umu.sePublications
1 - 14 of 14
rss atomLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
  • Public defence: 2017-11-23 09:00 A5_R0, Umeå
    Pietz, Grzegorz
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Innate immunity of human intestinal epithelium in childhood celiac disease: influences from celiac disease associated bacteria and dietary oats2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background & Aims: Celiac disease (CD) is a chronic inflammatory small-bowel enteropathy caused by permanent intolerance to gliadin in wheat gluten, and related proteins in ray and barley. It is disputed whether CD patients tolerate oats. The only treatment of CD is lifelong gluten-free diet (GFD). Only individuals that carry the HLA-DQ2 and/or DQ8 alleles, and eat gluten can develop CD. Dysbiosis in the gut microbiota is a suggested risk factor for CD. T cells in small intestinal mucosa, including intraepithelial lymphocytes (IELs), are known to be important in the pathogenesis of CD. In contrast, the role of intestinal epithelial cells (IECs) is poorly understood. In this thesis we investigated the role of IECs in the immune pathology of CD from duodenal mucosa of children with CD, clinical controls and treated CD. We also investigated the role of CD associated bacteria and oats supplemented GFD on the mucosal immune system.

    Results: A new CD-associated bacterium, Prevotella jejuni, was isolated and characterized. It is a saccharolytic and proteolytic anaerobe. More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were upregulated in IECs in active CD. In two in vitro models for intestinal epithelium, small intestine enteroids and T84 polarized tight monolayers, we showed that 70% of these genes were upregulated by interferon (IFN)-γ via the IRF1 pathway. IRF1 was also upregulated by the CD-associated bacteria P. jejuni and Actinomyces gravenitzii. IECs expressed the NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin (IL)-18, which induces IFN-γ in IELs. P. jejuni bound the intestinal epithelial cell lines T84, Caco2, HT29, and INT407, while Lachnoanaerobaculum umeaense preferentially bound Caco2. P. jejuni caused decreased transepithelial resistance over tight monolayers, while L. umeaense caused an increase. P. jejuni upregulated mRNAs for the detoxification molecules CYP1A1, CYP1A2, CYP1B1, and TIPARP, the chemokines CX3CL1, CXCL1, and CXCL10, the sialyltranserase ST3GAL4, and the inflammation promoting protein S100A3 in tight monolayers. L. umeaense upregulated the chemokines CCL20 and CXCL10, and down-regulated TLR2. In a randomized, double-blinded intervention trial comparing two study-groups, standard GFD and oat-containing GFD, we found that mRNAs for several immune effector molecules and tight junction proteins were only reduced in patients receiving GFD, but not in a substantial fraction of patients on GFD with oats. The down-regulatory cytokines IL-10 and TGF-β1, the cytotoxicity-activating NK-receptors NKG2C and NKG2E, and the tight junction protein claudin-4 remained elevated in the study group on GFD with oats.

    Conclusions: IECs are far from inactive in CD. A key factor in the epithelial reaction in CD appears to be over-expression of IRF1 in IECs. Dual activation of IRF1 and IRF1-regulated genes, both directly by P. jejuni and indirectly by IFN-γ via the IL-18-inflammasome, would drastically enhance the inflammatory response and lead to the pathological situation seen in active CD. P. jejuni harms the intestinal epithelium, i.e., it is a likely risk factor for CD, while L. umeaense strengthen barrier function and local immunity, possibly acting as a protective. A fraction of CD patients should avoid oats in the diet.

  • Public defence: 2017-11-24 09:00 Sal 135, Allmänmedicin, By 9A, Norrlands universitetssjukhus, Umeå
    Kardakis, Therese
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Strengthening lifestyle interventions in primary health care: the challenge of change and implementation of guidelines in clinical practice2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Lifestyle habits like tobacco use, hazardous use of alcohol, unhealthy eating habits and insufficient physical activity are risk factors for developing non-communicable diseases, which are the leading, global causes of death. Furthermore, ill health and chronic diseases are costly and put an increased burden on societies and health systems.  In order to address this situation, governmental bodies and organizations’ have encouraged healthcare providers to reorient the focus of healthcare and undertake effective interventions that support patients to engage in healthy lifestyle habits. In Sweden, national clinical practice guidelines (CPGs) on lifestyle interventions were released in 2011. However, the challenges of changing clinical practice and introducing guidelines are well documented, and health interventions face particular difficulties. The overall purpose of this thesis is to contribute towards a better understanding of the complexities of shifting primary health care to become more health oriented, and to explore the implementation environment and its effect on lifestyle intervention CPGs. The specific aims are to investigate how implementation challenges were addressed during the guideline development process (Study I), to investigate several dimensions of readiness for implementing lifestyle intervention guidelines, including aspects of the intervention and the intervention context (Study II), to explore the extent to which health care professionals are working with lifestyle interventions in primary health care, and to describe and develop a baseline measure of professional knowledge, attitudes and perceived organizational support for lifestyle interventions (Study III), and to assess the progress of implementing lifestyle interventions in primary care settings, as  well as investigate the uptake and usage of the CPGs in clinical practice (Study IV).

     

    Methods and results: Interviews were conducted with national guideline-developers (n=7). They were aware of numerous implementation challenges, and applied strategies and ways to address them during the guideline development process. The strategies adhered to four themes: (a) broad agreements and consensus about scope and purpose, (b) systematic and active involvement of stakeholders, (c) formalized and structured development procedures, and (d) openness and transparent development procedures. At the same time, the CPGs for lifestyle interventions challenged the development-model at the National Board of Health and Welfare (NBHW) because of their preventive and non-disease specific focus (I).

