| 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. |
- Nilsson, Maria, 1957-
(författare)
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Promoting health in adolescents : preventing the use of tobacco
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is a robust evidence base for the negative health effects from smoking. Smoking is linked to severe morbidity and to mortality, and kills up to half of its regular users. Tobacco use and production also bring other negative consequences such as economic loss for countries, poverty for individuals, child labour, deforestation and other environmental problems in tobacco growing countries. A combination of comprehensive interventions at different levels is needed to curb the tobacco epidemic. Tobacco control strategies at national levels in the western world often include components of information/education, taxation, legislative measures and influencing public opinion. Two approaches have dominated at the meso and micro levels: cessation support for tobacco users and prevention activities to support young people refraining from tobacco use. Smoking uptake is a complex process that includes factors at the societal level as well as social and individual characteristics. At national level, taxation and legislation can contribute to a societal norm opposing tobacco and creating a context for primary prevention aimed at tobacco free youth. There is no magic bullet in primary prevention. At the meso and micro levels, a continued development of knowledge on the underlying mechanisms and primary prevention methods is essential to prevent young people from starting to use tobacco. The overall aim of this thesis was to gain knowledge about factors that influence young people’s use of tobacco and of preventive mechanisms. The specific aims included to study the relation between Tobacco Free Duo, an intervention program targeting youth in Västerbotten County, and tobacco use prevalence. A specific interest was to explore the role adults can play in supporting young people to refrain from tobacco use. The thesis is based on four studies with three separate sets of data, two were quantitative and one was qualitative. The studies were conducted among adolescents (aged 13-15 yr) in Västerbotten County and on national level in Sweden (aged 13, 15 and 17 yr). Tobacco Free Duo is a school-based community intervention that started in 1993. An essential component of the intervention was to involve adults in supporting adolescents to stay tobacco free. Results showed decreased smoking in adolescents among both boys and girls in the intervention area during the study period of seven years. There was no change in a national reference group during the same time period. A bonus effect was a decrease in adult tobacco use in the intervention area. One out of four adults who supported a young person taking part in the intervention stopped using tobacco. In a qualitative assessment of young smokers, starting to smoke was described as a means of gaining control of their feelings and their situation during early adolescence. They expected adults to intervene against their smoking and claimed that close relations with caring adults could be a reason for smoking less or trying to quit smoking. In a quantitative study that used three decades of national data, over time adolescents became more positive toward parental action on children’s smoking. The adolescents strongly supported the idea of parental action, regardless of whether or not they themselves smoked. Adolescents preferred that actions from parents were dissuading their children from smoking, not smoking themselves, and not allowing their children to smoke at home. These results suggest that the Tobacco Free Duo program contributed to a reduction in adolescent smoking among both boys and girls. Using a multi-faceted intervention that includes an adolescent-adult partnership can decrease adolescent smoking uptake. Engaging adults as partners in tobacco prevention interventions that target adolescents has an important tobacco reducing bonus effect in the adults. The intervention has proven sustainable within communities. A growing majority of adolescents support parental interventions to help them refrain from tobacco. The findings dismiss the notion that adolescents ignore or even disdain parental practices concerning tobacco. A common and consequent norm against tobacco from both schools and parents using a supportive attitude can prevent tobacco use in young people.
