39449 research outputs found
Sort by
Evaluation of early chemotherapy response by combining static- and dynamic [18F]FDG-PET with diffusion-weighted MRI in subcutaneous patient-derived endometrial cancer mouse models
No full textBackground: The combination of carboplatin and paclitaxel is the standard chemotherapy for treatment of high-risk and recurrent endometrial cancer. Evaluation of treatment response by diagnostic imaging is routinely carried out months after start of treatment, and is based on changes in tumor size or appearance of new metastases. The aim of this study was to evaluate early chemotherapeutic response in two subcutaneous endometrial cancer mouse models generated from patient-derived organoids using static- and dynamic [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) and diffusion-weighted (DW) magnetic resonance imaging (MRI). Mice were injected bilaterally with endometrioid endometrial cancer grade 3 (EEC G3), International Federation of Gynaecology and Obstetrics (FIGO) stage 3C1 (Model A) or stage 1B (Model B) organoids (n = 15 mice). The mice were randomized into treatment (combined carboplatin and paclitaxel, nA=8 / nB=6 tumors) or control (saline, nA=8 / nB=8 tumors) groups. During tumor progression, the mice underwent T2-weighted (T2w) MRI, DW-MRI and dynamic [18F]FDG-PET at baseline/Day 0 (start of treatment), Day 3 (early) and Day 10 (endpoint) using a sequential PET-MRI small-animal scanner.
Results: At endpoint, tumor volumes at T2w-MRI (vMRI) were lower in the treatment groups in both models (p ≤ 0.029). The tumor metabolic rate (MRFDG) from dynamic PET, was significantly lower in the treatment group at the early timepoint (Day 3) and at the endpoint in Model A (p ≤ 0.042). In Model B, MRFDG was similar for both groups at Day 3 and at endpoint (p≥0.217). The 10 tumor voxels with the highest standardised uptake value (SUV10) from static [18F]-FDG-PET was significantly lower at endpoint in the treatment groups in both models (p ≤ 0.041), but not at the early timepoint (p≥0.083). Similarly, the tumor apparent diffusion coefficient (ADCmean) was significantly higher indicating treatment response at endpoint for treatment groups in both models (p ≤ 0.036).
Conclusions: Multimodal imaging is feasible for evaluation of early signs of treatment response in preclinical subcutaneous endometrial cancer models. The novel MRFDG dynamic PET imaging parameter seems most promising for detecting very early treatment response following chemotherapy.publishedVersio
Different Ways of Knowing: A Comparative Analysis of Perceived and Modeled Climate Change in Greenland
No full textAttempting to better understand how two different knowledge systems, such as experience-based knowledge and scientific knowledge compare and interact, this thesis dives into three case studies within Greenland. Here, qualitative data from climate modeling is analyzed and compared to the academic records of climate perceptions in the same regions. Across the regions of Avannaata, East and West Sermersooq, the recorded perceptions of change mostly corroborate the modeled data. However, some deviations occur, such as on the topic of precipitation in Avannaata. While the perceptions of change align with the records, showing a warming and increasingly unpredictable climate, these records of change show something the modeled data does not. Particularly interesting were the sentiments regarding the change, which showcased a nuanced and cultural view of the people within the climate, not just the climate itself. While the markers showcase the change well, exactly what this change means to people is better understood in the perceptual records of change. Here we see not just what climate changes are happening, but how they are experienced and relate to other aspects of their life, such as industry, culture, and politics. Rooted in climate, the two research questions I pose (\cref{subsec:problemStilling}), interact with complex and wicked problems. This thesis uses interdisciplinary methods to address a transdisciplinary topic of perceived climate change in Greenland. The complex and wicked issues that define the challenges call for reflexivity and participation. In this case, the framework of post-normal science (PNS) is an appropriate lens to view both the problem and potential future work. Acknowledging that while PNS might not be the answer or a solution to any of the problems, it might prove a useful tool to address these wicked climate issues.MasteroppgaveSDG350MAHF-SD
