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  • Vyakaranam, Achyut Ram
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Crona, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    C-11-hydroxy-ephedrine-PET/CT in the Diagnosis of Pheochromocytoma and Paraganglioma2019In: Cancers, ISSN 2072-6694, Vol. 11, no 6, article id 847Article in journal (Refereed)
    Abstract [en]

    Pheochromocytomas (PCC) and paragangliomas (PGL) may be difficult to diagnose because of vague and uncharacteristic symptoms and equivocal biochemical and radiological findings. This was a retrospective cohort study in 102 patients undergoing C-11-hydroxy-ephedrine (C-11-HED)-PET/CT because of symptoms and/or biochemistry suspicious for PCC/PGL and/or with radiologically equivocal adrenal incidentalomas. Correlations utilized CT/MRI, clinical, biochemical, surgical, histopathological and follow-up data. C-11-HED-PET/CT correctly identified 19 patients with PCC and six with PGL, missed one PCC, attained one false positive result (nodular hyperplasia) and correctly excluded PCC/PGL in 75 patients. Sensitivity, specificity, positive and negative predictive values of C-11-HED-PET/CT for PCC/PGL diagnosis was 96%, 99%, 96% and 99%, respectively. In 41 patients who underwent surgical resection and for whom correlation to histopathology was available, the corresponding figures were 96%, 93%, 96% and 93%, respectively. Tumor C-11-HED-uptake measurements (standardized uptake value, tumor-to-normal-adrenal ratio) were unrelated to symptoms of catecholamine excess (p > 0.05) and to systolic blood pressure (p > 0.05). In PCC/PGL patients, norepinephrine and systolic blood pressure increased in parallel (R-2 = 0.22, p = 0.016). C-11-HED-PET/CT was found to be an accurate tool to diagnose and rule out PCC/PGL in complex clinical scenarios and for the characterization of equivocal adrenal incidentalomas. PET measurements of tumor C-11-HED uptake were not helpful for tumor characterization.

  • Tabar, Laszlo
    et al.
    Dean, Peter B.
    Chen, Tony Hsiu-Hsi
    Yen, Amy Ming-Fang
    Chen, Sam Li-Sheng
    Fann, Jean Ching-Yuan
    Chiu, Sherry Yueh-Hsia
    Ku, May Mei-Sheng
    Wu, Wendy Yi-Ying
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Hsu, Chen-Yang
    Chen, Yu-Ching
    Beckmann, Kerri
    Smith, Robert A.
    Duffy, Stephen W.
    The incidence of fatal breast cancer measures the increased effectiveness of therapy in women participating in mammography screening2019In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 125, no 4, p. 515-523Article in journal (Refereed)
    Abstract [en]

    Background: Women and their health care providers need a reliable answer to this important question: If a woman chooses to participate in regular mammography screening, then how much will this choice improve her chances of avoiding a death from breast cancer compared with women who choose not to participate? Methods: To answer this question, we used comprehensive registries for population, screening history, breast cancer incidence, and disease-specific death data in a defined population in Dalarna County, Sweden. The annual incidence of breast cancer was calculated along with the annual incidence of breast cancers that were fatal within 10 and within 11 to 20 years of diagnosis among women aged 40 to 69 years who either did or did not participate in mammography screening during a 39-year period (1977-2015). For an additional comparison, corresponding data are presented from 19 years of the prescreening period (1958-1976). All patients received stage-specific therapy according to the latest national guidelines, irrespective of the mode of detection. Results: The benefit for women who chose to participate in an organized breast cancer screening program was a 60% lower risk of dying from breast cancer within 10 years after diagnosis (relative risk, 0.40; 95% confidence interval, 0.34-0.48) and a 47% lower risk of dying from breast cancer within 20 years after diagnosis (relative risk, 0.53; 95% confidence interval, 0.44-0.63) compared with the corresponding risks for nonparticipants. Conclusions: Although all patients with breast cancer stand to benefit from advances in breast cancer therapy, the current results demonstrate that women who have participated in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than do those who have not participated.

  • Liu, Haoyu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Waldén, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Cai, Demin
    Univ Calif Davis, Dept Biochem & Mol Med, Sacramento, CA 95817 USA.
    Ahl, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Bertilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Nyman, Margareta
    Lund Univ, Dept Food Technol Engn & Nutr, S-22100 Lund, Sweden.
    Holm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Dietary Fiber in Bilberry Ameliorates Pre-Obesity Events in Rats by Regulating Lipid Depot, Cecal Short-Chain Fatty Acid Formation and Microbiota Composition2019In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 6, article id 1350Article in journal (Refereed)
    Abstract [en]

    Obesity is linked to non-alcoholic fatty liver disease and risk factors associated to metabolic syndrome. Bilberry (Vaccinium myrtillus) that contains easily fermentable fiber may strengthen the intestinal barrier function, attenuate inflammation and modulate gut microbiota composition, thereby prevent obesity development. In the current study, liver lipid metabolism, fat depot, cecal and serum short-chain fatty acids (SCFAs) and gut microbiome were evaluated in rats fed bilberries in a high-fat (HFD + BB) or low-fat (LFD + BB) setting for 8 weeks and compared with diets containing equal amount of fiber resistant to fermentation (cellulose, HFD and LFD). HFD fed rats did not obtain an obese phenotype but underwent pre-obesity events including increased liver index, lipid accumulation and increased serum cholesterol levels. This was linked to shifts of cecal bacterial community and reduction of major SCFAs. Bilberry inclusion improved liver metabolism and serum lipid levels. Bilberry inclusion under either LFD or HFD, maintained microbiota homeostasis, stimulated interscapular-brown adipose tissue depot associated with increased mRNA expression of uncoupling protein-1; enhanced SCFAs in the cecum and circulation; and promoted butyric acid and butyrate-producing bacteria. These findings suggest that bilberry may serve as a preventative dietary measure to optimize microbiome and associated lipid metabolism during or prior to HFD.

  • Gustafsson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Lämås, Kristina
    Umeå University, Faculty of Medicine, Department of Nursing.
    Isaksson, Ulf
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Arctic Research Centre at Umeå University.
    Sandman, Per-Olof
    Umeå University, Faculty of Medicine, Department of Nursing. Department of Neurobiology, Care Sciences and Society, Division of Nursing, Karolinska Institutet, Stockholm, Sweden.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Constipation and laxative use among people living in nursing homes in 2007 and 20132019In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 19, article id 38Article in journal (Refereed)
    Abstract [en]

    Background: Constipation is a common condition among older people, particularly among people living in nursing homes, and the use of drugs such as opioids is one of many factors that contribute to its high prevalence. The aim of this study was to compare the prevalence of constipation and the use of laxatives between 2007 and 2013, to analyze constipation and laxative use among people who are prescribed opioids, and to identify factors associated with constipation. Methods: In 2007 and 2013, two surveys were performed in the county of Vasterbotten in Northern Sweden, comprising all those living in nursing homes. The Multi-Dimensional Dementia Assessment Scale was used to collect data regarding laxative, opioid and anticholinergic drug use, functioning in activities of daily living (ADL), cognition and symptoms of constipation. A comparison was made between 2820 people from 2007 and 1902 people from 2013. Results: The prevalence of symptoms of constipation among people living in nursing homes increased from 36% in 2007 to 40% in 2013. After controlling for age, sex, ADL, cognitive impairment and use of opioid and anticholinergic drugs, this difference was found to be statistically significant. When controlled for demographic changes, there was a statistically significant difference in the regular use of laxatives between the respective years, from 46% in 2007 to 59% in 2013. People prescribed opioids and anticholinergic drugs were at increased risk of constipation, while people with a higher ADL score were at decreased risk. Further, among people prescribed opioids and rated as constipated, 35% in 2007 and 20% in 2013 were not prescribed laxatives for regular use, a difference that was found to be statistically significant. Conclusions: The prevalence of symptoms of constipation increased between 2007 and 2013. Although there was a decrease between the years, there were still a number of people being prescribed with opioids and rated as constipated who were not treated with laxatives. This study therefore indicates that constipation remains a significant problem among people in nursing homes and also indicates that those prescribed opioids could benefit from an increased awareness of the risk of constipation and treatment, if required.

  • Public defence: 2019-09-27 10:15 Alan Turing, Linköping
    Mengist, Alachew
    Linköping University, Department of Computer and Information Science, Software and Systems.
    Methods and Tools for Efficient Model-Based Development of Cyber-Physical Systems with Emphasis on Model and Tool Integration2019Licentiate thesis, monograph (Other academic)
    Abstract [en]

    Model-based tools and methods are playing important roles in the design and analysis of cyber-physical systems before building and testing physical prototypes. The development of increasingly complex CPSs requires the use of multiple tools for different phases of the development lifecycle, which in turn depends on the ability of the supporting tools to interoperate. However, currently no vendor provides comprehensive end-to-end systems engineering tool support across the entire product lifecycle, and no mature solution currently exists for integrating different system modeling and simulation languages, tools and algorithms in the CPSs design process. Thus, modeling and simulation tools are still used separately in industry.

    The unique challenges in integration of CPSs are a result of the increasing heterogeneity of components and their interactions, increasing size of systems, and essential design requirements from various stakeholders. The corresponding system development involves several specialists in different domains, often using different modeling languages and tools. In order to address the challenges of CPSs and facilitate design of system architecture and design integration of different models, significant progress needs to be made towards model-based integration of multiple design tools, languages, and algorithms into a single integrated modeling and simulation environment.

    In this thesis we present the need for methods and tools with the aim of developing techniques for numerically stable co-simulation, advanced simulation model analysis, simulation-based optimization, and traceability capability, and making them more accessible to the model-based cyber physical product development process, leading to more efficient simulation. In particular, the contributions of this thesis are as follows: 1) development of a model-based dynamic optimization approach by integrating optimization into the model development process; 2) development of a graphical co-modeling editor and co-simulation framework for modeling, connecting, and unified system simulation of several different modeling tools using the TLM technique; 3) development of a tool-supported method for multidisciplinary collaborative modeling and traceability support throughout the development process for CPSs; 4) development of an advanced simulation modeling analysis tool for more efficient simulation.

