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  • Samad, Delan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Studenters reflektioner kring kommunikation: En analys av reflektionsuppsatser skrivna av farmacistudenter på år 3 och 52019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • Nikolasien Heimdal, Catharina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Tjenestefarmasøyters syn på Inhalasjonsveiledningen.: En intervjustudie som undersøker norske tjenestefarmasøyters tanker om nytten av tjenesten.2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • Al-Obaidi, Mays
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Läkemedelsundervisning i skolan: En enkätundersökning på gymnasieskole elever- och lärare i Skåne län2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Westin, Lars
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Regional Science (CERUM).
    Westin, Jonas
    Umeå University, Faculty of Social Sciences, Centre for Regional Science (CERUM).
    Planering av godstransporter på regional nivå: Modeller, verktyg och förvaltningspolitik2019Report (Other academic)
    Abstract [sv]

    Rapporten fokuserar på den kunskapsbrist som finns beträffande nuläget i det svenska gods­transport­nätverket på regional och lokal nivå. Det påverkar kommunikation och skapar osäkerhet i dialogen mellan aktörer inom transportplanering på regional och kommunal nivå. Som bakgrund diskuteras planeringsprocessen för gods­transporternas infrastruktur inom Trafikverket. Den relateras till planering på kommunal och regional nivå. Inom Trafikverket och dess föregångare har tyngdpunkten mellan nationell styrning och lokala förhandlingar varierat. Inom Trafikverket sker en förskjutning av fokus från nationell nivå till dialogprocesser med lokala planerare och näringsliv, från ”government” till ”governance”. Samtidigt är modell- och investeringskalkylsidan för åtgärder inom godstransporter mycket starkt nationellt fokuserad, med rötter i 1990-talets nationella produktivitetsproblematik. För godsplaneringen innebär det att representationen av de lokala och regionala godstransportnätverken är begränsad. Det skapar oklarheter i dialogprocesserna på regional och lokal nivå. Enskilda regioner har därför själva eller i samverkan med Trafikverket genomfört egna godsflödesenkäter och byggt regionala modeller. Några av dess presenteras i rapporten. Därpå diskuteras vilka verktyg och dataunderlag som behövs för att på ett bättre sätt stödja regional och lokal transportplanering för godstransporter.

  • Gruen, Sara
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Economics.
    Settling for Quality?: Estimating relative quality of life for Swedish counties using cross-migration data2019Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The main purpose on this thesis is to analyze utility differences between Swedish counties and to determine the relative quality of life (QoL) for these regions. This is achieved by using migration data to estimate the counties attractiveness in line with Tiebout’s (1957) idea that individuals reveales their preferences for a region by choosing where to settle. The methods used are mainly based on the work by Wall’s (2001) and Nakajima and Tabuchi (2011). I estimate a pooled OLS based on cross-county migration data for the period 2000 to 2016, which reveals that most of the Swedish counties have a relative QoL that does not differ from the average QoL for Sweden. However, some counties, mainly northern ones, seem to perform worse than the average. Additionally, I estimate the relative utility differentials for the Swedish counties and find that they have stayed relatively constant in relation to each other during the time period.

  • Rentoft, Matilda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Svensson, Daniel
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sjödin, Andreas
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Division of CBRN Security and Defence, FOI–Swedish Defence Research Agency, SE Umeå, Sweden.
    Olason, Pall I.
    Sjöström, Olle
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Unit of research, education and development, Region Jämtland Härjedalen, SE Östersund, Sweden.
    Nylander, Carin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Osterman, Pia
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sjögren, Rickard
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Netotea, Sergiu
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Science for Life Laboratory, Department of Biology and Biological Engineering, Chalmers University of Technology, SE Göteborg, Sweden.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Cederquist, Kristina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Chabes, Andrei
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    A geographically matched control population efficiently limits the number of candidate disease-causing variants in an unbiased whole-genome analysis2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 3, article id e0213350Article in journal (Refereed)
    Abstract [en]

    Whole-genome sequencing is a promising approach for human autosomal dominant disease studies. However, the vast number of genetic variants observed by this method constitutes a challenge when trying to identify the causal variants. This is often handled by restricting disease studies to the most damaging variants, e.g. those found in coding regions, and overlooking the remaining genetic variation. Such a biased approach explains in part why the genetic causes of many families with dominantly inherited diseases, in spite of being included in whole-genome sequencing studies, are left unsolved today. Here we explore the use of a geographically matched control population to minimize the number of candidate disease-causing variants without excluding variants based on assumptions on genomic position or functional predictions. To exemplify the benefit of the geographically matched control population we apply a typical disease variant filtering strategy in a family with an autosomal dominant form of colorectal cancer. With the use of the geographically matched control population we end up with 26 candidate variants genome wide. This is in contrast to the tens of thousands of candidates left when only making use of available public variant datasets. The effect of the local control population is dual, it (1) reduces the total number of candidate variants shared between affected individuals, and more importantly (2) increases the rate by which the number of candidate variants are reduced as additional affected family members are included in the filtering strategy. We demonstrate that the application of a geographically matched control population effectively limits the number of candidate disease-causing variants and may provide the means by which variants suitable for functional studies are identified genome wide.

  • Linderholm, Johan
    et al.
    Umeå University, Faculty of Arts, Department of historical, philosophical and religious studies.
    Geladi, Paul
    Department of Forest Biomaterials and Technology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Gorretta, Natalie
    UMR ITAP, IRSTEA, Centre de Montpellier, Montpellier, France.
    Bendoula, Ryad
    UMR ITAP, IRSTEA, Centre de Montpellier, Montpellier, France.
    Gobrecht, Alexia
    UMR ITAP, IRSTEA, Centre de Montpellier, Montpellier, France.
    Near infrared and hyperspectral studies of archaeological stratigraphy and statistical considerations2019In: Geoarchaeology, ISSN 0883-6353, E-ISSN 1520-6548, Vol. 34, no 3, p. 311-321Article in journal (Refereed)
    Abstract [en]

    The paper proposes a methodology based on near‐infrared (NIR) spectrometry for studying stratigraphy and depth profiles in archaeological excavations. The NIR spectra can be used to describe and complement the wet chemical analysis. Soil samples were collected from a 0.8 m deep stratigraphy of a Neolithic site that were analyzed by three different NIR instrumentations. Phosphate‐ and magnetic susceptibility and inductively‐coupled plasma mass spectrometry measurements were also conducted as reference analysis.

    Principal component analysis on the data from three different NIR instrumentations gave useful score plots that allowed grouping of the samples. The results from the lab spectrometer were most useful, although the hyperspectral NIR camera was the fastest method to obtain spectra of many samples from one image. The paper shows how the NIR spectral data can be used for multivariate analysis to get meaningful conclusions on archaeological soils and sediments, especially in terms of understanding site development/phases and soil formation.

  • Kallin, Niklas
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Sensor simulation Is - AGXUnity a viable platform for adding synthetic sensors2019Independent thesis Basic level (degree of Bachelor of Fine Arts), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    When developing algorithms for autonomous vehicles it is important to test several different scenarios many times. New and untested algorithms are prone to make errors which results in accidents. It is therefore preferred to use a simulation environment instead. Sensors used to determine the vehicle’s position must then be modelled. This thesis answers the question whether adding sensor simulation to an existing simulation platform (AGXUnity) is viable, or if using other existing options is preferred. To reach the goal, a function-based sensor is developed and its accuracy tested. Its performance is determined by simulation in a standard scene. Tests showed that the sensor had acceptable accuracy and performance. The conclusion is that AGXUnity is a viable platform for sensor simulation.