    A multiple case study was also conducted, using a mixed methods approach to gather data from key organizational individuals that were accountable for planning the implementation of CPGs (n=10), as well as health professionals and managers (n=340). Analysis of this data revealed that conditions for change were favorable in the two organizations that served as case studies, especially concerning change focus (health orientation) and the specific intervention (national guidelines on lifestyle interventions). Somewhat limited support was found for change and learning, and change format (national guidelines in general). Furthermore, factors in the outer context were found to influence the priority and timing of the intervention, as well as considerable inconsistencies across the professional groups (II). A cross-sectional study among physicians and nurses (n=315) in Swedish primary healthcare showed that healthcare professionals have a largely positive attitude and thorough overall knowledge of lifestyle intervention methods. However, both the level of knowledge and the involvement in patients’ lifestyle change, differed between professional groups. Organizational support like CPGs and the development of primary health care (PHC) collaborations with other stakeholders were identified as potential strategies for enhancing the implementation of lifestyle interventions in PHC (III).

    In addition to interviews and case studies, a longitudinal survey among health professionals (n=150; n=73) demonstrated that their use of methods to encourage patients to reduce or eliminate tobacco or alcohol use, had increased. The survey also indicated that nurses had increased the extent to which they addressed all four lifestyle habits. The progress of the implementation of CPGs on lifestyle interventions in PHC was somewhat limited, and important differences in physicians and nurses’ attitudes, as well as their use of the guidelines, were found (IV).

    Conclusions: Health orientation differs in many ways from more traditional fields in medicine. To strengthen the implementation of this very important (but not “urgent”) field in health care, it needs, first of all, to be prioritized at all levels! The results of the studies demonstrate relatively slow adoption of lifestyle intervention CPGs in clinical practice, and indicate room for improvement. The findings of this thesis can inform healthcare policy and research on further development of the health orientation perspective, as well as on the challenges of implementing CPGs on lifestyle interventions in primary care. In summary, this thesis presents important lessons learned regarding health orientation - from the development of CPGs in the field, via assessing healthcare organizations’ readiness to change and health professionals’ attitudes to methods to support patients with lifestyle changes.

  • Public defence: 2017-11-24 13:00 Hörsal D, Umeå
    Gunnarsson, Niklas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Chronic myeloid leukemia and cancer2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Chronic myeloid leukemia (CML) is a relatively rare hematological malignancy with a constant incidence of approximately 90 new cases each year in Sweden (0.9 cases/100 000 inhabitants). The etiology is largely unknown but high doses of ionizing radiation are a known but rare risk factor. The treatment options were for a long time limited to chemotherapies i.e. hydroxyurea and busulfan, interferon’s and allogeneic hematopoietic stem cell transplantation and the median survival were only about four years.

    Since the beginning of the 21st century a new way of treating CML has been introduced, the tyrosine kinase inhibitors (TKI), leading to a rapid decrease in leukemic cells and symptoms. Due to the TKIs, the overall 5-year survival is nowadays approximately 85 % and CML patients have time to develop other diseases, including other malignancies.

    The aims of this thesis was to investigate the present and future prevalence of CML and the prevalence of other malignancies prior and subsequent to the diagnosis of CML, malignancies among first-degree relatives of persons with CML. In addition, the incidence of autoimmune and chronic inflammatory diseases among patients with CML was also investigated.

     

    Methods

    From the Swedish CML register, data over nearly all Swedish CML patients from 2002 and forward were obtained for paper II-IV.

    For paper I, the Swedish cancer register was used to identify all Swedish CML patients since 1970 and the Swedish cause of death register was used to identify an eventual date of death for these patients. With a constant incidence and the relative survival rates for CML patients between 2006 and 2012 as a model, the present and future prevalence was calculated.

    For paper II-IV, data from the Swedish cancer register was used to identify other malignancies than CML. For paper II, information about autoimmune and chronic inflammatory diseases was retrieved from the Swedish national patient register.

    For paper II and IV, five controls matched for year of birth, gender and county of residence were randomly selected from the Swedish register of the total population. To calculate odds ratio (OR), conditional logistic regression was used.

    To calculate the risk of a second malignancy for paper III, Standardized incidence ratio (SIR) was used.

    In paper IV, first-degree relatives (parents, siblings and offsprings) for both cases and controls were retrieved from the Swedish multi-Generation Register, where persons born later than 1932 and registered in Sweden at some time since 1961 are registered.

     

    Results

    Prevalence and survival

    As shown in paper I, the 5-year overall survival for CML patients increased remarkably from 0.18 to 0.82 between 1970 and 2012. The prevalence increased from 3.9 to 11.9 per 100 000 inhabitants in Sweden between 1985 and 2012. By assuming no further improvements in relative survival as compared to the survival rates between 2006 and 2012, the prevalence by 2060 is expected to increase to 22.0 per 100 000 inhabitants. This corresponds to 2 587 CML patients as compared to 1 137 CML patients in 2012.

     

    Malignancies, autoimmune and chronic inflammatory diseases prior to CML

    In study II, more than 45 000 person-years of follow-up were evaluated in 984 CML patients diagnosed between 2002 and 2012. With an OR of 1.47 (95 % CI 1.20–1.82) and 1.55 (95 % CI 1.21–1.98), respectively, the prevalence of prior malignancies and autoimmune diseases were significantly increased as compared to matched controls. On the other hand, no association between CML and chronic inflammatory diseases was shown.

