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  • Bradby, Hannah
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Sociology.
    Placebo, participation and surgery2017Other (Other (popular science, discussion, etc.))
    Abstract [en]

    A therapeutic effect that cannot be attributed to an active ingredient of medication is termed ‘placebo’. The ‘placebo effect’ is far from a neutral description of the effect of ‘inert drugs’, being associated with the quackery and deception of sugar pills and snake oil. For example, upon launching a current consultation on prescribed items, NHS England’s chief executive described homeopathy as “at best a placebo and a misuse of scarce NHS funds”. Therapy harnessing the placebo effect is described as a waste of money. But given the relative cheapness of homeopathy and the ubiquity of the placebo effect, the opposite might be true and it could represent money well spent.

  • Public defence: 2017-09-29 09:15 B/B22, Uppsala
    Martijn, Joran
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Exploration of microbial diversity and evolution through cultivation independent phylogenomics2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Our understanding of microbial evolution is largely dependent on available genomic data of diverse organisms. Yet, genome-sequencing efforts have mostly ignored the diverse uncultivable majority in favor of cultivable and sociologically relevant organisms. In this thesis, I have applied and developed cultivation independent methods to explore microbial diversity and obtain genomic data in an unbiased manner. The obtained genomes were then used to study the evolution of mitochondria, Rickettsiales and Haloarchaea.

    Metagenomic binning of oceanic samples recovered draft genomes for thirteen novel Alphaproteobacteria-related lineages. Phylogenomics analyses utilizing the improved taxon sample suggested that mitochondria are not related to Rickettsiales but rather evolved from a proteobacterial lineage closely related to all sampled alphaproteobacteria.

    Single-cell genomics and metagenomics of lake and oceanic samples, respectively, identified previously unobserved Rickettsiales-related lineages. They branched early relative to characterized Rickettsiales and encoded flagellar genes, a feature once thought absent in this order. Flagella are most likely an ancestral feature, and were independently lost during Rickettsiales diversification. In addition, preliminary analyses suggest that ATP/ADP translocase, the marker for energy parasitism, was acquired after the acquisition of type IV secretion systems during the emergence of the Rickettsiales.

    Further exploration of the oceanic samples yielded the first draft genomes of Marine Group IV archaea, the closest known relatives of the Haloarchaea. The halophilic and generally aerobic Haloarchaea are thought to have evolved from an anaerobic methanogenic ancestor. The MG-IV genomes allowed us to study this enigmatic evolutionary transition. Preliminary ancestral reconstruction analyses suggest a gradual loss of methanogenesis and adaptation to an aerobic lifestyle, respectively.

    The thesis further presents a new amplicon sequencing method that captures near full-length 16S and 23S rRNA genes of environmental prokaryotes. The method exploits PacBio's long read technology and the frequent proximity of these genes in prokaryotic genomes. Compared to traditional partial 16S amplicon sequencing, our method classifies environmental lineages that are distantly related to reference taxa more confidently.

    In conclusion, this thesis provides new insights into the origins of mitochondria, Rickettsiales and Haloarchaea and illustrates the power of cultivation independent methods with respect to the study of microbial evolution.

    List of papers
    1. Single-cell genomics of a rare environmental alphaproteobacterium provides unique insights into Rickettsiaceae evolution
    Open this publication in new window or tab >>Single-cell genomics of a rare environmental alphaproteobacterium provides unique insights into Rickettsiaceae evolution
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    2015 (English)In: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 9, no 11, 2373-2385 p.Article in journal (Refereed) Published
    Abstract [en]

    The bacterial family Rickettsiaceae includes a group of well-known etiological agents of many human and vertebrate diseases, including epidemic typhus-causing pathogen Rickettsia prowazekii. Owing to their medical relevance, rickettsiae have attracted a great deal of attention and their host-pathogen interactions have been thoroughly investigated. All known members display obligate intracellular lifestyles, and the best-studied genera, Rickettsia and Orientia, include species that are hosted by terrestrial arthropods. Their obligate intracellular lifestyle and host adaptation is reflected in the small size of their genomes, a general feature shared with all other families of the Rickettsiales. Yet, despite that the Rickettsiaceae and other Rickettsiales families have been extensively studied for decades, many details of the origin and evolution of their obligate host-association remain elusive. Here we report the discovery and single-cell sequencing of 'Candidatus Arcanobacter lacustris', a rare environmental alphaproteobacterium that was sampled from Damariscotta Lake that represents a deeply rooting sister lineage of the Rickettsiaceae. Intriguingly, phylogenomic and comparative analysis of the partial 'Candidatus Arcanobacter lacustris' genome revealed the presence chemotaxis genes and vertically inherited flagellar genes, a novelty in sequenced Rickettsiaceae, as well as several host-associated features. This finding suggests that the ancestor of the Rickettsiaceae might have had a facultative intracellular lifestyle. Our study underlines the efficacy of single-cell genomics for studying microbial diversity and evolution in general, and for rare microbial cells in particular.

    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-267117 (URN)10.1038/ismej.2015.46 (DOI)000365091700005 ()25848874 (PubMedID)
    Funder
    Swedish Research Council, 621-2009-4813Swedish Research Council, 621-2011-4669EU, European Research Council, 310039-PUZZLE_CELLEU, European Research Council, 281633-EvoChlamy
    Available from: 2015-11-18 Created: 2015-11-18 Last updated: 2017-08-08Bibliographically approved
    2. Deep mitochondrial origin outside the sampled alphaproteobacteria
    Open this publication in new window or tab >>Deep mitochondrial origin outside the sampled alphaproteobacteria
    Show others...
    (English)Article in journal (Refereed) Submitted
    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-327305 (URN)
    Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2017-08-16
    3. Amplicon sequencing of the 16S-ITS-23S rRNA operon with long-read technology for improved phylogenetic classification of uncultured prokaryotes
    Open this publication in new window or tab >>Amplicon sequencing of the 16S-ITS-23S rRNA operon with long-read technology for improved phylogenetic classification of uncultured prokaryotes
    (English)Manuscript (preprint) (Other academic)
    National Category
    Evolutionary Biology Microbiology
    Identifiers
    urn:nbn:se:uu:diva-327307 (URN)
    Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2017-08-08
    4. First genomes of Marine Group IV archaea enlighten the evolutionary origins of Haloarchaea
    Open this publication in new window or tab >>First genomes of Marine Group IV archaea enlighten the evolutionary origins of Haloarchaea
    (English)Manuscript (preprint) (Other academic)
    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-327308 (URN)
    Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2017-08-08
    5. Deeply branching alphaproteobacteria illuminate early Rickettsiales evolution
    Open this publication in new window or tab >>Deeply branching alphaproteobacteria illuminate early Rickettsiales evolution
    (English)Manuscript (preprint) (Other academic)
    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-327309 (URN)
    Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2017-08-08
  • Deshapriya, J. D. P.
    et al.
    Univ Paris Diderot, UPMC Univ Paris 06, CNRS, Observ Paris,LESIA, 5 Pl J Janssen, F-92195 Meudon, France..
    Barucci, M. A.
    Univ Paris Diderot, UPMC Univ Paris 06, CNRS, Observ Paris,LESIA, 5 Pl J Janssen, F-92195 Meudon, France..
    Fornasier, S.
    Univ Paris Diderot, UPMC Univ Paris 06, CNRS, Observ Paris,LESIA, 5 Pl J Janssen, F-92195 Meudon, France..
    Feller, C.
    Univ Paris Diderot, UPMC Univ Paris 06, CNRS, Observ Paris,LESIA, 5 Pl J Janssen, F-92195 Meudon, France..
    Hasselmann, P. H.
    Univ Paris Diderot, UPMC Univ Paris 06, CNRS, Observ Paris,LESIA, 5 Pl J Janssen, F-92195 Meudon, France..
    Sierks, H.
    Max Planck Inst Sonnensyst Forsch, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    El-Maarry, M. R.
    Univ Bern, Phys Inst, Sidlerstr 5, CH-3012 Bern, Switzerland..
    Pajola, M.
    NASA, Ames Res Ctr, Moffett Field, CA 94035 USA..
    Barbieri, C.
    Univ Padua, Dept Phys & Astron G Galilei, Vic Osservatorio 3, I-35122 Padua, Italy..
    Lamy, P. L.
    CNRS, UMR 7326, Lab Astrophys Marseille, F-13388 Marseille 13, France.;Aix Marseille Univ, F-13388 Marseille 13, France..
    Rodrigo, R.
    CSIC, INTA, Ctr Astrobiol, E-28850 Madrid, Spain.;Int Space Sci Inst, Hallerstr 6, CH-3012 Bern, Switzerland..
    Koschny, D.
    European Space Agcy, Res & Sci Support Dept, NL-2201 Noordwijk, Netherlands..
    Rickman, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Theoretical Astrophysics. PAS Space Reserch Ctr, Poland.
    Agarwal, J.
    Max Planck Inst Sonnensyst Forsch, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    A'Hearn, M. F.
    Univ Maryland, Dept Astron, College Pk, MD 20742 USA..
    Bertaux, J. -L
    Bertini, I.
    Univ Padua, Dept Phys & Astron G Galilei, Vic Osservatorio 3, I-35122 Padua, Italy..
    Boudreault, S.
    Max Planck Inst Sonnensyst Forsch, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Cremonese, G.
    INAF, Osservatorio Astron Padova, Vicolo Osservatorio 5, I-35122 Padua, Italy..
    Da Deppo, V.
    CNR, IFN UOS Padova LUXOR, Via Trasea 7, I-35131 Padua, Italy..
    Davidsson, B. J. R.
    JPL, 4800 Oak Grove Dr, Pasadena, CA 91109 USA..
    Debei, S.
    Univ Padua, Dept Mech Engn, Via Venezia 1, I-35131 Padua, Italy..
    Deller, J.
    Max Planck Inst Sonnensyst Forsch, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    De Cecco, M.
    Univ Trento, UNITN, Via Mesiano 77, I-38100 Trento, Italy..
    Fulle, M.
    INAF, Osservatorio Astron Trieste, Via Tiepolo 11, I-34143 Trieste, Italy..
    Gicquel, A.
    Max Planck Inst Sonnensyst Forsch, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Groussin, O.
    CNRS, UMR 7326, Lab Astrophys Marseille, F-13388 Marseille 13, France.;Aix Marseille Univ, F-13388 Marseille 13, France..
    Gutierrez, P. J.
    CSIC, Inst Astrofis Andalucia, E-18080 Granada, Spain..
    Guettler, C.
    Max Planck Inst Sonnensyst Forsch, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Hofmann, M.
    Max Planck Inst Sonnensyst Forsch, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Hviid, S. F.
    DLR, Inst Planetary Res, Rutherfordstr 2, D-12489 Berlin, Germany..
    Ip, W.
    Natl Cent Univ, Inst Space Sci, Chungli 32054, Taiwan..
    Jorda, L.
    CNRS, UMR 7326, Lab Astrophys Marseille, F-13388 Marseille 13, France.;Aix Marseille Univ, F-13388 Marseille 13, France..
    Keller, H. U.
    TU Braunschweig, Inst Geophys & Extraterr Phys, D-38106 Braunschweig, Germany..
    Knollenberg, J.
    DLR, Inst Planetary Res, Rutherfordstr 2, D-12489 Berlin, Germany..
    Kramm, R.
    Max Planck Inst Sonnensyst Forsch, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Kuehrt, E.
    DLR, Inst Planetary Res, Rutherfordstr 2, D-12489 Berlin, Germany..
    Kueppers, M.
    ESA, ESAC, POB 78, E-28691 Villanueva De La Canada, Spain..
    Lara, L.
    CSIC, Inst Astrofis Andalucia, E-18080 Granada, Spain..
    Lazzarin, M.
    Univ Padua, Dept Phys & Astron G Galilei, Vic Osservatorio 3, I-35122 Padua, Italy..
    Lopez Moreno, J. J.
    CSIC, Inst Astrofis Andalucia, E-18080 Granada, Spain..
    Marzari, F.
    Univ Padua, Dept Phys & Astron G Galilei, Vic Osservatorio 3, I-35122 Padua, Italy..
    Mottola, S.
    DLR, Inst Planetary Res, Rutherfordstr 2, D-12489 Berlin, Germany..
    Naletto, G.
    CNR, IFN UOS Padova LUXOR, Via Trasea 7, I-35131 Padua, Italy.;Univ Padua, Dept Informat Engn, Via Gradenigo 6, I-35131 Padua, Italy.;Univ Padua, Ctr Studies & Act Space CISAS G Colombo, Via Venezia 15, I-35131 Padua, Italy..
    Oklay, N.
    Max Planck Inst Sonnensyst Forsch, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Perna, D.
    Univ Paris Diderot, UPMC Univ Paris 06, CNRS, Observ Paris,LESIA, 5 Pl J Janssen, F-92195 Meudon, France..
    Pommerol, A.
    Univ Bern, Phys Inst, Sidlerstr 5, CH-3012 Bern, Switzerland..
    Thomas, N.
    Univ Bern, Phys Inst, Sidlerstr 5, CH-3012 Bern, Switzerland..
    Tubiana, C.
    Max Planck Inst Sonnensyst Forsch, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Vincent, J. -B
    Spectrophotometry of the Khonsu region on the comet 67P/Churyumov-Gerasimenko using OSIRIS instrument images2016In: Monthly notices of the Royal Astronomical Society, ISSN 0035-8711, E-ISSN 1365-2966, Vol. 462, S274-S286 p.Article in journal (Refereed)
    Abstract [en]

    Our work focuses on the spectrophotometric analysis of selected terrain and bright patches in the Khonsu region on the comet 67P/Churyumov-Gerasimenko. Despite the variety of geological features, their spectrophotometric properties appear to indicate a similar composition. It is noticeable that the smooth areas in Khonsu possess similar spectrophotometric behaviour to some other regions of the comet. We observed bright patches on Khonsu with an estimation of >40 per cent of normal albedo and suggest that they are associated with H2O ice. One of the studied bright patches has been observed to exist on the surface for more than 5 months without a major decay of its size, implying the existence of potential sub-surface icy layers. Its location may be correlated with a cometary outburst during the perihelion passage of the comet in 2015 August, and we interpret it to have triggered the surface modifications necessary to unearth the stratified icy layers beneath the surface. A boulder analysis on Khonsu leads to a power-law index of -3.1 + 0.2/-0.3 suggesting a boulder formation, shaped by varying geological processes for different morphological units.