Tvangsplassering i barnevernsinstitusjon på grunnlag av lovbrudd - En kritisk analyse av bvl. § 6-2 (1) bokstav a
No full textMasteroppgave (70 sp) forskerlinjeJUS397MAJU
Estimating physical conditions supporting gradients of ATP concentration in the eukaryotic cell
No full textThe ATP molecule serves as an energy currency in eukaryotes (and all life), providing the energy needed for many essential cellular processes. But the extent to which substantial spatial differences exist in ATP concentration in the cell remains incompletely known. It is variously argued that ATP diffuses too quickly for large gradients to be established, or that the high rates of ATP production and use (sources and sinks) can support large gradients even with rapid diffusion—and microscopic models and detailed experiments in different specific cases support both pictures. Here, we attempt a mesoscopic investigation, using reaction-diffusion modeling in a simple biophysical picture of the cell to attempt to ask, generally, which conditions cause substantial ATP gradients to emerge within eukaryotic cells. If ATP sources (like mitochondria) or sinks (like the nucleus) are spatially clustered, large fold changes in concentration can exist across the cell; if sources and sinks are more spread, then rapid diffusion indeed prevents large gradients from being established. This dependence holds in model cells of different sizes, suggesting its generality across cell types. Our theoretical work will complement developing intracellular approaches exploring ATP concentration inside eukaryotic cells.publishedVersio
Overtaking solitary wave collisions for Whitham–Boussinesq systems
No full textThis study focuses on solitary waves and their pairwise interactions within two fully dispersive and weakly nonlinear models known as Whitham–Boussinesq systems. Solitary waves are numerically computed using an iterative Newton-type method, incorporating continuation in wave amplitude and speed. These computed solitary waves are then used as initial data to study overtaking collisions in both systems. Our findings show that both systems satisfy the geometric Lax-categorisation for two-soliton collisions. Additionally, numerical evidence suggests that one of the systems admits an algebraic Lax-categorisation, though within a different range than that originally demonstrated by Lax for the Korteweg–de Vries equation. However, this algebraic categorisation does not apply for the second system. Additionally, qualitative and numerical analyses of solitary waves governed by each Whitham–Boussinesq system, including their amplitude-velocity relations, are presented and compared using two independent approaches.publishedVersio
Queer Lawfare under the Far-Right: Legal and Rights-Based Mobilization by Queer Civil Society in Meloni’s Italy
No full textThis thesis explores how queer civil society actors in Italy engage in lawfare under a far-right-led government. In 2022, Giorgia Meloni became Italy’s first far-right prime minister in the history of the Italian Republic, marking a significant political shift with deep implications for queer people in the country. The current government has in fact used political and legal tools that target queer people and the organizations that fight for their rights.
The study examines how this hostile context reshapes the terrain of queer lawfare, analyzing how queer civil society actors legal and rights-based engage in strategies under the current political scenario.
The findings show that the closure of the legislative arena has prompted a strategic reorientation toward courts, seen as still independent and open to the actors’ claims. Yet judicial institutions in Italy offer only partial remedies, given structural constraints such as limited constitutional recognition for queer rights and a judiciary with restrained interpretive power. International arenas are also mobilized in response to the government’s hostility and institutional inertia, offering additional, though limited, avenues for pressure and recognition.
Administrative lawfare emerges as a key field of contention: bureaucratic tactics are used by the government to attack queer rights and restrict the operational space of queer organizations. This arena also escapes public scrutiny and parliamentary debate and remains difficult for civil society to access due to the lack of formal mechanisms for participation.