     

    Second malignancies

    In 868 CML patients, diagnosed between 2002 and 2011, 52 malignancies were observed in the Swedish cancer register, as shown in paper III. When compared to expected rates in the background population, a significantly increased risk of second malignancies with a SIR of 1.52 (95 % CI 1.13–1.99) was shown. When looking at specific cancer types, gastrointestinal as well as nose and throat cancer were significantly increased.

     

    Familial aggregation of malignancies

    984 CML patients were identified in paper IV. However, 184 had a birth date prior to 1932, subsequently only 800 patients were analyzed. Among them, 4 287 first-degree relatives were identified, compared to 20 930 first-degree relatives of the matched controls. 611 malignancies were retrieved; no significant increase of malignancies in first-degree relatives of CML patients was shown (OR 1.06; 95 % CI: 0.96–1.16).

     

    Conclusion

    Since CML patients nowadays have a high survival rate, the calculations in this thesis shows that the prevalence of CML will almost double by 2060. CML patients have an increased risk of developing malignancies prior and subsequent to the diagnosis of CML, suggesting a hereditary or acquired predisposition to develop cancer. Since there is no familial aggregation of malignancies in CML patients, a hereditary predisposition to develop cancer is unlikely to be part of the pathogenesis of CML, leaving an acquired predisposition more likely.

  • Public defence: 2017-12-01 10:00 Hörsal A, Samhällsvetarhuset, Umeå
    Grahn, Robert
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Treatment repeaters: re-entry in care for clients with substance use disorder within the Swedish addiction treatment system2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    According to the regulations contained in the Social Services Act (SFS 2001:453), Swedish social services have a legal responsibility to provide support, care, and treatment for individuals with substance use problems.  This law mandate those who are responsible to provide treatment to motivate drug users to actively seek treatment on a voluntary basis, ensuring an end to their dependence on drugs. Studies have shown that although the treatment system largely focuses on promoting abstinence, about two-thirds of client’s relapse into substance use within one year after completing treatment. This dissertation focuses broadly on clients who repeatedly enter and use treatment for substance use disorders in the Swedish addiction treatment system. The aim of this thesis is to examine and identify the population groups who are repeated treatment users of the Swedish treatment system for substance use disorder, including both the voluntary treatment and compulsory care. This thesis was based on three national level databases. The results showed that clients with a higher degree of problems and problems in different areas of life also had an increased risk of having treatment for substance use disorder repeatedly. Clients who were older, men, reported more years of polydrug and alcohol use to intoxication, reported more compulsory care episodes for substance use, had ever been charged with crime, had ever been in inpatient mental health treatment, and had a higher ASI mental health symptom composite score, were significantly more likely to report more voluntary addiction treatment episodes. The strongest significant association with the number of treatment episodes was the number of compulsory treatment episodes for alcohol and drugs. Individuals who experienced prior compulsory care including mandatory treatment through LVU (law (1990:52)), been in prison, and had children mandated to out-of-home care, were more likely to have two or more entries in the compulsory care system for substance use disorder. In addition, this analysis showed that 59% of clients mandated to compulsory care dropped-out during their compulsory care episode, and that younger clients were significantly more likely to drop-out. Those who drop-out were significantly more likely to experience negative outcomes, i.e. additional sentence to compulsory care and higher risk of mortality.  A hierarchal logistic regression model also identified that individuals with riskier childhood conditions were more likely to have had repeated entries to compulsory care for substance use disorder. The indirect effects showed that a family history of substance use disorder and psychiatric problems are both associated with higher probability of institutional care as a child i.e. LVU, and that in turn, mandated childhood institutional care is related to repeated compulsory care intakes as an adult. Individuals who use treatment for substance use disorder repeatedly have a higher degree of problems i.e. an exposed and problematic group of individuals characterized by problem in several different areas of life. Growing up in a home environment with unfavorable conditions, mandated care before the age of 18 (LVU), compulsory care for substance use disorder as an adult, children taken into out-of-home care, and crime are the factors that are primarily associated with repeated treatment for substance use. A change in the view of treatment for clients in need of repeated use of treatment seems important, and access to adapted continuous care efforts are crucial to counteract the risk of relapse after a treatment episode of voluntary or compulsory care. Further, it seems important to motivate the client to complete the compulsory care without any deviation, since this seems to have positive effects on their substance use disorder.

  • Public defence: 2017-12-01 13:00 Aulan, Sundsvalls sjukhus, Sundsvall
    Sjögren, Vilhelm
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Oral anticoagulation and stroke risk2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: The risk of ischaemic stroke in patients with atrial fibrillation (AF) and mechanical heart valve (MHV) prostheses can be reduced by oral anticoagulation (OAC), which increases the risk of serious bleeding. The aims of this thesis were [1] to find out how effective and safe warfarin is where treatment quality is high, i.e. Sweden, with proportion of time that patients spend within the therapeutic range (TTR) >70%, [2] whether there is evidence for administering low-molecular-weight heparin (LMWH) during temporary interruptions of OAC (bridging therapy), and whether non-vitamin K-dependent oral anticoagulants (NOACs) as a group, [3] or individually, [4] are more effective and safer than warfarin when used for stroke prevention in patients with AF.

