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  • Public defence: 2017-04-24 10:15 S213h, Umeå
    Lind, Yvette
    Umeå University, Faculty of Social Sciences, Department of Law.
    Crossing a border: a comparative tax law study on consequences of cross-border working in the Öresund- and the Meuse-Rhine regions2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    “Crossing a Border“- A Comparative Tax Law Study on Consequences of Cross-Border Working in the Öresund- and the Meuse-Rhine Regions is a doctoral thesis on tax law and social security law focused on cross-border commuting in the two cross-border regions of the Öresund and Meuse-Rhine. Two mayor aims are addressed: (1) To analyse the problems associated with cross-border working in the Öresund region caused by the legal divergence between Swedish and Danish tax law. The focus lies on individual taxation (primarily legislation related to residents and non-residents), and the social security contributions applicable to these cross-border workers, i.e. cross-border workers regulated in Article 15, Appendix 4, of the Nordic tax treaty also known as the Öresund treaty and the avoidance of double taxation (through the application of tax treaties between the states involved). (2) By comparing the problems, and solutions, associated with cross-border workers in the Meuse-Rhine region, contributions to discussions and analyses on de lege ferenda, in relation to the taxation of cross-border workers in the Öresund region (short-term and long-term) are made.   

    A comparative study is therefore done, comprising the four states of Sweden, Denmark, Belgium and the Netherlands. This study includes international tax law (domestic tax law, tax treaty law and EU tax law), European Union law and social security law. A theoretical framework comprising coherence, congruence, legal pluralism and polycentricity is applied to the thesis in order to discuss and highlight problems referable to the legal framework applicable to cross-border working. Problems which are discussed comprise, for instance, cross-border working in two or more states at the same time, lacking predictability when anticipating tax-and social security contributions and the lack of coherence and congruence between the tax- and social security systems of the studied states. 

  • Public defence: 2017-04-26 13:00 N320, Umeå
    Olsson, Jan
    Umeå University, Faculty of Social Sciences, Department of applied educational science.
    GeoGebra, Enhancing Creative Mathematical Reasoning2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The thesis consists of four articles and this summarizing part. All parts have focused on bringing some insights into how to design a didactical situation including dynamic software (GeoGebra) to support students’ mathematical problem solving and creative reasoning as means for learning. The four included articles are:

    I. Granberg, C., & Olsson, J. (2015). ICT-supported problem solving and collaborative creative reasoning: Exploring linear functions using dynamic mathematics software. The Journal of Mathematical Behavior, 37, 48-62.

    II. Olsson, J. (2017). The Contribution of Reasoning to the Utilization of Feedback from Software When Solving Mathematical Problems. International Journal of Science and Mathematics Education, 1-21.

    III. Olsson, J. Relations between task design and students’ utilization of GeoGebra. Mathematical Thinking and Learning. (Under review)

    IV. Olsson, J., & Granberg, C. Dynamic software, problem solving with or without guidelines, and learning outcome. Technology, Knowledge and Learning. (Under review)

    Background

    A common way of teaching mathematics is to provide students with solution methods, for example strategies and algorithms that, if followed correctly, will solve specific tasks. However, questions have been raised whether these teaching methods will support students to develop general mathematical competencies, such as problem solving skills, ability to reason and acquire mathematical knowledge. To merely follow provided methods students might develop strategies of memorizing procedures usable to solve specific tasks rather than drawing general conclusions. If students instead of being provided with algorithms, are given the responsibility to construct solution methods, they may produce arguments for why the method will solve the task. There is research suggesting that if those arguments are based on mathematics they are more likely to develop problem solving and reasoning-skill, and learn the included mathematics better. In such didactic situations, where students construct solutions, it is important that students have instructions and tasks that frame the activity and clarify goals without revealing solution methods. Furthermore, the environment must be responsive. That is, students need to receive responses on their actions. If students have an idea on how to solve (parts of) the given problem they need to test their method and receive feedback to verify or falsify ideas and/or hypotheses. Such activities could be supported by dynamic software. Dynamic software such as GeoGebra provides features that support students to quickly and easily create mathematical objects that GeoGebra will display as visual representations like algebraic expressions and corresponding graphs. These representations are dynamically linked, if anything is changed in one representation the other representations will be altered accordingly, circumstances that could be used to explore and investigate different aspects and relations of these objects. The first three studies included in the thesis investigate in what way GeoGebra supports creative reasoning and collaboration. These studies focus questions about how students apply feedback from GeoGebra to support their reasoning and how students utilize the potentials of GeoGebra to construct solutions during problem solving. The fourth study examine students’ learning outcome from solving tasks by constructing their methods.