  • Fors, Carina
    et al.
    Swedish National Road and Transport Research Institute, Traffic and road users, Human Factors in the Transport System.
    Johansen, Trond Cato
    Ramböll.
    Nordic certification system for roadmarking materials: Version 6:20192019Report (Other academic)
    Abstract [en]

    A Nordic certification system for road marking materials was introduced in 2015. The system is basedon documented performance measurements of material samples applied on test fields on public roads.The certification system includes both flat (type I) and structured/profiled (type II) markings, antiskidmaterials (materials with enhanced friction), temporary markings (Denmark only) and inlaid markings(Norway only). From 2019, the certification system will also include materials for hand applicationand materials with enhanced durability for illuminated high-traffic urban areas.

    Material tests are carried out at two test sites: one in Norway and one in Denmark. The tests fields aresituated on public roads and the tested materials are thus exposed to real traffic conditions and toweather conditions representative for the Nordic countries. The materials are followed up byperformance measurements during one or two years. The certification includes requirements oncoefficient of retroreflected luminance RL under dry and wet conditions, luminance coefficient underdiffuse illumination Qd, friction and colour coordinates. The number of wheel passages is measured atthe test sites annually. The certification system includes material identification, which allows forfuture material sampling and analysis.

    The certification system is based on the European standards EN 1824 Road marking materials – Roadtrials, EN 1436 Road marking materials – Road marking performance for road users, and EN 12802Road marking materials – Laboratory methods for identification.

    The report describes the certification system and how it is applied in the Nordic countries. Proceduresand methods that are used for application of materials and performance measurements are specified.

  • Färgforum 2019: hållbarhet : rapport2019Report (Other academic)
    Abstract [sv]

    Färgforum 2019 arrangerades 11–12 april 2019 av Riksantikvarieämbetet i samarbete med Sundsvalls kommun, Göteborgs universitet, Hantverkslaboratoriet, Statens fastighetsverk och Byggnadsvårdsföreningen. Konferensen hölls i stadshuset i Sundsvall. Rapporten sammanfattar de presentationer som hölls under konferensen och har sammanställts av Färgforums projektgrupp på Riksantikvarieämbetet.

  • Malm Lindberg, Ingrid
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Department of Theology, Studies in Faith and Ideologies.
    The Thought Experimenting Qualities of Kierkegaard's Fear and Trembling2019In: Religions, ISSN 2077-1444, E-ISSN 2077-1444, Vol. 10, no 6, article id 391Article in journal (Refereed)
    Abstract [en]

    In this article, I examine the possible thought experimenting qualities of SOren Kierkegaard's novel Fear and Trembling and in which way (if any) it can be explanatory. Kierkegaard's preference for pseudonyms, indirect communication, Socratic interrogation, and performativity are identified as features that provide the narrative with its thought experimenting quality. It is also proposed that this literary fiction functions as a Socratic-theological thought experiment due to its influences from both philosophy and theology. In addition, I suggest three functional levels of the fictional narrative that, in different ways, influence its possible explanatory force. As a theoretical background for the investigation, two accounts of literary cognitivism are explored: Noel Carroll's Argument Account and Catherine Elgin's Exemplification Account. In relation to Carroll's proposal, I conclude that Fear and Trembling develops a philosophical argumentation that is dependent on the reader's own existential contribution. In relation to Elgin's thought, the relation between truth and explanatory force is acknowledged. At the end of the article, I argue that it is more accurate to see the explanatory force of Fear and Trembling in relation to its exploratory function.

  • Cavanagh, Jorunn Pauline
    et al.
    Askarian, Fatemeh
    Pain, Maria
    Bruun, Jack-Ansgar
    Urbarova, Ilona
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Schmidt, Frank
    Johannessen, Mona
    Proteome profiling of secreted and membrane vesicle associated proteins of an invasive and a commensal Staphylococcus haemolyticus isolate2019In: Data in Brief, E-ISSN 2352-3409, Vol. 22, p. 914-919Article in journal (Refereed)
    Abstract [en]

    Bacterial membrane vesicles (MVs) mediate bacterial virulence by enabling secretion and long distance delivery of bacterial effector molecules. Staphylococcus haemolyticus has now been demonstrated to produce membrane vesicles (MVs). The protein content of S. haemolyticus MVs was identified by Mass spectrometry and compared to proteins identified in the total secretome. This information is presented in this data article. Further background and interpretation of the data can be found in the article: Comparative exoproteome profiling of an invasive and a commensal S. haemolyticus isolate (Cavanagh et al., in press). Data are available via Proteome Xchange with identifier PXD010389.

  • Procházka, Vladimir
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Theoretical Physics.
    Boundary gauge and gravitational anomalies from Ward identities2019In: Journal of High Energy Physics (JHEP), ISSN 1126-6708, E-ISSN 1029-8479, no 7, article id 047Article in journal (Refereed)
    Abstract [en]

    We consider the two-point functions of conserved bulk currents and energymomentum tensor in a boundary CFT defined on R_(1,2). Starting from the consistent forms of boundary gauge and gravitational anomalies we derive their respective contributions to the correlation functions in the form of anomalous Ward identities. Using the recently developed momentum space formalism we find an anomalous solution to each of these identities depending on a single undetermined form-factor. We study the solution in two different kinematic limits corresponding to small and large momentum p(n), perpendicular to the boundary. We find that the anomalous term interpolates between a non-local form resembling the standard anomaly-induced term in a two-dimensional CFT at small pn and Chern-Simons contact terms at large pn. Using this we derive some consistency conditions regarding the dependence of these anomalies on the boundary conditions and discuss possible cancellation mechanisms. These ideas are then demonstrated on the explicit example of free, massless three-dimensional fermion. In particular we manage to obtain the respective anomalies via a diagrammatic momentum space computation and expose the well- known relation between bulk parity anomaly and boundary gauge anomalies.

  • Zorgati, Habiba
    et al.
    ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore;Natl Univ Singapore, Dept Biochem, Singapore 117596, Singapore.
    Larsson, Mårten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore.
    Ren, Weitong
    Nanjing Univ, Collaborat Innovat Ctr Adv Microstruct, Dept Phys, Natl Lab Solid State Microstruct, Nanjing 210093, Jiangsu, Peoples R China.
    Sim, Adelene Y. L.
    ASTAR, Bioinformat Inst, Singapore 138671, Singapore.
    Gettemans, Jan
    Univ Ghent, Fac Med & Hlth Sci, Dept Biomol Med, Nanobody Lab, B-9000 Ghent, Belgium.
    Grimes, Jonathan M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England;Diamond Light Source Ltd, Didcot OX11 ODE, Oxon, England.
    Li, Wenfei
    Nanjing Univ, Collaborat Innovat Ctr Adv Microstruct, Dept Phys, Natl Lab Solid State Microstruct, Nanjing 210093, Jiangsu, Peoples R China.
    Robinson, Robert C.
    ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore;Vidyasirimedhi Inst Sci & Technol, Sch Biomol Sci & Engn, Rayong 21210, Thailand;Okayama Univ, Res Inst Interdisciplinary Sci, Okayama 7008530, Japan.
    The role of gelsolin domain 3 in familial amyloidosis (Finnish type)2019In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, no 28, p. 13958-13963Article in journal (Refereed)
    Abstract [en]

    In the disease familial amyloidosis, Finnish type (FAF), also known as AGeI amyloidosis (AGeI), the mechanism by which point mutations in the calcium-regulated actin-severing protein gelsolin lead to furin cleavage is not understood in the intact protein. Here, we provide a structural and biochemical characterization of the FAF variants. X-ray crystallography structures of the FAF mutant gelsolins demonstrate that the mutations do not significantly disrupt the calcium-free conformations of gelsolin. Small-angle X-ray-scattering (SAXS) studies indicate that the FAF calcium-binding site mutants are slower to activate, whereas G167R is as efficient as the wild type. Actin-regulating studies of the gelsolins at the furin cleavage pH (6.5) show that the mutant gelsolins are functional, suggesting that they also adopt relatively normal active conformations. Deletion of gelsolin domains leads to sensitization to furin cleavage, and nanobody-binding protects against furin cleavage. These data indicate instability in the second domain of gelsolin (G2), since loss or gain of G2-stabilizing interactions impacts the efficiency of cleavage by furin. To demonstrate this principle, we engineered non-FAF mutations in G3 that disrupt the G2-G3 interface in the calcium-activated structure. These mutants led to increased furin cleavage. We carried out molecular dynamics (MD) simulations on the FAF and non-FAF mutant G2-G3 fragments of gelsolin. All mutants showed an increase in the distance between the center of masses of the 2 domains (G2 and G3). Since G3 covers the furin cleavage site on G2 in calcium-activated gelsolin, this suggests that destabilization of this interface is a critical step in cleavage.

  • Wänström, Johan
    Linköping University, Department for Studies of Social Change and Culture, Centre for Municipality Studies – CKS. Linköping University, Faculty of Arts and Sciences.
    Motsatta ideal i den politiska styrningen av mindre kommuner: Mot en ny(gammal) kommunal politikerroll?2019Report (Other academic)
    Abstract [sv]

    Under senare år har det förts en diskussion om hur Sveriges kommuner ska styras. Tillitsdelegationen och dess uppdragsgivare (regeringen) vill till exempel se mindre målstyrning och framförallt mindre uppföljning och hårt ansvarsutkrävande till förmån för en politisk styrning som präglas mer av dialog och tillit. Mycket av den tidigare forskningen om målstyrning har genomförts på kommuner som är större än den svenska mediankommunen, det vill säga kommuner som har mer än 16 000 invånare. Den här studien gör istället nedslag i tre kommuner som alla har mindre än 16 000 invånare.

    Syftet med den här studien är att beskriva och analysera de olika ideal som präglar ledande politikers och tjänstepersoners reflektioner kring hur den politiska styrningen i mindre kommuner bör organiseras och utföras. Genom djupintervjuer med 14 ledande politiker och tjänstepersoner framkom två övergripande modeller för den politiska styrningen – modeller som i sin tur präglas av två övergripande ideal: närhet och distans.