  • Jeppsson, Sofia
    Umeå University, Faculty of Arts, Department of historical, philosophical and religious studies.
    The agential perspective: a hard-line reply to the four-case manipulation argument2019In: Philosophical Studies, ISSN 0031-8116, E-ISSN 1573-0883Article in journal (Refereed)
    Abstract [en]

    One of the most influential arguments against compatibilism is Derk Pereboom’s four-case manipulation argument. Professor Plum, the main character of the thought experiment, is manipulated into doing what he does; he therefore supposedly lacks moral responsibility for his action. Since he is arguably analogous to an ordinary agent under determinism, Pereboom concludes that ordinary determined agents lack moral responsibility as well. I offer a hard-line reply to this argument, that is, a reply which denies that this kind of manipulation is responsibility undermining. I point out that fully fleshed-out manipulated characters in fiction can seem morally responsible for what they do. This is plausibly because we identify with such characters, and therefore focus on their options and the reasons for which they act rather than the manipulation. I further argue that we ought to focus this way when interacting with other agents. We have no reason to trust the incompatibilist intuitions that arise when we regard manipulated agents from a much more detached perspective.

  • Tawhid Söderholm, Nora
    et al.
    Turkmen, Sahruh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Department of Obstetrics and Gynecology, Örnsköldsvik Hospital, Örnsköldsvik, Sweden.
    Impact of Epidural Analgesia in Labour onNeonatal and Maternal Outcomes2018In: Open Journal of Obstetrics and Gynecology, ISSN 2160-8792, E-ISSN 2160-8806, Vol. 8, p. 767-779Article in journal (Refereed)
    Abstract [en]

    AimTo evaluate the effect of epidural analgesia during labour on neonatal-maternal outcomes. 

    Methods: A retrospective cohort study of nulliparous parturients who gave birth in Vasternorrland County, Sweden, over a 2-year period between 2015 and 2016. Neonatal outcomes (Apgar score at 5 min and umbilical cord arterial blood gases), maternal outcomes (perineal injury, total bleeding volume and maternal satisfaction with birth) and labour parameters (mode of delivery and the durations of labour and postpartum hospital stay) were evaluated. 

    Results: The study cohort consisted of 1449 women with singleton pregnancies. Patients were divided into two groups according to whether during labour they were administered epidural analgesia using bupivacaine and sufentanil (EDA group, n = 615) or not (non-EDA group, n = 834). The rate of assisted vaginal delivery was significantly higher in the EDA group than in the non-EDA group (15.6% and 11.3%, respectively, p < 0.05), whereas the rates of caesarean section were similar. The duration of the active phase of labour was significantly longer in the EDA group than in the non-EDA group (489 ± 217 min versus 371 ± 210 min, respectively, p < 0.001). The Apgar score at 5 min and umbilical cord blood pH were lower and the base deficit greater in the EDA group (p < 0.001, p < 0.001 and p < 0.01, respectively). Bleeding volume was similar between the groups after adjusting for gestational age. Women in the EDA group were more satisfied with their labour experience, as measured by the visual analogue scale (p < 0.05). 

    Conclusion: The results of this study suggest that EDA affects delivery and neonatal-maternal outcomes negatively, but increases the mother’s satisfaction with labour.

  • Yeşilbaş, Merve
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Holmboe, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Boily, Jean-Francois
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Residence times of nanoconfined CO2 in layered aluminosilicates2019In: Environmental Science: Nano, ISSN 2051-8153, Vol. 6, no 1, p. 146-151Article in journal (Refereed)
    Abstract [en]

    Nanoconfinement of CO2 in layered aluminosilicates contributes to the capture and release of this greenhouse gas in soils. In this work, we show that the residence times of CO2 in montmorillonite are lowered by 15 min for each 1 degrees C increment in temperature during venting. Molecular simulations showed that activation energies of release are no more than half of the experimentally derived value of 34 kJ mol(-1). This raised the possibility of additional processes limiting CO2 mobility in real materials, including (chemi)sorption at reactive sites or frayed edges or defects. The residence times (approximate to 1616 min at -50 degrees C to approximate to 6 min at 60 degrees C) for some of the driest (approximate to 1.4 mmol H2O per g) montmorillonites that can be produced at ambient temperatures are readily lowered by inclusion of additional water. They are, in turn, prolonged again as the water content and interlayer spacing become smaller through venting. These efforts showed that soil-building clay minerals will lose their propensity to dynamically exchange CO2 as temperatures continue to rise, yet they may retain CO2 more efficiently in cold seasons as soils will become depleted in moisture content.

  • Sundström, Johan
    et al.
    Björkelund, Cecilia
    Giedraitis, Vilmantas
    Hansson, Per-Olof
    Högman, Marieann
    Janson, Christer
    Koupil, Ilona
    Kristenson, Margareta
    Lagerros, Ylva Trolle
    Leppert, Jerzy
    Lind, Lars
    Lissner, Lauren
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Ludvigsso, Jonas F.
    Nilsson, Peter M.
    Olsson, Håkan
    Pedersen, Nancy L.
    Rosenblad, Andreas
    Rosengren, Annika
    Sandin, Sven
    Snackerstrom, Tomas
    Stenbeck, Magnus
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Heart Center, Umeå University, Umeå.
    Weiderpass, Elisabete
    Wanhainen, Ers
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Fortier, Isabel
    Heller, Susanne
    Storgards, Maria
    Svennblad, Bodil
    Rationale for a Swedish cohort consortium2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 21-28Article in journal (Refereed)
    Abstract [en]

    We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.

  • Lysholm, Jack
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lindahl, Bertil
    Strong development of research based on national quality registries in Sweden2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 9-11Article in journal (Refereed)
    Abstract [en]

    The aim of the present paper is to describe how the use of national quality registries (NQRs) for research has evolved over the past decade in Sweden. All Swedish NQRs have reported their scientific activity (publications per year in peer-reviewed scientific journals) to the Swedish Association of Local Authorities and Regions since 2009, and the present report is based on available data from 2009-2016. The yearly number of publications of the 69 registries active in 2009 has increased from 121 to 496 in 2016. Seventeen of these registries published more than 10 papers in 2016; however, 12 NQRs did not publish any papers in 2016. An additional 77 papers were published in 2016 by the 34 NQRs started after 2009. In summary, there has been a strong development of quality registry-based research in Sweden over the last decade. However, there is still room for further increase of the use of research based on NQRs in Sweden.

  • Kaelin, Vera C.
    et al.
    van Hartingsveldt, Margo
    Gantschnig, Brigitte E.
    Fisher, Anne G.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Occupational Therapy. Department of Occupational Therapy, College of Health and Human Services, Colorado State University, Fort Collins, CO, USA.
    Are the school version of the assessment of motor and process skills measures valid for German-speaking children?2019In: Scandinavian Journal of Occupational Therapy, ISSN 1103-8128, E-ISSN 1651-2014, Vol. 26, no 2, p. 149-155Article in journal (Refereed)
    Abstract [en]

    Background: There are no validated assessment tools for evaluating quality of schoolwork task performance of children living in German-speaking Europe (GSE).

    Objective: To determine whether the international age-normative means of the School Version of the Assessment of Motor and Process Skills (School AMPS) are valid for use in GSE.

    Methods: The participants were 159 typically-developing children, 3-12 years, from GSE. We examined the proportions of School AMPS measures falling within +/- 2 standard deviation (SD) of the international age-normative means, and evaluated for significant group differences (p<0.05) in mean School AMPS measures between the GSE sample and the international age-normative sample using one-sample Z tests. When significant mean differences were found, we evaluated if the differences were clinically meaningful.

    Results: At least 95% of the GSE School AMPS measures fell within +/- 2 SD of the international age-normative means for the School AMPS. The only significant mean differences were for 6(p < 0.01) and 8-year-olds (p = 0.02), and only the 6-year-old school process mean difference was clinically meaningful.

    Conclusions: Because the only identified clinically meaningful difference was associated with likely scoring error of one rater, the international age-normative means of the School AMPS appear to be valid for use with children in GSE.

  • Fernandes Mariano, Tais
    Umeå University, Faculty of Arts, Department of language studies.
    An Outline of the Semantic Network of the Preposition Up in American English: A Corpus Study2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In this study an outline is presented of the semantic network of the preposition up in American English in sentences extracted from the Corpus of Contemporary American English (COCA), which was done to determine what the most common uses and meanings of the preposition are, as well as to determine if most of its possible meanings are concrete or abstract. The results show that there is a salient use and also prototypical meaning of up, and that these are major factors that impact the semantic network of the preposition. This study was designed to be a source of information for EFL students who struggle to understand how prepositions function in the English language, and also what the prepositions can actually represent in a sentence. Concomitantly, the goal is to give information about the preposition up in a way that will allow students to analyze other prepositions and perhaps even other word classes.