  • Giacomini, L.
    et al.
    Univ Padua, Dipartimento Geosci, Via G Gradenigo 6, I-35131 Padua, Italy..
    Massironi, M.
    Univ Padua, Dipartimento Geosci, Via G Gradenigo 6, I-35131 Padua, Italy..
    El-Maarry, M. R.
    Univ Bern, Phys Inst, Sidlerstr 5, CH-3012 Bern, Switzerland..
    Penasa, L.
    Univ Padua, Ctr Studies & Act Space CISAS G Colombo, Via Venezia 15, I-35131 Padua, Italy..
    Pajola, M.
    NASA Ames Res Ctr, Moffett Field, CA 94035 USA..
    Thomas, N.
    Univ Bern, Phys Inst, Sidlerstr 5, CH-3012 Bern, Switzerland..
    Lowry, S. C.
    Univ Kent, Sch Phys Sci, Canterbury CT2 7NZ, Kent, England..
    Barbieri, C.
    Univ Padua, Dipartimento Fis & Astron G Galilei, Vic Osservatorio 3, I-35122 Padua, Italy..
    Cremonese, G.
    INAF Osservatorio Astron Padova, Vic Osservatorio 5, I-35122 Padua, Italy..
    Ferri, F.
    Univ Padua, Ctr Studies & Act Space CISAS G Colombo, Via Venezia 15, I-35131 Padua, Italy..
    Naletto, G.
    Univ Padua, Dept Informat Engn, Via Gradenigo 6-B, I-35131 Padua, Italy..
    Bertini, I.
    Univ Padua, Ctr Studies & Act Space CISAS G Colombo, Via Venezia 15, I-35131 Padua, Italy..
    La Forgia, F.
    Univ Padua, Dipartimento Fis & Astron G Galilei, Vic Osservatorio 3, I-35122 Padua, Italy..
    Lazzarin, M.
    Univ Padua, Dipartimento Fis & Astron G Galilei, Vic Osservatorio 3, I-35122 Padua, Italy..
    Marzari, F.
    Univ Padua, Dipartimento Fis & Astron G Galilei, Vic Osservatorio 3, I-35122 Padua, Italy..
    Sierks, H.
    Max Planck Inst Sonnensyst Forschung, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Lamy, P. L.
    CNRS, UMR 7236, Lab Astrophys Marseille, 38 Rue Frederic Joliot Curie, F-13388 Marseille 13, France.;Aix Marseille Univ, 38 Rue Frederic Joliot Curie, F-13388 Marseille 13, France..
    Rodrigo, R.
    CSIC INTA, Ctr Astrobiol, E-28850 Madrid, Spain.;Int Space Sci Inst, Hallerstr 6, CH-3012 Bern, Switzerland..
    Rickman, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Theoretical Astrophysics. PAS Space Res Ctr, Poland.
    Koschny, D.
    European Space Res & Technol Ctr ESA, Sci Support Off, Keplerlaan 1,Postbus 299, NL-2201 AZ Noordwijk, Netherlands..
    Keller, H. U.
    TU Braunschweig, Inst Geophys & Extraterr Phys, D-38106 Braunschweig, Germany..
    Agarwal, J.
    Max Planck Inst Sonnensyst Forschung, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    A'Hearn, M. F.
    Univ Maryland, Dept Astron, College Pk, MD 20742 USA..
    Auger, A. -T
    Barucci, M. A.
    Univ Paris Diderot, Univ Paris 06, UPMC, LESIA Observ Paris,CNRS, 5 Pl J Janssen, F-92195 Meudon, France..
    Bertaux, J. -L
    Besse, S.
    European Space Res & Technol Ctr ESA, Sci Support Off, Keplerlaan 1,Postbus 299, NL-2201 AZ Noordwijk, Netherlands..
    Bodewits, D.
    Univ Maryland, Dept Astron, College Pk, MD 20742 USA..
    Da Deppo, V.
    CNR IFN UOS Padova LUXOR, Via Trasea 7, I-35131 Padua, Italy..
    Davidsson, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Theoretical Astrophysics.
    De Cecco, M.
    Univ Trento, Via Sommar 9, I-38123 Trento, Italy..
    Debei, S.
    Univ Padua, Dept Ind Engn, Via Venezia 1, I-35131 Padua, Italy..
    Fornasier, S.
    Univ Paris Diderot, Univ Paris 06, UPMC, LESIA Observ Paris,CNRS, 5 Pl J Janssen, F-92195 Meudon, France.;Univ Paris Diderot, Sorbonne Paris Cite, 4 Rue Elsa Morante, F-75205 Paris 13, France..
    Fulle, M.
    INAF Osservatorio Astron Trieste, Via Tiepolo 11, I-34014 Trieste, Italy..
    Groussin, O.
    CNRS, UMR 7236, Lab Astrophys Marseille, 38 Rue Frederic Joliot Curie, F-13388 Marseille 13, France.;Aix Marseille Univ, 38 Rue Frederic Joliot Curie, F-13388 Marseille 13, France..
    Gutierrez, P. J.
    Inst Astrofis Andalucia CSIC, E-18008 Granada, Spain..
    Guettler, C.
    Max Planck Inst Sonnensyst Forschung, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Hviid, S. F.
    Inst Planeten Forsch, Deutsch Zentrum Luft & Raumfahrt, Rutherfordstr 2, D-12489 Berlin, Germany..
    Ip, W. -H
    Jorda, L.
    CNRS, UMR 7236, Lab Astrophys Marseille, 38 Rue Frederic Joliot Curie, F-13388 Marseille 13, France.;Aix Marseille Univ, 38 Rue Frederic Joliot Curie, F-13388 Marseille 13, France..
    Knollenberg, J.
    Inst Planeten Forsch, Deutsch Zentrum Luft & Raumfahrt, Rutherfordstr 2, D-12489 Berlin, Germany..
    Kovacs, G.
    Max Planck Inst Sonnensyst Forschung, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Kramm, J. -R
    Kuehrt, E.
    Inst Planeten Forsch, Deutsch Zentrum Luft & Raumfahrt, Rutherfordstr 2, D-12489 Berlin, Germany..
    Kuppers, M.
    European Space Astron Ctr ESA, Operat Dept, POB 78, E-28691 Madrid, Spain..
    Lara, L. M.
    Inst Astrofis Andalucia CSIC, E-18008 Granada, Spain..
    Lopez Moreno, J. J.
    Inst Astrofis Andalucia CSIC, E-18008 Granada, Spain..
    Magrin, S.
    Univ Padua, Dipartimento Fis & Astron G Galilei, Vic Osservatorio 3, I-35122 Padua, Italy..
    Michalik, H.
    TU Braunschweig, Inst Datentech & Kommunikat Netze, Hans Sommer Str 66, D-38106 Braunschweig, Germany..
    Oklay, N.
    Max Planck Inst Sonnensyst Forschung, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Pommerol, A.
    Univ Bern, Phys Inst, Sidlerstr 5, CH-3012 Bern, Switzerland..
    Preusker, F.
    Inst Planeten Forsch, Deutsch Zentrum Luft & Raumfahrt, Rutherfordstr 2, D-12489 Berlin, Germany..
    Scholten, F.
    Inst Planeten Forsch, Deutsch Zentrum Luft & Raumfahrt, Rutherfordstr 2, D-12489 Berlin, Germany..
    Tubiana, C.
    Max Planck Inst Sonnensyst Forschung, Justus von Liebig Weg 3, D-37077 Gottingen, Germany..
    Vincent, J. -B
    Geologic mapping of the Comet 67P/Churyumov-Gerasimenko's Northern hemisphere2016In: Monthly notices of the Royal Astronomical Society, ISSN 0035-8711, E-ISSN 1365-2966, Vol. 462, S352-S369 p.Article in journal (Refereed)
    Abstract [en]

    The Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS), the scientific imaging system onboard the Rosetta mission, has been acquiring images of the nucleus of the comet 67P/Churyumov-Gerasimenko since 2014 August with a resolution which allows a detailed analysis of its surface. Indeed, data reveal a complex surface morphology which is likely the expression of different processes which occurred at different times on the cometary nucleus. In order to characterize these different morphologies and better understand their distribution, we performed a geologic mapping of comet's 67P Northern hemisphere in which features have been distinguished based on their morphological, textural and stratigraphic characteristics. For this purpose, we used narrow-angle camera images acquired in 2014 August and September with a spatial scale ranging from 1.2 to 2.4 m pixel(-1). Several different geologic units have been identified on the basis of their different surface textures, granulometry and morphology. Some of these units are distinctive and localized, whereas others are more common and distributed all over the Northern hemisphere. Moreover, different types of linear features have been distinguished on the basis of their morphology. Some of these lineaments have never been observed before on a comet and can offer important clues on the internal structures of the nucleus itself. The geologic mapping results presented here will allow us to better understand the processes which affected the nucleus' surface and thus the origin and evolutionary history of comet 67P/Churyumov-Gerasimenko.

  • Public defence: 2017-09-29 09:15 A1:111a, Uppsala
    Dyakova, Olga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology. Flinders University.
    The processing of natural images in the visual system2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Any image can be described in terms of its statistics (i.e. quantitative parameters calculated from the image, for example RMS-contrast, the skewness of image brightness distribution, and slope constant of an average amplitude spectrum).

    It was previously shown that insect and vertebrate visual systems are optimised to the statistics common among natural scenes. However, the exact mechanisms of this process are still unclear and need further investigation.

    This thesis presents the results of examining links between some image statistics and visual responses in humans and hoverflies.

    It was found that while image statistics do not play the main role when hoverflies (Eristalis tenax and Episyrphus balteatus) chose what flowers to feed on, there is a link between hoverfly (Episyrphus balteatus) active behaviours and image statistics. There is a significant difference in the slope constant of the average amplitude spectrum, RMS contrast and skewness of brightness distribution between photos of areas where hoverflies were hovering or flying. These photos were also used to create a prediction model of hoverfly behaviour. After model validation, it was concluded that photos of both the ground and the surround should be used for best prediction of behaviour. The best predictor was skewness of image brightness distribution.

    By using a trackball setup, the optomotor response in walking hoverflies (Eristalis tenax) was found to be influenced by the slope constant of an average amplitude spectrum. 

    Intracellular recording showed that the higher-order neuron cSIFE (The centrifugal stationary inhibited flicker excited) in the hoverfly (Eristalis tenax) lobula plate was inhibited by a range of natural scenes and that this inhibition was strongest in a response to visual stimuli with the slope constant of an average amplitude spectrum of 1, which is the typical value for natural environments. 

    Based on the results of psychophysics study in human subjects it was found that sleep deprivation affects human perception of naturalistic slope constants differently for different image categories (“food” and “real world scenes”).

    These results help provide a better understanding of the link between visual processes and the spatial statistics of natural scenes.

    List of papers
    1. In situ modeling of multimodal floral cues attracting wild pollinators across environments
    Open this publication in new window or tab >>In situ modeling of multimodal floral cues attracting wild pollinators across environments
    Show others...
    (English)In: Article in journal (Refereed) Submitted
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-328029 (URN)
    Available from: 2017-08-16 Created: 2017-08-16 Last updated: 2017-08-16
    2. Predicting unconstrained field flight behaviour from image statistics
    Open this publication in new window or tab >>Predicting unconstrained field flight behaviour from image statistics
    (English)In: Article in journal (Refereed) Submitted
    National Category
    Bioinformatics (Computational Biology)
    Identifiers
    urn:nbn:se:uu:diva-328030 (URN)
    Available from: 2017-08-16 Created: 2017-08-16 Last updated: 2017-08-16
    3. A higher order visual neuron tuned to the spatial amplitude spectra of natural scenes
    Open this publication in new window or tab >>A higher order visual neuron tuned to the spatial amplitude spectra of natural scenes
    Show others...
    2015 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, 8522Article in journal (Refereed) Published
    Abstract [en]

    Animal sensory systems are optimally adapted to those features typically encountered in natural surrounds, thus allowing neurons with limited bandwidth to encode challengingly large input ranges. Natural scenes are not random, and peripheral visual systems in vertebrates and insects have evolved to respond efficiently to their typical spatial statistics. The mammalian visual cortex is also tuned to natural spatial statistics, but less is known about coding in higher order neurons in insects. To redress this we here record intracellularly from a higher order visual neuron in the hoverfly. We show that the cSIFE neuron, which is inhibited by stationary images, is maximally inhibited when the slope constant of the amplitude spectrum is close to the mean in natural scenes. The behavioural optomotor response is also strongest to images with naturalistic image statistics. Our results thus reveal a close coupling between the inherent statistics of natural scenes and higher order visual processing in insects.

    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:uu:diva-264173 (URN)10.1038/ncomms9522 (DOI)000364930800007 ()26439748 (PubMedID)
    Funder
    Swedish Research Council, 2012-4740
    Note

    Supplementary information available for this article at http://www.nature.com/ncomms/2015/151006/ncomms9522/suppinfo/ncomms9522_S1.html

    Available from: 2015-10-06 Created: 2015-10-06 Last updated: 2017-08-16Bibliographically approved
    4. Sleep deprivation changes our perception of naturalness
    Open this publication in new window or tab >>Sleep deprivation changes our perception of naturalness
    Show others...
    (English)In: Article in journal (Refereed) Submitted
    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:uu:diva-328031 (URN)
    Available from: 2017-08-16 Created: 2017-08-16 Last updated: 2017-08-16
  • Public defence: 2017-09-29 13:00 Hedstrandsalen, Uppsala
    von Seth, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Oxygen delivery and mitochondrial dysfunction as assessed by microdialysis during interventions in experimental sepsis2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Early administration of broad-spectrum antibiotics is the first goal in sepsis treatment. Besides from bacteriostatic/bactericidal effects, some antibiotics may also modify the host´s response to infection. The novel antibiotic tigecycline may exert such properties; however, this property has not been evaluated in large-animal trials. We compared tigecycline with doxycycline and placebo in relation to anti-inflammatory, circulatory and organ dysfunction effects in a sterile pig model of sepsis. Doxycycline, but not tigecycline, reduced the inflammatory response as manifested by tumor necrosis factor alpha levels in plasma. Tigecycline, however, had a stabilizing effect on the circulation not exerted by doxycycline or placebo.

    To achieve rapid restoration of the circulating blood volume - another major goal in sepsis treatment - fluid bolus administration of is some-times practiced. In addition to crystalloids, albumin-containing solutions are suggested. Yet, some animal-experimental data suggests that rapid bolus administration of albumin reduces albumin’s plasma-expanding effect. We compared a rapid intravenous bolus of radiolabeled albumin with a slow infusion in a sterile pig model of sepsis. Rapid bolus of administration did not reduce plasma levels of albumin following administration and did not increase the amount of albumin that left the circulation.

    Inadequate oxygen delivery (DO2) by the circulation to the tissues may cause increased plasma lactate, which is the most striking effect of sepsis on the metabolism. However, experimental data and clinical trials refute this link, instead, suggesting other mechanisms, including impaired oxygen extraction, mitochondrial dysfunction and accelerated aerobic glycolysis. We investigated the impact of DO2, oxygen consumption (VO2), hemodynamic parameters and inflammatory response on plasma lactate and organ dysfunction in two experimental sepsis models. In the most severe cases of shock, with DO2, there was an increase in plasma lactate, but without a decrease in VO2, invalidating the assumption that the increase in lactate is due to anaerobic metabolism.

    To identify critical steps in the sepsis-induced increase in lactate, we inhibited the major energy-producing step in the electron transport chain (ETC). The combination of sepsis and ETC inhibition led to a cellular energy crisis. This finding suggests that early sepsis induces a partial mitochondrial dysfunction.

    List of papers
    1. Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia: a Prospective, Randomized and Placebo Controlled Trial
    Open this publication in new window or tab >>Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia: a Prospective, Randomized and Placebo Controlled Trial
    Show others...
    2015 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 43, no 6, 604-611 p.Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Antibiotics might, apart from an antimicrobial effect, also exert anti-inflammatory effects. The novel antibiotic tigecycline, potentially useful in septic shock from Gram-negative multi-resistant bacteria, is structurally related to antibiotics with known anti-inflammatory properties. However, its anti-inflammatory effects have previously not been explored in vivo. Using a sterile integrative porcine sepsis model, we investigated the anti-inflammatory and circulatory effects of tigecycline in comparison to doxycycline and placebo.

    METHODS: Eighteen pigs were randomized to receive tigecycline 100 mg, doxycycline 200 mg or placebo and subjected to 6 h endotoxin infusion at 0.5 μg x kg x h. Markers of inflammation, nitric oxide (NO) production, vascular permeability, hemodynamics, organ dysfunction, tissue metabolism and acid-base parameters were monitored.