    Materials and methods: All four studies were retrospective, based on the Swedish anticoagulation register Auricula, and done with merging of data from some or all of the National Patient Register, the Prescribed Drug Register, the Swedish Stroke Register (Riksstroke), and the Cause of Death Register. In studies 2–4, propensity score matching was performed to obtain treatment groups with similar risk profiles. Outcomes were defined as haemorrhages or thromboses requiring specialist care, or death. Haemorrhages were intracranial, gastrointestinal, or other. Thromboses were ischaemic stroke, systemic embolism, myocardial infarction, or venous thromboembolism (VTE).

    Study 1 described all patients on warfarin during 2006–2011, which was before the introduction of NOACs. Study 2 was a cohort study of all patients who had a planned interruption of warfarin during the same period. Study 3 included all 49,011 patients starting OAC for stroke prevention due to AF between 1 July 2011 and 31 December 2014, and study 4 all 64,382 patients with the same indication between 1 January 2013 and 31 December 2015.

    Results: Study 1 showed that for the 77,423 patients on warfarin with 217,804 treatment years, TTR was 77.4% for patients with AF, 74.5% with MHV, and 75.9% with VTE. Annual rates of intracranial bleeding were 0.38%, 0.51%, and 0.30%. In study 2, with 14,556 warfarin interruptions, the 30-day risk of a bleeding requiring specialist care was 0.64% for LMWH treated and 0.46% for controls. For patients with VTE as indication for OAC, bleeding rate with LMWH was significantly higher at 0.85% vs. 0.16% (hazard ratio 5.24, 95% confidence interval 1.39–19.77), but with no difference for patients with MHV or AF. The incidence of ischaemic complications was higher in the LMWH bridging group overall and for patients with MHV and AF, but not for patients with VTE. In study 3, for the 12,694 patients starting NOAC (10,392 treatment years) or matched warfarin patients (9,835 treatment years, TTR 70%) due to AF, annual incidence of ischaemic stroke and systemic embolism did not differ between the groups (1.35% vs. 1.58%), but risks of major bleedings and intracranial bleedings were significantly lower: 2.76% vs. 3.61% and 0.40% vs. 0.69%. In study 4, patients on individual NOACs (6,574 dabigatran, 8,323 rivaroxaban, 12,311 apixaban) were compared to 37,174 patients starting warfarin (in total 81,176 treatment years). No NOAC showed any difference in risk of ischaemic stroke or systemic embolism, but there were fewer intracranial bleedings, serious bleedings overall, and deaths for dabigatran and apixaban compared to warfarin. For patients starting rivaroxaban the risk of gastrointestinal bleeding was higher than for matched warfarin counterparts, with no significant differences in other bleeding risks, or mortality.

    Conclusions: Swedish warfarin treatment shows TTR levels that are high by international standards, correlating to low incidences of ischaemic and haemorrhagic events. LMWH bridging has not been proven beneficial, even for patients with MHV, meaning that bridging in general cannot be recommended. NOACs as a group were safer than high-quality warfarin treatment. Efficacy did not differ, even when comparing individual NOACs to warfarin, but there were fewer bleedings on dabigatran and apixaban. Although not more efficient than warfarin with a high TTR, NOACs should be the recommended first choice for OAC in AF, on the merit of lower bleeding risks.

  • Public defence: 2017-12-01 13:00 S213h, Samhällsvetarhuset, Umeå
    Alexeyeva, Irina
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Business Administration.
    Essays on Audit Fees and the Joint Provision of Audit and Non-Audit Services2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis examines the factors affecting audit and non-audit fees and the effects of the joint provision of audit and non-audit services on auditing.

    The first essay focuses on environmental factors. Using data for Swedish listed companies over a six year span, including pre-crisis, crisis and post-crisis periods, the essay investigates whether changing economic conditions affect the level of fees paid for audit and non-audit services. The finding suggests that auditors increase their risk premium for auditing during a financial crisis andtend to charge higher audit fees as a response to lower risk levels in the post-crisis period. On the other hand, a significant reduction in non-audit fees suggests that companies are less willing to invest in consulting services during thecrisis and post-crisis periods.

    The second essay also studies the effects of environmental factors on audit pricing. Using data for financial institutions in 24 European countries, the study examines whether the level of effort spent on the evaluation of fair values is higher for more uncertain fair values.The result suggests that an increasing level of complexity and risk requires greater audit effort. Furthermore, the results showthat the strength of a country’s institutional setting is positively associated with the effort spent on the evaluation of high uncertainty fair value estimates. The finding implies that auditors spend more effort in stronger regulated countries, possibly due to higher potential litigation costs.

    The third essay focuses on the factors related to an individual audit partner. Based on the data of publicly listed Swedish companies, it investigates whether partner special competencies are reflected in the prices charged for auditing. The findings show that partner industry expertise and client-specific expertise are associated with higher audit fees. A further finding isthat female partners are considerably under-represented among specialists. However,the under-representation of females among higher qualified partners does not seem to negatively affect their possibilities to earn higher fees.

    The fourth essay investigates how the joint provision of audit and non-audit services affects perceived knowledge spillover and audit efficiency. The essay makesuse of survey data from a large sample of Swedish auditors and finds that the levels of communication and trust are positively associated with knowledge spillover. The result further suggests that the information gained from the provision of non-audit services can reduce auditors’ effort (time) spent on different audit procedures, thereby increasing audit efficiency.