    Methods

    A didactical situation was designed to engage students in problem solving and reasoning supported by GeoGebra. That is, the given problems were not accompanied with any guidelines how to solve the task and the students were supposed to construct their own methods supported by GeoGebra. The students were working in pairs and their activities and dialogues were recorded and used as data to analyse their engagement in reasoning and problem solving together with their use of GeoGebra. This design was used in all four studies. A second didactical situation, differing only with respect of providing students with guidelines how to solve the task was designed. These didactical situations were used to compare students’ use of GeoGebra, their engagement in problem solving and reasoning (study III) and students’ learning outcome (study IV) whether the students solved the task with or without guidelines. In the fourth study a quantitative method was applied. The data from study IV consisted of students’ results during training (whether they managed to solve the task or not), their results on the post-test, and their grades. Statistical analysis where applied.

    Results

    The results of the first three studies show qualitative aspects of students solving of task with assistance of GeoGebra. GeoGebra was shown to support collaboration, creative mathematical reasoning, and problem solving by providing students with a shared working space and feedback on their actions. Students used GeoGebra to test their ideas by formulating and submitting input according to their questions and hypotheses. GeoGebra’ s output was then used as feedback to answer questions and verify/falsify hypotheses. These interactions with GeoGebra were used to move the constructing of solutions forward. However, the way students engage in problem solving and reasoning, and using GeoGebra to do so, is dependent on whether they were provided with guidelines or not. Study III and IV showed that merely the students who solved unguided tasks utilized the potential of GeoGebra to explore and investigate the given task. Furthermore, the unguided students engaged to a larger extent in problem solving and creative reasoning and they expressed a greater understanding of their solutions. Finally study IV showed that the students who managed to solve the unguided task outperformed, on posttest the students who successfully solved the guided task.

    Conclusions

    The aim of this thesis was to bring some insights into how to design a didactical situation, including dynamic software (GeoGebra), to support students' mathematical problem solving and creative reasoning as means for learning. Taking the results of the four studies included in this thesis as a starting point, one conclusion is that a didactical design that engage students to construct solutions by creative reasoning supported by GeoGebra may enhance their learning of mathematics. Furthermore, the mere presence of GeoGebra will not ensure that students will utilize its potential for exploration and analysis of mathematical concepts and relations during problem solving. The design of the given tasks will affect if this will happen or not. The instructions of the task should include clear goals and frames for the activity, but no guidelines for how to construct the solution. It was also found that when students reasoning included predictive argumentation for the outcomes of operations carried out by the software, they could better utilize the potential of GeoGebra than if they just, for example, submitted an algebraic representation of a linear function and then focused on interpreting the graphical output.

  • Public defence: 2017-04-28 09:00 Hörsal D, Unod T9, byggnad 1D, NUS, Umeå
    Popova, Dina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    In vitro cellular models for neurotoxicity studies: neurons derived from P19 cells2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Humans are exposed to a variety of chemicals including environmental pollutants, cosmetics, food preservatives and drugs. Some of these substances might be harmful to the human body. Traditional toxicological and behavioural investigations performed in animal models are not suitable for the screening of a large number of compounds for potential toxic effects. There is a need for simple and robust in vitro cellular models that allow high-throughput toxicity testing of chemicals, as well as investigation of specific mechanisms of cytotoxicity. The overall aim of the thesis has been to evaluate neuronally differentiated mouse embryonal carcinoma P19 cells (P19 neurons) as a model for such testing. The model has been compared to other cellular models used for neurotoxicity assessment: retinoic acid-differentiated human neuroblastoma SH-SY5Y cells and nerve growth factor-treated rat pheochromocytoma PC12 cells. The chemicals assessed in the studies included the neurotoxicants methylmercury, okadaic acid and acrylamide, the drug of abuse MDMA (“ecstasy”) and a group of piperazine derivatives known as “party pills”. Effects of the chemicals on cell survival, neurite outgrowth and mitochondrial function have been assessed.

