| 1. |
- Henningsson, Anna J, 1972-
(författare)
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Clinical, epidemiological and immunological aspects of Lyme borreliosis with special focus on the role of the complement system
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lyme borreliosis (LB) is the most common vector-borne disease in the Northern Hemisphere. The infection is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex, and it is transmitted to humans by ticks. LB is associated with several clinical manifestations, of which erythema migrans (EM) and neuroborreliosis (NB) are the most common inEurope. The course of the disease is usually benign, but can vary between individuals. The underlying pathogenic mechanisms are not fully understood, but the prognosis is probably determined by a complex interplay between the bacteria and the host’s immune response. Previous studies have indicated that a strong initial T helper (Th) 1-response followed by a Th2 response is beneficial for the clinical outcome in LB.The aims of this thesis were to follow the incidence of NB inJönköping County,Sweden, over time, to search for clinical and laboratory markers associated with the risk of developing long-lasting post-treatment symptoms, and to explore the role of the complement system as well as the relative balance between Th-associated cytokine/chemokine responses in LB.The number of NB cases, diagnosed by cerebrospinal fluid (CSF) analysis, increased from 5 to 10/100,000 inhabitants/year in Jönköping County during 2000-2005. Post-treatment symptoms persisting more than 6 months occurred in 13 %, and were associated with higher age, longer-lasting symptoms prior to treatment, higher levels of Borrelia-specific IgG in CSF, and reported symptoms of radiculitis. Facial palsy, headache and fever were frequent manifestations in children, whereas unspecific muscle and joint pain were the most commonly reported symptoms in older patients.Complement activation occurred both locally in the skin in EM and in CSF of NB patients. However, no activation could be detected in blood in NB patients. Elevated levels of C1q, C4 and C3a in CSF, along with correlation between C1q and C3a levels, suggest complement activation via the classical pathway locally in the central nervous system in NB. In vitro experiments with two clinical Borrelia isolates revealed that B. garinii LU59 induced higher complement activation in human plasma compared to B. afzelii K78 that recruited more of complement regulator factor H. To elucidate the role of complement in the phagocytosis process, experiments were performed using whole blood from healthy donors incubated with fluorescence-labelled spirochetes and different complement inhibitors. The results illustrated a central role of complement for phagocytosis of Borrelia spirochetes.We also studied the relative contribution of different Th-associated cytokines/chemokine responses in NB. The results support the notion that early NB is dominated by a Th1 response, eventually accompanied by a Th2 response. IL-17A was increased in CSF in half of the patients with confirmed NB, suggesting a hitherto unknown role of Th17 in NB.In conclusion, the risk of developing long-lasting post-treatment symptoms tend to increase mainly with age and duration of symptoms prior to treatment in NB. The complement system seems to play an important role in host defence to recognize and kill Borrelia spirochetes. However, complement activation in inappropriate sites or to an excessive degree may cause tissue damage, and therefore, the role of complement in relation to disease course needs to be studied further. Likewise, the role of Th17 in LB pathogenesis and host defence should be further evaluated in prospective studies.
