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Online communication and adolescent health. Exploring adolescent mental and physical health and online communication in the early 21st century: Longitudinal and cross-sectional perspectives
(University of Iceland, School of Education, Faculty of Health Promotion, Sport and Leisure Studies, 2025-09) Birgisson, Ottar; Erlingur Jóhannsson, G. Sunna Gestsdóttir; Deild heilsueflingar, íþrótta og tómstunda (HÍ); Faculty of Health Promotion, Sport & Leisure Studies (UI); Menntavísindasvið (HÍ); School of Education (UI)
In this thesis, I investigate the evolving relationship between online communication and adolescent mental and physical health, focusing on changes over time. The main aim was to assess how online communication relates to mental health outcomes (depression, anxiety, self-esteem, and body image) and physical health, measured as cardiorespiratory fitness (CRF). Additionally, how these relationships have changed in the early 21st century, during a period of significant transformations in online communication, was explored. Three datasets collected from Icelandic adolescents were used. 1) A cohort born in 1988 assessed in 2003 at age 15 (n = 385), 2) a cohort born in 1999 assessed in 2015 at age 15 (n = 302), and 3) the cohort born in 1999 followed up in 2017 at age 17 (n = 236). Measurements included self-reported online communication frequency, validated questionnaires assessing mental health, and objective CRF measurements using a maximal cycle ergometer test. Socioeconomic status (SES) was estimated based on parental education and living arrangements. Statistical analyses included descriptive statistics, multiple regression, analysis of variance, structural equation modeling, and mixed-effects models. Results showed that depressive symptoms increased among adolescent females between 2003 and 2015 while remaining stable for males. Anxiety levels and self- esteem did not change significantly for either sex. Body image improved slightly for males but was stable for females. By 2015, a significant relationship was found between online communication and an increase in depressive and anxiety symptoms in females but not in males. CRF declined from 2003 to 2015, and a negative association between CRF and mental health outcomes was observed. Lastly, online communication had a negative association with mental health and CRF at the age of 15, and that this relationship persisted until the age of 17, regardless of sex and SES. The findings highlight the complex dynamics of online communication and its impact on adolescent mental and physical health. Increased online communication appears to be linked to poorer mental health outcomes particularly for females, possibly mediated by social comparison. Declining CRF underscores the importance of promoting physical fitness alongside mental health interventions. To address these challenges, interventions should integrate both digital literacy and physical activity strategies. This study contributes to a deeper understanding of adolescent well-being in the digital age and provides a foundation for targeted interventions.
Tourist safety on adventure trips: Guide competencies and risk management strategies in the Arctic
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Life and Environmental Sciences, 2025-09) Hild, Barbara Olga; Gunnar Þór Jóhannesson; Líf- og umhverfisvísindadeild (HÍ); Faculty of Life and Environmental Sciences (UI); Verkfræði- og náttúruvísindasvið (HÍ); School of Engineering and Natural Science (UI)
Improving modelling of crustal deformation in relation to magmatic and geothermal processes
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Earth Sciences, 2025-09) Lanzi, Chiara; Freysteinn Sigmundsson; Jarðvísindadeild (HÍ); Faculty of Earth Sciences (UI); Verkfræði- og náttúruvísindi (HÍ); School of Engineering and Natural Sciences (UI)
Understanding small crustal deformation signals is important for improving volcano monitoring and hazard mitigation. Spatial and temporal ground displacement patterns were mapped with Global Navigation Satellite System (GNSS) geodesy and Interferometric analysis of Synthetic Aperture Radar (InSAR) images, allowing detection of millimeter- to centimeter-scale deformation. Geodetic modelling, through inversion or forward modelling, was used to infer deformation source parameters and increase understanding of volcanic, geothermal and tectonic processes. In summer 2018, a change in the pattern of ground deformation at the Krafla caldera coincided with increased pressure in a monitoring well. This occurred at a similar time as re-injection of water, in relation to geothermal utilization, was modified. The difference between GNSS and InSAR velocity fields from 2015–2018 and 2018–2020 reveals an inflation pattern with horizontal motion up to 8–10 mm/yr. Geodetic inversion shows that the difference velocity field can be fit with a 2.1–2.5 km deep point-source, near the magma-hydrothermal interface. The observations are broadly explained by local variations in intra-caldera crustal elasticity and pressure increase at ~2.2 km depth, consistent with the well data. The study also examined how local elastic and viscoelastic crustal and mantle properties at volcanoes located at divergent plate boundaries influence deformation by regional processes like plate spreading, using a Finite Element Method model to simulate local rheological anomalies beneath calderas and rifts. This approach helps explaining the observed decades-long subsidence at Krafla (1989–2018) and Askja (1985–2021). The results show that extensional forces and rheological anomalies can drive volcanic subsidence. At Krafla, this account for much of observed 2015-2018 subsidence, but only 20–30% at Askja. Finally, the ~40-60 mm subsidence during the 2021 Fagradalsfjall eruption was analyzed and evaluated how changes in deformation relate to changes in eruption rate, geochemistry of eruptive products, and eruptive style. Surface lava loading within 1-2 km significantly contributed to the subsidence. After removing this effect, geodetic inversion locates a 12–14 km deep sill source with volume contraction of 2127 Mm3. This research highlights the need to consider complex geological settings when interpreting small ground deformation signals, as multiple interacting processes may produce observed deformation.
Basalt lava degassing: mechanism and characterisation
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Earth Sciences, 2025-05) Levillayer, Nicolas; Olgeir Sigmarsson; Jarðvísindadeild (HÍ); Faculty of Earth Sciences (UI); Verkfræði- og náttúruvísindasvið (HÍ); School of Engineering and Natural Sciences (UI)
The volcanic gas composition emitted during basaltic eruptions is relatively well understood, but the emissions from cooling lava fields have been less studied, along with their environmental impacts. The study investigated the gas emission from crystallising lava, as well as the internal structure of lava and associated segregation veins. Gas samples were collected from the eruptive crater, cooling vents, and solidifying lava in Fagradalsfjall. The gas emissions were found rich in sulphur and sulphide-forming elements at the eruptive crater, while post-eruptive gas is richer in halogens, especially chlorine at the crystallising lava and fluorine at the cooling vent. Estimates of emissions from crystallising lava show significant release of metals that form chlorides. The relationship between emission and fractional crystallisation, along with segregation melt formation during lava solidification, was examined. The first minerals to from are anhydrous, forming a fully crystallised framework after 40-50% crystallisation. In the residual melt, volatile elements saturate and form a volume-rich gas phase. The gas presses the melt through the crystal framework, forming segregation veins. Chemical analyses of these veins reveal whether the gas phase escaped into the atmosphere or solidified with the melt. The similar compositions of segregation veins and gas from solidifying lava indicate a relationship between the internal lava evolution and lava degassing. Overall, the results show that gas emissions from lava are distinct from emissions at the vent but correlate well with the fractional emission of basalt melt, both in terms of origin and nature. The environmental impacts of heavy metal gas emissions from basalt lava are a worthy subject for future research.