    In Paper I, we describe a fluorescence-based microplate method to detect chemical-induced effects on neurite outgrowth in P19 neurons immunostained against the neuron-specific cytoskeletal protein βIII-tubulin. In Paper II, we show that P19 neurons are more sensitive than differentiated SH-SY5Y and PC12 cells for detection of cytotoxic effects of methylmercury, okadaic acid and acrylamide. Additionally, in P19 neurons and differentiated SH-SY5Y cells, we could demonstrate that toxicity of methylmercury was attenuated by the antioxidant glutathione. In Paper III, we show a time- and temperature-dependent toxicity produced by MDMA in P19 neurons. The mechanisms of MDMA toxicity did not involve inhibition of the serotonin re-uptake transporter or monoamine oxidase, stimulation of 5-HT2A receptors, oxidative stress or loss of mitochondrial membrane potential. In Paper IV, the piperazine derivatives are evaluated for cytotoxicity in P19 neurons and differentiated SH-SY5Y cells. The most toxic compound in both cell models was TFMPP. In P19 neurons, the mechanism of action of TFMPP included loss of mitochondrial membrane potential. In conclusion, P19 neurons are a robust cellular model that may be useful in conjunction with other models for the assessment of chemical-induced neurotoxicity.

  • Public defence: 2017-04-28 12:30 Lilla Hörsalen, KB3A9, Umeå
    Mathisen, Peter
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Environmental factors selecting for predation resistant and potentially pathogenic bacteria in aquatic environments2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The long history of co-existence of bacteria and their protozoan predators in aquatic environments has led to evolution of protozoa resistant bacteria (PRB). Many of these bacteria are also pathogenic to humans. However, the ecological drivers determining the occurrence of different types of PRB in aquatic environments, and the eco-evolutionary link between bacterial adaptation and the resulting implications for mammalian hosts are poorly known. This thesis examines the impact of nutrients and predation on PRB, as well as the ecological and evolutionary connection between their life in aquatic environments and mammalian hosts. In the first study seven bacterial isolates from the Baltic Sea were investigated for their plasticity of adaptation to predation. The response to predation showed large variation where some bacteria rapidly developed a degree of grazing resistance when exposed to predators. The rapid adaptation observed may result in bacterial communities being resilient or resistant to predation, and thus rapid adaptation may be a structuring force in the food web. With the aim to elucidate the link between occurrence of PRB and environmental conditions, a field study and a laboratory experiment were performed. In both studies three PRB genera were found: Mycobacterium, Pseudomonas and Rickettsia. PRB were found both in oligotrophic and eutrophic waters, indicating that waters of all nutrient states can harbor pathogenic bacteria. However, the ecological strategy of the PRB varied depending on environmental nutrient level and disturbance. Using an advanced bioinformatic analysis, it was shown that ecotypes within the same PRB genus can be linked to specific environmental conditions or the presence of specific protozoa, cyanobacteria or phytoplankton taxa. These environmental conditions or specific plankton taxa could potentially act as indicators for occurrence of PRB. Finally, using four mutants (with specific protein deletions) of the pathogenic and predation resistant Francisella tularensis ssp. holarctica, I found evidence of an eco-evolutionary connection between the bacterium´s life in aquatic and mammalian hosts (aquatic amoeba Acanthamoeba castellanii and a murine macrophage).  To a large extent F. t. holarctica use similar mechanisms to persist predation by protozoa and to resist degradation by mammal macrophages. To summarize I found a link between predation resistant bacteria in aquatic environments and bacteria that are pathogenic to mammals. Further, I showed that different environmental conditions rapidly selects for PRB with either intracellular or extracellular lifestyles. This thesis provides insights regarding environmental conditions and biomarkers that can be used for assessment of aquatic environments at risk for spreading pathogenic bacteria.  

