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  • Widerström, Micael
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Wiström, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Edebro, Helén
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Marklund, Elisabeth
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Backman, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Colonization of patients, healthcare workers, and the environment with healthcare-associated Staphylococcus epidermidis genotypes in an intensive care unit: a prospective observational cohort study2016In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 16, 743Article in journal (Refereed)
    Abstract [en]

    Background: During the last decades, healthcare-associated genotypes of methicillin-resistant Staphylococcus epidermidis (HA-MRSE) have been established as important opportunistic pathogens. However, data on potential reservoirs on HA-MRSE is limited. The aim of the present study was to investigate the dynamics and to which extent HA-MRSE genotypes colonize patients, healthcare workers (HCWs) and the environment in an intensive care unit (ICU).

    Methods: Over 12 months in 2006-2007, swab samples were obtained from patients admitted directly from the community to the ICU and patients transferred from a referral hospital, as well as from HCWs, and the ICU environment. Patients were sampled every third day during hospitalization. Antibiotic susceptibility testing was performed according to EUCAST guidelines. Pulsed-field gel electrophoresis and multilocus sequence typing were used to determine the genetic relatedness of a subset of MRSE isolates.

    Results: We identified 620 MRSE isolates from 570 cultures obtained from 37 HCWs, 14 patients, and 14 environmental surfaces in the ICU. HA-MRSE genotypes were identified at admission in only one of the nine patients admitted directly from the community, of which the majority subsequently were colonized by HA-MRSE genotypes within 3 days during hospitalization. Almost all (89%) of HCWs were nasal carriers of HA-MRSE genotypes. Similarly, a significant proportion of patients transferred from the referral hospital and fomites in the ICU were widely colonized with HA-MRSE genotypes.

    Conclusions: Patients transferred from a referral hospital, HCWs, and the hospital environment serve as important reservoirs for HA-MRSE. These observations highlight the need for implementation of effective infection prevention and control measures aiming at reducing HA-MRSE transmission in the healthcare setting.

  • Waern, Margda
    et al.
    Waern, Margda
    Kaiser, Niclas
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Salander Renberg, Ellinor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Psychiatrists' experiences of suicide assessment2016In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 16, 440Article in journal (Refereed)
    Abstract [en]

    Background: Clinical guidelines for suicide prevention often stress the identification of risk and protective factors as well as the evaluation of suicidal intent. However, we know very little about what psychiatrists actually do when they make these assessments. The aim was to investigate psychiatrists' own accounts of suicide assessment consultations, with a focus on their behaviors, attitudes and emotions.

    Method: Semi-structured in depth interviews were carried out with a purposive selection of 15 psychiatrists.

    Results: Thematic analysis revealed three main themes: understanding the patient in a precarious situation, understanding one's own reactions, and understanding how the doctor-patient relationship impacted on risk assessment and management decisions. Emotional contact and credibility issues were common subthemes that arose when the respondents talked about trying to understand the patient. The psychiatrists stressed the semi-intuitive nature of their assessments. Problems related to the use of risk factor assessments and rating scales were apparent. Assessment consultations could evoke physical and emotional symptoms of anxiety, and concerns about responsibility could lead to repressive management decisions. In situations of mutual trust, however, the assessment consultation could kick-start a therapeutic process.

    Conclusion: This study highlights psychiatrists' experiences in clinical suicide assessment situations. Findings have implications for professional development as well as for service delivery.

  • Sarneel, Judith M.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Ecology and Biodiversity Group and Plant Ecophysiology Group, Utrecht University, Utrecht, The Netherlands.
    Sarneel, Judith M.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Ecology and Biodiversity Group and Plant Ecophysiology Group, Utrecht University, Utrecht, The Netherlands.
    Effects of experimental snowmelt and rain on dispersal of six plant species2016In: Ecohydrology, ISSN 1936-0584, E-ISSN 1936-0592, Vol. 9, no 8, 1464-1470 p.Article in journal (Refereed)
    Abstract [en]

    Water flows affect dispersal of propagules of many plant species, and rivers and streams are therefore very important dispersal vectors. However, small water flows such as trough rain and snowmelt are much more common, but their effects on dispersal are barely studied. The importance of this form of dispersal deserves attention, especially when considering that climate change is predicted to change the amounts of rain and snow worldwide. Dispersal through melting snow and rain was addressed experimentally, using artificial soils mounted on slopes with different angles and subjected to a melting snow pack or an equivalent amount of dripping water. Seeds on the soil moved on average 3.02 cm (+/- 1.81 SE) in rain treatments and 0.23 cm (+/- 0.3 SE) in snowmelt treatments. Tracking plastic granules in field conditions further showed that snowmelt exhibited minimal dispersal capacity. Dispersal distances by rain were enhanced by increasing slope angles and with decreasing seed volume. Given that many species in cold environments have small seeds, dispersal by rain could provide an important (secondary) dispersal mechanism in these habitats.

  • Håkansson, Tatiana
    Umeå University, Faculty of Social Sciences, Department of Education.
    Håkansson, Tatiana
    Umeå University, Faculty of Social Sciences, Department of Education.
    Idrott som mötesplats: En kvalitativ studie om invandrarungdomars möte med svensk föreningsidrott2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Youth with foreign background is a group left out in the Swedish sports associations. The aim of the study is to understand what is often happening in the meeting of the youth with foreign background and the Swedish sports associations. Nine interviews have been carried out with boys and girls participating in the same sports team. The results have shown that there are some gender differences due to how their surrounding sees them. It is also shown that girls with foreign background have much lower representation in their team compared to boys. The conclusion is that it is very important for the youth to participate in the Swedish sports associations, with special emphasis on the significance of the relation between them and their leaders. However, barriers due to the cultural and language differences make the integration complicated. Nevertheless, sports activities themselves are very important for the youth with foreign background and play an important role in their social and cultural life and support their learning skills. Of vital importance is also the possibility of social getting together that sports activities offers youth with foreign background, such as sports camps and team building. Such activities outside the sports arenas have received very positive comments from those interviewed. Vital research in the field of integration through sports activities is rather scarce. The study indicates that additional research on integration through sports activities is called for.

  • Olsson, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Honkala, Emma
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Karhunen, Pekka J.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kok, Eloise H.
    HSV presence in brains of individuals without dementia: the TASTY brain series2016In: Disease Models and Mechanisms, ISSN 1754-8403, E-ISSN 1754-8411, Vol. 9, no 11, 1349-1355 p.Article in journal (Refereed)
    Abstract [en]

    Herpes simplex virus (HSV) type 1 affects a majority of the population and recent evidence suggests involvement in Alzheimer's disease aetiology. We investigated the prevalence of HSV type 1 and 2 in the Tampere Autopsy Study (TASTY) brain samples using PCR and sero-positivity in plasma, and associations with Alzheimer's disease neuropathology. HSV was shown to be present in human brain tissue in 11/584 (1.9%) of samples in the TASTY cohort, of which six had Alzheimer's disease neuropathological amyloid beta (A beta) aggregations. Additionally, serological data revealed 86% of serum samples tested were IgG-positive for HSV. In conclusion, we report epidemiological evidence of the presence of HSV in brain tissue free from encephalitis symptoms in a cohort most closely representing the general population (a minimum prevalence of 1.9%). Whereas 6/11 samples with HSV DNA in the brain tissue had A beta aggregations, most of those with A beta aggregations did not have HSV present in the brain tissue.

  • Haglund, Axel
    et al.
    Haglund, Axel
    Lindh, Asa U.
    Lysell, Henrik
    Renberg, Ellinor Salander
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Waern, Margda
    Runeson, Bo
    Interpersonal violence and the prediction of short-term risk of repeat suicide attempt2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 36892Article in journal (Refereed)
    Abstract [en]

    In this multi-center cohort study, suicide attempters presenting to hospital (N = 355, 63% women) were interviewed using the Karolinska Interpersonal Violence Scale (KIVS) and followed-up by medical record review. Main outcome was non-fatal or fatal repeat suicide attempt within six months. Also, repeat attempt using a violent method was used as an additional outcome in separate analyses. Data were analyzed for the total group and for men and women separately. Repeat attempts were observed within six months in 78 persons (22%) and 21 (6%) of these used a violent method. KIVS total score of 6 or more was associated with repeat suicide attempt within six months (OR = 1.81, CI 1.08-3.02) and predicted new attempts with a sensitivity of 62% and a specificity of 53%. A three-fold increase in odds ratio was observed for repeat attempt using a violent method (OR = 3.40, CI 1.22-9.49). An association between exposure to violence in adulthood and violent reattempt was seen in women (OR = 1.38, CI 1.06-1.82). The overall conclusions are that information about interpersonal violence may help predict short-term risk for repeat suicide attempt, and that structured assessment of interpersonal violence may be of value in risk assessment after attempted suicide.

  • Monteferrante, C. G.
    et al.
    Monteferrante, C. G.
    Jirgensons, A.
    Varik, Vallo
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia.
    Hauryliuk, VVasili
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia.
    Goessens, W. H. F.
    Hays, J. P.
    Evaluation of the characteristics of leucyl-tRNA synthetase (LeuRS) inhibitor AN3365 in combination with different antibiotic classes2016In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 11, 1857-1864 p.Article in journal (Refereed)
    Abstract [en]

    Aminoacyl tRNA synthetases are enzymes involved in the key process of coupling an amino acid to its cognate tRNA. AN3365 is a novel antibiotic that specifically targets leucyl-tRNA synthetase, whose development was halted after evaluation in phase II clinical trials owing to the rapid selection of resistance. In an attempt to bring AN3365 back into the developmental pipeline we have evaluated the efficacy of AN3365 in combination with different classes of antibiotic and characterized its mechanism of action. Although we detect no synergy or antagonism in combination with a range of antibiotic classes, a combination of AN3365 with colistin reduces the accumulation of AN3365-resistant and colistin resistance mutations. We also demonstrate that treatment with AN3365 results in the dramatic accumulation of the alarmone (p)ppGpp, the effector of the stringent response-a key player in antibiotic tolerance.