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| 2. |
- Duvetorp, Albert, 1980-
(författare)
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Different Aspects of Psoriasis : Comorbidity, Comedication and Disease Biomarkers
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psoriasis is a common heterogeneous inflammatory disease with its predominant manifestation occurring in the skin. The impact of this disease, however, extends far beyond the skin surface. During the last decades, mounting scientific evidence of psoriasis disease impact on quality of life, stigmatization and comorbidity has led to the predominant view that psoriasis care needs a holistic approach. Epidemiological research is needed to visualize the greater picture whereas research on disease pathomechanisms can provide answers to disease evaluation challenges, facilitate development of new treatments, and provide insights into mechanistical bridges explaining comorbidity occurrence. In study I of this thesis, serum S100A8/A9 was evaluated as a possible biomarker of psoriasis skin disease activity. Dramatic reductions in S100A8 and S100A9 and S100A8/A9 heterocomplex levels were found in lesional psoriasis skin after NB-UVB treatment without any significant reduction occurring in serum. Study II was designed as a retrospective, cross-sectional population study including the adult population of the county of Jönköping. The odds of having pharmacologically treated depression among individuals with psoriasis was compared to the odds of the background population. Psoriasis was associated with an elevated depression risk. Depression was more prevalent among women (both in the background population and among individuals with psoriasis). Young age was associated with higher odds for depression among individuals with psoriasis. Study III was based on the same study population as study II. In this study the comedication burden of individuals with psoriasis was compared to the background population. Comedication assessed were prescription drugs used to treat comorbidity associated with psoriasis in previous scientific publications. Patients with psoriasis were found to have a high comedication burden. Patients receiving systemic treatment for psoriasis had a higher number of different dispensed drugs suggesting that severe disease implies a higher risk of comorbid disease. Study IV was an exploratory study assessing numerous potential biomarkers for psoriasis disease activity. Extensive Luminex analysis of skin and serum samples collected during study I was performed. No serum mediator (potential biomarker of disease activity) showed a significant change after NB-UVB (following correction for multiple testing). In skin, NB-UVB had effects on mediators of the Th17 pathway and multiple chemokines but also previously undescribed or less explored disease mediators. Study II and III suggest that comorbidity and its comedication is common among Swedish psoriasis patients in contact with the health care system. This research reinforces the perception that a holistic approach is needed when treating patients with psoriasis. Behind the failure to identify a biomarker for skin disease activity in study I and IV lurks the questions to how, if or when inflammation in the skin affects systemic inflammation and in extension comorbid disease.
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| 3. |
- Lindau, Robert, 1989-
(författare)
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Immune regulation at the foetal-maternal interface; implications for healthy and complicated pregnancies
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- For a successful pregnancy, the maternal immune system must acquire tolerance towards the paternal antigens present in the semi-allogeneic foetus. This tolerance is mainly established locally at the foetal-maternal interface, where foetally-derived trophoblasts invade the maternal endometrium (called decidua during pregnancy) and come in close proximity to maternal immune cells. The decidua is populated by maternal immune cells of a unique composition, characterised by their suppressive phenotypes that are essential for maintaining tissue homeostasis. Accordingly, failure of immune tolerance can lead to pregnancy complications. Macrophages and regulatory T-cells are enriched in the decidua and are believed to play important roles in the establishment of tolerance. However, there is limited information regarding the factors that regulate their functions and if their function is compromised in pregnancy complications.The aim of this thesis was to further elucidate which factors are responsible for induction of the regulatory phenotypes of macrophages and T-cells found in the decidua, how tissue resident cells in the decidua contribute to this and if this system is compromised during pregnancy complications, such as preeclampsia and recurrent pregnancy loss.Decidual stromal cells (DSCs) constitute the largest population of tissue resident cells in the decidua. In an in vitro system of macrophage differentiation, we found that Isolated peripheral blood monocytes cultured in conditioned medium (CM) from DSCs acquired a high expression of the regulatory M2 markers CD163, CD209 and CD14, and a low expression of CD86, characteristics of decidual macrophages. This induction was in part mediated by macrophage-colony stimulating factor (M-CSF), as neutralising its effects reduced the expression of CD163. However, since only a partial reduction was reached, other factors are involved. Another likely candidate for this polarisation is interleukin (IL)-34, a second ligand for the M-CSF receptor. We showed that IL-34 is expressed by both DSCs and the foetal placenta. Further, in vitro, IL-34 was able to induce macrophages with similar properties as that of M-CSF-induced macrophages, with high expression of CD163, CD209 and CD14. This was also coupled to a cytokine secretion profile similar to M-CSF-induced macrophages, with high production of IL-10, low production of tumour necrosis factor (TNF) and no production of IL-12. We found no evidence of IL-34 being aberrantly expressed in placentas from preeclamptic women.In addition to promoting induction of macrophages with a regulatory phenotype, CM from DSCs promoted expansion of Foxp3+CD25bright regulatory T (Treg) cells in an in vitro polarisation system, in a SMAD3 dependent manner. Protein profiling of DSCs revealed limited production of the Th2 related IL-13, IL-4, IL-33 and thymic stromal lymphopoietin (TSLP), as well as no production of the Th17 related IL-17A and chemokine (C-C motif) ligand (CCL) 20. Instead we found that DSCs were more prone to production of regulatory factors, such as M-CSF, leukaemia inhibitory factor (LIF) and transforming growth factor (TGF)-β, albeit with addition of the more pro-inflammatory IL-6, chemokine (C-X-C motif) ligand (CXCL) 8 and the Th1-related CXCL10.We also investigated if the placenta´s ability to induce Treg cells and regulatory M2 macrophages is compromised in women with a history of unexplained recurrent pregnancy loss (uRPL) and if the placental secreted protein profile is skewed to a pro-inflammatory response in uRPL. Using surplus materials from chorionic villous sampling (CVS), we generated CM from placental tissue taken from healthy and uRPL pregnancies and used this to polarise macrophages and T-cells in vitro. We found no difference in the ability to induce Treg cells and regulatory M2 macrophages between the healthy group and the uRPL group. Likewise, no differences in the protein profile was observed between the two groups.Taken together, our findings imply that DSCs produce a variety of factors promoting foetal tolerance by induction of Treg cells and regulatory M2 macrophages. Furthermore, we also showed that the placenta retained its ability to induce Treg cells and regulatory M2 macrophages in women with a history of uRPL.