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| 3. |
- Andersson, Håkan A., 1948-
(författare)
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Svenska småföretags användning av reserveringar för resultatutjämning och intern finansiering
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Small firms often have inadequate access to the capital necessary for sucessful management. The Swedish Government introduced in the mid-1990s allowance rules that facilitate retention of profit for sole proprietorships and partnership firms. The tax credits arising from the allowances give certain benefits as a source of financing compared to traditional forms of credits. Among the more essential benefits are that the payment for some parts of the tax credit can be put on hold almost indefinitely, or alternatively never be paid. The firms are free to use these means, and the responsibility of future payment of the postponed tax debt stays with the individual firms. The comprehensive purpose of the dissertation may be stated as to increase the understanding of small Swedish firms, especially sole proprietorships, utilizing possibilities for allowances for income smoothing and internal financing. At the beginning the dissertation describes case studies, comprising a smaller selection of microfirms. With a starting-point from the accounted and reported income-tax returns, alternative calculations are made where additional positive tax and finance effects appear possible to obtain. One purpose of these studies is to increase the insight regarding the possibilities of income smoothing and internal financing that arise from utilizing these allowances. These studies also illuminate, to what extent and in what way they are being used in reality. Another objective of these studies is to give a more substantive insight into the technics behind the different allowances, appropriation to positive or negative interest rate allocation appropriation or dissolving of tax allocation reserve appropriation or dissolving of “expansion fund” Theories regarding the creation of resources, through building of capital, and theories on financial planning and strategy are studied. The purpose is to find support for the choice of theoretical grounded underlying independent variables that can be used in cross-sectional studies to explain the use of the possibilities of appropriations. Theories of finance that are of greatest interest, in the operationalisation of these variables, are theories that discuss the choices of different financing alternatives for small firms. The “pecking order theory”, describes the firm’s order of priority when choices of finance alternatives are made. The concept of “financial bootstrapping” expands the frame for different forms of financing choices that especially very small firms have at their disposal.The last part of the theoretical frame deals with the phenomenon of “income smoothing,” which can be translated as leveling out profits/losses. A number of financial and non-financial variables are supported by and operationalised from these financial theories e.g., return on sales, capital turnover, quick ratio and debt-to-equity ratio, respectively age, gender and line of business. Cross-sectional studies are implemented for the taxation years of 1996 and 1999, on databases that have been extracted from Statistics Sweden. The group of 87,276 sole proprietorships included in the study were required to complete tax returns and pay taxes for the business activity according to the supporting schedule, N2, information from the sole proprietorships’ income statement and balance sheet in an accounting statement that comes with the income tax return form. The possibilities of allowances are considered as dependent variables. The intention of the cross-sectional studies is to survey and describe the utilization of possible allowances, with the support of the financial and non-financial independent variables. The connection of these variables to the decision of sole proprietorships to appropriate to the tax allocation reserve is also summarized in a logistic regression model. A number of theoretically based propositions are made for the purpose of observing how the variables are connected to the chances that sole proprietorships actually appropriate to this form of allowance. Appropriation to the tax allocation reserve stands out as the most practiced form of allowance. The studies also clarify that utilization varies among different forms of allowances, but that not all firms that have the prerequisites to utilize the possibilities really do so to the full. A further utilization of the different possibilities of allowances is often conceivable. For the sole proprietorships that are not utilizing these possibilities, the allowances should be considered eligible as a contribution to internal financing and to increase access to capital.
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| 4. |
- Nilsson, Andreas, 1974-
(författare)
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Patient-controlled sedation in procedural care
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The need for procedural sedation is extensive and on the increase in numbers of patients. Minor treatments or diagnostic procedures are being performed with inadequate sedation or even without any sedatives or analgesics. Also, sedation techniques that support advanced, high-quality, in-patient care procedures representing easy performance and rapid recovery are requested for increased effectiveness. In this doctoral thesis, patient-controlled sedation (PCS) using propofol and alfentanil for surgical and diagnostic procedures was studied. The overall aim was to study aspects of safety, procedural feasibility and patients’ experiences. The main hypothesis was that PCS using only propofol is a safe and effective method for the induction and maintenance of moderate procedural sedation. The studies included were prospective, interventional, and in some cases, randomized and double-blinded.Data on cardiopulmonary changes, level of conscious sedation (bispectral index and Observer’s assessment of alertness/sedation [OAA/S]), pain, discomfort, anxiety, nausea (visual analogue scales), interventions performed by nurse anaesthetists, surgeons’ evaluation of feasibility, procedure characteristics, recovery (Aldrete score) and pharmacokinetic simulation of concentrations of drugs at the effect site supported the analysis and comparison between PCS and anaesthetist-controlled sedation and propofol PCS with or without alfentanil.PCS can be adjusted to cover a broad range of areas where sedation is needed, which, in this thesis, included burn care, gynaecological out-patient surgery and endoscopic procedures for the diagnosis and treatment of diseases in the bile ducts (endoscopic retrograde cholangiopancreatography [ERCP]). PCS for burn wound treatment demands the addition of alfentanil, but still seems to be safe. PCS was preferred by the patients instead of anaesthetist-controlled sedation. The addition of alfentanil to PCS as an adjunct to gynaecological surgical procedures also using local anaesthesia increases the surgeon’s access to the patients, but impairs safety. Apnoea and other such conditions requiring interventions to restore respiratory function were seen in patients receiving both alfentanil and propofol for PCS. Patients’ experiencing perioperative pain and anxiety did not explain the effect-site concentrations of drugs. Different gynaecological procedures and patients’ weights seemed to best explain the concentrations. For discomfort and pain during the endoscopic procedure (ERCP), propofol PCS performs almost the same as anaesthetist-performed sedation. Overall, as part of the pre-operative procedures, PCS does not seem to be time-consuming. In respect to the perioperative perspective, PCS supports rapid recovery with a low incidence of tiredness, pain, and post-operative nausea and vomiting (PONV).The data suggest that PCS further needs to be adapted to the patient, the specific procedure and the circumstances of sedation for optimal benefit and enhanced safety.