    RESULTS: Peak plasma tumor necrosis alpha (TNF-α) was lower in the doxycycline group (P=0.031) but not in the tigecycline group (P=0.86) compared to placebo with geometric mean plasma concentrations of 16, 79 and 63 ng x ml, respectively. Mean arterial pressure was higher 4-6 h in the tigecycline group with values at 6 h of 107± 9 mmHg compared to the placebo and doxycycline groups (85 ± 27 mmHg and 90 ± 32 mmHg, respectively) (P=0.025). The white blood cell and the neutrophil granulocyte counts were less reduced in the doxycycline group, but not in the tigecycline group at 4-6 h (P=0.009 and p=0.019, respectively). Other markers of inflammation, organ dysfunction, tissue metabolism and acid-base parameters were unaffected by tigecycline.

    CONCLUSIONS: Consistent with known anti-inflammatory properties, doxycycline yielded decreased TNF-α levels. Tigecycline did not affect cytokine levels but counteracted hypotension and hypoperfusion.

    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-244766 (URN)10.1097/SHK.0000000000000351 (DOI)000354734300013 ()25664982 (PubMedID)
    Available from: 2015-02-20 Created: 2015-02-20 Last updated: 2017-08-13Bibliographically approved
    2. Rapid Bolus Administration Does Not Increase the Extravasation Rate of Albumin: A Randomized Controlled Trial in the Endotoxemic Pig
    Open this publication in new window or tab >>Rapid Bolus Administration Does Not Increase the Extravasation Rate of Albumin: A Randomized Controlled Trial in the Endotoxemic Pig
    Show others...
    2017 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 47, no 4, 514-519 p.Article in journal (Refereed) Published
    Abstract [en]

    Some experimental data suggest that rapid bolus administration of albumin causes less plasma-expanding effects than slow, continuous infusion. To determine whether rapid bolus administration, in comparison with slow infusion, results in greater extravasation of albumin in experimental septic shock we performed a randomized controlled trial with 32 endotoxemic pigs. The animals were monitored and ventilated with standard intensive care equipment and given 10 mL x kg 5% albumin labeled with Technetium-99m, either as a rapid 15-minute bolus (Bolus group, n = 16) or as a 2-hour (h) infusion (Infusion group, n = 16). Radioactivity was monitored in plasma, extracellular microdialysate and urine for 6 h. Physiological parameters were monitored hourly. Radioactivity in the liver, spleen, kidney and lung was analyzed post-mortem.The plasma area under the curve (AUC) activity0-6h was 4.4 ± 0.9 x 10 in the Bolus group and 4.4 ± 1.1 x 10 counts x min x mL x h in the Infusion group. Blood hemoglobin levels increased in both groups, suggesting severe capillary leakage. Yet, there were no group differences in albumin radioactivity in plasma, muscle tissue, urine or in the post-mortem analysis of the organs. Following albumin administration, circulatory and respiratory parameters were similar in the two groups.In conclusion, the present results suggest that albumin might be given as a bolus without leading to increased extravasation of albumin, in contrast to previous animal experiments in rodents.

    Keyword
    Albumin, animal models, capillary leak syndrome, endotoxin, fluid resuscitation, sepsis
    National Category
    Infectious Medicine Hematology Surgery
    Identifiers
    urn:nbn:se:uu:diva-305826 (URN)10.1097/SHK.0000000000000761 (DOI)000396226300016 ()27749758 (PubMedID)
    Available from: 2016-10-23 Created: 2016-10-22 Last updated: 2017-08-13Bibliographically approved
    3. The role of oxygen delivery and inflammatory response on plasma lactate and organ dysfunction in experimental septic shock
    Open this publication in new window or tab >>The role of oxygen delivery and inflammatory response on plasma lactate and organ dysfunction in experimental septic shock
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Elevated plasma lactate and organ dysfunction in septic shock may be due to insufficient oxygen delivery (DO2). However, other mechanisms, as mitochondrial dysfunction or adrenergic glycolysis may contribute to elevated lactate. We conducted a retrospective cohort analysis of 104 pigs in bacteremic and endotoxemic shock to investigate the impact of DO2, oxygen consumption (VO2), hemodynamics and inflammatory response on elevation in plasma lactate, tissue metabolism and organ dysfunction in experimental bacteremic and endotoxemic shock.

    Experimental septic shock was induced by continuous infusion of live bacteria and endotoxin for 6 hours (h). Hemodynamic parameters and DO2 were measured with pulmonary artery catheters and oximetry. Lactate, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were analyzed in plasma. Muscle metabolism was investigated with microdialysis. At 3 h, DO2 was 289±68 mL x min-1 x m-2 (mean±SD) and plasma lactate levels were 2.9±1.2 mmol x L-1. Elevated plasma lactate was dependent on DO2, but only at DO2 levels <250 mL x min-1 x m-2. Despite increased plasma lactate and decreased DO2, no decrease in VO2 was seen. Muscle pyruvate levels increased and lactate-to-pyruvate ratio decreased. Urinary output, but not static lung compliance, was DO2-dependent. In a multiple regression model DO2, mean arterial pressure and IL-6 were the strongest predictors of increased plasma lactate. Urinary output, but not static lung compliance, was DO2-dependent.

    In muscle accelerated glycolysis contributes to increased lactate. In addition, inflammatory response, manifested as plasma IL-6 but not as TNF-a, was associated with an elevation in plasma lactate levels. 

    National Category
    Anesthesiology and Intensive Care
    Research subject
    Anaesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-326784 (URN)
    Available from: 2017-08-12 Created: 2017-08-12 Last updated: 2017-08-13
    4. Mitochondrial stress in early experimental sepsis revealed by electron transport chain inhibition
    Open this publication in new window or tab >>Mitochondrial stress in early experimental sepsis revealed by electron transport chain inhibition
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Increased plasma lactate in sepsis may not be due to insufficient oxygen

    delivery, but accelerated glycolysis and mitochondrial dysfunction may also contribute. To

    assess critical pathophysiological steps in non-ischemic lactate increase we studied the muscle metabolism with microdialysis in a sepsis model in pigs submitted to continuous E. coli infusion (sepsis group, n=12) for 3 hours (h). A control group (sham group, n=4) underwent the same procedures but did not receive E. coli. Protocolized interventions were applied to normalize oxygen delivery (DO2) and blood pressure. Metabolism was intervened locally via microdialysis catheters with the electron-transport chain inhibitor sodium cyanide and the inhibitor of the major energy consuming enzyme Na+/K+-ATPase ouabain.

    Results: All pigs in the sepsis group had positive blood cultures at 1 h. Median (range) Sequential Organ Failure Assessment (SOFA) score at 0 h was 0 (0-1) in both groups. At 3 h, SOFA increased to 6 (3-6) in the sepsis group but remained virtually unchanged in the sham group. Plasma lactate increased in the sepsis group despite that protocolized interventions maintained DO2.

    Sepsis accelerated glycolysis with a decrease in glucose, maintained or increased in lactate and pyruvate with a virtually normal lactate-to-pyruvate ratio (LPR) in microdialysate from catheters without intervention. The local cyanide intervention produced a severe energy crisis as evidenced by a dramatically elevated LPR, a lowered pyruvate and an increased lactate in both the sepsis and sham group. During sepsis, when the cyanide effect gradually diminished, this energy crisis normalized in the sham group but partly persisted in the sepsis group.

    Conclusions: Our findings suggest a reduction in mitochondrial oxidative capacity induced by sepsis, as revealed by cyanide inhibition. Decreasing energy consumption with a local ouabain intervention did not impact glucose and fat metabolism in sepsis or sham animals.

    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-327928 (URN)
    Available from: 2017-08-12 Created: 2017-08-12 Last updated: 2017-08-13
  • Golubitskiy, Yevgeniy
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Peace and Conflict Research.
    The Enemy of My Enemy is My Friend: The Role of Common Enemies in Post-Civil War Superordinate Identity Formation2017Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    This paper contributes to the literature on post-conflict identity in exploring the question: which conditions favor the success of superordinate identity formation among former conflict parties in post-civil war societies? Building on the social psychological literature on terror management theory (TMT) and optimal distinctiveness theory (ODT), it argues that the presence of a common enemy among former conflict parties increases the likelihood of successful superordinate identity formation. An in-depth qualitative comparative study on national identity in Bosnia and Herzegovina (BiH) after the 1992-1995 civil war and Lebanon after the 1975-1990 civil war is conducted in order to test the theoretical arguments of this paper. The empirical findings lend preliminary support to this hypothesis, yet also point to limits in the study’s theoretical framework, including the instability of an identity predicated upon a common enemy which may not exist in the future. This paper also identifies two alternative explanations to account for the outcomes observed in the two cases, including differences in the nature of the conflicts and the different ways consociationalism has been implemented in the two countries.

  • Public defence: 2017-09-29 10:00 Föreläsningssalen, Falu lasarett, Falun
    Carlsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Healthcare and patient factors affecting sick leave: From a primary health care perspective2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: For indeterminate reasons, there have been major variations in sick leave in Sweden, and many physicians have perceived sick leave assignments as burdensome.

    Aim: To gain more knowledge and understanding, from a perspective of primary health care, about factors in health care and patients that affect sick leave. Thereby help patients in the best way, facilitate the work of physicians and other health professionals involved in the rehabilitation process, and use the health care resources optimally.

    Methods: This thesis is based on a randomised controlled trial (RCT) in a primary health care centre with participants on short-term sick leave, due to pain and/or mental illness, who received a multidisciplinary assessment. Qualitative focus-group discussions with physicians in primary health care centres. A cohort of women on very long-term sick leave due to pain and/or mental illness, who lost sickness benefits due to a new time limit on sickness insurance, were randomised to multidisciplinary assessment and multimodal intervention (TEAM), or to Acceptance and Commitment Therapy (ACT). In an extended cohort, including some men on very long-term sick leave due to pain and/or mental illness, the importance of the motivation for return to work (RTW) was investigated.

    Results. Very early multidisciplinary assessment increased days on sick leave in the first three month period. Physicians at primary health care centres perceived sick leave assignments as burdensome, but clearer rules and cooperation with other professionals have made sick leave assignments less burdensome. TEAM intervention resulted in an increase in working hours per week as well as an increase in work-related engagements, compared to control in the RCT. Motivation for RTW was associated with RTW or increased employability in the rehabilitation of patients

    Conclusions: Continued studies are needed to find those who are at risk of long-term sick leave, the time when rehabilitation efforts should be started, and the content of rehabilitation. Collaboration in teams facilitates sick leave assignments for physicians at primary care health centres. Motivation for RTW might be a factor of importance for the effect of rehabilitation and needs to be studied further.

    List of papers
    1. Early multidisciplinary assessment was associated with longer periods of sick leave: A randomized controlled trial in a primary health care centre
    Open this publication in new window or tab >>Early multidisciplinary assessment was associated with longer periods of sick leave: A randomized controlled trial in a primary health care centre
    2013 (English)In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 31, no 3, 141-146 p.Article in journal (Refereed) Published
    Abstract [en]

    Objective

    To study the effects on sick leave from an early multidisciplinary assessment at a primary health care centre. Design. Randomized controlled trial.

    Setting

    Patients who saw GPs at a primary health care centre in mid-Sweden and asked for a sickness certificate for psychiatric or musculoskeletal diagnoses were invited to participate. Patients included were sick-listed for less than four weeks; 33 patients were randomized either to an assessment within a week by a physiotherapist, a psychotherapist, and an occupational therapist or to "standard care". The therapists used methods and tools they normally use in their clinical work.

    Main outcome measure

    Proportion of patients still sick-listed three months after randomization, total and net days on sick leave, and proportion who were on part-time sick leave.

    Results

    At follow-up after three months, in contrast to the pre-trial hypothesis, there was a trend toward a higher proportion of patients still sick-listed in the intervention group (7/18) as compared with the control group (3/15). The intervention group also had significantly longer sick-listing periods (mean 58 days) than the control group (mean 36 days) (p = 0.038). The proportion of patients who were part time sick-listed was significantly higher in the intervention group (10/18) than in the control group (2/15) (p = 0.027).

    Conclusions

    In this study an early multidisciplinary assessment was associated with longer periods on sick leave and more individuals on part-time sick leave.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-205930 (URN)10.3109/02813432.2013.811943 (DOI)000323243900005 ()23909930 (PubMedID)
    Available from: 2013-08-26 Created: 2013-08-26 Last updated: 2017-08-17Bibliographically approved
    2. General practitioners' perceptions of working with the certification of sickness absences following changes in the Swedish social security system: a qualitative focus-group study
    Open this publication in new window or tab >>General practitioners' perceptions of working with the certification of sickness absences following changes in the Swedish social security system: a qualitative focus-group study
    2015 (English)In: BMC Family Practice, ISSN 1471-2296, E-ISSN 1471-2296, Vol. 16, 21Article in journal (Refereed) Published
    Abstract [en]

    Background: Many physicians in Sweden, as well as in other countries, find the matter of certification of sickness absence (COSA) particularly burdensome. The issuing of COSAs has also been perceived as a work-environment problem among physicians. Among general practitioners (GPs) are the highest proportion of physicians in Sweden who experience difficulties with COSA. Swedish authorities have created several initiatives, by changing the social security system, to improve the rehabilitation of people who are ill and decrease the number of days of sick leave used. The aim of this study was to describe how GPs in Sweden perceive their work with COSA after these changes. Methods: A descriptive design with a qualitative, inductive focus-group discussion (FGD) approach was used. Results: Four categories emerged from the analysis of FGDs with GPs in Sweden: 1) Physicians' difficulties in their professional role; 2) Collaboration with other professionals facilitates the COSA; 3) Physicians' approach in relation to the patient; 4) An easier COSA process. Conclusions: Swedish GPs still perceived COSA to be a burdensome task. However, system changes in recent years have facilitated work related to COSA. Cooperation with other professionals on COSA was perceived positively.

    Keyword
    General practitioners, Primary health care, Focus group discussions, Sick leave, Certification of sickness absence, Social security system
    National Category
    Other Medical Sciences
    Identifiers
    urn:nbn:se:uu:diva-248186 (URN)10.1186/s12875-015-0238-5 (DOI)000350069200001 ()
    Available from: 2015-04-12 Created: 2015-03-30 Last updated: 2017-08-17Bibliographically approved
    3. Effectiveness of two vocational rehabilitation programmes in women with long-term sick leave due to pain syndrome or mental illness: 1-year follow-up of a randomized controlled trial
    Open this publication in new window or tab >>Effectiveness of two vocational rehabilitation programmes in women with long-term sick leave due to pain syndrome or mental illness: 1-year follow-up of a randomized controlled trial
    2017 (English)In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 49, no 2, 170-177 p.Article in journal (Refereed) Published
    Abstract [en]

    Objective: Mental illness and chronic pain are common reasons for long-term sick leave, typically more so for women. This study investigated the effects on return to work of 2 vocational rehabilitation programmes. Methods: In this randomized controlled study, 308 women were allocated to treatment with acceptance and commitment therapy, to multidisciplinary assessment and individualized rehabilitation interventions, or to a control group. Return-to-work at 12 months was assessed as: (i) returning to health insurance; (ii) number of reimbursed health insurance days during follow-up; (iii) self-reported change in working hours; (iv) a composite measure of self-reported change in work-related engagement. Results: The mean age of the Swedish study population was 48.5 years (standard deviation (SD) 6.3 years) and the mean time on sick leave 7.5 years (SD 3.2 years). There were no significant differences in reimbursed days or returning to the health insurance at 12 months. The multidisciplinary assessment and individualized rehabilitation interventions group, compared with control, reported a significant increase in working hours per week, as well as a significant increase in work-related engagement. Conclusion: Multidisciplinary assessments and individual rehabilitation interventions may improve the chance of return-to-work in women with long-term sick leave due to pain condition or mental illness.

