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Efficient Exploration of Chemical Kinetics -- Development and application of tractable Gaussian Process Models
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Physical Sciences, 2025-12-18) Goswami, Rohit; Hannes Jónsson; Physical Sciences (UI); Raunvísindadeild (HÍ); School of Engineering and Natural Sciences (UI); Verkfræði- og náttúruvísindasvið (HÍ)
Stjórnun efnakerfa í rúmi og tíma til að hafa áhrif á samverkandi efnahvörf hefur verið markmið efnafræðinnar allt frá dögum gullgerðarlistarinnar. Í dag er mat á afurðum og hraða efnahvarfa, ásamt mati á stöðugleika efna og efniviða, grundvallarverkefni í efnaiðnaði. Þrátt fyrir stökk í stærðfræðilegri líkanagerð, með nákvæmum lýsingum á rafeindaskipan til að lýsa fjöleinda skammtafræðikerfum, og þrátt fyrir aðgengi að stórauknu reikniafli (exascale), vantar enn skilvirkar aðferðir til að ákvarða hvarfhraða í stórum hermunum. Bein hermun á gangverki atóma takmarkast af stuttum tímaskala og litlum lengdarkvarða. Nýlega hefur orðið hröð framþróun í gerð vélrænna mættisfalla (machine learned potential functions), en þær krefjast stórra gagnagrunna sem inntaks og eru ekki hagnýtar þegar verkefnið er að skima hratt í gegnum þúsundir efna eða efniviða til að finna bestu kandídatana fyrir tæknilega nýtingu. Þær hafa ennfremur hingað til takmarkast við svæði þar sem atómin eru í stöðugri uppröðun og eru ekki áreiðanlegar fyrir hvarfástand (transition state regions) sem ákvarða að miklu leiti hvarfhraðann. Tilraunir til að kanna hvarfanet á sjálfvirkan hátt með nægilegri nákvæmni fela í sér of háan kostnað við reikninga í rafeindaskipan. Einfaldandi nálganir fyrir hraðaútreikninga gera ráð fyrir því að efnahvörf séu hægir ferlar miðað við titring atómanna svo að varmalegt jafnvægi náist og nýta því tölfræðilegar nálganir fyrir útreikninga á hvarfhraða. Í einföldustu nálguninni, kjörsveifilsnálgun (harmonic approximation) við virkjunarástandskenninguna (transition state theory), snúast þær um að finna fyrsta stigs söðulpunkta á orkuyfirborðinu sem lýsir því hvernig orka kerfisins er háð staðsetningu atómanna. Jafnvel þá er reikniþörfin við leit að söðulpunktum of mikil í mörgum tilfellum, sérstaklega þegar orka og atómkraftar eru fengnir úr reikningum í rafeindaskipaninni. Hröðun á söðulpunktaleit byggð á staðgengilslíkönum (surrogate models) hefur verið lýst sem vænlegri á nærri áratug, en hefur í reynd verið hömluð af mikilli yfirbyggingu og tölulegum óstöðugleika sem gera að engu ávinninginn í rauntíma.Þessi ritgerð kynnir lausn sem byggir á heildrænni nálgun á þessu verkefni sem samþættir hönnun á eðlisfræðilegri framsetningu, tölfræðilegu líkani og kerfisarkitektúr. Þessi hugmyndafræði birtist í Optimal Transport Gaussian Process (OT-GP) umgjörðinni, sem notar eðlisfræðilega meðvitaða (physics-aware) framsetningu byggða á mælikvörðum fyrir bestun flutnings (optimal transport) til að búa til þjappaðan og efnafræðilega viðeigandi staðgengil fyrir stöðuorkuyfirborðið. Þetta skilgreinir tölfræðilega trausta nálgun og notar markvissa sýnatöku til að draga úr reikniþörfinni. Samhliða endurskrifun á EON hugbúnaðinum fyrir hermun á löngum tímaskala, er sett fram styrktarnámsnálgun (reinforcement-learning) fyrir lágháttarfylgni (minimum mode following) aðferðina þegar lokaástand er ekki tiltekið og hnikateygjubands (nudged elastic band) aðferðina þegar bæði upphafs- og lokaástand eru tilgreind. Samanlagt marka þessar framfarir nýja hugmyndafræði fyrir hermun á efnahvörfum sem byggir á framsetningunni fyrst (representation-first) og er þjónustumiðuð (service-oriented). Árangur þessarar aðferðafræði er sýndur með stórum viðmiðunarprófunum sem sýna góða frammistöðu, greinda með líkönum Bayes. Með því að þróa aðferð fyrir afkastamikil opinn-hugbúnaðar (open-source) verkfæri, umbreytir þessi vinna gömlu fræðilegu loforði í hagnýta tól til að kanna gang og hraða efnahvarfa.
Young disabled people at times of transitioning: Possibilities and challenges ‘I don’t care what they think—I’m happy with who I am’
(University of Iceland, School of Social Sciences, Faculty of Sociology, Anthropology and Folkloristics, 2025-12-08) Ingimarsdóttir, Anna Sigrun; Snæfríður Þóra Egilson; Félagsfræði-, mannfræði- og þjóðfræðideild (HÍ); Faculty of Sociology, Anthropology and Folkloristics (UI); Félagsvísindasvið (HÍ); School of Social Sciences (UI)
Transitioning into adulthood presents challenges for all youth, but particularly so for young disabled people, whose lives are shaped by normative expectations around age and ability. This doctoral research explores young disabled people’s reflections and lived experiences regarding the possibilities and challenges they faced before, during, and beyond their transitions into adulthood. It investigates how deeply embedded societal assumptions about disability and youth shape their pathways, opportunities, and self-image during these critical life stages. This study comprises four articles. The first one explores how disabled children and youth understand their possibilities for participation and wellness at home, in school, and in their communities, and how socio-material conditions intersect to shape their situations. The second article highlights the views of young people currently navigating transitioning to adulthood well as those reflecting on their experiences retrospectively. It provides a broad view of the transitioning process by capturing both individual and shared experiences. The third article offers insights into young disabled people’s partying experiences, to understand what partying meant for them and how they navigated party spaces. The fourth article draws on the larger LIFE-DCY project and provides a reflexive account of its methodological, conceptual, and ethical considerations and synthesizes of key findings. The study was conducted within the framework of the LIFE-DCY project, funded by the Icelandic Centre for Research (174299-051), and employed a qualitative, multi-method research design. It included in-depth case studies with disabled children aged 11–15 and key figures in their lives, as well as focus groups with young disabled people aged 18–35. The research was informed by constructivist grounded theory and emphasized the co-construction of meaning between the researcher and the participants. Inspired by critical disability studies and youth studies, the research drew on the concepts of ableism and adultism to illuminate how normative structures and beliefs systematically constrained the young people’s experiences. In keeping with the principles of critical disability studies, the research was committed to centering on the voices and experiences of the young people, who were seen not only as participants but as experts with vital insights into their lives. The young disabled people actively sought to engage in transitional milestones and peer activities, which they saw as essential during their transition to adulthood. However, participation often involved navigating a range of barriers—such as inaccessible built environments, pervasive stereotypes, low expectations, and inadequate support. The findings showcase the widespread impact of ableist and adultist attitudes that shaped interactions in schools, services, and public life, often in ways that reduced opportunities for participation, belonging, and recognition. Whether, and to what extent, the young people were able to participate alongside their peers depended on socio-material arrangements such as access, the availability of appropriate support and how well they assimilated the taken-for-granted norms. While many sought to meet these norms to attain a valued adult life, they also pushed back against the ableist ideals underpinning them. The analysis yielded three key insights. First, the young disabled people had to navigate complex barriers - including inaccessible systems, low expectations, and limited opportunities to participate in meaningful settings. These challenges disrupted their transition to adulthood and hindered their efforts to move forward. Second, they were caught in a double-bind of ableism and adultism as they were simultaneously held back and held to impossible standards—expected to ‘act their age’ while being denied the support and freedoms typically associated with that age. Third, structural gaps and poorly aligned services compounded the young people´s marginalization, making it difficult for them to participate meaningfully in society on their own terms. These structural failures often had significant consequences for their sense of self, social inclusion, wellness, and their experience of emerging adulthood. The study highlights how dominant narratives about transition and adulthood draw upon rigid, linear, and able-bodied timelines that fail to account for the diversity of young people’s lives. Inaccessible environments, fragmented services, and normative assumptions create barriers that undermine young disabled people’s efforts to be seen, heard, and supported on their terms. Ultimately, this dissertation study contributes to ongoing discussions and debates in disability and youth research, advocating for a reimagining of transition frameworks, calling for more inclusive, flexible, and justiceoriented approaches that recognize the structural, cultural, and relational dimensions of growing up disabled. The findings highlight how ableist assumptions, often reinforced by inaccessible environments and a lack of awareness about their needs continue to shape how YDP are seen and treated in ways that undermine their emerging sense of self. Notions regarding transitioning and emerging adulthood are rigid and ingrained with unfair and often unrealistic markers that may fit some but not all.