    Vissa av respondenterna framhävde betydelsen av att ett större avstånd mellan styrande politiker och oppositionspolitiker för att på så sätt skapa förutsättningar för mer av majoritets- och framförallt konkurrensdemokrati. De förespråkade också ett större avstånd mellan politiker och tjänstemän där politikerna fokuserar på att styra genom mål och andra former av övergripande riktlinjer. Andra respondenter framhävde betydelsen av att olika aktörer – såväl politiker, tjänstepersoner som lokala medborgare, företag och föreningar – verkar i ett nära samspel där samförstånd snarare än konflikt eftersträvas. När förespråkare för mer distanserade relationer framhäver vikten av platsoberoende akademiskt förankrad kunskap (vilken framförallt förväntas finnas i den professionaliserade förvaltningen) framhäver de som förespråkar ett nära samspel ofta betydelsen av den lokalt förankrade kunskapen som finns och växer fram i samspelet mellan olika aktörer. När de som förespråkar mer distanserade relationer framhäver vikten av tilliten till övergripande principer och system, framhäver de som förespråkar ett nära samspel tilliten mellan enskilda individer.

    Det faktum att Sveriges kommuner ser olika ut i relation till en rad olika parametrar, såsom till exempel befolkningsmässig och geografisk storlek, gör att man har olika förutsättningar att genomföra någon form av universell styrmodell. Den här studien påvisar därutöver att såväl politiker som tjänstpersoner i olika kommuner sätter olika värde till olika ideal kopplade till den politiska styrningen – ideal som ofta behöver balanseras mot varandra.

  • Zisopoulos, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics. CERN, CH-1211 Geneva, Switzerland.
    Papaphilippou, Y.
    CERN, CH-1211 Geneva, Switzerland.
    Laskar, J.
    IMCCE, Observ Paris, 77 Ave Denfert Rochereau, F-75014 Paris, France.
    Refined betatron tune measurements by mixing beam position data2019In: PHYSICAL REVIEW ACCELERATORS AND BEAMS, E-ISSN 2469-9888, Vol. 22, no 7, article id 071002Article in journal (Refereed)
    Abstract [en]

    The measurement of the betatron tunes in a circular accelerator is of paramount importance due to their impact on beam dynamics. The resolution of the these measurements, when using turn-by-turn (TBT) data from beam position monitors, is greatly limited by the available number of turns in the signal. Because of decoherence from finite chromaticity and/ or amplitude detuning, the transverse betatron oscillations appear to be damped in the TBT signal. On the other hand, an adequate number of samples is needed, if precise and accurate tune measurements are desired. In this paper, a method is presented that allows for very precise tune measurements within a very small number of turns. The theoretical foundation of this method is presented with results from numerical and tracking simulations and experimental TBT data which are recorded at electron and proton circular accelerators.

  • Public defence: 2019-09-24 13:00 Belladonna, Linköping
    Bratengeier, Cornelia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Mechanisms of mechanically induced Osteoclastogenesis: in a novel in vitro model for bone implant loosening2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Total joint arthroplasty is the primary intervention in the treatment of end-stage osteoarthritis. Despite the high success rate, in some patients, the replacement will fail during their lifetime requiring a revision of the implant. These revisions are strenuous for the patient and costly for health care. Joint replacement at a younger age, in combination with a more active lifestyle, increases the need for an early revision of the joint prosthesis. The main reason for revision surgeries is aseptic loosening, a condition where the prosthesis is loosening due to bone degradation at the peri-prosthetic interface in the absence of infections. The most well-established pathological mechanism for aseptic loosening is related to wear particles, generated from different parts of the prosthesis that will trigger bone degradation and bone loss. In addition, early micromotions of the prosthesis and resulting local pressurized fluid flow in the peri-prosthetic interface (supraphysiological loading) have also been identified as a cause for aseptic loosening. However, it remains unknown what cells are the primary responders to supraphysiological loading, and what underlying physical, cellular and molecular mechanism that triggers osteoclast differentiation and osteolysis.

    In this thesis, we intended to shed light on three currently unknown aspects of mechanical loading-induced peri-prosthetic osteolysis, leading to aseptic loosening of orthopedic prostheses: (1)Which cells are the primary responder to supraphysiological loading? (2)What characteristics of the mechanical stimulus induce an osteo-protective or osteo-destructive response? (3)Which cellular mechano-sensing mechanisms are involved in an osteo-destructive response?

    We successfully implemented supraphysiological mechanical loading, mimicking the periprosthetic pressurized fluid flow around a loosening implant, in an in vitro model for bone implant loosening. Using this model, we uncovered the involvement of mesenchymal stem cells and myeloid progenitor cells (monocytes) in mechanical loading-induced peri-prosthetic osteolysis. Applying supraphysiological loading on cells from patients undergoing primary hip arthroplasty, successfully validated the in vitro model for the use of cells of human origin. We further identified in murine myeloid progenitor cells that a combination of high loading amplitude (3.0±0.2Pa), prolonged active loading duration per cycle (duty cycle 22%-50%), and rapid alterations in minimum/maximum values of the loading profile (square wave) is necessary to induce an osteo-destructive response. Further, the loading-induced ATP release and subsequent activation of the P2X7 receptor was essential for the release of soluble factors modulating osteoclastogenesis.

    In conclusion, we expect that the proposed new in vitro model is a helpful tool to further advance the knowledge in aseptic loosening, by uncovering the mechanoresponsive cellular mechanism to supraphysiological mechanical loading. The identification of the respondent cells in mechanical loading-induced prosthetic loosening gives the opportunity to deliver targeted treatment strategies. Furthermore, identifying the physical parameters that define the shift towards an osteo-destructive response emphasizes the importance of the prosthetic design and surgical technique to reduce mechanical loading-induced bone degradation around a prosthesis.

  • Tammimies, Kristiina
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Psychiat Res, Ctr Neurodev Disorders KIND,Div Neuropsychiat, Solna, Sweden.
    Li, Danyang
    Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Psychiat Res, Ctr Neurodev Disorders KIND,Div Neuropsychiat, Solna, Sweden.
    Rabkina, Ielyzaveta
    Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Psychiat Res, Ctr Neurodev Disorders KIND,Div Neuropsychiat, Solna, Sweden.
    Stamouli, Sofia
    Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Psychiat Res, Ctr Neurodev Disorders KIND,Div Neuropsychiat, Solna, Sweden.
    Becker, Martin
    Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Psychiat Res, Ctr Neurodev Disorders KIND,Div Neuropsychiat, Solna, Sweden.
    Nicolaou, Veronika
    Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Psychiat Res, Ctr Neurodev Disorders KIND,Div Neuropsychiat, Solna, Sweden.
    Berggren, Steve
    Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Psychiat Res, Ctr Neurodev Disorders KIND,Div Neuropsychiat, Solna, Sweden;Stockholm Hlth Serv, Child & Adolescent Psychiat, Stockholm, Sweden.
    Coco, Christina
    Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Psychiat Res, Ctr Neurodev Disorders KIND,Div Neuropsychiat, Solna, Sweden;Stockholm Hlth Serv, Child & Adolescent Psychiat, Stockholm, Sweden.
    Falkmer, Torbjörn
    Curtin Univ, Sch Occupat Therapy Social Work & Speech Pathol, Curtin Autism Res Grp, Bentley, WA, Australia;Linkoping Univ, Dept Med & Hlth Sci, Pain & Rehabil Ctr, Linkoping, Sweden.
    Jonsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry. Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Psychiat Res, Ctr Neurodev Disorders KIND,Div Neuropsychiat, Solna, Sweden;Stockholm Hlth Serv, Child & Adolescent Psychiat, Stockholm, Sweden.
    Choque-Olsson, Nora
    Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Psychiat Res, Ctr Neurodev Disorders KIND,Div Neuropsychiat, Solna, Sweden;Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.
    Bölte, Sven
    Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Psychiat Res, Ctr Neurodev Disorders KIND,Div Neuropsychiat, Solna, Sweden;Stockholm Hlth Serv, Child & Adolescent Psychiat, Stockholm, Sweden;Curtin Univ, Sch Occupat Therapy Social Work & Speech Pathol, Curtin Autism Res Grp, Bentley, WA, Australia.
    Association between Copy Number Variation and Response to Social Skills Training in Autism Spectrum Disorder2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 9810Article in journal (Refereed)
    Abstract [en]

    Challenges in social communication and interaction are core features of autism spectrum disorder (ASD) for which social skills group training (SSGT) is a commonly used intervention. SSGT has shown modest and heterogeneous effects. One of the major genetic risk factors in ASD is rare copy number variation (CNV). However, limited information exists whether CNV profiles could be used to aid intervention decisions. Here, we analyzed the rare genic CNV carrier status for 207 children, of which 105 received SSGT and 102 standard care as part of a randomized clinical trial for SSGT. We found that being a carrier of rare genic CNV did not have an impact on the SSGT outcome measured by the parent-report Social Responsiveness Scale (SRS). However, when stratifying by pathogenicity and size of the CNVs, we identified that carriers of clinically significant and large genic CNVs (> 500 kb) showed inferior SRS outcomes at post-intervention (P = 0.047 and P = 0.036, respectively) and follow-up (P = 0.008 and P = 0.072, respectively) when adjusting for standard care effects. Our study provides preliminary evidence that carriers of clinically significant and large genic CNVs might not benefit as much from SSGT as non-carriers. Our results indicate that genetic information might help guide the modifications of interventions in ASD.

  • Carlsson, Johanna
    et al.
    Egertsdotter, Ulrika
    Ganeteg, Ulrika
    Svennerstam, Henrik
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Nitrogen utilization during germination of somatic embryos of Norway spruce: revealing the importance of supplied glutamine for nitrogen metabolism2019In: Trees, ISSN 0931-1890, E-ISSN 1432-2285, Vol. 33, no 2, p. 383-394Article in journal (Refereed)
    Abstract [en]

    Key messageThis paper shows that germinating Norway spruce somatic embryos are dependent on the carbon and nitrogen supplied in the medium, and that supplied glutamine accounts for 50 % of assimilated nitrogen during germination.AbstractThe female megagametophyte, which provides the zygotic embryo with nitrogen (N), carbon (C) and energy during germination, is not present in Norway spruce (Picea abies) mature somatic embryos. Therefore, somatic embryos presumably rely on nutrients supplied in the germination medium in addition to their storage compounds accumulated during maturation. However, to what extent stored versus supplied compounds contribute to a somatic embryo germination is unclear. In this 24-day study, we addressed the above question by monitoring the biomass changes and the N and C budget during somatic embryo germination, under low-intensity red light. We found that the C and N storage reserves, accumulated during the maturation phase, were not sufficient to support the growth of the germinating somatic embryos, rather they were dependent on the medium components. In addition, in a previous study it has been found that glutamine (Gln) supplied in the medium was crucial for maintaining the primary amino acid (AA) metabolism and growth of the proliferating embryogenic cultures of Norway spruce (Carlsson et al., PLoS One 12(8):e0181785, 2017). Therefore, we hypothesised that Gln would be required as a significant source of N also during somatic embryo germination. By tracing the uptake of isotopically labelled N-sources from the medium and further into primary N assimilation, we found that Gln was the preferred source of N for the germinating somatic embryos, accounting for 50% of assimilated N. As the amounts of both arginine (Arg) and Gln were increased in the germinating somatic embryos, it also suggested that germination in low-intensity red light promoted N storage, similar to what has been observed in the zygotic embryo maturation in conifers (King, Gifford, Plant Physiol 113:1125-1135, 1997).