  • Karlsson, Terese
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Terese
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Persson, Emma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tumor Cell-Derived Exosomes from the Prostate Cancer Cell Line TRAMP-C1 Impair Osteoclast Formation and Differentiation2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, e0166284Article in journal (Refereed)
    Abstract [en]

    Skeletal metastatic disease is a deleterious consequence of dissemination of tumor cells from numerous primary sites, such as prostate, lung and breast. Skeletal metastases are still incurable, resulting in development of clinical complications and decreased survival for cancer patients with metastatic disease. During the last decade, tumor cell-derived microvesicles have been identified and suggested to be involved in cancer disease progression. Whether cancer exosomes are involved in tumor and bone cell interactions in the metastatic site is still, however, a rather unexplored field. Here we show that exosomes isolated from the murine prostate cancer cell line TRAMP-C1 dramatically decrease fusion and differentiation of monocytic osteoclast precursors to mature, multinucleated osteoclasts. The presence of tumor cell-derived exosomes also clearly decreased the expression of established markers for osteoclast fusion and differentiation, including DC-STAMP, TRAP, cathepsin K, and MMP-9. In contrast, exosomes derived from murine fibroblastic cells did not affect osteoclast formation. Our findings suggest that exosomes released from tumor cells in the tumor-bone interface are involved in pathological regulation of bone cell formation in the metastatic site. This further strengthens the role of tumor cell-derived microvesicles in cancer progression and disease aggressiveness.

  • Allas, Ular
    et al.
    Allas, Ular
    Toom, Lauri
    Selyutina, Anastasia
    Maeorg, Uno
    Medina, Ricardo
    Merits, Andres
    Rinken, Ago
    Hauryliuk, Vasili
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). University of Tartu, Institute of Technology, Nooruse 1, Tartu 50411, Estonia.
    Kaldalu, Niilo
    Tenson, Tanel
    Antibacterial activity of the nitrovinylfuran G1 (Furvina) and its conversion products2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 36844Article in journal (Refereed)
    Abstract [en]

    2-Bromo-5-(2-bromo-2-nitrovinyl) furan (G1 or Furvina) is an antimicrobial with a direct reactivity against thiol groups. It is active against Gram-positive and Gram-negative bacteria, yeasts and filamentous fungi. By reacting with thiol groups it causes direct damage to proteins but, as a result, is very short-living and interconverts into an array of reaction products. Our aim was to characterize thiol reactivity of G1 and its conversion products and establish how much of antimicrobial and cytotoxic effects are due to the primary activity of G1 and how much can be attributed to its reaction products. Stability of G1 in growth media as well as its conversion in the presence of thiols was characterized. The structures of G1 decomposition products were determined using NMR and mass-spectroscopy. Concentration-and time-dependent killing curves showed that G1 is bacteriostatic for Escherichia coli at the concentration of 16 mu g/ml and bactericidal at 32 mu g/ml. However, G1 is inefficient against non-growing E. coli. Addition of cysteine to medium reduces the antimicrobial potency of G1. Nevertheless, the reaction products of G1 and cysteine enabled prolonged antimicrobial action of the drug. Therefore, the activity of 2-bromo-5-(2-bromo-2-nitrovinyl) furan is a sum of its immediate reactivity and the antibacterial effects of the conversion products.

  • Semasaka, Jean Paul S.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. University of Rwanda College of Medicine and Health Sciences School of Public Health, Kigali, Rwanda.
    Semasaka, Jean Paul S.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. University of Rwanda College of Medicine and Health Sciences School of Public Health, Kigali, Rwanda.
    Krantz, Gunilla
    Nzayirambaho, Manasse
    Munyanshongore, Cyprien
    Edvardsson, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Judith Lumley Centre, La Trobe University, Melbourne, Australia.
    Mogren, Ingrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Self-reported pregnancy-related health problems and self-rated health status in Rwandan women postpartum: a population-based cross-sectional study2016In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 16, 340Article in journal (Refereed)
    Abstract [en]

    Background: Self-rated health status (SRH) can be used as a predictor of morbidity and mortality. Postpartum self-rated health has been used to estimate maternal morbidity and postpartum problems. Reproductive history factors are associated with poor self-rated health postpartum. This study investigated prevalence of self-reported health problems during first, second, and third trimesters of pregnancy, delivery, and postpartum. In addition, this study investigated SRH in Rwandan women up to 13 months from partus. Methods: This population-based, cross-sectional study collected data in 2014 using structured interviews (N = 921). Univariable analysis was used to identify variables that were associated with poor self-rated health status (poor-SRH). Logistic regression analyses were performed to identify factors associated with poor-SRH at one day, one week, and one month postpartum and at the time of the interview. Results: Mean time between latest delivery and the time of interview was 7.1 months. Prevalence of anaemia, hypertension, diabetes mellitus during pregnancy, and severe bleeding during pregnancy and labour were 15.0, 4.9, 2.4, and 3.7 %, respectively. The prevalence of poor-SRH was 32.2 % at one day postpartum, 7.8 % at one month, and 11.7 % at time of the interview. Hypertension during pregnancy and significant postpartum haemorrhage were associated with poor-SRH at one day and one week postpartum. Severe bleeding during pregnancy and labour were associated with poor-SRH at one week and one month postpartum. Infection and anaemia during pregnancy were associated with poor-SRH at one month postpartum and at the time of interview. The Kaplan-Meier curves illustrate restitution of health for most women during the study period. Conclusions: This population-based study reports a high prevalence of poor SRH status among Rwandan women in the early postpartum period. Identified factors associated with poor-SRH were severe bleeding, hypertension, infection, and anaemia during pregnancy and postpartum haemorrhage. These factors may be prevented or reduced by providing more frequent and specific attention during pregnancy and by providing timely measures that address complications during delivery, including adequate postpartum care.

  • Noh, H.
    et al.
    Noh, H.
    Alonso, G.
    Nair, Sujith
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Business Administration.
    Dahdi, Y.
    Biofuels: their emergence and implications for sustainability in aviation2015In: Energy and Sustainability V: Special Contributions / [ed] H.H Al-Kayiem; Brebbia, Wessex; S.S. Zubir, Ashurst: WIT Press, 2015, 103-111 p.Conference paper (Refereed)
    Abstract [en]

    The global aviation industry is facing complex and unpredictable market conditions with fluctuating oil prices and the adverse environmental impact of aircraft operations. Since the regulatory approval for biofuels, the first biojet fuel flight test in 2007, using a blend fuel, was a remarkable step towards having more test and schedule flights up to the year of 2014. The purpose of this paper is to engage this new alternative energy with the issues that airlines associate with sustainability, mainly focusing on aircraft operations and profitability. The key findings suggest that the uses of alternative energy need to be in parallel to the reliability and maintainability of the aircraft system, so that the adoption of biofuels can be effective.

  • Dobrenel, Thomas
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Institut Jean-Pierre Bourgin, Institut National de la Recherche Agronomique, AgroParisTech, Centre National de la Recherche Scientifique, Université Paris-Saclay, Versailles, France; Université Paris-Sud–Université Paris-Saclay, Orsay, France.
    Dobrenel, Thomas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Institut Jean-Pierre Bourgin, Institut National de la Recherche Agronomique, AgroParisTech, Centre National de la Recherche Scientifique, Université Paris-Saclay, Versailles, France; Université Paris-Sud–Université Paris-Saclay, Orsay, France.
    Mancera-Martinez, Eder
    Forzani, Celine
    Azzopardi, Marianne
    Davanture, Marlene
    Moreau, Manon
    Schepetilnikov, Mikhail
    Chicher, Johana
    Langella, Olivier
    Zivy, Michel
    Robaglia, Christophe
    Ryabova, Lyubov A.
    Hanson, Johannes
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Meyer, Christian
    The Arabidopsis TOR Kinase Specifically Regulates the Expression of Nuclear Genes Coding for Plastidic Ribosomal Proteins and the Phosphorylation of the Cytosolic Ribosomal Protein S62016In: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 7, 1611Article in journal (Refereed)
    Abstract [en]

    Protein translation is an energy consuming process that has to be fine-tuned at both the cell and organism levels to match the availability of resources. The target of rapamycin kinase (TOR) is a key regulator of a large range of biological processes in response to environmental cues. In this study, we have investigated the effects of TOR inactivation on the expression and regulation of Arabidopsis ribosomal proteins at different levels of analysis, namely from transcriptomic to phosphoproteomic. TOR inactivation resulted in a coordinated down-regulation of the transcription and translation of nuclear-encoded mRNAs coding for plastidic ribosomal proteins, which could explain the chlorotic phenotype of the TOR silenced plants. We have identified in the 5' untranslated regions (UTRs) of this set of genes a conserved sequence related to the 5' terminal oligopyrimidine motif, which is known to confer translational regulation by the TOR kinase in other eukaryotes. Furthermore, the phosphoproteomic analysis of the ribosomal fraction following TOR inactivation revealed a lower phosphorylation of the conserved Ser240 residue in the C-terminal region of the 40S ribosomal protein S6 (RPS6). These results were confirmed by Western blot analysis using an antibody that specifically recognizes phosphorylated Ser240 in RPS6. Finally, this antibody was used to follow TOR activity in plants. Our results thus uncover a multi-level regulation of plant ribosomal genes and proteins by the TOR kinase.

