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  • Disputas: 2017-10-19 13:00 KB.E3.01 (Lilla Hörsalen), KBC-huset, Umeå
    Larsson, Malin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Computational methods for analyzing dioxin-like compounds and identifying potential aryl hydrocarbon receptor ligands: multivariate studies based on human and rodent in vitro data2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are omnipresent and persistent environmental pollutants. In particular, 29 congeners are of special concern, and these are usually referred to as dioxin-like compounds (DLCs). In the European Union, the risks associated with DLCs in food products are estimated by a weighted sum of the DLCs’ concentrations. These weights, also called toxic equivalency factors (TEFs), compare the DLCs’ potencies to the most toxic congener, 2,3,7,8-tetrachloro-dibenzo-p-dioxin (2378- TCDD). The toxicological effects of PCDD/Fs and PCBs are diverse, ranging from chloracne and immunological effects in humans to severe weight loss, thymic atrophy, hepatotoxicity, immunotoxicity, endocrine disruption, and carcinogenesis in rodents.

    Here, the molecular structures of DLCs were used as the basis to study the congeneric differences in in vitro data from both human and rodent cell responses related to the aryl hydrocarbon receptor (AhR). Based on molecular orbital densities and partial charges, we developed new ways to describe DLCs, which proved to be useful in quantitative structure-activity relationship modeling. This thesis also provides a new approach, the calculation of the consensus toxicity factor (CTF), to condense information from a battery of screening tests. The current TEFs used to estimate the risk of DLCs in food are primarily based on in vivo information from rat and mouse experiments. Our CTFs, based on human cell responses, show clear differences compared to the current TEFs. For instance, the CTF of 23478-PeCDF is as high as the CTF for 2378-TCDD, and the CTF of PCB 126 is 30 times lower than the corresponding TEF. Both of these DLCs are common congeners in fish in the Baltic Sea. Due to the severe effects of DLCs and their impact on environmental and human health, it is crucial to determine if other compounds have similar effects. To find such compounds, we developed a virtual screening protocol and applied it to a set of 6,445 industrial chemicals. This protocol included a presumed 3D representation of AhR and the structural and chemical properties of known AhR ligands. This screening resulted in a priority list of 28 chemicals that we identified as potential AhR ligands.

  • Disputas: 2017-10-20 09:00 Aulan, Umeå
    Stecksén, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Stroke thrombolysis on equal terms?: implementation and ADL outcome2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Stroke thrombolysis is a method for restoring cerebral blood flow after ischemic stroke, with high priority in the Swedish national guidelines. implementation of stroke thrombolysis in Swedish routine stroke care has shown marked differences between demographic groups, hospital types, and regions. The general aim of this thesis were to examine the implementation of ischemic stroke thrombolysis in Swedish routine stroke care with an equity perspective; to gain more insight into the factors that influence implementation, how the treatment has reached patient groups, and differences in long-term outcomes between women and men. Analysis of data from research interviews with clinicians working within stroke care displayed that the facilitators of and barriers to the implementation of stroke thrombolysis could broadly be categorized into those related to individuals, to social interactions and context, and to organizational and resource issues. Key facilitating factors expressed in interviews were work pride and motivation, good leadership, involvement of all staff members in the implementation process, and quality assurance. Major barriers concerned lack of competence and experience, outdated attitudes regarding stroke management, counterproductive power structures, lack of continuity, and insufficient human resources. National quality register data displayed that stroke thrombolysis treatment expanded to reach more patients with mild deficits. Groups with higher education were more likely to receive treatment, compared to groups with lower educational level. These education group differences have, however, decreased over time in relative terms, but not in absolute terms. Further, there were considerable between-hospitals differences in treatment rates for patients with milder deficits, associated with hospital’s overall stroke thrombolysis rates. Moreover, larger non-university hospitals displayed treatment rate differences between educational groups that were not attributable to patient characteristics. Among thrombolysis-treated women and men, that was independent in ADL before their stroke and survived the first year post-stroke, women experienced higher probability to be dependent in ADL at both 3 and 12 months post-stroke, compared to men. This difference remained significant despite comprehensive adjustments for individual characteristics, symptom severity, and acute effects from stroke thrombolysis.

    This thesis displays that clinicians face barriers and facilitators at several levels, suggesting implementation interventions could be targeted towards both the individual-, the social interactions and context-, and also the organisation and available resources level. Assurance of clinicians’ individual competence, peer support, and clinical leadership seem to be important areas to intervene. Stroke thrombolysis rates have expanded over time, and an increase in stroke thrombolysis delivery to patients with mild stroke symptoms has contributed to this increase. However, it seems considerable differences between hospitals inhibit equity of care delivery. Further, socioeconomically disadvantaged groups receive less often stroke thrombolysis. Type of hospital seems to play a role, yet the reasons for this difference are not fully understood. This thesis also display that stroke thrombolysis-treated women that survive 1 year after stroke, appears to face higher risk for dependency in ADL, compared to men.