    Keyword
    return to work, vocational rehabilitation, multidisciplinary rehabilitation, acceptance and commitment therapy, chronic pain
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-317212 (URN)10.2340/1651977-2188 (DOI)28101560 (PubMedID)
    Available from: 2017-03-11 Created: 2017-03-11 Last updated: 2017-08-08Bibliographically approved
    4. Motivation for return to work and actual return to work among people on long-term sick leave due to pain syndrome or mental health conditions
    Open this publication in new window or tab >>Motivation for return to work and actual return to work among people on long-term sick leave due to pain syndrome or mental health conditions
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keyword
    Sick leave, motivation, return to work, sickness insurance, insurance medicine, public employment service, self-determination theory
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Research subject
    Family Medicine
    Identifiers
    urn:nbn:se:uu:diva-327288 (URN)
    Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2017-08-17Bibliographically approved
  • Public defence: 2017-10-07 13:15 Brusewitzsalen (sal 3312), Uppsala
    Friedner Parrat, Charlotta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Government.
    Change, Institutions, and International Organisations: Essays on the English School of International Relations2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall topic of this thesis is the English School understanding of international order, which I approach specifically by analysing the English School idea of international institutions and their change. The purpose is to develop the theory in a meta-theoretically conscious and coherent way. The three essays in this volume are independent in relation to each other, yet in some ways cumulative. Essays I and II aim to address primarily the question of how to conceptualise the current international order of multilateralism and international organisations. Essay I uses the empirical issue of UN reform to formulate one English School conceptualisation of international order, building specifically on the School’s central theme of international institutions. Essay II theoretically develops the tools of the English School for capturing how international institutions, according to English School theory the fundaments of international order, might change. Essay III approaches the meta-theoretical question of how change itself is understood in the English School, and how different theoretical readings of what we might mean by change give rise to different approaches to the normative question of what might be improvement in the international order. I argue that an internally coherent understanding of change in international society should emphasise change in institutions, made intelligible by ex-post narratives which contribute to establishing the discursive connection between practices and their normative legitimation, and guided by a sustained normative debate on the nature of improvement. This understanding of change signifies a much-needed addition to the English School toolbox, and brings a promise of a meta-theoretical grounding of the theory. In addition, it opens for similar theoretical inquiries into other IR theories.

    List of papers
    1. International Organization in International Society: UN Reform from an English School Perspective
    Open this publication in new window or tab >>International Organization in International Society: UN Reform from an English School Perspective
    2014 (English)In: Journal of International Organization Studies, ISSN 2191-2556, E-ISSN 2191-2564, Vol. 5, no 2, 7-22 p.Article in journal (Refereed) Published
    Place, publisher, year, edition, pages
    Berlin: UN Studies Association, 2014
    Keyword
    international relations, English School theory, United Nations, UN reform
    National Category
    Political Science (excluding Public Administration Studies and Globalization Studies)
    Research subject
    Political Science
    Identifiers
    urn:nbn:se:uu:diva-237089 (URN)
    Available from: 2014-11-26 Created: 2014-11-26 Last updated: 2017-08-14
    2. On the Evolution of Primary Institutions of International Society
    Open this publication in new window or tab >>On the Evolution of Primary Institutions of International Society
    (English)In: International Studies Quarterly, ISSN 0020-8833, E-ISSN 1468-2478Article in journal (Refereed) In press
    Abstract [en]

    English School theorists argue that primary institutions uphold order in international society. However, they disagree about what those primary institutions are. Moreover, comparatively little research tackles the links between primary institutions and secondary ones, embodied in international organizations. Yet, these different levels of international institutions contribute in specific ways to change and stability in international affairs. I argue that primary institutions should be understood as practice-based and continuously discursively constructed. This opens up the possibility to show how international organizations, although created by states, can themselves shape primary institutions. I illustrate my argument with examples from the UN Security Council. There are manifest tensions in the Security Council between the evolving primary institution of great power management, and the “frozen” secondary institution of membership rules, leading to the lock-in of the primary institution. Moreover, this type of tension between institutions, rather than stability and harmony among them, should be acknowledged as the normal state of affairs in international society.

    Keyword
    international relations, English School theory, international society, primary insitutions
    National Category
    Political Science (excluding Public Administration Studies and Globalization Studies)
    Research subject
    Political Science
    Identifiers
    urn:nbn:se:uu:diva-327968 (URN)
    Available from: 2017-08-14 Created: 2017-08-14 Last updated: 2017-08-14
    3. Change in International Society: How not to Recreate the 'First Debate' of International Relations
    Open this publication in new window or tab >>Change in International Society: How not to Recreate the 'First Debate' of International Relations
    (English)In: European Journal of International Relations, ISSN 1354-0661, E-ISSN 1460-3713Article in journal (Refereed) Submitted
    Abstract [en]

    The English School of International Relations is remarkably unclear on how to conceptualise change in between the idealist belief in progress and the Realist eternal cycles of recurrence in international affairs. This article seeks avoid this dead end by questioning the School’s understanding of change as a commonsensical concept, either taken for granted or treated as trivial. It is argued that change would be better understood as composed of three facets: one ontological (what is change?), one explanatory (what causes change?), and one normative (is change desirable?). This reconceptualization of change permits cross-checking the three facets against each other for internal coherence, but most importantly, it makes visible the underlying assumptions used to study change, so that history, causation and normative preferences can be openly scrutinized, questioned and defended rather than treated as self-evident. The resulting suggestion of an internally coherent understanding of change in international society as change in institutions, made intelligible by ex-post narratives which contribute to the discursive connection between practices and the norms, beliefs and expectations which make them institutions, and guided by a sustained normative debate on the nature of improvement, signifies a much-needed addition to the English School tool-kit. It brings a promise of a significant meta-theoretical overhaul of the theory, which, if taken up, will open up new horizons for the School. In addition, it opens for similar theoretical inquiries into other IR theories.

    Keyword
    international relations, English School, meta-theory, international society, international order, social facts
    National Category
    Political Science (excluding Public Administration Studies and Globalization Studies)
    Research subject
    Political Science
    Identifiers
    urn:nbn:se:uu:diva-327969 (URN)
    Available from: 2017-08-14 Created: 2017-08-14 Last updated: 2017-08-14
  • Evers, Markus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Administrativa sanktioner mot ledande befattningshavare i kreditinstitut: Särskilt om personligt ansvar för kreditinstituts överträdelser2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Lindahl, Linnea
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Tredjemanspantsättares regressrätt2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Ulfvensjö, Marcus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Paketering av fastigheter: Förfarandets framtid i ljuset av SOU 2017:272017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    År 2003 infördes lagstiftning som innebar att beskattningen av kapitalvinster på näringsbetingade andelar avskaffades. Syftet med lagstiftningen var att eliminera den principiellt felaktiga kedjebeskattningen av vinster i bolagssektorn som tidigare regler gav upphov till och att åtgärda den faktiska asymmetri som uppkommit genom internationell skatteplanering. Redan i och med de förarbeten som föranledde avskaffandet förutsågs att detta kunde leda till att dyrbarare tillgångar som producerats inom en koncern skulle komma att paketeras. En paketering går i princip till på så sätt att ett företag i en koncern inledningsvis avyttrar den ifrågavarande tillgången till ett dotterföretag. Överlåtelsen ska då enligt reglerna om underprisöverlåtelser behandlas som om tillgången avyttrats mot en ersättning motsvarande dess skattemässiga värde. Därefter säljs andelarna i dotterföretaget externt, dvs. till en aktör utanför koncernförhållandet, till marknadsvärdet. Andelarna är i normalfallet att anse som näringsbetingade, och då avyttrande av sådana inte är skattpliktigt sker sålunda ingen kapitalvinstbeskattning, vilket skulle ha varit fallet vid en direktförsäljning. Det ansågs dock inte motiverat att införa generella regler som motverkade detta.

    På grund av långa avskrivningstider för byggnader får förpackningar av just fastigheter stor ekonomisk betydelse, och för att säkerställa att skattereglerna inte särskilt gynnar vissa branscher eller vissa företag inom samma bransch har det ansetts motiverat att utreda de samhällsekonomiska effekterna av paketering. Mot bakgrund av detta beslutade regeringen den 11 juni 2015 att tillsätta en särskild utredare med uppdrag att se över vissa frågor inom fastighets- och stämpelskatteområdet. Betänkandet redovisades i mars 2017 genom SOU 2017:27, och omfattande lagändringar på området kom härigenom att föreslås.

    I denna uppsats ämnar jag framför allt se över de i utredningen framlagda förslagen, och uppsatsens huvudsakliga syfte är att bedöma om förändringarna utgör en lämplig utveckling på området.

  • Public defence: 2017-09-29 10:15 Hörsal 2, Uppsala
    Andersson, Josefine
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics.
    Insurances against job loss and disability: Private and public interventions and their effects on job search and labor supply2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Essay I: Employment Security Agreements, which are elements of Swedish collective agreements, offer a unique opportunity to study very early job search counselling of displaced workers. These agreements provide individual job search assistance to workers who are dismissed due to redundancy, often as early as during the period of notice. Compared to traditional labor market policies, the assistance provided is earlier and more responsive to the needs of the individual worker. In this study, I investigate the effects of the individual counseling and job search assistance provided through the Employment Security Agreement for Swedish blue-collar workers on job finding and subsequent job quality. The empirical strategy is based on the rules of eligibility in a regression discontinuity framework. I estimate the effect for workers with short tenure, who are dismissed through mass-layoffs. My results do not suggest that the program has an effect on the probability of becoming unemployed, the duration of unemployment, or income. However, the results indicate that the program has a positive effect on the duration of the next job.

    Essay II: The well-known positive relationship between the unemployment benefit level and unemployment duration can be separated into two potential sources; a moral hazard effect, and a liquidity effect pertaining to the increased ability to smooth consumption. The latter is a socially optimal response due to credit and insurance market failures. These two effects are difficult to separate empirically, but the social optimality of an unemployment insurance policy can be evaluated by studying the effect of a non-distortionary lump-sum severance grant on unemployment durations. In this study, I evaluate the effects on unemployment duration and subsequent job quality of a lump-sum severance grant provided to displaced workers, by means of a Swedish collective agreement. I use a regression discontinuity design, based on the strict age requirement to be eligible for the grant. I find that the lump-sum grant has a positive effect on the probability of becoming unemployed and the length of the completed unemployment duration, but no effect on subsequent job quality. My analysis also indicates that spousal income is important for the consumption smoothing abilities of displaced workers, and that the grant may have a greater effect in times of more favorable labor market conditions.

    Essay III: Evidence from around the world suggest that individuals who are awarded disability benefits in some cases still have residual working capacity, while disability insurance systems typically involve strong disincentives for benefit recipients to work. Some countries have introduced policies to incentivize disability insurance recipients to use their residual working capacities on the labor market. One such policy is the continuous deduction program in Sweden, introduced in 2009. In this study, I investigate whether the financial incentives provided by this program induce disability insurance recipients to increase their labor supply or education level. Retroactively determined eligibility to the program with respect to time of benefit award provides a setting resembling a natural experiment, which could be used to estimate the effects of the program using a regression discontinuity design. However, a simultaneous regime change of disability insurance eligibility causes covariate differences between treated and controls, which I adjust for using a matching strategy. My results suggest that the financial incentives provided by the program have not had any effect on labor supply or educational attainment.

  • Wänglund, Adam
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics, Byggteknik.
    Eriksson, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics, Byggteknik.
    UTVECKLING AV PROJEKTERINGSANVISNINGAR: En utredning rörande hur projekteringsanvisningar bör utformas2017Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In the process of erecting a building, the precursory design and planning stage is of paramount importance. The foremost managing tool during this stage constitutes of the design guidelines, established by the developer. This report contains a study of how to model said guidelines to achieve a more effective way of working, without compromising the final product, produced at the request of Swedish housing developer Småa AB. The study is based on a series of interviews, where persons involved in the design and planning stage have been asked to share their experiences and opinions about the process and how it affects the end result. The study is based on a series of interviews, where persons involved in the planning and design stage have been asked to share their experiences and opinions regarding the development process and how it affects the end result. During the processing of the collected material, three distinct subject areas emerged; the importance of clear design guidelines, what the design guidelines should cover and how to ensure the quality of the product. Based on these subject areas, the authors have devised a set of recommendations to ensure an effective working method and the quality of the end result.

  • Randahl, Karin
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Business Studies.
    Belcheva, Tanya
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Business Studies.
    Collaboration Towards a ‘Sustainability Transition’: A Case study of the Agri-food sector on Gotland, Sweden2017Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In Sustainable development studies, it has been established that food sector has a significantimpact on the environment and accordingly is a critical area for improvement. In addition,island regions particularly undergo a need for long-term sustainable development, due toisolation and high dependency on availability of local resources. Therefore, applyingsustainability into practise and incorporating its goals into strategic and operational levels ofmanagement decision-making, could use relatively more attention to proceed in thedevelopment. This study is looking at current work by regional authorities on the Swedishisland of Gotland in implementing sustainability transitions in the agri-food sector byscrutinising the industry actors’ involvement and attitudes. The research data was collectedvia analysis of governmental document and in-depth interviews with both industry andauthorities’ representatives and further evaluated with theories of governance, leadership andsustainability transitions. Yet, sustainability is such a complex issue interlinking economic,social and environmental aspects, so it requires more attention than initially perceived. Theresult indicates collaboration towards common goals benefits from trust and congruencebetween actors.

  • Public defence: 2017-09-30 09:15 Gunnesalen, Uppsala
    Edvinsson, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Attention Deficit/Hyperactivity Disorder in Adults: Prevalence, Psychiatric Comorbidities and Long-term Outcome2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Attention Deficit/Hyperactivity Disorder (ADHD) was originally thought to occur only in children, but is increasingly recognised as causing functional impairment also in adulthood. The overall aim of this thesis was to achieve a comprehensive understanding of ADHD in adulthood.

    A questionnaire based on the DSM-IV criteria of ADHD, reported childhood symptoms, reading and spelling problems, difficulties and suffering and general assessment of functioning (GAF) was distributed to three samples: the general population (GP), outpatient psychiatry (OPP) and female prison inmates. Symptoms consistent with ADHD were more than three times higher in the OPP sample than in the GP sample (6.6 versus 2.1%). ADHD symptoms and related problems occurred in 50% of the prison inmates.

    A cohort of 168 patients diagnosed with ADHD in adulthood was interviewed about current ADHD symptoms and psychiatric comorbidity on axis I and II. The lifetime prevalence of psychiatric comorbidity on axis I was 92% and current comorbidity, including autism spectrum disorders and Tourette’s syndrome, was 47%. The sex-specific pattern of the comorbid disor-ders was similar to that in the general population. Forty-six per cent of the patients endorsed the specific criteria for at least one personality disorder.

    After a mean follow-up of six years, there was remission of adult ADHD in about 30% of the patients, regardless of whether there was ongoing medication or not. There were no differences in function and quality of life, except for global general improvement, which was better in patients currently on medication.

    The most prevalent long-term side effects of pharmacological treatment with mainly stimulants were decreased appetite, dry mouth, anxiousness/restlessness and an increase in pulse frequency. The discontinuation rate was about 50%: 29% discontinued because of a perceived lack of effect, followed by elevated mood or hypomania (11%). No detectable evidence of tolerance and increased need for dosage over time was observed.