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| 4. |
- Abrahamson, Martin, 1977-
(författare)
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Shareholders and Cherry-Picking IPOs : Studies on Shareholders, Initial Public Offerings and Firm Ownership Structure
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation explores investor characteristics and shareholdings of publicly traded Swedish firms. The dissertation consists of an introductory chapter, three published papers, and one working paper. All four papers use Swedish data. Two of the studies examine initial public offerings (IPOs) and the ownership structure; one explores first-time shareholders, and one examines IPOs and first-time shareholders.Paper I studies IPOs with the focus on initial return, the allocation of the shares and inside holdings. The paper presents evidence on allocation of shares to institutional and individual investors. The paper highlights the information asymmetry between institutional and individual investors and shows a wealth transfer from old to new shareholders. The results also show that money left on the table is received primarily by institutions rather than individual investors.Paper II explores the characteristics of first-time shareholders (rookies). I portray the rookies of the stock market and present a model to explain portfolio characteristics. The results show that despite the trend of individuals leaving the stock market, there are new individuals investing in stocks. I also show that gender balance among individual shareholders is rather even, which contradicts approximations of previous studies in other countries. The paper also raises the concern of diversifying stock portfolios, as the average portfolio holds less than four shares for all individuals and less than two for rookies. Paper III studies the relationship between IPOs and rookies. The paper highlights whether rookies invest in IPOs. The results show that besides bringing new firms to the stock market, IPOs contribute to that market, as they attract rookies to invest in the IPOs. The results also show that the return for rookies investing in IPOs is lower compared with rookies investing in non-IPOs.Paper IV studies the relationship between offer price and post-IPO ownership structure. The paper uses price groups and two definitions of breadth of ownership in the analyses. The results show that firms can affect their post-IPO ownership structure through the offer price.
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| 5. |
- Ahlberg, Joakim, 1966-
(författare)
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Multi-unit common value auctions : theory and experiments
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Research on auctions that involve more than one identical item for sale was,almost non-existing in the 90’s, but has since then been getting increasing attention. External incentives for this research have come from the US spectrum, sales, the European 3G mobile-phone auctions, and Internet auctions. The policy relevance and the huge amount of money involved in many of them have helped the theory and experimental research advance. But in auctions where values are equal across bidders, common value auctions, that is, when the value depends on some outside parameter, equal to all bidders, the research is still embryonic.This thesis contributes to the topic with three studies. The first uses a Bayesian game to model a simple multi-unit common value auction, the task being to compare equilibrium strategies and the seller’s revenue from three auction formats; the discriminatory, the uniform and the Vickrey auction. The second study conducts an economic laboratory experiment on basis of the first study. The third study comprises an experiment on the multi-unit common value uniform auction and compares the dynamic and the static environments of this format.The most salient result in both experiments is that subjects overbid. They are victims of the winner’s curse and bid above the expected value, thus earning a negative profit. There is some learning, but most bidders continue to earn a negative profit also in later rounds. The competitive effect when participating in an auction seems to be stronger than the rationality concerns. In the first experiment, subjects in the Vickrey auction do somewhat better in small groups than subjects in the other auction types and, in the second experiment, subjects in the dynamic auction format perform much better than subjects in the static auction format; but still, they overbid.Due to this overbidding, the theoretical (but not the behavioral) prediction that the dynamic auction should render more revenue than the static fails inthe second experiment. Nonetheless, the higher revenue of the static auction comes at a cost; half of the auctions yield negative profits to the bidders, and the winner’s curse is more severely widespread in this format. Besides, only a minority of the bidders use the equilibrium bidding strategy.The bottom line is that the choice between the open and sealed-bid formats may be more important than the choice of price mechanism, especially in common value settings.