  • Disputas: 2017-10-20 09:00 Sal 135, By 9A, Umeå
    Diderichsen, Saima
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    It's just a job: a new generation of physicians dealing with career and work ideals2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Today, women constitute about half of medical students. However, women are still underrepresented in prestigious specialties such as surgery. Some suggest that this could be explained by women being more oriented towards work-life balance.

    Aim: The overall aim of this dissertation was to explore aspects of gender in work-life priorities, career plans, clinical experiences and negotiations of professional ideals among medical students and newly graduated doctors, all in a Swedish setting.

    Method: We based the analysis on data from two different sources: an extensive questionnaire exploring gender and career plans among medical students (paper I-III) and interviews with newly graduated doctors (study IV).

    In paper I, four classes of first- and final-year medical (N=507, response rate 85%) answered an open-ended question about their future life, 60% were women. We conducted a mixed methods design where we analyzed the answers qualitatively to create categories that could be analyzed quantitatively in the second stage.

    In paper II, five classes of final-year medical students  were included (N = 372, response rate 89%), and 58% were women. We studied their specialty preference and how they rated the impact that the motivational factors had for their choice. In order to evaluate the independent impact of each motivational factor for specialty preference, we used logistic regression.

    In paper III, final-year medical students answered two open-ended questions: “Can you recall an event that made you interested of working with a certain specialty?” and “Can you recall an event that made you uninterested of working with a certain specialty?”. The response rate was 62% (N = 250),  and 58% were women. The analysis was similar to paper I, but here we focused on the qualitative results.

    In paper IV, thematic interviews were conducted in 2014 and 2015. We made a purposeful sampling of 15 junior doctors, including nine women and six men from eight different hospitals. Data collection and analysis was inspired by constructivist grounded theory methodology.

    Results: When looking at the work-life priorities of medical students and junior doctors it is clear that both men and women want more to life than work in their ideal future. The junior doctors renounced fully devoted and loyal ideal and presented a self-narrative where family and leisure was important to cope and stay empathic throughout their professional lives.

    The specialty preferences and the highly rated motives for choosing them were relatively gender neutral. However, the gender neutrality came to an end when the final-year medical students described clinical experiences that affected their specialty preference. Women were more often deterred by workplace cultures, whereas men were more often deterred by knowledge area, suggesting that it is a male privilege to choose a specialty according to interest.

    Among the newly graduated doctors, another male privilege seemed to be that men were able to pass more swiftly as real doctors, whereas the women experienced more dissonance between their self-understanding and being perceived as more junior and self-doubting.

    Conclusions: The career plans and work-life priorities of doctors-to-be were relatively gender neutral. Both female and male doctors, intended to balance work not only with a family but also with leisure. This challenges the health care system to establish more adaptive and flexible work conditions.

    Gender segregation in specialty choice is not the result of gender-dichotomized specialty preferences starting in medical school. This calls for a re-evaluation of the understanding where gender is seen as a mere background characteristic, priming women and men for different specialties. 

  • Disputas: 2017-10-20 13:00 N430, Naturvetarhuset, Umeå
    Åberg, Katarina
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Biomass conversion through syngas-based biorefineries: thermochemical process integration opportunities2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The replacement of fossil resources through renewable alternatives is one way to mitigate global climate change. Biomass is the only renewable source of carbon available for replacing oil as a refining feedstock. Therefore, it needs to be utilized not just as a fuel but for both biochemical and thermochemical conversion through biorefining. Optimizing and combining various conversion processes using a system perspective to maximize the valorization, biomass usage, and environmental benefits is of importance. This thesis work has evaluated the integration opportunities for various thermochemical conversion processes within a biorefinery system.

    The aim for all evaluated concepts were syngas production through gasification or reforming. Two potential residue streams from an existing biorefinery were evaluated as gasification feedstocks, thereby combining biochemical and thermochemical conversion. Torrefaction as a biomass pretreatment for gasification end-use was evaluated based on improved feedstock characteristics, process benefits, and integration aspects. A system concept, “Bio2Fuels”, was suggested and evaluated for low-temperature slow pyrolysis as a way to achieve simultaneous biomass refinement and transport driven CO2 negativity.