"Sumir eru vaknaðir af svefni": "Þýskir" hugmyndastraumar og íslensk söguskoðun frá um 1750 til um 1850
(University of Iceland, School of Humanities, Faculty of Philosophy, History and Archaeology, 2025-11-26) Einarsson, Einar; Guðmundur Hálfdanarson; Deild heimspeki, sagnfræði og fornleifafræði (HÍ); Faculty of Philosophy, History and Archaeology (UI); Hugvísindasvið (HÍ); School of Humanities (UI)
Það hefur lengi verið vitað að sú menningarleg þjóðernisstefna sem átti uppruna sinn í Þýskalandi á síðari hluta átjándu aldar og við upphaf þeirrar nítjándu hafði talsverð áhrif á orðræðu og söguskoðun forvígismanna íslensku sjálfstæðisbaráttunnar á sama hátt og raunin var annars staðar á Norðurlöndunum. Það hefur lítt verið rannsakað með hvaða hætti og í gegnum hvaða leiðir þessar hugmyndir ruddu sér braut inn í orðræðu Íslendinga og hvernig þær smám saman höfðu áhrif á túlkun og viðhorf Íslendinga til fortíðarinnar. Markmið þessarar ritgerðar er að gera tilraun til þess að varpa ljósi á það hvernig og af hverju söguskoðun Íslendinga ummyndaðist á afar stuttu tímabili, frá því að vera frekar dæmigerð söguskoðun upplýsingarinnar (í sinni þýsku gerð) yfir í það að verða söguskoðun menningarlegrar þjóðernisstefnu, en jafnframt að setja það ferli í samhengi við þróun yfir lengri tíma. Í ritgerðinni er einnig lagt mat á það hvernig þessi áhrif bárust til Íslendinga og hvernig þau birtust í tjáningu þeirra, hvort sem um ræðir skáldskap eða pólitísk skrif, í bundnu máli og óbundnu. Það getur varla talist einkennilegt eða óvenjulegt að megináhrifin á þessa þróun skuli hafi borist frá Þýskalandi. Þaðan höfðu hugmynda- og menningarstraumar streymt til Ísland og annarra Norðurlanda öldum saman. Oft bárust þessi áhrif til Íslendinga í gegnum Danmörku en stundum var einnig um bein áhrif að ræða. Í Þýskalandi var tekið við áhrifum sunnar úr álfunni, yfirleitt frá Ítalíu og Frakklandi, sem síðan voru aðlöguð þýskum aðstæðum og bárust loks til Norðurlandanna. Í því samhengi mætti nefna upplýsinguna, sem tók talsverðum breytingum í Þýskalandi, eða öllu heldur mætti segja að þar hafi eingöngu verið tekið við sumum þáttum upplýsingarinnar, öðrum alls ekki. Hugmyndir um móðurmálsrækt og málhreinsun, sem höfðu borist frá Ítalíu til Frakklands og þaðan til Þýskalands urðu til þess að þar þróuðust hugmyndir um samlífi tungumáls og þjóðar, um upprunalegt ómengað tungumál sem tengdist tilvist þjóðarinnar órofa böndum. Þessar hugmyndir bárust til Íslands með upplýsingunni og mynduðu ákveðinn grunn sem síðar yrði byggt á. Eftir frönsku byltinguna og styrjaldirnar sem af henni hlutust, auk tilkomu rómantíkur og hughyggju varð til í Þýskalandi sú gerð menningarlegrar þjóðernisstefnu sem barst til Norðurlanda. Þróunina frá orðræðu upplýsingarinnar til menningarlegrar þjóðernisstefnu má glöggt greina í skrifum Íslendinga, frá Eggerti Ólafssyni, í gegnum Baldvin Einarsson og Fjölnismenn, til Jóns Sigurðssonar. Það sem hafði verið hefðbundin söguskoðun Íslendinga frá því á sautjándu öld ummyndaðist í flestum grundvallaratriðum á aðeins nokkurra áratuga skeiði og varð að sögu-skoðun menningarlegrar þjóðernisstefnu — söguskoðun sjálfstæðisbaráttunnar — sem var ráðandi viðhorf á Íslandi langt fram eftir tuttugustu öld.
Large-scale Proteomics for Disease Prediction, Health Evaluation, and Personalized Medicine
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Electrical and Computer Engineering, 2025-12) Eiríksdóttir, Þjóðbjörg; Magnús Örn Úlfarsson; Rafmagns- og tölvuverkfræðideild (HÍ); Faculty of Electrical and Computer Engineering (UI); Verkfræði- og náttúruvísindasvið (HÍ); School of Engineering and Natural Sciences (UI)
Biomarkers derived from plasma proteomics enable personalized medicine by guiding prevention and treatment, selecting clinical trial participants, and evaluating therapeutic response. Plasma protein levels are influenced by both genetic and environmental factors, and they reflect current health, whereas genotypes are stable. Therefore, proteins are an important source of biomarkers of current health, which can be used to monitor disease progression and regression. With advances in high-throughput technologies, such as the Olink and SomaScan platforms, it is now possible to measure thousands of proteins in blood across tens of thousands of individuals.Here, large-scale proteomics data are integrated with machine learning to develop protein-based biomarkers that capture individual variation in health and disease risk. Using large plasma proteomics datasets of ∼5,000 (SomaScan) or ∼3,000 (Olink) plasma protein levels we identified protein-disease associations and derived protein risk scores (ProtRSs) for more than a hundred diseases. For many diseases, considerable improvement was observed, while for others, the ProtRSs improved baseline prediction negligibly. To disentangle genetic and environmental contributions, we analysed genotype-adjusted plasma protein levels. Generally, this adjustment strengthened the association with disease phenotypes, suggesting that changes in plasma protein levels are usually the consequences of disease rather than the cause.ProtRSs for death, atherosclerotic cardiovascular disease (ASCVD) events, and coronary artery disease (CAD) were developed further, and robustly tested against established baselines. Non-linear models and feature selection models were tested, but Lasso penalized linear models were generally found to be among the best performing models. The mortality risk score outperformed predictors based on conventional mortality risk factors and correlated with measures of frailty in an independent dataset. In ASCVD and CAD prediction, ProtRSs significantly improved established models, albeit modestly, in independent datasets. For CAD prediction, a polygenic risk score (PRS) for CAD also improved upon established risk models, with the best performance achieved when protein and PRSs were combined, while a metabolite risk score did not add further benefit.In addition, we used plasma protein levels to determine organ age, i.e., the biological age of organs, and compared these with chronological age to calculate organ age gaps. Positive organ age gaps were associated with multiple diseases, and negative age gaps with good health, though the organ-specificity varied across organs. We further separated organ-specific ageing from ageing shared across all organs, generating organ-specific age gaps that showed higher organ specificity and a shared age gap that was a stronger predictor of mortality than any individual organ age gap. This organ age approach could potentially help with understanding age and disease-related changes in organs, but it currently has limitations that make direct assumptions about changes with age difficult.On the whole, this work gives insight into the uses and limitations of plasma proteomics for clinical applications and medical research in general.
More than the shoulder? Kinematics of the jump throw and factors influencing shoulder problems in handball
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025-11-21) Árnason, Kári; Kristín Briem, Atli Ágústsson; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Aims: Shoulder problems are common in handball and known risk factors include decreased shoulder rotational strength, limited shoulder rotational mobility, and sudden increases in training and competition load. The throwing motion is a large movement, and previous research has linked proximal segments´ force production to throwing velocity. Nevertheless, the influence of lower body strength and trunk rotation power (TRP) on shoulder problems in handball players has not been investigated prospectively. Similarly, the association between internal shoulder load (subjective perception of load) vs. external shoulder load (e.g. number of throws in a match) measurements and shoulder problems among handball players is unknown. Despite the jump throw being the most common throwing technique in handball, very few motion analyses of it have been conducted. Moreover, the extent to which proximal segments’ kinematics influence more distal segments, such as the shoulder, is unknown, as are possible kinematic differences between different positions. The aims of this thesis were to examine the association between pre-season strength and power in the lower body and trunk, and shoulder problems among handball players, to perform a 3D motion analysis of the jump throw and, to investigate whether internal or external shoulder load measurements were more consistently associated with shoulder problems. Increased knowledge of this topic might influence injury prevention via better load management, either by ensuring adequate pre-season strength and power or by regulating training/competition shoulder load.Methods: This thesis is based on results from three research papers. Paper I included 42 male handball players. Pre-season measurements of peak lower body strength, peak trunk rotation power (TRP), and peak external and internal rotation strength in the throwing shoulder were conducted before the 2022–2023 season. Participants were followed throughout a whole regular season (31 weeks), where they answered a weekly questionnaire specially designed to document the prevalence and severity of overuse problems, and an additional question regarding participation-related shoulder load (PSL – subjective experience of shoulder load (internal load)) during the previous week. Paper II involved 31 female handball players. The same pre-season protocol as used in paper I was conducted before the 2023–2024 season and participants answered the same questionnaire throughout the season (29 weeks). Performance data, including the total number of shots per player in all league matches were collected from HBstatz (official statistical provider for the Icelandic Handball Federation) and defined as external shoulder load. For paper I and II, the association between pre-season strength and power and the prevalence and severity of shoulder problems was assessed with the Spearman´s rho correlation coefficient. The influence of pre-season strength and power on the association between internal and external shoulder load, and the severity of shoulder problems was examined with a mixed model ANOVA. Paper III involved a 3D motion analysis of 41 male top-division players performing a jump throw, conducted before the 2022–2023 season. The correlation between proximal and distal segments´ kinematics was assessed and differences in jump throw kinematics between playing positions were analysed with an independent t-test. The explanatory strength of proximal segments´ kinematics on the variance in shoulder internal rotation (IR) angular velocity was assessed by using a stepwise regression model. Results: The results from paper I (male players) showed a negative correlation between pre-season ER strength and the prevalence of shoulder problems (rs=-0.34, p=0.029). A main effect was observed showing a positive relationship between PSL and the severity of shoulder problems (p<0.001). A significant interaction was observed between PSL and pre-season TRP in terms of their influence on the severity of shoulder problems, as males with pre-season TRP one standard deviation (SD) below the group´s mean had a stronger association between the severity score and PSL. The findings from paper II (female players) showed a positive correlation between peak lower body strength (rs=0.40, p=0.03) and peak ER shoulder strength (rs=0.38, p=0.04), and the prevalence of substantial shoulder problems. A main effect was again observed for PSL, with higher PSL associated with higher severity score (p<0.001). However, a negative association was found between the external shoulder load and the severity of shoulder problems (p=0.04). A significant interaction was observed between PSL and peak lower body strength, TRP, and ER shoulder strength in terms of their influence on the severity of shoulder problems. Female players with pre-season strength and power one SD above the group´s mean showed a stronger association between the severity score and PSL. Paper III showed that hip and pelvis kinematics explained 44% of the variance in shoulder IR angular velocity. Significant differences were found between positions with center/back players displaying higher angular velocities in all measured segments, except trunk rotation, and greater range of motion excursion in the hips, pelvis, and trunk compared to wing/pivot players. Conclusions: The findings suggest that low pre-season TRP in male players may make the throwing shoulder more vulnerable for an increase in load. Pre-season training should therefore emphasize TRP training for male players. However, the results highlight the complex interaction between multiple risk factors for shoulder problems in female players and suggest that PSL (internal load) is more consistently associated with shoulder problems in handball, compared to external load. The results also underscore the role of proximal segments´ kinematics in terms of an efficient jump throw performance, and that different on-field demands likely influence kinematic differences between central/back vs wing/pivot players. It is therefore important to tailor strength training accordingly to each player’s on-field demands.