  • Public defence: 2017-04-28 13:00 Nbvh 1031, Norra beteendevetarhuset, Umeå
    Diehl, Monika
    Umeå University, Faculty of Social Sciences, Department of Education.
    -Måste det här vara som en väckelserörelse?: en studie om (det som kallas) entreprenöriellt lärande i grundskolan, utifrån Basil Bernsteins begreppsapparat2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this compilation thesis is to describe prerequisites for what, in a Swedish educational context, is often called ‘entrepreneurial learning’ and to examine the possible influence that this has on school practice. The study was carried out in two lower secondary schools and was guided by the following two research questions. First, how is entrepreneurial learning reflected in educational practice regarding teaching, learning and assessment? Second, how has the phenomenon of entrepreneurship been recontextualized in educational discourse through politics and policy? Basil Bernstein’s concepts and theories have consistently been the point of departure for analysis. Altogether, 52 classroom observations were made, particularly focusing on the subjects of social science, science and mathematics. In addition, 8 individual interviews with teachers and 15 group interviews with pupils were conducted. For decades, national and international policy documents have promoted the need for a creative, innovative and flexible future working force; bringing this about has highly involved the education system. In Sweden, entrepreneurship was inscribed in the curriculum in 2011, and it is meant to run like a thread throughout education. In this study the broad approach of entrepreneurship in education, which is about generating an entrepreneurial mindset, is focused. Research points out various difficulties and dilemmas regarding the implementation of entrepreneurial learning. These difficulties and dilemmas are connected to concerns about perceived difficulties in relation to differences in school subjects, pupils’ backgrounds, degree of managerial support and/or collegial consensus and cooperation. The main findings are linked to recurrent difficulties regarding teaching methods and assessments in relation to entrepreneurial learning. Curricula and syllabi express explicit learning outcomes, which both teachers and learners perceive as being challenging to combine with entrepreneurial classroom work. This in turn links to an aspect which is often addressed in research—that is, the question about whether to use traditional or entrepreneurial (progressive) teaching methods. Curricula express a need for both, and teachers often find it difficult to find a functioning balance between them, not least because of current societal discussions and demands. In many respects, the implementation of entrepreneurial learning sends mixed messages. On the one hand, pupils are meant to develop entrepreneurial skills and competencies through cooperation and interaction within groups, and, on the other hand, the essence of entrepreneurship indicates competition; this is yet another dilemma addressed in the study. The study shows that, due to the schools’ different prerequisites regarding, for instance, teachers’ approaches and understandings and the schools’ catchment areas, entrepreneurial learning is performed somewhat different. Bernstein’s concepts and theories offer tools to explain and understand different aspects, including dilemmas and difficulties in relation to both classroom practice and social discourse.