  • Andresen, Liis
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Andresen, Liis
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Tenson, Tanel
    Hauryliuk, Vasili
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Cationic bactericidal peptide 1018 does not specifically target the stringent response alarmone (p)ppGpp2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 36549Article in journal (Refereed)
    Abstract [en]

    The bacterial stringent response is a key regulator of bacterial virulence, biofilm formation and antibiotic tolerance, and is a promising target for the development of new antibacterial compounds. The intracellular nucleotide (p)ppGpp acts as a messenger orchestrating the stringent response. A synthetic peptide 1018 was recently proposed to specifically disrupt biofilms by inhibiting the stringent response via direct interaction with (p) ppGpp (de la Fuente-Nunez et al. (2014) PLoS Pathogens). We have interrogated the specificity of the proposed molecular mechanism. When inhibition of Pseudomonas aeruginosa planktonic and biofilm growth is tested simultaneously in the same assay, peptides 1018 and the control peptide 8101 generated by an inversion of the amino acid sequence of 1018 are equally potent, and, importantly, do not display a preferential activity against biofilm. 1018 inhibits planktonic growth of Escherichia coli equally efficiently either when the alleged target, (p) ppGpp, is essential (MOPS media lacking amino acid L-valine), or dispensable for growth (MOPS media supplemented with L-valine). Genetic disruption of the genes relA and spoT responsible for (p) ppGpp synthesis moderately sensitizes-rather than protects-E. coli to 1018. We suggest that the antimicrobial activity of 1018 does not rely on specific recognition of the stringent response messenger (p) ppGpp.

  • Ganai, Rais A.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Howard Hughes Medical Institute, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, USA.
    Ganai, Rais A.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Howard Hughes Medical Institute, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, USA.
    Zhang, Xiao-Ping
    Heyer, Wolf-Dietrich
    Johansson, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Strand displacement synthesis by yeast DNA polymerase epsilon2016In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 44, no 17, 8229-8240 p.Article in journal (Refereed)
    Abstract [en]

    DNA polymerase epsilon (Pol epsilon) is a replicative DNA polymerase with an associated 3'aEuro"5' exonuclease activity. Here, we explored the capacity of Pol epsilon to perform strand displacement synthesis, a process that influences many DNA transactions in vivo. We found that Pol epsilon is unable to carry out extended strand displacement synthesis unless its 3'aEuro"5' exonuclease activity is removed. However, the wild-type Pol epsilon holoenzyme efficiently displaced one nucleotide when encountering double-stranded DNA after filling a gap or nicked DNA. A flap, mimicking a D-loop or a hairpin structure, on the 5' end of the blocking primer inhibited Pol epsilon from synthesizing DNA up to the fork junction. This inhibition was observed for Pol epsilon but not with Pol delta, RB69 gp43 or Pol eta. Neither was Pol epsilon able to extend a D-loop in reconstitution experiments. Finally, we show that the observed strand displacement synthesis by exonuclease-deficient Pol epsilon is distributive. Our results suggest that Pol epsilon is unable to extend the invading strand in D-loops during homologous recombination or to add more than two nucleotides during long-patch base excision repair. Our results support the hypothesis that Pol epsilon participates in short-patch base excision repair and ribonucleotide excision repair.

  • Sundström, Joel
    et al.
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Sundström, Joel
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Nilsson, Robin
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Gör ditt bästa: En litteraturstudie om prestationskrav i skolan2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Denna litteraturstudie syftar till att undersöka hur skolelever kan påverkas av prestationskrav och hur de kan hantera detta samt om hur eventuella skillnader mellan tjejer och killar kan se ut. Barn och ungdomars psykiska hälsa i Sverige har under de senaste åren fått alltmer uppmärksamhet i media och samhällsdebatter. En del forskare menar att hälsotillståndet bland barn och ungdomar i Sverige idag har försämrats och att det kan vara kopplat till samhällets stigande välfärd samt andra samhällsförändringar, vilket kan ha bidragit till orealistiska krav på livet och välbefinnandet. Studien har en hermeneutisk ansats. Relevanta forskningsartiklar och rapporter analyserades genom tematisk analys. I studien användes prestationskrav, stress, hanteringsstrategier, kapabilitet och genus som några teoretiska utgångspunkter.  Resultat som framkom i studien visar att prestationskrav ofta finns närvarande i skolan och är något som påverkar eleverna i olika utsträckning. Studiens slutsatser handlar om att skolan anses vara bättre på att generera stress än vad den är på att ge verktyg för att hantera den. Eleverna hanterar kraven på olika sätt som kan ha positiv eller negativ utgång. Viktiga faktorer för elevernas hantering av skolgången är inflytande och kontroll samt stöd från omgivningen såsom lärare, föräldrar, familj och vänner. 

  • Hellström, Gustav
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Hellström, Gustav
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Klaminder, Jonatan
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Finn, Fia
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Persson, Lo
    Alanärä, Anders
    Jonsson, Micael
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Fick, Jerker
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Brodin, Tomas
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    GABAergic anxiolytic drug in water increases migration behaviour in salmon2016In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, 13460Article in journal (Refereed)
    Abstract [en]

    Migration is an important life-history event in a wide range of taxa, yet many migrations are influenced by anthropogenic change. Although migration dynamics are extensively studied, the potential effects of environmental contaminants on migratory physiology are poorly understood. In this study we show that an anxiolytic drug in water can promote downward migratory behaviour of Atlantic salmon (Salmo salar) in both laboratory setting and in a natural river tributary. Exposing salmon smolt to a dilute concentration of a GABAA receptor agonist (oxazepam) increased migration intensity compared with untreated smolt. These results implicate that salmon migration may be affected by human-induced changes in water chemical properties, such as acidification and pharmaceutical residues in wastewater effluent, via alterations in the GABAA receptor function.

  • Eggenschwiler, Reto
    et al.
    Eggenschwiler, Reto
    Moslem, Mohsen
    Fráguas, Mariane Serra
    Galla, Melanie
    Papp, Oliver
    Naujock, Maximilian
    Fonfara, Ines
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Max Planck Institute for Infection Biology, Department of Regulation in Infection Biology, Berlin, Germany.
    Gensch, Ingrid
    Wähner, Annabell
    Beh-Pajooh, Abbas
    Mussolino, Claudio
    Tauscher, Marcel
    Steinemann, Doris
    Wegner, Florian
    Petri, Susanne
    Schambach, Axel
    Charpentier, Emmanuelle
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Cathomen, Toni
    Cantz, Tobias
    Improved bi-allelic modification of a transcriptionally silent locus in patient-derived iPSC by Cas9 nickase2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 38198Article in journal (Refereed)
    Abstract [en]

    Homology directed repair (HDR)-based genome editing via selectable long flanking arm donors can be hampered by local transgene silencing at transcriptionally silent loci. Here, we report efficient bi-allelic modification of a silent locus in patient-derived hiPSC by using Cas9 nickase and a silencing-resistant donor construct that contains an excisable selection/counter-selection cassette. To identify the most active single guide RNA (sgRNA)/nickase combinations, we employed a lentiviral vector-based reporter assay to determine the HDR efficiencies in cella. Next, we used the most efficient pair of sgRNAs for targeted integration of an improved, silencing-resistant plasmid donor harboring a piggyBac-flanked puro Delta tk cassette. Moreover, we took advantage of a dual-fluorescence selection strategy for bi-allelic targeting and achieved 100% counter-selection efficiency after bi-allelic excision of the selection/counter-selection cassette. Together, we present an improved system for efficient bi-allelic modification of transcriptionally silent loci in human pluripotent stem cells.

  • Forsman, Stina
    et al.
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Forsman, Stina
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Nordenstedt, Lina
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    ”Är det någon som känner igen sig?”: En kvalitativ studie om barns upplevelser av att växa upp med en psykiskt sjuk förälder2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Barn till personer med psykisk problematik är en grupp som fått relativt lite uppmärksamhet i samband med förälderns insjuknande. Få studier beskriver hur deras tankar gått under tiden deras föräldrar varit sjuka. Denna studie syftar till att undersöka hur barn beskriver sina upplevelser av att växa upp med en psykiskt sjuk förälder. Genom att granska barns egna beskrivningar på hemsidan kuling.nu kan en organisk bild av erfarenheter, toppar och dalar samt känslor skapa en bild av en vardag få människor pratar öppet om. 41 inlägg publicerade mellan år 2016 och år 2010 granskades genom en kvalitativ konventionell innehållsanalys. Några av de resultat som kan utläsas visar att barnens upplevelser kan få följder såsom ensamhet, mental ohälsa eller utveckling av destruktiva hanteringsstrategier. Genom att söka sig till internetforum finner de gemenskap, kan få information om sjukdomar och kanske hjälp med att bearbeta sina upplevelser. Känslan av att vara den enda personen i hela världen som har en annorlunda förälder kan reduceras eller elimineras.

  • Gunnarsson, Åsa
    et al.
    Umeå University, Faculty of Social Sciences, Umeå Forum for Studies on Law and Society.
    Gunnarsson, Åsa
    Umeå University, Faculty of Social Sciences, Umeå Forum for Studies on Law and Society.
    Eriksson, Martin
    Umeå University, Faculty of Social Sciences, Umeå Forum for Studies on Law and Society.
    Discussion Paper on Tax Policy and Tax Principles in Sweden, 1902-20162017Report (Refereed)
    Abstract [en]

    The long time perspective on tax principles and tax policies in this discussion paper identifies some of the most important and relevant contexts for major Swedish tax reforms from 1902 until the present time. Until the 1991 tax reform principles played a significant role in tax law design. The relation between principles and legal concepts was quite consistent.

    However, the 1991 tax reform seems to mark the end of a period when Swedish governments, with a certain regularity, initiated tax reforms to tackle contemporary economic and social challenges. In spite of several initiatives, proposed in well investigated study commission reports, no comprehensive tax reforms have been launched during a quarter of a decade. Instead hundreds of small, partial reforms have been implemented in tax law. Together with a new budgetary framework these gradual changes have changed the overall revenue basis for the public sector and the welfare state. In tandem with this development, the policy discourse on taxing for economic growth has increasingly gained in influence.

    Even though environmental sustainability, and later also fiscal sustainability, have been prominent in the design of the tax system, we also note that Swedish tax policy has potential to further integrate important economic and social sustainability goals such as gender equality, social inclusion and income distribution.