  • Avenel, Christophe
    et al.
    CADESS Med AB, Uppsala, Sweden.
    Tolf, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Carlbom, Ingrid
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. CADESS Med AB, Uppsala, Sweden.
    Glandular Segmentation of Prostate Cancer: An Illustration of How the Choice of Histopathological Stain Is One Key to Success for Computational Pathology2019In: Frontiers in Bioengineering and Biotechnology, E-ISSN 2296-4185, Vol. 7, article id 125Article in journal (Refereed)
    Abstract [en]

    Digital pathology offers the potential for computer-aided diagnosis, significantly reducing the pathologists' workload and paving the way for accurate prognostication with reduced inter-and intra-observer variations. But successful computer-based analysis requires careful tissue preparation and image acquisition to keep color and intensity variations to a minimum. While the human eye may recognize prostate glands with significant color and intensity variations, a computer algorithm may fail under such conditions. Since malignancy grading of prostate tissue according to Gleason or to the International Society of Urological Pathology (ISUP) grading system is based on architectural growth patterns of prostatic carcinoma, automatic methods must rely on accurate identification of the prostate glands. But due to poor color differentiation between stroma and epithelium from the common stain hematoxylin-eosin, no method is yet able to segment all types of glands, making automatic prognostication hard to attain. We address the effect of tissue preparation on glandular segmentation with an alternative stain, Picrosirius red-hematoxylin, which clearly delineates the stromal boundaries, and couple this stain with a color decomposition that removes intensity variation. In this paper we propose a segmentation algorithm that uses image analysis techniques based on mathematical morphology and that can successfully determine the glandular boundaries. Accurate determination of the stromal and glandular morphology enables the identification of the architectural pattern that determine the malignancy grade and classify each gland into its appropriate Gleason grade or ISUP Grade Group. Segmentation of prostate tissue with the new stain and decomposition method has been successfully tested on more than 11000 objects including well-formed glands (Gleason grade 3), cribriform and fine caliber glands (grade 4), and single cells (grade 5) glands.

  • Public defence: 2019-09-20 10:15 ACAS, Linköping
    Larsson, L. Viktor
    Linköping University, Department of Management and Engineering, Fluid and Mechatronic Systems. Linköping University, Faculty of Science & Engineering.
    Control of Hybrid Hydromechanical Transmissions2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis deals with control aspects of complex hybrid hydromechanical transmissions for heavy mobile working machines. Control problems are identified and solved to facilitate the implementation and use of these systems.

    Fuel prices and environmental concerns have increased the interest in hybrid hydromechanical transmissions for heavy mobile working machines. Hybridisation, the introduction of a secondary energy source in the transmission, offers attractive improvements in terms of both fuel efficiency and performance. These improvements are, in turn, enabled by software control. A complex transmission architecture has several components that need to interact in a stable manner. In addition, optimal utilisation of the added energy source is required to maximise fuel savings. Meanwhile, there is a strong trend towards automation, where many of the operator’s difficult control tasks need to be managed by computers. Sophisticated control strategies are therefore needed, along with a deeper understanding of dynamic properties.

    Previous research on the control of hybrid hydromechanical transmissions has primarily focussed on on-road applications. The working conditions of heavy working machines place different requirements on the transmission, which is also reflected in the control strategy.

    This thesis highlights the importance of fast response of the variable displacement pump/motors used in hybrid hydromechanical transmissions. Their central position in the interface between hydraulics and mechanics makes their dynamic performance a limiting factor both for the stability of the transmission control loops and in the realisation of smooth mode shifts in multiplemode transmissions. Dynamic models and control strategies for displacement actuators are derived and validated in simulation and experiments. A linear model for dynamic analysis of a general hybrid hydromechanical transmission for heavy working machines is derived and a powertrain control strategy based on decoupled control is proposed. The strategy is verified in simulations and experiments in hardware-in-the-loop simulations, and may be used in a working machine with or without a human operator.

