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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.
Preoperative Optimization in Total Joint Arthroplasty. Infection risk and health effect. Cooperation of hospital and primary health care.
(University of Iceland, Faculty of Medicine, School of Health Sciences, 2026-09-26) Sigurðardóttir, María; Sigurbergur Kárason; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Lower extremity total joint arthroplasty (TJA) reduces pain and improves quality of life in individuals with end-stage osteoarthritis, with the majority of cases achieving long-lasting, favorable outcomes. However, infectious complications at the surgical site can be devastating and costly for both patients and society, requiring repeated surgeries and prolonged antibiotic treatment, and they are associated with increased morbidity and mortality. This has led to growing interest in preoperative optimization programs aimed at improving modifiable risk factors for infection, such as obesity, diabetes, anemia, malnutrition, smoking, and physical inactivity. These programs vary in design and scope, and most are retrospective. Little has been published about their efficacy. The aim of this project was to implement and evaluate a structured preoperative optimization pathway to reduce infectious and general complications after TJA and to assess its impact on patient health overall. Methods This was a prospective case control study examining a multifactorial optimization process coordinated between hospital and primary health care. Patients in the control group were already on the TJA waiting list and had received conventional preoperative preparation. They were included one week before surgery. Patients in the intervention group were enrolled during a visit at the outpatient orthopedic clinic after referral from primary health care 6 –12 months before surgery. Initial assessment included blood tests and BMI recording, followed by a primary health care visit within three weeks for review and management. Patients with BMI ≥ 40 were referred to a clinical nutritionist, and those with vitamin D < 50 nmol/L were advised to take supplements. Malnutrition risk was also assessed. One week before surgery, both groups underwent blood tests and BMI measurements and completed a questionnaire regarding preoperative preparation. Both groups then received the same follow-up. Data collected included demographics, surgery details, comorbidities (ASA physical status classification), laboratory values, transfusions, hospital stay length, complications, and mortality. Superficial surgical site infections (SSIs), periprosthetic joint infections (PJIs), reoperations, new diagnoses, postoperative health events, and Emergency Room (ER) visits and hospital/Intensive Care Unit (ICU) admissions were recorded. Results The control group consisted of 738 of 744 consenting patients included in the study one week before operation. Operations took place between August 2018 and September 2020. The intervention arm consisted of 746 of 1,010 consenting patients included at a median of 307 days before operation. Operations in this group took place between march 2019 and december 2022, with 259 exclusions in cases in which patients declined surgery when offered. Surgery took place during the COVID-19 pandemic in 5% of cases in the control group versus 77% in the intervention group. The initial results came from the control group as patients in this group underwent surgery earlier. These results revealed an association between obesity and dysglycemia/diabetes and superficial SSI, suggesting potential benefits of risk factor modification. The optimization process within the intervention group resulted in improvement in patient engagement and in metrics such as weight, anemia, HbA1c, and vitamin D. The baseline characteristics of the two groups one week before operation were similar except that the intervention group had substantially more comorbidities (ASA class 3-4, 32% versus 23%). Despite having more comorbidities, the intervention group presented lower rates of superficial SSI at 6 weeks post-op when adjusted for age, sex, and ASA class (OR 0.64, 95% CI 0.42–0.97). Overall surgical site complications were also lower (11.3% vs. 15.7%; difference 4.5%, 95% CI -8.0 to -1.0). At one year, superficial SSI was less common in the intervention group (5.9% vs. 7.9%, HR 0.67, 95% CI 0.45–1.01), though this finding was not statistically significant. In the control group, elevated BMI (≥ 30) and HbA1c (≥ 42 mmol/mol) were associated with superficial SSI, but this association was not observed in the intervention group. At three years, PJI was more common in the intervention group (2.0% versus 1.1%, HR 1.80, 95% CI 0.76–4.30), though the difference between groups was not significant. Most PJIs developed from superficial SSI (80% in the intervention group and 88% in the control group), with 95% of the superficial SSIs in the intervention group and 98% in the control group occurring within six weeks. Progression from superficial SSI to PJI was more common in the intervention group (27.3%) compared to the control group (12.1%). At three years, there was no significant difference between the groups regarding new health-related diagnosis and events nor mortality. Conclusion A structured preoperative optimization pathway improved modifiable risk factors and reduced short-term superficial SSIs and surgical site complications. However, it did not significantly affect long-term rates of SSIs, PJIs, or overall health and mortality. External factors, such as the COVID-19 pandemic and transfer of TJA to other facilities, may have influenced results. These findings highlight the need for prospective studies on optimization programs and further evaluation of organizational and practice changes in patient care.