    Syngas was identified as a very suitable intermediate product for residue streams from biochemical conversion. Resulting syngas composition and quality showed hydrolysis residue as suitable gasification feedstock, providing some adjustments in the feedstock preparation. Gasification combined with torrefaction pretreatment demonstrated reduced syngas tar content. The co-gasification of biogas and wood in a FBG was successfully demonstrated with increased syngas H2/CO ratio compared to wood gasification, however high temperatures (≥1000°C) were required for efficient CH4 conversion. The demonstrated improved feedstock characteristics for torrefied biomass may facilitate gasification of biomass residue feedstocks in a biorefinery. Also, integration of a torrefaction unit on-site at the biorefinery or off-site with other industries could make use of excess low-value heat for the drying step with improved overall thermal efficiency. The Bio2Fuels concept provides a new application for slow pyrolysis. The experimental evaluation demonstrated significant hydrogen and carbon separation, and no significant volatilization of ash-forming elements (S and Cl excluded)  in low-temperature (<400°C) pyrolysis. The initial reforming test showed high syngas CH4 content, indicating the need for catalytic reforming.

    The collective results from the present work indicate that the application of thermochemical conversion processes into a biorefinery system, making use of by-products from biochemical conversion and biomass residues as feedstocks, has significant potential for energy integration, increased product output, and climate change mitigation.

  • Disputas: 2017-10-26 13:00 Betula, byggnad 6M NUS (målpunkt L), Umeå
    Strömvall, Kerstin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Extratumoral effects of highly aggressive prostate cancer2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Prostate cancer (PC) is the most common cancer in Sweden. Most patients have slow growing tumors that will not cause them any harm within their lifetime, but some have aggressive tumors and will die from their disease. The ability of current clinical practice to predict tumor behavior and disease outcome is limited leading to both over- and undertreatment of PC patients. The men who die from their disease are those that develop metastases. It is therefore of great value to find better and more sensitive prognostic techniques, so that metastatic spread can be detected (or predicted) at an early time point, and so that appropriate treatment can be offered to each subgroup of patients. The aim of this thesis was to investigate if, and by what means, highly aggressive prostate tumors influence extratumoral tissues such as the non-malignant parts of the prostate and regional lymph nodes (LN), and also if any of our findings could be of prognostic importance. Gene- and protein expression analysis were the main methods used to address these questions. Our research group has previously introduced the expression Tumor Instructed (Indicating) Normal Tissue (TINT), and we use the term TINT-changes when referring to alterations in non-malignant tissue due to the growth of a tumor nearby or elsewhere in the body. In the Dunning rat PC-model we found that MatLyLu (MLL)-tumors, having a high metastatic ability, caused pre-metastatic TINT-changes that differ from those caused by AT1-tumors who have low metastatic ability. Prostate-TINT surrounding MLL-tumors had elevated immune cell infiltration, and gene ontology enrichment analysis suggested that biological functions promoting tumor growth and metastasis were activated in MLL- while inhibited in AT1-prostate-TINT. In the regional LNs we found signs of impaired antigen presentation, and decreased quantity of T cells in the MLL-model. One of the downregulated genes in the MLL-LNs was Siglec1 (also known as Cd169), expressed by LN resident macrophages that are important for antigen presentation. When examining metastasis-free LN tissue from PC patients we found CD169 expression to be a prognostic factor for PC-specific survival, and reduced expression was linked to an increased risk of PC-specific death. Some of our findings in prostate- and LN-TINT could be seen already when the tumors were very small suggesting that differences in TINT-changes between tumors with different metastatic capability can be detected early in tumor progression. However, before coming of use in the clinic more research is needed to better define a suitable panel of prognostic TINT-factors as well as the right time window of when to use them.

  • Disputas: 2017-10-27 09:00 Aulan, Vårdvetarhuset, Umeå
    Sundqvist, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Forced repatriation of unaccompanied asylum-seeking refugee children: towards an interagency model2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Introduction Not all children seeking asylum without parents or other relatives are entitled to residence permits. In the last few years, more than one in four unaccompanied asylum-seeking refugee children have been forced to repatriate, either to their home country or to a transit country. Mostly the children refuse to leave the country voluntarily, and it becomes a forced repatriation. Five actors collaborate in the Swedish child forced repatriation process: social workers, staff at care homes, police officers, Swedish Migration Board officers and legal guardians. When a child is forced to repatriate, the Swedish workers involved must consider two different demands. The first demand requires dignified repatriation, which is incorporated from the European Union’s (EU’s) Return Directive into Swedish Aliens Act. The second demand requires that the repatriation process be conducted efficiently, which means that a higher number of repatriation cases must be processed. The fact that the same professionals have different and seemingly contradictory requirements places high demands on the involved collaborators. Two professionals have a legal responsibility for the children until the last minute before they leave Sweden: social workers and police officers. That makes them key actors in forced repatriation, as they carry most of the responsibility in the process. Further, they often work with children who are afraid what will happen when they return to their home country and often express their fear through powerful emotions. Being responsible and obliged to carry out the government’s decision, despite forcing children to leave a safe country, may evoke negative emotional and mental stress for the professionals involved in forced repatriation.