  • Dahal, Prabin
    et al.
    World Wide Antimalarial Resistance Network WWARN, Oxford, England;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, WorldWide Antimalarial Resistance Network WWARN, Oxford, England.
    Simpson, Julie Anne
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostatist, Melbourne, Vic, Australia.
    Abdulla, Salim
    Ifakara Hlth Inst, Dar Es Salaam, Tanzania.
    Achan, Jane
    MRC Unit, Banjul, Gambia.
    Adam, Ishag
    Univ Khartoum, Fac Med, Khartoum, Sudan.
    Agarwal, Aarti
    Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Malaria Branch, Atlanta, GA USA.
    Allan, Richard
    Mentor Initiat, Fajara, Gambia.
    Anvikar, Anupkumar R.
    Natl Inst Malaria Res, Sector 8, Dwarka, New Delhi 110077, India.
    Arinaitwe, Emmanuel
    Infect Dis Res Collaborat, Kampala, Uganda.
    Ashley, Elizabeth A.
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England;Myanmar Oxford Clin Res Unit, Yangon, Myanmar.
    Awab, Ghulam Rahim
    Mahidol Univ, Fac Trop Med, Bangkok, Thailand;Minist Publ Hlth, Islam Republ Afghanistan, Kabul, Afghanistan.
    Bassat, Quique
    Ctr Investigacao Saude Manhica CISM, Maputo, Mozambique;Univ Barcelona, Hosp Clin, ISGlobal, Barcelona, Spain;ICREA, Pg Lluis Companys 23, Barcelona 08010, Spain.
    Bjorkman, Anders
    Karolinska Inst, Depatment Microbiol Tumour & Cell Biol, Stockholm, Sweden.
    Bompart, Francois
    Sanofi Access Med, Gentilly, France.
    Borrmann, Steffen
    Kenya Med Res Inst Kilifi, Kilifi, Kenya;Wellcome Trust Res Programme, Kilifi, Kenya;Heidelberg Univ, Sch Med, Dept Infect Dis, Heidelberg, Germany.
    Bousema, Teun
    Radboud Inst Hlth Sci, Radboudumc Nijmegen, Nijmegen, Netherlands;Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands.
    Broek, Ingrid
    Centrum Infectieziektebestrijding, Epidemioloog Epidemiol Surveillance RIVM, Bilthoven, Netherlands.
    Bukirwa, Hasifa
    African Field Epidemiol Network, Kampala, Uganda.
    Carrara, Verena I.
    Shoklo Malaria Res Unit, Mae Sot, Bangkok, Thailand;Mahidol Oxford Univ Res Unit, Bangkok, Thailand.
    Corsi, Marco
    Private Consultancy Drug Dev Trop Dis, Sigma Tau SpA Ind Farmaceutiche Riunite, Pomezia, Rome, Italy.
    Cot, Michel
    Univ Paris 05, Sorbonne Paris Cite, MERIT, IRD, F-75006 Paris, France.
    D'Alessandro, Umberto
    MRC Unit, Fajara, Gambia;London Sch Hyg & Trop Med, London, England.
    Davis, Timothy M. E.
    Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia.
    de Wit, Marit
    Med Sans Frontieres Operat Ctr Amsterdam, Geneva, Switzerland.
    Deloron, Philippe
    Univ Paris 05, Sorbonne Paris Cite, MERIT, IRD, F-75006 Paris, France.
    Desai, Meghna
    Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Malaria Branch, Atlanta, GA USA.
    Dimbu, Pedro Rafael
    Natl Malaria Control Program, Luanda, Angola.
    Djalle, Djibrine
    Inst Pasteur, BP 923, Bangui, Cent Afr Republ.
    Djimde, Abdoulaye
    Univ Sci Techn & Technol Bamako, Fac Pharm, Malaria Res & Training Ctr, Dept Epidemiol Parasit Dis, Bamako, Mali.
    Dorsey, Grant
    Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
    Doumbo, Ogobara K.
    Univ Sci Techn & Technol Bamako, Malaria Res & Training Ctr, Dept Epidemiol Parasit Dis, Fac Med & Odonto Stomatol, Bamako, Mali.
    Drakeley, Chris J.
    London Sch Hyg & Trop Med, Dept Infect & Immun, London, England.
    Duparc, Stephan
    Med Malaria Venture, Geneva, Switzerland.
    Edstein, Michael D.
    Australian Army Malaria Inst, Brisbane, Qld, Australia.
    Espie, Emmanuelle
    R&D Ctr, GSK Vaccines, Clin & Epidemiol Dept, Epicentre, Ave Fleming 20,1300 Wavre,8 Rue St Sabin, F-75011 Paris, France.
    Faiz, Abul
    Malaria Res Grp, Chittagong, Bangladesh;Dev Care Fdn, Dhaka, Bangladesh.
    Falade, Catherine
    Univ Ibadan, Coll Med, Dept Pharmacol & Therapeut, Ibadan, Nigeria.
    Fanello, Caterina
    Univ Oxford, Nuffield Dept Med, Ctr Global Hlth, Oxford, England.
    Faucher, Jean-Francois
    Besancon Univ Med Ctr, Dept Infect Dis, Mother & Child Hlth Trop Res Unit, Inst Rech Dev IRD, Besancon, France.
    Faye, Babacar
    Univ Cheikh Anta Diop, Fac Med, Dept Med Parasitol, Dakar, Senegal.
    Fortes, Filomeno de Jesus
    Natl Malaria Control Program, Luanda, Angola.
    Gadalla, Nahla B.
    Sudanese Amer Med Assoc, Fairfax, VA USA.
    Gaye, Oumar
    Univ Cheikh Anta Diop, Dept Med Parasitol, Fac Med, Dakar, Senegal.
    Gil, J. Pedro
    Karolinska Inst, Div Pharmacogenet, Dept Physiol & Pharmacol, Drug Resistance Unit, Stockholm, Sweden;Univ Lisbon, Ctr Biodivers Funct & Integrat Gen, Fac Ciencias, Lisbon, Portugal.
    Greenwood, Brian
    London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London, England.
    Grivoyannis, Anastasia
    Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
    Hamed, Kamal
    Basilea Pharmaceut Int Ltd, Basel, Switzerland;Novartis Pharmaceut, E Hanover, NJ USA.
    Hien, Tran Tinh
    Oxford Univ Clin Res Unit OUCRU, Ctr Trop Med, Wellcome Trust Major Overseas Program MOP, Oxford, England.
    Hughes, David
    Novartis Int AG, Basel, Switzerland.
    Humphreys, Georgina
    Wellcome Trust Res Labs, London, England;World Wide Antimalarial Resistance Network WWARN, London, England.
    Hwang, Jimee
    US Centers Dis Control & Prevent, Div Parasit Dis & Malaria, US Presidents Malaria Initiat Malaria Branch, Atlanta, GA USA;Univ Calif San Francisco, San Francisco, CA 94143 USA;Global Hlth Grp, San Francisco, CA 94143 USA.
    Ibrahim, Maman Laminou
    Ctr Rech Med & Saniataire CERMES, Niamey, Niger.
    Janssens, Bart
    Medecins Sans Frontieres, Phnom Penh, Belgium.
    Jullien, Vincent
    Univ Paris 05, Assistance Publique Hop Paris, Serv Pharmacol Clin, Paris, France;Grp Hosp Cochin Saint Vincent Paul, Inserm U663, WWARN, Paris, France.
    Juma, Elizabeth
    Kenya Govt Med Res Ctr, Nairobi, Kenya.
    Kamugisha, Erasmus
    Weill Bugando Univ Coll Hlth Sci, Mwanza, Tanzania.
    Karema, Corine
    Minist Hlth, Natl Malaria Control Program TRAC Plus, Kigali, Rwanda.
    Karunajeewa, Harin A.
    Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia.
    Kiechel, Jean R.
    Drugs Neglected Dis initiat, Geneva, Switzerland.
    Kironde, Fred
    Islam Univ Uganda, Habib Med Sch, Kampala, Uganda.
    Kofoed, Poul-Erik
    Bandim Hlth Project, Indepth Network, Apartado 861, Bissau, Guinea Bissau;Lillebaelt Hosp, Hlth Serv Res Unit, Vejle, Denmark;IRS Univ Southern Denmark, Vejle, Denmark;Kolding Cty Hosp, Dept Paediat, Kolding, Denmark.
    Kremsner, Peter G.
    Univ Tubingen, Inst Trop Med, Tubingen, Germany;Ctr Recherches Medic Lambarene, Lambarene, Gabon.
    Lameyre, Valerie
    Sanofi Access Med, Gentilly, France.
    Lee, Sue J.
    Mahidol Univ, Fac Trop Med, Bangkok, Thailand;Churchill Hosp, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England.
    Marsh, Kevin
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England;Wellcome Trust Res Programme, Kilifi, Kenya;Kenya Govt Med Res Ctr, Kilifi, Kenya.
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Mayxay, Mayfong
    Mahosot Hosp, Lao Oxford Mahosot Hospital, Wellcome Trust Res Unit, Microbiol Lab, Viangchan, Laos.
    Menan, Herve
    Univ Cocody, Dept Parasitol, Fac Pharm, Abidjan, Cote Ivoire;Univ Hlth Sci, Minist Hlth, Fac Postgraduate Studies, Viangchan, Laos.
    Mens, Petra
    Acad Med Ctr, Med Microbiol Parasitol, Amsterdam, Netherlands.
    Mutabingwa, Theonest K.
    Hubert Kairuki Mem Univ, Dar Es Salaam, Tanzania;London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London, England.
    Ndiaye, Jean-Louis
    Univ Cheikh Anta Diop, Fac Med, Parasitol & Mycol Lab, Dakar, Senegal.
    Ngasala, Billy E.
    Muhimbili Univ Hlth & Allied Sci, Dept Parasitol, Dar Es Salaam, Tanzania;Karolinska Inst, Dept Med Solna, Infect Dis Unit, Malaria Res, Stockholm, Sweden.
    Noedl, Harald
    Med Univ Vienna, Vienna, Austria.
    Nosten, Francois
    Univ Oxford, Nuffield Dept Med Res Bldg, Ctr Trop Med & Global Hlth, Old Rd Campus, Oxford, England;Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Shoklo Malaria Res Unit, Mae Sot, Thailand.
    Offianan, Andre Toure
    Inst Pasteur Cote Ivoire, Malariol Dept, Abidjan, Cote Ivoire.
    Oguike, Mary
    London Sch Hyg & Trop Med, Dept Immunol & Infect, London, England.
    Ogutu, Bernhards R.
    Kenya Govt Med Res Ctr, Kisumu, Kenya;US Army Med Res Unit, Kisumu, Kenya.
    Olliaro, Piero
    UNICEF, UNDP, World Bank, WHO TDR, Geneva, Switzerland.
    Ouedraogo, Jean Bosco
    Inst Rech Sci Sante, Direct Regionale Ouest, Bobo Dioulasso, Burkina Faso;Ctr Muraz Bobo Dioulasso, Non Transmissible Dis Dept, Bobo Dioulasso, Burkina Faso.
    Piola, Patrice
    Inst Pasteur Cambodge, Phnom Penh, Cambodia.
    Plowe, Christopher V.
    Duke Univ, Duke Global Hlth Inst, Durham, NC USA.
    Plucinski, Mateusz M.
    US Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Malaria Branch, US Presidents Malaria Initiat, Atlanta, GA USA;Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA USA.
    Pratt, Oliver James
    Minist Hlth & Social Welf, Natl Malaria Control Program, Monrovia, Liberia.
    Premji, Zulfikarali
    Muhimbili Univ Coll Hlth Sci, Dar Es Salaam, Tanzania.
    Ramharter, Michael
    Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Bernhard Nocht Inst Trop Med, Dept Trop Med, Hamburg, Germany.
    Rogier, Christophe
    Div Expertise & Def Hlth strategy, Cent Directorate, French Mil Hlth Serv, Paris, France;IRBA, Bretigny Sur Orge, France;URMITE, UMR 6236, Marseille, France.
    Rombo, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Rosenthal, Philip J.
    Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
    Sawa, Patrick
    Human Hlth Div, Int Ctr Insect Physiol & Ecol, Mbita, Kenya.
    Schramm, Birgit
    Epicentre, Paris, France.
    Sibley, Carol
    WWARN, Oxford, England;Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
    Sinou, Veronique
    Aix Marseille Univ, INSERM, SSA, IRBA,MCT, Marseille, France.
    Sirima, Sodiomon
    GRAS, 06 BP 10248, Ouagadougou 06, Burkina Faso.
    Smithuis, Frank
    Myanmar Oxford Clin Res Unit, Oxford, England.
    Staedke, Sarah G.
    Infect Dis Res Collaborat, Kampala, Uganda;London Sch Hyg & Trop Med, Dept Clin Res, London, England.
    Sutanto, Inge
    Univ Indonesia, Dept Parasitol, Fac Med, 6 Salemba Raya, Jakarta 10430, Indonesia.
    Talisuna, Ambrose Otau
    WHO, Reg Off Afr, Brazzaville, Rep Congo;Univ Oxford, Nuffield Dept Med, Ctr Trop Med & Global Hlth, Oxford, England.
    Tarning, Joel
    WorldWide Antimalarial Resistance Network, Oxford, England;Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.
    Taylor, Walter R. J.
    Mahidol Univ, Fac Trop Med, Bangkok, Thailand.
    Temu, Emmanuel
    MENTOR Initiat, Crawley, England.
    Thriemer, Kamala L.
    Charles Darwin Univ, Menzies Sch Hlth Res, Global & Trop Hlth Div, Darwin, NT, Australia.
    Thuy, Nhien Nguyen
    Oxford Univ Clin Res Unit OUCRU, Wellcome Trust Major Overseas Program MOP, Ctr Trop Med, Oxford, England.
    Udhayakumar, Venkatachalam
    Ctr Dis Control & Prevent, Ctr Global Hlth, Div Parasit Dis & Malaria, Malaria Branch & Presidents Malaria Initiat, Atlanta, GA USA.
    Ursing, Johan
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC C1, Solna, Sweden;Danderyd Hosp, Dept Infect Dis, Danderyd, Sweden.
    van Herp, Michel
    Operat Ctr Brussels, Med Sans Frontieres, Brussels, Belgium;Univ Amsterdam, Acad Med Ctr, Div Infect Dis, Ctr Trop Med & Travel Med, Amsterdam, Netherlands.
    van Vugt, Michele
    Whitty, Christopher
    London Sch Hyg & Trop Med, Dept Infect & Trop Dis, Malaria Partnership, London, England.
    William, Yavo
    Univ Cocody, Dept Parasitol, Fac Pharm, Abidjan, Cote Ivoire.
    Winnips, Cornelis
    NovartisInternat AG, Basel, Switzerland.
    Zongo, Issaka
    Inst Rech Sci Sante, Direct Regionale lOuest, Bobo Dioulasso, Burkina Faso.
    Guerin, Philippe
    World Wide Antimalarial Resistance Network WWARN, Oxford, England;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England.
    Price, Ric N.
    World Wide Antimalarial Resistance Network WWARN, Oxford, England;Menzies Sch Hlth Res Charles Darwin Univ, Darwin, NT, Australia;Churchill Hosp, Ctr Clin Vaccinol & Trop Med, Oxford, England.
    Stepniewska, Kasia
    World Wide Antimalarial Resistance Network WWARN, Oxford, England;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, WorldWide Antimalarial Resistance Network WWARN, Oxford, England.
    Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis2019In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 18, article id 225Article in journal (Refereed)
    Abstract [en]

    Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections.

    Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model.

    Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold.

    Conclusions: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.