Innritun nýnemahópa og námsframvinda í framhaldsskóla út frá efnislegri, félagslegri og menningarlegri stöðu nemenda á tímum samkeppnisprófa.
(University of Iceland, School of Education, 2025-09) Jónsson, Þorlákur Axel; Amalía Björnsdóttir, Ólöf Garðarsdóttir; Menntavísindasvið (HÍ); School of Education (UI)
Það varðar miklu fyrir bæði einstaklinga og þjóðfélag að nemendum vegni vel í námi og því ekki að undra að bæði stjórnvöld og almenningur hafi sýnt framhaldsskólum áhuga. Framhaldsskólastigið hefur verið í deiglu breytinga af hálfu yfirvalda menntamála en á sama tíma sætt gagnrýni fræðimanna sem hafa dregið upp mynd af takmörkuðum framgangi í námi og skólakerfi sem endurnýi félagslega lagskiptingu þjóðfélagsins. Á fyrsta áratug 21. aldar var tímabili fjölgunar framhaldsskóla við það að ljúka. Athygli yfirvalda beindist að aukinni skilvirkni framhaldsskólakerfisins með styttri námstíma og minna brotthvarfi nemenda. Átök í þjóðfélaginu um þessar breytingar ásamt áralangri reynslu af kennslu í framhaldsskóla vakti spurningar höfundar um hvaða félagslegu gangvirki væru að verki í framhaldsskólakerfinu og urðu þær hvati þessarar rannsóknar. Rannsökuð var innritun nýnema í framhaldsskóla og námsframvinda þeirra út frá efnislegri, félagslegri og menningarlegri stöðu þeirra á tíma samkeppnisprófa, sem voru hin samræmdu próf við lok grunnskóla; próf sem réðu því hver gæti innritast í hvaða framhaldsskóla. Rannsóknin tekur til árgangs nemenda sem hóf framhaldsskólanám árið 2006 og honum fylgt eftir fram til 2012. Rannsóknarspurningar voru um að hvaða marki einkenni þeirra hópa nýnema sem innrituðust í einstaka skóla væru til marks um félagslega aðgreiningu og hver tengsl þjóðfélagsstöðu og námsgengis í framhaldsskóla hafi verið. Til þess að svara þeim var ljósi varpað á tengsl þjóðfélagsstöðu og námsárangurs meðal nýnemahópa framhaldsskóla, hvernig nemendur notuðu möguleika sína til þess að velja skóla, hver námsstaða hópsins var í lok rannsóknartímabilsins 2012 og hvernig þessi atriði tengdust þjóðfélagsstöðu nemenda og einstaka framhaldsskólum. Í ritgerðinni var leitað skýringa á þeim félagslegu ferlum sem réðu gangi mála við innritun og námsframvindu. Leitað var svara við því hvort skýringar á því í hvaða skóla nemendur innrituðust beri að leita í félagslegum bakgrunni þeirra eða í eigin framlagi í námi, hvort og hver áhrif af rýmri reglum við innritun á höfuðborgarsvæðinu hafi verið á þá félagslegu ferla sem að verki voru við innritunina. Rannsóknarefni af þessu tagi hafa fengið vaxandi athygli bæði alþjóðlega og á Íslandi. Til grundvallar rannsókninni voru notaðar tvenns konar fræðahefðir innan félagsfræði menntunar. Annars vegar kenning Bourdieu um mikilvægi skólakerfisins í endurnýjun félagslegra yfirráðatengsla í krafti samsvörunar menningarauðs nemenda og skóla. Hins vegar kenning Coleman um hlut athafna nemenda út frá þjóðfélagsstöðu í félagslegum ferlum sem móti bæði athafnirnar og þær félagslegu aðstæður sem þarfnast skýringa.Byggt var á gögnum frá opinberri stjórnsýslu og úr fjölþjóðlegu yfirgripsmiklu rannsóknarverkefni (PISA). Gögnin voru annars vegar skrár Hagstofu Íslands yfir skólavist nemenda og hvaða prófum þeir luku á tímabilinu og hins vegar svör nemenda við spurningum sem lagðar voru fyrir þá í PISA könnuninni vorið 2006. Gögnin taka til þess árgangs nemenda sem fæddur var árið 1990. Þau eru með