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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. |
- Berglund, Mats, 1970-
(författare)
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Massans röst : Upplopp och gatubråk i Stockholm 1719–1848
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis examines riots and street violence in Stockholm between 1719 and 1848. By studying open conflicts, the thesis explores changes in societal power structures which otherwise are hidden. The study shows how these levels of power and conflict structures interacted with one another and thereby contributed to the social development during the period; from a patriarchal society of privilege to a society based on a democratic view of the world. The thesis focuses on three collective actors; the people, the authorities and the press.The investigation of the people in the crowds shows that the military element, as well as the lower strata of labourers and servants, was significant in the early events. However, in later phases, middle class groupings such as burghers and civil servants, dominated the masses. These changes in the social composition of the crowds are tightly connected to a similar change in the aims of the riots; from local issues to national policy matters.Tactics of the authorities in their encounter with street disturbances also changed during the period, from passive observation by the police in the 18th century to an active military confrontational approach in the 19th century. The legal base was however strong throughout the period. The parties attached great importance to court proceedings, and knowledge of the legal system was surprisingly good among the common people.During the second half of the period, the press became firmly established. At the turn of the century 1800, there were two short glimpses of free press in connection to the political turbulence in 1792 and 1809. But it was mainly from the 1830's that the newspaper editors became significant actors in the riots. The popular demands for international news and politics gradually grew stronger during the period. A bottom-up perspective thus shows that popular political involvement in a significant way helped to pave the way for the coming breakthrough of democracy.
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| 7. |
- Chang, Liu, 1986-
(författare)
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Ghost in the shell : Studies on subsurface oxygen in oxide-derived copper nanocube catalysts
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With the passage of time and the advancement of our industrial civilization, environmental concerns have become more and more recognized since the 1990s. Carbon dioxide reduction reactions are capable of converting carbon dioxide into valuable hydrocarbons and reducing the carbon emission from the combustion of fossil fuels. This is a promising direction for sustainable energy resources given that the scarcity of fossil fuels is becoming more threatening to the survival of mankind. In recent years, oxide-derived metal nanostructures have been synthesized and show unique catalytic features. Recently, Sloan et al. synthesized a novel oxide-derived copper nanocube structure, which showed a high selectivity toward ethylene over methane and low overpotentials. In this work, the presence of subsurface oxygen in the catalyst surface is tested with density functional theory (DFT) calculations, as a complement to experimental x-ray photoelectron spectroscopy. Due to limitations on the scale of modeling with DFT, the results indicate a very low stability of subsurface oxygen, which give rise to a question if subsurface oxygen would be stable with a reasonably large cluster model. Self-consistent charge density functional tight binding (SCC-DFTB) is adopted to investigate a nanocube model. In this model, a manually reduced cuprious oxide nanocube is constructed and investigated. Subsurface oxygen atoms close to facets are found to be more stable inside. A higher degree of disorder is proposed to be the cause of this difference in stabilizing subsurface oxygen atoms between the slab and nanocube models. The presence of subsurface oxygen enhances the adsorption of CO on the Cu(100) surface, increasing the likelihood for adsorbed CO molecules to dimerize, which is the rate determining step for ethylene production on Cu(100) under low-overpotential conditions. With subsurface electronegative atoms such as oxygen or fluorine, it is also found that the d-band scaling relation could be broken.