  • Hughes, Patrick William
    Max Planck Institute for Plant Breeding Research, Germany.
    Between semelparity and iteroparity: Empirical evidence for a continuum of modes of parity2017In: Ecology and Evolution, ISSN 2045-7758, E-ISSN 2045-7758, Vol. 7, no 20, p. 8232-8261Article in journal (Refereed)
    Abstract [en]

    The number of times an organism reproduces (i.e., its mode of parity) is a fundamental life‐history character, and evolutionary and ecological models that compare the relative fitnesses of different modes of parity are common in life‐history theory and theoretical biology. Despite the success of mathematical models designed to compare intrinsic rates of increase (i.e., density‐independent growth rates) between annual‐semelparous and perennial‐iteroparous reproductive schedules, there is widespread evidence that variation in reproductive allocation among semelparous and iteroparous organisms alike is continuous. This study reviews the ecological and molecular evidence for the continuity and plasticity of modes of parity—that is, the idea that annual‐semelparous and perennial‐iteroparous life histories are better understood as endpoints along a continuum of possible strategies. I conclude that parity should be understood as a continuum of different modes of parity, which differ by the degree to which they disperse or concentrate reproductive effort in time. I further argue that there are three main implications of this conclusion: (1) that seasonality should not be conflated with parity; (2) that mathematical models purporting to explain the general evolution of semelparous life histories from iteroparous ones (or vice versa) should not assume that organisms can only display either an annual‐semelparous life history or a perennial‐iteroparous one; and (3) that evolutionary ecologists should base explanations of how different life‐history strategies evolve on the physiological or molecular basis of traits underlying different modes of parity.

  • Hughes, P. William
    Max Planck Institute for Plant Breeding Research, Germany; University of Cologne, Germany.
    Minimal-Risk Seed Heteromorphism: Proportions of Seed Morphs for Optimal Risk-Averse Heteromorphic Strategies2018In: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 9, article id 1412Article in journal (Refereed)
    Abstract [en]

    Seed heteromorphism is the reproductive strategy characterized by the simultaneous production of multiple seed types. While comparing heteromorphic to monomorphic strategies is mathematically simple, there is no explicit test for assessing which ratio of seed morphs minimizes fitness variance, and hence offers a basis for comparing different heteromorphic strategies. Such a test may be particularly valuable when more than two distinct morphs are present, since many strategies may have equivalent geometric fitnesses. As noted by Gillespie (1974), in these cases avoiding rare but evolutionarily important instances of severe reductions in fitness involves the minimization of variation in fitness—i.e., risk. Here I compute the optimal proportions of two or more seed morphs for heteromorphic strategies that either: (1) minimize total fitness variance; or (2) maximize the fitness-risk ratio—i.e., the “extra” fitness accrued per unit of “extra” fitness variance. This work thereby provides a testable null hypothesis to estimate the optimal frequencies of seed morphs when multiple heteromorphic strategies have evolved in environments with severe fitness risks. Moreover, it also permits the calculation of expected seed morph frequencies when more than two seed morphs are produced.

  • Hughes, P. William
    et al.
    Max Planck Institute for Plant Breeding Research, Germany.
    Simons, Andrew M.
    Microsatellite evidence for obligate autogamy, but abundant genetic variation in the herbaceous monocarp Lobelia inflata (Campanulaceae)2015In: Journal of Evolutionary Biology, ISSN 1010-061X, E-ISSN 1420-9101, Vol. 28, no 11, p. 2068-2077Article in journal (Refereed)
    Abstract [en]

    Although high levels of self‐fertilization (>85%) are not uncommon in nature, organisms reproducing entirely through selfing are extremely rare. Predominant selfers are expected to have low genetic diversity because genetic variation is distributed among rather than within lineages and is readily lost through genetic drift. We examined genetic diversity at 22 microsatellite loci in 105 individuals from a population of the semelparous herb Lobelia inflata L. and found (i) no evidence of heterozygosity through outcrossing, yet (ii) high rates of genetic polymorphism (2–4 alleles per locus). Furthermore, this genetic variation among lineages was associated with phenotypic traits (e.g. flower colour, size at first flower). Coupled with previous work characterizing the fitness consequences of reproductive timing, our results suggest that temporal genotype‐by‐environment interaction may maintain genetic variation and, because genetic variation occurs only among lineages, this simple system offers a unique opportunity for future tests of this mechanism.

  • Diamanti, Klev
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Cavalli, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pan, Gang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kumar, Chanchal
    AstraZeneca, R&D BioPharmaceut, Translat Sci & Expt Med, Early Cardiovasc Renal & Metab, Gothenburg, Sweden;Karolinska Inst, AstraZeneca Integrated CardioMetab Ctr KI AZ ICMC, Dept Med, Huddinge, Sweden.
    Skrtic, Stanko
    AstraZeneca AB, Pharmaceut Technol & Dev, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden.
    Grabherr, Manfred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Komorowski, Jan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Polish Acad Sci, Inst Comp Sci, Warsaw, Poland.
    Wadelius, Claes
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 9653Article in journal (Refereed)
    Abstract [en]

    Type 2 diabetes (T2D) mellitus is a complex metabolic disease commonly caused by insulin resistance in several tissues. We performed a matched two-dimensional metabolic screening in tissue samples from 43 multi-organ donors. The intra-individual analysis was assessed across five key metabolic tissues (serum, visceral adipose tissue, liver, pancreatic islets and skeletal muscle), and the inter-individual across three different groups reflecting T2D progression. We identified 92 metabolites differing significantly between non-diabetes and T2D subjects. In diabetes cases, carnitines were significantly higher in liver, while lysophosphatidylcholines were significantly lower in muscle and serum. We tracked the primary tissue of origin for multiple metabolites whose alterations were reflected in serum. An investigation of three major stages spanning from controls, to pre-diabetes and to overt T2D indicated that a subset of lysophosphatidylcholines was significantly lower in the muscle of pre-diabetes subjects. Moreover, glycodeoxycholic acid was significantly higher in liver of pre-diabetes subjects while additional increase in T2D was insignificant. We confirmed many previously reported findings and substantially expanded on them with altered markers for early and overt T2D. Overall, the analysis of this unique dataset can increase the understanding of the metabolic interplay between organs in the development of T2D.

  • Hughes, Patrick William
    et al.
    Max Planck Institute for Plant Breeding Research, Germany; University of Cologne, Germany.
    Soppe, Wim J. J.
    Albani, Maria C.
    Seed traits are pleiotropically regulated by the flowering time gene PERPETUAL FLOWERING 1 (PEP1) in the perennial Arabis alpina2019In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 28, no 5, p. 1183-1201Article in journal (Refereed)
    Abstract [en]

    The life cycles of plants are characterized by two major life history transitions—germination and the initiation of flowering—the timing of which are important determinants of fitness. Unlike annuals, which make the transition from the vegetative to reproductive phase only once, perennials iterate reproduction in successive years. The floral repressor PERPETUAL FLOWERING 1 (PEP1), an ortholog of FLOWERING LOCUS C, in the alpine perennial Arabis alpina ensures the continuation of vegetative growth after flowering and thereby restricts the duration of the flowering episode. We performed greenhouse and garden experiments to compare flowering phenology, fecundity and seed traits between A. alpina accessions that have a functional PEP1 allele and flower seasonally and pep1 mutants and accessions that carry lesions in PEP1 and flower perpetually. In the garden, perpetual genotypes flower asynchronously and show higher winter mortality than seasonal ones. PEP1 also pleiotropically regulates seed dormancy and longevity in a way that is functionally divergent from FLC. Seeds from perpetual genotypes have shallow dormancy and reduced longevity regardless of whether they after‐ripened in plants grown in the greenhouse or in the experimental garden. These results suggest that perpetual genotypes have higher mortality during winter but compensate by showing higher seedling establishment. Differences in seed traits between seasonal and perpetual genotypes are also coupled with differences in hormone sensitivity and expression of genes involved in hormonal pathways. Our study highlights the existence of pleiotropic regulation of seed traits by hub developmental regulators such as PEP1, suggesting that seed and flowering traits in perennial plants might be optimized in a coordinated fashion.

  • Public defence: 2019-09-13 10:15 K3, Kåkenhus, Norrköping
    Liu, Yu
    Linköping University, Department of Science and Technology, Physics, Electronics and Mathematics. Linköping University, Faculty of Science & Engineering.
    A Data-centric Internet of Things Framework Based on Public Cloud2019Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The pervasive application of Internet of Things (IoT) has been seen in many aspects in human daily life and industrial production. The concept of IoT originates from traditional machine-to-machine (M2M) communications which aimed at solving domain-specific and applicationspecific problems. Today, the rapid progress of communication technologies, the maturation of Internet infrastructures, the continuously reduced cost of sensors, and emergence of more open standards, have witnessed the approaching of the expected IoT era, which envisions full connectivity between the physical world and the digital world via the Internet protocol. The popularity of cloud computing technology has enhanced this IoT transform, benefiting from the superior computing capability and flexible data storage, let alone the security, reliability and scalability advantages.

    However, there are still a series of obstacles confronted by the industry in deployment of IoT services. First, due to the heterogeneity of hardware devices and application scenarios, the interoperability and compatibility between link-layer protocols, sub-systems and back-end services are significantly challenging. Second, the device management requires a uniform scheme to implement the commissioning, communication, authorization and identity management to guarantee security. Last, the heterogeneity of data format, speed and storage mechanism for different services pose a challenge to further data mining.

    This thesis aims to solve these aforementioned challenges by proposing a data-centric IoT framework based on public cloud platforms. It targets at providing a universal architecture to facilitate the deployment of IoT services in massive IoT and broadband IoT categories. The framework involves three representative communication protocols, namely WiFi, Thread and Lo-RaWAN, to enable support for local, personal, and wide area networks. A security assessment taxonomy for wireless communications in building automation networks is proposed as a tool to evaluate the security performance of adopted protocols, so as to mitigate potential network flaws and guarantee the security. Azure cloud platform is adopted in the framework to provide device management, data processing and storage, visualization, and intelligent services, thanks to the mature cloud infrastructure and the uniform device model and data model. We also exhibit the value of the study by applying the framework into the digitalization procedure of the green plant wall industry. Based on the framework, a remote monitoring and management system for green plant wall is developed as a showcase to validate the feasibility. Furthermore, three specialized visualization methods are proposed and a neuron network-based anomaly detection method is deployed in the project, showing the potential of the framework in terms of data analytics and intelligence.