    Aim The overall aim of this study is to explore and analyse forced repatriation workers’ collaboration and perceived mental health, with special focus on social workers and police officers in the Swedish context.

    Materials and methods The study combines a qualitative and quantitative research design in order to shed light at both a deep and general level on forced repatriation. In qualitative substudy I, a qualitative case study methodology was used in one municipality in a middle-sized city in Sweden. The municipality had a contract regarding the reception of unaccompanied asylum-seeking refugee children iv with the Swedish Migration Board. The municipality in focus has a population of more than 100,000 inhabitants. The city in which the data were collected has developed a refugee reception system where unaccompanied asylumseeking refugee children are resettled and await a final decision regarding their permit applications. This situation made it possible to recruit participants who had worked with unaccompanied refugee children without a permit. Semi-structured interviews were conducted with a total of 20 social workers, staff at care homes, police officers, Swedish Migration Board officers and legal guardians. A thematic approach was used to analyse the data. In quantitative substudies II, III and IV, a national survey of social workers (n = 380) and police officers (n = 714), with and without experience of forced repatriation, was conducted. The questionnaires included sociodemographic characteristics, the Swedish Demand-Control Questionnaire, Interview Schedule for Social Interaction, Ways of Coping Questionnaire and the 12- item General Mental Health Questionnaire. Factor analysis, correlational analysis, and univariate and multivariable regression models were used to analyse the data.

    Results The qualitative results in substudy I showed low levels of collaboration among the actors (social workers, staff at care homes, police officers, Swedish Migration Board officers and legal guardians) and the use of different strategies to manage their work tasks. Some of them used a teamwork pattern, showing an understanding of the different roles in forced repatriation, and were willing to compromise for the sake of collaboration. Others tended to isolate themselves from interaction and acted on the basis of personal preference, and some tended to behave sensitively, withdraw and become passive observers rather than active partners in the forced repatriation. The quantitative results in substudy II showed that poorer mental health was associated with working with unaccompanied asylum-seeking refugee children among social workers but not among police officers. Psychological job demand was a significant predictor for mental health among social workers, while psychological job demand, decision latitude and marital status were predictors among police officers. Substudy III showed that both social workers and police officers reported relatively high access to social support. Furthermore, police officers working in forced repatriation with low levels of satisfaction with social interaction and close emotional support increased the odds of psychological disturbances. In substudy IV, social workers used more escape avoidance, distancing and positive-reappraisal coping, whereas police officers used more planful problem solving and self-controlling coping. Additionally, social workers with experience in forced repatriation used more planful problem solving than those without experience.

    Conclusions In order to create the most dignified forced repatriation, based on human dignity, for unaccompanied asylum-seeking refugee children and with healthy actors, a forced repatriation system needs: overall statutory national guidance, interagency collaboration, actors working within a teamworking pattern, forced repatriation workers with reasonable job demands and decision latitude, with a high level of social support and adaptive coping strategies. The point of departure for an interagency model is that it is impossible to change the circumstances of the asylum process, but it is possible to make the system more functional and better adapted to both the children’s needs and those of the professionals who are set to handle the children. A centre for unaccompanied asylum-seeking refugee children, consisting of all actors involved in the children’s asylum process sitting under the same roof, at the governmental level (Swedish Migration Board, the police authority) and municipality level (social services, board of legal guardians), can meet all requirements.

  • Disputas: 2017-10-27 09:00 Hörsal D Unod T9, Umeå
    Lindqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    The role of the type I interferons and viperin during neurotropic flavivirus infection2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Flaviviruses are globally distributed pathogens that cause millions of human infections annually. One of the most detrimental outcomes of flavivirus infection is encephalitis, which is caused by neurotropic flaviviruses such as West Nile virus (WNV), Japanese encephalitis virus (JEV), and Tick-borne encephalitis virus (TBEV). The type I interferons (IFNs) are powerful cytokines, and they are known as the first line of defense against viral infection. IFNs are expressed at low or undetectable levels at the basal state, but recognition of invading pathogens triggers a robust IFN response. After synthesis, IFN is secreted and acts in an autocrine or paracrine manner by binding to the interferon-α/β receptor (IFNAR) receptor, which is expressed on the surface of all nucleated cells. Binding to IFNAR mediates a downstream cascade that triggers expression of hundreds of interferon-stimulated genes (ISGs). Some ISGs express signaling molecules to amplify the response while others are potent antiviral proteins that can efficiently limit viral infection. The impact of the type I IFN response in tick-borne flavivirus infection was not previously known. We found that the type I IFN response was crucial for protection of mice against neurotropic infection with tick-borne flaviviruses such as TBEV and Langat virus (LGTV). The response was needed both in the periphery as well as in the central nervous system (CNS), as transgenic mice lacking either peripherally or CNS-located IFNAR both succumbed to LGTV infection. Although we found that the local IFN response within the CNS is essential for protection against lethal LGTV infection, the cells responsible for the local IFN production were not known.