  • Mackay, Heather
    Umeå University, Faculty of Social Sciences, Department of Geography.
    A feminist geographic analysis of perceptions of food and health in Ugandan cities2019In: Gender, Place and Culture: A Journal of Feminist Geography, ISSN 0966-369X, E-ISSN 1360-0524Article in journal (Refereed)
    Abstract [en]

    This article contributes to a feminist geographic analysis of how urban food and health environments and non-communicable disease experience may be being constructed, and contested, by healthcare professionals (local elites) in two secondary Ugandan cities (Mbale and Mbarara). I use thematic and group interaction analysis of focus group data to explore material and discursive representations. Findings make explicit how healthcare professionals had a tendency to prescribe highly classed and gendered assumptions of bodies and behaviours in places and in daily practices. The work supports the discomfort some have felt concerning claims of an African nutrition transition, and is relevant to debates regarding double burden malnutrition. I argue that a feministic analysis, and an intersectional appreciation of people in places, is advantageous to food and health-related research and policy-making. Results uncover and deconstruct a dominant patriarchal tendency towards blaming women for obesity. Yet findings also exemplify the co-constructed and malleable nature of knowledge and understandings, and this offers encouragement.

  • van der Horst, Sjors
    et al.
    Snel, Berend
    Hanson, Johannes
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Molecular Plant Physiology, Institute of Environmental Biology, Utrecht University, Utrecht, The Netherlands; Theoretical Biology and Bioinformatics, Department of Biology, Utrecht University, Utrecht, The Netherlands .
    Smeekens, Sjef
    Novel pipeline identifies new upstream ORFs and non-AUG initiating main ORFs with conserved amino acid sequences in the 5 ' leader of mRNAs in Arabidopsis thaliana2019In: RNA: A publication of the RNA Society, ISSN 1355-8382, E-ISSN 1469-9001, Vol. 25, no 3, p. 292-304Article in journal (Refereed)
    Abstract [en]

    Eukaryotic mRNAs contain a 5' leader sequence preceding the main open reading frame (mORF) and, depending on the species, 20%-50% of eukaryotic mRNAs harbor an upstream ORF (uORF) in the 5' leader. An unknown fraction of these uORFs encode sequence conserved peptides (conserved peptide uORFs, CPuORFs). Experimentally validated CPuORFs demonstrated to regulate the translation of downstream mORFs often do so in a metabolite concentration-dependent manner. Previous research has shown that most CPuORFs possess a start codon context suboptimal for translation initiation, which turns out to be favorable for translational regulation. The suboptimal initiation context may even include non-AUG start codons, which makes CPuORFs hard to predict. For this reason, we developed a novel pipeline to identify CPuORFs unbiased of start codon using well-annotated sequence data from 31 eudicot plant species and rice. Our new pipeline was able to identify 29 novel Arabidopsis thaliana (Arabidopsis) CPuORFs, conserved across a wide variety of eudicot species of which 15 do not initiate with an AUG start codon. In addition to CPuORFs, the pipeline was able to find 14 conserved coding regions directly upstream and in frame with the mORF, which likely initiate translation on a non-AUG start codon. Altogether, our pipeline identified highly conserved coding regions in the 5' leaders of Arabidopsis transcripts, including in genes with proven functional importance such as LHY, a key regulator of the circadian clock, and the RAPTOR1 subunit of the target of rapamycin (TOR) kinase.

  • Ragnarsson, Oskar
    et al.
    Olsson, Daniel S.
    Chantzichristos, Dimitrios
    Papakokkinou, Eleni
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Segerstedt, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Petersson, Maria
    Berinder, Katarina
    Bensing, Sophie
    Hoybye, Charlotte
    Eden Engström, Britt
    Burman, Pia
    Bonelli, Lorenza
    Follin, Cecilia
    Petranek, David
    Erfurth, Eva Marie
    Wahlberg, Jeanette
    Ekman, Bertil
    Åkerman, Anna-Karin
    Schwarcz, Erik
    Bryngelsson, Ing-Liss
    Johannsson, Gudmundur
    The incidence of Cushing's disease: a nationwide Swedish study2019In: Pituitary, ISSN 1386-341X, E-ISSN 1573-7403, Vol. 22, no 2, p. 179-186Article in journal (Refereed)
    Abstract [en]

    Background: Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden.

    Methods: Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.

    Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05).

    Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.

  • Klemenčič, Marina
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
    Asplund-Samuelsson, Johannes
    Dolinar, Marko
    Funk, Christiane
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Phylogenetic Distribution and Diversity of Bacterial Pseudo-Orthocaspases Underline Their Putative Role in Photosynthesis2019In: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 10, article id 293Article in journal (Refereed)
    Abstract [en]

    Orthocaspases are prokaryotic caspase homologs – proteases, which cleave their substrates after positively charged residues using a conserved histidine – cysteine (HC) dyad situated in a catalytic p20 domain. However, in orthocaspases pseudo-variants have been identified, which instead of the catalytic HC residues contain tyrosine and serine, respectively. The presence and distribution of these presumably proteolytically inactive p20-containing enzymes has until now escaped attention. We have performed a detailed analysis of orthocaspases in all available prokaryotic genomes, focusing on pseudo-orthocaspases. Surprisingly we identified type I metacaspase homologs in filamentous cyanobacteria. While genes encoding pseudo-orthocaspases seem to be absent in Archaea, our results show conservation of these genes in organisms performing either anoxygenic photosynthesis (orders Rhizobiales, Rhodobacterales, and Rhodospirillales in Alphaproteobacteria) or oxygenic photosynthesis (all sequenced cyanobacteria, except Gloeobacter, Prochlorococcus, and Cyanobium). Contrary to earlier reports, we were able to detect pseudo-orthocaspases in all sequenced strains of the unicellular cyanobacteria Synechococcus and Synechocystis. In silico comparisons of the primary as well as tertiary structures of pseudo-p20 domains with their presumably proteolytically active homologs suggest that differences in their amino acid sequences have no influence on the overall structures. Mutations therefore affect most likely only the proteolytic activity. Our data provide an insight into diversification of pseudo-orthocaspases in Prokaryotes, their taxa-specific distribution, and allow suggestions on their taxa-specific function.

  • Sobhy, Haitham
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Kumar, Rajendra
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Lewerentz, Jacob
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Lizana, Ludvig
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Division of CBRN Security and Defence, FOI–Swedish Defence Research Agency, Umeå, Sweden.
    Highly interacting regions of the human genome are enriched with enhancers and bound by DNA repair proteins2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4577Article in journal (Refereed)
    Abstract [en]

    In specific cases, chromatin clearly forms long-range loops that place distant regulatory elements in close proximity to transcription start sites, but we have limited understanding of many loops identified by Chromosome Conformation Capture (such as Hi-C) analyses. In efforts to elucidate their characteristics and functions, we have identified highly interacting regions (HIRs) using intra-chromosomal Hi-C datasets with a new computational method based on looking at the eigenvector that corresponds to the smallest eigenvalue (here unity). Analysis of these regions using ENCODE data shows that they are in general enriched in bound factors involved in DNA damage repair and have actively transcribed genes. However, both highly transcribed regions as well as transcriptionally inactive regions can form HIRs. The results also indicate that enhancers and super-enhancers in particular form long-range interactions within the same chromosome. The accumulation of DNA repair factors in most identified HIRs suggests that protection from DNA damage in these regions is essential for avoidance of detrimental rearrangements.