Understanding Hydrogen Sulfide Mineral Storage: Joint Geophysical Surveying and Geochemical Modeling at the Nesjavellir Geothermal Site, Iceland
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Earth Sciences, 2025-12-05) Ciraula, Daniel; Halldór Geirsson; Faculty of Earth Sciences; Jarðvísindadeild; School of Engineering and Natural Sciences; Verkfræði- og náttúruvísindi
The physical and chemical processes that occur in the subsurface as fluids and rocks interact play a central role in shaping subsurface geochemical systems. However, capturing these fluid-rock interactions in the field is difficult, as these processes occur hidden from direct observation. Both geochemical and geophysical methods provide complementary insights into the complex fluid-rock interactions, but the disciplines are not commonly used together. This thesis aims to integrate reactive transport geochemical modeling with time-lapse geophysical surveying to better understand and monitor fluid-rock interactions associated with hydrogen sulfide (H₂S) mineral storage in basalt, focusing on the Nesjavellir geothermal site (SW Iceland). In the mineral storage approach, injected H₂S reacts with basalt-sourced iron to form the mineral pyrite. The direct current and induced polarization (DCIP) geophysical method is sensitive to pyrite abundance through the chargeability parameter and is therefore evaluated as a novel monitoring tool for H₂S mineral storage. This research integrates DCIP surveying with reactive transport models that couple fluid flow and transport with geochemical reactions to predict the fluid-rock interactions and provide insight into geochemical processes controlling the DCIP response. Reactive transport models presented here show that H₂S mineral storage is effective under the current injection conditions, with up to 87% of the injected H₂S mineralizing as pyrite over 25 years of continuous injection. Consequently, H₂S contamination of the nearby Lake Thingvellir is expected to be minimal (<0.013 µmol/L). However, faults with high permeability pose a potential risk for contaminating the surface water. Lithologic and hydrologic controls strongly impact H₂S mineralization: it is greatest in high-permeability hyaloclastites with abundant basaltic glass and in fresh, olivine-rich lava flows; high porosity and temperature accelerate iron release and pyrite formation; and permeability governs the spatial distribution of pyrite precipitation, although high fluid flow in permeable zones can limit the fluid-rock interactions required for pyrite formation. H₂S mineralization is maximized in high-permeability hyaloclastites containing abundant basaltic glass and fresh lava flows containing abundant Fe-rich olivine. High porosity and elevated temperature accelerate basalt dissolution and iron release, enhancing H₂S mineralization. Permeability controls the spatial distribution of H₂S-rich water and subsequent pyrite precipitation. However, high fluid flow rates in permeable zones can limit fluid-rock interactions. Inversion of the 3D flow model constrained by borehole fluid temperature data reveals high permeabilities up to 9.7×10⁻¹¹ m² in hyaloclastite units. The permeability values agree with estimates derived from a petrophysical relationship linking permeability, changes in electrical resistivity between 1985 and 2020, and smectite abundance, as predicted by reactive transport simulations over the same period. Multiple-porosity models indicate that slow, diffusion-dominated transport in the rock matrix enhances fluid–rock interactions, with up to 97% of the total pyrite formation occurring within the rock matrix. This highlights the importance of considering diffusive processes in multiple-porosity frameworks to accurately simulate H₂S mineral storage in fractured basalt. Assessing DCIP monitoring capabilities at Nesjavellir shows increases in chargeability in wireline DCIP logs from injection wells injecting H₂S-rich water at rates of 12.5-149 L/s. The wireline measurements, taken 40 days apart, capture changes consistent with reactive transport model predictions of pyrite formation within 3.25 m of the borehole. In contrast, DCIP surface measurements show no significant change in chargeability following six months of continuous injection. Field-scale reactive transport models illustrate that low signal-to-noise ratios at the injection depths and small chargeability responses from dispersed pyrite mineralization limit the monitoring capability of surface DCIP. Synthetic DCIP datasets generated from reactive transport models show that cross-borehole DCIP surveying improves upon the surface DCIP approach by measuring chargeability changes at injection depths, but the method remains limited by data noise and weak chargeability signals. Overall, this thesis provides innovative ways of integrating geochemical and geophysical approaches and provides a comprehensive, non-invasive approach to enhance hydrogeological monitoring capabilities.
Tectonic and volcanic strong ground motion in Iceland: from empirical modelling to physics-based simulations
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Civil and Environmental Engineering, 2025-11) Hernández Aguirre, Victor Moises; Rajesh Rupakhety, Roberto Paolucci; Umhverfis- og byggingarverkfræðideild (HÍ); Faculty of Civil and Environmental Engineering (UI); Verkfræði- og náttúruvísindasvið (HÍ); School of Engineering and Natural Sciences (UI)
This dissertation presents advances in computational methods for the estimation of earthquake ground motion with applications to seismic hazard assessment in Iceland and beyond. The focus is on three-dimensional physics-based simulations (PBS), that with the growing accessibility of high-performance computing, have become a standard tool for simulating earthquake ground motions. Three main topics are addressed. First, the 3D seismic response of the Mexico City basin was investigated through PBS. The results show that when the seismic source is close to the basin, the incoming wave field deviates significantly from the commonly assumed vertically propagating S-waves. Moreover, surface waves are generated at the basin edges well after the direct arrivals, which elongates ground-motion duration. They have mostly prograde motion consistent with the Rayleigh fundamental mode. These results highlight how PBS can be effectively used in complex geological environments.The second topic focuses on strong ground motions generated by volcano-tectonic earthquakes in the Reykjanes Peninsula. Analysis of recent events shows unusually large peak ground accelerations and long-period amplitudes, in some cases exceeding the 475-year return period design spectra. The events display hybrid characteristics between volcano-tectonic and long-period earthquakes, and their scaling and attenuation differ from those of purely tectonic earthquakes. To account for these differences, a dedicated ground-motion model (GMM) for volcanic earthquakes in Iceland was developed, providing an essential tool for improving seismic hazard estimates in the Reykjanes Peninsula, the Capital area, and other volcanic regions worldwide.The third part of this work advances PBS methodologies through improvements in both finite-source characterization and broadband ground-motion simulation. A new pseudo-dynamic rupture framework was introduced to generate realistic heterogeneous source models, enabling semi-automatic construction of complex kinematic ruptures. Validated with the 2000 South Iceland earthquakes, this approach allows deterministic simulations to account for source uncertainties and reproduce the high-frequency content of ground motion. In addition, the ANN2BB (Artificial Neural Network to BroadBand) hybrid simulation technique was enhanced with transfer learning, combining global and limited local datasets. This refinement reduces overfitting, corrects distance-related biases, and extends broadband ground-motion prediction to regions with sparse instrumental records, such as Iceland.Overall, the developments presented in this dissertation improve the predictability power and scope of computational earthquake ground-motion estimation. They contribute to a better understanding of basin effects in large urban areas, to a more accurate treatment of volcanic seismicity in hazard assessment, and to the refinement of PBS that are increasingly entering engineering practice.
Toddler Sociality: Co-constructing the peer group through embodied interactions
(University of Iceland, School of Education, Faculty of education and pedagogy, 2025-11-27) Gunnarsdóttir, Bryndís; Amanda Bateman; Deild menntunnar og marbreytileika (HÍ); Faculty of education and pedagogy (UI); Menntavísindasvið (HÍ); School of Education (UI)
This PhD research project explores toddlers’ sociality and competence within peer interactions, focusing on their use of embodied strategies to actively participate and co-construct their peer group, create a sense of togetherness and form a ‘mutual we’. The research project was conducted in a toddler room in an early childhood education and care (ECEC) setting in Iceland and is an ethnomethodological (EM) study applying multimodal conversation analysis (CA) to examine these embodied strategies. The research offers an original contribution by challenging traditional views of toddlers as passive onlookers, demonstrating their active engagement and sophisticated social behaviours.The research project is structured around three sub-studies, each presented in a research article. The first article investigates the embodied strategies toddlers use to initiate interactions with their peers, highlighting the importance of gaze and touch as initiation strategies. The second article explores how toddlers use humour and environmental resources to initiate and sustain interactions within the peer group. The third article examines how toddlers use observation and imitation as a pre-opening in the co-construction of peer interactions. The study contributes to the growing body of knowledge on toddler social experiences within ECEC settings. The findings highlight their agency in shaping social relationships and peer culture. Overall, this thesis provides unique and valuable insights into the new and emerging area of toddler sociality, emphasising their active role in peer interactions and their ability to co-construct social relationships independent of adult interactional interventions.The data was collected over a 9-month period using participant observations through video recordings and field notes as the methods used. The interactions observed were transcribed according to recognised multimodal CA transcription conventions. The findings of this research underscore the value of multimodal CA as a methodological approach for studying toddlers’ interactions, providing detailed and nuanced insights into the embodied strategies toddlers use to navigate their social worlds. Ethnomethodology and multimodal conversation analysis therefore provide a robust theoretical and methodological framework for conducting this type of research and the findings of this study contribute to an original way of conceptualising toddler sociality and toddler social competence in ECEC.The findings have implications for policy and practice in early childhood education, advocating for a more nuanced understanding of toddler sociality and the importance of supporting peer interactions in ECEC settings. The findings also offer practical implications for early childhood teachers. Even though this study did not examine the role of the teachers in toddler peer interactions, by understanding the importance of embodied interactions and the sophisticated ways toddlers engage with their peers, it is my belief that teachers can better support and enhance toddler sociality and peer interactions by providing specific care and education in ECEC settings that offer support and opportunities for toddlers to interact and build a ‘mutual we’ with their peers.