    Astrocytes are one of the most abundant cell types within the CNS, but their role in neurotropic flavivirus infection was not fully characterized. In other viral infections, astrocytes are potent IFN producers, thus we were interested in characterizing the role of the type I IFN response in astrocytes during neurotropic flavivirus infection and its contribution to flavivirus pathogenesis. We found that upon flavivirus infection, astrocytes mount a strong type I IFN response that protects neighboring astrocytes from TBEV, JEV, WNV, and ZIKV infection. Furthermore, IFN signaling was found to protect astrocytes from TBEV-induced cytopathic effects. However, the ISGs that mediated these effects were not known.

    In vitro studies of viperin, which was discovered in 2001 as an ISG with broad antiviral activity, has shown strong antiviral activity against TBEV, but its role in vivo and mode of action in flavivirus infection was not known. Using mice deficient in viperin, we wanted to determine the role of viperin in flavivirus infection. We found that viperin plays a region-specific role in the brain by controlling LGTV replication in the olfactory bulb and cerebrum. Remarkably, viperin was able to inhibit TBEV replication in primary cortical neurons isolated from the cerebrum but not in granule cell neurons isolated from the cerebellum. Furthermore, IFN treatment failed to compensate for loss of viperin in cortical neurons, indicating that viperin might be the most important ISG against TBEV in cortical neurons. Interestingly, we also found that viperin is needed for the IFN-mediated antiviral response against WNV and ZIKV in cortical neurons. Thus, viperin showed broad but region-specific antiviral mechanisms against different flaviviruses.

    Although viperin has been shown to inhibit many viruses, the molecular antiviral mechanism is not clear and appears to differ between viruses. We performed a co-immunoprecipitation (CoIP) screen to identify TBEV proteins that could interact with viperin, and prM, E, NS2A, NS2B, and NS3 were identified. Interaction of viperin with NS3 resulted in degradation of the viral protein. We screened NS3 of JEV, yellow fever virus (YFV), ZIKV, and TBEV. Interestingly, although all NS3 proteins tested interacted with viperin, only those of ZIKV, and TBEV were significantly degraded by viperin. The degradation of NS3 correlated well with the antiviral activity of viperin, as only TBEV and ZIKV were inhibited.

    In summary, this work revealed the importance of the local type I IFN response in the brain during neurotropic infections by flaviviruses. We identified astrocytes to be an important IFN producer within the CNS during neurotropic flavivirus infection. Astrocytes release type I IFN quickly after viral infection, and this interferon protects neighboring neurons and astrocytes from infection. Furthermore, viperin, a very potent antiviral ISG, is highly expressed in astrocytes and it is essential for controlling viral replication and mediating viral clearance in both neurons and astrocytes of the cerebrum. We also found that viperin specifically targeted the NS3 proteins of TBEV and ZIKV for degradation.

    Fulltekst tilgjengelig fra 2018-10-27 10:31
  • Disputas: 2017-10-27 10:00 KB.E3.03 (Stora hörsalen, Carl Kempe-salen), KBC-huset, Umeå
    Näsström, Elin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Diagnosis of acute and chronic enteric fever using metabolomics2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Enteric (or typhoid) fever is a systemic infection mainly caused by Salmonella Typhi and Salmonella Paratyphi A. The disease is common in areas with poor water quality and insufficient sanitation. Humans are the only reservoir for transmission of the disease. The presence of asymptomatic chronic carriers is a complicating factor for the transmission. There are major limitations regarding the current diagnostic methods both for acute infection and chronic carriage. Metabolomics is a methodology studying metabolites in biological systems under influence of environmental or physiological perturbations. It has been applied to study several infectious diseases, with the goal of detecting diagnostic biomarkers. In this thesis, a mass spectrometry-based metabolomics approach, including chemometric bioinformatics techniques for data analysis, has been used to evaluate the potential of metabolite biomarker patterns for diagnosis of enteric fever at different stages of the disease.