Multi-Hazard Assessment of Long-Span Bridges, Considering the Effects of Seismic and Wind Action
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Civil and Environmental Engineering, 2025-06) Jami, Abdul Matin; Rajesh Rupakhety; Umhverfis-og byggingarverkfræðideild (HÍ); Faculty of Civil and Environmental Engineering (UI); Verkfræði- og náttúrufræðisvið (HÍ); School of Engineering and Natural Sciences (UI)
This PhD research project focuses on the multi-hazard evaluation of long-span bridges and the development of novel solutions to improve the effectiveness of structural control schemes. In particular, the study investigates seismic response mitigation using passive devices such as tuned mass dampers and lead rubber bearings. The research aims to examine the response of both uncontrolled and passively controlled long-span bridges, specifically suspension and cable-stayed types, subjected to near-fault earthquake excitations and strong wind forces. A key objective is to quantify the probabilities of exceeding various performance limit states and to establish fragility functions for these structures under combined seismic and wind hazards. The project further explores the feasibility and efficiency of passive control systems in reducing structural fragility. These objectives are motivated by several core research questions. First, due to their considerable length and inherent flexibility, suspension and cable-stayed bridges are especially vulnerable to long-period and impulsive motions characteristic of near-fault earthquakes. The study seeks to understand the extent to which near-fault effects compromise the safety of such bridges and whether their fragility under these conditions is significantly greater than under ordinary ground motions. It also evaluates the effectiveness and practicality of using passive control devices, such as tuned mass dampers, to mitigate this fragility. In addition, the research addresses how the combined effects of stochastic wind and seismic loads can be integrated into fragility analysis and the implications for design practice. To investigate these questions, detailed finite element models were developed using SAP2000, MATLAB, and OpenSees. The models include a three-span concrete bridge, multiple five-span concrete bridges, a 300-meter span cable-stayed bridge in Iceland (Ölfusá River), and a 1500-meter span suspension bridge in China (Runyang River). Wind forces were simulated using stochastic processes based on the spectral representation method, while seismic input was derived from real ground motion records from past earthquakes. A novel simulation methodology was also implemented to generate over 55,000 pulse-type near-fault ground motions for comprehensive evaluation of their effects. The findings indicate that well-optimized passive control systems can significantly reduce structural responses under both seismic and wind loading. Fragility analyses confirm the effectiveness of tuned mass dampers in decreasing structural vulnerability and, in certain cases, enhancing pier moment capacity, particularly when vertical seismic components are considered. The study also identifies bridge bearings as critical elements influencing overall seismic performance, underscoring the importance of post-earthquake inspection and design strategies that facilitate their replacement. Given Iceland’s proximity to active fault lines, the results highlight the importance of accounting for near-fault effects in the seismic design and long-term resilience of critical infrastructure.
Án titils
(University of Iceland, School of Health Science, Faculty of Medicine, 2024-11) Sverrisdottir, Ingigerdur Solveig; Sigurður Yngvi Kristinsson; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Abstract Introduction and aims: Multiple myeloma (MM) is a haematological malignancy caused by abnormal plasma cell proliferation in the bone marrow. All MM cases are preceded by a precursor condition, monoclonal gammopathy of undetermined significance (MGUS), which does not require any treatment. Risk factors for MGUS are sex, age, pesticide exposure, and ethnicity, and studies have indicated an increased risk of MGUS in individuals with autoimmune disorders. MGUS has been associated with worse survival compared to the general population. Survival of MM has increased recently, mainly due to advances in treatment. However, MM patients typically suffer from comorbidities, which may influence survival. Parental longevity generally increases survival, but studies regarding longevity in specific diagnoses have yielded conflicting results. The impact of parental longevity on MGUS and MM remains unclear. Using population-based data, the first part (study I) investigated if parental longevity affected survival among MGUS and MM patients. The second part (study II) aimed to study the prevalence and impact of comorbidities on the survival of MM patients using the same data as in study I. The third part (study III) investigated if autoimmune diseases were associated with a diagnosis of MGUS in a screened population. Methods: In study I, we analysed parental longevity and survival in individuals with MGUS, MM, and their respective controls in Sweden, 1988-2013. All individuals diagnosed with MM in the Swedish Cancer Registry and those with MGUS in a nationwide MGUS cohort were included with four population-based controls. All individuals had a registered parent in the Swedish Multigenerational Registry. The Cox proportional hazard model evaluated the effect of parental longevity on survival, with longevity defined as exceeding 90 years of age. In study II, we investigated comorbidity and survival. All individuals registered with MM in the Swedish Cancer Registry 1990-2013 were included. Cause and date of death were identified from the Cause of Death Registry, and information on comorbidities was retrieved from the Swedish Patient Registry. A Cox model was used to analyse survival in relation to comorbidities. Study III was a cross-sectional study within the Iceland Screens Treats or Prevents Multiple Myeloma study, iStopMM, where 75,422 individuals over 40 years were screened for MGUS. Information on autoimmune disorders was gathered from the Icelandic Patient Registry. Poisson regression was used to calculate prevalence ratios (PRs) of MGUS in individuals with or without an autoimmune disease. Results: In study I, 6,812 individuals with MGUS and 19,110 controls, as well as 4,675 MM patients with 13,398 controls, were included. Parental longevity was associated with a decreased risk of death in MM and MGUS (hazard ratio (HR) 0.92; 95% vi confidence interval (CI): 0.84-0.99 and HR 0·87; 95%CI: 0.78-0.96, respectively). In study II, 13,656 patients with MM were analysed, with 54% having at least one comorbidity at diagnosis. Comorbidity increased the risk of death compared to previously healthy MM patients (HR 1.19; 95% CI: 1.14-1.25). The survival decreased with the increasing number of comorbid conditions at diagnosis, with HR 1.38 (95% CI: 1.30-1.47) for 2 comorbidities and HR 1.72 (95% CI: 1.62-1.83) for three or more comorbidities. The Charlson Comorbidity Index, CCI, had low c-statistic and area under the curve (AUC) or poor survival prediction in relation to comorbidities. In study III, 75,422 individuals were screened for MGUS, where 10,818 participants had an autoimmune disorder, of whom 599 had MGUS, with 61 a prior clinical diagnosis of MGUS. Autoimmune disorder was not associated with MGUS (PR 1.05; 95%CI: 0.97- 1.15). However, autoimmune diseases were associated with a prior clinical diagnosis of MGUS (PR 2.11; 95% CI: 1.64-2.70). Conclusions: Our findings demonstrate that host characteristics influence survival in patients with MM and MGUS. We found that a longer parental lifespan reduced the risk of death in both groups. This suggests that parental longevity, influenced by genetic and environmental factors, can have a survival advantage even in a malignant condition such as MM. In study II, we found that comorbidities are common in MM, with an increased risk of mortality with an increasing number of comorbidities. This underscores the vulnerability of MM patients at diagnosis and highlights the necessity of considering comorbidities when selecting treatment to avoid under- or over-treatment, which can negatively impact survival. In study III, we did not observe a correlation between autoimmune diseases and MGUS in a screened population. However, a clear association was found between a prior clinical diagnosis of MGUS and autoimmune disorders. This finding indicates that previous studies, not based on screened populations, were subject to ascertainment bias. Therefore, we do not recommend screening for MGUS in patients with an autoimmune disorder.
