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  • Davoine, Celine
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Abreu, Ilka N.
    Khajeh, Khalil
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Blomberg, Jeanette
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Kidd, Brendan N.
    Kazan, Kemal
    Schenk, Peer M.
    Gerber, Lorenz
    Nilsson, Ove
    Moritz, Thomas
    Björklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Functional metabolomics as a tool to analyze Mediator function and structure in plants2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 6, e0179640Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mediator is a multiprotein transcriptional co-regulator complex composed of four modules; Head, Middle, Tail, and Kinase. It conveys signals from promoter-bound transcriptional regulators to RNA polymerase II and thus plays an essential role in eukaryotic gene regulation. We describe subunit localization and activities of Mediator in Arabidopsis through metabolome and transcriptome analyses from a set of Mediator mutants. Functional metabolomic analysis based on the metabolite profiles of Mediator mutants using multivariate statistical analysis and heat-map visualization shows that different subunit mutants display distinct metabolite profiles, which cluster according to the reported localization of the corresponding subunits in yeast. Based on these results, we suggest localization of previously unassigned plant Mediator subunits to specific modules. We also describe novel roles for individual subunits in development, and demonstrate changes in gene expression patterns and specific metabolite levels in med18 and med25, which can explain their phenotypes. We find that med18 displays levels of phytoalexins normally found in wild type plants only after exposure to pathogens. Our results indicate that different Mediator subunits are involved in specific signaling pathways that control developmental processes and tolerance to pathogen infections.

  • Chatzittofis, Andreas
    et al.
    Savard, Josephine
    Arver, Stefan
    Görts Öberg, Katarina
    Hallberg, Jonas
    Nordström, Peter
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men2017Ingår i: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 6, nr 2, 187-193 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods: This case-control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire-Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery-Asberg Depression Rating Scale - Self-rating. Results: Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion: Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion: Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men.

  • Li, Zhen
    et al.
    De La Torre, Amanda R.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. Department of Plant Sciences, University of California-Davis, Davis, CA.
    Sterck, Lieven
    Cánovas, Francisco M.
    Avila, Concepción
    Merino, Irene
    Antonio Cabezas, Jose
    Teresa Cervera, Maria
    Ingvarsson, Pär K.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. Department of Plant Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Van de Peer, Yves
    Single-Copy Genes as Molecular Markers for Phylogenomic Studies in Seed Plants2017Ingår i: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 9, nr 5, 1130-1147 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Phylogenetic relationships among seed plant taxa, especially within the gymnosperms, remain contested. In contrast to angio-sperms, for which several genomic, transcriptomic and phylogenetic resources are available, there are few, if any, molecular markers that allow broad comparisons among gymnosperm species. With few gymnosperm genomes available, recently obtained transcriptomes in gymnosperms are a great addition to identifying single-copy gene families as molecular markers for phylogenomic analysis in seed plants. Taking advantage of an increasing number of available genomes and transcriptomes, we identified single-copy genes in a broad collection of seed plants and used these to infer phylogenetic relationships between major seed plant taxa. This study aims at extending the current phylogenetic toolkit for seed plants, assessing its ability for resolving seed plant phylogeny, and discussing potential factors affecting phylogenetic reconstruction. In total, we identified 3,072 single-copy genes in 31 gymnosperms and 2,156 single-copy genes in 34 angiosperms. All studied seed plants shared 1,469 single-copy genes, which are generally involved in functions like DNA metabolism, cell cycle, and photosynthesis. A selected set of 106 single-copy genes provided good resolution for the seed plant phylogeny except for gnetophytes. Although some of our analyses support a sister relationship between gnetophytes and other gymnosperms, phylogenetic trees from concatenated alignments without 3rd codon positions and amino acid alignments under the CAT + GTR model, support gnetophytes as a sister group to Pinaceae. Our phylogenomic analyses demonstrate that, in general, single-copy genes can uncover both recent and deep divergences of seed plant phylogeny.

  • Sahu, Sanjaya Kumar
    et al.
    Kumar, Manish
    Chakraborty, Sohini
    Banerjee, Srijon Kaushik
    Kumar, Ranjeet
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Department of Chemistry, Bose Institute, Kolkata, India.
    Gupta, Pushpa
    Jana, Kuladip
    Gupta, Umesh D.
    Ghosh, Zhumur
    Kundu, Manikuntala
    Basu, Joyoti
    MicroRNA 26a (miR-26a)/KLF4 and CREB-C/EBP beta regulate innate immune signaling, the polarization of macrophages and the trafficking of Mycobacterium tuberculosis to lysosomes during infection2017Ingår i: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 13, nr 5, e1006410Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    For efficient clearance of Mycobacterium tuberculosis (Mtb), macrophages tilt towards M1 polarization leading to the activation of transcription factors associated with the production of antibacterial effector molecules such as nitric oxide (NO) and proinflammatory cytokines such as interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha). At the same time, resolution of inflammation is associated with M2 polarization with increased production of arginase and cytokines such as IL-10. The transcriptional and post-transcriptional mechanisms that govern the balance between M1 and M2 polarization, and bacteria-containing processes such as autophagy and trafficking of Mtb to lysosomes, are incompletely understood. Here we report for the first time, that the transcription factor KLF4 is targeted by microRNA-26a (miR-26a). During Mtb infection, downregulation of miR-26a (observed both ex vivo and in vivo) facilitates upregulation of KLF4 which in turn favors increased arginase and decreased iNOS activity. We further demonstrate that KLF4 prevents trafficking of Mtb to lysosomes. The CREB-C/EBP beta signaling axis also favors M2 polarization. Downregulation of miR-26a and upregulation of C/ebpbeta were observed both in infected macrophages as well as in infected mice. Knockdown of C/ebpbeta repressed the expression of selected M2 markers such as Il10 and Irf4 in infected macrophages. The importance of these pathways is substantiated by observations that expression of miR-26a mimic or knockdown of Klf4 or Creb or C/ebpbeta, attenuated the survival of Mtb in macrophages. Taken together, our results attribute crucial roles for the miR-26a/KLF4 and CREB-C/EBP beta signaling pathways in regulating the survival of Mtb in macrophages. These studies expand our understanding of how Mtb hijacks host signaling pathways to survive in macrophages, and open up new exploratory avenues for host-targeted interventions.

  • Ding, Ming
    et al.
    Huang, Tao
    Bergholdt, Helle K. M.
    Nordestgaard, Borge G.
    Ellervik, Christina
    Qi, Lu
    Frazier-Wood, Alexis C.
    Aslibekyan, Stella
    North, Kari E.
    Voortman, Trudy
    Graff, Mariaelisa
    Smith, Caren E.
    Lai, Chao-Qiang
    Varbo, Anette
    Lemaitre, Rozenn N.
    de Jonge, Ester A. L.
    Fumeron, Frederic
    Corella, Dolores
    Wang, Carol A.
    Tjonneland, Anne
    Overvad, Kim
    Sorensen, Thorkild I. A.
    Feitosa, Mary F.
    Wojczynski, Mary K.
    Kahonen, Mika
    Ahmad, Shafqat
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Psaty, Bruce M.
    Siscovick, David S.
    Barroso, Ines
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hernandez, Dena
    Ferrucci, Luigi
    Bandinelli, Stefania
    Linneberg, Allan
    Sandholt, Camilla Helene
    Pedersen, Oluf
    Hansen, Torben
    Schulz, Christina-Alexandra
    Sonestedt, Emily
    Orho-Melander, Marju
    Chen, Tzu-An
    Rotter, Jerome I.
    Allison, Mathew A.
    Rich, Stephen S.
    Sorli, Jose V.
    Coltell, Oscar
    Pennell, Craig E.
    Eastwood, Peter R.
    Hofman, Albert
    Uitterlinden, Andre G.
    Zillikens, MCarola
    van Rooij, Frank J. A.
    Chu, Audrey Y.
    Rose, Lynda M.
    Ridker, Paul M.
    Viikari, Jorma
    Raitakari, Olli
    Lehtimaki, Terho
    Mikkila, Vera
    Willett, Walter C.
    Wang, Yujie
    Tucker, Katherine L.
    Ordovas, Jose M.
    Kilpelainen, Tuomas O.
    Province, Michael A.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA; Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Arnett, Donna K.
    Tanaka, Toshiko
    Toft, Ulla
    Ericso, Ulrika
    Franco, Oscar H.
    Mozaffarian, Dariush
    Hu, Frank B.
    Chasman, Daniel I.
    Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study2017Ingår i: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 356, j1000Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. DESIGN Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. SETTING CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. PARTICIPANTS Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. MAIN OUTCOME MEASURES The instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. RESULTS Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). CONCLUSION The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.

  • Löfstrand, Tord
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Determination of gestational age and lung maturity: phospholipids, creatinine and phosphatase in amniotic fluid1976Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
  • Boquist, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    The endocrine pancreas in the Chinese hamster: studies on non-diabetic, alloxan-treated, zinc-deficient, and spontaneously diabetic animals1969Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
  • Perris, Hjördis
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    A multifactorial study of life events in depressed patients1982Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The aim of this study was an attempted elucidation of the possible pathogenic role of life events in the onset and development of depression. Although several authors seem to agree that the impact of life events should be seen in relation to the person experiencing them, no comprehensive studies have been published so far where life events have been analysed in relation to the vulnerability of the individual who becomes depressed. The present study was inspired by Freud’s concept of ”Ergänzungsreihe”, and was based on the general assumption that biological as well as psychological and social factors contribute greatly to modifying an individual’s vulnerability to external events.