The Normalization of Silencing: The Interplay between Nurses' Experience of Working Conditions and Gender Equality Ideals
(University of Iceland, School of Social Sciences, Faculty of Sociology, Anthropology and Folkloristics, 2025-12-09) Þorsteinsdóttir, Klara; Ingólfur V. Gíslason; Félagsfræði-, mannfræði- og þjóðfræðideild (HÍ); Faculty of Sociology, Anthropology and Folkloristics (UI); Félagsvísindasvið (HÍ); School of Social Sciences (UI)
Despite Iceland’s reputation as one of the most gender equal countries in the world and the idea that gender equality is an intrinsic part of Iceland’s national identity, the country’s labor market is highly gender segregated. This is particularly the case in female-dominated sectors such as education and the caring professions. As a case in point men make up about 5% of nursing staff in Iceland, which is low compared to countries with similar levels of gender equality, such as the other Nordic countries. As a female-dominated profession, nursing has long been linked to vocation and altruism, where the commitment to help and care for others is considered one of the most fundamental attributes of the professions’ identity. The feminized construct of care may be a key factor in discouraging men in Iceland from entering the nursing profession. Moreover, working conditions of nurses in Iceland have been characterized by understaffing and high rates of attrition due to work-related health problems. Considering the gender imbalance in the nursing profession, the aim of this dissertation is to explore nurses’ perceptions of the interplay between their working conditions and gender equality ideals in Iceland, focusing on power relations and occupational well-being. The dissertation is based on data collected through semi-structured interviews with 31 nurses working at the National University Hospital of Iceland, 24 women and 7 men. The interviews centered on the participants’ expectations for the job and what prompted them to become nurses. Working arrangements, the impact of working conditions on their health, communication and cooperation with colleagues and supervisors and possibilities for autonomy and professional development were also topics of discussion. In the first article the theoretical approach describes the multiple and often incompatible tasks of nurses. The other two articles draw on social constructionist and poststructuralist feminist theories. Analysis of the interviews was guided by reflexive thematic analysis, and the results were presented in three articles. The first article addresses various dimensions of power dynamics in the nurses’ work, considering the demanding working conditions, interactions and cooperation with other professions and the effects of the gender imbalance. The findings reveal that the working life of the participants is characterized by deep-rooted traditions concerning gender and roles in the hospital hierarchy. As a symbol of the power imbalances and restricted autonomy which they experience, nurses’ working space and professional boundaries are spatially and symbolically neglected by other professionals. The result is the nurses feel that their professionalism is undermined. To deliver necessary professional care, they make compromises at the expense of their own health. This sometimes borders on being unethical, while the nurses seek a balance between their professional conviction and expectations of the organization. In their opinion, attracting iv more men nurses could enhance equality and positive atmosphere. Working on wards with a balanced gender ratio is for them a liberating experience. The second article focuses on effects of gender-based stereotypes on career choices and work life of the participants, in which these stereotypes turn out to have substantial influence. The women describe how they glid ‘naturally’ into nursing while the men faced that ideas of masculinity classified them as deviant. The men also had to define for themselves the content of nursing and caring to justify their place in the profession. Stereotyping also strongly influence on-the-job experiences of woman nurses, whose work contributions and knowledge tend to be less valued than those of the men nurses due to notions that associate women with weakness and submission. The woman nurses believe that men nurses can be positive role models for them in being assertive and speak their mind when they are subjected to oppressive behavior. The third article addresses how nurses’ prior expectations for the job compare to their actual work life. The findings reveal how stereotypes about feminine submission prevail on the wards where only women nurses work. Strict rules require the nurses to stay on the ward for the entire shift, resulting in gender isolation from participating in the general space of the hospital. They experience a lack of trust and support from their superiors, and that the hospital management practices put the hospital's interests above the nurses' well-being. This experience of indifference has harmful effects for nurses, their clients and many parts of society. It is a major cause of nurses leaving work and influences their experience of discrepancy between their aspirations for the job and reality of work. Most of the female participants had found it difficult to make ends meet financially and workload had negatively affected them and their families. The results from the articles indicate that the feminization of nursing as subservient helps explain the associated gender imbalance and disempowerment nurses experience at work. Attracting more men nurses could enhance gender equality but may prove difficult due to gendered stereotypes of nurses. It is also a task that requires extensive societal discussion on the power of stereotyping and the definition of gender equality. Considering the nurses' poor working conditions, hospital management must revise the occupational policy and qualification requirements of managers and supervisors. The situation may be different in other nurses’ workplaces. In this dissertation, my assumptions are that a profession’s gender equality status must be understood/examined in the context of working conditions, health protection, professional recognition, autonomy and respect. The findings indicate that the participants experience unhealthy working conditions and a lack of support from their supervisors and the hospital management. Strong hierarchical power, sustained by stereotypical essentialist ideas, limits nurses’ professional recognition. The findings also indicate that the feminization of nursing disempowers women nurses and deters men from entering the nursing profession. It can therefore be concluded that the participants do not enjoy the rights and conditions that are prerequisites for gender equality.
Geochemical Characteristics, Geothermal Heat Flux Distribution and Sustainable Yield Assessment of Geothermal Reservoirs in Shandong, China
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Earth Sciences, 2025-11-17) Zheng, Tingting; Guðni Axelsson; Jarðvísindadeild (HÍ); Faculty of Earth Sciences (UI); Verkfræði- og náttúruvísindasvið (HÍ); School of Engineering and Natural Sciences (UI)
Shandong, one of China's most populous provinces, faces growing pressure to shift to carbon-neutral energy to mitigate climate change. Situated on the eastern margin of the North China Craton, it has a tectono-magmatic history that favours extensive geothermal resources. This thesis presents an integrated geoscientific investigation into two representative geothermal system types in Shandong Province: (1) convective geothermal systems hosted in intrusive rock that feature active natural recharge and discharge through permeable fractures and faults, located in the Shandong Peninsula; and (2) conductive geothermal systems hosted in sandstone, with limited natural recharge, in the Dezhou area. Geochemical and isotopic analyses of geothermal waters from the Shandong Peninsula indicate a predominantly meteoric origin, variably modified by seawater mixing, water–rock interaction or mineral salt leaching, and shallow groundwater mixing. Reservoir temperatures are estimated to range from 70 to 160°C. Two geothermal system types are identified: (1) deep (~2–5 km) circulation systems associated with major fault zones, with higher reservoir temperatures and isotopic signatures of mixed “old” and modern waters; and (2) shallow circulation systems controlled by minor fractures, displaying minimal water–rock interaction and local seawater influence. Further geothermal exploration in the Shandong Peninsula may be feasible through deeper boreholes targeting higher temperature waters. In Dezhou, the Guantao Formation sandstone reservoir is evaluated through a combination of long-term monitoring, reinjection experiments, lumped parameter modelling and volumetric energy balance calculations. The results indicate that a reinjection rate of 90 percent can help sustain a total yield for the area of approximately 1300 L/s during the heating season and average 500 L/s annually, while satisfying constraints on maximum water level depth and minimal thermal breakthrough risk over a 100-year time frame. These results highlight the critical importance of effective reinjection and sustainable management in maintaining reservoir performance in closed sedimentary geothermal systems. Heat-flux mapping across both regions, yields estimated values ranging from 40 to 200 mW/m² and values for most sites clustering between 60 and 80 mW/m². Superimposed high-flux anomalies, that commonly exceed 100 mW/m², are examined in detail to delineate their spatial distribution and controlling mechanisms, including elevated basal heat input and deep-large fault-focused convective upflow. The outcome of this research contributes to a strategic framework for future geothermal exploration and development, particularly targeting deeper and higher-temperature resources in structurally favourable zones.