  • Asklund, Ina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Hamberg, Katarina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Umefjord, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sjöström, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    User Experience of an App-Based Treatment for Stress Urinary Incontinence: Qualitative Interview Study2019In: Journal of Medical Internet Research, ISSN 1438-8871, E-ISSN 1438-8871, Vol. 21, no 3, article id e11296Article in journal (Refereed)
    Abstract [en]

    Background: Stress urinary incontinence (SUI) affects 10%-39% of women. Its first-line treatment consists of lifestyle interventions and pelvic floor muscle training (PFMT), which can be performed supervised or unsupervised. Health apps are increasing in number and can be used to improve adherence to treatments. We developed the Tät app, which provides a 3-month treatment program with a focus on PFMT for women with SUI. The app treatment was evaluated in a randomized controlled trial, which demonstrated efficacy for improving incontinence symptoms and quality of life. In this qualitative interview study, we investigated participant experiences of the app-based treatment.

    Objective: This study aimed to explore women’s experiences of using an app-based treatment program for SUI.

    Methods: This qualitative study is based on telephone interviews with 15 selected women, with a mean age of 47 years, who had used the app in the previous randomized controlled trial. A semistructured interview guide with open-ended questions was used, and the interviews were transcribed verbatim. Data were analyzed according to the grounded theory.

    Results: The results were grouped into three categories: “Something new!” “Keeping motivation up!” and “Good enough?” A core category, “Enabling my independence,” was identified. The participants appreciated having a new and modern way to access a treatment program for SUI. The use of new technology seemed to make incontinence treatment feel more prioritized and less embarrassing for the subjects. The closeness to their mobile phone and app features like reminders and visual graphs helped support and motivate the women to carry through the PFMT. The participants felt confident that they could perform the treatment program on their own, even though they expressed some uncertainty about whether they were doing the pelvic floor muscle contractions correctly. They felt that the app-based treatment increased their self-confidence and enabled them to take responsibility for their treatment.

    Conclusions: Use of the app-based treatment program for SUI empowered the women in this study and helped them self-manage their incontinence treatment. They appreciated the app as a new tool for supporting their motivation to carry through a slightly challenging PFMT program.

    Trial Registration: ClinicalTrials.gov NCT01848938; https://clinicaltrials.gov/ct2/show/NCT01848938 (Archived by WebCite at https://clinicaltrials.gov/ct2/show/NCT01848938)

  • Bergqvist, Oscar
    et al.
    Umeå University, Faculty of Social Sciences, Department of applied educational science.
    Kling, Olof
    Umeå University, Faculty of Social Sciences, Department of applied educational science.
    Spelifiering: ett lärarperspektiv2018Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Spelifiering är praktiken att använda mekanik från spel i icke-spelkontext för att höja användarens motivation och det är ett relativt nytt begrepp som får växande utrymme i skolan. Trots att det redan gjorts en hel del forskning på området finns det en avsaknad av studier som undersöker spelifiering från ett lärarperspektiv. Syftet med denna studie är därför att bilda kunskap om lärares användning av spelifiering i sin undervisning. För att belysa lärares erfarenheter har semistrukturerade intervjuer genomförts med sex olika lärare som sade sig använda spelifiering i sin undervisning. En tematisk innehållsanalys har resulterat i beskrivningar av lärarnas upplevelser och erfarenheter kring användningen av spelifiering i undervisningen. Resultaten visar att lärarna har svårt att skilja spelbaserat lärande och spelifiering från varandra. De visar även spelifierat (och spelbaserat) lärande som positivt för elevernas motivation och inlärning, och att det låter lärarna nå ut till eleverna på nya sätt. Samtliga lärare tog upp vikten av ett lustfyllt lärande, och de hade även roligt själva i sitt användande av spel och spelifiering. De resonerade vidare kring utmaningar med sitt arbetssätt och konstaterade att spelifiering bör användas med eftertanke då externa motiverande element, som exempelvis belöningar, kan ta fokus från lärandet.

  • Mattsson, Sandra
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Microscopy techniques for studying polymer-polymer blends2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Semiconductors are used in many electronic applications, for example diodes, solar cells and transistors. Typically, semiconductors are inorganic materials, such as silicon and gallium arsenide, but lately more research and development has been devoted to organic semiconductors, for example semiconducting polymers. One of the reasons is that polymers can be customized, to a greater extent than inorganic semiconductors, to create a material with desired properties. Often, two polymers are blended to obtain the desired function, but two polymers do not usually result in an even blend. Instead they tend to separate from each other to varying degrees. The morphology of the blend affects the material properties, for example how efficiently it can convert electricity to light.

    In this project, thin films consisting of polymer blends were examined using microscopy techniques for the purpose of increasing our understanding of the morphology of such blends. One goal was to investigate whether a technique called correlative light and electron microscopy can be useful for examining the morphology of these films. In correlative light and electron microscopy, a light microscope and an electron microscope are used in the same location in order to be able to correlate the information from the two microscopes. The second goal was to learn about the morphology of the thin films using various microscopy techniques.

    The polymers used were Super Yellow and poly(ethylene oxide) with large molecular weight. Super Yellow is a semiconducting and light-emitting polymer while poly(ethylene oxide) is an isolating and non-emitting polymer that can crystallize. In the blend films, large, seemingly crystalline structures appeared. The structures could be up to 1 mm in the lateral direction, while the films were only approximately 170 nm thick. These structures could grow after the films had dried and their shapes were similar to those of poly(ethylene oxide) crystals. Consequently, there is reason to believe that it is the poly(ethylene oxide) that makes up the seemingly crystalline structures, but the structures also emitted more light than the rest of the film, and Raman spectroscopy showed that there was Super Yellow in the same location as the crystals.

    Among the microscopy techniques used, phase contrast microscopy was particularly interesting. This method visualizes differences in optical path length and was useful for studying polymer blends when the polymers have different indices of refraction. Correlating light and electron microscopy showed that there was a pronounced topographical difference between the seemingly crystalline regions and the rest of the thin film. Light microscopy has a limited resolution due to diffraction, but as long as the resolution of the light microscope is sufficient for seeing phase separation, correlative light and electron microscopy turned out to be a good method for studying the morphology of thin films of polymer blends.

  • Kumar, Rajendra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics. Integrated Science Lab, Umeå University, Umeå, Sweden.
    Lizana, Ludvig
    Umeå University, Faculty of Science and Technology, Department of Physics. Integrated Science Lab, Umeå University, Umeå, Sweden.
    Stenberg, Per
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Division of CBRN Security and Defence, FOI-Swedish Defence Research Agency, Umeå, Sweden.
    Genomic 3D compartments emerge from unfolding mitotic chromosomes2019In: Chromosoma, ISSN 0009-5915, E-ISSN 1432-0886, Vol. 128, no 1, p. 15-20Article in journal (Refereed)
    Abstract [en]

    The 3D organisation of the genome in interphase cells is not a randomly folded polymer. Rather, experiments show that chromosomes arrange into a network of 3D compartments that correlate with biological processes, such as transcription, chromatin modifications and protein binding. However, these compartments do not exist during cell division when the DNA is condensed, and it is unclear how and when they emerge. In this paper, we focus on the early stages after cell division as the chromosomes start to decondense. We use a simple polymer model to understand the types of 3D structures that emerge from local unfolding of a compact initial state. From simulations, we recover 3D compartments, such as TADs and A/B compartments that are consistently detected in chromosome capture experiments across cell types and organisms. This suggests that the large-scale 3D organisation is a result of an inflation process.

  • Storm Mienna, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Glas, Linnéa
    Umeå University, Faculty of Medicine, Department of Odontology.
    Magnusson, My
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ilgunas, Aurelija
    Umeå University, Faculty of Medicine, Department of Odontology.
    Häggman-Henrikson, Birgitta
    Umeå University, Faculty of Medicine, Department of Odontology. Department of Orofacial pain and Jaw function, Malmö Universiy, Malmö, Sweden.
    Wänman, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Patients' experiences of supervised jaw-neck exercise among patients with localized TMD pain or TMD pain associated with generalized pain2019In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate temporomandibular disorder (TMD) patients’ experiences of a supervised jaw-neck exercise programme.