  • Public defence: 2017-12-01 13:00 Samhällsvetarhuset, Hörsal A, Umeå
    Sabo, Josefin
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History.
    Reglerad sprängkraft: dynamiten, staten och den svenska civila sprängmedelsindustrin 1858-19502017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The development of new innovations in explosives was an important part of the industrialization process from the mid-nineteenth century. The establishment of the world´s first nitroglycerin factory – Nitroglycerin Aktiebolaget (NA) in Stockholm in 1864 started a process replacing gunpowder with nitroglycerin and from 1868 by the safer invention dynamite. This affected both the long-term relationships between the mining industry and the powder mills and the demand from new industries for efficient and safe explosives. Even though the explosives industry was a small industry, it was of great importance for many other industries and for economic transformation. With dynamite and its successors, society also faced new risks. As a result, an extensive legislation was developed at an early stage which was supplemented with further supervision from a government authority in various organizations from 1895.

    The aim of the thesis is to investigate and analyze the major decision-making processes of the Swedish civilian explosives industry during the period 1858-1950. The purpose of the work is to contribute to gaining knowledge about how the society´s regulation of different industries has evolved and how state and private actors have acted in the development of new regulations. The work is structured around three main questions. The first question is about how the Swedish explosives industry developed during the period. How did the technological development of the industry and the explosives look like and had this any impact on the questions the actors within the industry drove? The second question is about how the dynamite industry was regulated. What did the regulations contain and how was the control organized? How did rights and obligations look like and how was the industry affected by this? The third question concerns the regulatory process itself. How and why did the regulations change and which actors were involved in the various changes? How did the Government and the actors act and can we see shifts over time between their different roles and interests?

    The study concludes that NA was the actor that, by using different methods, managed to gain the greatest influence over the regulatory process. Although the traditional established powder mill industry competed with NA at an early stage, it was nevertheless the initial, high-tech company that was involved in creating new national regulations in negotiation with the regulating authorities. This was a process of regulatory capture where NA, by combining both direct and indirect capture methods, managed to gain influence over regulations in the long run. A parallel but slightly different characteristic of this regulatory capture process is risk minimization for the public. Despite the occurrence of regulatory capture the regulations developed in a kind of a co-regulation system where the regulators became dependent on NA to provide the technical and practical expertise needed to build the necessary regulatory framework.

  • Public defence: 2017-12-08 09:00 Sal E04, R1, Umeå
    Fordell, Helena
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Virtual Reality for Enriched Rehabilitation of Stroke Patients with Spatial Neglect: Diagnostics and the Rehabilitation Effect on Spatial Attention and Neuronal Activity2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Approximately a third of all stroke patients develop spatial neglect, a debilitating symptom associated with poor outcome. Spatial neglect is clinically defined as a deficit in processing and responding to stimuli presented on the contralesional side of the body, or the space surrounding that side of the body. The heterogenetic, multi-sensory nature of the symptoms renders it difficult to diagnose and treat; therefor effective methods for screening and intervention for neglect are needed. Virtual reality (VR) is a method of brain–computer interaction that involves realtime simulation of an environment, scenario or activity that allows for user interaction and targets multiple senses. We hypothesize that VR can facilitate identification of spatial neglect in stroke patients and that training with this interface will improve patient’s functional outcome, through stimulation to neuronal networks including those controlling attention.

    Objective: The objective was to construct and validate a computerized test battery for spatial neglect and to investigate its usability in stroke patients. Also to design and develop a VR rehabilitation method for spatial neglect and to evaluate its effects on spatial attention and on neuronal activity in the brain.

    Method: We designed, developed and evaluated a new concept for assessment (VR-DiSTRO®) and training (RehAtt®) of spatial attention, using VR technology. The hardware consisted of a PC, monitor, 3D-glasses and a force feedback device to control the tasks (i.e., a robotic pen). The software enabled targets to be moved, rotated and manipulated in the 3D environment using the robotic pen. RehAtt® made it possible to combine intense visual scanning training, multi-sensory stimulation (i.e., audio, visual, tactile) and sensory-motor activation of the contralesional arm. In a first study on 31 stroke patients we performed a construct validation of VR-DiSTRO® against Rivermead Behavioural Test Battery (BIT) and investigated the usability. In a second study, 15 subjects with chronic spatial neglect (symptoms >6 month) had self-training, 3 x 1 hour for 5 weeks using RehAtt®. Outcome were measured by changes in neglect tests and in Cathrine Bergego Scale (CBS). Training-related changes in neuronal activity of the brain was studied using fMRI during task and in resting state.

    Results: VR-DiSTRO® correctly identified all patients with neglect. The sensitivity was 100% and the specificity 82% for VR-DiSTRO® compared to BIT. Usability was high and no side-effects were noted. Using repeated measurement analysis, improvements due to the RehAtt® intervention were found for Baking tray task (p < 0.001), Star cancellation test (p = 0.006) and Extinction test (p = 0.05). Improvements were also seen in the Posner task as fewer missed targets (p = 0.024). Improvement in activities of daily living (CBS) was shown immediately after training (p < 0.01) and patients still reported improvement at 6 months follow-up. Trainingrelated changes in neuronal activity were seen as an increased task-evoked brain activity in prefrontal and temporal cortex, mainly outside the attention network but in related cortical areas. During resting state, changes in network connectivity were seen after intervention with RehAtt® in the Dorsal Attention Network (DAN) and interhemispheric connectivity.

    Conclusion: VR-DiSTRO® identified visuospatial neglect in stroke patients quickly and with a high accuracy. RehAtt® training improved in spatial attention in chronic neglect with transfer to functions in daily living. Increased neuronal brain activity was found in and between attention networks and related brain structures. This could represent a compensatory effect in addition to sign of a restorative effect from the RehAtt training. The results obtained in this study are promising, encourage further development of the methods and merit for further studies.