    A result of the study is to show the complexity of a national agenda on tax policy. Legally enshrined goals and principles cannot easily be superseded with tax policies on a supranational level, particularly if these policies are solely drawn from macroeconomic analysis on the mechanisms and trajectories of economic crises.

  • Johansson, Maria
    et al.
    Johansson, Maria
    Sandström, Camilla
    Umeå University, Faculty of Social Sciences, Department of Political Science.
    Pedersen, Eja
    Ericsson, Göran
    Factors governing human fear of wolves: moderating effects of geographical location and standpoint on protected nature2016In: European Journal of Wildlife Research, ISSN 1612-4642, E-ISSN 1439-0574, Vol. 62, no 6, 749-760 p.Article in journal (Refereed)
    Abstract [en]

    This study analyses psychological antecedents of feelings of fear of wolves in a proportional sample of the Swedish population (national sample, n = 545) and in a sample of people in counties with wolf presence (regional sample, n = 1,892). Structural equation modelling of survey data suggests a dual pathway to self-reported fear. One path encompasses the appraisal of the environmental context operationalised as a potential wolf encounter. The second path concerns the appraisal of the social context assessed as social trust in managing authorities. The relative importance of the paths differs between the national and the regional sample, and between people in the administrative centre of the region and the regional periphery. We show that the public's fear of wolves should be addressed both at an individual level, focusing on situations with potential encounters, and at a collective level, by strengthening the trust between the public and authorities, and regional variation should be considered.

  • Salminen, Eero
    et al.
    Salminen, Eero
    Virtanen, Pasi
    Mikkola, Jyri-Pekka
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Laboratory of Industrial Chemistry and Reaction Engineering, Process Chemistry Centre, Åbo Akademi University, Åbo-Turku, Finland.
    Alkaline ionic liquids applied in supported ionic liquid catalyst for selective hydrogenation of citral to citronellal2014In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 2, 3Article in journal (Refereed)
    Abstract [en]

    The challenge in preparation of ionic liquids containing a strong alkaline anion is to identify a suitable cation which can tolerate the harsh conditions induced by the anion. In this study, a commercial quaternary ammonium compound (quat) benzalkonium [ADBA] (alkyldimethylbenzylammonium) was used as a cation in the synthesis of different alkaline ionic liquids. In fact, the precursor, benzalkonium chloride, is a mixture of alkyldimethylbenzylammonium chlorides of various alkyl chain lengths and is commonly used in the formulation of various antiseptic products. The prepared ionic liquids were utilized as Supported Ionic Liquid Catalysts (SILCAs). Typically, a SILCA contains metal nanoparticles, enzymes, or metal complexes in an ionic liquid layer which is immobilized on a solid carrier material such as an active carbon cloth (ACC). The catalysts were applied in the selective hydrogenation of citral to citronellal which is an important perfumery chemical. Interestingly, 70% molar yield toward citronellal was achieved over a catalyst containing the alkaline ionic liquid benzalkonium methoxide.

  • Henricson, Anders
    et al.
    Henricson, Anders
    Nilsson, Kjell G.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Trabecular metal tibial knee component still stable at 10 years: An RSA study of 33 patients less than 60 years of age2016In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 87, no 5, 504-510 p.Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Total knee replacement (TKR) in younger patients using cemented components has shown inferior results, mainly due to aseptic loosening. Excellent clinical results have been reported with components made of trabecular metal (TM). In a previous report, we have shown stabilization of the TM tibial implants for up to 5 years. In this study, we compared the clinical and RSA results of these uncemented implants with those of cemented implants. Patients and methods - 41 patients (47 knees) aged 60 years underwent TKR. 22 patients (26 knees) received an uncemented monoblock cruciate-retaining (CR) tibial component (TM) and 19 patients (21 knees) received a cemented NexGen Option CR tibial component. Follow-up examination was done at 10 years, and 16 patients (19 knees) with TM tibial components and 17 patients (18 knees) with cemented tibial components remained for analysis. Results - 1 of 19 TM implants was revised for infection, 2 of 18 cemented components were revised for knee instability, and no revisions were done for loosening. Both types of tibial components migrated in the first 3 months, the TM group to a greater extent than the cemented group. After 3 months, both groups were stable during the next 10 years. Interpretation - The patterns of migration for uncemented TM implants and cemented tibial implants over the first 10 years indicate that they have a good long-term prognosis regarding fixation

  • Wahlberg, Per
    et al.
    Wahlberg, Per
    Lundmark, Anders
    Nordlund, Jessica
    Busche, Stephan
    Raine, Amanda
    Tandre, Karolina
    Rönnblom, Lars
    Sinnett, Daniel
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Pastinen, Tomi
    Lönnerholm, Gudmar
    Syvänen, Ann-Christine
    DNA methylome analysis of acute lymphoblastic leukemia cells reveals stochastic de novo DNA methylation in CpG islands2016In: Epigenomics, ISSN 1750-1911, Vol. 8, no 10, 1367-1387 p.Article in journal (Refereed)
    Abstract [en]

    Aim: To identify regions of aberrant DNA methylation in acute lymphoblastic leukemia (ALL) cells of different subtypes on a genome-wide scale. Materials & methods: Whole-genome bisulfite sequencing (WGBS) was used to determine the DNA methylation levels in cells from four pediatric ALL patients of different subtypes. The findings were confirmed by 450k DNA methylation arrays in a large patient set. Results: Compared with mature B or T cells WGBS detected on average 82,000 differentially methylated regions per patient. Differentially methylated regions are enriched to CpG poor regions, active enhancers and transcriptional start sites. We also identified approximately 8000 CpG islands with variable intermediate DNA methylation that seems to occur as a result of stochastic de novo methylation. Conclusion: WGBS provides an unbiased view and novel insights into the DNA methylome of ALL cells.

  • Rönnqvist, Carina
    Rönnqvist, Carina
    Församlade svenskar: Etnicitet och religion i Alberta 1898-19502004In: Befolkningshistoriska perspektiv: Festskrift till Lars-Göran Tedebrand / [ed] Redaktionskommitté Anders Brändström, Sören Edvinsson, Tom Ericsson och Peter Sköld, Umeå: Umeå universitet , 2004, 293-317 p.Chapter in book (Other academic)
  • Gatimu, Samwel Maina
    et al.
    Gatimu, Samwel Maina
    Milimo, Benson Williesham
    San Sebastian, Miguel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Nursing I, University of the Basque country.
    Prevalence and determinants of diabetes among older adults in Ghana2016In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 16, 1174Article in journal (Refereed)
    Abstract [en]

    Background: Diabetes is one of the leading non-communicable diseases in Africa, contributing to the increasing disease burden among the old adults. Thus, the aim of this study was to determine the prevalence and determinants of diabetes among adults aged 50 years and above in Ghana. Methods: A cross sectional study based on data collected from Study of Ageing and Adult Health (SAGE) Wave 1 from 2007 to 2008. Data was collected from 5565 respondents of whom 4135 were aged 50+ years identified using a multistage stratified clusters design. Bivariate and hierarchical multivariable logistic regression models were used to examine the association of the determinants and diabetes. Results: The weighted prevalence of diabetes among the adults aged 50 years and above in Ghana was 3.95% (95% Confidence Interval: 3.35-4.55) with the prevalence being insignificantly higher in females than males (2.16%, 95% CI: 1. 69-2.76 vs. 1.73%, 95% CI: 1.28-2.33). Low level of physical activity (Adjusted Odds Ratio [AOR] 2.11, 95% CI: 1.21-3.69) and obesity (AOR 4.81, 95% CI: 1.92-12.0) were associated with increased odds of diabetes among women while old age (AOR 2.58, 95% CI: 1.29-5.18) and university (AOR 12.8, 95% CI: 4.20-39.1), secondary (AOR 3.61, 95% CI: 1.38-9.47) and primary education (AOR 2.71, 95% CI: 1.02-7.19) were associated with increased the odds of diabetes among men. Conclusion: The prevalence of diabetes among old adults shows a similar trend with that of the general population. However, the prevalence may have been underestimated due to self-reporting and a high rate of undiagnosed diabetes. In addition, the determinants of diabetes among older adults are a clear indication of the need for diabetes prevention programme targeting the young people and that are gender specific to reduce the burden of diabetes at old age. Physical activity and nutrition should be emphasised in any prevention strategy.

  • Gabrielsson, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Gabrielsson, Linda
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Mattsson, Sofia
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy2016In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 82, no 4, 932-942 p.Article, review/survey (Refereed)
    Abstract [en]

    Palmitoylethanolamide (PEA) has been suggested to have useful analgesic properties and to be devoid of unwanted effects. Here, we have examined critically this contention, and discussed available data concerning the pharmacokinetics of PEA and its formulation. Sixteen clinical trials, six case reports/pilot studies and a meta-analysis of PEA as an analgesic have been published in the literature. For treatment times up to 49days, the current clinical data argue against serious adverse drug reactions (ADRs) at an incidence of 1/200 or greater. For treatment lasting more than 60days, the number of patients is insufficient to rule out a frequency of ADRs of less than 1/100. The six published randomized clinical trials are of variable quality. Presentation of data without information on data spread and nonreporting of data at times other than the final measurement were among issues that were identified. Further, there are no head-to-head clinical comparisons of unmicronized vs. micronized formulations of PEA, and so evidence for superiority of one formulation over the other is currently lacking. Nevertheless, the available clinical data support the contention that PEA has analgesic actions and motivate further study of this compound, particularly with respect to head-to-head comparisons of unmicronized vs. micronized formulations of PEA and comparisons with currently recommended treatments.