þversniði varðandi námsárangur og þjóðfélagsstöðu en langsniði varðandi námsframvindu á framhaldsskólastigi. Mikilvægustu breytur rannsóknarinnar voru efnisleg, félagsleg og menningarleg staða nemenda eða þjóðfélagsstaða, viðhorf nemenda til grunnskólans sem þau gengu í og einkunnir þeirra á samræmdum prófum í stærðfræði og íslensku. Breytunni fyrir þjóðfélagsstöðu var oftast skipt upp í þá kvarða yfir menntun foreldra, stöðu þeirra á vinnumarkaði og efnislegar eigur heimila sem mynduðu hann. Við tölfræðilega úrvinnslu var sett fram lýsandi tölfræði og gerðar voru línulegar- og tvíkosta fjölbreytu aðhvarfsgreiningar fyrir nemendahópinn í heild og fyrir einstaka framhaldsskóla. Einnig voru gerðar línulegar- og tvíkosta fjölstiga fjölbreytu aðhvarfsgreiningar þar sem athugað var hvaða munur kom fram á milli nemendahópa framhaldsskóla leiðrétt fyrir einkennum einstakra nemenda. Þeim aðferðum hefur lítið verið beitt í íslenskum menntarannsóknum fram til þessa en ritgerðin er framlag í að kynnast möguleikum slíkrar tölfræðigreiningar og að koma orðfæri hennar á íslenskt mál. Niðurstöður rannsóknarinnar sýna að félagsleg aðgreining var áberandi við innritun í einstaka skóla og munaði miklu á þjóðfélagsstöðu nýnemahópa þeirra skóla sem innrituðu nemendur með hæstu stöðuna og þeirra sem innrituðu nemendur með lægstu stöðuna. Munur á meðaleinkunnum nýnemahópa í íslensku og stærðfræði á samræmdum prófum við lok grunnskólans var einnig mikill. Hægt er að túlka innritunina sem félagslegt aðgreiningarferli, en með þeim fyrirvara að takmörkuð tengsl einstakra þátta hins félagslega uppruna við mun milli framhaldsskóla draga úr skýringargildi þeirrar hugmyndar. Einnig er hægt að túlka niðurstöður tölfræðilegra greininga sem svo að nám nemenda hafi verið lykilatriði fyrir vegferð þeirra um framhaldsskólakerfið frekar en félagslegur bakgrunnur. Fyrri námsárangur reyndist hafa meira að segja bæði um innritun og námsgengi í framhaldsskóla en allar aðrar breytur sem athugaðar voru. Þetta gilti bæði fyrir hóp nemenda í heild og fyrir framhaldsskóla sem heild. Einkunnir í stærðfræði í grunnskóla skýrðu breytileikann í námslokum með sterkum og markverðum hætti. Samkvæmt því skipti takmörkuðu máli fyrir námsframvindu á framhaldsskólastigi í hvaða tiltekna framhaldsskóla nemendur innrituðust. Þættir tengdir menntun og menningu heimila, þættir á borð við lengd skólagöngu foreldra, hámenningarlegar eigur og bókaeign heimila, tengdust námsárangri, innritun og námslokum á framhaldsskólastigi meira heldur en þættir tengdir atvinnustöðu, efnislegum gæðum eða tekjum heimila. Athygli vekur að stúlkur af lágum stigum virðast hafa notað góðan námsárangur í grunnskóla til þess að innritast í tiltekna framhaldsskóla þar sem þjóðfélagsstaða var almennt hærri en þeirra sjálfra. Einnig virðast hærri einkunnir á samræmdum prófum hafa verið nemendum á landsbyggðinni hvatning til þess að halda áfram námi. Ritgerðin bætir við þekkingu á því hvernig innritun var háttað þegar samkeppnispróf réðu möguleikum nemenda á innritun í skóla í norrænu skólakerfi verðleika. Framhaldsskólakerfið hefur tekið breytingum frá því þessi ritgerð drepur niður fæti. Samræmd samkeppnispróf eru ekki lengur lögð fyrir nemendur í lok grunnskóla og námstími til stúdentsprófs hefur verið styttur. Stjórnvöld menntamála hafa lýst nauðsyn þess að frekari skipulagsbreytingar verði gerðar á