  • Public defence: 2017-12-08 09:00 KB.E3.01, Umeå
    Borén, Eleonora
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Off-gassing from thermally treated lignocellulosic biomass2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Off-gassing of hazardous compounds is, together with self-heating and dust explosions, the main safety hazards within large-scale biomass storage and handling. Formation of CO, CO2, and VOCs with concurrent O2 depletion can occur to hazardous levels in enclosed stored forest products. Several incidents of CO poisoning and suffocation of oxygen depletion have resulted in fatalities and injuries during cargo vessel discharge of forest products and in conjunction with wood pellet storage rooms and silos. Technologies for torrefaction and steam explosion for thermal treatment of biomass are under development and approaching commercialization, but their off-gassing behavior is essentially unknown.

    The overall objective of this thesis was to provide answers to one main question: “What is the off-gassing behaviour of thermally treated lignocellulosic biomass during storage?”. This was achieved by experimental studies and detailed analysis of off-gassing compounds sampled under realistic conditions, with special emphasis on the VOCs.

    Presented results show that off-gassing behavior is influenced by numerous factors, in the following ways. CO, CO2 and CH4 off-gassing levels from torrefied and stream-exploded biomass and pellets, and accompanying O2 depletion, are comparable to or lower than corresponding from untreated biomass. The treatments also cause major compositional shifts in VOCs; emissions of terpenes and native aldehydes decline, but levels of volatile cell wall degradation products (notably furans and aromatics) increase. The severity of the thermal treatment is also important; increases in torrefaction severity increase CO off-gassing from torrefied pine to levels comparable to emissions from conventional pellets, and increase O2 depletion for both torrefied chips and pellets. Both treatment temperature and duration also influence degradation rates and VOC composition. The product cooling technique is influential too; water spraying in addition to heat exchange increased CO2 and VOCs off-gassing from torrefied pine chips, as well as O2 depletion. Moreover, the composition of emitted gases co-varied with pellets’ moisture content; pellets of more severely treated material retained less moisture, regardless of their pre-conditioning moisture content. However, no co-variance was found between off-gassing and pelletization settings, the resulting pellet quality, or storage time of torrefied chips before pelletization. Pelletization of steam-exploded bark increased subsequent VOC off-gassing, and induced compositional shifts relative to emissions from unpelletized steam-exploded material. In addition, CO, CO2 and CH4 off-gassing, and O2 depletion, were positively correlated with the storage temperature of torrefied softwood. Similarly, CO and CH4 emissions from steam-exploded softwood increased with increases in storage temperature, and VOC off-gassing from both torrefied and steam-exploded softwood was more affected by storage temperature than by treatment severity. Levels of CO, CO2 and CH4 increased, while levels of O2 and most VOCs decreased, during storage of both torrefied and steam-exploded softwood.CO, CO2 and O2 levels were more affected by storage time than by treatment severity. Levels of VOCs were not significantly decreased or altered by nitrogen purging of storage spaces of steam-exploded or torrefied softwood, or controlled headspace gas exchange (intermittent ventilation) during storage of steam-exploded bark.

    In conclusion, rates of off-gassing of CO and CO2 from thermally treated biomass, and associated O2 depletion, are comparable to or lower than corresponding rates for untreated biomass. Thermal treatment induces shifts in both concentrations and profiles of VOCs. It is believed that the knowledge and insights gained provide refined foundations for future research and safe implementation of thermally treated fuels as energy carriers in renewable energy process chains.

  • Public defence: 2017-12-08 09:00 Aulan, Kiruna
    Ramstad, Robin
    Umeå University, Faculty of Science and Technology, Department of Physics. Swedish Institute of Space Physics, Kiruna.
    Ion escape from Mars: measurements in the present to understand the past2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Present-day Mars is a cold and dry planet with a thin CO2-dominated atmosphere comprising only a few ­­­mbar pressure at low altitudes. However, the Martian surface is marked with valley networks, hydrated mineral clays, carbonates and the remains of deltas and meandering rivers, i.e. traces of an active hydrological cycle present early in the planet's geological history. A strong greenhouse effect, and thus a thicker atmosphere, would have been required to sustain a sufficiently warm environment, particularly under the weaker luminosity of the early Sun. The fate of this early atmosphere is currently unknown.

    While several mechanisms can remove atmospheric mass over time, a prominent hypothesis suggests that the lack of an intrinsic Earth-like global magnetic dipole has allowed the solar wind to erode the early Martian atmosphere by imparting energy to the planet's ionosphere which subsequently flows out as ion escape, over time depleting the greenhouse gasses and collapsing the ancient hydrological cycle. Previous studies have found insignificant ion escape rates under present-day conditions, however, the young Sun emitted significantly stronger solar wind and photoionizing radiation flux compared to the present. The geological record establishes the time of collapse of the hydrological cycle, estimated to have occurred in the mid-late Hesperian period (~3.3 billion years ago) at latest. To constrain the amount of atmosphere lost through ion escape since, we use the extensive database of ion flux measurements from the Analyzer of Space Plasmas and Energetic Atoms (ASPERA-3) particles package on the Mars Express orbiter (2004-present) to quantify the ion escape rate dependence on upstream solar wind and solar radiation conditions.