    In Paper I, metabolite patterns related to acute enteric fever were investigated. Human plasma samples from patients in Nepal with culture-confirmed S. Typhi or S. Paratyphi A infection were compared to afebrile controls. A metabolite pattern discriminating between acute enteric fever and afebrile controls, as well as between the two causative agents of enteric fever was detected. The strength of using a panel of metabolites instead of single metabolites as biomarkers was also highlighted. In Paper II, metabolite patterns for acute enteric fever, this time focusing only on S. Typhi infections, were investigated. Human plasma from patients in Bangladesh with culture-positive or -negative but clinically suspected S. Typhi infection were compared to febrile controls. Differences were found in metabolite patterns between the culture-positive S. Typhi group and the febrile controls with a heterogeneity among the suspected S. Typhi samples. Consistencies in metabolite patterns were found to the results from Paper I. In addition, a validation cohort with culture-positive S. Typhi samples and a control group including patients with malaria and infections caused by other pathogens was analysed. Differences in metabolite patterns were detected between S. Typhi samples and all controls as well as between S. Typhi and malaria. Consistencies in metabolite patterns were found to the primary Bangladeshi cohort and the Nepali cohort from Paper I. Paper III focused on chronic Salmonella carriers. Human plasma samples from patients in Nepal undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage were compared to non-carriage controls. The Salmonella carriage samples were distinguished from the non-carriage controls and differential signatures were also found between the S. Typhi and S. Paratyphi A carriage samples. Comparing metabolites found during chronic carriage and acute enteric fever (in Paper I) resulted in a panel of metabolites significant only during chronic carriage. This work has contributed to highlight the potential of using metabolomics as a tool to find diagnostic biomarker patterns associated with different stages of enteric fever.

  • Disputas: 2017-10-27 10:00 Hörsal B, Samhällsvetarhuset, Umeå
    Österlind, Malin
    Umeå universitet, Samhällsvetenskapliga fakulteten, Pedagogiska institutionen.
    Strävan efter samhällsförbättring: idrottspolitiska problematiseringar och lösningsstrategier för formandet av den nyttiga idrotten och den idrottande individen2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Sport and sport participation is generally believed to positively contribute to society and individuals and have become important to welfare policy in the westernised world. Simultaneously, there has been an increased political and academic interest in turning sport policy, sport and sport participation into a relevant object of study and evaluation. The overall aim of this dissertation is to develop knowledge on contemporary sport policy and evaluation in relation to ideas about the social significance of sport and sport participation. The purpose is to critically examine how sport policy evaluations, their problematisations and solution proposals help to shape particular images of the good society, good sports and the ideal sport participant. Three research questions are posed: (1) Through what ways of thinking, speaking and knowing are societal and sport policy problems, goals and ideals defined? (2) Through what techniques, methods and strategies are solutions proposed to solve the problems and achieve desired goals and ideals? (3) How are different types of individual and collective (non-)soughtafter subjectivities anticipated and shaped? Drawing on the concept of governmentality, the study focuses on the governing of sport's and the sport participant's conduct, the political problematisations and rationalities regarding this conduct, and the strategies proposed to enhance this conduct. The governmental role of evaluation, knowledge production and scientific expertise is given specific attention. The gradual shifts in governmental rationalities and technologies, from a social form of governing to an advanced liberal form of governing, in the Swedish welfare state provide an overall framework of the study. Two kinds of empirical materials are analysed. First, final reports of sport political government Commissions of inquiries, published in the Swedish Government Official Reports (SOU) from 1922-2008, are analysed. Second, reports of sport political evaluations, published by the Swedish Research Council for Sport Science (CIF) from 2011-2015, are analysed. The analysis reported on in article 1 shows that citizens' 'good' and 'healthy' behaviour and bodies are a focus of problematisation throughout the studied period. In relation to this, sport is seen as an important tool and solution. Parallel to the increased critique of sport in contemporary times, a neo-liberal governmentality is embraced which in turn affects how 'problems' and 'solutions' are thought of in individualistic and rational ways. The analysis reported on in article 2 shows that the 2008 government Commission adopted two main 'problematics'. The democratic problematic concerned a commitment to issues of democracy and equality of opportunities and specified a particular problem of sport; sport excludes rather than includes. The health problematic concerned a commitment to issues of public health and physical activity and focused on a particular problem of the population: people are physically inactive and unhealthy. The argument being proposed in article 2 is that these two problematics construct the ‘problem’ of sport and the sport (non)participant in specific ways, drawing on particular forms of knowledge and discourse, with certain implications for the judgements made and the solutions proposed by the Commission. The analysis reported on in article 3 demonstrates three strategies of evaluation and governing: strategies of representation; deliberation; and reflexivity. The argument being proposed in article 3 is that these three strategies draw on different yet overlapping forms and methods of knowledge about sport participation and thereby also produce different (non-)sport participant subject positions. The analysis reported on in article 4 offers an alternative theoretical conceptualisation, based on governmentality, of the Swedish sports model and shows how sport policy, governing and power can be seen in the light of shifting forms of governmental rationality (i.e. governing from a social point of view to an advanced liberal way of governing). In conclusion, the analyses provided in the thesis as a whole suggest that processes of societal and political improvement in contemporary political governing of sport and sport participation, involves particular images of the good society, good sports and the ideal sport participant.