The Use of Artificial Intelligence for Diagnosis and Outcome Prediction in Primary Care
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025-02-27) Ellertsson, Steindor; Emil Lárus Sigurðsson, Hrafn Loftsson; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
In recent years, the ability of Artificial Intelligence (AI) to analyze and predict various variables within medicine has advanced significantly. Part of this progress can be attributed to the availability of larger electronic datasets; however, there is still a shortage of high-quality data for training AI models for use within the healthcare system. Electronic health records contain vast amounts of data, and with increased interoperability, diverse datasets are emerging that can be cross-referenced and potentially used to train AI models. Doctors' summary notes from patient interviews are a major component of medical records and include descriptions of the patient's medical history, examination, findings, and the doctor’s assessment and plan. These notes should, therefore, contain all the necessary information to train AI models to predict patient diagnoses and outcomes. The objective of this doctoral thesis was: 1) to investigate whether doctors’ summary notes from patient medical records could be used to train AI models to predict diagnoses and outcomes for patients in primary care; and 2) to study which factors the models use to reach a conclusion and compare these to the elements doctors rely on. The thesis is based on studies described in three papers—the first two were retrospective, and the third was prospective. In the first study, an AI model was trained to predict primary headache diagnoses based on labeled diagnostic features from doctors' summary notes following patient interviews in primary care, which resulted in one of four common primary headache diagnoses. The study compared the model’s performance to that of three resident physicians and three family medicine specialists. The model's internal functionality was also evaluated using Shapley Additive Explanations (SHAP) values, which indicate which input features have the most significant impact on each output. In the second paper, an AI model was trained on Clinical Features (CFs) from labeled notes of doctors who treated primary care patients diagnosed with one of the following respiratory symptom codes over a specific period: J00, J15, J20, J44, and J45. In both the first and second studies, a methodology was applied to remove low-content text notes and maximize the quality of the dataset from which the models learned. The third study evaluated the model trained in the second study, with minor adjustments, using a prospective approach in a single primary care clinic in Iceland's capital area. In the first study, the model achieved a higher weighted average sensitivity, positive predictive value, and Matthews Correlation Coefficient (MCC) than the weighted average of the doctors. The specificity of five out of six doctors was higher than that of the model. SHAP value analysis indicated that the model relies on similar diagnostic features as doctors for each diagnosis. In the second study, the model categorized patients into risk groups, where the outcomes of patients in lower-risk groups reflected those likely to have mild symptoms that resolve without intervention. No cases of pneumonia or patients with lung infiltrates on Chest X-Rays (CXRs) were detected in the lower-risk groups. In the third study, one patient with pneumonia was categorized in a lower-risk group but was later found to have a normal lung CXR, suggesting a likely misdiagnosis. All other patients with pneumonia on CXR were in high-risk groups. Two patients were diagnosed with lung cancer, both in the highest risk group. The results of the first study indicated that the AI model performed as well or slightly better than the groups of GP trainees and GP specialists in diagnosing primary headaches. SHAP value analysis showed that the models rely on similar clinical features to doctors when making diagnoses. The results of the second study suggested that the AI model could safely triage primary care patients with respiratory infections. The model categorized patients with truly severe respiratory conditions into high-risk groups, while those with milder symptoms were placed in low-risk groups. The third study demonstrated that the model could stratify patients in real clinical settings so that patients with severe respiratory conditions were categorized as high risk, while those with mild symptoms were categorized as low risk. Two patients diagnosed with pneumonia by doctors, whom the model classified as low risk, were subsequently found to have normal lung images. The doctoral thesis concludes that AI models trained on clinical features extracted from physicians’ summary notes can have significant utility in primary healthcare.
The role of the psychobiological stress response to a lung cancer diagnosis in tumor biology and survival
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025-06-06) Harðardóttir, Hrönn; Unnur Anna Valdimarsdóttir; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Lung cancer is the second and third most common cancer among men and women in the Nordic countries and the leading cause of all cancer deaths. Receiving a cancer diagnosis, particularly lung cancer, is an extremely stressful experience that may have further health consequences for the patients. Psychological distress activates the sympathetic nervous system, which can enhance tumor progression. Data is scarce on the psychobiological stress response during the diagnostic work-up and diagnosis of lung cancer as well as its potential role in prognostic markers and survival. The LUCASS study (LUng CAncer, Stress and Survival) is a prospective cohort study designed to investigate the psycho-biological stress responses in patients undergoing a diagnostic work-up for suspected lung cancer. Eligible participants were referred to the University Hospital, Reykjavík, Iceland (2015-2018) and Uppsala, Sweden (2018-2020), with clinical and/or radiographical changes suggestive of lung cancer. They underwent a diagnostic work-up that led to a definitive lung cancer diagnosis in 201 out of 286 participants (70.3%). The assessment of psychological stress and relevant biomarkers of stress was integrated with clinical evaluation at two time points, i.e., during the diagnostic work-up and at a follow-up visit 1-3 weeks later, but before treatment. We then assessed the development of these psychobiological indicators during the diagnostic work-up, and their association with tumor markers and survival. This thesis is based on two peer-reviewed published papers (Studies I and II) and two manuscripts (Studies III and IV), with the overarching aim of determining the development of symptoms and biomarkers of psychological distress during the diagnostic process and its association with disease progression and survival. In Study I, we assessed mental health symptoms and urinary catecholamines in 167 patients before and after diagnosis of lung cancer or non-malignant lung pathology. Patients diagnosed with lung cancer experienced a post-diagnosis increase in psychological distress (measured with HADS-T, Hospital Anxiety and Depression Scale, Total score) (p=0.0096), while patients with non-malignant lung pathology showed a reduction in distress (p=0.070). Both urinary epinephrine (E) (p=0.001) and norepinephrine (NE) (p=0.032) levels were higher before the diagnosis among patients diagnosed with lung cancer as compared to those with non-malignant lung pathology. An indication of associations between changes from pre-to-post diagnosis in perceived distress and changes in urinary catecholamine levels was detected. We observed no cross-sectional association between psychological distress and urinary levels of catecholamines before or after the diagnosis of lung cancer. In Study II, we studied symptoms of acute traumatic stress (measured with the Impact of Event Scale-Revised, IES-R) after the diagnosis of lung cancer, among 89 participantsin the Icelandic arm of the study. In this patient group, 52% reported medium to high symptom levels of acute traumatic stress (IES-R > 23) at a median of 16 days after diagnosis, with 24% meeting screening criteria of acute post-diagnostic traumatic stress suggestive of clinical significance (IES-R > 32). Optimal doctor-patient (β= -9.1, 95%CI: -14.9 to -3.3) and family communication (β= -8.6, 95%CI: -14.3 to -2.9) were associated with lower symptom levels of acute traumatic stress after the lung cancer diagnosis. In Study III, we studied pre-diagnostic perceived distress levels among 52 patients undergoing thoracic surgery for non-small cell lung cancer (NSCLC), at a median of 28.5 days after diagnosis. Tumor cell β2-adrenergic receptors (β2AR), Ki-67 levels, and CD31 microvessel density (MVD) were assessed in tumor tissue by immunostaining. We observed a strong association between psychological distress (HADS total score of >13, HADS-T >13) and tumor cell β2AR-levels (OR 12.6, p=0.010) as well as indications of associations with a history of psychiatric disorder, resilience, and levels of social support. We found no statistically significant associations between β2AR-levels with tumor stage nor tumor proliferation. In Study IV, we examined the association between pre-diagnostic distress levels and urinary catecholamines with lung cancer-specific mortality among 145 patients diagnosed with NSCLC. Pre-diagnostic symptoms of distress (HADS-T >13) were associated with lung cancer-specific death among patients with early-stage disease (TNM-stage I-II) during late (>3 years) (HR 8.6, 95%CI 2.1-35.1), but not early (<3 years) (HR 1.3, 95%CI: 0.3-5.1) follow-up period. No significant association between distress levels and survival was observed among patients with advanced-stage disease (TNM stage III-IV). Higher pre-diagnostic urinary norepinephrine levels were associated with increased lung cancer-specific mortality (HR 2.0, 95%CI 1.1-3.5) among all patients during the entire observation period. In summary, undergoing a diagnostic work-up and receiving a lung cancer diagnosis is associated with an increase in psychological distress and high levels of acute traumatic stress following the diagnosis. Urinary levels of catecholamines were already elevated before the lung cancer diagnosis was established, with no clear link to distress levels at that time point. Nevertheless, we demonstrate that pre-diagnostic psychological distress is strongly associated with levels of β2-adrenergic receptor levels on the tumor cells, which in previous studies have been linked to prognosis. Finally, high pre-diagnostic distress and urinary-NE levels before lung cancer diagnosis were associated with lung cancer-specific survival. Further studies are warranted on the complex links between patients’ mental distress at diagnosis, tumor biology, and survival in lung cancer.