  • Public defence: 2017-05-04 09:30 KBE301, Lilla Hörsalen (KBC), Umeå
    Vasconcelos, Francisco Rivera
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Effects of warming and browning on benthic and pelagic ecosystem components in shallow lakes2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The majority of lakes on Earth are shallow, unproductive and located at high latitudes. These lakes are experiencing big changes due to climate change, where two environmental drivers operate simultaneously, browning and warming. How they affect lake ecosystems is not well understood. Here, I addressed this issue by using a theoretical and an experimental approach. In particular, I generated model predictions and compared them with the results of a realistic large-scale experiment, where browning and warming were manipulated in a factorial design. In addition, model outcomes were compared with data from 12 unproductive lakes sampled along a gradient of browning. Another novelty of my thesis is that it integrates benthic and pelagic food web components in the model and experimental approaches. I found that browning affected the resources availability for benthic and pelagic producers in the model and in the experiment. With browning, benthic primary producers became increasingly light limited and declined, while pelagic producers became less nutrient limited and increased. Pelagic nutrient limitation was alleviated by two non-exclusive mechanisms. Browning directly enriched the water with nutrients, and browning indirectly increased the nutrient flowing from the sediment to the pelagic habitat via suppression of benthic producers. To tease apart these two mechanisms I applied structural equation modeling (SEM). The indirect evidence by SEM suggests that both mechanisms contributed equally to the pelagic nutrient concentration in the experiment. Interestingly, a model food web with only primary producers shows similar qualitative behavior as a food web with grazers and carnivores included. This happens because carnivorous fish exert strong top-down control in the more productive habitat, which relaxes grazing pressure on primary producers and increases resource limitation in the adjacent habitat. Biomass of benthic and pelagic consumers followed the same pattern as their resources. The lake data were largely congruent with model expectations and supported the findings of the experiment. Furthermore, the model also predicted a negative relationship between total phosphorus and both primary and fish production, which was observed across the 12 lakes. Warming effects were more complex. The model predicts that warming effects should depend on browning and are expected to be strongest in the more productive of the two (benthic and pelagic) habitats. For example, at low levels of browning the biomasses of benthic algae and fish are expected to decline with warming, which was observed in the experiment. In contrast, observed warming effects at high levels of browning deviated from model expectations. The mechanisms by which browning and warming interactively affect lake food webs are still poorly understood. This thesis offers a conceptual foundation for their further study through the integration of within- and between-habitat interactions.

  • Public defence: 2017-05-05 09:00 Hörsal E04, byggnad 6E, Norrlands universitetssjukhus, Umeå
    Lundberg, Ida
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Molecular understanding of KRAS- and BRAF-mutated colorectal cancers2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Colorectal cancer (CRC) is the third most commonly diagnosed malignancy in both men and women, and one of the leading causes of cancer-related deaths worldwide. One frequently mutated pathway involved in oncogenesis in CRC is the RAS/RAF/MAP kinase pathway. Oncogenic activation of KRAS and BRAF occur in 30‒40% and 5‒15% of all CRCs, respectively, and the mutations are mutually exclusive. Even though KRAS and BRAF are known to act in the same pathway, KRAS- and BRAF-mutated CRCs have different clinical and histopathological features. For example, BRAF mutation in CRC is tightly linked to microsatellite instability (MSI) and a CpG island methylator phenotype (CIMP), which is not seen in KRAS-mutated tumours. BRAF-mutated CRCs are also more often found in right-sided tumours. However, the underlying molecular reasons for these differences have not yet been defined.

    The overall aim of this thesis was to investigate molecular differences between KRAS- and BRAF-mutated CRCs to understand how KRAS and BRAF mutations differentially affect tumour progression. We used an in vitro cell culture system to explore molecular differences between KRAS- and BRAF-mutated CRCs and verified our findings using CRC tissue specimens from the Colorectal Cancer in Umeå Study (CRUMS).

    We found that BRAF mutation, but not KRAS mutation, was associated with expression of the stem cell factor SOX2. Furthermore, SOX2 was found to be correlated to a poor patient prognosis, especially in BRAF-mutated cancers. We further investigated the role of BRAF in regulation of SOX2 expression and found that SOX2 is at least partly regulated by BRAF in vitro. We continued by investigating the functional role of SOX2 in CRC and found that SOX2-expressing cells shared several characteristics with cancer stem cells, and also had down-regulated expression of the intestinal epithelial marker CDX2. There was a strong correlation between loss of CDX2 expression and poor patient prognosis, and patients with SOX2 expression were found to have a particularly poor prognosis when CDX2 levels were down-regulated. In conclusion, in these studies we identified a subgroup of BRAF-mutated CRCs with a particularly poor prognosis, and having a cancer stem cell-like appearance with increased expression of SOX2 and decreased expression of CDX2.