    To conclude, Symptoms of ADHD is highly overrepresented in OPP and in female inmates compared with the GP. Furthermore, adults diagnosed with ADHD have a high lifetime prevalence of psychiatric comorbidity. Long-term pharmacological treatment with stimulants is safe with relatively mild and tolerable adverse effects. Continued medication, however, is not related to remission.

    List of papers
    1. ADHD-related symptoms among adults in out-patient psychiatry and female prison inmates as compared with the general population
    Open this publication in new window or tab >>ADHD-related symptoms among adults in out-patient psychiatry and female prison inmates as compared with the general population
    2010 (English)In: Uppsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 1, 30-40 p.Article in journal (Refereed) Published
    Abstract [en]

    Objective. To compare the prevalence of symptoms consistent with attention deficit hyperactivity disorder (ADHD) and related problems in adults in the general population, out-patient psychiatry (where females are in majority), and female convicts. Method. A questionnaire based on the DSM-IV criteria of ADHD, reported childhood symptoms, reading and spelling problems, difficulties and suffering, and general assessment of functioning (GAF) was distributed to samples of the general population, open care psychiatry, and female prison inmates. Completed questionnaires were received from 517/1000, 349/400, and 50/65 of the three samples, respectively. Results. Symptoms consistent with ADHD were more than three times higher in out-patient psychiatry than in the general population (6.6% versus 2.1%), with a male-to-female ratio of 1.6-1.7. The severity of symptoms and frequencies of associated disabilities were similar in men and women. ADHD symptoms and related problems occurred in 50% of the female prisoners, which is similar to male prisoners according to the literature. Conclusion. The high prevalence of symptoms and disabilities of ADHD in women should lead to awareness of the disorder in both sexes and be addressed in terms of diagnostic work-up, treatment, and rehabilitation.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-136943 (URN)10.3109/03009730903532333 (DOI)000275061700005 ()20085506 (PubMedID)
    Available from: 2010-12-15 Created: 2010-12-14 Last updated: 2017-09-07Bibliographically approved
    2. Gender differences of axis I and II comorbidity in subjects diagnosed with attention-deficit hyperactivity disorder as adults
    Open this publication in new window or tab >>Gender differences of axis I and II comorbidity in subjects diagnosed with attention-deficit hyperactivity disorder as adults
    Show others...
    2013 (English)In: Acta Neuropsychiatrica, ISSN 0924-2708, E-ISSN 1601-5215, Vol. 25, no 3, 165-174 p.Article in journal (Refereed) Published
    Abstract [en]

    Objective: To investigate gender differences in psychiatric comorbidity patients diagnosed with attention-deficit hyperactivity disorder (ADHD) as adults. Methods: Interviews about current ADHD symptoms and psychiatric comorbidity on axis I and II (Structured Clinical Interview for DSM-IV axis I and axis II) were conducted in a clinical cohort of 168 patients (78 women, 90 men). Independent information on childhood and current symptoms was collected from parents, partners and patient files. Results: The lifetime prevalence of psychiatric comorbidity on axis I reached 92%, and current comorbidity, including autism spectrum disorders and Tourette's syndrome, was 47%. Women had a higher lifetime prevalence of mood and eating disorders compared with men, where substance-use disorders were more frequent. Ten per cent of patients fulfilled diagnostic criteria for a personality disorder. When excluding the general diagnostic criteria, 46% of the patients endorsed the specific criteria for at least one personality disorder. Gender differences were identified with predominance of histrionic personality traits in women and conduct disorder in men. Conclusion: Patients diagnosed with ADHD as adults display an extremely high lifetime axis I comorbidity with a gender-specific pattern similar to the general population. No gender differences were identified with regard to personality disorders; however, an increased prevalence of deviant personality traits was confirmed. This study stresses the importance of evaluating comorbidity among patients diagnosed with ADHD as adults to secure optimal treatment.

    Keyword
    ADHD, adults, comorbidity, gender
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-204118 (URN)10.1111/j.1601-5215.2012.00682.x (DOI)000320550800006 ()
    Available from: 2013-07-22 Created: 2013-07-22 Last updated: 2017-09-07Bibliographically approved
    3. Six-Year Outcome in Subjects Diagnosed with Attention-Deficit/Hyperactivity Disorder as Adults
    Open this publication in new window or tab >>Six-Year Outcome in Subjects Diagnosed with Attention-Deficit/Hyperactivity Disorder as Adults
    (English)In: Article in journal (Other academic) Submitted
    National Category
    Medical and Health Sciences Psychiatry
    Identifiers
    urn:nbn:se:uu:diva-327890 (URN)
    Available from: 2017-08-11 Created: 2017-08-11 Last updated: 2017-09-07
    4. Long-Term Tolerability and Safety of Pharmacological Treatment of Adult Attention-Deficit/Hyperactivity Disorder
    Open this publication in new window or tab >>Long-Term Tolerability and Safety of Pharmacological Treatment of Adult Attention-Deficit/Hyperactivity Disorder
    (English)In: Article in journal (Other academic) Submitted
    National Category
    Psychiatry
    Identifiers
    urn:nbn:se:uu:diva-327891 (URN)
    Available from: 2017-08-11 Created: 2017-08-11 Last updated: 2017-09-07
  • Public defence: 2017-09-28 09:15 Rosénsalen, Uppsala
    Pallangyo, Eunice
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    "If really we are committed things can change starting from us providers" Improving postpartum care: A facilitation intervention at government-owned health institutions in a low-resource suburb in Dar es Salaam, Tanzania2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Globally, postpartum care is a neglected area in the continuum of maternal and newborn services. Facilitation interventions focusing on addressing local problems report positive results in improving the health of mothers and newborns in low-resource settings. 

    The aim of this thesis was to investigate a facilitation intervention to improve postpartum care at government-owned health institutions in a low-resource suburb of Dar es Salaam, Tanzania. A before-and-after study design was used to describe and evaluate the intervention in this thesis. Data were collected using mixed methods in the intervention group and the control group, before and after the intervention and were used for making comparisons.  

    The baseline studies showed that postpartum care practices were next to non-existent at the institutions, that most healthcare providers had high levels of knowledge, positive attitudes towards postpartum care and declared themselves ready to engage in its improvement. Mothers coming with their newborns for immunisation were satisfied with the services. 

    The intervention to improve postpartum care involved healthcare providers in six geographical clusters, each including 3–6 institutions, with one facilitator for each cluster. Using a participatory approach, they facilitated colleagues in identifying and addressing the provision of postpartum care at institutions. Data were collected among healthcare providers, facilitators and mothers using: focus group discussions; questionnaires; observations; and interviews, and by making field notes, written at each institution. 

    In the intervention, facilitators and healthcare providers used four strategies to improve postpartum care:increasing awareness and knowledge on postpartum care of healthcare providers and mothers; mobilising professional and material resources; improving care routines, communication and documentation; and promoting an empowering and collaborative work style. 

    The endline evaluation showed that postpartum care was conducted in the intervention group with some care items performed for 80% of observed mothers. The quality grading, which involved nine experts and was based on national guidelines, showed that none of the healthcare providers reached the level of good quality of care. In the comparison group, postpartum care continued to be next to non-existent. The healthcare providers’ knowledge increased in both groups but to a higher extent in the intervention group. The t-test indicated a significant difference in knowledge between the intervention and comparison groups and between before and after the intervention in both groups. The difference in differences for knowledge was 1.3. The attitudes showed no major difference between baseline and endline in the intervention and comparison groups. 

    This facilitation intervention was an acceptable and applicable approach and indicates promising results in improving the quality of postpartum care and in increasing mothers’ attendance.

    List of papers
    1. A baseline mixed methods study on postpartum care among health professionals in Tanzania
    Open this publication in new window or tab >>A baseline mixed methods study on postpartum care among health professionals in Tanzania
    2017 (English)In: African Journal of Midwifery and Women's Health, ISSN 1759-7374, Vol. 11, no 3, 115-122 p.Article in journal (Refereed) Published
    Abstract [en]

    Background: Globally, postpartum care (PPC) is a neglected part of maternal and neonatal health, despite 50% of maternal deaths occuring in the first weeks after childbirth.

    Aim: The study aimed to assess knowledge, attitudes and practices among providers of PPC in government institutions in two low-resource suburbs of Dar es Salaam: Ilala and Temeke.

    Methods: Health professionals ( n =149) at all levels of care completed a knowledge and attitudes questionnaire. A checklist was used to observe 25 health professionals at reproductive and child health units, and 38 mothers were interviewed on exit. χ 2 - and logistic regression tests were used to analyse the outcomes. Field notes were analysed qualitatively.

    Findings: Overall, 64% of health professionals had high knowledge and most had positive attitudes towards PPC. Level of education was found to be positively associated with positive attitudes towards PPC (OR=2.5 CI 95% 1.03–6.13). PPC consultations with mothers and newborns during the first week after childbirth were found to be few or nonexistent. Mothers who came with newborns for BCG immunisation were mostly satisfied with the services.

    Conclusion: Quality improvement is required at the structure and process levels of the health system in order to provide holistic PPC consultations.

    Keyword
    Postpartum care, knowledge, Practice, Tanzania
    National Category
    Health Sciences Obstetrics, Gynecology and Reproductive Medicine
    Identifiers
    urn:nbn:se:uu:diva-327324 (URN)
    Available from: 2017-08-09 Created: 2017-08-09 Last updated: 2017-08-11Bibliographically approved
    2. "If really we are committed things can change, starting from us": Healthcare providers' perceptions of postpartum care and its potential for improvement in low-income suburbs in Dar es Salaam, Tanzania
    Open this publication in new window or tab >>"If really we are committed things can change, starting from us": Healthcare providers' perceptions of postpartum care and its potential for improvement in low-income suburbs in Dar es Salaam, Tanzania
    Show others...
    2017 (English)In: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 11, 7-12 p.Article in journal (Refereed) Published
    Abstract [en]

    Objective

    To explore healthcare providers' perceptions of the current postpartum care (PPC) practice and its potential for improvement at governmental health institutions in low-resource suburbs in Dar es Salaam, Tanzania.

    Design

    Qualitative design, using focus group discussions (8) and qualitative content analysis.

    Setting

    Healthcare institutions (8) at three levels of governmental healthcare in Ilala and Temeke suburbs, Dar es Salaam.

    Participants

    Registered, enrolled and trained nurse-midwives (42); and medical and clinical officers (13).

    Results

    The healthcare providers perceived that PPC was suboptimal and that they could have prevented maternal deaths. PPC was fragmented at understaffed institutions, lacked guidelines and was organized in a top-down structure of leadership. The participants called for improvement of: organization of space, time, resources, communication and referral system; providers' knowledge; and supervision and feedback. Their motivation to enhance PPC quality was high.

    Key conclusions

    The HCP awareness of the suboptimal quality of PPC, its potential for promoting health and their willingness to engage in improving care are promising for the implementation of interventions to improve quality of care. Provision of guidelines, sensitization of providers to innovate and maximize utilization of existing resources, and supportive supervision and feedback are likely to contribute to the sustainability of any improvement.

    Keyword
    Focus group, HCP, Postpartum care, Quality of care, Tanzania
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology Obstetrics, Gynecology and Reproductive Medicine
    Identifiers
    urn:nbn:se:uu:diva-319552 (URN)10.1016/j.srhc.2016.09.001 (DOI)000394066700002 ()28159132 (PubMedID)
    Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2017-08-11Bibliographically approved
    3. Implementation of a facilitation intervention to improve postpartum care in a low resource suburb in Dar es Salaam, Tanzania
    Open this publication in new window or tab >>Implementation of a facilitation intervention to improve postpartum care in a low resource suburb in Dar es Salaam, Tanzania
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keyword
    Intervention, facilitation, knowledge translation, quality of care
    National Category
    Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-327348 (URN)
    Available from: 2017-08-09 Created: 2017-08-09 Last updated: 2017-08-11
    4. Improved postpartum care after a participatory facilitation intervention in Dar es Salaam, Tanzania: a mixed method evaluation
    Open this publication in new window or tab >>Improved postpartum care after a participatory facilitation intervention in Dar es Salaam, Tanzania: a mixed method evaluation
    Show others...
    2017 (English)In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 10, no 1, 1295697Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    In order to improve the health and survival of mothers/newborns, the quality and attendance rates of postpartum care (PPC) must be increased, particularly in low-resource settings.

    OBJECTIVE:

    To describe outcomes of a collegial facilitation intervention to improve PPC in government-owned health institutions in a low-resource suburb in Dar es Salaam, Tanzania.

    METHODS:

    A before-and-after evaluation of an intervention and comparison group was conducted using mixed methods (focus group discussions, questionnaires, observations, interviews, and field-notes) at health institutions. Maternal and child health aiders, enrolled nurse midwives, registered nurse midwives, and medical and clinical officers participated. A collegial facilitation intervention was conducted and healthcare providers were organized in teams to improve PPC at their workplaces. Facilitators defined areas of improvement with colleagues and met regularly with a supervisor for support.

    RESULTS:

    The number of mothers visiting the institution for PPC increased in the intervention group. Some care actions were noted in more than 80% of the observations and mothers reported high satisfaction with care. In the comparison group, PPC continued to be next to non-existent. The healthcare providers' knowledge increased in both groups but was higher in the intervention group. The t-test showed a significant difference in knowledge between the intervention and comparison groups and between before and after the intervention in both groups. The difference of differences for knowledge was 1.3. The providers perceived the intervention outcomes to include growing professional confidence/knowledge, improved PPC quality, and mothers' positive response. The quality grading was based on the national guidelines and involved nine experts and showed that none of the providers reached the level of good quality of care.

    CONCLUSIONS:

    The participatory facilitation intervention contributed to improved quality of PPC, healthcare providers' knowledge and professional confidence, awareness of PPC among mothers, and increased PPC attendance.

    Keyword
    Healthcare providers, Tanzania, facilitation, postpartum care, quality
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-322208 (URN)10.1080/16549716.2017.1295697 (DOI)000401284900001 ()28498737 (PubMedID)
    Available from: 2017-05-17 Created: 2017-05-17 Last updated: 2017-08-11Bibliographically approved
  • Engervall, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    A method to empirically investigatedesign manipulations2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Marketplaces, similar to conventional e-commerce websites, rely on conversions asprimary source of income. Conversions are visitors turned into customers, anda condition for this to happen is that visitors stay on the marketplace and interactwith its content. A visitor that does not interact at all is considered a bouncedvisitor and is added to a metric called bounce rate. Plick requested a concretemethod for executing a design experiment on their website where multiple designmanipulations could be run in parallel and record data individually. During the thesis,said method was built and an experiment was executed with four uniquedesign manipulations that were developed by combining two factors, compactness andvendor credibility. These factors were found through a theoretical analysisbased on human visual functioning and emotional design. The experiment showedpotential for both the theory and the method, but no statistically significantdifferences between the implemented design manipulations were found. The furtheruse of this method is discussed as well as how to achieve a statisticallysignificant result.

  • Gillgren, Andreas
    Analysis of spatial subdomains in the Generalized Weighted Residual Method: Optimization of the distribution of spatial subdomains in one spatial dimension2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The Generalized Weighted Residual Method (GWRM) is a recently developed time- spectral method for parabolic or hyperbolic initial-value partial differential equations. In this paper, spatial subdomains, used in this method, are analyzed. Subdomains are used to enhance efficiency by dividing entire domains into smaller parts that can be independently solved for and then combined to get the final solution.

    An automatic grid mapping algorithm for spatial subdomains, called "Compressive Method", is presented and applied to Burgers' viscous equation. The error of the solution, as compared to the analytic solution, is compared for this compressive Method and the uniform grid case. Results show that accuracy can be gained at a small extra cost, using this compressive Method. Conclusions are that this adaptive algorithm shows great potential for further development. 