    Materials and methods: The study used a mixed method design. All patients were diagnosed with myalgia according to the Research Diagnostic Criteria for TMD and divided into local myalgia (n = 50; 38 women, mean age 43 yrs, SD 14), and myalgia with generalized pain (n = 28; 27 women, mean age 43 yrs, SD 13). Patients participated in a ten-session supervised exercise programme that included relaxation, coordination and resistance training of the jaw, neck and shoulders. After the 10 sessions an evaluation form was filled out including both open- and closed-ended questions. The quantitative analysis was based on closed-ended questions concerned experience, adaptation and side-effects from the exercise programme. The qualitative analysis was employing inductive content analysis of open-ended questions.

    Results: Patients reported similar positive overall experiences of exercise regardless of diagnosis, although more individuals in the general pain group experienced pain during training (57%) compared to the local pain group (26%; p = .015). Patients in both groups shared similar experiences and acknowledged the possibility to participate in an individualized and demanding exercise programme. They expressed feelings of being noticed, taken seriously and respectful care management to be key factors for successful treatment outcome. The exercise programme was acknowledged as a valuable part of treatment.

    Conclusion: The hypothesis generated was that individualized and gradually demanding exercise in the rehabilitation process of TMD stimulates self-efficacy and confidence in chronic TMD patients regardless of whether the pain was localized or combined with wide-spread pain.

  • Kolan, Shrikant S
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Lidström, Tommy
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Mediavilla, Tomás
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Dernstedt, Andy
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Björk, Karl
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Marcellino, Daniel
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Growth-inhibition of cell lines derived from B cell lymphomas through antagonism of serotonin receptor signaling2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4276Article in journal (Refereed)
    Abstract [en]

    A majority of lymphomas are derived from B cells and novel treatments are required to treat refractory disease. Neurotransmitters such as serotonin and dopamine influence activation of B cells and the effects of a selective serotonin 1A receptor (5HT1A) antagonist on growth of a number of B cell-derived lymphoma cell lines were investigated. We confirmed the expression of 5HT1A in human lymphoma tissue and in several well-defined experimental cell lines. We discovered that the pharmacological inhibition of 5HT1A led to the reduced proliferation of B cell-derived lymphoma cell lines together with DNA damage, ROS-independent caspase activation and apoptosis in a large fraction of cells. Residual live cells were found ‘locked’ in a non-proliferative state in which a selective transcriptional and translational shutdown of genes important for cell proliferation and metabolism occurred (e.g., AKT, GSK-3β, cMYC and p53). Strikingly, inhibition of 5HT1A regulated mitochondrial activity through a rapid reduction of mitochondrial membrane potential and reducing dehydrogenase activity. Collectively, our data suggest 5HT1A antagonism as a novel adjuvant to established cancer treatment regimens to further inhibit lymphoma growth.

  • Bjureberg, Johan
    et al.
    Ohlis, Anna
    Ljotsson, Brjann
    D'Onofrio, Brian M.
    Hedman-Lagerlöf, Erik
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Sahlin, Hanna
    Lichtenstein, Paul
    Cederlöf, Martin
    Hellner, Clara
    Adolescent self-harm with and without suicidality: cross-sectional and longitudinal analyses of a Swedish regional register2019In: Journal of Child Psychology and Psychiatry and Allied Disciplines, ISSN 0021-9630, E-ISSN 1469-7610, Vol. 60, no 3, p. 295-304Article in journal (Refereed)
    Abstract [en]

    Background: Self-harm is common and there is a need for studies that investigate the relevance of this behavior in clinical samples to inform risk assessment and treatment. The objectives in the current studies were to compare clinical and psychosocial correlates and subsequent adverse outcomes in youth who present to child and adolescent mental health services (CAMHS) with self-harm only (SH), self-harm with suicidality (SH+SU), with those without any indication of SH or SH+SU.

    Methods: We conducted a case-control study and a longitudinal cohort study using data from a regional clinical care register, and Swedish national registers. The case-control study included all patients (5-17 years) between 2011 and 2015 (N = 25,161). SH and SH+SU cases were compared with controls (patients without SH) regarding a range of correlates. The longitudinal study included former CAMHS patients (N = 6,120) who were followed for a median time of 2.8 years after termination of CAMHS contact regarding outcomes such as clinical care consumption, social welfare recipiency, and crime conviction.

    Results: In the case-control study, both the SH and SH+SU groups received more clinical care, had lower global functioning, and higher odds of having mental disorders compared to controls. In most comparisons, the SH+SU group had more problems than the SH group. In the longitudinal study, the same pattern emerged for most outcomes; for example, the adjusted hazard ratio for recurrent care due to self-harm was 23.1 (95% confidence interval [CI], 17.0-31.4) in the SH+SU group compared to 3.9 (95% CI, 2.3-6.7) in the SH group.

    Conclusions: Adolescent patients presenting with self-harm have higher risks for adverse outcomes than patients without self-harm. Suicidality in addition to self-harm is associated with more severe outcomes, importantly recurrent episodes of care for self-harm.

  • Ott, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Mannchen, Julie K.
    Jamshidi, Fariba
    Werneke, Ursula
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Sunderby Research Unit.
    Management of severe arterial hypertension associated with serotonin syndrome: a case report analysis based on systematic review techniques2019In: Therapeutic Advances in Psychopharmacology, ISSN 2045-1253, E-ISSN 2045-1261, Vol. 9, p. 1-32Article, review/survey (Refereed)
    Abstract [en]

    Serotonin syndrome is thought to arise from serotonin excess. In many cases, symptoms are mild and self-limiting. But serotonin syndrome can become life threatening, when neuromuscular hyperexcitability spins out of control. Uncontainable neuromuscular hyperexcitability may lead to cardiovascular complications, linked to extreme changes in blood pressure. Currently, there is little guidance on how to control blood pressure in hyperserotonergic states. We report a case with treatment-resistant arterial hypertension, followed by a clinical review (using systematic review principles and techniques) of the available evidence from case reports published between 2004 and 2016 to identify measures to control arterial hypertension associated with serotonin syndrome. We conclude that classic antihypertensives may not be effective for the treatment of severe hypertension associated with serotonin syndrome. Benzodiazepines may lower blood pressure. Patients with severe hypertension not responding to benzodiazepines may benefit from cyproheptadine, propofol or both. In severe cases, higher cyproheptadine doses than currently recommended may be necessary.

  • Ögren, Anton
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Economics.
    Determinants behind Household Saving Behavior: -Empirical analysis on 15 OECD countries2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This paper investigates the factors behind what determine household saving behaviour. Observing the persistence differences of household saving ratio in OECD countries, serves as the base for the empirical study. Taking stance from economic theory and previous papers to formulate the method and likely explanatory variables suitable for this study, a model is specified based on the theoretical and empirical discussions.

    The result of the empirical analysis estimation finds that the explanatory variables accomplish to explain some of the household saving behaviour. Confirming and expanding on the discussion on the theoretical and empirical discussions. Factors such as uncertainty and fiscal policy are found to have a significant effect on household saving, while failing to prove other established determinants, like demographic factors. Among other included factors considered.

  • Bergström, Anna
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Grundvatten i Aitiks gruvområde: En utvärdering av grundvattenkvalitet och provtagningspunkter2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of this study was to evaluate the quality of the groundwater around the Aitik copper mine- one of Europe’s largest copper mine located 15 km outside of Gällivare, Sweden - as well the placement of the groundwater pipes around the area. The study also included a survey of what kind of terms, regarding groundwater that may become relevant in the future for an activity of Aitik’s size and type. Monitoring data was analysed between the years 2014 – 2018 for the parameters; pH, SO4, Cd, Co, Cu, Zn, Ni and U. The correlation between the parameters where tested and the monitoring data where compared to the Swedish Environmental Protection Agency criteria for groundwater as well to the groundwater chemistry from a reference area nearby, Liikavaara Östra. The result of the study shows that low pH raises the mobility of the metals Cd, Co, Cu, Zn and Ni. The result also indicates that SO4, Ni and Co are higher than the reference area but that the groundwater overall shows small signs of being affected by sulphide weathering. Therefore, metals can’t be excluded from originating from high background contents. The geographic analyse shows that the groundwater pipes are well placed in compared with the water flow direction and that two of the pipes can be excluded from sampling. Future terms regarding groundwater will likely regard protective measures and quantity restrictions. Still monitoring groundwater quality is very important to control environmental impact of the activity and to prevent deterioration of quality in the future.

  • Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Desmin and dystrophin abnormalities in upper airway muscles of snorers and patients with sleep apnea2019In: Respiratory Research, ISSN 1465-993X, Vol. 20, article id 31Article in journal (Refereed)
    Abstract [en]

    The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea. Cytoskeletal proteins desmin and dystrophin were morphologically evaluated in the uvula muscle of 22 patients undergoing soft palate surgery due to snoring and sleep apnea and in 10 healthy controls. The muscles were analysed with immunohistochemical methods, and swallowing function was assessed using videoradiography. Desmin displayed a disorganized pattern in 21 +/- 13% of the muscle fibres in patients, while these fibers were not present in controls. Muscle fibres lacking desmin were present in both patients and controls, but the proportion was higher in patients (25 +/- 12% vs. 14 +/- 7%, p = 0.009). The overall desmin abnormalities were significantly more frequent in patients than in controls (46 +/- 18% vs. 14 +/- 7%, p < 0.001). In patients, the C-terminus of the dystrophin molecule was absent in 19 +/- 18% of the desmin-abnormal muscle fibres. Patients with swallowing dysfunction had 55 +/- 10% desmin-abnormal muscle fibres vs. 22 +/- 6% in patients without swallowing dysfunction, p = 0.002. Cytoskeletal abnormalities in soft palate muscles most likely contribute to pharyngeal dysfunction in snorers and sleep apnea patients. Plausible causes for the presence of these abnormalities is traumatic snoring vibrations, tissue stretch or muscle overload.

  • Curic, Emina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Vilka faktorer påverkar valet av orala antikoagulantia som strokeprofylax vid förmaksflimmer?: En enkätstudie bland hälsopersonal i Sverige2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Engström, Thomas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Studenters reflektioner om skäl till att läsa farmaci och studieteknik: Analys av reflektiva uppgifter inom introduktionskursen på farmaciprogrammen vid Umeå universitet2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Nilsson, Linda
    et al.
    Umeå University, Faculty of Social Sciences, Department of Education.
    Lindholm, Maria
    Umeå University, Faculty of Social Sciences, Department of Education.
    Följderna av en kommunalt organiserad fortbildning: En kvalitativ studie om hur en kommunsatsning påverkat pedagogers uppfattningar om användningen av lågaffektivt bemötande.2019Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Skolor och ibland hela kommuner utbildar ständigt sin personal för att implementera nya förhållningssätt och pedagogiska metoder i verksamheterna. Studiens syfte var att belysa på vilket sätt en kommunal satsning påverkat hur pedagoger uppfattar och använder sig av lågaffektivt bemötande som metod i mötet med elever med problemskapande beteenden. Studiens teoretiska utgångspunkt utgjordes av relationellt och kategoriskt perspektiv, tillsammans med Blossings modell för ett förändringsarbete. Kvalitativ forskningsansats med semistrukturerade intervjufrågor har använts för att fånga pedagogers uppfattningar om metoden och urvalet bestod av tolv pedagoger som samtliga deltog i kommunens satsning. Deltagandet i föreläsningarna var på lika villkor, men förutsättningarna för en lyckad implementering visades varierar mellan skolorna i den undersökta kommunen. En slutsats i studien var att kommunens satsning påverkade pedagogers uppfattningar och medvetenhet om lågaffektivt bemötande positivt. Studien påvisade ökad medvetenhet i användningen av metoden samt vilken betydelse relationen har i mötet med problemskapande beteende. Det framkom att tid, ork och affektsmitta var missgynnande faktorer i arbetet med lågaffektivt bemötande. Studien indikerade på brister i genomförandet av implementeringen av den nya metoden och visade även att det möjligen sker viss kategorisering av elever med problemskapande beteende i skolan, medvetet eller omedvetet.

  • Mansour, Christina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Utmaningar och möjligheterför svenska öppenvårdsapotek: Utmaningar och möjligheterför svenska öppenvårdsapotek2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • Khudadad Kramali, Akram
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Bruk av hypnotika og anxiolytika hos voksne befolkningen 35-54 år: Reseptregisteret 2013- 20162019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • Abutaleb, Hind
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Biverkningar avsolskyddsprodukter: Retrospektiv analys av allvarliga biverkningarinrapporterade till Läkemedelsverket underperioden 2013–20172019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • Georgiadis, Panagiotis
    et al.
    Gavriil, Marios
    Rantakokko, Panu
    Ladoukakis, Efthymios
    Botsivali, Maria
    Kelly, Rachel S
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Kiviranta, Hannu
    Vermeulen, Roel C H
    Späth, Florentin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hebbels, Dennie G A J
    Kleinjans, Jos C S
    de Kok, Theo M C M
    Palli, Domenico
    Vineis, Paolo
    Kyrtopoulos, Soterios A
    DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia2019In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 126, p. 24-36Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To characterize the impact of PCB exposure on DNA methylation in peripheral blood leucocytes and to evaluate the corresponding changes in relation to possible health effects, with a focus on B-cell lymphoma.

    METHODS: We conducted an epigenome-wide association study on 611 adults free of diagnosed disease, living in Italy and Sweden, in whom we also measured plasma concentrations of 6 PCB congeners, DDE and hexachlorobenzene.

    RESULTS: We identified 650 CpG sites whose methylation correlates strongly (FDR < 0.01) with plasma concentrations of at least one PCB congener. Stronger effects were observed in males and in Sweden. This epigenetic exposure profile shows extensive and highly statistically significant overlaps with published profiles associated with the risk of future B-cell chronic lymphocytic leukemia (CLL) as well as with clinical CLL (38 and 28 CpG sites, respectively). For all these sites, the methylation changes were in the same direction for increasing exposure and for higher disease risk or clinical disease status, suggesting an etiological link between exposure and CLL. Mediation analysis reinforced the suggestion of a causal link between exposure, changes in DNA methylation and disease. Disease connectivity analysis identified multiple additional diseases associated with differentially methylated genes, including melanoma for which an etiological link with PCB exposure is established, as well as developmental and neurological diseases for which there is corresponding epidemiological evidence. Differentially methylated genes include many homeobox genes, suggesting that PCBs target stem cells. Furthermore, numerous polycomb protein target genes were hypermethylated with increasing exposure, an effect known to constitute an early marker of carcinogenesis.

    CONCLUSIONS: This study provides mechanistic evidence in support of a link between exposure to PCBs and the etiology of CLL and underlines the utility of omic profiling in the evaluation of the potential toxicity of environmental chemicals.

  • Tükenmez, Hasan
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Edström, Isabel
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Kalsum, Sadaf
    Braian, Clara
    Ummanni, Ramesh
    Lindberg, Stina
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Chemical Biology Consortium Sweden (CBCS).
    Sundin, Charlotta
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lerm, Maria
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Larsson, Christer
    Corticosteroids protect infected cells against mycobacterial killing in vitro2019In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 511, no 1, p. 117-121Article in journal (Refereed)
    Abstract [en]

    The effect of corticosteroids on human physiology is complex and their use in tuberculosis patients remains controversial. In a high-throughput screening approach designed to discover virulence inhibitors, several corticosteroids were found to prevent cytolysis of fibroblasts infected with mycobacteria. Further experiments with Mycobacterium tuberculosis showed anti-cytolytic activity in the 10 nM range, but no effect on bacterial growth or survival in the absence of host cells at 20 mu M. The results from a panel of corticosteroids with various affinities to the glucocorticoid- and mineralocorticoid receptors indicate that the inhibition of cytolysis most likely is mediated through the glucocorticoid receptor. Using live-imaging of M. tuberculosis-infected human monocyte-derived macrophages, we also show that corticosteroids to some extent control intracellular bacteria. In vitro systems with reduced complexity are to further study and understand the interactions between bacterial infection, immune defense and cell signaling. (C) 2019 The Authors. Published by Elsevier Inc.