    To test this hypothesis the occurrence of life events was studied by means of a semistructured interview in a consecutive series of 206 depressed patients of both sexes treated as in- or outpatients* and the results have been analysed in relation to a series of variables which could be assumed to be of importance in modifying the vulnerability of the patients. The main hypothesis was that the more vulnerable the individual was in relation to each of the investigated factors, the fewer events would be necessary to produce a depressive breakdown and the more negative would be the experience of such events. Biological, psychological and clinical variables were taken into account in different parts of the present study.

    The results support the view that the impact of life events should be seen idiosyncratically and in relation to the specific vulnerability of each individual. Furthermore the study illustrates a fruitful approach for further studies aimed at a closer understanding of the role of external events in the development of a depressive illness.

  • Näsman, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    The limbic-hypothalamic-pituitary-adrenal axis in Alzheimer's disease1994Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Dysfunction of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis is a common finding in advanced dementia. In this study, the function of the LHPA axis at different levels was investigated in patients with dementia and in healthy elderly.

    A subtle disturbance in the feedback regulation of the LHPA axis was found in patients with early (i.e., mild to moderate) Alzheimer’s disease (AD). After 0.5 mg dexamethasone, serum cortisol levels were less suppressed in AD patients and plasma adrenocorticotropin (ACTH) levels were lower as compared with healthy elderly. After stimulation with human corticotropin-releasing hormone a blunted ACTH response was found in AD patients while relative serum cortisol, déhydroépiandrostérone, and androstenedione responses were increased. Significant correlations were found between low plasma ACTH levels and temporal lobe atrophy and between low peak plasma ACTH levels and hippocampal atrophy measured with computer tomography. Patients with advanced AD and multi-infarct dementia had lower basal levels of déhydroépiandrostérone sulphate in combination with no difference in cortisol levels, resulting in a high cortisol/DHAS ratio. The difference persisted after adjustments for age and sex in a multivariate analysis. In patients with early AD, basal serum levels of dehydroepiandrosterone and androstenedione were increased, and this increase was accentuated after stimulation with ACTH. Peripheral glucocorticoid sensitivity was examined by skin vasoconstrictor blanching tests. Patients with AD and patients treated with glucocorticoids showed skin blanching at higher clobetasol concentrations than healthy elderly.

    These findings justify further investigations on the role of LHPA axis dysfunction in Alzheimer’s disease and its possible importance for the pathophysiology of the disease.

  • Korsman, Tom
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Acidification trends in Swedish lakes: an assessment of past water chemistry conditions using lake sediments1993Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    This thesis presents temporal perspectives of lake acidification in Sweden. Sediment records have been used to study timing, trends and causes of acidification, and two different techniques for assessing past lake-water acidity are presented.

    A new technique for pH prediction, based on near-infrared (NIR) spectroscopy of surface sediments, is developed. This study shows that there is a pH related fraction of lake sediments that can be recorded by NIR analysis. Relationships between NIR spectra of surface sediment samples and measured lake-water pH values, and between NIR spectra of sediment cores and historical pH values inferred by diatom analysis, are modelled by partial least squares regression. The prediction errors of the models are comparable to those obtained by modelling of diatom and lake-water pH data. By further development NIR spectroscopy can become useful for inferring past pH, as well as several other lake-water parameters, from sediment cores.

    Diatom-based predictive models, using multivariate calibration methods, are developed for inferences of lake-water pH, alkalinity and colour. These models are used to provide a regional assessment of recent lake acidification in the provinces of Västerbotten and Norrbotten, northern Sweden. The study shows that a pH decline has occurred in some southeastern lakes, but that most of the lakes have not faced significant changes in lake-water pH, alkalinity and colour. The inferred water chemistiy changes are discussed in relation to atmospheric deposition and land-use.

    In a study of eight acid-sensitive Swedish boreal-forest lakes a past-analogue approach is used to test whether contemporary expansion of conifers could cause lake acidification. Water chemistry changes associated with the natural pre-historic colonization and expansion of spruce in Sweden (—3000 years B.P.), at times of background atmospheric acidity, are inferred to evaluate the acidification ability of spruce per se on surface waters. This study shows that under natural, unpolluted conditions spruce colonization and expansion did not cause lake acidification.

    In a synthesis of palaeolimnological acidification research in Sweden a general model for pH- development for acid clear-water lakes in southern Sweden is presented. The pH-development from the last déglaciation to present time can be divided into four different periods; (i) a natural long-term acidification period (12000 B.P. - 2300 B.P., or later), with a gradual decrease in pH resulting from declining fluxes of base cations from catchment soils; (ii) a human induced alkalization period (2300 B.P. - 1900 A.D.), with a pH increase due to human activities in the catchments; (iii) the recent acidification period (about 1900 A.D. - present), when pH decreased towards 4.5 due to acid deposition and possibly ceased land-use; and (iv) the liming period (1970s - present), when pH often increases to values above 7 following lime treatment to counteract acidification. The implications of these past pH changes for the concept of contemporary lake acidification and for liming policy are outlined.

  • Bergman, Maud
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Chemical and thermodynamic studies of dental gold alloys with special reference to homogenization, electrochemical corrosion and cluster formation1976Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
  • Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Distribution of puumala virus in Sweden1997Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Puumala virus, belonging to the genus hantavirus, is the causative agent of nephropathia epidemica (NE), a relatively mild form of hemorrhagic fever with renal syndrome. Puumala virus occurs endemically in Central and Northern Europe and Western Russia. In Sweden, NE is reported from the northern and central parts but virtually not at all from the southern part of the country. The bank vole (Clethrionomys glareolus) is the main reservoir of Puumala virus and humans are infected by inhalation of aerosolized animal secreta. In northern Sweden, the density of the bank vole population varies cyclically in intervals of 3-4 years and the incidence of NE shows a covariation.

    The prevalence of serum antibodies to hantaviruses in northern Sweden was studied in a stratified and randomly selected adult population sample comprising 1538 subjects. As expected, the prevalence increased with age. There was no difference between men and women, which was unexpected based on a male:female ratio of > 2:1 in clinical reports. By use of an immunofiuorescent assay, a seroprevalence of 5.4% and by a newly developed enzyme-linked immunosorbent assay (ELISA) with recombinant Puumala virus nucleocapsid protein as antigen, a prevalence of 8.9% was recorded. This is about or more than ten times higher than what would be calculated from clinical reports.

    By use of the ELISA, an occupational risk of acquisition of Puumala virus infection was demonstrated. Serum samples from 910 farmers and 663 referent subjects living in various rural parts of Sweden were tested. Among farmers from the Puumala virus-endemic northern and central parts of the country, the seroprevalence (12.9%) was higher (p=0.01) than in referents (6.8%). In the southern part of Sweden, only 2/459 persons had antibodies. Only a limited number of children with NE had been previously reported. In a separate study, 32 children with Puumala virus infection were identified and the clinical picture of NE in children was found to be similar to that of adult cases.

    Variations in the prevalence of Puumala virus in the bank vole population within an endemic region are not well known. Here, a higher mean rodent density and a higher prevalence of Puumala virus-specific serum antibodies were recorded in the vicinity of households afflicted with NE than in rural control areas. The data indicated that the risk of exposure locally within an endemic region may vary widely and tentatively suggested that a threshold density of bank voles might be necessary to achieve before effective spread of Puumala virus within the rodent population may occur.

    There is no firm evidence of the occurrence of Puumala virus among wild living animals other than rodents. A study of Swedish moose, an animal which is ecologically well characterized, was performed. Convincing evidence of past Puumala virus infection was found in 5/260 moose originating from Puumala virus-endemic areas but in none of 167 animals from nonendemic areas. Based on the low seroprevalence recorded, moose seemed to serve as endstage hosts rather than being active parts of the enzootic circle of transmission.

    In conclusion, the present investigations confirmed that the exposure to Puumala virus is geographically well restricted in Sweden. Seroprevalence studies indicated that only a minor proportion of individuals infected with Puumala virus are clinically reported, with a bias in favour of men. NE was confirmed to occur in children, with a clinical picture similar to that of adults. An occupational risk was defined for acquisition of Puumala virus infection. Studies in rodents suggested that there may be wide local variations within a limited area in the risk of exposure to Puumala virus. The studies validated the usefulness of a newly developed ELISA based on recombinant nucleocapsid peptides of hantaviruses and finally, methodological progress was reached when Puumala virus was, for the first time, successfully isolated from a Scandinavian patient.

  • Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Dialysis Procedures Alter Metabolic Conditions2017Ingår i: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 9, nr 6, 548Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    A progressive chronic kidney disease results in retention of various substances that more or less contribute to dysfunction of various metabolic systems. The accumulated substances are denominated uremic toxins. Although many toxins remain undetected, numerous newly defined toxins participate in the disturbance of food breakdown. In addition, toxic effects may downregulate other pathways, resulting in a reduced ability of free fatty acid breakdown by lipoprotein lipase (LPL) and hepatic lipase (HL). Dialysis may even worsen metabolic functions. For LPL and HL, the use of heparin and low molecular weight heparin as anticoagulation during hemodialysis (HD) initiate a loss of these enzymes from their binding sites and degradation, causing a temporary dysregulation in triglyceride breakdown. This lack of function will cause retention of the triglyceride containing lipids for at least 8 h. In parallel, the breakdown into free fatty acids is limited, as is the energy supply by them. This is repeated thrice a week for a normal HD patient. In addition, dialysis will cause a loss of amino acids and disturb glucose metabolism depending on the dialysates used. The addition of glucose in the dialysate may support oxidation of carbohydrate and the retention of Amadori products and subsequent tissue alterations. To avoid these effects, it seems necessary to further study the effects of anticoagulation in HD, the extent of use of glucose in the dialysate, and the supplementation of amino acids.