  • Carboni, Marco
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Naylor, Andrew J.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Valvo, Mario
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Younesi, Reza
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Unlocking high capacities of graphite anodes for potassium-ion batteries2019In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 9, no 36, p. 21070-21074Article in journal (Refereed)
    Abstract [en]

    Graphite is considered a promising candidate as the anode for potassium-ion batteries (KIBs). Here, we demonstrate a significant improvement in performance through the ball-milling of graphite. Electrochemical techniques show reversible K-intercalation into graphitic layers, with 65% capacity retention after 100 cycles from initial capacities and extended cycling beyond 200 cycles. Such an affinity of the graphite towards storage of K-ions is explained by means of SEM and Raman analyses. Graphite ball-milling results in a gentle mechanical exfoliation of the graphene layers and simultaneous defect formation, leading to enhanced electrochemical performance.

  • Public defence: 2019-09-20 09:00 Berzeliussalen, Linköping
    Carlén, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Exercise Testing in Firefighters: Work Capacity and Cardiovascular Risk Assessment in a Low-Risk Population2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background. Firefighting is one of the most physically demanding occupations and it requires a high cardiorespiratory fitness level.

    Pre-duty medical evaluation of firefighters includes fitness testing and assessment of cardiac health to ensure that firefighters meet the minimum physical fitness standard and to ensure that they are not at increased risk of cardiac events. The medical evaluation methods for Swedish firefighters are regulated by the Swedish Work Environment Authority and include a 6 min constant workload treadmill (TM) test for fitness evaluation in which the firefighter wears full smoke diving equipment and a maximal effort exercise electrocardiography test (ExECG) at cycle ergometer (CE) for assessment of cardiac health. Previously, fitness was also evaluated by cycle ergometry.

    The standard parameter for evaluation of ischaemic heart disease (IHD) is exercise-induced ST depression. In general, exercise testing of asymptomatic low-risk individuals is discouraged due to low sensitivity and specificity for IHD, generating both false-positive and false-negative test results. Heart rate (HR) adjustment of the ST-segment response has been shown to be superior to simple ST depression to evaluate cardiac ischaemia in some populations, but has not been extensively evaluated in an occupational setting.

    Methods. We retrospectively analysed a cohort of 774 firefighters who were asymptomatic at the time of the testing.

    In paper I, test approval, HR response, and calculated oxygen uptake from TM tests and CE tests for 424 firefighters (44±10 years) were compared.

    Paper II methodologically described the process for data extraction, processing, and calculation of ExECG data from a clinical database. Procedures for noise assessment, error checking, and computerized calculation of ST/HR parameters were described.

    In paper III, ExECG and medical records of 521 male firefighters (44±10 years) were studied. During 8.4 ± 2.1 years of follow-up, IHD was verified angiographically in 12 subjects. The predictive value of HR-adjusted ST variables (ST/HR index, ST/HR slope, and ST/HR loop) for IHD was evaluated.

    In paper IV, subjects with objectively verified IHD were excluded and factors associated with exercise-induced nonischaemic ST depression were studied in the remaining 509 males (46±11 years).

     

    Results. The firefighters had an average maximal exercise capacity of 281 ± 36 W (range 186-467 W) achieved by incremental CE exercise. To enable comparison, the maximal workload was converted to the workload sustainable for 6 min. It was more common to pass the 6 min TM fitness test but to fail the supposedly equivalent CE test rather than vice versa.

    Twenty percent of the firefighters developed an ST depression of ≥o.1 mV in at least one lead during exercise and half of the firefighters had a horizontal or downsloping ST depression. While an abnormal ST response associated with an increased risk for IHD only in V4, both an abnormal ST/HR index and an abnormal ST/HR slope associated with IHD in three leads each. Clockwise rotation of the ST/HR loop was infrequent in all precordial leads (1%), but it associated with an increased risk for IHD.

    In the subgroup without evidence of coronary artery disease, age and the HR response associated with ST depression, whereas hypertension, hyperlipidaemia, diabetes, blood pressure response, and exercise capacity did not.

     

    Conclusions. Even though the calculated oxygen uptake was higher for the TM test than for the supposedly equivalent CE test, the higher treadmill approval rate may indicate that the fitness requirement for Swedish firefighters has been lowered by changing the test modality.

    Exercise-induced ST depression was common in asymptomatic physically active men, although there were only a few cases of IHD during follow-up. If performing ExECG in asymptomatic, low-risk populations, ST/HR analysis could be given more importance. However, the limited clinical value of ExECG in low-risk populations was emphasised and needs to be reconsidered.

    In asymptomatic, physically active men without coronary artery disease, false-positive ST depressions can be partially explained by HR variables rather than by common cardiovascular risk factors and blood pressure response to exercise.

  • Public defence: 2019-09-11 10:00 Samhällsvetarhuset Hörsal D, Umeå
    Vaassen, Bram
    Umeå University, Faculty of Arts, Department of historical, philosophical and religious studies.
    Causal after all: a model of mental causation for dualists2019Doctoral thesis, monograph (Other academic)
    Abstract [en]

    In this dissertation, I develop and defend a model of causation that allows for dualist mental causation in worlds where the physical domain is physically complete.

    In Part I, I present the dualist ontology that will be assumed throughout the thesis and identify two challenges for models of mental causation within such an ontology: the exclusion worry and the common cause worry. I also argue that a proper response to these challenges requires a thoroughly lightweight account of causation, i.e. an account that allows for causes to be metaphysically distinct from the phenomena that produce or physically necessitate their effects.

    In Part II, I critically evaluate contemporary responses to these challenges from the philosophical literature. In particular, I discuss (i) List and Stoljar’s criticism of exclusion worries, (ii) Kroedel’s alternative dualist ontology, (iii) concerns about the notion of causal sufficiency, and (iv) Lowe’s models of dualist mental causation. I argue that none of these proposals provide independent motivation for a thoroughly lightweight account of causation and therefore leave room for improvement.

    In the first four chapters of Part III, I develop a thoroughly lightweight model of causation, which builds on interventionist approaches to causation. First, I explain how so-called ‘holding fixed’-requirements in standard interventionist accounts stand in the way of dualist mental causation. I then argue that interventionist accounts should impose a robustness condition on causal correlations and that, with this condition in place, the ‘holding fixed’-requirements can be weakened such that they do allow for dualist mental causation. I dub the interventionist model with such weakened ‘holding fixed’-requirements ‘insensitive interventionism’, argue that it can counter the exclusion worry as well as the common cause worry, and explain under which circumstances it would predict there to be dualist mental causation. Importantly, these circumstances might, for all we know, hold in the actual world.

    In the final three chapters of Part III, I defend insensitive interventionism against some objections. I consider the objection that causation must be productive, the objection that causes must (in some sense) physically necessitate their effects, and the objection that insensitive interventionism is too permissive. I respond by drawing from the literature on causation by absences and on the relation between causation and fundamental physics. Overall, insensitive interventionism performs as well as standard interventionist accounts. I conclude that insensitive interventionism is a credible model of causation.

  • Dahl, Christoffer
    Kristianstad University, Faculty of Education, Avdelningen för humaniora.
    Voices of female and male authorship: legitimations and discourses in literature textbooks2018In: IARTEM e-journal, ISSN 1837-2104, ISSN 1837-2104, Vol. 10, no 1-2, p. 5-22Article in journal (Refereed)
    Abstract [en]

    The literature textbook contains a range of voices (e.g. the textbook writer, the authors, experts etc.) who legitimize certain perspectives on the authorship (Dahl 2015). The aim of this paper is to discuss how voices are used and combined to legitimize female and male authorship in five literature textbooks for upper secondary schools in Sweden. The analysis is based on Theo van Leeuwen’s (2007) concept of legitimation, Bakhtin’s (1991) concept of voice and Norman Fairclough’s (1992) concept of intertextuality and interdiscursivity. Intertextuality focuses on how voices, i.e. explicit references, are used to authorize a specific perspective on the authorship. Interdiscursivity highlights texts as social practices constituted by combinations of voices, discourses and genres. My analysis of interdiscursivity examines how voices and discourses are articulated in the legitimation of the authorship and how it is realized linguistically. The result indicates differences in how male and female authorship are legitimized. Typical for the discourse of the male authorship is that the textbook writer’s voice interacts with the voices of the author and authorities in literature, shaping a homophonic discourse in which literary concepts and theory are predominant. The male authorship is legitimized as artistically significant in the history of literature. In comparison, the legitimization of the female authorship is characterized by a monophonic discourse with few references to authorities in literature. Interdiscursively, the voice of the textbook writer is more evaluative and authoritative, and the legitimations focus on the author’s social and empathetic ability. The result raises questions about the construction of male and female identities and didactic implications regarding language, identity and power in textbooks.

  • Barclay, Victoria K. H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Tyrefors, Niklas L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Johansson, I. Monika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Pettersson, Curt E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Acidic transformation of nordiazepam can affect recovery estimate during trace analysis of diazepam and nordiazepam in environmental water samples by liquid chromatography-tandem mass spectrometry2019In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 411, no 17, p. 3919-3928Article in journal (Refereed)
    Abstract [en]

    In this study, a special interest was focused on the stability of diazepam and nordiazepam in aqueous samples at acidic and neutral pH. The aim of the study was to isolate and illustrate one of the many possible sources of error that can be encountered when developing and validating analytical methods. This can be of particular importance when developing multi-analyte methods where there is limited time to scrutinize the behavior of each analyte. A method was developed for the analysis of the benzodiazepines diazepam and nordiazepam in treated wastewater. The samples were extracted by solid phase extraction, using SPEC C18AR cartridges, and analyzed by the use of liquid chromatography, with a C18 stationary phase, coupled to tandem mass spectrometry. Environmental water samples are often acidified during storage to reduce the microbial degradation of the target compounds and to preserve the sample. In some cases, the samples are acidified before extraction. In this study, it was found that a chemical equilibrium between nordiazepam and a transformation product could cause inaccurately high extraction recovery values when the samples were stored at low sample pH. The stability of nordiazepam was shown to be low at pH3. Within 12days, 20% of the initial concentration of nordiazepam was transformed. Interestingly, the transformed nordiazepam was shown to be regenerated and reformed to nordiazepam during sample handling. At a sample pH of 7, diazepam and nordiazepam were stable for 12days. It was concluded that great care must be taken when acidifying water samples containing nordiazepam during storage or extraction. The storage and the extraction should be conducted at neutral pH if no internal standard is used to compensate for degradation and conversion of nordiazepam. The developed method was validated in treated wastewater and applied for the quantification of diazepam and nordiazepam in treated wastewater samples.