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| 6. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 7. |
- Jogmark, Marina
(författare)
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Den regionala transformationsprocessens sociala dimension : Karlskrona1989-2002
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- How can we understand places and their development processes from a social perspective? The aim of this case study is to understand the emergence of an IT-industry in Karlskrona between 1989-2002 from a social capital perspective. Historically, the production and the form of life of the population in Karlskrona, has been characterized by the fact that Karlskrona is a naval city, which for several centuries has had a naval base and a naval ship yard. Karlskrona is also an interesting case to study because of the stagnation in the economy and the insignificant prospects for industrial renewal in the late 1980s. Despite these conditions, something happens that for a short period of time changes the local structure both in terms of production and population. How can we understand the social dimension of such a change?In a narrated form this case study highlights how the transformation of Karlskrona contain both bridging and bonding forms of social relations. The main purpose of this dissertation is accordingly to understand which networks of relations the key participants of the study are a part of and get resources from. The study also aim to highlight structures for action around the development of the IT-industry in relation to the ties that bind in the already established industrial specialization in Karlskrona, in other words the lasting relationships tied to the naval base, the navy and the naval yard. From this viewpoint questions are asked regarding what kind of social relations appear, both in the new and the old Karlskrona, and what it is in particular that characterizes the new social capital that makes up the key participants room to manoeuvre in the process of transformation for Karlskrona. The phenomenon where the place Karlskrona appears as socially divided between exchanges within the context of the new and the already established industry, is illustrated as two pillars of social capital. The pillars are assumed to be separated at the beginning of the transformation, and then they change as people live their lives and are included in new types of exchanges with each other. From the case specific study of the transformation of Karlskrona between 1989-2002, other, more general analytical connections are made in the discussion about how the dynamics of the transformation could be made possible, and why it stopped. From the theoretical viewpoint of social capital the dissertation follows a discussion about the lessons which can be learnt regarding the question how we can view places and their transformation processes. The conclusions particularly emphasize the importance of how newcomers can contribute as well as the crucial role held by border crossers when it comes tocreate linking social capital of the place.
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| 8. |
- K. Nilsson, Annika, 1971-
(författare)
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Enforcing Environmental Responsibilities : A Comparative Study of Environmental Administrative Law
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is about the distrubution of responsibilities in the environmental law enforcement procedure, between the state and the individual environmental actor. The state and its public authorities have a fundamental environmental responsibility. This responsibility is nevertheless shared with the actors. Actor responsibilities include taking sufficient precautionary measures, and controling the own activities. This also covers responsibilities for knowledge and investigation, which are in focus in the thesis analysis. Such responsibilities are enforced by administrative authorities. Enforcement, however, also entails exercise of public power against the individual, and thus warrants proper procedure and safeguards of legal certainty. Such procedural responsibilities include ensuring decision making materials to support their exercise of authority. It also means that the authority has formulate clearly to the actor what their legal duties are, and what they need to do to avoid further enforcement. These administrative duties may entail the authority taking over the actor's information responsibilities under environmental law. Enforcement of actor responsibilities thus becomes inconsistent, or even contraproductive. This thesis comprises analysis of the meeting of environmental and administrative law in the enforcement situation. The analysis is focused on balancing effective implementation and enforcement of policy aims, and the safeguards of the individual's rights and freedoms. The aims is to find ways to coordingate instead of prioritising these objectives. The research is based on a comparative study and analysis of the enforcement systems of Sweden, the United Kingdom (England and Wales), and the Netherlands. The importance of distinguising between the different purposes and aims of the responsibilities is argued. Actor responsibilities for precaution and information should be recognised also in the enforcement procedure. A communicative enforcement procedure, and more purposive assessment of the proper distribution of responsibilities in the individual case may provide both effective enforcement and legal certainty.