skólastigi framhaldsskólans á borð við sameiningar framhaldsskóla. Það hlýtur að vera umhugsunarefni að svo mikill munur skuli koma fram á þjóðfélagsstöðu nýnemahópa framhaldsskóla. Hvort sem það er einkenni skilvirkni kerfisins, stéttaskiptingar, eða bæði, hlýtur það einkenni framhaldsskólakerfisins að fá athygli stjórnvalda. Áhugavert væri að rannsaka hvaða áhrif afnám samræmdra prófa hefur haft á félagslega aðgreiningu innan framhaldsskólakerfisins. Ritgerðin er því framlag til stefnumótunar í framhaldsskólakerfinu með því að draga fram eiginleika þess og virkni áður en það fékk þá umgjörð sem nú er. Þrátt fyrir hina félagslegu aðgreiningu er ályktað að skólakerfi framhaldsskóla hafi haft sterk einkenni þess að vera sanngjarn samvinnuvettvangur þar sem verðleikar hafi ráðið för frekar en uppruni. Þörf er á frekari rannsóknum til þess að greina skipulag skólastarfs og skólakerfis framhaldsskóla. Tryggja þarf að nemendur njóti jafnræðis þannig að hæfileikar þeirra og atorka ráði vegferð þeirra í skólakerfinu
Ölvis rímur sterka og Bragða-Ölvis saga. Handrit, miðlun og þróun
(Háskóli Íslands, Hugvísindasvið, Íslensku- og menningardeild, 2025-09-04) Freysdóttir Njarðvík, Teresa Dröfn; Aðalheiður Guðmundsdóttir; Íslensku- og menningardeild (HÍ); Faculty of Icelandic and Comparative Cultural Studies (UI); Hugvísindasvið (HÍ); School of Humanities (UI)
Rannsókn þessi fjallar um Ölvis rímur sterka og Bragða-Ölvis sögu og miðast við að endurmeta aldur rímnanna sem og prósagerðarinnar, auk þess sem leitast er við að varpa ljósi á þróun íslenskra bókmennta með sérstakri áherslu á Ölvis rímur sterka og Bragða-Ölvis sögu. Í upphafi er fjallað um þróun rímnahefðarinnar fram til siðbreytingar, og í framhaldinu eru rímurnar og sagan athugaðar og settar í samhengi við bókmenntaþróun síðmiðalda. Textaútgáfur á rímunum og sögunni, eftir öllum varðveittum textavitnum, fylgja verkinu í viðauka, þar sem efnið er að mestu óútgefið. Rannsóknin miðast því ekki einungis við það að auka við þekkingu á bókmenntaflóru Íslands á fyrri öldum, sagnaþróun og samblöndun hefða, heldur tryggir hún einnig aðgengi að þessum áður óútgefnu textum og kemur þeim þar með inn í fræðilega jafnt sem almenna umræðu. Í ritgerðinni er leitast við að útskýra íslenska bókmenntahefð og sagnaþróun og skilja hvernig frásagnir „flökkuðu“ á milli bókmenntategunda og voru aðlagaðar í breytilegu formi í takt við samfélagið. Leitast er við að aldursgreina rímurnar og prósagerðina, greina samband þeirra innbyrðis (breytingar á efnistökum, lesbrigði og tilfærslu milli miðlunarforma) en einnig samband þeirra út á við (þ.e. tengsl við annað efni og hvernig efnið um Ölvi passar inn í bókmenntahefð og þróun á Íslandi). Spurt verður hvaða efni hafi legið að baki rímunum og hvernig efnið um Ölvi tengist fornaldarsögum, riddarasögum og konungasögum, en formgerð, eða flétta, í rímunum virðist benda til þess að flóknari, lengri og ítarlegri frásögn hafi verið uppspretta rímnaflokksins um Ölvi. Þar sem rímur voru, næstum undantekningarlaust, ortar eftir áður skrifuðum og þekktum sögum er ekki fjarri lagi að spyrja hvort efnið um Ölvi sé komið frá glataðri prósafrásögn. Í framhaldinu er svo spurt hversu gamlar Ölvis rímur sterka eru og hvenær sagan sem lá að baki hafi verið þekkt, hvaða sagnahefð efnið tilheyri og hvaða þróun sé greinileg af breytingum þess. Að lokum er spurt eftir