    Tumour progression is regulated by interactions with cells of the immune system. We found that BRAF-mutated CRCs were more highly infiltrated by Th1 lymphocytes than BRAF wild-type tumours, while the opposite was true for KRAS-mutated CRCs. Interestingly, we found that part of this difference is probably caused by differences in secreted chemokines and cytokines between KRAS- and BRAF-mutated CRCs, stimulating different arms of the immune response.

    Altered levels of expression of miRNAs have been seen in several malignancies, including CRC. We found that BRAF- and KRAS-mutated CRCs showed miRNA signatures different from those of wild-type CRCs, but the expression of miRNAs did not distinguish KRAS-mutated tumours from BRAF-mutated tumours.

    In summary, our findings have revealed possible molecular differences between KRAS- and BRAF-mutated CRCs that may explain some of the differences in their clinical and histopathological behaviour.

  • Public defence: 2017-05-12 09:00 KB.E3.01 Lilla Hörsalen, Umeå
    Jonna, Venkateswara Rao
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Class I Ribonucleotide Reductases: overall activity regulation, oligomerization, and drug targeting2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ribonucleotide reductase (RNR) is a key enzyme in the de novo biosynthesis and homeostatic maintenance of all four DNA building blocks by being able to make deoxyribonucleotides from the corresponding ribonucleotides. It is important for the cell to control the production of a balanced supply of the dNTPs to minimize misincorporations in DNA. Because RNR is the rate-limiting enzyme in DNA synthesis, it is an important target for antimicrobial and antiproliferative molecules. The enzyme RNR has one of the most sophisticated allosteric regulations known in Nature with four allosteric effectors (ATP, dATP, dGTP, and dTTP) and two allosteric sites. One of the sites (s-site) controls the substrate specificity of the enzyme, whereas the other one (a-site) regulates the overall activity.  The a-site binds either dATP, which inhibits the enzyme or ATP that activates the enzyme. In eukaryotes, ATP activation is directly through the a-site and in E. coli it is a cross-talk effect between the a and s-sites. It is important to study and get more knowledge about the overall activity regulation of RNR, both because it has an important physiological function, but also because it may provide important clues to the design of antibacterial and antiproliferative drugs, which can target RNR.

    Previous studies of class I RNRs, the class found in nearly all eukaryotes and many prokaryotes have revealed that the overall activity regulation is dependent on the formation of oligomeric complexes. The class I RNR consists of two subunits, a large α subunit, and a small β subunit. The oligomeric complexes vary between different species with the mammalian and yeast enzymes cycle between structurally different active and inactive α6β2 complexes, and the E. coli enzyme cycles between active α2β2 and inactive α4β4 complexes. Because RNR equilibrates between many different oligomeric forms that are not resolved by most conventional methods, we have used a technique termed gas-phase electrophoretic macromolecule analysis (GEMMA). In the present studies, our focus is on characterizing both prokaryotic and mammalian class I RNRs. In one of our projects, we have studied the class I RNR from Pseudomonas aeruginosa and found that it represents a novel mechanism of overall activity allosteric regulation, which is different from the two known overall activity allosteric regulation found in E. coli and eukaryotic RNRs, respectively.  The structural differences between the bacterial and the eukaryote class I RNRs are interesting from a drug developmental viewpoint because they open up the possibility of finding inhibitors that selectively target the pathogens. The biochemical data that we have published in the above project was later supported by crystal structure and solution X-ray scattering data that we published together with Derek T. Logan`s research group.

    We have also studied the effect of a novel antiproliferative molecule, NSC73735, on the oligomerization of the human RNR large subunit. This collaborative research results showed that the molecule NSC73735 is the first reported non-nucleoside molecule which alters the oligomerization to inhibit human RNR and the molecule disrupts the cell cycle distribution in human leukemia cells.