Insights from the bone marrow: Characterization of monoclonal gammopathy of undetermined significance through flow cytometry analysis of plasma cells
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025-06) Óskarsson, Jón Þórir; Sigurður Yngvi Kristinsson; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Introduction and aims: Multiple myeloma (MM) is a hematological malignancy, characterized by the proliferation and accumulation of malignant plasma cells in the bone marrow (BM), leading to overproduction of monoclonal protein (M-protein) and/or free light-chains (FLC). MM is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic condition common among older adults (affecting around 3-5% of individuals aged 50 or older), progressing to MM and related disorders at a rate of approximately 1% per year. Although the overall risk of progression is relatively low, MGUS is a heterogeneous condition. Some individuals exhibit rapid malignant transformation, while others may follow an indolent clinical course. Consequently, accurate risk assessment and optimal clinical management represent key challenges in MGUS care. Multiparameter flow cytometry (MFC) provides immunophenotypic characterization at the single-cell level, enabling direct detection of plasma cell clonality based on aberrant antigen expression patterns. Although not routinely used in the diagnostic work-up of MGUS, MFC can complement traditional serological markers and potentially improve diagnostic accuracy and risk stratification. The clinical utility of MFC in this context is evaluated in this thesis, based on three studies. The first study aimed to develop a predictive model for assessing hemodilution in BM aspirates, which causes underestimation of plasma cell proportions. The second study aimed to refine the use of serum FLC ratio as a surrogate marker for plasma cell clonality in light-chain MGUS (LC-MGUS). The third study investigated the frequency and clinical significance of clonal plasma cell detection in IgA and IgG MGUS. Methods: All three studies were based on immunophenotypic analysis of BM samples from participants in the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) population-based screening study. The EuroFlow next-generation flow (NGF) MM-minimal residual disease method was used to identify and quantify phenotypically aberrant (clonal) plasma cells and other cell populations in the BM. In the first study, first and second pull BM aspirated samples, used as references for optimal and suboptimal sample quality, were compared to identify markers of hemodilution. The most discriminatory populations were combined using linear discriminant analysis to develop the Bone Marrow Quality Index (BMQI). Validation included experimentally induced hemodilution. In the second study, the relationship between serum FLC ratio and clonal plasma cell detection by NGF was assessed to define an optimal FLC ratio cutoff. Longitudinal FLC dynamics and progression outcomes were used to evaluate the clinical relevance of the identified threshold. In the third study, NGF was used to assess clonal plasma cell detection in IgA and IgG MGUS. Clinical outcomes, including the rate of transient M-proteins and disease progression, were evaluated by clonal plasma cell detection status. Results: In study I, 351 BM samples from 219 individuals with plasma cell disorders were included. Second pull samples showed significantly reduced plasma cell proportions relative to paired first pull samples (median ratio 0.31; p<0.001). Nucleated red cells and myeloid precursors provided the most robust discrimination between first and second pull samples (area under the curve (AUC) values of 0.87 and 0.85), and were combined into the BMQI. BMQI scores correlated with plasma cell percentages and experimentally induced hemodilution. In study II, clonal plasma cells were detected in 53.6% of BM samples from LC-MGUS individuals and all those with more advanced disease. Serum FLC ratio strongly predicted clonal plasma cell presence, with an optimal cutoff of 3.15 (AUC=0.98; 96.7% sensitivity and 91.7% specificity). Individuals with FLC ratios between 1.65-3.15 showed stable FLC values and no progression, while those with ratios >3.15 exhibited overall increasing FLC ratio and significantly higher rates of progression to smoldering or active MM. In study III, clonal plasma cells were detected in 79.1% of MGUS individuals, and more frequently in IgA MGUS (93.3%) than IgG MGUS (71.2%; p<0.05). All MGUS cases without detectable clonal plasma cell population had either transient M-protein (52.6%) or a low-level stable IgG M-proteins (47.4%), and none progressed to more advanced disease over a median follow-up of five years. Conclusions: Altogether, MFC enables sensitive detection of clonal plasma cells and can improve diagnostic characterization in MGUS. The BMQI provides an objective, reproducible measure of BM sample quality and can inform interpretation of MFC-based plasma cell analysis. A refined FLC ratio cutoff of 3.15 improves diagnostic specificity in LC-MGUS and immunophenotypic confirmation of plasma cell clonality might be useful in borderline cases in this subgroup. Additionally, absence of clonal plasma cells identifies an MGUS subset with an indolent clinical course, characterized by transient or low-level IgG M-proteins, and no disease progression. Integrating standardized MFC methods, such as NGF, into MGUS evaluation may enhance diagnostic precision and inform individualized follow-up strategies.
"Tell all the Truth but tell it slant—": A Slant Approach to Analyzing Literature after 9/11
(University of Iceland, School of Humanities, Faculty of Languages and Culture, 2025-06) Thors, Margrét Ann; Giti Chandra; Mála- og menningardeild (HÍ); Department of Languages and Cultures (UI); Hugvísindasvið (HÍ); School of Humanities (UI)
This dissertation argues for a new, “slant” approach to analyzing post-9/11 literature, defined here as any work of literature published after September 11, 2001. Existing scholarship on post-9/11 literature tends to focus exclusively on novels that deal directly and explicitly with the attacks and their aftermath. I lay out a different strategy for conceptualizing and analyzing post-9/11 literature—a strategy that considers not only works that bear an obvious link to 9/11, but also, and perhaps more importantly, works whose engagement with 9/11 is indirect and/or oblique. The central assumption of this project is that just as the effects of 9/11 are often implicit in our contemporary world, so too are they often implicit in contemporary literature. The study is divided into five chapters. The first chapter reviews existing scholarship on post-9/11 literature, and then conducts close readings of three novels: Mohsin Hamid’s The Reluctant Fundamentalist (2007), Amy Waldman’s The Submission (2011), and Ayad Akhtar’s Homeland Elegies (2020). These books engage directly with 9/11 but do so in a fashion much different from the first wave of 9/11 fiction, where most of the unofficial canon of 9/11 literature resides. The next four chapters include case study analyses of nine novels published after 9/11. The purpose of these chapters is to demonstrate different ways in which seemingly non-9/11 novels can be productively read through a 9/11 lens. Chapter Two analyzes Cormac McCarthy’s The Road (2006), Kevin Powers’ The Yellow Birds (2012), and Celeste Ng’s Our Missing Hearts (2020) with respect to 9/11, paying special attention to the waves of panic, confusion, and trauma that characterized the early days after the attacks. Chapter Three considers novels that humanize the post-9/11 “Other” and offer tempered notes of hope regarding the redemptive power of art: Khaled Hosseini’s The Kite Runner (2003) and Christy Lefteri’s The Beekeeper of Aleppo (2019). Chapter Four analyzes works that explore post-9/11 belonging and identity, particularly among characters of color: Jhumpa Lahiri’s novel The Namesake (2003), Mira Nair’s adaption of The Namesake to the big screen (2007), and Chimamanda Ngozi Adichie’s novel Americanah (2013). Finally, Chapter Five analyzes works that evidence a renewed interest in and relevance of religion after 9/11 and wrestle with big existential questions: Marilynne Robinson’s Gilead (2004) and Ruth Ozeki’s A Tale for the Time Being (2013). The seeds of this slant approach to analyzing post-9/11 literature can be found in much of the existing scholarship in this field, including in foundational works by Richard Gray, Kristiaan Versluys, Martin Randall, Birgit Däwes, Ann Keniston, Jeanne Follansbee Quinn, and Arin Keeble, among others. However, no scholars have as yet fleshed out this fledgling approach. The ultimate goal of this research is to expand the notion of what can be considered a 9/11 novel, and, in so doing, to broaden the understanding of how 9/11 shows up—often undercover, often hidden in nooks and crannies—in contemporary literature, and also in contemporary life.