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| 9. |
- Nilsson, Erik A. A., 1986-
(författare)
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Degradation Mechanisms of Heat Resistant Steel at Elevated Temperatures : In an Iron Ore Pelletizing Industry
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis focuses on the different degradation mechanisms of the stainless steel in a travelling grate in a Grate-Kiln iron ore pellet indurator. The travelling grate is a conveyor belt that transports green-body pellets to a rotary kiln while the pellets are being dried and pre-heated to a temperature of 900-1100 °C by recycled hot air. After unloading of the pellets to the rotary-kiln for further sintering, the travelling grate is cooled in room temperature while returning to the loading zone of the wet pellets.The steel was tested during thermal cycling in a test-rig, in order to simulate the influence of thermo mechanical fatigue and oxide spallation. The influence of erosion-deposition was investigated in a modified horizontal industrial combustion kiln at 800 °C, with slag and coal from production used as erosive media and combustion fuel, respectively. The influence of minor alloying additions of Mn, Si and Ti on the microstructure was explored by eight different casted alloy compositions. Isothermal heat treatments were performed at 800 °C during 200 hours on steel immersed in deposits recovered from a travelling grate in production.The three main degradation mechanisms found in this work are thermal spallation, erosion-deposition and deposit induced accelerated corrosion (DIAC). Thermal spallation of the oxide layer is caused by the thermal expansion difference between the oxide and the metal during heating and cooling. It has been found that Ti improves the spallation resistance while Si reduces it. Spallation of deposits is another cause believed to increase the degradation. Erosion-deposition appears due to simultaneous erosion and deposition of particles on the travelling grate that causes erosion or deposition depending on the amount of alkali metals in the environment. The velocity of the particles also influences erosion and deposition in the way that higher velocities increase erosion. DIAC is proposed to form on the travelling grate due to the concentration of chloride- and sulphate containing alkali metals in the deposits. Other than these major degrading mechanisms, minor degradation mechanisms such as internal oxidation, sigma formation, carburization and sensitization towards inter-granular attack have been found inside the steel during heating. Thermo mechanical fatigue (TMF) causes intergranular cracks in the material of the travelling grate. Casting issues such as micro-segregation have also been addressed in this thesis.A few different ways to improve degradation resistance have been proposed, such as homogenization heat treatments, optimization of process parameters and inhibitor solutions.
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| 10. |
- Nilsson, Per A., 1957-
(författare)
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Studying abroad : exploring mobility, expectations and experiences among mobile students
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with the experiences and outcomes of temporarily studying abroad, via follow-up studies, aiming to explore international student mobility with a focus on the individual’s perspective. The specific research questions, dealing with the individual students’ expectations and experiences, are addressed in three papers. The fourth paper is a framing of these studies, using results from a global study.The first research question connects to the attractiveness of international study experiences: Q1. What are the individual’s expectations for studying abroad, among inbound and outbound students, and what are the students’ reported experiences compared with these expectations? The second research question connects to the mobility culture of youth: Q2. Does students’ reported life satisfaction change in any way after studying abroad?A main finding for outbound students was an appreciation of courses offered at the destination higher education institution that were not available at Umeå University. The students also had a desire to change their environment and have new experiences. Conversely, the desire to work abroad in the future was lower after returning home. A major finding for inbound students was that they assigned higher value to personal development than academic development. The experience made the students positive in regard to working abroad. Inbound students reported significantly higher satisfaction at follow-up six months later for the domains somatic health and activities of daily living. For both in- and outbound students, experiencing a new culture was more important than pure academic experiences.When the experience was compared with the expectation, in most cases the outcomes were positively related for both in- and outbound students. The motives for international study were primarily related to personal achievements, indicating a fulfilment of one’s potential and curiosity about a sojourn abroad.Finally, the results from the Umeå studies were compared with a global survey. The Umeå studies shows that the respondents viewed studying abroad as an important experience and as a merit later in life. The global survey results indicate that the transition from education to the world of work is of increasing importance to students, and that it matters more for non-European students. The global study showed that employability, teaching ability, expert lectures, and course organization are important to international students.
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