    The Martian ion escape rate is shown to be insensitive to solar wind parameters with a weak inverse dependence on solar wind dynamic pressure, and linearly dependent on solar ionizing photon flux, indicating efficient screening of the bulk ionosphere by the induced magnetic fields. The impact of an extreme coronal mass ejection is studied and found to have no significant effect on the ion escape rate. Instead, intense solar wind is shown to only increase the escaping energy flux, i.e. total power of escaping ions, without increasing the rate by accelerating already escaping ions. The orientation of the strongest magnetized crustal fields are shown to modulate the ion escape rate, though to have no significant time-averaged effect. We also study the influence of solar wind and solar radiation on the major Martian plasma boundaries and discuss factors that might limit the ion escape rate, including solar wind-ion escape coupling, which is found to be ≲1% and decreasing with increased solar wind dynamic pressure. The significant escape rate dependencies found are extrapolated back in time, considering the evolution of solar wind and ionizing radiation, and shown to account for only 4.8 ± 1.1 mbar equivalent surface pressure loss since the time of collapse of the Martian hydrosphere in the Hesperian, with ~6 mbar as an upper estimate. Extended to the late Noachian period (3.9 billion years ago), the found dependencies can only account for ≲10 mbar removed through ion escape, an insignificant amount compared to the ≳1 bar surface pressure required to sustain a warm climate on early Mars.

  • Public defence: 2017-12-08 09:00 N320, Umeå Universitet, Umeå
    Renström, Lina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    The involvement of the TNF-alpha system in skeletal muscle in response to marked overuse2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Painful conditions having the origin within the musculoskeletal system is a common cause for people to seek medical care. Between 20-40% of all visits to the primal care in Sweden are coupled to pain from the musculoskeletal system. Muscle pain and impaired muscle function can be caused by muscles being repetitively overused and/or via heavy load. Skeletal muscle is a dynamic tissue which can undergo changes in order to fulfill what is best for optimal function. However, if the load is too heavy, morphological changes including necrosis, as well as pain can occur. The extension of the skeletal muscle is the tendon. Tendinopathy refers to illness and pain of the tendon. The peritendinous tissue is of importance in the features related to tendon pain. Common tendons/origins being afflicted by tendinopathy/pain are the Achilles tendon and the extensor origin at the elbow region.    Tumor necrosis factor alpha (TNF-alpha) is a cytokine that is involved in several biological processes. It is well-known for its involvement in the immune system and is an important target for inflammatory disorders such as rheumatoid arthritis. It is not known to what extent the TNF-alpha system is involved in the process of muscle inflammation and damage due to overuse.

       Studies were conducted on rabbit and human tissue, tissues that either had undergone an excessive loading activity or tissue that was removed with surgery due to painful conditions. The tissues were evaluated via staining for morphology, in situ hybridization and immunofluorescence.

       Unilateral experimental overuse of rabbit muscle (soleus muscle) led to morphological changes in the soleus muscle tissue bilaterally. The longer the experiment extended, the more was the tissue affected. This included infiltration of white blood cells in the tissue (myositis) and abnormal muscle fiber appearances. TNF-alpha mRNA was seen in white blood cells, in muscle fibers interpreted to be in a reparative stage and in white blood cells that had infiltrated into necrotic muscle fibers.  There was an upregulation in expressions of TNF receptor type 1 (TNFR1) and TNF receptor type 2 (TNFR2) in muscles that were markedly overused, with expressions in white blood cells, fibroblasts, blood vessel walls and muscle fibers. Immunoreactions for the receptors were seen in nerve fascicles of markedly overused muscles but only occasionally in normal muscles. The upregulations were seen for both experimental and contralateral sides. Overall the two receptors showed somewhat different expression patterns. Tendinopathy is associated with an increase in blood flow and infiltration of white blood cells in the tissue adjacent to the tendon. It is called the peritendinous tissue and is also richly innervated. The white blood cells and the blood vessels walls in this tissue were showing immunoreaction for TNFR1 and TNFR2. Two types of nerve fascicles were found in this tissue, one normally appearing when staining for nerve markers and one type with signs of axonal loss. The latter had clearly strong immunoreactions for TNFR1 and TNFR2.

       The findings suggest that the TNF-alpha system is involved in both myopathies occurring due to overuse and in features in the peritendinous tissue in the tendinopathy situation. TNF-alpha and its receptors seem to be involved in degeneration but also in regeneration and healing of the tissue. The findings also suggest that TNF-alpha has effects on nerves showing axonal loss. The changes in the TNF-alpha system were seen both on the experimental side and contralaterally.

  • Public defence: 2017-12-08 09:00 A103 (Astrid Fagraeus), byggnad 6A, Umeå
    Wirebrand, Lisa
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Global regulatory factors that impact metabolic and lifestyle choices in Pseudomonas putida2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pseudomonas putida strains have a broad metabolic capacity and are innately resistant to many harmful substances – properties that make them of interest for a number of industrial and biotechnological application. They can rapidly adapt to changes in physico-chemical parameters in the soil and water environments they naturally inhabit. Like other bacteria, they have evolved both specific and cross-acting global regulatory circuits to control endurance traits and life style choices in order to survive. Three such survival tactics are 1) the ability to control flagella-mediated motility to search for metabolically favourable locations, 2) to produce protective biofilm structures to resist environmental insults, and 3) to distinguish the energetically most favourable carbon source amongst an array on offer. These processes are often co-ordinated regulated by intersecting networks that are controlled by global signalling molecules (second messengers) such as the nucleotides ppGpp and c-di-GMP, and globally acting proteins.