The research also highlights how organizations social lawfare is used, often at the local level, by queer organizations to achieve legitimacy, counteract anti-queer narratives and make their claims understandable, before aiming for legal change. This dimension intersects with what emerges as a broader strategy of adaptation and contestation by queer civil society actors respond, who adapt their tactics to the increasingly constrained space, while simultaneously contesting the government’s actions behind those constraints.Master's Thesis in Politics and Governance of Global ChallengesGOV380MASV-GLGO
Endotypes of hypertensive disorders of pregnancy across lifetime reproductive history and cardiometabolic outcomes
No full textBakgrunn: Nyoppstått forhøyet blodtrykk i svangerskapet (HDP) er forbundet med økt risiko for hjerte- og karsykdom hos mor. Det har vært voksende interesse for å bruke hele svangerskapshistorien for å identifisere klinisk relevante undertyper av HDP. Imidlertid har det meste av forskningen på området hittil ikke brukt informasjon hentet fra suksessive svangerskap.
Mål: Målet var å identifisere ulike HDP-undertyper gjennom å studere HDP-mønstrenenes assosiasjoner til kardiometabolsk sykdom.
Metoder: Vi brukte data fra Medisinsk fødselsregister i Norge, koblet til Dødsårsaksregisteret. Vi brukte moren som analyseenhet. Variabelen HDP ble generert fra fødselregisterdata om hypertensjon i svangerskapet, preeklampsi, eklampsi, og HELLP (hemolyse, økt leverenzym og lavt blodplatetall).
Resultater: Vi identifiserte tre undertyper HDP som kan ha betydning for videre forskning. Artikkel I viste at mødre med HDP, med fødsel til termin, og med senere fødsler uten HDP hadde samme risiko for død av hjerte- og karsykdom som mødre uten HDP. Artikkel II viste at mødre med HDP og for tidlig fødte barn med stor fødselsvekt, og mødre med bare et barn har den høyeste risiko for å dø av hjerte-karsykdom. Artikkel III viste at svangerskapsdiabetes og HDP er assosiert. Blant kvinner som opplever både svangerskapsdiabetes og HDP opptrer dette hyppigst i samme svangerskap. Blant kvinner som opplever begge komplikasjonene i ulike svangerskap er det vanligst å ha svangerskapsdiabetes etter et svangerskap med HDP.
Konklusjoner: Mødre med HDP har en heterogen risiko for død med hjerte-og karsykdom som dødsårsak. Viktige faktorer for assosiasjonen mellom hjerte- og karsykdom og HDP inkluderer antall fødsler, antall fødsler med HDP, rekkefølge av HDP fødsler, gestasjonsalder, og barnets størrelse.Background: A history of hypertensive disorders of pregnancy (HDP) is associated with long-term cardiometabolic diseases. There is increasing momentum in the field of HDP research to use life-course outcomes to identify clinically relevant subtypes of HDP. However, most of this research has focused on individual pregnancies with HDP and has not considered lifetime reproductive history.
Aims: The aims of this thesis were to identify endotypes of HDP by exploring patterns across the mother’s life course and their relationship to cardiometabolic diseases.
Methods: Population-based data was retrieved from the Medical Birth Registry of Norway and linked to the Norwegian cause of death registry. The main variable of interest was HDP, generated from the registry data on gestational hypertension, preeclampsia, eclampsia, and HELLP (hemolysis, elevated liver enzymes, low platelets).
Results: In Paper I, mothers with HDP and term delivery in their first birth and later births without HDP did not have increased risk of cardiovascular disease (CVD) mortality. In Paper II, mothers with HDP, preterm delivery, a larger than average infant, and only one lifetime birth were at exceptionally high risk of CVD death. In Paper III, HDP was associated with gestational diabetes, and co-occurred most often in the same pregnancy. The most common pattern of co-occurrence in different pregnancies across reproductive history was gestational diabetes mellitus in a pregnancy after HDP.