  • Mutie, Pascal M.
    et al.
    Giordano, Giuseppe N.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Lund Univ, Skane Univ Hosp, Dept Clin Sci, Harvard Sch Publ Hlth, Univ Oxford, Radcliff Dept Med.
    Lifestyle precision medicine: the next generation in type 2 diabetes prevention?2017Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 15, 171Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The driving force behind the current global type 2 diabetes epidemic is insulin resistance in overweight and obese individuals. Dietary factors, physical inactivity, and sedentary behaviors are the major modifiable risk factors for obesity. Nevertheless, many overweight/obese people do not develop diabetes and lifestyle interventions focused on weight loss and diabetes prevention are often ineffective. Traditionally, chronically elevated blood glucose concentrations have been the hallmark of diabetes; however, many individuals will either remain 'prediabetic' or regress to normoglycemia. Thus, there is a growing need for innovative strategies to tackle diabetes at scale. The emergence of biomarker technologies has allowed more targeted therapeutic strategies for diabetes prevention (precision medicine), though largely confined to pharmacotherapy. Unlike most drugs, lifestyle interventions often have systemic health-enhancing effects. Thus, the pursuance of lifestyle precision medicine in diabetes seems rational. Herein, we review the literature on lifestyle interventions and diabetes prevention, describing the biological systems that can be characterized at scale in human populations, linking them to lifestyle in diabetes, and consider some of the challenges impeding the clinical translation of lifestyle precision medicine.

  • Loeb, Stacy
    et al.
    Ventimiglia, Eugenio
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Division of Experimental Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Universita Vita-Salute San Raffaele, Milan, Italy.
    Salonia, Andrea
    Folkvaljon, Yasin
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden .
    Meta-Analysis of the Association Between Phosphodiesterase Inhibitors (PDE5Is) and Risk of Melanoma2017Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 109, nr 8, djx086Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The US Food and Drug Administration recently announced the need to evaluate the association between PDE5is and melanoma. We performed a meta-analysis on the association between PDE5i and melanoma using random effects models and examined whether it met Hill's criteria for causality. A systematic search of Medline, EMBASE, and the Cochrane Library from 1998 to 2016 identified three case-control studies and two cohort studies, including a total of 866 049 men, of whom 41 874 were diagnosed with melanoma. We found a summary estimate indicating an increased risk of melanoma in PDE5i users (relative risk = 1.12, 95% confidence interval = 1.02 to 1.23). However, there was no difference in risk between men with low and high exposure to PDE5i, and risk was higher for in situ melanoma than localized and high-risk melanoma, suggesting a lack of dose response and biological gradient. PDE5i use was also associated with basal cell cancer, suggesting a lack of specificity and likely confounding by ultraviolet exposure. Thus, although this meta-analysis found a statistically significant association between PDE5i and melanoma, it did not satisfy Hill's criteria for causality.

  • Persson, Emilia
    et al.
    Gustafsson, Christian
    Nordström, Fredrik
    Sohlin, Maja
    Gunnlaugsson, Adalsteinn
    Petruson, Karin
    Rintelä, Niina
    Hed, Kristoffer
    Blomqvist, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Zackrisson, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nyholm, Tufve
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Olsson, Lars E.
    Siversson, Carl
    Jonsson, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    MR-OPERA: a multicenter/multivendor validation of magnetic resonance imaging–only prostate treatment planning using synthetic computed tomography images2017Ingår i: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 99, nr 3, 692-700 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To validate the dosimetric accuracy and clinical robustness of a commercially available software for magnetic resonance (MR) to synthetic computed tomography (sCT) conversion, in an MR imaging–only workflow for 170 prostate cancer patients.

    Methods and Materials: The 4 participating centers had MriPlanner (Spectronic Medical), an atlas-based sCT generation software, installed as a cloud-based service. A T2-weighted MR sequence, covering the body contour, was added to the clinical protocol. The MR images were sent from the MR scanner workstation to the MriPlanner platform. The sCT was automatically returned to the treatment planning system. Four MR scanners and 2 magnetic field strengths were included in the study. For each patient, a CT-treatment plan was created and approved according to clinical practice. The sCT was rigidly registered to the CT, and the clinical treatment plan was recalculated on the sCT. The dose distributions from the CT plan and the sCT plan were compared according to a set of dose-volume histogram parameters and gamma evaluation. Treatment techniques included volumetric modulated arc therapy, intensity modulated radiation therapy, and conventional treatment using 2 treatment planning systems and different dose calculation algorithms.

    Results: The overall (multicenter/multivendor) mean dose differences between sCT and CT dose distributions were below 0.3% for all evaluated organs and targets. Gamma evaluation showed a mean pass rate of 99.12% (0.63%, 1 SD) in the complete body volume and 99.97% (0.13%, 1 SD) in the planning target volume using a 2%/2-mm global gamma criteria.

    Conclusions: Results of the study show that the sCT conversion method can be used clinically, with minimal differences between sCT and CT dose distributions for target and relevant organs at risk. The small differences seen are consistent between centers, indicating that an MR imaging–only workflow using MriPlanner is robust for a variety of field strengths, vendors, and treatment techniques.

  • Rösblad, Birgit
    Visual and proprioceptive control of arm movements: studies of development and dysfunction1994Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The aim of this dissertation was to examine the role of sensory information for control of goal-directed arm movements in children. The role of visual and proprioceptive information on the target for end point accuracy was examined in normal 4- to 12-year- old children (Study I), and in children with motor impairments (Study II). Accuracy in pointing with the unseen hand was found to improve rapidly during the age period tested, with the most pronounced development taking place in the preschool years. Visual specification of the target was superior to proprioceptive specification for all age groups tested. The performance of children with motor impairments was more variable than that of the non-impaired children, and this effect was most pronounced when visual information about the target was unavailable. The importance of visual information for controlling the transport and handling part of reaching movements were examined in normal 6- to 8-year-old children (Study III), and in children with developmental coordination disorders (Study IV). Object handling required visual information on both target and hand. For the transport phase of the movement visual information on target was sufficient, and sight of hand did not improve performance. The young children were relatively more impaired than the older children when lacking adequate visual information. The children with developmental coordination disorders responded to the withdrawal of visual information in a similar way to that of the normally developed children. A discontinuity at 7 years of age in the development of perceptual control of pointing movements, observed in Study I, was further investigated and confirmed in study V. In this study the ability to control movements visually and prorioceptively was also investigated and found to develop in parallel rather than one being a prerequisite for the other.

  • Nilsson, Per A.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för geografi och ekonomisk historia. International Office.
    The Swedish Experience of International Student Mobility2017Ingår i: On the verge of a new era: value, viability and visibility of international education / [ed] Riikka Vanhanen, Jyrki Holappa, Jyväskylä: JAMK University of Applied Sciences Library , 2017, 25-31 s.Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    The internationalisation of education started in the late 1970s when the wording in the Swedish Higher Education Act was changed, emphasising that higher education institutions (HEI) should promote understanding of other countries and of international circumstances. This also opened the door for other changes in Swedish regulations, such as the study aid system, allowing more students to study abroad. However, the greatest boost to international student mobility was when Sweden entered the Erasmus Programme in 1992 (Lundgren & Nilsson, 2009).

    It is clear that there are political ambitions when it comes to international student mobility. Politicians set the roles for mobility through political decisions about studying in a foreign country, regulations for migration, student loans, recognition for foreign degrees, etc. There is also a global education market being developed outside Sweden. More countries have an interest in the business of international education and the commodification of education due to a decrease of public HEI funding (Knight, 2012). This means that market solutions have entered the global scene, which countries around the world have to adjust to, including Sweden. The aim with this article is to highlight some of the Swedish experiences in regard to international student mobility.

  • Niklasson, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Spectral analysis of the heart rate variability: a methodological study1993Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Heart rate and other cardiovascular variables are not steady but fluctuate over time. The evolution of computer technology the last 2 decades has made detailed analysis of the fluctuations possible and has focused the attention to the information content of the variability.

    Autonomic nervous influence on the heart can be assessed by measuring the heart rate variability from R-R intervals in the electrocardiogram. Applications have been developed in many fields where the pathophysiological features of the patients include autonomic dysfunction.

    This thesis is based on clinical studies and model studies compared with results from healthy volunteers. Two patient groups, with familial amyloidosis and with myotonic dystrophy, were evaluated using simple indexes of heart rate variability. Signs of autonomic dysfunction which is a dominant clinical feature in familial amyloidosis with polyneuropathy was confirmed by abnormal heart rate variability indexes. In myotonic dystrophy heart rate variability was normal but recumbent and standing plasma catecholamines were elevated. Reassessment of the heart rate variability with spectral analysis confirmed the results.

    The integral pulse frequency modulation (IPFM) model can be used as a simple analogy of the interface between autonomic activity and the cardiac pacemaker. Computer simulations using the IPFM model revealed marked differences in the estimated modulating variability depending on whether the intervals between simulated beats or the frequency of beats was analyzed. Comparison with data from healthy volunteers indicated that the IPFM model was valid and that heart rate should be preferred instead of R-R intervals for variability measurements.

    Beat-by-beat heart rate can be viewed as an irregular sample of the underlying autonomic activity. Spectral analysis of simulated heart rate variability data using the IPFM model showed attenuation of high frequency variability with decreasing mean heart rate and with increasing variability mean frequency. Application of these results on data from healthy volunteers suggest that the effects can be significant in actual variability measurements.

    Cholinergic blockade resulted in reduced heart rate variability at all spectral frequencies. Adrenergic beta-blockade reduced high-frequency variability in standing position indicating that high-frequency variability might partly be sympathetically mediated.

  • Wikman, Marianne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    To desire and to choose: aspects of women's and men's urge to have children1994Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The aim of this study was to increase available knowledge about women's and men’s desire for pregnancy and for a child/children to serve as a basis for further studies of problems and inconsistencies in the reproductive sphere. The motivation to become a parent was hypothesized as being not only of an existential, social, interpersonal and intrapsychic character but also a biologically anchored personality trait.