    In the first part of my thesis I present evidence that the PP4397 protein of P. putida is responsible for slowing down flagella-driven motility in response to c-di-GMP signalling from a dual-functional c-di-GMP turnover protein termed PP2258. This connection is expanded upon to present a potential signal transduction pathway from a surface located receptor to PP2258 and the c-di-GMP responsive PP4397 protein, and from there to the flagella motors to determine flagella performance. The transcriptional regulatory studies that accompany this work suggest a means by which transcriptional control may serve to initiate a co-ordinated blocking of de novo flagella biogenesis and slowing-down flagella rotation – two processes needed to enter the biofilm mode of growth. 

    Exiting from a biofilm matrix is also a c-di-GMP elicited behaviour, prompted when nutrients become scarce. In my second piece of work I present evidence that hunger-signals in the form of ppGpp directly control transcription to elevate the levels of a c-di-GMP degrading protein – BifA – which lies at the heart of programed biofilm dispersal. 

    The final part of my thesis, concerns how the global regulatory proteins Hfq and Crc act at multiple levels to subvert catabolism of phenolics to favour other preferred sources of carbon. Evidence is presented that this involves a two-tiered translational repression – one at the level of the master regulator of the system, and another at the level of the catabolic enzymes. This study also revealed a hitherto unsuspected role of Crc in maintenance of an IncP-2 plasmid within a bacterial population. This latter finding has implications for a wide variety of processes encoded by the IncP-2 group of Pseudomonas-specific mega-plasmids.

    The full text will be freely available from 2018-06-08 00:00
  • Public defence: 2017-12-08 10:00 Hörsal F, Humanisthuset, Umeå
    Lindblom, Ina
    Umeå University, Faculty of Arts, Department of historical, philosophical and religious studies.
    Känslans patriark: sensibilitet och känslopraktiker i Carl Christoffer Gjörwells familj och vänskapskrets, ca 1790-18102017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This dissertation is a study of how the culture of sensibility was expressed in the everyday practices and social relations of the Gjörwell family. Headed by publicist, publisher and royal librarian Carl Christoffer Gjörwell (1731-1811), the Gjörwell family served as the centre of a wide circle of friends in late 18th-century Stockholm. Gjörwell has been regarded as one of the first Swedish representatives of 18th-century sensibility as well as an archetype of the Swedish cult of friendship. Due to his effusive emotional expressiveness and passionate friendships with other men, Gjörwell has largely been derided as effeminate by researchers from the 19th century onwards.

    Using theoretical perspectives from the field of the history of emotions (more concretely the perspectives of William Reddy, Barbara Rosenwein and Monique Scheer) this study centres on the emotional practices of the Gjörwell family, especially taking aspects of gender, class, sexuality and power into account. Gjörwell’s vast collection of family and friendship correspondence forms the empirical basis of this study.

    This study shows that the Gjörwell family and circle of friends in many ways could be regarded as an emotional community in which primarily emotions of happiness and joy are expressed. Furthermore, this study shows how the exercise of power could form part in the creation of an emotional community, as Gjörwell makes constant attempts to influence the way family members and friends manage their emotions, strongly dissuading them from the expression of melancholy.

    Although he has been viewed as effeminate by posterity, Gjörwell in fact regards himself as manly. This is due to his ability to remain joyful through adversities which testifies to his strong, and therefore manly, nervous organisation. This study thus further illustrates how a marked shift in masculine gender norms took place between the 18th and 19th centuries.

    This study also shows how expression of tender emotion could be a way of reinforcing personal status. This was due to the close association made between sensibility and virtue, in itself a central concept during this era. As Gjörwell is denied recognition in his professional life, the expression of tender emotion – and thus of virtue – becomes an important aspect of his personal life. 

  • Public defence: 2017-12-08 10:00 Hörsal B, Samhällsvetarhuset, Umeå
    Marsja, Erik
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Attention capture by sudden and unexpected changes: a multisensory perspective2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main focus for this thesis was cross-modal attention capture by sudden and unexpected sounds and vibrations, known as deviants, presented in a stream the same to-be-ignored stimulus. More specifically, the thesis takes a multisensory perspective and examines the possible similarities and differences in how deviant vibrations and sounds affect visual task performance (Study I), and whether the deviant and standard stimuli have to be presented within the same modality to capture attention away from visual tasks (Study II). Furthermore, by presenting spatial deviants (changing the source of the stimuli from one side of the body to the other) in audiotactile (bimodal), tactile, and auditory to-be-ignored, it explores whether bimodal stimuli are more salient compared to unimodal (Study III). In addition, Study III tested the claims that short-term memory is domain-specific.

    In line with previous research, Study I found that both auditory and tactile deviants captured attention away from the visual task. However, the temporal dynamics between the two modalities seem to differ. That is, it seems like practice causes the effect of vibratory deviants to reduce, whereas this is not the case for auditory deviants. This suggests that there are central mechanisms (detection of the change) and sensory-specific mechanisms.

    Study II found that the deviant and standard stimuli must be presented within the same modality. If attention capture by deviants is produced by a mismatch within a neural model predicting upcoming stimuli, the neural model is likely built on stimuli within each modality separately.

    The results of Study III revealed that spatial and verbal short-term memory are negatively affected by a spatial change in to-be-ignored sequences, but only when the change is within a bimodal sequence. These results can be taken as evidence for a unitary account of short-term memory (verbal and spatial information stored in the same storage) and that bimodal stimuli may be integrated into a unitary percept that make any change in the stream more salient.