Growth and characterization of Mn-based magnetic MAX phases: The quest for room temperature ferromagnetism
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Sciences, 2025) Thorsteinsson, Einar Baldur; Friðrik Magnus; Raunvísindadeild (HÍ); Faculty of Physical Sciences (UI); Verkfræði- og náttúruvísindasvið (HÍ); School of Engineering and Natural Sciences (UI)
MAX fasar eru fjöldskylda af atómlagskiptum efnum, með efnaformúluna Mn+1AXn, þar sem algengasta útgáfan er M2AX. Hefðbundin samsetning er með hliðarmálmi (M), frumefni úr A-hópi (A), og annað hvort kolefni eða nitri (X) og í M2AX fasa raða frumefnin sér í aðgreind atómlög í röðinni M-A-M-X-M-A-M-X. Á undarförnum árum hefur úrval frumefna sem geta verið í hverju sæti aukist samhliða því að nýjar efnasamsetningar hafa uppgötvast. Í þessari ritgerð verður MAX fasinn Mn2GaC notaður sem grunnur til að útvíkka í aðrar samsetningar með því að skipta út mangani (Mn) fyrir króm (Cr), járn (Fe) og skandín (Sc). Markmiðið er að rannsaka seguleiginleika þessara nýju MAX fasa. Seguleiginleikar einkristallaðra Mn2GaC húða á MgO(111) undirlagi eru rannsakaðir sérstaklega við lág hitastig. Við sjáum að seglun við 5 T svið breytist aðeins lítilega með hitastigi, gagnstætt við áður birtar vísindagreinar. Ástæðan fyrir þessum mismun er ófullnægandi frádráttur á ólínulega bakgrunninum frá MgO undirlögunum. Mælingar á segulmisáttun í tveimur Mn2GaC sýnum með mismunandi kristalstefnum sýna að (000l) kristalplönin eru auðseglandi. Skandín er svo notað til að breyta efnisuppröðuninni frá stöðluðum MAX fasa, yfir í svo kallaðan i-MAX fasa, sem hefur kagome atómuppröðun í plani sýnisins til viðbótar við lagskiptinguna. Þessi uppröðun myndast ef 1/3 af Mn er skipt út fyrir Sc, sem gefur efnajöfnuna (Mn2/3Sc1/3 )2GaC. Þessar húðir eru ræktaðar sem einkristallar á MgO(111), Al2O3 (0001) og SiC-4H(001) undirlög, þar sem SiC gefur bestu gæðin á kristalnum. Seguleiginleikar þessa fasa eru rannsakaðir og niðurstaðan er að hann er andjárnsegull. Með því að skipta út Mn fyrir Cr til að mynda (Mn1−xCrx)2GaC með x ≤ 0,29, þá fæst töluverð járnseglandi svörun við stofuhita, og Curie hitastig sem nær upp í 489 K. Sterkasta merkið fæst við x = 0,12, með 370 kA/m mettunarseglun, 176 kA/m segulleif, og afseglunarsvið upp á 16,8 mT við stofuhita. Þetta er í fyrsta skipti sem sterk járnseglandi svörun fæst við eða yfir stofuhita í MAX fasa, sem markar stór tímamót. (Mn1−xCrx)2GaC húðirnar voru ræktaðar bæði sem einkristallar á MgO(111) undirlög og fjölkristallar á Si/SiO2 undirlög, sem bæði skila svipuðum seguleiginleikum. Þetta opnar á frekari möguleika til hagnýtingar á seglandi MAX fösum. Rannsóknir á efnablöndunni (Mn1−xFex)2GaC, með 0,05 ≤ x ≤ 0,38, sýna að Fe virðist fara inn í MAX fasann samkvæmt röntgenmælingum. Aftur á móti kemur í ljós að jafnvel fyrir minnsta magnið x = 0,05, þá myndast antiperovskite fasinn (Mn1−xFex)3GaC. Með því að bæta við Cr og mynda (Mn1−x−yFexCry)2GaC, þá eykst stöðugleiki MAX fasans, sem gefur nánast fasahrein sýni með x = 0,11, y = 0,21 og einungis snefil af antiperovskite fasanum. Þetta sýni hafði sambærilega seguleiginleika á við sýni með Cr y = 0,29 og engu járni, en það var með aðeins lægra Curie hitastig.
Genetics and biomarkers of movement disorders
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025) Skuladottir, Astros Th.; Kári Stefánsson, Hreinn Stefánsson, Ólafur Árni Sveinsson; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Hreyfitaugaraskanir eru meðal algengustu taugasjúkdóma en sjúkdómsmyndun þeirra er enn að miklu leyti óljós. Fjölskylduskjálfti og Parkinsons sjúkdómur (PD) eru algengustu hreyfitaugaraskanirnar og í auknum mæli hafa fundist sameiginlegir erfðaáhættuþættir. Fjölskylduskjálfti hefur lengi verið talinn erfast með ríkjandi hætti á meðan PD er þekktur fyrir að vera flókinn og hafa fjölþættar orsakir. Takmarkaðar rannsóknir hafa verið framkvæmdar til að finna erfðaþætti sem hafa áhrif á sjúkdómsmyndun og áreiðanleg lífmerki sem aðstoða við að greina sjúkdómana snemma. Markmið þessarar ritgerðar var að bera kennsl á erfðaáhættuþætti sem varpa ljósi á undirliggjandi boðferla og sjúkdómsmyndun, og finna lífmerki sem geta greint eða spáð fyrir um hreyfitaugaraskanirnar með meiri nákvæmni og fyrr í sjúkdómsferlinu.Fyrsta markmiðið var að bera kennsl á erfðabreytileika sem hafa áhrif á fjölskylduskjálfta og að skýra hlutverk þeirra í sjúkdómsmyndun. Í Grein I framkvæmdum við víðtæka erfðamengjaleit (e. genome-wide association study) í sjö gagnasettum og í framhaldinu safngreindum (e. meta-analysis) við niðurstöðurnar með áður birtum gögnum. Í safngreiningunni bárum við saman erfðaupplýsingar frá 16.480 einstaklingum með fjölskylduskjálfta og yfir 1,9 milljón einstaklingum án skjálfta. Við bárum kennsl á 12 algenga erfðabreytileika á 11 genasetum í erfðamenginu, þar af voru 8 áður óþekktir. Greiningar á tjáningar- og próteingögnum (e. eQTL og pQTL) og merkingar á prótein kóðandi breytileikum (e. coding variant annotation) bentu á sjö líkleg orsakagen, þar á meðal CA3 og CPLX1, sem hafa þekkt hlutverk í skjálftastjórnun og á taugamótum. Genahópagreining (e. gene-set enrichment) sýndi tengsl við dópamínvirkar og GABAvirkar taugafrumur, Rho GTPasa- og streitustjórnunarboðferla, sem eru bæði þekktar frumur og ferlar í hreyfistjórnun. Erfðafylgni (e. genetic correlation) milli fjölskylduskjálfta og PD, kvíða og þunglyndis var jákvæð, sem bendir til sameiginlegra líffræðilegra boðferla. Ekki fundust sjaldgæfir erfðabreytileikar sem hafa mikil áhrif á sjúkdómsmyndun í fjölskyldum með fjölskylduskjálfta í íslenskum ættfræðigögnum. Þessar niðurstöður eru þvert á áður birtar hugmyndir um Mendelskar erfðir í fjölskylduskjálfta og styðja þar með að fjölskylduskjálfti er fjölgena.Annað markmiðið var að leita að genum þar sem tap á virkni próteinafleiðunnar eykur áhættu á PD. Í Grein II voru bornar saman heilraðgreindar erfðaupplýsingar frá 8.647 einstaklingum með PD við upplýsingar frá 777.693 einstaklingum án sjúkdóms í genabyrðigreiningu (e. gene burden analysis) og áhrif sjaldgæfra breytileika á PD í hverju geni í erfðamenginu voru metin. Við fundum að breytileikar sem valda tapi á virkni ITSN1 gensins hafa mestu áhrif á áhættu PD sem skráð hefur verið. Berar ITSN1 breytileikanna greinast átta árum fyrr en aðrir og yngsti einstaklingurinn greindist 27 ára. Virknirannsóknir (e. functional studies) sýna að ITSN1 gegnir mikilvægu hlutverki í clathrin-tengdum flutningi á taugamótum og í stýringu á frumugrind með örvun á Rho GTPösum, líkt og genin LRRK2, SYNJ1 og DNAJC6, sem eru öll þekktir PD erfðaáhættuþættir. Þessar niðurstöður benda á að truflun á flutningi taugamótablaðra og frumugrindarvirkni eru boðferlar sem eru miðlægir í meinmyndun PD.Þriðja markmiðið var að finna lífmerki sem gagnast við greiningu og til að meta framgang PD. Í Grein III mældum við magn 2.941 próteina í mænu- og blóðvökvasýnum frá Svíþjóð. Sýnin komu bæði frá einstaklingum án taugaraskana og einstaklingum sem voru greindir með PD. Sýnin frá einstaklingum með PD voru tekin við greiningu og á hverju ári í átta ár eftir greiningu. Við mældum einnig blóðvökvasýni úr einstaklingum frá tveimur öðrum afturvirkum gagnasettum sem leyfði okkur að meta próteinmagn að minnsta kosti 10 árum fyrir sjúkdóm. Einnig sóttum við mænu- og blóðvökva próteinmælingar úr þremur öðrum gagnasettum. Við framkvæmdum pQTL greiningu á mænuvökvamælingunum, safngreindum bæði mænu- og blóðvökvamælingar úr nýgreindum einstaklingum með PD, skoðuðum próteinbreytingar yfir tíma, frá að minnsta kosti 10 árum fyrir greiningu og í allt að 8 ár eftir greiningu, og einnig bjuggum við til prótein skor úr blóðvökvamælingum. Við fundum mörg lofandi lífmerki í blóðvökva, þar á meðal integrin prótein eins og ITGAV, ITGAM, ITGA11 og ITGB2, sem voru lægri hjá sjúklingum á öllum stigum sjúkdómsins, fyrir greiningu, snemma í sjúkdómi og lækkaði með framgangi hans. Við sýndum einnig fram á að HIP1R, gen sem tekur þátt í flutningi á taugamótablöðrum eins og ITSN1, er líklegt orsakagen í PD vegna þess að sami breytileiki er áhættuþáttur fyrir PD, lækkar HIP1R tjáningu í litla heila og lækkar HIP1R próteinmagn í mænuvökva. Við sýndum að Dopa Decarboxylase (DDC) getur verið notaður sem lífmerki í mænuvökva en ekki blóðvökva. Þetta er vegna þess að gildi próteinsins hækkar í mænuvökva í einstaklingum sem eru ekki byrjaðir að taka lyf við sjúkdómnum en ekki í blóðvökva frá sömu einstaklingum. Þessar niðurstöður benda til vefjasértækrar tjáningar. Í framhaldi, fundum við að próteinmynstur í mænu- og blóðvökva var mismunandi, sem undirstrikar mikilvægi þess að skoða blóðvökva við rannsóknir á PD.Saman veita þessar þrjár rannsóknir nýja innsýn í erfðir og sjúkdómsmyndun fjölskylduskjálfta og PD og auka skilning okkar á hreyfiröskunum. Þær leiða í ljós nýja áhættuþætti, orsakagen og klínískt gagnleg lífmerki til að greina PD fyrr og fylgjast með framvindu sjúkdómsins. Þessar rannsóknir sýna fram á sameiginlega sjúkdómsferla á borð við flutning á taugamótablöðrum og frumugrindarvirkni og styðja einnig samþættingu erfða- og próteingagna til að skilja hreyfitaugaraskanir.