    The first part of the study deals with the development of a method for collecting valid information concerning this intimate and personal sphere of life and to categorize this information into measurable dimensions. A questionnaire was constructed and factor analysis was used as a statistical tool. There are two versions of the final instrument, one for women and one for men. Interviews were used as a means of testing the validity of the instrument. Experiences from the methodological development process revealed that it was meaningful to deal with the issue though suitable wording was not easily found.

    In the main part of the study, two large populations, one reference group of 416 women and 329 men of fertile ages and one group of expecting parents, 369 women and 345 men, were investigated by means of the questionnaire. Attitudes were dominated by two opposing views of children: 'Children mean existential satisfaction' and 'Children mean restriction of freedom'. This confirmed the findings of earlier studies and clinical experience that ambivalence is a natural phenomenon, that may be associated with feelings of guilt. The view of one's own parents as models in parenthood was a third important dimension. The view of the child's sex was a fourth important and complex dimension.

    The similarities between women and men were striking. There were only subtle differences between reference women and pregnant women. Reference men and child-expecting men had different response patterns, child-expecting men emphasizing more the advantages of having children.

    In the last part of the study 48 women were followed during pregnancy and after childbirth using the questionnaire and determination of levels of the intestinal peptide gastrin. Gastrin may be a marker of energy-storing characteristics, thus influencing reproductive capacity. There were some attitudinal differences between 0-parous women and parous women, the latter agreeing less with the view of 'children as restriction of freedom'. The view of 'children as existential satisfaction' was agreed with more after childbirth than during pregnancy. The view of one’s own parents as models in parenthood correlated with the levels of gastrin during this period.

  • Gustafsson, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Mattsson, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Gallego, Gisselle
    Students' satisfaction with a web-based pharmacy program in a re-regulated pharmacy market2017Ingår i: Pharmacy, ISSN 2226-4787, E-ISSN 1913-4711, Vol. 5, nr 3, E47Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In response to the shortage of pharmacists in Northern Sweden, a web-based Bachelor of Science in Pharmacy program was established at Umeå University in 2003. In 2009, the Swedish pharmacy market was re-regulated from a state monopoly to an open market, but it is unknown what impact this has had on education satisfaction. The objectives of this study were to examine the level of satisfaction among graduates from a web-based pharmacy program and to describe what subjects and skills students would have liked more or less of in their education. A secondary objective was to compare the level of satisfaction before and after the Swedish pharmacy market was re-regulated. A cross-sectional survey was conducted in 2015 with all alumni who had graduated from the pharmacy program between 2006 and 2014 (n = 511), and responses to questions about graduates' satisfaction with the program were analyzed (n = 200). Most graduates (88%) agreed or strongly agreed that the knowledge and skills acquired during their education were useful in their current job. The graduates stated that they would have wanted more applied pharmacy practice and self-care counselling, and fewer social pharmacy and histology courses. Further, 82% stated that they would start the same degree program if they were to choose again today, and 92% agreed or strongly agreed that they would recommend the program to a prospective student. Graduates were more likely to recommend the program after the re-regulation (p = 0.007). In conclusion, pharmacy graduates were very satisfied with their education, and no negative effects of the re-regulation could be observed on program satisfaction.

  • Kristensen, Bo Traberg
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stroke in young adults in northern Sweden1998Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Objectives. To study different aspects of cerebral venous and arterial occlusive disease including cerebrospinalfluid hydrodynamics, epidemiology, aetiology, genetics, metabolic and haemostatic disorders, andcognitive function in young adults in Northern Sweden.

    Methods. Cerebrospinal fluid hydrodynamics were investigated with a constant pressure infusion methodin patients with superior sagittal sinus thrombosis. Ten patients were studied with serial examinations, upto 15 years after the onset of the disease.

    Epidemiological data on ischaemic stroke in young adults aged 18 to 44 years were collected to calculateincidence and mortality based on the WHO Northern Sweden MONICA register of acute strokeevents. One hundred and seven consecutive patients aged 18-44 years with ischaemic stroke referred toUmeå university hospital were studied prospectively during a five-year period and were extensively evaluatedaccording to a standardized protocol. During follow-up at least three months after onset 102 and 80patients, respectively, were evaluated for disturbances in the fibrinolytic system and in the metabolism ofhomocysteine. A comprehensive neuropsychological battery was performed in a subset of 20 patients withinfratentorial infarcts.

    Results and conclusions. All patients with superior sagittal sinus thrombosis demonstrated a marked increasein intracranial pressure due to raised pressure in the sagittal sinus. A striking feature was the persistentintracranial pressure increase with only a slow decline over time.

    The incidence rate for ischaemic stroke was higher than previously reported from most countries inWestern Europe. The higher incidence was not explained by a higher prevalence of atherosclerotic vasculopathy. In spite of extensive evaluation, including advanced cardiac imaging, the cause of ischaemic strokein young adults still remains uncertain or unknown in most cases.

    Patients had lowered tissue plasminogen activator activity and increased plasminogen activator inhibitortype 1 activity. Increased fibrinogen levels and tissue plasminogen activator mass concentration wereindependently associated with ischaemic stroke. Metabolic perturbations were closely interrelated with tissueplasminogen activator and plasminogen activator inhibitor type 1 activity. Elevated plasma fibrinogenlevels and abnormalities in the fibrinolytic system in conjunction with metabolic perturbations may be importantcontributors to an increased stroke risk among young adults.

    Stroke patients had an exaggerated increase in total homocysteine levels after methionine loading.Abnormal responsivity to methionine loading was associated with higher tissue plasminogen activatormass concentration, plasminogen activator inhibitor 1 levels and lower tissue plasminogen activator activity. Abnormal homocysteine metabolism may provide an additional thrombogenetic risk, partly mediatedby interactions with the fibrinolytic system.

    Circumscribed infratentorial lesions (mainly cerebellar) impaired central aspects of attention andworking memory, and inflicted damage upon visuospatial skills. In contrast, these patients may not sufferfrom global intellectual impairment and difficulties with respect to memory for previous events. The prognosisis favorable in terms of neurological deficits and handicap, but cognitive disability may be the mostsignificant problem in adapting to their former occupations.Key w ords. Cerebral venous thrombosis, cerebrospinal fluid dynamics, ischaemic stroke, young adults, epidemiology,fibrinolysis, homocysteine, cerebellar infarct, neuropsychology.

  • Gärling, Anita
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Parents' perceptions of children's accident risk1988Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The purpose of the present thesis was, first, to study how parents and other adults percieve or judge children’s accident risk, and, secondly, to relate such judgements to the subjects’ preferences for and satisfaction with different residential conditions.

    A theoretical framework is proposed which assumes that judgements of children’s accident risk are based on beliefs about what causes accidents to children. Such beliefs are furthermore assumed to be acquired more often from indirect sources than from own direct experiences. Nevertheless, because of parents’ higher motivation to protect their children, they are assumed to differ from other adults who are not parents with respect to their causal models and, as a consequence, their risk perceptions.

    To test some implications of the theoretical framework, three empirical studies were carried out in which parents and nonparents were requested to judge the risk children run of having accidents under different circumstances and to judge the strengths of five causes of such accidents, the parent, the child, the environment, other people, and chance. In two of the studies the subjects were also requested to express their preferences for different residential neighborhoods varying in traffic conditions, or satisfaction with their own residential conditions either as it is or if changed in different ways.

    Support for the implications of the theoretical framework was obtained in that causal explanations of accidents were shown to play a decisive role for judgements of accident risk. However, very slight differences were found between parents’ and nonparents’ causal models and risk perceptions. The results furthermore indicated that accident risk was of importance for parents’ satisfaction with their residential conditions if changes with perceived accident consequences were implemented. In this respect parents differed from nonparents. For the latter other things than children’s accident risk tended to be more important.

  • Hoffman, Victoria
    et al.
    Söderström, Lars
    Samuelsson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Self-management of stress urinary incontinence via a mobile app: two-year follow-up of a randomized controlled trial2017Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 96, nr 10, 1180-1187 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction. We investigated the long-term effects of using a mobile app to treat stress urinary incontinence with a focus on pelvic floor muscle training. Material and methods. A previous randomized controlled trial of 123 women aged 27-72 years found that three months of self-managing stress urinary incontinence with support from the Tat((R)) app was effective. We followed up the women in the app group (n=62) two years after the initial trial with the same primary outcomes for symptom severity (International Consultation on Incontinence Questionnaire Short Form) and condition-specific quality of life (ICIQ-Lower Urinary Tract Symptom Quality of Life) and compared the scores with those at baseline. Results. Of the 62 women, 61 and 46 (75.4%), respectively, participated in three-month and two-year follow-ups. Baseline data did not differ between responders and non-responders at follow-up. The mean decreases in International Consultation on Incontinence Questionnaire Short Form and ICIQ-Lower Urinary Tract Symptom Quality of Life scores after two years were 3.1 (95% confidence interval 2.0-4.2) and 4.0 (95% confidence interval 2.1-5.9), respectively. Of the 46 women, four (8.7%) rated themselves as very much better, nine (19.6%) as much better, and 16 (34.8%) as a little better. The use of incontinence protection products decreased significantly (p=0.04), and the proportion of women who felt they could contract their pelvic muscles correctly increased from 14/46 (30.4%) at baseline to 31/46 (67.4%) at follow-up (p<0.001). Conclusions. Self-management of stress urinary incontinence with support from the Tat((R)) app had significant and clinically relevant long-term effects and may serve as first-line treatment.