Mechanistic insights into the role of KMT2D in Kabuki syndrome 1
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025-06) Halldórsdóttir, Sara Tholl; Hans Tómas Björnsson; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Kabuki syndrome type 1 (KS1) is a Mendelian disorder of the epigenetic machinery (MDEM) caused by heterozygous pathogenic variants in the histone methyltransferase 2 D (KMT2D). KS is a multi-organ disorder with variable phenotypic presentations among different individuals. Among the most common features seen are distinctive facial characteristics, intellectual disability and growth deficiency. Beyond its established role in histone methylation, KMT2D has been suggested to play a role in additional cellular functions such as differentiation of various cell lines. The aims of this thesis were to get a better understanding of how KMT2D plays a role in KS disease phenotypes. To achieve this, we used three approaches. First, we generated a novel KS mouse model with the patient specific missense variant R5230H corresponding to R5179H in humans. This variant is located within the FYR-N domain, a domain that has been found enriched for KS specific missense variants. The patient harboring this variant had classical features of KS indicating that this is a disease-causing variant. To predict consequences of the R5230H substitution on protein structure we used AlphaFold3. The prediction did not suggest structural changes of the protein with this amino acid substitution. However, we observed changes in surface charge which might affect ability to interact with other proteins. A Western blot showed that the substitution does not alter KMT2D protein stability nor global H3K4 methylation. Our mouse model displays core KS features described in a previous loss-of-function mouse model with the exception of the defects in adult neurogenesis. Additionally, the model displayed a novel phenotype of unilateral renal agenesis. To investigate the function of KMT2D specifically in bone development, we utilized a previously published chondrocyte model with KMT2D deficiency (Kmt2d-/-) that is known to display precocious differentiation. We found that these cells exhibit decreased cell cycling and proliferation capacity. Pathway enrichment analysis of differentially expressed genes revealed upregulation of factors participating in hypoxic response and glycolysis. Consistently, we observed upregulation of Hif1a expression and increased lactate secretion throughout differentiation. To determine whether dysregulation of these pathways contributes to premature hypertrophy, we knocked down Hif1a in Kmt2d-/- cells during differentiation to inhibit the hypoxia response, but did not observe any changes in the differentiation rate. Additionally, we induced hypoxia signaling in Kmt2d+/+ cells by lowering the oxygen levels during differentiation, thereby promoting anaerobic glycolysis. However, this did not accelerate differentiation, suggesting that neither hypoxia nor glycolysis is the primary driver of the observed precocious differentiation. To examine the underlying cause of pathway dysregulation in Kmt2d-/- cells, we performed a Seahorse Mito Stress test to assess mitochondrial function. We observed reduced mitochondrial respiration in Kmt2d-/- cells compared with Kmt2d+/+ cells, accompanied by increased superoxide (•O2-) production. Under low energy requirements, hydrogen peroxide (H2O2) accumulation was neutralized through an upregulation of the antioxidant response via Nfe2l2. However, with increasing energy demand during differentiation, Kmt2d-/- cells showed a nine-fold increase in H2O2 accumulation compared with Kmt2d+/+ cells. By limiting oxygen availability or targeting mitochondrial reactive oxygen species (ROS) with drugs, we successfully reduced ROS levels, rescuing early senescence and preventing terminal hypertrophy. To elucidate the role of KMT2D in defective chondrocyte differentiation, we performed CUT&RUN for H3K4me1, H3K4me3 and KMT2D. Our analysis revealed that KMT2D was primarily located at promoter regions and consistently, we observed the most significant effect on H3K4me3. Previous research in the same chondrocyte model reported a bidirectional transcriptional effect following KMT2D loss. Cross-examination of these datasets showed that the transcriptional changes were largely associated with H3K4me3 but not H3K4me1 alterations. Motif analysis of KMT2D genomic binding suggested that KMT2D co-localizes with multiple transcription factors involved in chondrocyte differentiation and metabolism. Notably, one of the enriched transcription factors was E2F4, a known cell cycle repressor and a potential regulator of mitochondrial metabolism. Furthermore, mass spectrometry suggests a direct interaction between KMT2D and E2F4, which was absent in Kmt2d-/- cells. Finally, among the KMT2D target genes, four: Mpc2, Aco1, Acly and Mdh1, are known to be directly involved in mitochondrial metabolism. Collectively, our findings highlight the complexity of KMT2D function in organ development, which appears to be both cell type- and stage-specific. We established a novel mouse model that serves as a valuable tool for studying KS disease progression and potential therapeutic strategies. Lastly, our results provide compelling evidence that in chondrocytes, KMT2D plays a critical role in differentiation through its regulation of mitochondrial metabolism.