Attention in the crowd: probing ensemble perception attentional dependencies
(University of Iceland, School of Health Sciences, Faculty of Psychology, 2025-11-25) Lukashevich, Anton; Heida Maria Sigurdardottir; Sálfræðideild (HÍ); Department of Psychology (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Ensemble perception enables the rapid extraction of summary statistics from visual scenes, bypassing capacity limitations, but its dependence on attention remains debated. This thesis investigates whether ensemble processing operates automatically or requires attentional resources, focusing on low- and mid-level features like orientation and length, through three studies combining behavioural paradigms and electroencephalography (EEG).Paper I examined automatic detection of ensemble mean orientation changes using visual mismatch negativity (vMMN) in oddball tasks. Attended changes elicited P3 component, but unattended changes produced no vMMN, indicating no pre-attentive processing. Paper II tested automatic parsing of spatially intermixed objects into categories based on feature distributions. vMMN emerged for length-based segmentation but not orientation alone, suggesting feature-specific automaticity. Paper III manipulated spatial attention via Posner cueing; ensemble orientation judgments dropped to chance on invalid cues, unlike single items, confirming attention's necessity.Overall, findings demonstrate that ensemble perception is not fully automatic, particularly for orientation, requiring spatial and selective attention for accurate extraction. Implications extend to visual cognition theories, emphasizing attention's gating role in summary statistics processing.
Participation of children and young people in research. Opportunities and challenges.
(University of Iceland, School Education, Faculty of Education and Diversity, 2025-11) Árnadóttir, Hervör Alma; Guðrún Kristinsdóttir, Sissel Seim; Deild menntunnar og marbreytileika (HÍ); Faculty of Education and Diversity (UI); Menntavísindasvið (HÍ); School of Education (UI)
The aim of this doctoral thesis is to increase knowledge and understanding of how children and young people (CYP) can be supported to participate in social research on issues that concern them. Particular emphasis is placed on highlighting the challenges researchers face when seeking access to CYP, and how these challenges relate to methods, approaches and children's rights to participate in discussions and decisions concerning their own lives and circumstances. The study addresses the following questions: What ethical and methodological challenges do researchers need to overcome in order to obtain support of gatekeepers to gain access to CYP for participation in social research? How do practitioners in child protection services understand the practical implications of CYP’s participation in social research? How can research methods be adapted to overcome the challenges of involving CYP in research? The study is grounded in a perspective informed by critical social constructionism and childhood studies, in which CYP are regarded as key social actors who shape their environments. Accordingly, their participation is considered essential in research. The study discusses methods that have proven useful in eliciting CYP’s experiences and perspectives, particularly in sensitive contexts. To gain insight into the subject, the study examines the experiences and perspectives of child protection practitioners who serve as gatekeepers when researchers seek access to CYP, as well as the experiences of researchers who have conducted research involving CYP. It also draws on existing data to reflect the perspectives of parents and CYP regarding participation in research and data from CYP about the usefulness of creative methods when working with CYP. The study is based on four peer-reviewed papers. The first paper explores the current state of knowledge regarding the challenges faced by researchers in this field. The second paper examines researchers’ experiences in gaining access to CYP who receive support due to difficult life circumstances, and their interactions with formal and informal gatekeepers. The third paper focuses on practitioners working with CYP in child protection services and their perspectives on supporting researchers in gaining access. Lastly, the fourth paper discusses how creative and artistic methods can support CYP in discussing sensitive topics. The findings reveal a complex and challenging process for researchers seeking access to CYP in vulnerable situations for research participation. Applications for access must navigate a hierarchy of formal and informal gatekeepers who are responsible for safeguarding children's rights to protection and participation. Challenges are evident in the lengthy approval processes, often resulting in extended delays or rejections, frequently without clear justification. Researchers depend on the goodwill of practitioners occupying key positions within this hierarchy, each of whom must dedicate time and energy to determine whether or not to support access to the target group. Researchers associate these delays and reluctance with a perceived lack of interest in research among practitioners and with assumptions about children's competencies, both of which significantly influence whether applications for access are considered or granted. Practitioners working in child protection, who act as gatekeepers, report limited time for engaging with research-related tasks and criticise researchers for submitting unclear research plans. These plans often lack sufficient explanation of researchers' competence in working with CYP, strategies to ensure child safety and justifications for involving CYP directly rather than relying on adults as informants. Frequently, the plans also fail to adequately describe researchers' prior experience or use of appropriate methods. Many practitioners consider it inappropriate to burden CYP in vulnerable circumstances by asking them to participate in research, particularly when discussing matters of which they may have limited understanding. According to practitioners, researchers should avoid compromising CYP’s safety through participation and instead focus on utilising existing data collected by practitioners. To enhance CYP's direct participation in research, researchers must prioritise the careful and professional development of their research designs. They need to invest time in building relationships and trust with gatekeepers, demonstrate how they will ensure children's safety and exhibit competence in using appropriate creative methods that can foster meaningful participation. Safeguarding CYP's rights requires enhancing researchers' competence in working with CYP and improving practitioners' knowledge of childhood studies and the concept of participation. Such efforts are necessary to challenge dominant protectionist attitudes among practitioners that limit CYP’s actual opportunities to influence their lives and circumstances
“Trafficking is a heavy word” Quranic education for knowledge, liberation and power in Guinea-Bissau
(University of Iceland, School of Social Sciences, Faculty of Sociology, Anthropology and Folkloristics, 2025-10-05) Boiro, Hamadou; Jónína Einarsdóttir; Félagsfræði-, mannfræði- og þjóðfræðideild (HÍ); Faculty of Sociology, Anthropology and Folkloristics (UI); Félagsvísindasvið (HÍ); School of Social Sciences (UI)
Þessi doktorsritgerð í mannfræði fjallar um Fulbe drengi frá Gíneu-Bissá sem eru sendir í kóranskóla í Senegal. Um er að ræða umdeilda venju sem hefur víða verið stimpluð sem mansal barna vegna þess að drengirnir betla á götum úti sem hluta af kórannámi sínu. Yfirgrípandi rannsóknarspurning snýr að því hvers vegna heimamenn telji að hugtakið „mansal“ í þessu samhengi sé „þungt orð“ og hvernig þeir bregðast við alþjóðlegum aðgerðum til að hefta för drengjanna til Senegal, banna betl og senda þá aftur heim til Gíneu-Bissá. Aðgerðrirnar eru umdeildar og stangast á við trúar- og menningarlegar hefðir og félagslegar aðstæður þar sem drengirnir búa. Rannsóknin byggir á langtíma vettvangsrannsókn að hætti mannfræðinnar sem fram fór á árunum 2009 til 2020, þar sem notast var við þátttökuathuganir, viðtöl og rýnihópa. Þátttakendur voru trúarlegir leiðtogar og kennarar (cerembe) sem hafa verið sakaðir um mansal, kóranskóladrengir (almube) sem flokkaðir eru sem fórnarlömb mansals, foreldrar þeirra og annað heimafólk. Niðurstöðurnar storka ríkjandi frásögnum frjálsra félagasamtaka og alþjóðastofnana um að sárafátækt og vanþekking séu meginástæður þess að foreldrar sendi syni sína í kórannám til Senegal. Andstætt slíkum hugmyndum þá sýnir rannsóknin að fjölskyldur, sérstaklega meðal Fulbe Djiahabe sem eru afkomendur þræla, velja trúarlega menntun sem leið til félagslegs hreyfanleika, valda og frelsis. Rannsóknin sýnir hvernig trúarleg þekking eykur táknrænt vald trúarleiðtoganna og gerir jaðarsettum hópum kleift að bæta virðingarstöðu sína og vinna gegn fordómum. Doktorsritgerðin kallar eftir afnýlenduvæðingu aðgerða gegn meintu mansali barna og sýnir hvernig þær bæti ekki stöðu drengjanna, nema að síður sé. Aðgerðirnar taka ekki tillit til menningarbundinna hugmynda, t.d. um betl sem gagnkvæma athöfn og hugtaksins merkingarbær þjáning, sem er þjáning sem leiðir til jákvæðrar niðurstöðu. Rannsóknin sýnir að heimsending drengjanna til Gíneu-Bissá leiðir til ringulreiðar, stimplunar og átaka í samfélagi þeirra. Samtímis þjónar heimsendingin mörgum, stundum andstæðum, hagsmunum. Frjáls félagasamtök tryggja áframhaldandi fjármögnun sína, ekki síst þegar þau snúa sama hópi drengja aftur og aftur til heimalandsins. Þá hafa fjölskyldur drengjanna og kóranskólakennarar byrjað að nýta sér hana sem ókeypis far heim fyrir drengina áður en árstíðabundnir annatímar byrja, en þeir snúa svo aftur til Senegal að þeim loknum. Fræðilegi rammi ritgerðarinnar sameinar kenningar Quijano um nýlenduvæðingu valds og þekkingar, kenningu Foucault um tengsl valds og þekkingar og hugmyndum Bourdieu um táknrænt vald. Þessi samruni fræðilegra sjónarhorna varpar ljósi á hvernig alþjóðleg og staðbundin valdakerfi, þekkingarsköpun og andstaða eru að verki samtímis, og opinberar hvernig alþjóðleg barnavernd einkennist af nýlenduhugarfari sem heimamenn mæta með andstöðu. Rannsóknin dregur fram misræmi á milli alþjóðlegra aðgerða gegn mansali, byggðar á vestrænum, lagalegum og siðferðilegum viðmiðum lituðum af nýlenduhugsun, sem leiða til glæpavæðingar hefða og samfélaga, og staðbundinna sjónarmiða um hvað teljist vera virðingarvert uppeldi barna. Doktorsritgerðin er framlag til mannfræði og umræðu um alþjóðlega stefnumótun og varpar ljósi á takmarkanir algildra inngripa og lagalegra aðgerða til að bæta aðstæður barna sem búa við erfiðar aðstæður. Hún hvetur til aðgerða sem taka mið af aðstæðum, vinnu gegn kerfislægum ójöfnuði, og stuðningi við staðbundna valkosti til menntunar. Forsenda árangurs er að umgangast trúarleiðtoga, foreldra og annað heimafólk af virðingu. Rannsóknin er ákall um afnýlenduvæðingu alþjóðlegrar barnaverndar og hvetur fræðimenn og fagfólk til að viðurkenna fjölbreytileika bernskunnar og óskir foreldra um fjölþætta menntun fyrir börn sín á sama tíma og velferð þeirra er tryggð.