hvaða leiðum efnið varðveittist og hvernig það breyttist við tilfærslu á miðlunarformum og milli handrita, hvaða lögmál eru bundin við frásagnarformið og hvar mörk skrifarans til að hafa áhrif á textann liggja. Reynt verður að svara þeim spurningum hvenær og hvernig prósagerðin varð til og hvað breytist við tilfærslu efnis milli miðla, svo sem frá prósa yfir í rímur og aftur úr rímum yfir í prósa. Leitast verður við að skýra tengsl Ölvis rímna sterka við aðra rímnaflokka og rímnahefðina í heild sinni ásamt tengslum Bragða-Ölvis sögu við bókmenntir miðalda og aðrar afleiddar rímnasögur. Áhersla er lögð á að tengja söguna bókmenntaþróun á Íslandi og þróun rímnahefðarinnar á elstu skeiðum. Í þessu samhengi verður spurt hvað breytingar á efninu og textanum geti sagt okkur um ritunartímann, samfélagið sem varðveitti söguna og hugmyndafræði þess.
Towards Unsettling the Auto-institution of Colonial Logics: Methodological Self-reflexivity and the Sociogenic Reconfiguration of Social Structures and Cognitive Regularities
(University of Iceland, School of Humanities, Faculty of Icelandic and Comparative Cultural Studies, 2025-05-27) Nassar, Claude; Björn Þorsteinsson; Íslensku- og menningardeild (UI); Faculty of Icelandic and Comparative Cultural Studies (UI); Hugvísindasvið (HÍ); School of Humanities (UI)
This dissertation is concerned with a migratory mode of experiencing a modernised and globalised social environment, tracing a trajectory whose origin lies in the territories of the polity of Lebanon. It develops an understanding of the modern order that accounts for the systemic (re)emergence of social domination with in it. Such an understanding is grounded in a decolonial philosophical framework informed by theories on epistemology and cognition, developed through a methodology in which auto-ethnography, systems studies, artistic practice, and casual conversations, intersect. This dissertation studies collectively formed narratives and auto-instituting social systems; it is a formulation of experiences and experiments with and within social systems in relation to different levels of organisation, through a perspective informed by experiences of displacement due to crises—wars and economic crises. Specifically, it explores the situated relational expression of the processes through which the modern order is reproduced on different levels (scales) of organisation, to then think through the socio-political importance and urgency of the redefinition of organisational logics, systematically enacted patterns, and narratives within collectives held together by intersectional alignments, rather than by managerial structures. Accordingly, this dissertation investigates the colonial institution of a globalised modern mode of social organisation in order to argue that modern social structures limit the human experience to possibilities that reproduce the modern order and its colonial logic. By drawing from the work of Sylvia Wynter and Frantz Fanon, it investigates the auto-institution of a modern/colonial logic within modes of being, knowing, and material provisioning, to then explore how the automatic reproduction of modern relational structures can be unsettled to make way for situated, communal, and emergent structures.
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.

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