  • Wennstig, Anna-Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Department of Oncology, Sundsvall Hospital, Sundsvall, Sweden.
    Garmo, Hans
    Isacsson, Ulf
    Gagliardi, Giovanna
    Rintelae, Niina
    Lagerqvist, Bo
    Holmberg, Lars
    Blomqvist, Carl
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Nilsson, Greger
    The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors2019In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 14, article id 40Article in journal (Refereed)
    Abstract [en]

    BackgroundTo assess the relationship between radiation doses to the coronary arteries (CAs) and location of a coronary stenosis that required intervention after three-dimensional conformal radiotherapy (3DCRT) for breast cancer (BC).MethodsThe study population consisted of 182 women treated for BC in Sweden between 1992 and 2012. All women received 3DCRT and subsequently underwent coronary angiography due to a suspected coronary event. CA segments were delineated in the patient's original planning-CT and radiation doses were recalculated based on the dose distribution of the original radiotherapy (RT) plan. The location of the CA stenosis that required intervention was identified from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Logistic regression analysis was used to assess the relationship between CA radiation doses and risk of a later coronary intervention at this specific location.ResultsThe odds ratio (OR) varied by radiation dose to the mid left anterior descending artery (LAD) (p=0.005). Women receiving mean doses of 1-5 Gray (Gy) to the mid LAD had an adjusted OR of 0.90 (95% CI 0.47-1.74) for a later coronary intervention compared to women receiving mean doses of 0-1Gy to the mid LAD. In women receiving mean doses of 5-20Gy to the mid LAD, an adjusted OR of 1.24 (95% CI 0.52-2.95) was observed, which increased to an OR of 5.23 (95% CI 2.01-13.6) for mean doses over 20Gy, when compared to women receiving mean doses of 0-1Gy to the mid LAD.ConclusionsIn women receiving conventional 3DCRT for BC between 1992 and 2012, radiation doses to the LAD remained high and were associated with an increased requirement of coronary intervention in mid LAD. The results support that the LAD radiation dose should be considered in RT treatment planning and that the dose should be kept as low as possible. Minimising the dose to LAD is expected to diminish the risk of later radiation-induced stenosis.

  • Zaki, Rafdzah
    et al.
    Roffeei, Siti Norsyuhada
    Hii, Yien Ling
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Yahya, Abqariyah
    Appannan, Mahesh
    Said, Mas Ayu
    Wan, Ng Chiu
    Aghamohammadi, Nasrin
    Hairi, Noran Naqiah
    Bulgiba, Awang
    Quam, Mikkel Brandon
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Public perception and attitude towards dengue prevention activity and response to dengue early warning in Malaysia2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 2, article id e0212497Article in journal (Refereed)
    Abstract [en]

    An early warning system for dengue is meant to predict outbreaks and prevent dengue cases by aiding timely decision making and deployment of interventions. However, only a system which is accepted and utilised by the public would be sustainable in the long run. This study aimed to explore the perception and attitude of the Malaysian public towards a dengue early warning system. The sample consisted of 847 individuals who were 18 years and above and living/working in the Petaling District, an area adjacent to Kuala Lumpur, Malaysia. A questionnaire consisting of personal information and three sub-measures of; i) perception, ii) attitude towards dengue early warning and iii) response towards early warning; was distributed to participants. We found that most of the respondents know about dengue fever (97.1%) and its association with climate factors (90.6%). Most of them wanted to help reduce the number of dengue cases in their area (91.5%). A small percentage of the respondents admitted that they were not willing to be involved in public activities, and 64% of them admitted that they did not check dengue situations or hotspots around their area regularly. Despite the high awareness on the relationship between climate and dengue, about 45% of respondents do not know or are not sure how this can be used to predict dengue. Respondents would like to know more about how climate data can be used to predict a dengue outbreak (92.7%). Providing more information on how climate can influence dengue cases would increase public acceptability and improve response towards climate-based warning system. The most preferred way of communicating early warning was through the television (66.4%). This study shows that the public in Petaling District considers it necessary to have a dengue warning system to be necessary, but more education is required.

  • Henriksson, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Unit of Research, Education and Development, Region jämtland Härjedalen, Östersund, Sweden.
    Ulvenstam, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Unit of Research, Education and Development, Region jämtland Härjedalen, Östersund, Sweden.
    Soderstrom, Lars
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Unit of Research, Education and Development, Region jämtland Härjedalen, Östersund, Sweden.
    Increase in ticagrelor use over time is associated with lower rates of ischemic stroke following myocardial infarction2019In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 19, no 1, p. 1-11, article id 51Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo evaluate the impact of a rapid change in preferred treatment from clopidogrel to ticagrelor on the risk of ischemic stroke following acute myocardial infarction (AMI).MethodsData for AMI patients treated with either clopidogrel or ticagrelor were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). Patients were divided into two cohorts, each covering a two-year time period; the initial prescription of ticagrelor (20 Dec 2011) was used as a cut-off point. Patients in the early cohort (n=23,447) were treated with clopidogrel, while those in the later cohort (n=24,227), were treated with either clopidogrel (47.9%) or ticagrelor (52.1%). Kaplan-Meier analyses were used to assess the risk of ischemic stroke over time, with multivariable Cox regression analyses used to identify predictors of ischemic stroke.ResultsOf 47,674 patients, there were 1203 cases of ischemic stroke. Cumulative Kaplan-Meier incidence estimates of ischemic stroke after one year were 2.8% vs. 2.4% for the early and late cohorts, respectively (p=0.001). Older age, hypertension, diabetes, previous stroke, congestive heart failure, atrial fibrillation, and ST-elevation myocardial infarction were associated with an increased risk of ischemic stroke. Percutaneous coronary intervention and statins at discharge were associated with a decreased risk of ischemic stroke, as was higher estimated glomerular filtration rate. Membership of the late cohort correlated with a 13% reduction in the relative risk of ischemic stroke.ConclusionsThe introduction of ticagrelor as well as an improved management of AMI was associated with a lower rate of ischemic stroke in a relatively unselected AMI population.

  • Dudding, Tom
    et al.
    Haworth, Simon
    Lind, Penelope A.
    Sathirapongsasuti, J. Fah
    Tung, Joyce Y.
    Mitchell, Ruth
    Colodro-Conde, Lucia
    Medland, Sarah E.
    Gordon, Scott
    Elsworth, Benjamin
    Paternoster, Lavinia
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Sweden ; Department of Nutrition, Harvard. Chan School of Public Health, Harvard University, Boston USA.
    Thomas, Steven J.
    Martin, Nicholas G.
    Timpson, Nicholas J.
    Agee, Michelle
    Alipanahi, Babak
    Auton, Adam
    Bell, Robert K.
    Bryc, Katarzyna
    Elson, Sarah L.
    Fontanillas, Pierre
    Furlotte, Nicholas A.
    Hicks, Barry
    Hinds, David A.
    Huber, Karen E.
    Jewett, Ethan M.
    Jiang, Yunxuan
    Kleinman, Aaron
    Lin, Keng-Han
    Litterman, Nadia K.
    McCeight, Jennifer C.
    McIntyre, Matthew H.
    McManus, Kimberly F.
    Mountain, Joanna L.
    Noblin, Elizabeth S.
    Northover, Carrie A. M.
    Pitts, Steven J.
    Poznik, David
    Shelton, Janie F.
    Shringarpure, Suyash
    Tian, Chao
    Vacic, Vladimir
    Wang, Xin
    Wilson, Catherine H.
    Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci2019In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, p. 1-12, article id 1052Article in journal (Refereed)
    Abstract [en]

    Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alter the odds of developing non-specific mouth ulcers and replicate these in an independent cohort (n = 355,744) (lead variant after meta-analysis: rs76830965, near IL12A, OR 0.72 (95% CI: 0.71, 0.73); P = 4.4e-483). Additional effect estimates from three independent cohorts with more specific phenotyping and specific study characteristics support many of these findings. In silico functional analyses provide evidence for a role of T cell regulation in the aetiology of mouth ulcers. These results provide novel insight into the pathogenesis of a common, important condition.