  • Disputas: 2017-10-27 13:00 Hörsal B, 9 tr, Umeå
    Doohan, Isabelle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Surviving a major bus crash: experiences from the crash and five years after2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background Major road traffic crashes (RTCs) can have a significant impact on the survivors, their family, and their friends, as well as on emergency personnel, volunteers, and others involved. However, survivors’ perspectives are rare or missing in research on major RTCs in Sweden. A comprehensive understanding of the survivors and their experiences is also lacking. By studying what it is like to survive a major RTC, the care and support provided to survivors can be adapted and improved.

    The overall aim is to broaden the understanding of the short- and long-term consequences and experiences of surviving a major bus crash.

    Methods The contexts are two bus crashes that occurred in Sweden, in February 2007 and December 2014. In total, the participants are 110 out of the 112 survivors, and the data is collected through telephone interviews, official reports, and medical records at one month, three months, and five years after the crashes. Analysis methods include qualitative content analysis, descriptive statistics, thematic analysis, and mixed methods research analysis.

    Results One month after the crash, most of the survivors were experiencing minor or major physical and/or psychological stress in their everyday lives (Study I). Four main findings were identified regarding their experiences of immediate care (Study II): prehospital discomfort, lack of compassionate care, dissatisfaction with crisis support, and satisfactory initial care and support. The importance of compassion and being close to others was also highlighted. Five years after the bus crash in Rasbo (Study III), survivors were still struggling with physical injuries and mental problems. Other long-term consequences were a lasting sense of connectedness among fellow passengers, a gratitude for life, as well as feelings of distress in traffic, especially in regard to buses. The main findings from study IV indicated that injury severity did not seem to affect mental health, and that social aspects were important to the recovery process. There was an interconnection among survivors in which they seemed to be linked to each other’s recovery.

    Conclusion A strong need for short- and long-term social and psychological support in terms of compassion and community is evident in all the studies. The survivors ought to be acknowledged as capable and having the resources to contribute to their own and their fellow survivors’ recovery and health. There is a need for greater understanding of how different the survivors are, with each one of them having various physical, psychological, social, and existential needs. 

  • Disputas: 2017-10-27 13:00 N420, Umeå
    Fodor, Szabolcs
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Towards semi-automation of forestry cranes: automated trajectory planning and active vibration damping2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Forests represent one of the biggest terrestrial ecosystems of Earth, that can produce important raw renewable materials such as wood with the help of sun, air and water. To efficiently extract these raw materials, the tree harvesting process is highly mechanized in developed countries, meaning that advanced forestry machines are continuously used to fell, to process and to transport the logs and biomass obtained from the forests. However, working with these machines is demanding both mentally and physically, which are known factors to negatively affect operator productivity. Mental fatigue is mostly due to the manual operation of the on-board knuckleboom crane, which requires advanced cognitive work with two joystick levers, while the most serious physical strains arise from cabin vibrations. These vibrations are generated from knuckleboom crane vibrations as a result of aggressive manual operation.

    To enhance operator workload, well-being, and to increase productivity of the logging process, semi-automation functions are suggested, which are supervised automatic executions of specific work elements. Some of the related issues are addressed in the current thesis. Therefore, the content is divided into: (1) the design and development of a semi-automation function focused only on the base joint actuator (slewing actuator) of a knuckleboom crane, and (2) active vibration damping solutions to treat crane structure vibrations induced by the main lift cylinder (inner boom actuator). The considered reference machine is a downsized knuckleboom crane of a forwarder machine, which is used to pick up log assortments from a harvesting site.

    The proposed semi-automation function presented in the first part could be beneficial for operators to use during log loading/unloading scenarios. It consists from a closed-loop position control architecture, to which smooth reference slewing trajectories are provided by a trajectory planner that is automated via operator commands. The used trajectory generation algorithms are taken from conventional robotics and adapted to semi-automation context with proposed modifications that can be customizable by operators.