  • Bengtsson, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Nykvist, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Ljung, Alvin
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Internet of Things: Uppkopplade sensorer med Raspberry Pi2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    I detta projekt, som gjorts på uppdrag av IoT Sverige, har en produkt skapats åt derasDemorum för att visa hur Internet of Things fungerar och vad man kan använda dettill. Rapporten beskriver hur arbetet har utformats fram till den färdiga produktensom, utifrån deras önskemål, består av en koldioxid- och en rörelsesensor koppladetill en enkortsdator. Med hjälp av kodade skript skickas den insamlade datan till enserver placerad på ett så kallat moln. I grafer på en hemsida kan man därefter se datan illustrativt och det enda man då behöver är en dator med internetuppkoppling.

  • Ottosson, Alexander
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Cinderella and the Snow Queen: Advancing the Protection Against Discrimination in the ECHR2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Sjöö, Henrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Obehörig vinst som rättsgrund: Ett cirkelresonemang möjligt att ta sig runt?2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    En undersökning av det juridiska institutet obehörig vinst och dess eventuella användning som rättsgrund i svensk rätt.

    Mot bakgrund av att obehörig vinst i delar av doktrinen på senare tid föreslagits såsom rättsgrundande faktum i ett antal HD-avgöranden undersöks denna praxis. Främst behandlas situationer av obehöriga nyttjanden av annans egendom samt misstagsbetalningar. Även komparativa inslag förekommer.

  • Lager, Julius
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Fördelningen av anskaffningsvärdet vid förvärv av byggnad med tomträtt2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Uppsatsen utreder hur fördelningen av anskaffningsvärdet bör ske när byggnad förvärvas tillsammans med tomträtt. 

  • Gülözen, Tülin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Visselblåsarlagens förhållande till mobbning på arbetsplatsen2017Independent thesis Advanced level (professional degree), 300 HE creditsStudent thesis
  • Munthe, Linn
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Hyreskontrakt som går upp i rök: En diskussion om lämpligheten i bestämmelsen att hyresavtalet förfaller om lägenheten förstörs2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Elfversson, Emma
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Peace and Conflict Research.
    Peace and Politics: Promoting durable solutions to communal conflicts2017Report (Other (popular science, discussion, etc.))
  • Skwarcan-Bidakowski, Alexander
    Institutionen för Reaktorfysik.
    Nuclear reactor core model for the advancednuclear fuel cycle simulator FANCSEE. Advanceduse of Monte Carlo methods in nuclear reactorcalculations2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    A detailed reactor core modeling of the LOVIISA-2 PWR and FORSMARK-3BWR was performed in the Serpent 2 Continuous Energy Monte-Carlocode.Both models of the reactors were completed but the approximations ofthe atomic densities of nuclides present in the core differedsignificantly.In the LOVIISA-2 PWR, the predicted atomic density for the nuclidesapproximated by Chebyshev Rational Approximation method (CRAM)coincided with the corrected atomic density simulated by the Serpent2 program. In the case of FORSMARK-3 BWR, the atomic density fromCRAM poorly approximated the data returned by the simulation inSerpent 2. Due to boiling of the moderator in the core of FORSMARK-3,the model seemed to encounter problems of fission density, whichyielded unusable results.The results based on the models of the reactor cores are significantto the FANCSEE Nuclear fuel cycle simulator, which will be used as adataset for the nuclear fuel cycle burnup in the reactors.

  • Hamdan, Qusay
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Business Studies.
    Unfastening Screws of Consumer Behavior towards More Sustainable Decisions2017Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
  • Johan, Silfwerin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Government.
    En odemokratisk skolnedläggning?: Fallstudie av en skolnedläggningsprocess i Ludvika Kommun.2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • Gray, Bradford H.
    et al.
    Urban Institute.
    Winblad, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Sarnak, Dana O.
    The Commonwealth Fund.
    Sweden’s Esther Model: Improving Care for Elderly Patients with Complex Needs.2016Report (Other academic)
  • Gray, Bradford H.
    et al.
    Urban Institute.
    Winblad, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Sarnak, Dana O.
    The Commonwealth Fund.
    Sweden’s Senior Alert Program: How an Information System Can Reduce Health Risks Among the Elderly2016Report (Other academic)
  • Larsson, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Algebra and Geometry.
    λ-Calculus and Decidability2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • Hindlycke, Christoffer
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Algebra and Geometry.
    The relative consistency of the Axiom of Choice and the Generalized Continuum Hypothesis with the Zermelo-Fraenkel axioms: The constructible sets L2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • Spångberg, Christian
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    En studie om regleringen av nanomaterial: -      i The Toxic Substances Control Act (TSCA) och Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Wiröstrand, Ludvig
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Lilla blåljusutredningen: En undersökning om ett förstärkt straffrättsligt skydd för vissa yrkesgrupper2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Odengran, Christina
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Drag along, tag along och överlåtelsebegränsningar - något om tolkning av aktieägaravtal2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Lang, Karl-Staffan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Bedrägeribrottets skaderekvisit: Särskilt om avtalsbedrägeri och uppfyllelsebedrägeri2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Hansson, Ellen
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Med rätten att vara rasist?: Om det svenska skyddet av rasistiska åsikter2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Holmstrom, Joakim
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Fotboll och arbetsrätt: När juridiken möter idrotten2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Hedman, Carl
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Uppskjutet offentliggörande av insiderinformation: En analys av artikel 17(4)(b) marknadsmissbruksförordningen2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Aspengren, Lisa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Ensamkommande marockanska barns rätt till uppehållstillstånd: en fråga om asyl och praktiska verkställighetshinder2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • Eliasson Godonou, Samuel
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control.
    Dynamic torque clutch control for heavy duty vehicles using a backlash size and position observer2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This master's thesis investigated the possibility to control the clutch torque in order to better traverse a Scania vehicles powertrain backlash. When traversing a backlash the torque difference between the two gears will at the time of contact excite oscillations in the powertrain, and by controlling the torque these oscillations can be minimized. The master's thesis solves this issue in three major steps. First a Simulink model was created to mimic the actual vehicles powertrain as closely as possible. It was created using mostly Simdriveline components and then validated by comparing simulations to measurements from real drives. After that backlash position and backlash size observers were created in order to estimate them. Using the developed Simulink model these observers could then be evaluated, and the backlash position observer proved to be very precise while the backlash size observer was not as precise but still usable. Finally a control strategy was devised, by using the estimates from the developed observers it was supposed to control the clutch torque in a better way than previously done. The controller was a switching controller that simply used the full engine torque while the backlash was in contact, and a P controller to control the clutch torque while performing a backlash traverse. The controller proved to perform well and was robust to errors in the backlash size. Future work to be done could be to develop a shaft torque observer for use in the already developed observers.

  • Johansson, Jim
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences.
    Utilizing Energy Storage Applied on Floating Wind Turbine Economics Using a Spot-Price Based Algorithm2017Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In this paper, a new algorithm for utilizing energy storage is proposed and applied on floating wind turbine economics. The proposed algorithm’s decision making on storing energy or selling electricity onto the grid is based on the electricity price, which makes it unique and different from similar algorithms. From the literature review, it was concluded Ocean Renewable Energy Storage to be most suitable with the Spar-Type and Semi-Submersible floating wind turbine to which the paper is based upon. The objective of this paper is to find the suitable ratio of energy storage versus wind farm, find the product of increase in wholesale, and evaluate whether the proposed method makes the hybrid economically sound. The algorithm was applied on spot-price data from Denmark due to its large share of wind energy with wind data from off the coast of Morro Bay in California, USA. Additionally, a sensitivity analysis is applied to evaluate to energy storage cost impact as well as evaluate the algorithm by lowering the required energy storage size.

     

    Using the algorithm, the wind farm must account for nine days’ worth of energy production with a product of energy storage versus wind farm ratio of 1.42. The wholesale price increased with 11.9-21.5% for the four years studied, however, all financial results favored not utilizing energy storage. By the results derived from the sensitivity analysis, it was concluded that with future cost reductions, the algorithm will still favor no energy storage. However, by fine tuning the algorithm to reduce the need for storage, positive financial result might be achievable. The key to achieve a profitable result seems to rely on minimizing the need for energy storage, to which the proposed algorithm fail to achieve. Conclusively, spot-price decision-based energy storing is not economically sound.

  • Public defence: 2017-09-29 13:00 Fåhraeus Hall, Rudbecklaboratoriet, Uppsala
    Garousi, Javad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Development of ADAPT-based tracers for radionuclide molecular imaging of cancer2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    ABD-Derived Affinity Proteins (ADAPTs) is a novel class of small engineered scaffold proteins based on albumin-binding domain (ABD) of streptococcal protein G. High affinity ADAPT  binders against various therapeutic targets can be selected.  In this thesis, we report a development of ADAPT-based radionuclide imaging agents providing high sensitivity and specificity of molecular imaging of HER2 expression in disseminated cancers.

    We investigated the feasibility of the use of ADAPTs as imaging agents and influence of molecular design and radiolabeling chemistry on in vivo targeting and biodistribution properties of the tracers.

    In Paper I we demonstrated the feasibility of the use of anti-HER2 ADAPT6 molecule as a high contrast imaging agent;

    In Paper II we evaluated the influence of composition of histidine-containing tag on in vivo biodistribution of ADAPT-based tracers labeled with 99mTc using 99mTc(CO)3 binding to histidine-containing tags and 111In using DOTA chelator at N-terminus;

    In Paper III we evaluated the influence of different aspects of N-terminus leading sequence on targeting including effect of sequence size on clearance rate and effect of the composition of the sequence on biodistribution profile;

    In Paper IV, we evaluated the influence of residualizing properties and positioning of the label on biodistribution and targeting; and

    In Paper V, we compared tumor-targeting properties of the ADAPT6 labeled at C-terminus with 99mTc using N3S chelator and 111In using DOTA chelator.

    In conclusion, ADAPTs constitute a very promising class of targeting probes for molecular imaging providing high contrast. Molecular design of the ADAPT proteins and chelators/linkers for labeling has an appreciable effect on their imaging properties.

    List of papers
    1. ADAPT, a novel scaffold protein-based probe for radionuclide imaging of molecular targets that are expressed in disseminated cancers
    Open this publication in new window or tab >>ADAPT, a novel scaffold protein-based probe for radionuclide imaging of molecular targets that are expressed in disseminated cancers
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    2015 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 75, no 20, 4364-4371 p.Article in journal (Refereed) Published
    Abstract [en]

    Small engineered scaffold proteins have attracted attention as probes for radionuclide-based molecular imaging. One class of these imaging probes, termed ABD-Derived Affinity ProTeins (ADAPT), have been created using the albumin-binding domain (ABD) of streptococcal protein G as a stable protein scaffold. In this study, we report the development of a clinical lead probe termed ADAPT6 that binds HER2, an oncoprotein overexpressed in many breast cancers that serves as a theranostic biomarker for several approved targeting therapies. Surface-exposed amino acids of ABD were randomized to create a combinatorial library enabling selection of high affinity binders to various proteins. Further, ABD was engineered to rapidly purify ADAPT6, eradicate its binding to albumin and enable rapid blood clearance. Incorporation of a unique cysteine allowed site-specific conjugation to a maleimido derivative of a DOTA chelator, enabling radionuclide labeling, 111In for SPECT imaging and 68Ga for PET imaging. Pharmacological studies in mice demonstrated that the fully engineered molecule 111In/68Ga-DOTA-(HE)3-ADAPT6 was specifically bound and taken up by HER2-expressing tumors, with a high tumor-to-normal tissue ratio in xenograft models of human cancer. Unbound tracer underwent rapid renal clearance followed by high renal reabsorption. HER2-expressing xenografts were visualized by gamma-camera or PET by one hour post-infusion. PET experiments demonstrated feasibility for discrimination of xenografts with high or low HER2 expression. Our results offer a preclinical proof of concept for the use of ADAPT probes for non-invasive in vivo imaging.

    National Category
    Medical Genetics
    Identifiers
    urn:nbn:se:uu:diva-262291 (URN)10.1158/0008-5472.CAN-14-3497 (DOI)000365601900013 ()26297736 (PubMedID)
    Funder
    Swedish Cancer Society, 2012/354Swedish Research Council, 521-2012-2228Swedish Research Council, 621-2012-5088
    Note

    First two authors (Garousi and Lindbo) contributed equally

    Last two authors (Tolmachev and Hober) contributed eaually

    Available from: 2015-09-12 Created: 2015-09-12 Last updated: 2017-08-10
    2. Influence of Histidine-Containing Tags on the Biodistribution of ADAPT Scaffold Proteins.
    Open this publication in new window or tab >>Influence of Histidine-Containing Tags on the Biodistribution of ADAPT Scaffold Proteins.
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    2016 (English)In: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 27, no 3, 716-726 p.Article in journal (Refereed) Published
    Abstract [en]

    Engineered scaffold proteins (ESP) are high-affinity binders that can be used as probes for radionuclide imaging. Histidine-containing tags enable both efficient purification of ESP and radiolabeling with (99m)Tc(CO)3. Earlier studies demonstrated that the use of a histidine-glutamate-histidine-glutamate-histidine-glutamate (HE)3-tag instead of the commonly used hexahistidine (H6)-tag reduces hepatic uptake of radiolabeled ESP and short peptides. Here, we investigated the influence of histidine-containing tags on the biodistribution of a novel type of ESP, ADAPTs. A series of anti-HER2 ADAPT probes having H6- or (HE)3-tags in the N-termini were prepared. The constructs, (HE)3-ADAPT6 and H6-ADAPT6, were labeled with two different nuclides, (99m)Tc or (111)In. The labeling with (99m)Tc(CO)3 utilized the histidine-containing tags, while (111)In was attached through a maleimido derivative of DOTA conjugated to the N-terminus. For (111)In-labeled ADAPTs, the use of (HE)3 provided a significantly (p < 0.05) lower hepatic uptake at 1 h after injection, but there was no significant difference in hepatic uptake of (111)In-(HE)3-ADAPT6 and H6-ADAPT6 at later time points. Interestingly, in the case of (99m)Tc, (99m)Tc(CO)3-H6-ADAPT6 provided significantly (p < 0.05) lower uptake in a number of normal tissues and was more suitable as an imaging probe. Thus, the influence of histidine-containing tags on the biodistribution of the novel ADAPT scaffold proteins was different compared to its influence on other ESPs studied so far. Apparently, the effect of a histidine-containing tag on the biodistribution is highly dependent on the scaffold composition of the ESP.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-286833 (URN)10.1021/acs.bioconjchem.5b00677 (DOI)000372478600026 ()26781756 (PubMedID)
    Funder
    Swedish Cancer Society, CAN 2015/350Swedish Research Council, 2015-02353, 621-2012-5088
    Note

    First two authors (Lindbo and Garousi) contributed equally

    Available from: 2016-04-21 Created: 2016-04-21 Last updated: 2017-08-10Bibliographically approved
    3. Influence of the N-Terminal Composition on Targeting Properties of Radiometal-Labeled Anti-HER2 Scaffold Protein ADAPT6
    Open this publication in new window or tab >>Influence of the N-Terminal Composition on Targeting Properties of Radiometal-Labeled Anti-HER2 Scaffold Protein ADAPT6
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    2016 (English)In: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 27, no 11, 2678-2688 p.Article in journal (Refereed) Published
    Abstract [en]

    Radionuclide-imaging-based stratification of patients to targeted therapies makes cancer treatment more personalized and therefore more efficient. Albumin-binding domain derived affinity proteins (ADAPTs) constitute a novel group of imaging probes based on the scaffold of an albumin-binding domain (ABD). To evaluate how different compositions of the N-terminal sequence of ADAPTs influence their biodistribution, a series of human epidermal growth factor receptor type 2 (HER2)-binding ADAPT6 derivatives with different N-terminal sequences were created: GCH6DANS (2), GC(HE)3DANS (3), GCDEAVDANS (4), and GCVDANS(5). These were compared with the parental variant: GCSS(HE)3DEAVDANS (1). All variants were site-specifically conjugated with a maleimido-derivative of a DOTA chelator and labeled with (111)In. Binding to HER2-expressing cells in vitro, in vivo biodistribution as well as targeting properties of the new variants were compared with properties of the (111)In-labeled parental ADAPT variant 1 ((111)In-DOTA-1). The composition of the N-terminal sequence had an apparent influence on biodistribution of ADAPT6 in mice. The use of a hexahistidine tag in (111)In-DOTA-2 was associated with elevated hepatic uptake compared to the (HE)3-containing counterpart, (111)In-DOTA-3. All new variants without a hexahistidine tag demonstrated lower uptake in blood, lung, spleen, and muscle compared to uptake in the parental variant. The best new variants, (111)In-DOTA-3 and (111)In-DOTA-5, provided tumor uptakes of 14.6 ± 2.4 and 12.5 ± 1.3% ID/g at 4 h after injection, respectively. The tumor uptake of (111)In-DOTA-3 was significantly higher than the uptake of the parental (111)In-DOTA-1 (9.1 ± 2.0% ID/g). The tumor-to-blood ratios of 395 ± 75 and 419 ± 91 at 4 h after injection were obtained for (111)In-DOTA-5 and (111)In-DOTA-3, respectively. In conclusion, the N-terminal sequence composition affects the biodistribution and targeting properties of ADAPT-based imaging probes, and its optimization may improve imaging contrast.