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| 8. |
- Englund, Hillevi, 1980-
(författare)
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Soluble amyloid-β aggregates in Alzheimer’s disease
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Soluble oligomeric aggregates of the amyloid-β (Aβ) peptide are suggested to initiate Alzheimer's disease (AD), leading to impaired synapse signalling, widespread neuronal death and loss of cognitive functions. These aggregates seem tightly linked to disease progression, and have therefore gained much attention as potential novel disease markers. In this thesis soluble oligomeric Aβ aggregates in general, and the Aβ protofibril species in particular, have been investigated with the aim to quantify and determine their role in AD pathogenesis. Sandwich-ELISAs specifically measuring Aβ42 peptides are widely used both in AD research and as complements for clinical diagnosis. Here it was demonstrated that presence of soluble Aβ aggregates disturbs such analyses, making it difficult to interpret the results. This discovery was made through analyses of samples from cell- and mouse models carrying the AD causing 'Arctic' APP mutation. When analyzed by ELISA, Aβ42 levels were reduced in Arctic samples, in contrast to levels measured by denaturing SDS-PAGE Western blot. The same divergence in Aβ42-levels between analyses was observed in CSF samples from Down syndrome infants. The discrepancy between methods was hypothesized to be due to presence of soluble Aβ aggregates leading to impaired ELISA detection caused by epitope masking. This was confirmed by developing a protofibril specific ELISA, by which samples from Arctic cell- and mouse models were demonstrated to have enhanced Aβ protofibril levels. AD patients have reduced ELISA-measured Aβ42-levels in CSF compared to healthy controls. To test if this reduction was due to oligomeric Aβ species present in AD CSF, Aβ42-levels were analyzed under both denaturing and non-denaturing conditions. These two measures were combined and an Aβ42 oligomer ratio established. Higher ratios were found in AD patients than healthy controls, implying that Aβ oligomers are present in CSF during Alzheimer pathogenesis. The observations from AD patients and young Down syndrome individuals suggest that Aβ42 oligomer formation is an early mechanism of AD pathogenesis, which potentially could be used as a biomarker to monitor disease development.
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| 9. |
- 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
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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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| 10. |
- Hallberg, David, 1978-
(författare)
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Lifelong learning : The social impact of digital villages as community resource centres on disadvantaged women
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this research was to enhance the understanding of what affects the social impact of ICT in lifelong learning on disadvantaged women.In contributing to the field of social informatics, this research employs behavioural theories as strategy and analytic possibilities. This research mainly used the Kenyan digital villages as CRCs as settings but did also look beyond such establishments to provide a more solid picture. The studies were located in Kenya with complementary studies in Bolivia, Cameroon, Sri Lanka, and Sweden. The main strategies and methods used were case study, comparative education approaches, and observations and interviewing techniques.The findings suggest that ICT and CRCs have the potential to support disadvantaged women and their lifelong learning. However, the positive social impacts are limited because the arrangement of them generally does not favour vernacular languages, illiterate users, female owners and users, or non-students. In general, the use of ICT was sometimes perceived as forced, which is both a barrier and a stressor in the use of ICT in lifelong learning. It also emerged from the comparative studies that discussions among the participants in the CRCs largely covered issues in respect to 1) family and reproduction and 2) self-esteem, i.e. what settles the matter of the social impact of ICT in lifelong learning depends on change attitude among men and women. With minimal if not zero self-esteem a change that would make the difference or break a woman’s “legendary status quo” in order for a woman to feel that she can reach her goal or ambitions in lifelong learning would be difficult. Hence the lack of self-esteem is a stressor in itself.This research is valuable for stakeholders delving into issues of development and learning using ICTs, not only in Kenya but in a broader, global perspective.
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