Teaching visual arts as an approach to moral education: An autoethnographic account of my research project
(University of Iceland, School of Education, 2025-11-04) Olafsson Waage, Ingimar; Atli Harðarson og Ólafur Páll Jónsson; Deild faggreinakennslu (HÍ); Subject Teacher Education (UI); Menntavísindasvið (HÍ); School of Education (UI)
This doctoral dissertation, composed of five peer-reviewed articles along with a Kappa, details an intervention study designed by the author and carried out in collaboration with three visual arts teachers during art classes at an elementary school in the capital area of Iceland. The research focused on exploring the potential for enhancing moral education through discussions about visual art and art-making, based on selected virtues. The theoretical foundation is rooted in Aristotle’s virtue ethics and its modern adaptations, particularly Neo-Aristotelianism and Aristotelian Character Education. The author also draws on John Dewey’s educational and aesthetic philosophy, Rudolf Arnheim’s theories on the interaction of perception and thinking, Susanne Langer’s writings on art and inner life, and Maxine Greene’s views on the role of art and imagination in education and the teacher’s role within that context. The ontological basis of the study is pragmatic, and the author employed a mixed- methods research approach, including focus group interviews, thematic analysis of student texts, observation of their artworks, and action research, wherein the author holistically reflected on the research process. The work weaves together two distinct dimensions: an exploration of the role and potential of visual arts education in fostering moral development, and an autoethnographic study of the author’s own development as an artist, teacher, and researcher, particularly in light of the value of educational research and the role of the teacher. At the outset, the author intended to investigate how visual arts education might contribute to moral development, especially in terms of what is called “virtue literacy”— a construct developed by the Jubilee Centre for Character and Virtues at the University of Birmingham in the UK. The research aimed to develop new methods and educational materials for moral education where the arts, especially visual arts, would play a central role. The intervention, lasting eight weeks, involved creative projects in art classes that emphasised virtues such as courage and friendship. Students also regularly engaged in philosophical discussions about selected artworks that the author believed contained moral undertones or content. Before and after the intervention, questionnaires were administered to both the participating students and a control group. Statistical analysis of the survey data indicated that the intervention did not have a statistically significant effect on students’ moral vocabulary. However, this finding contrasted with impressive student artworks and their written reflections, which indicated meaningful contemplation and insights. This constitutes the first dimension of the study. This outcome led the author to recognise more clearly his own inseparable role as artist, teacher, and researcher, highlighting that the organic whole of human interaction in the classroom cannot be detached from the technical aspects of curriculum, teaching methods, interventions, and assessment. To better understand his role in this context, the author undertook an action research project, forming the second dimension of the study. The main findings of the research underscore the importance of giving students opportunities to reflect on artworks and discuss their thoughts and emotions in relation to those works and their own lives. The results also show that elementary school students can grapple with complex moral questions and articulate their thoughts about them, even if they have not fully developed linguistic mastery. It can be inferred that reflection on artworks and participation in discussions about them may be a valuable complement to traditional curriculum content in elementary education. Furthermore, the results highlight the crucial role of the teacher in creating a safe and trusting classroom environment that enables meaningful learning. On the other hand, the findings also indicate that due to traditions and expectations about the content and focus of visual arts education, teachers might expect to face challenges, though these can be met with patience, reflection, care, and respect
Role of MITF in olfactory bulb neurons. Putative MITF target genes in neurons and the effects of its loss in the aging olfactory bulb.
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025) Mechmet, Fatich; Pétur Henry Petersen, Eiríkur Steingrímsson; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Microphthalmia-associated transcription factor (MITF) is a master regulator in melanocytes and plays and important role in mast cells. Mitf is also expressed in the mitral and tufted (M/T) cells which are projection neurons (PNs), in the olfactory bulb (OB). Lack of MITF leads to neuronal hyperactivity in primary M/T cells but the general function of MITF in neurons is currently unknown. In this study, putative MITF target genes in M/T cells of mice were identified. They differ from target genes in other cell types including melanocytes and can be grouped into two categories: those likely to be involved in inhibiting neuronal activity and those specific to a subgroup of tufted cells called middle tufted cells (mTCs). This work also shows that the mTCs are reduced in number in the absence of Mitf, suggesting a role for Mitf in the generation or survival of the mTCs and/or their function. Altered response to odors is also observed in Mitfmi-vag9/mi-vga9 mice, indicating a role of MITF in olfactory adaptation. Aging affects various brain structures and sensory systems, including the OB, resulting in a decline in olfactory ability. Decline in the OB is associated with early signs of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, the underlying reasons remain unclear. Primary PNs from OBs of young Mitfmi-vga9/mi-vga9 mice show hyperactivity, potentially linked to reduced expression of the potassium channel subunit Kcnd3/Kv4.3, which impacts intrinsic plasticity. In aged Mitfmi-vag9/mi-vag9 mice, reduced olfactory ability was observed without any signs of neuroinflammation or reduction in neuronal number. An increase in the expression of genes coding for potassium channel subunits was found in the OBs of aged Mitfmi-vga9/mi-vga9 mice. This suggests that increased expression of potassium channel subunits in aging Mitfmi-vga9/mi-vga9 mice may compensate for or stabilize neuronal hyperactivity observed in the OB of young Mitfmi-vga9/mi-vga9 mice.
The Impact of Smoothened Cholesterol-Binding Pocket Mutations on Hedgehog Signaling and Osteoarthritis
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025-10) Smith, Abbi Elise; Sara Sigurbjörnsdóttir and Eiríkur Steingrímsson; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
A genome wide association study identified a risk variant of Smoothened (p.Arg173Cys; SMOR173C) associated with hip osteoarthritis. Smoothened (SMO), a 7-transmembrane G protein coupled receptor-like protein, is a key component of the hedgehog signal transduction mechanism. The hedgehog signaling pathway is known to be activated in osteoarthritic chondrocytes, but this was the first identified osteoarthritis risk variant in a hedgehog pathway gene. Interestingly, even though hedgehog signaling is elevated in osteoarthritis tissues, structural analysis predicted the SMOR173C variant to reduce the binding capability of SMO to cholesterol. The binding of cholesterol to the extracellular domain of SMO was recently discovered to be a critical step in SMO activation. As such, the predicted effect of this variant on SMO conflicts with the current known relationship between hedgehog signaling and osteoarthritis. Thus, the aim of the studies described in this thesis was to elucidate the role of the SMOR173C variant in the development of osteoarthritis. To determine whether the SMOR173C variant alters downstream hedgehog signaling activity, we introduced the mutation to the prechondrogenic cell line, ATDC5 in two ways: by overexpressing the human SMO protein containing the SMOR173C mutation, and by generating an endogenously expressing mutation by restoring a null allele in the ATDC5 Smo-null cell line. We showed in both models that the SMOR173C did not abolish downstream hedgehog signaling activity, disproving the structural predictions for the variant. Additionally, we microinjected hSMOR173C mRNA into smo-/- zebrafish embryos and showed that the hSMOR173C mRNA more efficiently recovered a normal morphological phenotype than the hSMOWT mRNA or mRNAs with mutations known to abolish cholesterol binding and downstream hedgehog signaling. To determine the effect of the SMOR173C mutation on osteoarthritis development, we developed a three-dimensional hydrogel cell culture system to better recapitulate the native environment of chondrocytes and found that in the hydrogel system the ATDC5 cells showed indications of precocious differentiation when compared to ATDC5 cell cultured in differentiation medium in a monolayer. Next, we used a cytokine cocktail to stimulate the ATDC5 cells and drive them toward an osteoarthritis-like phenotype. Then we employed both methods using the endogenous mutant ATDC5 cell lines. Cells expressing the R173C variant expressed more than three-fold elevated levels of Mmp13 mRNA at baseline. The effect increased to over four-fold elevation in response to cytokine treatment. As MMP13 is a key catabolic enzyme responsible for cartilage degradation in osteoarthritis, we concluded that chronically increased MMP13 mRNA expression could be responsible for the increased risk of hip osteoarthritis associated with the SMOR173C variant. Finally, we used evolutionary and phylogenetic analyses of smo mutations in teleost fish to identify sites predicted to cause species diversification. We paired this information with clinical reports of disease and cancer driven by SMO mutations to gain a better understanding of the genetic plasticity of SMO. We also found a gene-dose response in the transgenic smo+/- zebrafish with evidence of a heterochronic shift in hedgehog signaling-driven developmental processes: somitogenesis and chondrogenesis. From this we concluded that smo is permissive of mutations largely located outside of the transmembrane domain and likely contributed to species diversification related to jaw structure and body plan morphologies throughout evolutionary history in teleost fishes. The human clinical data follow the same trend: SMO variants associated with skeletal changes lie outside the transmembrane domain, while oncogenic SMO mutations largely occur within the transmembrane domain. This project used in vitro and in vivo models to investigate the role of the SMOR173C variant in downstream hedgehog signaling as well as an osteoarthritis-like phenotype and identified a potentially pathological increase in Mmp13 mRNA expression associated with the SMOR173C variant that likely contributes to osteoarthritis initiation and progression.