    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-312075 (URN)10.1021/acs.bioconjchem.6b00465 (DOI)000388430700011 ()27740752 (PubMedID)
    Funder
    Swedish Cancer Society, CAN 2015/350Swedish Research Council, 2015-02353Swedish Research Council, 621-2012-5088
    Available from: 2017-01-04 Created: 2017-01-04 Last updated: 2017-08-10Bibliographically approved
    4. Radionuclide tumor targeting using ADAPT scaffold proteins: aspects of label positioning and residualizing properties of the label
    Open this publication in new window or tab >>Radionuclide tumor targeting using ADAPT scaffold proteins: aspects of label positioning and residualizing properties of the label
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    2017 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667Article in journal (Refereed) Accepted
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-327415 (URN)
    Available from: 2017-08-10 Created: 2017-08-10 Last updated: 2017-08-11
    5. Comparative evaluation of tumor targeting using anti-HER2 ADAPT scaffold protein labeled at C-terminus with  indium-111 and technetium-99m
    Open this publication in new window or tab >>Comparative evaluation of tumor targeting using anti-HER2 ADAPT scaffold protein labeled at C-terminus with  indium-111 and technetium-99m
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-327416 (URN)
    Available from: 2017-08-10 Created: 2017-08-10 Last updated: 2017-08-10
  • Wild, de, Marc Noël
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences.
    A VIEW INTO FUTURE POTENTIAL ICE THROW POLICIES AND THEIR EFFECT ON THE YIELD OF A VIRTUAL WIND FARM2017Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    There is a growth of wind power development in icing climates, in which ice accumulation on objects takes place. This leads to specific challenges including ice throw, the detachment of ice from wind turbine blades. The lack of understanding of the ice throw phenomenon among authorities leads to the fact that there is no coherence in the applied ice throw mitigation policies in various countries and regions, which can cause safety- and financial hazards for wind farms in icing climates.

    This research focusses on ice throw risk mitigation methods and their effect on a wind farms yield. Qualitative research is applied, interviewing six experts in the field of cold climate wind power development. The participants are from academic, public and private research institutions in five countries. The qualitative research focusses on policies that are plausible but non-preferred, as well as preference suggestions from the experts on how to treat the ice throw risks. The non-preferred policies involve shutting down wind farms during icing periods and conditionally allowed operation with applied heating systems. These policy scenarios are applied to a virtual wind farm near Slagnäs, Sweden, in order to indicate the impact on the yield and underline the impact that these policies would have on the turnover of a wind farm in a sever icing climate.

    The non-preferred policies have a significant impact on the Slagnäs wind farms yield with 2,28% annual yield losses in case of 200 annual icing hours. Apart from the impact on yield, the policies might not reduce the danger of ice throw significantly, as from a standing still turbine, detached ice can still travel a horizontal distance of up to one time the turbine height. Therefore, policies should according to the interviewed experts not focus on limitations, however focus on understanding risks and taking appropriate action for risk mitigation. International guidelines are the best tool to create a deeper understanding of ice throw risk assessments and their limitations, as well as an understanding of risk mitigation methods. In this case, the risk assessment process shall be standardised, however the risk mitigation methods shall be site specific.

  • Public defence: 2017-09-29 10:00 Hambergsalen, Uppsala
    Rasmusson, Kristina
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Modeling of geohydrological processes in geological CO2 storage – with focus on residual trapping2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Geological storage of carbon dioxide (CO2) in deep saline aquifers is one approach to mitigate release from large point sources to the atmosphere. Understanding of in-situ processes providing trapping is important to the development of realistic models and the planning of future storage projects. This thesis covers both field- and pore-scale numerical modeling studies of such geohydrological processes, with focus on residual trapping. The setting is a CO2-injection experiment at the Heletz test site, conducted within the frame of the EU FP7 MUSTANG and TRUST projects.

    The objectives of the thesis are to develop and analyze alternative experimental characterization test sequences for determining in-situ residual CO2 saturation (Sgr), as well as to analyze the impact of the injection strategy on trapping, the effect of model assumptions (coupled wellbore-reservoir flow, geological heterogeneity, trapping model) on the predicted trapping, and to develop a pore-network model (PNM) for simulating and analyzing pore-scale mechanisms.

    The results include a comparison of alternative characterization test sequences for estimating Sgr. The estimates were retrieved through parameter estimation. The effect on the estimate of including various data sets was determined. A new method, using withdrawal and an indicator-tracer, for obtaining a residual zone in-situ was also introduced.

    Simulations were made of the CO2 partitioning between layers in a multi-layered formation, and parameters influencing this were identified. The results showed the importance of accounting for coupled wellbore-reservoir flow in simulations of such scenarios.

    Simulations also showed that adding chase-fluid stages after a conventional CO2 injection enhances the (residual and dissolution) trapping. Including geological heterogeneity generally decreased the estimated trapping. The choice of trapping model may largely effect the quantity of the predicted residual trapping (although most of them produced similar results). The use of an appropriate trapping model and description of geological heterogeneity for a site when simulating CO2 sequestration is vital, as different assumptions may give significant discrepancies in predicted trapping.

    The result also includes a PNM code, for multiphase quasi-static flow and trapping in porous materials. It was used to investigate trapping and obtain an estimated trapping (IR) curve for Heletz sandstone.

    List of papers
    1. Analysis of alternative push-pull-test-designs for determining in situ residual trapping of carbon dioxide
    Open this publication in new window or tab >>Analysis of alternative push-pull-test-designs for determining in situ residual trapping of carbon dioxide
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    2014 (English)In: International Journal of Greenhouse Gas Control, ISSN 1750-5836, Vol. 27, 155-168 p.Article in journal (Refereed) Published
    Abstract [en]

    Carbon dioxide storage in deep saline aquifers is a promising technique to reduce direct emissions of greenhouse gas to the atmosphere. To ensure safe storage the in situ trapping mechanisms, residual trapping being one of them, need to be characterized. This study aims to compare three alternative single-well carbon dioxide push-pull test sequences for their ability to quantify residual gas trapping. The three tests are based on the proposed test sequence by Zhang et al. (2011) for estimating residual gas saturation. A new alternative way to create residual gas conditions in situ incorporating withdrawal and a novel indicator-tracer approach has been investigated. Further the value of additional pressure measurements from a nearby passive observation well was evaluated. The iTOUGH2 simulator with the EOS7C module was used for sensitivity analysis and parameter estimation. Results show that the indicator-tracer approach could be used to create residual conditions without increasing estimation uncertainty of S-gr. Additional pressure measurements from a passive observation well would reduce the uncertainty in the S-gr estimate. The findings of the study can be used to develop field experiments for site characterization.

    Keyword
    CO2, CCS, Site characterization, Field test, Residual saturation, Single-well test
    National Category
    Energy Systems
    Identifiers
    urn:nbn:se:uu:diva-232013 (URN)10.1016/j.ijggc.2014.05.008 (DOI)000340319600012 ()
    Available from: 2014-09-12 Created: 2014-09-12 Last updated: 2017-08-15Bibliographically approved
    2. Distribution of injected CO2 in a stratified saline reservoir accounting for coupled wellbore-reservoir flow
    Open this publication in new window or tab >>Distribution of injected CO2 in a stratified saline reservoir accounting for coupled wellbore-reservoir flow
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    2015 (English)In: Greenhouse Gases: Science and Technology, E-ISSN 2152-3878, Vol. 5, no 4, 419-436 p.Article in journal (Refereed) Published
    Abstract [en]

    Geological storage in sedimentary basins is considered a viable technology in mitigating atmospheric CO2 emissions. Alternating high and low permeability strata are common in these basins. The distribution of injected CO2 among such layers affects e.g. CO2 storage efficiency, capacity and plume footprint. A numerical study on the distribution of injected CO2 into a multi-layered reservoir, accounting for coupled wellbore-reservoir flow, was carried out using the T2Well/ECO2N code. A site-specific case as well as a more general case were considered. Properties and processes governing the distribution of sequestrated CO2 were identified and the potential to operationally modify the distribution was investigated. The distribution of CO2 was seen to differ from that of injected water, i.e. it was not proportional to the transmissivity of the layers. The results indicate that caution should be taken when performing numerical simulations of CO2 injection into layered formations. Ignoring coupled wellbore-reservoir flow and instead adopting a simple boundary condition at the injection well, such as an inflow rate proportional to the transmissivity of each layer, may result in significant underestimation of the proportion of CO2 ending up in the shallower layers, as not all relevant processes are accounted for. This discrepancy has been thoroughly investigated and quantified for several CO2 sequestration scenarios.

    Keyword
    CCS, flow distribution, geological storage, layered formation, wellbore model
    National Category
    Oceanography, Hydrology, Water Resources
    Identifiers
    urn:nbn:se:uu:diva-263036 (URN)10.1002/ghg.1477 (DOI)000360356800007 ()
    Funder
    EU, FP7, Seventh Framework Programme, 227286EU, FP7, Seventh Framework Programme, 309067
    Available from: 2015-09-30 Created: 2015-09-24 Last updated: 2017-08-15Bibliographically approved
    3. A simulation study of the effect of trapping model, geological heterogeneity and injection strategies on CO2 trapping
    Open this publication in new window or tab >>A simulation study of the effect of trapping model, geological heterogeneity and injection strategies on CO2 trapping
    2016 (English)In: International Journal of Greenhouse Gas Control, ISSN 1750-5836, E-ISSN 1878-0148, Vol. 52, 52-72 p.Article in journal (Refereed) Published
    Abstract [en]

    Industrial CO2 emissions to the atmosphere can be reduced through geological storage, where the gas is injected into the subsurface and trapped by several mechanisms. Residual and solubility trapping are two important processes providing trapping, and their effectiveness ultimately determines the feasibility of geological storage. By means of numerical modeling, a systematic analysis was made concerning the factors potentially affecting trapping, to guide the planned injection experiments at the Heletz test injection site. The effect of enhanced-trapping injection strategies along with the role of geological heterogeneity and the choice of trapping model (TM) were evaluated. The results showed that adding chase-fluid stages to a conventional CO2 injection enhanced the trapping. Taking into account the geological heterogeneity decreased trapping, as this retarded the buoyant migration, resulting in less imbibition and residual trapping. The choice of TM was significant, with the simplified Land TM producing the highest trapping, and the Aissaoui TM the lowest. The results stress the importance of using an appropriate TM as well as heterogeneity model for the site in question for any predictive modeling of CO2 sequestration, as different assumptions may lead to significant discrepancies in the predicted trapping.

    Keyword
    CCS, Capillary trapping, Hysteresis, Injection strategies, Residual trapping, Solubility trapping
    National Category
    Earth and Related Environmental Sciences
    Identifiers
    urn:nbn:se:uu:diva-303260 (URN)10.1016/j.ijggc.2016.06.020 (DOI)000381728300006 ()
    Funder
    EU, FP7, Seventh Framework Programme, 227286; 309067
    Available from: 2016-09-16 Created: 2016-09-15 Last updated: 2017-08-15Bibliographically approved
    4. Residual trapping of carbon dioxide during geological storage – insight gained through a pore-network modeling approach
    Open this publication in new window or tab >>Residual trapping of carbon dioxide during geological storage – insight gained through a pore-network modeling approach
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    (English)In: Article in journal (Other academic) Submitted
    National Category
    Earth and Related Environmental Sciences
    Identifiers
    urn:nbn:se:uu:diva-327991 (URN)
    Available from: 2017-08-15 Created: 2017-08-15 Last updated: 2017-08-15
  • Alsharari, Zayed
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Dietary Intake, Fatty Acid Biomarkers, and Abdominal Obesity: Population-Based Observational Studies2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis was to investigate the associations between fatty acid (FA) biomarkers, carbohydrate intake, and abdominal obesity (AO) and related anthropometric measures in a population-based cohort of men and women in Stockholm County. The overall hypothesis was that dietary fat quality assessed by serum and adipose tissue FA composition, and dietary intake of especially carbohydrates is associated with AO. FA composition was assessed by liquid gas chromatography, and AO was measured as waist circumference (WC), waist hip ratio (WHR) and sagittal abdominal diameter (SAD). Dietary intake was assessed by 7-day food records.

    Papers I, II, III, and IV were all observational studies based on a Swedish population in Stockholm County (n=5460). A sub-cohort of only men (n=301) was included in Papers II, III, and IV.

    In Paper I, serum proportions of the polyunsaturated FA (PUFA), linoleic acid (LA) (18:2n6), was inversely associated with AO in both men and women, whereas a positive association was observed between the saturated FA (SFA), palmitic acid (PA) (16:0) and AO measures. These findings support recent interventional studies suggesting that a higher relative intake of PUFA (LA) from vegetable oils as compared with 16:0 is associated with decreased abdominal adiposity.

    In Paper II, we investigated whether biomarkers of dietary fat quality were related to the corresponding FA intake from fat-rich foods reported in a short food frequency questionnaire (FFQ). Serum proportions of the long-chain n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) were higher among men with higher total fish intake. Serum LA was higher among men who reported a consumption of more than 5 g/d of margarine. Absolute agreement between intakes assessed with FFQ of 60YO and 7-day food record of "Kost och Metabola syndromet"/"Diet and the Metabolic syndrome" (KOMET) was highest for alcohol, total fish, and eggs. Weighted Kappa statistics revealed the strongest agreement for alcohol, margarine, and fruits.

    In Paper III, carbohydrate intake was inversely associated with 16:0 in serum phospholipids (PL). Disaccharide and alcohol intake was positively and non-linearly associated with palmitoleic acid (16:1) and stearoyl-CoA-desaturase (SCD) activity in PL. Alcohol was consistently associated with higher SFA and monounsaturated FA (MUFA).