  • Public defence: 2017-05-12 09:00 E04_R1, Umeå
    Sandén, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Efficacy and safety of warfarin treatment in venous thromboembolic disease2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    As a major cause of morbidity and mortality treatment of venous thromboembolism is important, with the correct use of anticoagulants it is possible to greatly reduce both mortality and morbidity. Warfarin is among the most widely used anticoagulants being effective in treatment and prevention of venous thromboembolism with few negative side effects other than bleeding complications. With a narrow therapeutic window warfarin treatment requires constant monitoring and adjustments to stay effective without an increased bleeding risk.

    The aim of this thesis was to study the efficacy and safety of warfarin treatment in venous thromboembolic disease.

    Methods

    Using AuriculA, the Swedish national quality register for atrial fibrillation and anticoagulation, a cohort was created of patients registered with warfarin treatment during the study time January 1st 2006 to December 31th 2011, including all different indications for anticoagulation. In all four studies the study design was retrospective with information added to the cohort from the Swedish national patient register about background data and endpoints in form of bleeding complications in all studies and thromboembolic events in study 1 and 2. In study 3 and 4 information was added from the cause of death register about occurrence of death and in study 3 cause of death. In study 3, information from the prescribed drugs register about retrieved prescriptions of acetylsalicylic acid was added.

    Results

    In study 1 the mean TTR was found to be high both among patients managed at primary healthcare centres and specialised anticoagulation clinics at 79.6% and 75.7%. There was no significant difference in rate of bleeding between the two types of managing centres being 2.22 and 2.26 per 100 treatment years. In study 2 no reduction in complication rate with increasing centre TTR was seen for patients with atrial fibrillation with few centres having centre TTR below 70% (2.9%), in contrast to previous findings by Wan et al(1). For those with warfarin due to VTE where a larger proportion of the centres had centre TTR below 70% (9.1%) there was a reduction in complication rate with increasing centre TTR. Among the 13859 patients with treatment for VTE in study 3 age (HR 1.02, CI 95% 1.01-1.03), hypertension (HR 1.29, CI 95%1.02-1.64), Cardiac failure (HR 1.55, CI 95% 1.13-2.11), chronic obstructive pulmonary disease (HR 1.43, CI 95% 1.04- 1.96), alcohol abuse (HR 3.35, CI 95% 1.97-5.71), anaemia (HR 1.77, CI 95% 1.29-2.44) and a history of major bleeding (HR 1.75, CI 95% 1.27-2.42) increased the risk of bleeding during warfarin treatment. In study 4 both those with high iTTR and those with low INR variability had a low rate of bleedings at 1.27 (1.14-1.41) or 1.20 (0.94-1.21) per 100 treatment years compared to those with low iTTR and high INR variability having a rate of bleeding at 2.91 (2.61-3.21) or 2.61 (2.36-2.86) respectively. Those with the combination of both low iTTR and high INR variability had an increased risk of bleeding, hazard ratio HR 3.47 (CI 95 % 2.89-4.17). The quartile with both the lowest iTTR and the highest INR variability had an increased risk of bleeding with a hazard ratio 4.03 (3.20-5.08) and 3.80 (CI 95%, 3.01-4.79) compared to the quartile with the highest iTTR and lowest INR variability.

    Conclusion

    It is possible to achieve a safe warfarin treatment both in specialised anticoagulation centres and in primary health care. At initiation of treatment some of the patients at high risk of bleeding can be identified using knowledge about their background. With the use of quality indicators as TTR and INR variability during treatment those at high risk of complications can be identified and analysing treatment quality on centre level gives an opportunity to identify improvement areas among managing centres. With the addition of new treatment options warfarin can still be the most suitable option for some patients, being safe and effective when well managed.

  • Public defence: 2017-05-12 10:15 Hörsal B, Samhällsvetarhuset, Umeå
    Brännström, Malin
    Umeå University, Faculty of Social Sciences, Department of Law.
    Skogsbruk och renskötsel på samma mark: En rättsvetenskaplig studie av äganderätten och renskötselrätten2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    In the northern parts of Sweden forestry and Sami reindeer herding are exercised on the same land and there is an ongoing land use dispute between the land users. Land ownership and reindeer herding rights, based on immemorial prescription and customary law, are parallel property rights to the same land. Studies have concluded that the legal framework does not sufficiently reflect the property rights perspective of the land use conflict. This study examines the legal framework that regulates the relationship between forestry and reindeer herding from a property rights perspective. Starting points of the study are basic aspects of property rights, such as the right to use, decide on and benefit economically from property and the legal protection required in relation to others. Comparisons are made with the legal frameworks that regulate other relationships within real estate law, including e.g. neighbors, easements, joint facilities and utility easement.