  • Lundberg, Anna
    Lundberg, Anna
    De kom till kurhuset: Studier av sociala konsekvenser i kyrkobokföringsmaterialet2004In: Befolkningshistoriska perspektiv: Festskrift till Lars-Göran Tedebrand / [ed] Redaktionskommitté Anders Brändström, Sören Edvinsson, Tom Ericsson och Peter Sköld, Umeå: Umeå universitet , 2004, 161-182 p.Chapter in book (Other academic)
  • Enell, Anja
    et al.
    Enell, Anja
    Lundstedt, Staffan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Arp, Hans Peter H.
    Josefsson, Sarah
    Cornelissen, Gerard
    Wik, Ola
    Kleja, Dan Berggren
    Combining Leaching and Passive Sampling To Measure the Mobility and Distribution between Porewater, DOC, and Colloids of Native Oxy-PAHs, N-PACs, and PAHs in Historically Contaminated Soil2016In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 50, no 21, 11797-11805 p.Article in journal (Refereed)
    Abstract [en]

    Different methods to quantify soil porewater concentrations of contaminants will provide different types of information. Passive sampling measurements give freely dissolved porewater concentrations (C-pw,C-free), while leaching tests provide information on the mobile concentration (C-pw,C-leach), including contaminants associated with dissolved organic carbon (DOC) and particles/colloids in the porewater. This study presents a novel combination of these two measurements, to study the sorption and mobility of polycyclic aromatic compounds (PACs) to DOC and particulate organic carbon (POC) in 10 historically contaminated soils. The PACs investigated were polycyclic aromatic hydrocarbons (PAHs), oxygenated-PAHs, and nitrogen containing heterocyclic PACs. Observed C-pw,C-leach was up to 5 orders of magnitude higher than C-pw,C-free; implying large biases when C-pw,C-leach is used to assess bioavailability or soil partitioning. Sorption of PACs to DOC and POC was important for the mobility of compounds with log K-OW > 4. Average DOC/water-partitioning coefficients (K-DOC) correlated well with KOW (log K-DOC = 0.89 x log K-OW +1.03 (r(2) = 0.89)). This relationship is likely more accurate for historically contaminated soils than previously published data, which suffer from artifacts caused by problems in measuring C-pw,C-free correctly or not using historically contaminated soils. POC/water-partitioning coefficients (K-POC) were orders of magnitude larger than corresponding K-DOC, suggesting sorption to mobile particles/colloids is the dominant mechanism for PAC mobility.

  • De Samber, Bjorn
    et al.
    De Samber, Bjorn
    Niemiec, Maria J.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Microbial Immunology Research Group, Hans Knöll Institute / Leibniz-Institute for Natural Product Research and Infection Biology, Jena, Germany.
    Laforce, Brecht
    Garrevoet, Jan
    Vergucht, Eva
    De Rycke, Riet
    Cloetens, Peter
    Urban, Constantin F.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Vincze, Laszlo
    Probing Intracellular Element Concentration Changes during Neutrophil Extracellular Trap Formation Using Synchrotron Radiation Based X-Ray Fluorescence2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, e0165604Article in journal (Refereed)
    Abstract [en]

    High pressure frozen (HPF), cryo-substituted microtome sections of 2 mu m thickness containing human neutrophils (white blood cells) were analyzed using synchrotron radiation based X-ray fluorescence (SR nano-XRF) at a spatial resolution of 50 nm. Besides neutrophils from a control culture, we also analyzed neutrophils stimulated for 1-2 h with phorbol myristate acetate (PMA), a substance inducing the formation of so-called Neutrophil Extracellular Traps (or NETs), a defense system again pathogens possibly involving proteins with metal chelating properties. In order to gain insight in metal transport during this process, precise local evaluation of elemental content was performed reaching limits of detection (LODs) of 1 ppb. Mean weight fractions within entire neutrophils, their nuclei and cytoplasms were determined for the three main elements P, S and Cl, but also for the 12 following trace elements: K, Ca, Mn, Fe, Co, Ni, Cu, Zn, Se, Br, Sr and Pb. Statistical analysis, including linear regression provided objective analysis and a measure for concentration changes. The nearly linear Ca and Cl concentration changes in neutrophils could be explained by already known phenomena such as the induction of Ca channels and the uptake of Cl under activation of NET forming neutrophils. Linear concentration changes were also found for P, S, K, Mn, Fe, Co and Se. The observed linear concentration increase for Mn could be related to scavenging of this metal from the pathogen by means of the neutrophil protein calprotectin, whereas the concentration increase of Se may be related to its antioxidant function protecting neutrophils from the reactive oxygen species they produce against pathogens. We emphasize synchrotron radiation based nanoscopic X-ray fluorescence as an enabling analytical technique to study changing (trace) element concentrations throughout cellular processes, provided accurate sample preparation and data-analysis.

  • Public defence: 2017-01-27 10:15 S205H, Samhällsvetarhuset, Umeå
    Liljenfeldt, Johanna
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History, Economic and social geography.
    Liljenfeldt, Johanna
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History, Economic and social geography.
    Where the Wind Blows: the socio-political geography of wind power development in Finland, Norway and Sweden2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis analysis the planning process for large-scale wind power development in Finland, Norway and Sweden. The aim is to explore the emerging power relations and socio-economic dynamics of the negotiation, planning and realization of this new development. The thesis employs an energy justice framework to capture the opportunities different stakeholders have to take part in and influence wind power development processes (‘procedural justice’), and how the potential benefits and burdens of wind power development are divided between stakeholders (‘distributional justice’). The study’s setup is an embedded sequential mixed methods research design, which includes analysis of policy documents, in-dept interviews, observations, as well as register based population data.

    The thesis shows how power relations on both a structural level and an actor level are used to exert power and influence over the planning process for wind power development. On a structural level, the results indicate that transformations in EU directives and national planning laws and guidelines in Finland, Norway and Sweden in recent years have been more focused on speed and efficiency in planning processes than on legitimacy issues. The changes that have been implemented seem to point to diminishing opportunities for broad participation and debate in wind power planning processes, in favour of more top-down processes with a specific, sectoral focus on developing wind power. On the actor level, perceived improper behaviour by different actors within the planning process can further limit the possibilities for participation. People refrain from participating in planning processes, for instance, if they feel that they are treated disrespectfully or if there have occurred procedural errors that undermine the legitimacy of the formal planning process. However, participation in formal planning processes is not the only way to influence planning processes. There are a number of more informal channels, such as using the media or the Internet, lobbying, or rallying local support, that can and have been used by stakeholders to tap into the formal planning process to try to affect its outcomes. Such informal activities have a considerable spatial and scalar reach, the importance of which is that stakeholders utilizing such measures have the possibility to affect not only the local wind power project under debate, but also developments in other places and attitudes towards wind power more generally.

    As concerns distributional issues, the results of the thesis show that the evidence of distributional inequality concerning wind power development on the national scale in Sweden is not very strong; but if such inequalities exist, there are possibilities to redistribute the benefits from wind power to those who are burdened by the developments. Distributional injustice related to wind power development is thus not an evident problem, generally speaking, in Sweden today. However, if this state is to remain, procedural aspects related to the continued development of wind power need to be kept in mind, as procedural and distributional inequalities are intimately related. Of specific concern is the need to address formal and informal procedures that marginalize stakeholder participation in planning processes, but it is equally important to also consider who is to be included in or excluded from negotiations and the distribution of local economic benefits connected to specific wind power projects.

  • Public defence: 2017-02-03 09:00 Föreläsningssal A, Psykiatriska kliniken, Målpunkt F, Plan O, Umeå
    Rajalin, Mia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Rajalin, Mia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Distal risk factors, interpersonal functioning & family skills training in attempted suicide2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Suicidal behavior is an important global health problem affecting also significant others. Both genetic and environmental influences play an important role in the development of suicidal behavior. There is a need of interventions for family and friends after a suicide attempt. The aim of this thesis was to assess the impact of family history of suicide (FHS) and early life adversity (ELA) on severity of suicidal behavior and on level of interpersonal problems in suicide attempters. Furthermore it aimed to evaluate a DBT-based skills training program, Family Connections (FC), for relatives and friends of suicide attempters.

    Methods Studies I and II included 181 suicide attempters. FHS was assessed with the Karolinska Self-Harm History Interview or in patient records. ELA was assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to interpersonal violence in childhood. Suicide intent was measured with the Freeman scale. Interpersonal problems were assessed with the Inventory of Interpersonal Problems (IIP).

    Study III, a pilot study evaluating the effect of FC for family members of suicide attempters, included 13 participants who completed the program with pre- and post-questionnaires. The experience of burden was assessed with the Burden Assessment Scale (BAS), general wellbeing with Brief Symptom Inventory (BSI) and level of depression was assessed with Beck Depression Inventory (BDI). The Swedish scale Questions About Family Members (QAFM) was used to explore the quality of the participants’ relationship with the patient and the Quality of Life Inventory (QOLI) was used to measure satisfaction with life situation.

    Study IV included 132 family members, and investigated the feasibility and preliminary efficacy of FC in psychiatric care. Participants were assessed pre- and post-intervention with the following self-report questionnaires: BAS, QAFM and Five Facet Mindfulness Questionnaire.

    Results Male suicide attempters with FHS made more serious and well planned suicide attempts and had higher suicide risk. FHS and exposure to interpersonal violence as a child were independent predictors of suicide in male suicide attempters. Regarding interpersonal problems, suicide attempters with FHS had significantly more often an intrusive personal style, indicating that they might have an impaired ability to create stable, long-lasting relationships. In the pilot study the participants reported a significant reduction in burden, an improved psychic health and an improvement in the relationship with the patient after completing FC. In the fourth study, FC showed to be feasible and effectively implemented in a psychiatric outpatient services clinic. Regarding burden, results were in line with the pilot study, with a significant reduction in all subscales in BAS.

    Conclusions High-risk patients call for a consideration of both ELA and FHS in clinical suicide risk assessment. In suicide attempters at biological risk, suicide might be prevented with the early recognition of environmental risks. Further, the interpersonal problems associated with FHS may cause difficulties for suicide attempters to accept or benefit from treatment, and caregivers should take into account the characteristics of the suicide attempter´s interpersonal functioning. The results from the pilot study provide support for the need and importance of an educational program addressed specifically to family members of suicide attempters. Preliminary results support the feasibility and potential value of an implementation of FC in psychiatric open care clinics.