  • Troiano, Giuseppe
    et al.
    Caponio, Vito Carlo Alberto
    Boldrup, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Gu, Xiaolian
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Lo Muzio, Lorenzo
    Sgaramella, Nicola
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Wang, Lixiao
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Expression of the long non-coding RNA HOTAIR as a prognostic factor in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis2017Ingår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, nr 42, 73029-73036 s.Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Introduction: Long noncoding RNAs (lncRNAs) are often dysregulated in cancer tissue and seem to play an important role in neoplastic processes. Recent studies have shown that the HOX transcript antisense intergenic RNA (HOTAIR) may play a role as a marker of prognosis in squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to perform a meta-analysis of studies focused on the prognostic role of HOTAIR in SCCHN.

    Results: At the end of the selection process, four studies were considered eligible for inclusion in the meta-analysis, comprising a total of 271 patients. Meta-analysis revealed that high expression of HOTAIR was associated with poor overall survival (HR, 1.90; 95% CI: [1.42, 2.53]; p < 0,0001), advanced tumor stage (OR, 3.44; 95% CI: [1.84, 6.43]; p < 0,001) and lymph-node metastasis (OR, 3.31; 95% CI: [1.24, 8.79]; p = 0,02).

    Materials and Methods: The literature search was performed in the following databases: PUBMED, SCOPUS, EMBASE and Web of Science, in order to find studies that met the inclusion criteria.

    Conclusions: Findings from this systematic review and meta-analysis revealed that HOTAIR represents a potential biomarker of prognosis in patients with squamous cell carcinoma of the head and neck.

  • Niklasson, André
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Dialogue Systems Using Web-based Language Tools2017Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Chatbots in commercial environments are on the rise with the release of several web-based language understanding tools. The vast majority of the dialogue systems deployed today uses very primitive state-machine architectures to model their interactions. These primitive approaches are reliable and easy to implement but the dialogue becomes very unnatural and the system always has the initiative in the conversation. The positive features of being easy to build, and the ability to easily retain control over the system normally supersedes the shortcomings.This thesis proposes a dialogue model that utilizes new approaches for dialogue modeling but aims to be easy to congure. The proposed dialogue management strategy is implemented in a prototype dialogue system. Developers are able to model their dialogues using an XML dialogue description. The system utilizes LUIS.ai, a recently launched web-based language tool for sentence analysis. LUIS.ai is evaluated together with the prototype dialogue system.i

  • Thomson, Suzanne E.
    et al.
    Charalambous, Chloe
    Smith, Carol-Anne
    Tsimbouri, Penelope M.
    Déjardin, Theophile
    Kingham, Paul J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Hart, Andrew M.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). The Centre for Cell Engineering, College of Medical, Veterinary and Life Sciences, University of Glasgow, University Avenue, Hillhead, Glasgow G128QQ, UK; Canniesburn Plastic Surgery Unit, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, UK.
    Riehle, Mathis O.
    Microtopographical cues promote peripheral nerve regeneration via transient mTORC2 activation2017Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 60, 220-231 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite microsurgical repair, recovery of function following peripheral nerve injury is slow and often incomplete. Outcomes could be improved by an increased understanding of the molecular biology of regeneration and by translation of experimental bioengineering strategies. Topographical cues have been shown to be powerful regulators of the rate and directionality of neurite regeneration, and in this study we investigated the downstream molecular effects of linear micropatterned structures in an organotypic explant model. Linear topographical cues enhanced neurite outgrowth and our results demonstrated that the mTOR pathway is important in regulating these responses. mTOR gene expression peaked between 48 and 72 h, coincident with the onset of rapid neurite outgrowth and glial migration, and correlated with neurite length at 48 h. mTOR protein was located to glia and in a punctate distribution along neurites. mTOR levels peaked at 72 h and were significantly increased by patterned topography (p < 0.05). Furthermore, the topographical cues could override pharmacological inhibition. Downstream phosphorylation assays and inhibition of mTORC1 using rapamycin highlighted mTORC2 as an important mediator, and more specific therapeutic target. Quantitative immunohistochemistry confirmed the presence of the mTORC2 component rictor at the regenerating front where it co-localised with F-actin and vinculin. Collectively, these results provide a deeper understanding of the mechanism of action of topography on neural regeneration, and support the incorporation of topographical patterning in combination with pharmacological mTORC2 potentiation within biomaterial constructs used to repair peripheral nerves.

    Statement of Significance: Peripheral nerve injury is common and functionally devastating. Despite microsurgical repair, healing is slow and incomplete, with lasting functional deficit. There is a clear need to translate bioengineering approaches and increase our knowledge of the molecular processes controlling nerve regeneration to improve the rate and success of healing. Topographical cues are powerful determinants of neurite outgrowth and represent a highly translatable engineering strategy. Here we demonstrate, for the first time, that microtopography potentiates neurite outgrowth via the mTOR pathway, with the mTORC2 subtype being of particular importance. These results give further evidence for the incorporation of microtopographical cues into peripheral nerve regeneration conduits and indicate that mTORC2 may be a suitable therapeutic target to potentiate nerve regeneration.

  • Chen, Genqiang
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China.
    Wu, Guochao
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Alriksson, Björn
    Wang, Wei
    Hong, Feng F.
    Jönsson, Leif J.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bioconversion of waste fiber sludge to bacterial nanocellulose and use for reinforcement of CTMP paper sheets2017Ingår i: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 9, nr 9, 458Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Utilization of bacterial nanocellulose (BNC) for large-scale applications is restricted by low productivity in static cultures and by the high cost of the medium. Fiber sludge, a waste stream from pulp and paper mills, was enzymatically hydrolyzed to sugar, which was used for the production of BNC by the submerged cultivation of Komagataeibacter xylinus. Compared with a synthetic glucose-based medium, the productivity of purified BNC from the fiber sludge hydrolysate using shake-flasks was enhanced from 0.11 to 0.17 g/(L x d), although the average viscometric degree of polymerization (DPv) decreased from 6760 to 6050. The cultivation conditions used in stirred-tank reactors (STRs), including the stirring speed, the airflow, and the pH, were also investigated. Using STRs, the BNC productivity in fiber-sludge medium was increased to 0.32 g/(L x d) and the DPv was increased to 6650. BNC produced from the fiber sludge hydrolysate was used as an additive in papermaking based on the chemithermomechanical pulp (CTMP) of birch. The introduction of BNC resulted in a significant enhancement of the mechanical strength of the paper sheets. With 10% (w/w) BNC in the CTMP/BNC mixture, the tear resistance was enhanced by 140%. SEM images showed that the BNC cross-linked and covered the surface of the CTMP fibers, resulting in enhanced mechanical strength.

  • Dahlgren Lindström, Adam
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Structured Prediction using Voted Conditional Random FieldsLink Prediction in Knowledge Bases2017Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Knowledge bases are useful in the validation of automatically extracted information, and for hypothesis selection during the extraction process. Building knowledge bases is a dfficult task and the process is bound to miss facts. Therefore, the existence of facts can be estimated using link prediction, i.e., by solving the structured prediction problem.It has been shown that combining directly observable features with latent features increases performance. Observable features include, e.g., the presence of another chain of facts leading to the same end point. Latent features include, e.g, properties that are not modelled by facts on the form subject-predicate-object, such as being a good actor. Observable graph features are modelled using the Path Ranking Algorithm, and latent features using the bilinear RESCAL model. Voted Conditional Random Fields can be used to combine feature families while taking into account their complexity to minimize the risk of training a poor predictor. We propose a combined model fusing these theories together with a complexity analysis of the feature families used. In addition, two simple feature families are constructed to model neighborhood properties.The model we propose captures useful features for link prediction, but needs further evaluation to guarantee effcient learning. Finally, suggestions for experiments and other feature families are given.

  • Allgardsson, Anders
    et al.
    Andersson, C. David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Akfur, Christine
    Worek, Franz
    Linusson, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Ekström, Fredrik
    An unusual dimeric inhibitor of acetylcholinesterase: cooperative binding of crystal violet2017Ingår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 9, 1433Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer's disease and myasthenia gravis. In a previous high throughput screening campaign, we identified the dye crystal violet (CV) as an inhibitor of AChE. Herein, we show that CV displays a significant cooperativity for binding to AChE, and the molecular basis for this observation has been investigated by X-ray crystallography. Two monomers of CV bind to residues at the entrance of the active site gorge of the enzyme. Notably, the two CV molecules have extensive intermolecular contacts with each other and with AChE. Computational analyses show that the observed CV dimer is not stable in solution, suggesting the sequential binding of two monomers. Guided by the structural analysis, we designed a set of single site substitutions, and investigated their effect on the binding of CV. Only moderate effects on the binding and the cooperativity were observed, suggesting a robustness in the interaction between CV and AChE. Taken together, we propose that the dimeric cooperative binding is due to a rare combination of chemical and structural properties of both CV and the AChE molecule itself.

  • Stenling, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    The enterocyte in small intestinal adaption: an experimental and clinicopathological study with special reference to the ultrastructure of the brush border1984Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Stenling, Roger; THE ENTEROCYTE IN SMALL INTESTINAL ADAPTION. An expe­rimental and clinicopathological study with special reference to the ultrastructure of the brush border. Umeå Univ, Med Di ss, New Series 122 - ISSN 0346-6612.

    The small intestine mucosa is known to be able to adapt itself to several kinds of both physiological and pathological conditions. The adaptive patterns of the structure of the enterocytes, particularly their apical surface (brush border), were studied in three models: (1) in rats, subjected to antrectomy or antral exclusion, combined with gastroduodenostomy and gastrojejunostomy; (2) in rats with alloxan dia­betes; (3) in children with coeliac disease; a) in its active phase; b) after long-term treatment with gluten-free diets; c) after long-term challenge with dietary gluten following treatment; d) after short-term elimination of dietary gluten. Gut mucosa from fasting or fed, normal or sham-operated rats, fasting cats, and short-statured children with no signs of gastrointestinal disease served as controls. - The specimens were prepared for light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Quantitation of structural variables was achieved by means of LM and TEM morphometrical procedures.