Clausal nominalization in Icelandic
(University of Iceland, School of Humanities, Faculty of Icelandic and Comparative Cultural Studies, 2025-06) Garofalo, Mirko; Jóhannes Gísli Jónsson; ; Íslensku- og menningardeild (HÍ); Faculty of Icelandic and Comparative Cultural Studies (UI); Hugvísindasvið (HÍ); School of Humanities (UI)
This doctoral dissertation is the first extensive analysis of nominalized clauses in contemporary Icelandic. Its main objective is to explain: a) the role of the demonstrative pronoun það ‘that’ (see Garofalo (2020)) when it introduces a clausal complement; b) its syntactic distribution; and c) the structural difference between nominalized and non-nominalized clauses. The results of this analysis are mainly built upon naturalistic examples from the Icelandic Gigaword Corpus (Steingrímsson (2019)), and judgment tasks, which consist of 20 questionnaires with 25 sentences each, as well as interviews. This dissertation claims that the main role of það is to check the case, gender and number features that target the relevant clausal complement and which can only be checked by DPs. In the absence of such features, það is unnecessary and is therefore dropped. However, það is not dropped if a head that subcategorizes for a clausal complement bears a feature that triggers Merge of a DP (see Heck and Müller (2007)), or if a clause is moved from its merge position to check a D-feature, e.g. to Spec,T. The hypothesis presented here differs from previous accounts on clausal nominalization in Icelandic, in particular Thráinsson (1979), who claimed, following Kiparsky and Kiparsky (1971), that factivity is the main trigger of clausal nominalization in Icelandic: factive predicates would tend to select more complex structures for their complements (i.e., nominalized clauses) than non-factives. The results presented in this thesis show that factivity is inadequate to clearly explain the distribution of clausal nominalization across syntactic positions. Various facts support the main hypothesis of this dissertation. Non-nominalized clauses are preferable in positions where nominative and accusative case are assigned, except in e.g. Spec,T and Spec,Appl, where nominalization is mandatory in absence of extraposition. On the other hand, dative and genitive are highly likely to trigger clausal nominalization. A similar contrast can also be observed with post-copular clauses, where the determiner, which agrees with the gender and number of the subject, is dispreferred if it has to surface in neuter singular, but it is more likely to emerge if the gender and/or the number features of the pronoun are non-default. These results indicate that default features related to case, gender and number, such as nominative, singular or neuter, are not formal features to check in narrow syntax, which cause það to be dropped. Such a conclusion aligns with theories which, for instance, consider nominative and accusative configurationally derived, like Dependent Case Theory (see e.g. Yip et al. (1987); Marantz (2000); Preminger (2011)). From a structural perspective, this dissertation also proposes that nominalized clauses are DPs and non-nominalized clauses emerge as CPs at the surface. However, all clauses that are merged in DP positions are originally merged as DPs and only undergo a process of structural removal if they land in a position in which no feature needs to be checked by það, yielding a non-nominalized clause. These claims are supported by the fact that: a) an item can only be extracted from a clausal argument if it is not nominalized; b) nominalized clauses as well as DPs are ungrammatical when they replace the clausal complement of verbs like þvinga ‘force’ or hjálpa ‘help’. As for structural removal, it is supported by the fact that obligatory nominalization caused by lexical case assignment can be altered by extraction, which causes það to become ungrammatical while the extracted DP item has its case overwritten with lexical case. This suggests that the DP shell is not longer present to check case. By comparing clausal nominalization in Icelandic and other languages (Swedish, German, Persian and Russian), this dissertation also shows that, independently of whether a language displays a morphological case system, structural case does not trigger clausal nominalization. Lexical case, on the other hand, triggers clausal nominalization specifically in those languages that have a morphological case system. Moreover, languages without a morphological case system tend to generalize how nominalized clauses are distributed: nominalization can become optional across all syntactic positions (as in Swedish) or it can become mandatory in situ as a general rule (this is the case of Persian). However, all the languages studied in this comparison show that clausal subjects must be nominalized in Spec,T unless they can escape that position. This suggests that D-feature checking is a common trigger of clausal nominalization cross-linguistically.
A Nationwide Study on Primary Aldosteronism in Iceland. From Detection to Immunohistochemistry and Genetic Testing.
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025-06-10) Gunnarsdóttir, Hrafnhildur; Helga Ágústa Sigurjónsdóttir; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Introduction Primary aldosteronism (PA) is the most common cause of secondary hypertension (HT), accounting for up to 29% of cases of resistant HT and 14% in general practice. Familial hyperaldosteronism (FH) is a rare cause of PA. The most common presentation of PA is HT with normal potassium levels. PA is widely underdiagnosed, and diagnostic delay reduces treatment efficacy. Early detection and specialized treatment are crucial as PA carries significantly higher cardiovascular risk than essential HT. Adrenal venous sampling (AVS) is the gold standard method to differentiate between unilateral and bilateral PA. Adrenalectomy is potentially curative for the unilateral group, while bilateral disease is managed with mineralocorticoid receptor antagonists (MRA). Immunohistochemistry (IHC) has advanced the histopathological diagnosis of unilateral PA and shown potential in predicting outcomes. Standardized methods for outcome evaluation were introduced recently. The aims of this thesis were to investigate the incidence of PA in Iceland during the study period and assess whether it is underdiagnosed. Additionally, to compare results from screening and confirmatory tests between AVS subgroups and evaluate treatment outcomes. Another objective was to assess long-term outcomes and follow-up needs by classifying patients based on IHC. Finally, we aimed to explore the role of the posture test (PT) and screen the appropriate patients for FH. Methods In 2007, an evidence-based PA work-up protocol was introduced in Landspítali National University Hospital of Iceland. The study cohort consisted of all adults diagnosed with PA during the 10-year period 2007–2016. Screening was performed by measuring morning serum aldosterone, direct renin concentration and 24-hour urinary excretion of aldosterone (UEA). PA was confirmed through the recumbent saline infusion test. All patients underwent adrenal computed tomography (CT) and a 4-hour PT. AVS was used for subtyping. Unilateral PA was treated with laparoscopic adrenalectomy and bilateral PA was managed with MRA. During follow-up visits, blood pressure (BP) was measured, need for potassium supplementation evaluated, and antihypertensive treatment assessed. Outcomes were evaluated based on the alterations in BP, count of antihypertensives, and need for potassium supplementation. Clinical outcomes were further assessed using the Primary Aldosterone Surgical Outcome criteria and the Primary Aldosteronism Medical Outcome criteria. IHC was performed to reevaluate routinely stained tissue samples and histopathological diagnoses using The International Histopathology Consensus for Unilateral Primary Aldosteronism (HISTALDO). Outcomes v were compared between HISTALDO subgroups and the need for follow-up was evaluated. First-degree relatives within the study cohort were screened for FH. Results Between 2007 and 2016, the incidence of confirmed PA in Iceland was 58 cases, 47% (n = 27) had unilateral disease and 53% (n = 31) bilateral. All patients had hypokalaemia at case detection or during work-up. Compared to the bilateral group, the unilateral group had a significantly higher UEA (33,9 vs. 24,6 μg, p < 0,001), post- infusion aldosterone levels (385 vs. 251 pmol/l, p = 0,01), and a higher frequency of adrenal nodules (19/27 vs. 10/31, p = 0,008). The bilateral group was significantly more responsive to posture (206% vs. 56%, p = 0,002). The PT had 81% sensitivity and 45% specificity for detecting bilateral PA. The combination of CT and PT was 96% specific and 32% sensitive for detecting unilateral PA. The AVS success rate was 86% (57/66), with 7/9 failed AVS performed on women (p = 0,08). Following IHC, classical histopathology was identified in 85% (22/26) of the unilateral group, with 23% (6/26) alteration of histopathological diagnoses. During follow-up, both the unilateral and bilateral group experienced significant reductions in systolic BP (p < 0,001, both groups), antihypertensive use (p = 0,002, p = 0,04, respectively), and potassium supplementation needs (p < 0,001, both groups). All patients with classical histopathology who achieved complete clinical success at 12 months (n = 5) remained normotensive without antihypertensives throughout the follow-up period (4–10 years). FH screening among brothers (n = 2) within the cohort yielded negative results. Conclusions This study highlights the underdiagnosis of PA in Iceland as the incidence was low and all patients in the cohort had hypokalaemia. Most cases presented with severe PA, emphasizing the need for increased awareness and broader screening indications at earlier stages of the disease. Unilateral PA was associated with more severe disease at presentation and a more significant reduction in antihypertensive use during follow-up, indicating better treatment response. The combination of PT and CT was highly specific for detecting unilateral PA. IHC improved histopathological diagnosis and was essential for accurate diagnosis. Additionally, follow-up could be individualized based on IHC results, though further research is needed to confirm this. Overall, our study underlines the need for improved screening, a simpler work-up, and personalized treatment and follow-up strategies to optimize PA care.
Mobility Patterns in Time and Space. Planning and Managing for Sustainable Tourism.