  • Public defence: 2017-01-27 09:00 N200, Naturvetarhuset, Umeå
    Ekestubbe, Sofie
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Ekestubbe, Sofie
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Timing and targeting of Type III secretion translocation of virulence effectors in Yersinia2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The Type III secretion system (T3SS) is an important virulence mechanism that allows pathogenic bacteria to translocate virulence effectors directly into the cytoplasm of eukaryotic host cells to manipulate the host cells in favor of the pathogen. Enteropathogenic Yersinia pseudotuberculosis use a T3SS to translocate effectors, Yops, that prevent phagocytosis by immune cells, and is largely dependent on it to establish and sustain an infection in the lymphoid tissues of a mammalian host. Translocation into a host cell requires specific translocator proteins, and is tightly controlled from both the bacterial and host cell cytoplasm. We aimed to investigate two of the regulatory elements, YopN and LcrV, to gain more insight into the translocation mechanism. Two separate regulatory complexes regulate expression and secretion of Yops, however, the processes are linked so that expression is induced when secretion is activated. A complex, including YopD, prevents expression of Yops, while YopN-TyeA and LcrG block secretion. LcrV is required to relieve the secretion block, by sequestering LcrG. We verified that LcrG binds to the C-terminal part of LcrV, which is consistent with what has been shown in Y. pestis. In addition to their regulatory roles, both LcrV and YopD are translocators and are assumed to interact at the bacterial surface, where LcrV promotes insertion of YopB and YopD into the host cell membrane. However, here we show that purified YopD failed to interact with LcrV, instead YopD solely interacted with a complex of LcrV-LcrG. This indicates that LcrV and YopD interact in the bacterial cytosol, which may be important for regulation of Yop expression and secretion. The established role of YopN is to block secretion prior to host cell contact. We found that deleting the central region (amino acids 76-181) had no effect on the regulatory role of YopN in expression and secretion of Yops. Interestingly, we found that, even though the YopN∆76-181 mutant secreted the translocators with similar kinetics as the wild type strain, translocation of the effector YopH, into HeLa cells, was significantly reduced. Consequently, the YopN∆76-181 mutant was unable to block phagocytosis, almost to the same level as the ∆lcrV mutant which is completely unable to translocate YopH. Our results indicate that YopN is involved in the translocation step in addition to its role in regulating secretion. Further, we show that the amino terminal of LcrV, in the context of translocation, is involved in the early intracellular targeting of YopH in order to block phagocytosis efficiently and sustain an in vivo infection. LcrV mutants that failed to efficiently target YopH intracellularly were severely attenuated also for in vivo virulence. All together, we show that LcrV and YopN are involved in more steps in the regulation of translocation, than what was known before. Our studies also highlight that early translocation is essential for Yersinia to block phagocytosis, which in the end is essential for in vivo virulence.

  • Public defence: 2017-02-03 10:00 Stora hörsalen (KB.E3.03), Umeå
    Berg, Lotta
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Berg, Lotta
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Exploring non-covalent interactions between drug-like molecules and the protein acetylcholinesterase2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The majority of drugs are small organic molecules, so-called ligands, that influence biochemical processes by interacting with proteins. The understanding of how and why they interact and form complexes is therefore a key component for elucidating the mechanism of action of drugs. The research presented in this thesis is based on studies of acetylcholinesterase (AChE). AChE is an essential enzyme with the important function of terminating neurotransmission at cholinergic synapses. AChE is also the target of a range of biologically active molecules including drugs, pesticides, and poisons. Due to the molecular and the functional characteristics of the enzyme, it offers both challenges and possibilities for investigating protein-ligand interactions. In the thesis, complexes between AChE and drug-like ligands have been studied in detail by a combination of experimental techniques and theoretical methods. The studies provided insight into the non-covalent interactions formed between AChE and ligands, where non-classical CH∙∙∙Y hydrogen bonds (Y = O or arene) were found to be common and important. The non-classical hydrogen bonds were characterized by density functional theory calculations that revealed features that may provide unexplored possibilities in for example structure-based design. Moreover, the study of two enantiomeric inhibitors of AChE provided important insight into the structural basis of enthalpy-entropy compensation. As part of the research, available computational methods have been evaluated and new approaches have been developed. This resulted in a methodology that allowed detailed analysis of the AChE-ligand complexes. Moreover, the methodology also proved to be a useful tool in the refinement of X-ray crystallographic data. This was demonstrated by the determination of a prereaction conformation of the complex between the nerve-agent antidote HI-6 and AChE inhibited by the nerve agent sarin. The structure of the ternary complex constitutes an important contribution of relevance for the design of new and improved drugs for treatment of nerve-agent poisoning. The research presented in the thesis has contributed to the knowledge of AChE and also has implications for drug discovery and the understanding of biochemical processes in general.

  • Torstensson, Elin
    et al.
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Torstensson, Elin
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Vernersson, Josefin
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Centrala faktorer i arbetet med barn och unga: Fem behandlingssekreterare berättar2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • Olsson, Moa
    et al.
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Olsson, Moa
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Nyman, Sandra
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Återföreningsprocessen: En kvalitativ studie om socialsekreterares erfarenheter av att verka för återföreningar mellan föräldrar och familjehemsplacerade barn2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Ungefär ett barn i varje normalstor skolklass har någon gång under sin uppväxt varit placerade i familjehems- eller institutionsvård och såväl frivilliga- som tvångsplaceringar ökar i Sverige. När barn placeras i samhällsvård ska socialnämnden verka för att möjliggöra återförening mellan barn och föräldrar samt hjälpa föräldrarna att åtgärda de brister som förorsakat placering. Studien syftar till att undersöka hur socialtjänsten kan verka för återföreningar mellan vårdnadshavare och barn som är placerade med frivillighet eller tvång i familjehem på grund av brister i hemmiljön. Halvstrukturerade kvalitativa intervjuer med fem socialsekreterare från fem olika kommuner genomfördes för att besvara syftet. Studien visar att det förekom stora kommunala skillnader i hur och när socialtjänsten verkar för återföreningar. De flesta intervjupersoner önskade att de kunde arbeta mer stöttande för föräldrar vars barn är placerade, men uppgav tiden som hinder för sådana insatser. Studien argumenterar för att socialtjänstens ökade fokus på effektivitet och evidens kan vara en orsak till att föräldrastöd och ett aktivt återföreningsarbete inte prioriteras i den sociala barnavården. I syfte att öka möjligheten till föräldrastöd och återföreningar presenterar studien ett åtgärdsförslag, i form av tillhandahållande av en extern föräldrasekreterare vars uppdrag skulle vara att stötta föräldrar med placerade barn.

  • Samoilenko, Anna
    et al.
    Samoilenko, Anna
    Karimi, Fariba
    Edler, Daniel
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Kunegis, Jerome
    Strohmaier, Markus
    Linguistic neighbourhoods: explaining cultural borders on Wikipedia through multilingual co-editing activity2016In: EPJ Data Science, ISSN 2193-1127, Vol. 5, 9Article in journal (Refereed)
    Abstract [en]

    In this paper, we study the network of global interconnections between language communities, based on shared co-editing interests of Wikipedia editors, and show that although English is discussed as a potential lingua franca of the digital space, its domination disappears in the network of co-editing similarities, and instead local connections come to the forefront. Out of the hypotheses we explored, bilingualism, linguistic similarity of languages, and shared religion provide the best explanations for the similarity of interests between cultural communities. Population attraction and geographical proximity are also significant, but much weaker factors bringing communities together. In addition, we present an approach that allows for extracting significant cultural borders from editing activity of Wikipedia users, and comparing a set of hypotheses about the social mechanisms generating these borders. Our study sheds light on how culture is reflected in the collective process of archiving knowledge on Wikipedia, and demonstrates that cross-lingual interconnections on Wikipedia are not dominated by one powerful language. Our findings also raise some important policy questions for the Wikimedia Foundation.

  • Schlickum, Marcus
    et al.
    Schlickum, Marcus
    Hedman, Leif
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Fellander-Tsai, Li
    Visual-spatial ability is more important than motivation for novices in surgical simulator training: a preliminary study2016In: International Journal of Medical Education, ISSN 2042-6372, E-ISSN 2042-6372, Vol. 7, 56-61 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate whether surgical simulation performance and previous video gaming experience would correlate with higher motivation to further train a specific simulator task and whether visual-spatial ability would rank higher in importance to surgical performance than the above. It was also examined whether or not motivation would correlate with a preference to choose a surgical specialty in the future and if simulator training would increase the interest in choosing that same work field. Methods: Motivation and general interest in surgery was measured pre- and post-training in 30 medical students at Karolinska Institutet who were tested in a laparoscopic surgical simulator in parallel with measurement of visual-spatial ability and self-estimated video gaming experience. Correlations between simulator performance metrics, visual-spatial ability and motivation were statistically analyzed using regression analysis. Results: A good result in the first simulator trial correlated with higher self-determination index (r = -0.46, p=0.05) in male students. Visual-spatial ability was the most important underlying factor followed by intrinsic motivation score and finally video gaming experience (p=0.02, p=0.05, p=0.11) regarding simulator performance in male students. Simulator training increased interest in surgery when studying all subjects (p=0.01), male subjects (p=0.02) as well as subjects with low video gaming experience (p=0.02). Conclusions: This preliminary study highlights individual differences regarding the effect of simulator training on motivation that can be taken into account when designing simulator training curricula, although the sample size is quite small and findings should be interpreted carefully.