    Differentiation of the rat enterocytes from the base to the crest of the villi was structurally reflected by doubling of their apical cell area, an increase in cell height, and a decrease of both nuclear and mitochondrial volume densities. In mature normal rat enterocytes, high- -power SEM showed regularly arranged, nude microvilli in thir apical surfaces, whereas in cat and man the apical surfaces were covered by a thick glycocalyx. - Fasting for 24 hours decreased the total length of the rat small intestine and the height of the enterocytes. Antrectomy and antral exclusion with gastrojejunostomy produced an increase of the apical surfaces of the enterocytes of the seif-emptying duodenal blind loop, whereas no changes occurred after antrectomy with gastroduodeno­stomy. In the jejunum, the apical surface area was reduced both after antrectomy and antral exclusion. In the diabetic rats a slight decrease of the apical surface area, together with an elongation of both the vil­li and the crypts, was observed in the jejunum, whereas no structural changes occurred in the duodenal mucosa.

    Both in active coeliac disease and after long-term challenge with dietary gluten, SEM analyses showed uniformly destructed villi. The api­cal surfaces of the enterocytes were frequently convex and irregular in size and delineation (the surface of the normal enterocytes was polygo­nal and flat). Ultrastructurally, the apical surfaces were severely damaged with a distortion of the glycocalyx and with marked irregularity of the microvilli. - After gluten elimination, the surface ultrastructu­re of the enterocytes in the coeliac gut mucosa generally showed a rapid, clear-cut restoration despite a remaining severe atrophy of the villi. Successful dietary treatment (after about one year of gluten-free diet) restored the small intestine mucosa to normal as assessed both by LM and low-power SEM. In contrast, high-power SEM often disclosed per­sisting lesions of the enterocytes. Another provocation with gluten for up to 9 days in clinically healed coeliac mucosa did not significantly alter the surface ultrastructure of the enterocytes.

  • Björnstig, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Snowmobile, motorcycle and moose-car accidents: aspects on injury control1985Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Injuries related to snowmobiles, motorcycles and moose-car collisions have increased. The aim of the present thesis was to analyse mechanisms and consequences in fatal and non-fatal accidents of these types, and to penetrate possible preventive measures.

    Snowmobiles

    The median age of the injured was 30 and of the killed 32, males pre­dominating. A majority of the accidents occurred during weekends, and especially the fatal accidents occurred after dark. The extremities were the most commonly injured parts of the body, however, drowning, crushed chest and cranial injuries caused most of the fatalities. Among the fatalities, four out of five were under the influence of alcohol. The present Swedish laws regarding snowmobiles seem well motivated. "Built-in" safety measures in the construction of the snowmobiles, pro­perly designed snowmobile tracks and functional search and rescue sys­tems could reduce the injuries.

    Motorcycles

    The median age was 19 years for both the traffic injured and the kil­led. Half of the traffic accidents were collisions with other motor ve­hicles. In the fatally injured group, also collisions with fixed road­side objects were common. Of the fatally injured, more than every fifth person died in an accident where alcohol was an influential factor. In the injured group, lower extremity injuries (especially in off-road riding) were common and among the fatalities most riders died from injuries to the head or chest. Out of one thousand motorcycle riders interviewed, 45% reported wobbling experiences (8% reported severe wobbling). Possible injury reducing measures include increasing the licensing age, more discriminating driving test, "built-in" restriction of the motorcycle's top speed, elimination of motorcycles prone to wobbling, and a more intensive traffic supervision (speeding, alco­hol).

    Moose-car collisitions

    The median age of the drivers was 38 years. Most collisions happened at dusk or when dark (3/4). The median collision speed was 70 km/h. The damage to the car was typical, the roof and the windshield pillars were deformed downwards and backwards. The broken windshield was often pressed into the passenger compartment. Most of the injured car occu­pants suffered cuts predominantly to the head and upper extremities. Nearly all the fatally injured died of head and neck injuries. The injuries may be reduced by strengthening the roof and the windshield pillars, and by introducing anti 1 acerati ve windshields.

  • Kinsman, John
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    de Bruijne, Kars
    Jalloh, Alpha M.
    Harris, Muriel
    Abdullah, Hussainatu
    Boye-Thompson, Titus
    Sankoh, Osman
    Jalloh, Abdul K.
    Jalloh-Vos, Heidi
    Development of a set of community-informed Ebola messages for Sierra Leone2017Ingår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, nr 8, e0005742Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The West African Ebola epidemic of 2013-2016 was by far the largest outbreak of the disease on record. Sierra Leone suffered nearly half of the 28,646 reported cases. This paper presents a set of culturally contextualized Ebola messages that are based on the findings of qualitative interviews and focus group discussions conducted in 'hotspot' areas of rural Bombali District and urban Freetown in Sierra Leone, between January and March 2015. An iterative approach was taken in the message development process, whereby (i) data from formative research was subjected to thematic analysis to identify areas of community concern about Ebola and the national response; (ii) draft messages to address these concerns were produced; (iii) the messages were field tested; (iv) the messages were refined; and (v) a final set of messages on 14 topics was disseminated to relevant national and international stakeholders. Each message included details of its rationale, audience, dissemination channels, messengers, and associated operational issues that need to be taken into account. While developing the 14 messages, a set of recommendations emerged that could be adopted in future public health emergencies. These included the importance of embedding systematic, iterative qualitative research fully into the message development process; communication of the subsequent messages through a two-way dialogue with communities, using trusted messengers, and not only through a one-way, top-down communication process; provision of good, parallel operational services; and engagement with senior policy makers and managers as well as people in key operational positions to ensure national ownership of the messages, and to maximize the chance of their being utilised. The methodological approach that we used to develop our messages along with our suggested recommendations constitute a set of tools that could be incorporated into international and national public health emergency preparedness and response plans.

  • Alexandersson, Mimmi
    Umeå universitet, Samhällsvetenskapliga fakulteten, Juridiska institutionen.
    Arbetsgivarens möjlighet att avsluta en arbetstagares anställning vid samarbetssvårigheter och vilken hänsyn tas till kollegorna?2017Självständigt arbete på avancerad nivå (magisterexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • Hansson, Oskar
    et al.
    Janelidze, Shorena
    Hall, Sara
    Magdalinou, Nadia
    Lees, Andrew J.
    Andreasson, Ulf
    Norgren, Niklas
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Constantinescu, Radu
    Zetterberg, Henrik
    Blennow, Kaj
    Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder2017Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, nr 10, 930-937 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, and can therefore improve the diagnostic workup of parkinsonian disorders. Methods: The study included 3 independent prospective cohorts: the Lund (n 5 278) and London (n 5 117) cohorts, comprising healthy controls and patients with PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), as well as an early disease cohort (n 5 109) of patients with PD, PSP, MSA, or CBS with disease duration <= 3 years. Blood NfL concentration was measured using an ultrasensitive single molecule array (Simoa) method, and the diagnostic accuracy to distinguish PD from APD was investigated. Results: We found strong correlations between blood and CSF concentrations of NfL (p >= 0.73-0.84, p <= 0.001). Blood NfL was increased in patients with MSA, PSP, and CBS (i.e., all APD groups) when compared to patients with PD as well as healthy controls in all cohorts (p, 0.001). Furthermore, in the Lund cohort, blood NfL could accurately distinguish PD from APD (area under the curve [AUC] 0.91) with similar results in both the London cohort (AUC 0.85) and the early disease cohort (AUC 0.81). Conclusions: Quantification of blood NfL concentration can be used to distinguish PD from APD. Blood-based NfL might consequently be included in the diagnostic workup of patients with parkinsonian symptoms in both primary care and specialized clinics.

  • Saedén, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Snabb DNA extraktion för ”Point-of-Care” sekvensering och analys2017Självständigt arbete på grundnivå (yrkesexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • Gillemyr, Rikard
    Umeå universitet, Humanistiska fakulteten, Institutionen för idé- och samhällsstudier.
    Ansvarsgapet och moraliskt ansvar2017Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • Disputation: 2017-11-03 10:00 KB.E3.01 (Lilla Hörsalen), Umeå
    Ochtrop, Philipp
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Selective protein functionalisation via enzymatic phosphocholination2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Proteiner utgör huvudbeståndsdelen av alla biomolekyler i en cell. Dessa är involverade i alla cellulära processer som bestämmer cellens egenskaper. För att förstå de cellulära processerna är det nödvändigt att förstå proteinernas funktion på molekylär nivå. Att studera proteiner i deras naturliga omgivning, det vill säga inuti en cell eller i ett cellextrakt, är en stor utmaning i dagens livsvetenskaper. Eftersom proteiner är kemiskt lika varandra så är det svårt att skilja ett från tusentals andra. Att specifikt märka proteiner för att skilja ut dem från bakgrunden har blivit ett viktigt arbetssätt i modern biokemi och cellbiologi. Avhandlingen beskriver utvecklandet av en ny metod för reversibel och kovalent enzymatisk märkning baserat på fosfokolinering/defosfokolinering av en kort aminosyrasekvens i intakta proteiner. En syntesmetod för att framställa onaturliga CDP-kolinderivat har etablerats vilket tillåter oss att framställa CDP-kolin som bär en funktionalitet, vilket kan vara ett färgämne eller en affinitetstagg. Dessa onaturliga CDP-kolinderivat accepteras som co-substrat av enzymet AnkX från Legionella pneumophila vilket transfererar den funktionaliserade delen av CDP-kolinderivatet till en kort aminosyrasekvens baserad på AnkX’s naturliga substrat vid infektion, det lilla GTPaset Rab1. Under avhandlingsarbetets gång identifierades den kortaste aminosyrasekvensen som känns igen av AnkX, endast de åtta aminosyrorna TITSSYYR är nödvändiga för igenkänning av AnkX. Dessa åtta aminosyror kan genetiskt infogas i början, slutet eller mitt i ett protein för igenkänning och funktionalisering via AnkX och våra syntetiska CDP-kolinderivat. Vid Legionellainfektion i eukaryota celler klyvs fosfokolineringen efter en viss tid, eftersom Legionella pneumophila producerar ett fosfodiesteras, Lem3, som tar bort de fosfokolineringar som AnkX har installerat när de inte längre behövs. Vi har använt Lem3 för att ta bort märkning i sekvensen TITSS(PC)YYR, vilket gör vår strategi helt reversibel. Vi har kunnat demonstrera att AnkX-Lem3 systemet accepterar ett brett spektrum av CDP-kolinderivat, vilket gör metoden till den första av sitt slag, eftersom den är fullt reversibel. Vi har vidare undersökt vilka proteiner AnkX reagerar med inuti celler, vi använde oss av ett CDP-kolinderivat funktionaliserat med biotin, vilket har tillåtit oss att fiska ut alla de proteiner som fosfokolineras av AnkX. Förutom de små GTPaserna i Rab-familjen så identifierade vi även IMPDH2, ett enzym som reglerar det hastighetsbestämmande steget i syntesen av guanosin-nukleotider. Detta är mycket intressant, eftersom det leder till frågan ifall Legionella pneumophila manipulerar sin värdcell genom att förändra mängden GTP i förhållande till ATP.