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Life and Environmental Sciences, 2025-06-23) Thórhallsdóttir, Gyda; Gunnar Þór Jóhannesson; Líf- og umhverfisvísindadeild (HÍ); Faculty of Life and Environmental Sciences (UI); Verk- og náttúruvísindasvið (HÍ); School of Engineering and Natural Sciences (UI)
This study evaluates a novel methodological approach for analyzing tourism mobility patterns in time and space within regions characterized by core-periphery mobility patterns, with Iceland and its key nature-based destinations serving as the study area. Traditional analyses often rely on overnight stay data; however, this approach fails to capture the full scope of visitor behavior in core-periphery contexts, where tourists frequently base themselves in urban cores and undertake day trips to rural peripheries. This study aims to enhance understanding of tourism mobility patterns in Iceland in relation to the aims of the Icelandic tourism authorities to improve sustainable tourism planning and management. The study emphasizes methodological advancements and the integration of diverse datasets to enhance analytical accuracy. Vehicle counters at nature-based destinations were employed to track visitor movements, enabling comparison with overnight stay data and departure data from Keflavík International Airport. Converting vehicle counts into visitor estimates formed the basis of the methodological exploration detailed in Papers 1 and 2. Paper 3 utilized these data to analyze mobility patterns across Iceland. Paper 4 tested Bluetooth sensors in the Jökulsárlón area, assessing their utility for tracking directional vehicle flows. The findings highlight the efficacy and cost-efficiency of automated methods. These tools overcome limitations related to recall bias and provide robust baseline data on mobility patterns. While these methods offer valuable insights, understanding the underlying motivations behind mobility patterns necessitates supplementary approaches. This methodology represents a significant advancement in studying tourism mobility in core-periphery regions, such as the Arctic regions.
The role of acoustic signals in interactions within and between species of cetaceans
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Life and Environmental Sciences, 2025-06) Selbmann, Anna; Arnar Pálsson; Líf- og umhverfisvísindadeild (HÍ); Faculty of Life and Environmental Sciences (UI); Verkfræði- og náttúrufræðisvið (HÍ); School of Engineering and Natural Sciences (UI)
Sound is an important mode for communication and mediates a variety of interactions within and between species. Sociality is thought to promote complexity in communication systems. Cetaceans are highly vocal and social and thus provide excellent models to study acoustic communication. This thesis aimed to investigate the role of acoustic signals in mediating interactions within and between species by examining the acoustic communication of Icelandic killer whales (Orcinus orca), their interactions with long-finned pilot whales (Globicephala melas) and the role of acoustics within the interactions. A detailed description of the acoustic repertoire of killer whales showed that it is largely shared across locations around Iceland, but that some locations also have unique call types that are not recorded elsewhere. Specific combinations of calls occurred more often than expected by chance and were recorded from several locations and different social clusters. Interactions between long- finned pilot whales and killer whales were common whenever both species co-occurred. While varying in intensity, these interactions appeared to be antagonistic and mediated acoustically. Killer whales showed clear avoidance responses to playbacks of long-finned pilot whale sounds, marked by fast and directed movement away from the sound source, initial increases in calling rate followed by a strong decrease, and increased cohesion and alignment of group members. These results show that Icelandic killer whales have a complex acoustic communication system, and that acoustics also plays an important role in mediating interactions with long-finned pilot whales, therefore demonstrating the importance of sound to these highly social marine top predators.
Mobilities in Melrakkaslétta. Ethnographic inquiry into placemaking, tourism and other mobilities on the margins
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Life and Environmental Sciences, 2025-06) Barðadóttir, Þórný; Gunnar Þór Jóhannesson; Katrín Anna Lund; Líf- og umhverfisvísindadeild (HÍ); Life and Environmental Sciences (UI); Verkfræði- og náttúruvísindasvið (HÍ); School of Engineering and Natural Sciences (UI)
This doctoral research explores the entanglements of placemaking, mobilities and the making of margins in the context of tourism. The research examines how places come to be and are transformed in relation to various mobilities within as well as through connections. This means investigating how mobilities can be both creators and undoers of margins, caused by distances, lacking connections, or both. The research makes use of flat ontology and relational materialism which rejects traditional dualism to instead assume that reality is created through interconnected, ever-evolving entanglements of material human and more-than-human relations. The research is qualitative, based on ethnographic investigation, and its main methods are participatory observation, interviews and conversations in the field of research, Melrakkaslétta peninsula. Melrakkaslétta is the northernmost area of the Icelandic mainland, situated far north of the main routes of domestic travel. The peninsula is furthermore about as far from the country’s main entering hub as is geographically possible within the country. The research investigates what makes the place Melrakkaslétta, how it has evolved and transformed in relation to more-than-human mobilities. The novelty of the research is its approach of conducting tourism research in a non-touristy rural area and it demonstrates the agency of mobilities in the creation of centres and margins, not least in the context of the potential of rural tourism development.
Investigating DNA methylation dynamics in normal and epigenetic machinery deficient neurodevelopment
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025-06-19) Ouyang, Juan; Hans Tómas Björnsson; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Epigenetic machinery (EM) factors are essential for modulating chromatin states and regulating gene expression. The Mendelian disorders of the epigenetic machinery (MDEM), caused by the mutations in the EM, often result in shared phenotypes, including intellectual disability and growth dysregulation. Many individuals with an MDEM diagnosis exhibit DNA methylation (DNAm) abnormalities in peripheral blood cells. However, whether DNAm dysregulation in MDEMs functionally links these two overlapping phenotypes remains unclear. In this thesis, we aim to identify potentially functionally important DNAm loci that show changes across multiple EM deficient neuronal models. We utilized CRISPR-Cas9 technology to individually knockout (KO) 46 EM genes in a disease relevant cell type, murine neuronal progenitor cells (mNPCs). We then assessed the whole-genome DNAm signatures via Oxford Nanopore Technology (ONT) sequencing. In parallel, we established a neuronal developmental model and observed some DNAm alterations during neuronal maturation. In this study, we observed extensive global demethylation in Dnmt1KOs, whereas Kmt2aKOs exhibited relatively mild DNAm changes. Despite the limited overlap in differentially methylated regions (DMRs) in cells with these two KOs, we uncovered a substantial overlap in differentially expressed genes (DEGs), with a strong positive correlation between the shared DEGs. These shared DEGs were enriched in pathways associated with neuronal development and transcripts involved in exit from the cell cycle, aligning with the increased number of TUBB3+ neurons in both KOs. In Dnmt1KOs, DMRs were significantly enriched in binding sites for key transcription factors (TFs), including EGR1, SP1, and MYC. The targets of these TFs also showed differential expression, suggesting a functional interplay between Dnmt1-mediated DNAm and TF activity. This highlights a potential crosstalk between DNMT1 and TFs in regulating gene expression in mNPCs. Beyond individual KO analyses, we systematically investigated DNAm patterns across all 46 EM-KOs. While most exhibited subtle DNAm alterations, notable exceptions such as Dnmt1 and Dnmt3b, showed more sizable DNAm changes. We identified 108 putative DMRs across 46 EM-KOs, with enrichment in promoter regions, suggesting a role for EMs in modulating promoter DNAm states. We therefore leveraged non-negative matrix factorization (NMF) to systematically cluster EM based on their DNAm profiles in promoters of protein coding genes, yielding 3 distinct EM clusters. Although a subset of EMs in each cluster exhibited disrupted neuronal maturation rates, these phenotypic changes did not entirely align with EM classification. Leveraging our experimental setup using cells derived from an F1 hybrid model (B6J paternal × FVB/NJ maternal), we identified allele-specific differentially methylated regions (AS-DMRs) using single nucleotide polymorphisms (SNPs). In control samples, we detected 1,074 AS-DMRs, some of which were disrupted in EM-KOs. Finally, phasing analysis revealed a single genome-wide significant DMR located in the 3´UTR of Zic4, which was differentially expressed during neuronal maturation. Functional validation via Zic4 knockdown experiments demonstrated impaired neuronal maturation, underscoring the potential role of Zic4 in EM-related neurodevelopmental processes. Our studies provide a valuable strategy of integrating ONT and RNA sequencing to investigate DNAm dynamics and gene expression changes in a disease relevant model (neurons). This integrative approach enables the detection of subtle but biologically meaningful candidates that may serve as therapeutic targets or diagnostic markers for MDEMs.