  • Ekestubbe, Sofie
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Ekestubbe, Sofie
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Bröms, Jeanette E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Edgren, Tomas
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Fällman, Maria
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Francis, Matthew S.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Forsberg, Åke
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    The amino-terminal part of the needle-tip translocator LcrV of Yersinia pseudotuberculosis is required for early targeting of YopH and in vivo virulence2016In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 6, 175Article in journal (Refereed)
    Abstract [en]

    Type III secretion systems (T3SS) are dedicated to targeting anti-host effector proteins into the cytosol of the host cell to promote bacterial infection. Delivery of the effectors requires three specific translocator proteins, of which the hydrophilic translocator, LcrV, is located at the tip of the T3SS needle and is believed to facilitate insertion of the two hydrophobic translocators into the host cell membrane. Here we used Yersinia as a model to study the role of LcrV in T3SS mediated intracellular effector targeting. Intriguingly, we identified N-terminal IcrV mutants that, similar to the wild-type protein, efficiently promoted expression, secretion and intracellular levels of Yop effectors, yet they were impaired in their ability to inhibit phagocytosis by J774 cells. In line with this, the YopH mediated dephosphorylation of Focal Adhesion Kinase early after infection was compromised when compared to the wild type strain. This suggests that the mutants are unable to promote efficient delivery of effectors to their molecular targets inside the host cell upon host cell contact. The significance of this was borne out by the fact that the mutants were highly attenuated for virulence in the systemic mouse infection model. Our study provides both novel and significant findings that establish a role for LcrV in early targeting of effectors in the host cell.

  • Gaida, James E.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. University of Canberra Research Institute for Sport and Exercise (UCRISE); Discipline of Physiotherapy, University of Canberra.
    Gaida, James E.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. University of Canberra Research Institute for Sport and Exercise (UCRISE); Discipline of Physiotherapy, University of Canberra.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation. Institute of Sport Exercise and Health, University College Hospital London.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Cook, Jill L.
    A pilot study on biomarkers for tendinopathy: lower levels of serum TNF-alpha and other cytokines in females but not males with Achilles tendinopathy2016In: BMC Sports Science Medicine and Rehabilitation, ISSN 2052-1847, Vol. 8, 5Article in journal (Refereed)
    Abstract [en]

    Background: Achilles tendinopathy is a painful musculoskeletal condition that is common among athletes, and which limits training capacity and competitive performance. The lack of biomarkers for tendinopathy limits research into risk factors and also the evaluation of new treatments. Cytokines and growth factors involved in regulating the response of tendon cells to mechanical load have potential as biomarkers for tendinopathy. Methods: This case-control study compared serum concentration of cytokines and growth factors (TNF-alpha, IL-1 beta, bFGF, PDFG-BB, IFN-gamma, VEGF) between individuals with chronic Achilles tendinopathy and controls. These were measured in fasting serum from 22 individuals with chronic Achilles tendinopathy and 10 healthy controls. Results were analysed in relation to gender and physical activity pattern. Results: TNF-alpha concentration was lower in the entire tendinopathy group compared with the entire control group; none of the other cytokines were significantly different. TNF-alpha levels were nevertheless highly correlated with the other cytokines measured, in most of the subgroups. Analysed by gender, TNF-alpha and PDGF-BB concentrations were lower in the female tendinopathy group but not the male tendinopathy group. A trend was seen for lower IL-1 beta in the female tendinopathy group. Physical activity was correlated with TNF-alpha, PDGF-BB and IL-1 beta to varying extents for control subgroups, but not for the female tendinopathy group. No correlations were seen with BMI or duration of symptoms. Conclusions: This pilot study indicates a lower level of TNF-alpha and PDGF-BB, and to some extent IL-1 beta among females, but not males, in the chronic phase of Achilles tendinopathy. It is suggested that future studies on tendinopathy biomarkers analyse male and female data separately. The lack of correlation between cytokine level and physical activity in the female tendinopathy group warrants further study.

  • Alemu, Andinet Worku
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Alemu, Andinet Worku
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    San Sebastian, Miguel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Determinants of survival in adult HIV patients on antiretroviral therapy in Oromiyaa, Ethiopia2010In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 3, 5398Article in journal (Refereed)
    Abstract [en]

    Background: The antiretroviral treatment (ART) scale-up service has been a recent development in Ethiopia, but its impact on mortality has not been well investigated. The aim of this study was to assess the early survival outcome of the scale-up service by utilizing routine hospital data.

    Methods: All adult HIV/AIDS patients who started on antiretroviral treatment in Shashemene and Assela hospitals from January 1, 2006 to May 31, 2006 were included and followed up for 2 years. Data were extracted from standard patient medical registrations. Kaplan-Meier curves were used to estimate survival probability and the Cox proportional hazard model was applied to determine predictors of mortality. Two alterative assumptions (real case and worst case) were made in determining predictors of mortality.

    Results: The median age of patients was 33 years and 57% were female. Eighty-five percent had CD4 <200 cells/mu L with a median CD4 count of 103 cells/mu L. The median survival time was 104.4 weeks. A total of 28 (10.3%) deaths were observed during the 2-year period and 48 patients (18%) were lost to follow up. The majority of deaths occurred in the first 4 months of treatment. In multivariate analysis, 2-year survival was significantly associated with the clinical stage of the disease, baseline hemoglobin, and cotrimoxazole prophylaxis therapy (CPT) at or before ART initiation in both assumptions. The median CD4 count and body weight showed a marked improvement during the first 6 months of treatment, followed by stagnation thereafter.

    Conclusion: The study has shown an overall low mortality but a high loss to follow-up rate of the cohort. Advanced clinical stage, anemia, low body weight, and lack of CPT initiation were independent predictors of mortality - but not gender. CPT initiation should be encouraged in routine HIV care services, and patient retention mechanisms have to be strengthened. Stagnation in immunological and weight recovery after the first 6 months should be further investigated. The utilization of routine data should be encouraged in order to facilitate appropriate decision making.

  • Nilsson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adamo, Hanibal
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 19608Article in journal (Refereed)
    Abstract [en]

    Lysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects. Here we show that orthotopic implantation of rat prostate AT-1 tumour cells increased LOX and LOXLs mRNA expressions in the tumour and in the surrounding non-malignant prostate tissue. Inhibition of LOX enzymes, using Beta-aminopropionitrile (BAPN), initiated before implantation of AT-1 cells, reduced tumour growth. Conversely, treatment that was started after the tumours were established resulted in unaffected or increased tumour growth. Moreover, treatment with BAPN did not suppress the formation of spontaneous lymph node metastases, or lung tumour burden, when tumour cells were injected intravenously. A temporal decrease in collagen fibre content, which is a target for LOX, was observed in tumours and in the tumour-adjacent prostate tissue. This may explain why early BAPN treatment is more effective in inhibiting tumour growth compared to treatment initiated later. Our data suggest that the enzymatic function of the LOX family is context-dependent, with both tumour-suppressing and tumour-promoting properties in prostate cancer. Further investigations are needed to understand the circumstances under which LOX inhibition may be used as a therapeutic target for cancer patients.

  • Nabbing, Robin
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nabbing, Robin
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Engström, Kim
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Behovsfrämjande ledarskap och dess longitudinella relation till anställdas sjukfrånvaro: Autonomi, kompetens och samhörighet i arbetet som medierande mekanismer2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Sickness absenteeism due to social and organisational reasons is increasing and the total cost of work-related illnesses in Sweden amounts to 70 billion krona each year in form of loss of production and health care expenses. Though leadership is assumed to play a central role in follower’s absenteeism-patterns, research exploring this relationship is scarce. The purpose of this study was to explore the longitudinal relationship between need-supportive leadership and sick leave, and to explore whether satisfaction of the basic psychological needs is related to and mediate the association between leadership and sickness absenteeism. Self-assessment data was collected with Need Support at Work scale and Need Satisfaction at Work scale from municipal employees (N = 589, 58% women, age span = 19-66 years) in a town in northern Sweden and was related to records of absence. The results show that need-supportive leadership is indirectly related to absenteeism through the satisfaction of the basic psychological needs. They also indicate a direct negative effect of need-supportive leadership on absence-spells over 40 days. These findings contribute with a theoretical understanding on how leaders affect follower’s absenteeism-patterns and can be used to guide organisational interventions.

  • Grauman, Sven
    et al.
    Grauman, Sven
    Boethius, Jakob
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Department of Anaesthesia and Intensive Care, Östersund Hospital, Östersund, Sweden.
    Regional Anaesthesia Is Associated with Shorter Postanaesthetic Care and Less Pain Than General Anaesthesia after Upper Extremity Surgery2016In: Anesthesiology Research and Practice, ISSN 1687-6962, E-ISSN 1687-6970, 6308371Article in journal (Refereed)
    Abstract [en]

    Introduction: For surgery on the upper extremity, the anaesthetist often has a choice between regional anaesthesia (RA) and general anaesthesia (GA). We sought to investigate the possible differences between RA and GA after upper extremity surgery with regard to postoperative patient comfort. Methods: This is a retrospective observational study that was performed at an acute care secondary referral centre. One hundred and eighty-seven procedures involving orthopaedic surgery on the upper extremity were included. The different groups (RA and GA) were compared regarding the primary outcome variable, length of stay in Postanaesthesia Unit, and secondary outcome variables, opioid consumption and nausea treatment. Results: RA was associated with significantly shorter median length of stay (99 versus 171 minutes). In the GA group, 32% of the patients received opioid analgesics and 21% received antiemetics. In the RA group, none received opioid analgesics and 3% received antiemetics. Conclusion: In this observational study, RA was superior to GA for surgery of the upper extremity regarding Postanaesthesia Care Unit length of stay, number of doses of analgesic, and number of doses of antiemetic administered.