  • Gutebrand, Kristoffer
    Umeå universitet, Humanistiska fakulteten, Institutionen för idé- och samhällsstudier.
    Ett Drogfritt Samhälle: En filosofisk förfrågan om Sveriges narkotikapolitik2017Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Sveriges narkotikapolitik har en tydlig noll vision; Sverige skall bli ett drogfritt samhälle. För att uppnå det målet följer Sverige en så kallad nolltoleransmodell, vilket innebär en strikt policy som säger att all hantering och bruk oavsett volym och syfte är olagligt. Jag argumenterar att det är en skadlig och ineffektiv policy att applicera på drogproblematiken i Sverige och argumenterar därför istället för att införa en så kallad skadereducerande policy. Detta är istället en policy som accepterar att droger är en del av samhället. En sådan policy jobbar främst med förebyggande och behandlande åtgärder, jag argumenterar för en avkriminalisering av personligt bruk av drog. Jag kommer använda mig av empirisk källor och moralfilosofiska argument för att påvisa att en skadereducerade policy gynnar samhället både ur ett socialt och ekonomiskt perspektiv.

  • Cochard, Aurélie
    Umeå universitet, Humanistiska fakulteten, Institutionen för idé- och samhällsstudier.
    Kvinnliga medborgarskolan vid Fogelstads kursverksamhet: - mellan kvinnorörelsens två vågor2017Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [en]

    This paper analyses the Fogelstad Citizen School for Women in relation to first andsecond-wave feminism in Sweden. The school was established not long after women in Sweden were given the right to vote in 1921, with the purpose of educating women in civic education, in order for them to be able to make use of their newly gained rights.The school and its founders had thus a close connection to the ideas of Swedish first-wave feminism. On the other hand, the school shut down in 1954, about a decade before second-wave feminism is considered to have started in Sweden in the late 1960’/70’s. Hence, the school was active between two so-called “waves”. By analysing specific ideas on women expressed through course notes from the school’s later years, 1939–1945, this paper explores ideas about women that women’s specific qualities were emphasised in order to argue for women’s increased participation in society, while contextualising with other contemporary tendencies and events in Swedish society. A closer examination shows that specifically the school’s founders and its teacher in citizenship, Ebba Holgersson, were promoting gender essentialism, emphasising women’s nurturing characteristics and using it as an argument for women to participate more in societal and political matters. The results further imply that while this period cannot be attributed a specific feminist “wave” with regards to how a social movement’s wave it was defined, it was nonetheless a period where feminist ideas flourished and thus worked as bridge between first and second-wave feminism.

  • Boberg, Felicia
    Umeå universitet, Humanistiska fakulteten, Institutionen för idé- och samhällsstudier.
    Krigsfånge eller flykting?: Svenska interneringsläger för utländsk militär personal2017Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • Larsen, Øyvind
    et al.
    Hodne, Fritz
    Health Conditions, Population and Physicians in Norway 1814-1986. Notes on the Development of a Profession.1988Ingår i: Society, Health and Population during the Demographic Transition / [ed] Anders Brändström and Lars-Göran Tedebrand, Stockholm: Almqvist and Wiksell International , 1988, 331-341 s.Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • Johansson, Petter
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Temporal spawning divergence in European whitefish (Coregonus lavaretus): The first steps towards reproductive isolation in young populations (70-171 years)2017Självständigt arbete på avancerad nivå (masterexamen), 40 poäng / 60 hpStudentuppsats (Examensarbete)
    Abstract [en]

    A critical step in ecological speciation is the development of reproductive isolation. The processes leading up to reproductive isolation are difficult to study since they often occur over very long time periods. Populations of European whitefish (Coregonus lavaretus) has gone through reticulate divergent evolution in many Scandinavian lakes during the last 10 000 years. Some populations even exhibit morphological and genetic divergence that involves adaptations to different niches during the first 100-200 years after introduction. This observed rapid diversification into different ecological niches makes whitefish a useful model species for studying ecological speciation and early population divergence. By assessing divergence for three traits in recently introduced whitefish populations, this study aims to elucidate the processes that lead to adaptive phenotypic divergence and reproductive isolation. Whitefish populations of known age (71-170 years) were sampled on their spawning grounds and characterized with respect to, 1) length of spawning season, 2) temporal segregation based on body size, and 3) temporal segregation based on the number of gill rakers. I found that the length of the spawning season and body size differences between early and late spawners increased with population age. No such trend was observed for differences in gill rakers between early and late spawners, but significant divergence within some of the older populations was detected. I conclude that these young whitefish populations have taken the first steps toward reproductive isolation between ecotypes that differs in body size (a highly plastic trait) and gill raker numbers (a trait under strong genetic control).

  • Öhman Mägi, Daniel
    Umeå universitet, Humanistiska fakulteten, Institutionen för idé- och samhällsstudier.
    Mening och moral: - Är minimal moralisk anständighet nödvändigt för ett meningsfullt liv?2017Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    In this thesis, I argue for the hypothesis that a minimal moral decency is in fact a criterion for livinga meaningful life. To argue that point I present four different arguments about the relation between morality and a meaningful life. These four arguments are grounded in different forms of theories that discuss the concept and conceptions of meaning and a meaningful life. The four arguments are built on the philosophies of: John Cottingham, Laurence Thomas, Susan Wolf and Thaddeus Metz. Two of the arguments are in favor of morality being a criterion for a meaningful life while the other two are against it. The most powerful argument against morality being a part of a meaningful life is built on Metz fundamentality theory which is presented last in the thesis. When we look closer upon Metz description of anti-matter, which can be considered to be the opposite of meaning, come to the conclusion that when avoiding certain anti-matter we live lives with a minimal form of moral decency. The conclusion of this thesis is that a minimal moral decency is in fact a criterion for a meaningful life.

  • Huber, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Henriksson, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Jakobsson, Stina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Nurse-led telephone-based follow-up of secondary prevention after acute coronary syndrome: One-year results from the randomized controlled NAILED-ACS trial2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 9, e0183963Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Secondary prevention after acute coronary syndrome (ACS) could reduce morbidity and mortality, but guideline targets are seldom reached. We hypothesized that nurse-led telephone- based intervention would increase adherence.

    Methods. The NAILED ACS trial is a prospective, controlled, randomized trial. Patients admitted for ACS at Ostersund hospital, Sweden, were randomized to usual follow-up by a general practitioner or a nurse-led intervention. The intervention comprised telephone follow-up after 1 month and then yearly with lifestyle counselling and titration of medications until reaching target values for LDL-C (< 2.5 mmol/L) and blood pressure (BP; < 140/90 mmHg) or set targets were deemed unachievable. This is a 12-month exploratory analysis of the intervention.

    Results. A total of 768 patients (396 intervention, 372 control) completed the 12-month follow-up. After titration at the 1-month follow-up, mean LDL-C was 0.38 mmol/L (95% CI 0.28 to 0.48, p< 0.05), mean systolic BP 7 mmHg (95% CI 4.5 to 9.2, p< 0.05), and mean diastolic BP 4 mmHg (95% CI 2.4 to 4.1, p< 0.05) lower in the intervention group. Target values for LDL-C and systolic BP were met by 94.1% and 91.9% of intervention patients and 68.4% and 65.6% of controls (p< 0.05). At 12 months, mean LDL was 0.3 mmol/L (95% CI 0.1 to 0.4, p < 0.05), systolic BP 1.5 mmHg (95% CI -1.0 to 4.1, p = 0.24), and mean diastolic BP 2.1 mmHg (95% CI 0.6 to 3.6, p < 0.05) lower in the intervention group. Target values for LDL-C and systolic BP were met in 77.7% and 68.9% of intervention patients and 63.2% and 63.7% of controls (p< 0.05 and p = 0.125).

    Conclusion. Nurse-led telephone-based secondary prevention was significantly more efficient at improving LDL-C and diastolic BP levels than usual care. The effect of the intervention declined between 1 and 12 months. Further evaluation of the persistence to the intervention is needed.