    Further, the proposed active vibration damping solutions are aimed to reduce vibrations of the knuckleboom crane excited by the inner boom actuator due to aggressive manual commands. First, a popular input shaping control technique combined with a practical switching logic was investigated to deal with the excited payload oscillations. This technique proved to be useful with a fixed crane pose, however it did not provide much robustness in terms of different link configurations. To tackle this problem an H2-optimal controller is developed, which is active in the pressure feedback-loop and its solely purpose is to damp the same payload oscillations. During the design process, operator commands are treated and explained from input disturbance viewpoint.

    All of the hypothesis throughout this thesis were verified with extensive experimental studies using the reference machine.

  • Disputas: 2017-11-03 10:00 KB.E3.01 (Lilla Hörsalen), Umeå
    Ochtrop, Philipp
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Selective protein functionalisation via enzymatic phosphocholination2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Proteins are the most abundant biomolecules within a cell and are involved in all biochemical cellular processes ultimately determining cellular function. Therefore, to develop a complete understanding of cellular processes, obtaining knowledge about protein function and interaction at a molecular level is critical. Consequently, the investigation of proteins in their native environment or in partially purified mixtures is a major endeavour in modern life sciences. Due to their high chemical similarity, the inherent problem of studying proteins in complex mixtures is to specifically differentiate one protein of interest from the bulk of other proteins. Site-specific protein functionalisation strategies have become an indispensable tool in biochemical- and cell biology studies. This thesis presents the development of a new enzymatic site-specific protein functionalisation strategy that is based on the reversible covalent phosphocholination of short amino acid sequences in intact proteins. A synthetic strategy has been established that allows access to functionalised CDP-choline derivatives carrying fluorescent reporter groups, affinity tags or bioorthogonal handles. These CDP-choline derivatives serve as co-substrates for the bacterial phosphocholinating enzyme AnkX from Legionella pneumophila, which transfers a phosphocholine moiety to the switch II region of its native target protein Rab1b during infection. We identified the octapeptide sequence TITSSYYR as the minimum recognition sequence required to direct the AnkX catalysed phosphocholination and demonstrated the functionalisation of proteins of interest carrying this recognition tag at the N- or C-terminus as well as in internal loop regions. Moreover, this covalent modification can be hydrolytically reversed by the action of the Legionella enzyme Lem3, which makes the labeling strategy the first example of a covalent and reversible approach that is fully orthogonal to current existing methodologies. Thus, the here presented protein functionalisation approach holds the potential to increase the scope of possible labeling strategies in complex biological systems. In addition to the labeling of tagged target proteins, a CDP-choline derivative equipped with a biotin affinity-tag was synthesised and used in pull-down experiments to investigate the substrate scope of AnkX and to elucidate the role of protein phosphocholination during Legionella pneumophila infection.

  • Disputas: 2017-11-03 10:15 S Hörsal A, Samhällsvetarhuset, Umeå
    Åberg, Kajsa G.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för geografi och ekonomisk historia, Kulturgeografi.
    "Anyone could do that": Nordic perspectives on competence in tourism2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In academic reasoning, as well as policy rhethoric, much attention has been drawn to the low thresholds to employment and entrepreneurship in tourism. The purpose of this thesis is to go beyond the simplified images and examine the educational characteristics of the tourism workforce in a way that includes both a geographical and work task related aspect. By employing a sequential mix of methods, two perspectives on competence in tourism are presented. First, the actual presence of formal education within the workforce is mapped and discussed based on descriptive analyses of register data. Thereafter, thematic analyses of interviews are used to allow for a discussion on underlying reasoning of recruitment. The theoretical point of departure is that the workforce is a crucial input factor of the production process in labour intense service sectors such as tourism. However, the access to a suitable workforce differs between destinations. It is therefore imperative to scrutinize its characteristics in order to set relevant strategies for development, as well as education.

    The thesis contains four individual papers and an introductory section. The first two papers are based on register data on the Swedish national workforce in the years 2000, 2005 and 2010. The results show that the general level of formal education is not exceptionally low in tourism and that it is rather linked to geography than occupational sector. There was also confirmed to be a mismatch between tourism-specific education and work in tourism. In the second part of the thesis, focus is turned to the managerial segment within destination development. The geographical scope includes the northern region of Sweden and one case study area each in Norway and Finland. The empirical material shows that tourism-specific education was not prioritized when recruiting for destination management.

    The empirical findings are brought together in the concluding discussion of the thesis. It is there suggested that reasoning on the educational characteristics of the tourism workforce needs to  include the diversity of local preconditions and needs relating to geography and work tasks.