  • Fors, Uno
    et al.
    Stockholm Univ, Dept Comp & Syst Sci DSV, Stockholm, Sweden.
    Kamwesiga, Julius T.
    Uganda Allied Hlth Examinat Board, Kampala, Uganda;Karolinska Inst, Div Occupat Therapy, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Eriksson, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Research in Disability and Habilitation. Karolinska Inst, Div Occupat Therapy, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    von Koch, Lena
    Karolinska Inst, Div Occupat Therapy, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Karolinska Univ Hosp, Theme Neuro, Stockholm, Sweden.
    Guidetti, Susanne
    Karolinska Inst, Div Occupat Therapy, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    User evaluation of a novel SMS-based reminder system for supporting post-stroke rehabilitation2019In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 19, article id 122Article in journal (Refereed)
    Abstract [en]

    Background: According to WHO stroke is a growing societal challenge and the third leading cause of global disease-burden estimated using disability-adjusted life years. Rehabilitation after stroke is an area of mutual interest for health care in many countries. Within the health care sector there is a growing emphasis on ICT services to provide clients with easier access to information, self-evaluation, and self-management. ICT-supported care programs possible to use in clients' home environments are also recommended when there are long distances to the health care specialists. The aim of this study was to evaluate the technical usability of a SMS-based reminder system as well as user opinions when using such a system to assist clients to remember to perform daily rehabilitation activities, to rate their performance and to allow Occupational therapists (OT's) to track and follow-up clients' results over time.

    Methods: Fifteen persons with stroke were invited to participate in the study and volunteered to receive daily SMS-based reminders regarding three activities to perform on a daily basis as well as answer daily SMS-based questions about their success rate during eight weeks. Clients, a number of family members, as well as OTs were interviewed to evaluate their opinions of using the reminder system.

    Results: All clients were positive to the reminder system and felt that it helped them to regain their abilities. Their OTs agreed that the reminder and follow-up system was of benefit in the rehabilitation process. However, some technical and other issues were limiting the use of the system for some clients. The issues were mostly linked to the fact that the SMS system was based on a Swedish phone number, so that all messages needed to be sent internationally.

    Conclusion: In conclusion, it seems that this type of SMS-based reminder systems could be of good use in the rehabilitation process after stroke, even in low income counties where few clients have access to Internet or smart phones, and where access to healthcare services is limited. However, since the results are based on clients', OTs' and family members' expressed beliefs, we suggest that future research objectively investigate the intervention's beneficial effects on the clients' physical and cognitive health.

  • Lahng, Herman
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Jesajæ caput V versione et notis philologicis illustratum, quod ... p. p. Mag. Hermannus Lahng ... et Hollst. Ulric. Svartling Sudermanno-Nericii. In Audit. Gust. die XIII Dec. MDCCCXV. H. A. M. S., d. 11815Dissertation (older thesis) (Other academic)
  • Lagerlöf, Petrus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Præcipuas rationes amicos devinciendi specimine ethico-politico leviter adumbratas, ... sub moderamine ... Dn. Petri Lagerlööf ... publicæ candidorum censuræ, ad d. [ ] Maii, anni M. MDXCVIII. eâ, quâ decet, observantià subiicit Al. Reg. Martinus Brytzenius. O-Gothus.1698Dissertation (older thesis) (Other academic)
  • Lagerlöf, Petrus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Equites sive de ordinibus equestribus disquisitio, quam ... præside ... Petro Lagerlööf ... placido bonorum examini submittit Gustavus Carlson Adlerfelt, in academiæ Upsaliensis auditorio veteri majori ad d. [ ] Junii, anni M. DC. LXXXXVI1696Dissertation (older thesis) (Other academic)
  • Lagerlöf, Petrus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Romana sub Augusto Felicitas quam brevi dissertatione delineatam indulgente hoc ipsum collegio philosophico, in regia Upsaliensi academia, sub præsidio ... Petri Lagerlööf ... publicæ bonorum censuræ excutiendam ventilandamque placide submittit Olof Gyllenborg in auditorio Gustaviano majori, ad diem [12] Junii A. O. R. M DC XCV. horis ante meridiem solitis.1695Dissertation (older thesis) (Other academic)
  • Lagerlöf, Petrus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Specimen meletematis philosophici bipartiti de ingenio humano indultu amplissimi ordinis philosophici in incluto ad Salam Musarum Athenæo, moderante ... Dn. Petro Lagerlööf ... qua par est modestia edit, & publico examini submittit Johannes Gene Ol. fil. Angerm. in auditorio Gustaviano Maj. die 15. Junii Anni M. DC. XCII.1692Dissertation (older thesis) (Other academic)
  • Lagerlöf, Petrus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Suspiciones de astrorum influxu, quas ... sub præsidio præclarissimi viri Dn. Petri Lagerlööf Eloq. Prof. Ord. examini publico subjicit Johan Upmarck E. fil. Upsal. In Audit. majori Gustav. horis ante meridiem solitis [ ] Anno M.DC.LXXXVIII.1688Dissertation (older thesis) (Other academic)
  • Lagergren, Anders
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    De imminutis in Svecia per nobilitatem opibus coronæ regiæque potestatis. Ab a. 1560 ad 1680. Dissertatio quam venia ampl. facult. philos. Upsal. p. p. mag. Andreas Lagergren ... et Axelius Theod. Bergius stip. reg. Sudermannus. In audit. Gustav. die III Junii MDCCCXXXVII. h. p. m. s. P. II1837Dissertation (older thesis) (Other academic)
  • Lagergren, Anders
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    De imminutis in Svecia per nobilitatem opibus coronæ regiæque potestatis. Ab a. 1560 ad 1680. Dissertatio quam venia ampl. facult. philos. Upsal. p. p. mag. Andreas Lagergren ... et Henricus Aminson Sudermannus. In audit. Gustav. die III Junii MDCCCXXXVII. h. a. m. s. P. I1837Dissertation (older thesis) (Other academic)
  • Læstadius, Petrus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    De periodis historiæ medii et recentioris ævi dissertatio academica. Cujus partem secundam ... Mag. Petrus Læstadius ambulatorius verbi divini minister in Lapponia Pitensi et Ericus Omberg Norrlandus. In Audit. Gustav. die XXIII Aprilis MDCCCXXXI. H. P. M. S., d. 21831Dissertation (older thesis) (Other academic)
  • Læstadius, Petrus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    De periodis historiæ medii et recentioris ævi dissertatio academica. Cujus partem primam ... Mag. Petrus Læstadius ambulatorius verbi divini minister in Lapponia Pitensi et Carolus Augustus Alin Vestmanno Dalcarlus. In Audit. Gust. die XXIII Aprilis MDCCCXXXI. H. A. M. S., d. 11831Dissertation (older thesis) (Other academic)
  • Landerbeck, Nils
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio de spirali logarithmica. Quam, ... præside Mag. Nicol. Landerbeck ... pro gradu philosophico p. p. Er. Sam. Ödmann, Al. Reg. Hels. In Audit. Gustaviano d. III Jun. MDCCCIX. H. A. M. S.1809Dissertation (older thesis) (Other academic)
  • Landerbeck, Nils
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio de arearum curvilinearum expressionibus quando coordinatæ a quadraturis pendeant. Quam, ... præside Mag. Nicol. Landerbeck ... pro gradu philosophico p. p. Petrus Schönberg Stip. Grönw. Westmanno-Dalekarlus. In Audit. Gustaviano d. XXVII Maji MDCCCIX. H. A. M. S.1809Dissertation (older thesis) (Other academic)
  • Landerbeck, Nils
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio de discrimine solutionis geometricæ ex delectu principii, quam ... præside Mag. Nicol. Landerbeck ... pro gradu philosophico p. p. Sveno Fridericus Pihlberg a sacris stip. Lindel. Suderm. Ner. In Audit. Gust. die XIII Maji. MDCCCIX. H. A. M. S.1809Dissertation (older thesis) (Other academic)
  • Landerbeck, Nils
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio de lineis curvis ex motu puncti aliud in recta progrediens directe sectantis, ortis. Quam ... præside Mag. Nicol. Landerbeck ... pro gradu philosophico p. p. Laurentius Jacobus Isander, Uplandus. In Audit. Gustaviano d. XXIX April. MDCCCIX. H. A. M. S.1809Dissertation (older thesis) (Other academic)
  • Landerbeck, Nils
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio de quadratice dinostratiana quam ... præside Mag. Nicol. Landerbeck ... censuræ modeste offert Carolus Gustavus Spens comes Vestrogothus in Audit. Gust. Maj. die XII Dec. MDCCCVII. H. A. M. S.1807Dissertation (older thesis) (Other academic)
  • Landerbeck, Nils
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Propositiones quædam geometricæ, quas ... præside Mag. Nicol. Landerbeck, ... pro gradu philosophico p. p. Petr. Gust. Boivie, ... Uplandus. In Aud. Gust. Maj. d. IV Jun. MDCCCVI. H. A. M. S.1806Dissertation (older thesis) (Other academic)
  • Landerbeck, Nils
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio de resolutione fractionum binominalium in rationales. Quam ... præside Mag. Nicol. Landerbeck, ... pro gradu p. p. Johannes Er. Kumlander Wetsmannus. In Aud. Gust. Maj. die XIV Maji MDCCCVI. H. A. M. S.1806Dissertation (older thesis) (Other academic)
  • Landerbeck, Nils
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio de indole arcuum hyperbolæ æquilateræ. Quam ... præside Mag. Nicol. Landerbeck, ... pro gradu p. p. Joh. Petr. Fröberg Westmannus. In Audit. Gust. Majori die XXX Apr. MDCCCVI. H. S.1806Dissertation (older thesis) (Other academic)
  • Landerbeck, Nils
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio de harmonia quadraturæ hyperbolæ æquilateræ et rectificationis prarabolæ Apollonianæ. Quam ... præside Mag. Nicol. Landerbeck, ... pro gradu p. p. Dav. Ud. Widén stip. Flod. Ostrogothus. In Audit. Gust. Majori die XXVI Apr. MDCCCVI . H. A. M. S.1806Dissertation (older thesis) (Other academic)