    The study concludes that the relationship between land ownership and reindeer herding rights can be understood only against the background of historical events such as colonization and demarcation. The rights are more independent of each other than other legal relations and can be compared to a double ownership. It is further concluded that the Forestry Act is based on the assumption that reindeer herding is primarily a public interest that needs protection. Land owners have a far-reaching right to use forests that causes damages to reindeer pasture lands that is not in accordance with the legal nature of the reindeer herding right. Further, central elements usually used to regulate property rights relations are missing, e.g. mutual consideration, damages and judicial review.

    The study also examines if the legal framework is in accordance with the constitutional protection of property in Chapter 2 Section 15 of the constitutional Instrument of Government and Article 1 of the First Protocol to the European Convention on Human Rights. It is concluded that the legal framework has several deficiencies in this respect. Elements are discussed that can be implemented in law to appropriately reflect the property rights studied.

  • Public defence: 2017-05-12 13:15 Hörsal C, Lindellhallen, Umeå
    Walther, Daniel
    Umeå University, Faculty of Social Sciences, Department of Political Science.
    Till death do us part: a comparative study of government instability in 28 European democracies2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is rooted in the research tradition known as coalition politics, where governments, political parties and political institutions are the central focus. The main emphasis here is on government instability and the question of why governments in modern parliamentary democracies often come to an end before the next regular election. In five distinct but interrelated papers, the thesis explores the issue of early government termination and how it is affected by public support, economic developments and the functioning of the state apparatus. The studies included in this thesis generally take a quantitative approach and make use of a dataset that contains 640 governments in 29 European democracies. Their joint goal is to improve our understanding of when early termination happens by introducing and testing new explanatory factors as well as by improving how previously identified factors are modelled.

    The first paper focuses on Central and Eastern Europe. It shows that the stability of governments in that region is affected by slightly different factors than those that impact on governments in Western Europe. In particular, ideological factors and political institutions are found to be less important in Central and Eastern Europe while the formal power basis of the government and the country’s economic performance matter more. In the second paper, co-authored with Professor Torbjörn Bergman, the state is brought into government stability research. The paper shows that countries with a lower quality of governance and a less efficient public sector have less stable governments. This is mainly because government parties struggle to achieve their policy goals when the state apparatus is inefficient and corrupt.

    Paper 3, co-written with Associate Professor Johan Hellström, looks at how different types of governments respond to economic challenges. In particular, this paper demonstrates that the same changes in economic circumstances (e.g. increases in unemployment or inflation) have different effects on cabinet stability depending on which type of government is in charge. Single party governments are better equipped to deal with economic changes, because they are better positioned to devise new policy responses without having to compromise with other parties. Coalition governments, in contrast, become significantly more likely to terminate early when the economy takes a turn for the worse.

    Finally, over the course of two papers I first explore new techniques for analysing polling data and then use them to empirically test whether governments sometimes choose termination as a way to cope with bad poll numbers. Most of the existing techniques for pooling polls and forecasting elections were explicitly designed with two party systems in mind. In Paper 4, I test some of these techniques to determine their usefulness in complex, multiparty systems, and I develop some improvements that enable us to take advantage of more of the information in the data. In the final paper, I combine the two themes of polling and government stability by looking at how changes in government popularity affect the likelihood of premature dissolution. I find that governments, particularly single party governments, do, in fact, use terminations as a strategic response to changes in their popularity among the public. When support is high, governments tend to opportunistically call an early election, whereas they tend to abandon or reshuffle the government when support is low.