  • Lindkvist, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Lindkvist, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Feldman, Inna
    Assessing outcomes for cost-utility analysis in mental health interventions: mapping mental health specific outcome measure GHQ-12 onto EQ-5D-3L2016In: Health and Quality of Life Outcomes, ISSN 1477-7525, E-ISSN 1477-7525, Vol. 14, 134Article in journal (Refereed)
    Abstract [en]

    Background: Many intervention-based studies aiming to improve mental health do not include a multi-attribute utility instrument (MAUI) that produces quality-adjusted life-years (QALYs) and it limits the applicability of the health economic analyses. This study aims to develop 'crosswalk' transformation algorithm between a measure for psychological distress General Health Questionnaire (GHQ-12) and MAUI EuroQoL (EQ-5D-3L). Methods: The study is based on a survey questionnaire sent to a random sample in four counties in Sweden in 2012. The survey included GHQ-12 and EQ-5D instruments, as well as a question about self-rated health. The EQ-5D index was calculated using the UK and the Swedish tariff values. Two OLS models were used to estimate the EQ-5D health state values using the GHQ-12 as exposure, based on the respondents (n = 17, 101) of two counties. The algorithms were applied to the data from two other counties, (n = 15, 447) to check the predictive capacity of the models. Results: The final models included gender, age, self-rated health and GHQ-12 scores as a quantitative variable. The regression equations explained 40 % (UK tariff) and 46 % (Swedish tariff) of the variances. The model showed a satisfying predictive capacity between the observed and the predicted EQ-5D index score, with Pearson correlation = 0.65 and 0.69 for the UK and Swedish models, respectively. Conclusion: The algorithms developed in this study can be used to determine cost-effectiveness of services or interventions that use GHQ-12 as a primary outcome where the utility measures are not collected.

  • Dahlin, Anna M.
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Dahlin, Anna M.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ghasimi, Soma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Relation between Established Glioma Risk Variants and DNA Methylation in the Tumor2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 10, e0163067Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies and candidate gene studies have identified several genetic variants that increase glioma risk. The majority of these variants are non-coding and the mechanisms behind the increased risk in carriers are not known. In this study, we hypothesize that some of the established glioma risk variants induce aberrant DNA methylation in the developing tumor, either locally (gene-specific) or globally (genome-wide). In a pilot data set including 77 glioma patients, we used Illumina beadchip technology to analyze genetic variants in blood and DNA methylation in matched tumor samples. To validate our findings, we used data from the Cancer Genome Atlas, including 401 glioblastoma patients. Consensus clustering identified the glioma CpG island methylator phenotype (gCIMP) and two additional subgroups with distinct patterns of global DNA methylation. In the pilot dataset, gCIMP was associated with two genetic variants in CDKN2B-AS1, rs1412829 and rs4977756 (9p21.3, p = 8.1 x 10(-7) and 4.8 x 10(-5), respectively). The association was in the same direction in the TCGA dataset, although statistically significant only when combining individuals with AG and GG genotypes. We also investigated the relation between glioma risk variants and DNA methylation in the promoter region of genes located within 30 kb of each variant. One association in the pilot dataset, between the TERT risk variant rs2736100 and lower methylation of cg23827991 (in TERT; p = 0.001), was confirmed in the TCGA dataset (p = 0.001). In conclusion, we found an association between rs1412829 and rs4977756 (9p21.3, CDKN2B-AS1) and global DNA methylation pattern in glioma, for which a trend was seen also in the TCGA glioblastoma dataset. We also found an association between rs2736100 (in TERT) and levels of methylation at cg23827991 (localized in the same gene, 3.3 kbp downstream of the risk variant), which was validated in the TCGA dataset. Except for this one association, we did not find strong evidence for gene-specific DNA methylation mediated by glioma risk variants.

  • Maraba, Noriah
    et al.
    Maraba, Noriah
    Karat, Aaron S.
    McCarthy, Kerrigan
    Churchyarda, Gavin J.
    Charalambous, Salome
    Kahn, Kathleen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt); School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; INDEPTH Network, Accra, Ghana .
    Grant, Alison D.
    Chihota, Violet
    Verbal autopsy-assigned causes of death among adults being investigated for TB in South Africa2016In: Transactions of the Royal Society of Tropical Medicine and Hygiene, ISSN 0035-9203, E-ISSN 1878-3503, Vol. 110, no 9, 510-516 p.Article in journal (Refereed)
    Abstract [en]

    Background: Adults being investigated for TB in South Africa experience high mortality, yet causes of death (CoD) are not well defined. We determined CoD in this population using verbal autopsy (VA), and compared HIV- and TB-associated CoD using physician-certified verbal autopsy (PCVA) and InterVA-4 software. Methods: All contactable consenting caregivers of participants who died during a trial comparing Xpert MTB/RIF to smear microscopy were interviewed using the WHO VA tool. CoD were assigned using PCVA and InterVA-4. Kappa statistic (K) and concordance correlation coefficient (CCC) were calculated for comparison. Results: Among 231 deaths, relatives of 137 deceased were interviewed. Of the 137 deceased 76 (55.4%) were males, median age 41 years (IQR 33-50). PCVA assigned 70 (51.1%) TB immediate CoD (44 [62.8%] pulmonary TB; 26 [37.1%] extra-pulmonary TB); 21 (15.3%) HIV/AIDS-related; and 46 (33.5%) other CoD. InterVA-4 assigned 48 (35.0%) TB deaths; 49 (35.7%) HIV/AIDS-related deaths; and 40 (29.1%) other CoD. Agreement between PCVA and InterVA-4 CoD was slight at individual level (K=0.20; 95% CI 0.10-0.30) and poor at population level (CCC 0.67; 95% CI 0.38-0.99). Conclusions: TB and HIV are leading CoD among adults being investigated for TB. PCVA and InterVA agreement at individual level was slight and poor at population level. VA methodology needs further development where TB and HIV are common.

  • Svanlund, Madeleine
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Svanlund, Madeleine
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Klienters självbild och dess samband med allians och behandlingsutfall i utbildningspsykoterapi2016Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Syftet med föreliggande studie var att i utbildningsterapi undersöka klientskattad självbild vid terapistart och dess samband med allians och behandlingsutfall, där behandlingsutfall definierades som förändring i utfallsvariablerna mellan terapistart och terapislut. Nittioåtta klienter som genomgick terapi på Psykologmottagningen vid Umeå Universitet deltog i studien. Självbild mättes med Structural Analysis of Social Behavior (SASB), allians med Working Alliance Inventory (WAI) och behandlingsutfall med Symptoms Checklist (SCL-90) och Outcome Questionnaire (OQ-45). En korrelationsanalys visade att högre nivåer av självkritik och av negativ självbild hade ett samband med lägre allians vid terapistart. Det fanns vidare ett samband mellan högre nivåer av självskyddande och av positiv självbild hos klienterna, och mindre förändring i allians mellan terapistart och terapislut. Slutligen hade högre nivåer av negativ självbild ett samband med bättre behandlingsutfall, och högre nivåer av positiv självbild var kopplad till sämre behandlingsutfall. Resultaten indikerar att klienters självbild kan vara relevant för terapeuter att undersöka, och att klienters självbild vid terapistart har mer koppling till behandlingsutfall än till allians. Mer forskning behövs på området.

  • Therése, Näslund
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Therése, Näslund
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Reinholdsson, Sophia
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    The features behind relationship satisfaction in friendship and romantic relationships2016Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Relationship satisfaction is positively related to life satisfaction and subjective well-being. The main aim of this thesis was to investigate what features that may explain satisfaction and dissatisfaction in friendship versus romantic relationships, and to compare the results. This study also aimed to examine the association between perceived loneliness and the degree of satisfaction in friendship versus romantic relationships. A questionnaire was distributed to a group of 93 university students between the ages of 18 to 41 years. Through thematic analysis it was found that balance, communication, closeness, support, trust, understanding, safety and conflict management were satisfying features in both types of relationships. Lacks of these features were found to be dissatisfying. Other dissatisfying features in romantic relationships were worry, lack of time and stress and in friendship relationships feelings of alienation and superficial relationships were dissatisfying features. Statistical analyses showed a negative association between friendship satisfaction and perceived loneliness. A tendency to a similar association with romantic relationship satisfaction emerged. Yet, there were also indications of the reverse in regard to romantic relationship satisfaction. Moreover, the possibility that friendship relationships might be more important than romantic relationships for university students in order for them not to feel lonely was discussed.

  • Adner, Kristin
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Adner, Kristin
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Axelsson, Therese
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Acceptance and Commitment Therapy i arbetet med barn och ungdomar: Behandlares erfarenheter och upplevelser av att anpassa och utöva metoden2016Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This study has examined therapists’ adjustments of ACT with children and adolescents and experiences of practicing the method with said group. Interviews were conducted with seven psychologists and data was analyzed using thematic analysis. Results showed general child-therapeutic adjustments, combining ACT with tCBT and modifications of the ACT principles. Challenges were working with a context with a different agenda, to be flexible and daring to be active and weird. Another challenge was working with a method that isn’t implemented in the workplace and has an uncertain future. Possibilities included using ACT for oneself, working towards positive goals and having fun. Additionally, a view of ACT as a philosophy of life was presented. Dilemmas concerning the use of a method lacking evidence were also presented. Future research can examine the impact of the different ACT principles on psychological flexibility in youths and how challenges in treatment can be overcome.

  • Svensson, Lisa
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Svensson, Lisa
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Elvin Johansson, Lovisa
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Multifamiljeterapi vid behandling av ungdomar med anorexia nervosa: En pilotstudie med fokus på behandlingsinterventioner och familjeklimat2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Multi-family therapy (MFT) is a relatively new treatment for adolescents with anorexia nervosa (AN) in Sweden. The aim of this pilot study was to investigate how patients, mothers and fathers perceived interventions in MFT and if there was a change in family climate after treatment. In total 14 patients, 14 mothers and 14 fathers were examined with the two questionnaires Behandlingstillfredsställelse and Family climate scale (FCS). The results showed that the following interventions in MFT were perceived as helpful for all groups; discussions in large and small groups, group meals, exercises, games and role play. Family climate was significantly improved over time regarding the dimensions closeness and distance. A difference between patients and mothers was found in how they experienced closeness as mothers reported lower closeness than patients. An interaction effect was found regarding chaos as the patients and mothers reported a decrease in chaos while the fathers reported a slight increase. The results indicate that all the interventions in MFT are helpful and that, by and large, family climate improves after treatment. Further research with a larger sample is required to confirm these findings.