  • Ibrahim Faras, Fatima
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Inverkan av utvärtes kräm på hudens barriärfunktion: En randomiserad, kontrollerad och bilateral studie2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • Hamid Elamin, Ayat
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Structural studies of enterotoxigenic E. coli type II heat-labile enterotoxins2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • Niemi, Marcus
    et al.
    Umeå University, Faculty of Social Sciences, Department of Informatics.
    Mårtensson, Gustav
    Umeå University, Faculty of Social Sciences, Department of Informatics.
    SKAPA ENGAGEMANG PÅ SOCIALA MEDIER: Hur man fångar en användares genuina intresse2019Independent thesis Basic level (degree of Bachelor), 180 HE creditsStudent thesis
    Abstract [en]

    While social media continues to grow, we are seeing more and more companies trying to adapt to the new platforms. As a constantly evolving marketspace finding the best way to spread information is not as clear cut as it used to be. Paying for air-time has been changed to paying for promotion on the platforms och paying for prints has been changed to paying for visibility in consumers feeds. But paying to accomplish this reach is but a small part in the equation. Being able to have the information spread by the consumers is the goal for many companies. But what motivates consumers to share posts, pictures and videos? The purpose of this study is to generate knowledge and understanding as to what might cause consumers to share posts. By focusing on the platform Facebook and the ten most shared and liked posts in Sweden we aim to break down the reasons that attributed to their spread. Interviews and observations have been conducted and the data generated has served to identify aspects that stimulate engagement and a willingness to share post.

  • Westberg, Annica
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Characterization of mini-tablets: Evaluation of disintegrationand dissolution methods2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Källbäck, Lina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Optimering av triturationenlevotyroxin i cellulosa: Monitorering av parametrar som påverkar homogenitet och halt läkemedel2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Public defence: 2019-04-26 09:00 Hörsal d Unod T 9, Umeå
    Espaillat, Akbar
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Uncovering novel cell wall chemistries in gram negative bacteria: from development or dedicated peptidoglycan chemometric tools to functional genomics2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Bacteria are surrounded by an external cell wall whose main component is a polymeric net-like structure called the peptidoglycan (PG) or murein sacculus. PG plays crucial roles in bacterial physiology (eg morphogenesis, growth fitness and regulation of innate immunity). Based on the characteristics of this macromolecule, bacteria are grouped as gram negative and positive. Gram negatives present a thin PG layer in the periplasmic space, while Gram positive bacteria contain one thick multi-layered sacculus covering the cytoplasmic membrane. Although the PG sacculus is widely conserved between bacteria, variations in its chemical structure (ie sugars and peptide components) have been reported as a coping mechanism to stress. For example, V. choleraeis able to downregulate PG biosynthesis through non-canonical D-amino acids (NCDAAs) cell wall editing when entering stationary phase. NCDAAs production relies on Bsr enzymes, broad spectrum racemases which are expressed in V. cholerae under the control of stress sigma factor RpoS. In this thesis, we present a comprehensive study that allows us to determine the basic structural and biochemical features required for prominent D-amino acid production by Bsr enzymes.

    V. cholerae’s PG editing by NCDAAs revealed the existence of previously unappreciated  chemical modification in the cell wall of bacteria. Such an observation made us question whether the latest technology could reveal, otherwise undetectable, novel PG traits and furthermore, revisit the existence of murein in bacteria which were previously defined as PG-less. Finally, these studies would promote a global assessment of the degree of PG-chemical variability at a Kingdom scale.

    On the search for novel functional chemistries and associated mechanisms of cell wall regulation, we analysed the cell wall of hundreds of different species. Here, I present two proof of concept studies: i) investigation of the existence of PG in the Plantomycetes Kuenenia stuttgartiensis, a species previously classified as PG-less; and ii) PG chemical diversity within Class Alphaproteobacteria. To do so, we developed and experimentally validated an innovative chemometric pipeline to rapidly analyse large PG datasets. Chemometric analyses revealed 3 PG clusters within Alphaproteobacteria, which included unprecedented PG modifications widely conserved in family Acetobacteria: amidation at the α-(L)-carboxyl of meso-diaminopimelic acid and the presence of (1–3) cross-linked muropeptides between L-Ala and D-(meso)-diaminopimelate residues from adjacent moieties. Fluctuations of the relative abundance of these PG traits were growth phase and media composition dependent. Functional studies demonstrated that Acetobacteria atypical muropeptides enabled cellular protection against Type VI secreted endopeptidases and negatively affected innate immune system recognition suggesting relevant functional roles in the environmental adaptability of these bacteria.

  • Public defence: 2019-04-26 09:00 Sal E04, Umeå
    Al-Alawi, Kamila
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Team-based approach in the management of diabetes at primary health care level in Muscat, Oman: challenges and opportunities2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: The growth of type 2 diabetes is considered an alarming epidemic in Oman. The efficient team-based approach to diabetes management in primary health care is an essential component for providing ideal diabetic care. This thesis aimed to explore the current situation related to team-based management of type 2 diabetes in public Primary Health Care Centres (PHCCs) under the Ministry of Health (MOH) in Oman, including the various challenges associated with diabetes management and the most preferable Human Resources for Health (HRH) management mechanism, and to examine how this could be optimized from provider and patient perspectives.

    Materials and methods: The entire project was conducted in Muscat Governorate and was based on one quantitative and three qualitative studies. In the quantitative study, 26 public PHCCs were approached through cross-sectional study. The core diabetes management team recommended by the MOH for PHCCs in Oman was explored in terms of their competencies, values, skills, and resources related to the team-based approach to diabetes management. For the qualitative studies, five public purposely-selected PHCCs were approached. The diabetes consultations conducted by the core members and other supportive members involved in diabetes management were observed and later the Primary Health Care Providers (PHCPs) were interviewed. The different approaches explored challenges related to diabetes management and the most preferable HRH mechanism by PHCPs. Seven type 2 diabetes patients with different gender, employment status, and education were consequently interviewed to explore their perceptions towards the current diabetes management service and their opinions towards nurse-led clinics.

    Results: The survey provided significant and diverse perceptions of PHCPs towards their competencies, values, skills, and resources related to diabetes management. Physicians considered themselves to have better competencies than nurses and dieticians. Physicians also scored higher on team-related skills and values compared with health educators. In terms of team-related skills, the difference between physicians and nurses was statistically significant and showed that physicians perceived themselves to have better skills than nurses. Confusion about the leadership concept among PHCPs with a lack of pharmacological, technical, and human resources was also reported. The observations and interviews with PHCPs disclosed three different models of service delivery at diabetes management clinics. The challenges explored involved PHCCs’ infrastructure, nurses’ knowledge, skills, and non-availability of technical and pharmaceutical support. Other challenges that evolved into the community were cultural beliefs, traditions, health awareness, and public transportation. Complete implementation of task-sharing mechanisms within the team-based approach was selected by all PHCPs as the most preferable HRH mechanism. The selection was discussed in the context of positive outcomes, worries, and future requirements. The physicians stated that nurses’ weak contribution to the team within the selected mechanism could be the most significant aspect. Other members supported the task-sharing mechanism between physicians and nurses. However, type 2 diabetes patients’ non-acceptance of a service provided by the nurses created worries for the nurses. The interviews with type 2 diabetes patients disclosed positive perceptions towards the current diabetes management visits; however, opinions towards nurse-led clinics varied among the patients.

    Conclusions and recommendations: The team-based approach at diabetes management clinics in public PHCCs in Oman requires thoughtful attention. Diverse presence of the team members can form challenges during service delivery. Clear roles for team members must be outlined through a solid HRH management mechanism in the context of a sharp leadership concept. Nurse-led clinics are an important concept within the team; however, their implementation requires further investigation. The concept must involve clear understandings of independence and interdependence by the team members, who must be educated to provide a strong gain for team-based service delivery.