Impact of anticoagulation and immunosuppressive drugs on the prognosis of patients with colorectal cancer: a population-based study
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025-10-01) Agustsson, Arnar; Einar Stefán Björnsson; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Nýgengi ristil- og endaþarmskrabbameina fer vaxandi og eru þau ein algengasta orsök andláta vegna krabbameina. Oftast greinast þau vegna blæðingartengdra einkenna frá meltingarvegi og blóðþynningarlyf hafa verið tengd við auknar líkur á blæðingum frá þessum krabbameinum. Hins vegar er það ekki rannsakað hvaða áhrif blóðþynningarlyf geti haft á orsakir meltingavegsblæðinga, hvort þau auki greiningar þessara krabbameina og geti leitt til snemmgreiningar. Engar rannsóknir hafa kannað hvort stigun ristilkrabbameinsins eða lifun einstaklinga á blóðþynningu sé frábrugðin við almennt þýði. Þá hafa rannsóknir á áhrifum hjartamagnýl á lifun einstaklinga ekki borið saman um hvort hjartanagnýl sé verndandi og þá ekki með hvaða hætti það væri verndandi. Hvorki sterar né bólgueyðandi gigtarlyf (e. DMARDs) hafa verið rannsökuð hvort þau geti haft áhrif á lifun einstaklinga með ristil- og endaþarmskrabbamein, en þau hafa bæði sýnt bæta lifun í há áhættu sjúklingahópum. Efni og aðferðir: Allar fjórar rannsóknirnar voru lýðgrundaðar afturskyggnar rannsóknir sem byggðu á gagnagrunnum. Fyrsta rannsóknin nýtti blóðþynningargagnagrunn til að kanna orsakir meltingarvegsblæðinga frá 2014-2019. Hinar þrjár rannsóknirnar byggðu á gagnagrunni yfir alla sjúklinga sem greindust með ristil- og endaþarmskrabbamein frá 2000- 2019 á Íslandi og báru saman lyfjanotkun fyrir greiningu og útkomur vegna krabbameins. Lyfjaupplýsingum var safnað beint úr uppflettingum sjúkraskráa fyrir blóðþynningarlyf og hjartamagnýl, og svo fengust upplýsingar um stera og bólgueyðandi gigtarlyf frá Lyfjagagnagrunni Landlæknis. Niðurstöður: Í fyrsta hluta verkefnisins reyndust 12.005 einstaklingar vera á blóðþynningu og af þeim greindust 752 með meltingarvegsblæðingar, þar af 273 (36%) sem höfðu bráða efri meltingarvegsblæðingu og 391 (52%) bráða neðri. Bæði ristil- og endaþarmskrabbamein (OR 3.7, 95% CI: 2.0 – 7.0, p< 0.001). Sjúklingar á hjartamagnýli höfðu svipaða heildarlifun en betri krabbameinssértæka lifun (HR: 0.79, 95% CI (0.65 – 0.95), p= 0.01). Í fjórða hluta voru 2388 sjúklingar og þar af 816 (34%) sem tóku stera og 91 (3.8%) sem tóku bólgueyðandi gigtarlyf. Sjúklingar sem tóku stera voru að jafnaði eldri og oftar kvenkyns. Sterahópurinn hafði svipaða heildarlifun, klára en ómarktæka fylgni við verri krabbameinssértæka lifun (HR: 1.15, 95% CI (0.96 – 1.38), p= 0.12) og verri sjúkdómsfría lifun (HR: 1.14, 95% CI (1.03 – 1.27), p= 0.02) miðað við samanburðarhópinn. Sjúklingar sem notuðu bólgueyðandi gigtarlyf voru af svipuðum aldri, kyni og með svipaða fylgisjúkdómabyrði og samanburðarhópurinn en voru oftar með krabbamein á stigi I (32% vs 21%, p= 0.02). Hópurinn á bólgueyðandi gigtarlyfjum hafði sambærilega heildarlifun og samanburðarhópurinn og krabbameinssértæka lifun. Ályktun: Niðurstöður þessara rannsókna renna frekari stoðum undir þá kenningu að blóðþynningarlyf geti leitt til snemmgreiningar einstaklinga með ristil- og endaþarmskrabbamein. Blóðþynningarlyf tengdust oftar blæðingartengdum einkennum sem orsökuðust af ristil- og endaþarmskrabbameini og blóðþynningarhópurinn hafði betri krabbameinssértæka lifun. Þetta undirstrikar mikilvægi þess að einstaklingar á blóðþynningu séu undir vökulu eftirliti. Hjartamagnýl tengdist betri krabbameinssértækri lifun, mögulega með því að draga úr eða hindra meinvörp. Steranotkun tengdist verri sjúkdómsfrírri lifun og með fylgi við verri krabbameinssértæka lifun. Bólgueyðandi gigtarlyf tengdust hærra hlutfalli sjúklinga á stigi I, en virtust ekki hafa nein teljandi áhrif á lifun. Niðurstöður rannsóknarinnar á sterum og bólgueyðandi gigtarlyfjum gefa tilefni til frekari rannsókna á þessu sviði til að kanna til hlýtar áhrif þeirra á útkomur einstaklinga með ristil- og endaþarmskrabbamein.
A bioinformatics approach to uncover the role of the epigenetic machinery in neurodevelopment
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025-09-19) okay, kaan; Hans Tómas Björnsson, Kasper Daniel Hansen; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
The epigenetic machinery (EM) comprises molecular components, such as enzymes and protein complexes, that place, remove, or read epigenetic marks on histone tails and DNA, or remodel the chromatin, thereby regulating gene accessibility and expression. Pathogenic variants in these EM genes cause the Mendelian Disorders of the Epigenetic Machinery (MDEMs), a group of rare disorders with unifying phenotypes, including intellectual disability (ID) and growth dysregulation. However, the underlying mechanisms behind these overlapping phenotypes have not been extensively studied. One unifying feature is that many of these disorders have distinct DNA methylation (DNAm) abnormalities in blood samples; however, the relevance of this in disease-associated cell types, such as neurons, remains unclear. Furthermore, despite clinical reports of tumor risk in certain MDEMs, the underlying molecular basis of cancer susceptibility in patients with MDEMs is poorly understood. To address these gaps, this thesis pursues three aims: First, identifying functionally important EM domains using large-scale pathogenic missense variant (PMV) enrichment analysis; second, investigating shared DNAm and transcriptional abnormalities across multiple EM gene knockouts (KOs) in hippocampal murine neuronal progenitor cells (mNPCs). Through haplotype-resolved methylation profiling, imprinting control region (ICR) analysis, and gene expression integration, this aim uncovers convergent disruptions underlying MDEM pathogenesis; third, characterizing mutational signatures in hippocampal mNPCs after EM gene disruption to evaluate potential impairments in DNA damage response (DDR). Together, these aims integrate genomic, epigenomic, transcriptomic, and mutational analyses to advance our understanding of EM gene function and its role in the pathogenesis of MDEMs. Chapter I presents a domain-centric analysis of EM genes based on PMV enrichment, identifying functionally important domains and their roles in Rubinstein-Taybi (RSTS) and Menke-Hennekam (MKHK) syndromes. Among 21 EM genes, 71.4% exhibited significant PMV enrichment in a single, most often the epigenetically canonical, domain. Notably, enrichment in non-epigenetic domains in a subset of EM genes suggests alternative functions and suggests that some of these may need to be reclassified. Syndrome-specific domain enrichment was observed from PMVs in RSTS and MKHK: RSTS variants clustered in the enzymatic HAT domain, while MKHK variants enriched non-enzymatic domains, with structural modeling implicating defects in SUMOylation and phosphorylation. These insights refine the link between protein domain disruption and disease phenotype, offering a framework for mechanistically informed diagnostics and future therapeutic targeting in MDEM. vii Chapter II investigates the effects of EM gene loss on DNAm and gene expression using an mNPC model derived from F1 off-springs of B6 and FVB mouse strains. KO of 46 EM genes, paired with long-read whole-genome sequencing (WGS), haplotype phasing, and RNA-seq, revealed multi-omic disruptions during early neuronal development. While most KOs induced subtle DNAm changes, promoter methylation analysis identified an EM gene cluster enriched for proteins interacting with DNAm writers or erasers, implicating indirect regulation of DNAm via protein-protein interactions (PPIs). Transcriptomic profiling revealed convergent expression changes in Dnmt1- and Kmt2a-KOs, both showing premature differentiation phenotypes. No DNAm abnormality was shared between these two EM-KOs detected, which suggests transcriptional dysregulation, rather than methylation dysregulation, plays a critical role in the premature differentiation observed here. However, it is not clear whether this is a primary or secondary effect. Haplotype-resolved methylomes revealed thousands of haplotype-specific differentially methylated regions (DMRs), associated with cis regulating methylation quantitative trait loci (cis-mQTLs). Abnormal methylation in imprinting control regions (ICRs) was observed in a subset of EM-KOs, suggesting EM involvement in ICR regulation. Collectively, these results demonstrate that EM gene disruption can result in epigenetic and transcriptional convergence, offering mechanistic insight into MDEM pathogenesis. Chapter III explores the relationship between EM gene loss and DDR in MDEMs, using the same mNPC dataset used in Chapter II. Although no overall significant increase in somatic variant load was observed in EM-KOs compared to controls, B6 controls showed significantly higher variant loads than FVB, likely due to differences in genetic background. A higher somatic variant load than expected by chance was observed in Asxl3, Crebbp, Kmt2d, Kmt2e, Lbr, Tdrd3, and Msl3-KOs, implicating putative roles of these genes in DDR. Among these, Kmt2e, Msl3, and Tdrd3 may represent novel candidates playing a role in the DNA damage response. Mutational signature analysis revealed shared enrichment of two trinucleotide signatures, SBS30 (base excision repair, BER) and SBS44 (mismatch repair, MMR), between multiple EM-KOs, suggesting shared DNA repair impairments. Together, these findings indicate that specific EM gene disruptions may compromise genome integrity and elevate cancer risk in a subset of MDEMs. Collectively, these chapters integrate domain-centric, multi-omic, and mutational analyses to elucidate the diverse, context-dependent functions of EM genes in neurodevelopmental and associated disorders.

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