Conclusions: Mothers with a history of HDP have a heterogenous risk of cardiometabolic disease death depending on characteristics across every birth in their lifetime reproductive history. Factors to consider when predicting CVD mortality may include lifetime number of pregnancies, number of HDP pregnancies, order of HDP pregnancies, gestational age at delivery, and infant size.Doktorgradsavhandlin
Pharmacokinetic-pharmacodynamic modelling in a clinical pilot study of rituximab in multiple sclerosis: Towards personalized dosing interval
No full textAims: Rituximab (RTX) is used off-label for relapsing–remitting multiple sclerosis, although dosing regimens vary. Observational data suggest the standard 6-month interval may be extended and individualized. We aimed to develop a pharmacokinetic–pharmacodynamic (PKPD) model to describe patient-specific RTX concentrations and CD19+ lymphocyte counts.
Methods: Thirteen treatment-naïve patients initiated RTX treatment with 1000 mg intravenously. Blood samples were collected at 6 time points during the following 6 months. RTX concentrations and CD19+ lymphocyte counts were used to compare different PKPD using the nonlinear mixed-effects software Monolix.
Results: Initial pharmacokinetics of RTX could be described by a 1-compartment model with nonlinear target-mediated elimination of rituximab. Introduction of CD19+ lymphocyte counts as a pharmacodynamic marker resulted in comparable performance of a 1-compartment and a 2-compartment model and can provide descriptions of RTX concentrations and CD19+ lymphocyte counts in individual patients. In both models, nonspecific clearance (CL) contributes approximately 10 times more to the overall elimination than target-mediated clearance (kdeg,1; CL [1/day] = 0.075 ± 0.035 [median 0.061], kdeg,1 [mm−3/day] = 0.125 ± 0.311 [median 0.007] and CL [1/day] = 0.036 ± 0.027 [median 0.026], kdeg,1 [mm−3/day] = 0.004 ± 0.002 [median 0.003]).
Conclusions: The PKPD models were able to describe the data both in patients exhibiting enduring CD19+ lymphocyte depletion and in patients exhibiting signs of early CD19+ lymphocyte repopulation. Additional data are required to validate and advance models for prediction of repopulation dynamics and, eventually, individualized RTX dosing.acceptedVersio
Resilience, reflexivity, and decolonization: policy narratives in Kalaallit Nunaat
No full textBackground: Kalaallit Nunaat (Greenland) is undergoing rapid socio-economic and environmental transformations, particularly due to climate change, shifting governance structures and aspirations for political independence. These developments necessitate resilient policy approaches to support sustainable regional development while addressing historical and contemporary power dynamics.
Aim: This paper examines policy narratives in Kalaallit Nunaat, analyzing how they shape resilience building processes. Specifically, it explores the interplay between system oriented and community resilience approaches in national and regional policymaking.
Method: A policy narrative analysis was conducted through a review of national strategies, government reports and other public policy documents from 2011 to 2020. The study applies a decolonial lens to examine how these narratives frame resilience, governance and development priorities in Kalaallit Nunaat.
Results: Four key narratives were identified: (1) the independence narrative, (2) the regional inequality narrative, addressing governance centralization and disparities between Nuuk and smaller settlements; (3) socio-economic and demographic challenges narrative, highlighting population decline, labour market issues and social inequalities; and (4) and climate change narrative, framing environmental shifts as both risks and economic opportunities. While all narratives prioritize independence, they differ in their perspectives on governance structure, local agency, and resilience building strategies. The study finds that policy narratives often assume resilience as an outcome of economic growth and political reforms, rather than a structured community driven process.
Conclusion: A decolonial approach to policy development in Kalaallit Nunaat requires centering community perspectives and strengthening locally driven decision-making processes. Rather than treating resilience as an assumed outcome of economic growth, policies should actively support long-term resilience-builidng by addressing structural inequalities, ensuring inclusive governance and integrating local knowledge into decision-making. By balancing community driven priorities with national governance reforms, policies can better support sustainable and equitable development.publishedVersio
Gaveerververs adgang til ekstinksjon etter tinglysingsloven §§ 20 og 27
No full textMasteroppgaveJUS399MAJUR-2MAJU