Scaling limits of weighted random tree-like planar maps
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Physical Science, 2025-04) Amankwah, Daniel; Sigurður Örn Stefánsson; Raunvísindadeild (HÍ); Faculty of Physical Sciences (UI); Verkfræði- og náttúrufræðisvið (HÍ); School of Engineering and Natural Sciences (UI)
The topic for this thesis lies in the scope of random planar maps. We investigate scaling limits of some models of discrete planar maps which are by construction “tree-like”. Specifically, we consider some models of “Halin-like” maps and series-parallel maps. The main aim is to study how some fundamental limiting objects appear as scaling limits of these models, hence affirming their universality properties. The Brownian Continuum Random tree (CRT), originally introduced by David Aldous is one of such limiting objects and has been known to be the limit of various different discrete models of uniformly sampled and weighted planar maps. The stable looptrees, due to Curien and Kortchemski is also of significant interest in this thesis. They are known to arise as scaling limit of models of tree-like maps for the case when each face in the maps is assigned a heavy tailed weight so that a typical face is in the domain of attraction of a stable law. One motivation for this thesis is to understand how these convergences generically happen for maps characterized via exclusion of minors. To our knowledge, series-parallel maps known to be characterized by not containing $K_4$ as a minor is the largest known collection of maps, defined by the exclusion of minors, which admits the CRT as a scaling limit.
An isoform specific role of the autophagy protein ATG7 in cancer
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2025-06-02) Larat, Clémence; Margrét Helga Ögmundsdóttir; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Autophagy is a cellular degradation process, important for maintaining cellular homeostasis. It has been shown to be involved in cancer initiation and development, either in a tumour-suppressive or promotive manner. The protein ATG7 is known to be essential for autophagy initiation by catalysing the lipidation of ATG8 proteins. Previously, we identified a short isoform, termed ATG7(2), which lacks 27 amino acids in the active domain of the protein, compared with the full-length ATG7(1), and is unable to lipidate ATG8 proteins. ATG7 is known to play a role in cancer progression and metastasis, and this role has long been associated with autophagy. However, recent studies suggest that this role could be, in part, autophagy-independent. Additionally, ATG7 has been shown to regulate YAP translocation to the nucleus, which is associated with poor prognosis in pancreatic adenocarcinoma (PAAD). Indeed, YAP is active in the nucleus, where it binds with a transcription factor, TEAD, to regulate the expression of genes involved in proliferation, migration, and immune regulation. Its activity is negatively regulated by the Hippo pathway, which is often dysregulated in cancer. To understand the role of ATG7(2), we analysed clinical data from publicly available databases. First, we analysed the correlation between ATG7(1) or ATG7(2) expression with survival across cancers. This showed that high ATG7(2) expression is linked with poor prognosis in PAAD. Then, we quantified the mRNA expression of ATG7(1) and ATG7(2) in healthy versus cancerous pancreatic samples and observed an increase in the expression of both isoforms in the tumour samples. When analysing this in PAAD clinical stages, we observed increased ATG7(2) expression in Stage IV compared with other stages. Finally, our analysis revealed that immuno-active tumours express higher levels of ATG7(2) than immunologically quiet ones, across cancers. Using CRISPR/Cas9 in a PAAD cell line, we selectively knocked out the canonical isoform ATG7(1) or total ATG7. We performed proliferation and migration assays on clones expressing different levels of endogenous ATG7(2). While total knock-out of ATG7 was linked with slow migration, ATG7(1)-/- showed faster proliferation and migration, especially with high levels of ATG7(2). To further explore the effect of ATG7(2) on PAAD, we performed cell fractionation to study the nuclear translocation of YAP in the different CRISPR cell lines. ATG7(1)-/- cells exhibited accumulation of YAP in both the cytoplasm and nucleus, while total ATG7 knock-out cells showed limited accumulation of YAP, and decreased nuclear translocation compared with the control cells. Together, these results suggest that ATG7(2) could regulate YAP activity in PAAD cells and drive migration and proliferation in an autophagy-independent manner. Finally, we used siRNA to specifically knock down ATG7(2) in control and ATG7(1)-/- cells. This led to decreased migration and proliferation rates in both cell types, as well as decreased YAP nuclear translocation and transcriptional activity in ATG7(1)-/- cells compared with control siRNA. This project highlights the importance of ATG7(2) in cancer, as well as its potential interest as a therapeutic target.
Inclusion of immigrant students in Iceland: Interplay of practices in compulsory schools, teacher education and research
(University of Iceland, School of Education, 2025-06) Wozniczka, Anna Katarzyna; Hafdís Guðjónsdóttir, Dr Per-Åke Rosvall; Deild kennslu- og menntunarfræði (HÍ); Faculty of education and pedagogy (UI); Menntavísindasvið (HÍ); School of Education (UI)
The rapid growth of immigration to Iceland in the past two decades has increased diversity in schools, sparking interest in educational research on multiculturalism and inclusion. This doctoral study investigates how schools, teacher education, and research practices influence immigrant students’ experiences in educational settings. Specifically, it examines how Icelandic compulsory schools, in rural and urban environments, along with teacher education and research, address opportunities for inclusion. The primary research question guiding this study is: How do the education system and education research engage with immigrant students to promote, develop, and sustain inclusive practices that leverage everyone’s social, linguistic, and cultural resources? This study fills a gap in existing research on inclusive and multicultural education by examining the interplay among research, teacher education, and school practices. It contributes to scholarship by offering a more inclusive perspective on cultural diversity in education. This research employs diverse qualitative methods, including observations, semi-structured interviews with educators and immigrant students, a collaborative self-study with teacher educators, and a critical autobiography that explores the researcher’s role. The data were coded, thematically analysed, and interpreted using the frameworks of inclusion, critical pedagogy, and the ecology of equity. Key findings highlight the critical role of teachers as agents of inclusion. Despite having limited experience and/or resources, many teachers actively engage all students in learning. Local support and caring relationships in schools further enhance students’ sense of belonging. However, systemic challenges such as resource limitations and demographic changes require broader reforms. Findings from teacher educators emphasise the importance of fostering classroom dialogue to engage diverse student groups, while the researcher’s critical autobiography underscores the necessity of reflexivity to avoid imposing personal biases. Together, these five articles provide theoretical, empirical, and practical insights into how inclusion of immigrant students is understood and enacted in schools, teacher education, and research. This work highlights the importance of cross-sector collaboration to promote equity and inclusion within Iceland’s increasingly diverse educational landscape.

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