  • de Boer, Lieke
    et al.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dayan, Peter
    Backman, Lars
    Guitart-Masip, Marc
    Attenuation of dopamine-modulated prefrontal value signals underlies probabilistic reward learning deficits in old age2017Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 6, e2642Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Probabilistic reward learning is characterised by individual differences that become acute in aging. This may be due to age-related dopamine (DA) decline affecting neural processing in striatum, prefrontal cortex, or both. We examined this by administering a probabilistic reward learning task to younger and older adults, and combining computational modelling of behaviour, fMRI and PET measurements of DA D1 availability. We found that anticipatory value signals in ventromedial prefrontal cortex (vmPFC) were attenuated in older adults. The strength of this signal predicted performance beyond age and was modulated by D1 availability in nucleus accumbens. These results uncover that a value-anticipation mechanism in vmPFC declines in aging, and that this mechanism is associated with DA D1 receptor availability.

  • Hörnell, Agneta
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Berg, Christina
    Forsum, Elisabet
    Larsson, Christel
    Sonestedt, Emily
    Akesson, Agneta
    Lachat, Carl
    Hawwash, Dana
    Kolsteren, Patrick
    Byrnes, Graham
    De Keyzer, Willem
    Van Camp, John
    Cade, Janet E.
    Greenwood, Darren C.
    Slimani, Nadia
    Cevallos, Myriam
    Egger, Matthias
    Huybrechts, Inge
    Wirfalt, Elisabet
    Perspective: An Extension of the STROBE Statement for Observational Studies in Nutritional Epidemiology (STROBE-nut): Explanation and Elaboration2017Ingår i: Advances in Nutrition, ISSN 2161-8313, Vol. 8, nr 5, 652-678 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Nutritional epidemiology is an inherently complex and multifaceted research area. Dietary intake is a complex exposure and is challenging to describe and assess, and links between diet, health, and disease are difficult to ascertain. Consequently, adequate reporting is necessary to facilitate comprehension, interpretation, and generalizability of results and conclusions. The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement is an international and collaborative initiative aiming to enhance the quality of reporting of observational studies. We previously presented a checklist of 24 reporting recommendations for the field of nutritional epidemiology, called "the STROBE-nut." The STROBE-nut is an extension of the general STROBE statement, intended to complement the STROBE recommendations to improve and standardize the reporting in nutritional epidemiology. The aim of the present article is to explain the rationale for, and elaborate on, the STROBE-nut recommendations to enhance the clarity and to facilitate the understanding of the guidelines. Examples from the published literature are used as illustrations, and references are provided for further reading.

  • Prymula, Roman
    et al.
    Szenborn, Leszek
    Silfverdal, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wysocki, Jacek
    Albrecht, Piotr
    Traskine, Magali
    Gardev, Asparuh
    Song, Yue
    Borys, Dorota
    Safety, reactogenicity and immunogenicity of two investigational pneumococcal protein-based vaccines: results from a randomized phase II study in infants2017Ingår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 35, nr 35B, 4603-4611 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Vaccination with formulations containing pneumococcal protein antigens such as pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) may extend serotype-related protection of pneumococcal conjugate vaccines (PCVs) against Streptococcus pneumoniae.

    Methods: This phase II, multi-center, observer-blind trial conducted in Europe (NCT01204658) assessed 2 investigational vaccines containing 10 serotype-specific polysaccharide conjugates of PHiD-CV and either 10 or 30 mu g of dPly and PhtD each. Infants randomized 1:1:1:1 received 4 doses of PHiD-CV/dPly/PhtD-10, PHiD-CV/c1Ply/PhtD-30, PHiD-CV, or 13-valent PCV (PCV13), co-administered with DTPa-HBV-IPV/Flib, at ages 2, 3, 4 and 12-15 months. Occurrences of fever >40.0 degrees C following primary vaccination with PHiD-CV/dPly/PhtD vaccines compared to PHiD-CV (non-inferiority objective), dose superiority, safety and immunogenicity were assessed.

    Results: 575 children received primary vaccination, and 564 booster vaccination. The non-inferiority objective was met; no fever >40.0 degrees C causally related to vaccination was reported during primary vaccination. Incidence of adverse events appeared similar between the 3 PHiD-CV groups. Serious adverse events were reported in 13, 9, 21 (1 related to vaccination), and 17 children in the PHiD-CV/c1Ply/PhtD-10, PHiD-CV/dPly/PhtD-30, PHiD-CV, and PCV13 groups, respectively. PHiD-CV/dPly/PhtD-30 was superior to PHiD-CV/c1Ply/PhtD-10 in terms of post-dose 3 anti-Ply and Anti-PhtD antibody levels. Anti-Ply and anti-PhtD antibody levels were higher in both PHiD-CV/dPly/PhtD groups than in controls and increased from post-primary to post-booster timepoint. Post-primary and booster vaccination, for each PHiD-CV serotype, >= 98.5% of participants in PHiD-CV/dPly/PhtD groups had antibody concentrations >= 0.2 mu g/mL, except for 6B (>= 72.3%) and 23 F (>= 82.7%) post-primary vaccination. Similar results were observed in the PHiD-CV group. Immune responses to protein D and DTPa-HBV-IPV/Hib were within similar ranges for the 3 PHiD-CV groups.

    Conclusion: Both PHiD-CV/dPly/PhtD formulations co-administered with DTPa-HBV-IPV/Hib in infants were well-tolerated and immunogenic for dPly and PhtD antigens, while immune responses to serotype-specific, protein D and co-administered antigens did not appear altered in comparison to PHiD-CV group. 

  • Forsell, Erik
    et al.
    Bendix, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Holländare, Fredrik
    Szymanska von Schultz, Barbara
    Nasiell, Josefine
    Blomdahl-Wetterholm, Margareta
    Eriksson, Caroline
    Kvarned, Sara
    Lindau van der Linden, Johanna
    Söderberg, Elin
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Sweden.
    Wide, Katarina
    Kaldo, Viktor
    Internet delivered cognitive behavior therapy for antenatal depression: A randomised controlled trial2017Ingår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 221, 56-64 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Major depression occurs in 5-10% of pregnancies and is associated with many negative effects for mother and child, yet treatment options are scarce. To our knowledge, this is the first published randomised controlled trial on Internet delivered Cognitive Behavior Therapy (ICBT) for this group.

    Objective: To test the efficacy of a pregnancy adapted version of an existing 10-week ICBT-program for depression as well as assessing acceptability and adherence.

    Design: Randomised controlled trial.

    Setting: Online and telephone.

    Population or sample: Self-referred pregnant women (gestational week 10-28 at intake) currently suffering from major depressive disorder.

    Methods: 42 pregnant women (gestational week 12-28) with major depression were randomised to either treatment as usual (TAU) provided at their antenatal clinic or to ICBT as an add-on to usual care.

    Main outcome measures: The primary outcome was depressive symptoms measured with the Montgomery-Asberg depression rating scale-self report (MADRS-S). The Edinburgh Postnatal Depression Scale and measures of anxiety and sleep were used. Credibility, satisfaction, adherence and utilization were also assessed.

    Results: The ICBT group had significantly lower levels of depressive symptoms post treatment (p < 0.001, Hedges g = 1.21) and were more likely to be responders (i.e. achieve a statistically reliable improvement) (RR = 0.36; p = 0.004). Measures of treatment credibility, satisfaction, utilization, and adherence were comparable to implemented ICBT for depression.

    Limitations: Small sample size and no long-term evaluation.

    Conclusion: Pregnancy adapted ICBT for antenatal depression is feasible, acceptable and efficacious. These results need to be replicated in larger trials to validate these promising findings.

  • Munneke, Antoon Frans
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Företagsekonomi.
    Cornu, Manuel
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Företagsekonomi.
    The influence of the age difference on trust between young managers and older subordinates: A qualitative study among employees of a Dutch multinational production company2017Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    An aging population results in retirement ages going up and the age difference between subordinates and managers growing bigger. Despite an extensive literature review on trust within organizations, we have not been able to identify studies related to the influence of age difference between managers and their subordinates. The main purpose of this thesis is to gain a deeper understanding of the influence of age difference on trust in relationships between managers and subordinates, and more specifically how the age difference influences the trust in the relationship with their older subordinates. Our research question has been formulated as follows:

    How does age difference influence trust between young managers and their older subordinates?

    Despite studies on trust increasing in popularity over the last years, we identified a research gap since there is no previous studies addressing the influence of age difference on trust between managers and subordinates. Specifically, the influence of the age difference between young managers and older subordinates and the trust between them in their relationship.

    In order to fulfil the purpose of our thesis we have conducted a qualitative research, where we gathered qualitative data through the use of semi-structured interviews. These interviews were conducted in a Dutch multinational production company employing approximately 25.000 employees. By analysing the data we gathered through our semi-structured interviews and relating it to the theoretical framework we built up from pre-existing literature, we were able to answer our research question.

    As a theoretical foundation, we have used the key theories on trust: trust, factors of perceived trustworthiness, antecedent of trustworthy behaviour and employee-organisation relationship. The findings demonstrate that the age difference has influence on an individual’s behaviour, employee expectations and factors of trust. We found an influence of the age difference on benevolence as well as for ability. Young managers are perceived to have different values than older subordinates, resulting in an influence on integrity. Factors related to the social exchange influence trust in other ways as interpersonal relationships have been found to influence the age difference. Finally, the age difference does influence individuals and relational factors due to the expectations of young managers being perceived as strengthening trust with their subordinates.

    Our thesis has contributed to the theory of trust by gaining a deeper knowledge of the influence of age difference on trust between managers and their subordinates. Also we have opened up new areas for research concerning the influence of age difference on trust in other industries or reversed situations. Our thesis has provided management scholars and managers with a deeper understanding of trust in manager-subordinate relationships, providing young managers with theories on how to improve their relationships with their older subordinates.