    Results of Paper IV indicated that total carbohydrate intake was inversely associated with measures of AO and central fat distribution, WHR and SAD, respectively. Likewise, monosaccharide intake was associated with lower AO. In contrast, alcohol intake was associated with AO prevalence and all anthropometric measurements.

    In conclusion, serum SFA (palmitic acid) was positively associated with AO, whereas n-6 PUFA (linoleic acid) was associated with lower AO. High intake of total carbohydrate and monosaccharides were associated with lower AO. Overall, these results support a beneficial role on adiposity of diets that are higher in polyunsaturated fat (vegetable oils) and total carbohydrates compared with saturated fat.

    List of papers
    1. Serum Fatty Acids, Desaturase Activities and Abdominal Obesity - A Population-Based Study of 60-Year Old Men and Women
    Open this publication in new window or tab >>Serum Fatty Acids, Desaturase Activities and Abdominal Obesity - A Population-Based Study of 60-Year Old Men and Women
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    2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, e0170684Article in journal (Refereed) Published
    Abstract [en]

    Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary fat quality affects abdominal fat content, where palmitic acid and linoleic acid influence abdominal obesity differently, while effects of n-3 polyunsaturated fatty acids are less studied. Also, fatty acid desaturation may be altered in abdominal obesity. We aimed to investigate cross-sectional associations of serum fatty acids and desaturases with abdominal obesity prevalence in a population-based cohort study. Serum cholesteryl ester fatty acids composition was measured by gas chromatography in 60-year old men (n = 1883) and women (n = 2015). Cross-sectional associations of fatty acids with abdominal obesity prevalence and anthropometric measures (e.g., sagittal abdominal diameter) were evaluated in multivariable-adjusted logistic and linear regression models, respectively. Similar models were employed to investigate relations between desaturase activities (estimated by fatty acid ratios) and abdominal obesity. In logistic regression analyses, palmitic acid, stearoyl-CoA- desaturase and Delta 6-desaturase indices were associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals) for highest versus lowest quartiles were 1.45 (1.19-1.76), 4.06 (3.27-5.05), and 3.07 (2.51-3.75), respectively. Linoleic acid, alpha-linolenic acid, docohexaenoic acid, and Delta 5-desaturase were inversely associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals): 0.39 (0.32-0.48), 0.74 (0.61-0.89), 0.76 (0.62-0.93), and 0.40 (0.33-0.49), respectively. Eicosapentaenoic acid was not associated with abdominal obesity. Similar results were obtained from linear regression models evaluating associations with different anthropometric measures. Sex-specific and linear associations were mainly observed for n3-polyunsaturated fatty acids, while associations of the other exposures were generally non-linear and similar across sexes. In accordance with findings from short-term trials, abdominal obesity was more common among individuals with relatively high proportions of palmitic acid, whilst the contrary was true for linoleic acid. Further trials should examine the potential role of linoleic acid and its main dietary source, vegetable oils, in abdominal obesity prevention.

    Place, publisher, year, edition, pages
    PUBLIC LIBRARY SCIENCE, 2017
    National Category
    Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-319131 (URN)10.1371/journal.pone.0170684 (DOI)000396176100074 ()28125662 (PubMedID)
    Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2017-08-08Bibliographically approved
    2. Comparison of a 21-item food questionnaire with a 7-day dietary registration andbiomarkers of fat intake in a Swedish cohort of 60-year-old adults.
    Open this publication in new window or tab >>Comparison of a 21-item food questionnaire with a 7-day dietary registration andbiomarkers of fat intake in a Swedish cohort of 60-year-old adults.
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Purpose. To evaluate a 21-item food frequency questionnaire (FFQ) in men participating in a

    large cohort of Swedish 60-year-old adults (60YO).

    Methods. A self-reported FFQ (including 21 qualitative and semi-quantitative questions) was completed by >2000 men as part of a detailed baseline examination. A subsample of 301 men was included in a subsequent study in which detailed dietary habits were determined by a 7-day food record. Spearman rank correlations (r) and weighted Kappa (Kw) statistics were used to compare food intake categories in FFQ and 7-day food record. Furthermore, fatty acid (FA) composition in serum cholesteryl esters, assessed concurrent with the FFQ completion, was used to evaluate intakes of specific fat-rich foods from the FFQ.

    Results. We found good agreement between FFQ and food records for the reported intake of

    alcohol (r=0.72, Kw=0.51), margarine (r=0.60, Kw=0.33), and fruit (r=0.49, Kw=0.31), reasonably good agreement for total fish (r=0.25, Kw=0.23), and egg (r=0.35, Kw=0.28), but poor agreement for other food groups such as bread, cheese, vegetables and cookies. In addition, serum proportions of long-chain n-3 polyunsaturated FAs and pentadecanoic acid were significantly higher in men with greater intakes of fish and cheese, respectively.

    Conclusion. In this evaluation of a short FFQ against 7-d food records and serum biomarkers of fat intake we found that the FFQ reasonably well reflected the intake of certain food groups (e.g. alcohol, fish, and margarine), but performed less accurate for other food groups. Firm and overall

    conclusions on validity are confined by the time-lag between the test and the reference method.

    Keyword
    validation, food frequency questionnaire, biomarkers of fat intake
    National Category
    Medical and Health Sciences
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-327199 (URN)
    Available from: 2017-08-07 Created: 2017-08-07 Last updated: 2017-08-08
    3. Association between carbohydrate intake and fatty acids in the de novo lipogenic pathwayin serum phospholipids and adipose tissue among 63-year old men
    Open this publication in new window or tab >>Association between carbohydrate intake and fatty acids in the de novo lipogenic pathwayin serum phospholipids and adipose tissue among 63-year old men
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Background: Fatty acid composition in blood and adipose tissue is useful to reflect dietary fat

    quality, although the utility of even-chain saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) has been debated. Since SFA also can be produced via de novo lipogenesis (DNL), and desaturated to MUFA, it has been proposed that these fatty acids may reflect carbohydrate-induced DNL. We aimed to test the hypothesis that high carbohydrate intake, especially sugars, is related to SFA and MUFA in serum and adipose tissue.

    Methods: Validated 7-day food records were collected and fatty acid composition in serum phospholipids (PL) and adipose tissue (AT) were measured in 63-year-old men (n=299). Stearoyl-CoA desaturate (SCD) activities in AT and PL were estimated by the palmitoleic acid (16:1) to palmitic acid (16:0) ratio. Associations of dietary carbohydrate, disaccharides,  monosaccharides, carbohydrate-to-fiber ratio, and alcohol with the sum of even-chain SFA, 16:0, 16:1, and SCD activity were assessed using linear regression models with and without adjustment for BMI. Non-linear trends were evaluated using restricted cubic splines. In a subsample (n=81) with RNA measured in AT biopsies, associations of dietary carbohydrate and alcohol with SCD gene expression were assessed using linear regression models.

    Results: In BMI-adjusted models, intake of carbohydrates was inversely associated with palmitic acid in PL (P=0.005). Disaccharide intake was non-linearly associated with 16:1 and SCD activity in PL (P for nonlinear trend ≤0.02), with the lowest values observed in the mid tertile. Alcohol intake was linearly associated with 16:0 in PL (P<0.001) and with 16:1 (P<0.001) and SCD activity (P ≤0.005) in AT. Alcohol intake was non-linear associated (P≤0.02) with 16:1 and SCD activity in PL; with initially stable levels at lower intakes that rapidly increased at intakes above median. In the subsample, we found no associations between carbohydrate intake and SCD gene expression (P ≥0.08).

    Conclusion: In this Swedish population, we found no evidence to suggest that higher carbohydrate intake or sugar-rich foods or beverages is reflected by higher SFA in PL and AT.

    Instead, alcohol was consistently associated with higher SFA and MUFA.

    Keyword
    fatty acid, saturated fatty acids, carbohydrate, phospholipid
    National Category
    Medical and Health Sciences
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-327205 (URN)
    Available from: 2017-08-07 Created: 2017-08-07 Last updated: 2017-08-08
    4. CarbohydrateIntake and Abdominal Obesity in Swedish Men
    Open this publication in new window or tab >>CarbohydrateIntake and Abdominal Obesity in Swedish Men
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    ABSTRACT

    Background/Objectives: Associations between carbohydrates, particularly simple sugar and starch, and abdominal anthropometric measures appears controversial. However, the role of dietary carbohydrate intake in obesity and abdominal obesity has been debated, and few studies have been conducted in Nordic populations. We aim to examine the associations between carbohydrate quantity and quality, and anthropometric measures in Swedish men.

    Subjects/Methods: A cross-sectional investigation of 301 63-year-old men was conducted. Six men were excluded due to missing data on dietary intake and anthropometric measures, leaving 295 men for the present study. Healthy men were recruited from the Swedish 60YO cohort of men and women who had a health screening between 1997 to 1999. Carbohydrate and alcohol intake were assessed by a 7-days food record. The examination included anthropometric measurements (e. g., weight, BMI, WC, WHR, and SAD), fasting blood samples, and a comprehensive questionnaire. Spearman rank correlation and linear regression models were performed to assess relations between dietary intakes and anthropometric measures. Intakes of macronutrients were energy-adjusted according to the residual method. Logistic regression models were used to calculate odds ratios (OR) and 95% CI for abdominal obesity per intake tertiles.

    Results: Intakes of carbohydrate, monosaccharide, fibers, and fruits and vegetables correlated negatively with anthropometric measures of overall obesity (BMI) and AO (WC, WHR, and SAD). Total carbohydrate intake was significantly inversely associated with WHR and SAD. Likewise, monosaccharide intake was significantly associated with lower BMI, WC, WHR, and SAD. In contrast, alcohol intake was significantly associated with weight, BMI, WC, and SAD (Table 4). Alcohol intake was associated with AO (P for linear trend 0.002). Men in the highest tertile of alcohol intake were almost three times as likely to have AO compared to the men in the lowest tertile of intake, OR (95% CI): 2.93 (1.40-6.16). There was no evidence of non-linear association between the macronutrients and AO.

    Conclusion: In this Swedish population of older men, higher intakes of total carbohydrates and monosaccharides were associated a more favorable body fat distribution and lower abdominal adiposity. Men with higher alcohol intake were more likely to have AO as compared with a lower intake.

    Keyword
    carbohydrate intake, abdominal obesity, anthropometric measures.
    National Category
    Medical and Health Sciences
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-327277 (URN)
    Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2017-08-08
  • Hellström-Lindahl, Ewa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Åberg, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Ericsson, Cecilia
    AstraZeneca R&D, SE-43150 Molndal, Sweden..
    O'Mahony, Gavin
    AstraZeneca R&D, SE-43150 Molndal, Sweden..
    Johnström, Peter
    Karolinska Inst, Karolinska Univ Hosp, AstraZeneca PET Sci Ctr, Personalised Healthcare & Biomarkers, SE-17176 Stockholm, Sweden..
    Skrtic, Stanko
    AstraZeneca R&D, SE-43150 Molndal, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, SE-41345 Gothenburg, Sweden..
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Toward molecular imaging of the free fatty acid receptor 12017In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 54, no 7, 663-668 p.Article in journal (Refereed)
    Abstract [en]

    Molecular imaging of the free fatty acid receptor 1 (FFAR1) would be a valuable tool for drug development by enabling in vivo target engagement studies in human. It has also been suggested as a putative target for beta cell imaging, but the inherent lipophilicity of most FFAR1 binders produces high off-target binding, which has hampered progress in this area. The aim of this study was to generate a suitable lead compound for further PET labeling. In order to identify a lead compound for future PET labeling for quantitative imaging of FFAR1 in human, we evaluated tritiated small molecule FFAR1 binding probes ([H-3]AZ1, [H-3]AZ2 and [H-3]TAK-875) for their off-target binding, receptor density and affinity in human pancreatic tissue (islets and exocrine) and rodent insulinoma. [H-3]AZ1 showed improved specificity to FFAR1, with decreased off-target binding compared to [H-3]AZ2 and [H-3]TAK-875, while retaining high affinity in the nanomolar range. FFAR1 density in human islets was approximately 50% higher than in exocrine tissue. AZ1 is a suitable lead compound for PET labeling for molecular imaging of FFAR1 in humans, due to high affinity and reduced off-target binding.

  • Aaboud, M.
    et al.
    Bergeås, Elin Kuutmann
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Brenner, Richard
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ekelöf, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellert, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ferrari, Arnaud
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Gradin, P.O. Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Madsen, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Öhman, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Rangel-Smith, Camilla
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zwalinski, L.
    Precision measurement and interpretation of inclusive W+, W- and Z/gamma* production cross sections with the ATLAS detector2017In: European Physical Journal C, ISSN 1434-6044, E-ISSN 1434-6052, Vol. 77, no 6, 367Article in journal (Refereed)
    Abstract [en]

    High-precision measurements by the ATLAS Collaboration are presented of inclusive W+ -> l(+) nu, W- -> l(-) (nu) over bar and Z/gamma* -> ll (l = e, mu) Drell-Yan production cross sections at the LHC. The data were collected in proton-proton collisions at root s = 7 TeV with an integrated luminosity of 4.6 fb(-1). Differential W+ and W- cross sections are measured in a lepton pseudorapidity range vertical bar eta(l)vertical bar < 2.5. Differential Z/gamma* cross sections are measured as a function of the absolute dilepton rapidity, for vertical bar y(ll)vertical bar < 3.6, for three intervals of dilepton mass, m(ll), extending from 46 to 150 GeV. The integrated and differential electron- and muon-channel cross sections are combined and compared to theoretical predictions using recent sets of parton distribution functions. The data, together with the final inclusive e(+/-) p scattering cross-section data from H1 and ZEUS, are interpreted in a next-to-next-to-leading-order QCD analysis, and a new set of parton distribution functions, ATLAS-epWZ16, is obtained. The ratio of strange-to-light sea-quark densities in the proton is determined more accurately than in previous determinations based on collider data only, and is established to be close to unity in the sensitivity range of the data. A new measurement of the CKM matrix element vertical bar V-cs vertical bar is also provided.

  • Aaboud, M.
    et al.
    Bergeås, Elin Kuutmann
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Bokan, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Brenner, Richard
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    De Bruin, Pedro Sales
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ekelöf, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellert, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ferrari, Arnaud
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Gradin, P.O. Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Madsen, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Mårtensson, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Öhman, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Rangel-Smith, Camilla
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zwalinski, L.
    Measurement of jet fragmentation in Pb plus Pb and pp collisions at root s(NN)=2.76 TeV with the ATLAS detector at the LHC2017In: European Physical Journal C, ISSN 1434-6044, E-ISSN 1434-6052, Vol. 77, no 6, 379Article in journal (Refereed)
    Abstract [en]

    The distributions of transverse momentum and longitudinal momentum fraction of charged particles in jets are measured in Pb+Pb and pp collisions with the ATLAS detector at the LHC. The distributions are measured as a function of jet transverse momentum and rapidity. The analysis utilises an integrated luminosity of 0.14 nb(-1) of Pb+Pb data and 4.0 pb(-1) of pp data collected in 2011 and 2013, respectively, at the same centre-of-mass energy of 2.76 TeV per colliding nucleon pair. The distributions measured in pp collisions are used as a reference for those measured in Pb+Pb collisions in order to evaluate the impact on the internal structure of jets from the jet energy loss of fast partons propagating through the hot, dense medium created in heavy-ion collisions. Modest but significant centrality-dependent modifications of fragmentation functions in Pb+Pb collisions with respect to those in pp collisions are seen. No significant dependence of modifications on jet p(T) and rapidity selections is observed except for the fragments with the highest transverse momenta for which some reduction of yields is observed for more forward jets.