastián (Helsingin yliopisto, 2021)
    Harmful alcohol use is a global public health challenge. Socioeconomic differences in alcohol-attributable harm are higher than in all-cause mortality and Finland has one of the highest socioeconomic differences in alcohol-attributable harm in European countries. Lower socioeconomic groups typically experience greater alcohol-attributable harm, despite reporting lower levels of alcohol use. This “alcohol harm paradox” can be the result of differential biases in the measurement of alcohol use, differential vulnerability to the effects of alcohol or reverse causality. What explains the alcohol harm paradox remains largely unknown. This study investigated the existence and patterns of socioeconomic differences in volume of alcohol use and drinking patterns in Finland and Chile (two countries with high alcohol use and harm); examined changes in the prevalence and socioeconomic correlates of alcohol use disorders (AUD) in Finland between 2000 and 2011; and examined whether differential biases in the measurement of volume of alcohol use (using alcohol biomarkers as objective measures of alcohol use) and behavioural risk factors and their joint effects with each other and with socioeconomic status (SES) could explain the alcohol harm paradox. We used data from national health surveys in Finland and also Chile in Sub-study I. The study population were adults residing permanently in Finland. Income and education were used as indicators of SES. Central measurements included alcohol use (volume and heavy episodic drinking), alcohol biomarkers (GGT, CDT, ALT and AST), smoking, body mass index as well as sociodemographic factors. We used structured interviews to assess 12-month and lifetime AUD and linked data from population surveys to mortality data. Outcomes were indicators of alcohol use, 12-month and lifetime prevalence of AUD and alcohol-attributable mortality. Statistical methods included the concentration index, logistic and Cox proportional hazards models and causal mediation analysis. Abstinence was higher among lower socioeconomic groups than in higher socioeconomic groups in Finland and Chile, while heavy episodic drinking was modestly higher among people with lower SES in Finland. Estimated prevalence of 12-month AUD in Finland decreased from 4.6% in 2000 to 2.0% in 2011. We did not find evidence to support the existence of educational differences in AUD in 2000 or 2011. Participants in the lowest income quintile experienced 2.1 times higher risk of alcohol-attributable mortality, despite reporting lower levels of alcohol use. Alcohol biomarkers explained a very small fraction of the socioeconomic differences in alcohol-attributable mortality. We found strong joint (or interactive) effects for SES and alcohol use and SES and smoking. However, smoking, body mass index and their joint effects with income explained a relatively small proportion (18%) of the effect of income on alcohol-attributable mortality. Our findings confirm the existence of the alcohol harm paradox in Finland and support the need for targeted alcohol policies for lower socioeconomic groups and a broader policy agenda for tackling structural determinants of health.