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  • Public defence: 2019-09-14 10:00 Rudbecksalen, Uppsala
    Mitran, Bogdan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Uppsala University.
    Prostate cancer theranostics using GRPR antagonist RM262019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The malignant transformation of cells is often associated with an alteration of their molecular phenotype, resulting in overexpression of several cell surface proteins. Gastrin-releasing peptide receptor (GRPR) and prostate-specific membrane antigen (PSMA) are examples of such pro-teins that are expressed at a high density in prostate cancer. GRPR is primarily expressed in earlier stages of prostate cancer and tends to decrease with disease progression. This expression pattern indicates that GRPR could be a promising target for imaging and treatment of oligometa-static prostate cancer, an early step in prostate cancer progression characterized by limited meta-static spread. In contrast, the expression of PSMA increases with cancer progression and is significantly upregulated as tumors dedifferentiate into higher grade, in androgen-insensitive and metastatic lesions.

    This thesis is based on five original articles (papers I-V) and focuses on the preclinical de-velopment of radiotracers for imaging and treatment of prostate cancer. The work can be divided into three distinct parts: (1) the development and optimization of GRPR-antagonist RM26 for high contrast PET and SPECT imaging of oligometastatic prostate cancer (papers I-III), (2) the preclinical evaluation of 177Lu-labeled RM26 as a potential candidate for peptide receptor radionuclide therapy (PRRT) in GRPR-expressing tumors, alone or in combination with anti-HER2 antibody trastuzumab (paper IV), and (3) the development of a bispecific heterodimer targeting both PSMA and GRPR in prostate cancer (paper V).

    We have demonstrated that the in vitro and in vivo properties of GRPR antagonist RM26 are strongly influenced by the choice of chelator-radionuclide complex and that long-lived radionuclides are desirable for high-contrast imaging. Furthermore, our data indicate that 55Co-NOTA-PEG2-RM26 has remarkable potential for next-day high-contrast PET imaging of GRPR-expressing tumors. Experimental PRRT using 177Lu-DOTAGA-PEG2-RM26 resulted in a pronounced inhibition of tumor growth and a significantly longer median survival. Interestingly, survival was further improved when trastuzumab was co-injected with 177Lu-DOTAGA-PEG2-RM26. These data indicate that blocking HER2 with trastuzumab decreased the repairing ability of irradiated cells. Finally, we developed a heterodimer (NOTA-DUPA-RM26) for imaging GRPR and PSMA expression in prostate cancer shortly after administration.

    In conclusion, we have successfully developed and preclinically evaluated radioconjugates for GRPR-directed theranostics in oligometastatic prostate cancer using the bombesin antagonistic analog RM26.

  • Public defence: 2019-09-13 09:15 Häggsalen, Uppsala
    Aktekin, Burak
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    The Electrochemistry of LiNi0.5-xMn1.5+xO4-δ in Li-ion Batteries: Structure, Side-reactions and Cross-talk2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The use of Li-ion batteries in portable electronic products is today widespread and on-going research is extensively dedicated to improve their performance and energy density for use in electric vehicles. The largest contribution to the overall cell weight comes from the positive electrode material, and improvements regarding this component thereby render a high potential for the development of these types of batteries. A promising candidate is LiNi0.5Mn1.5O4 (LMNO), which offers both high power capability and energy density. However, the instability of conventional electrolytes at the high operating potential (~4.7 V vs. Li+/Li) associated with this electrode material currently prevents its use in commercial applications.

    This thesis work aims to investigate practical approaches which have the potential of overcoming issues related to fast degradation of LNMO-based batteries. This, in turn, necessitates a comprehensive understanding of degradation mechanisms. First, the effect of a well-known electrolyte additive, fluoroethylene carbonate is investigated in LNMO-Li4Ti5O12 (LTO) cells with a focus on the positive electrode. Relatively poor cycling performance is found with 5 wt% additive while 1 wt% additive does not show a significant difference as compared to additive-free electrolytes. Second, a more fundamental study is performed to understand the effect of capacity fading mechanisms contributing to overall cell failure in high-voltage based full-cells. Electrochemical characterization of LNMO-LTO cells in different configurations show how important the electrode interactions (cross-talk) can be for the overall cell behaviour. Unexpectedly fast capacity fading at elevated temperatures is found to originate from a high sensitivity of LTO to cross-talk.

    Third, in situ studies of LNMO are conducted with neutron diffraction and electron microscopy. These show that the oxygen release is not directly related to cation disordering. Moreover, microstructural changes upon heating are observed. These findings suggest new sample preparation strategies, which allow the control of cation disorder without oxygen loss. Following this guidance, ordered and disordered samples with the same oxygen content are prepared. The negative effect of ordering on electrochemical performance is investigated and changes in bulk electronic structure following cycling are found in ordered samples, accompanied by thick surface films on surface and rock-salt phase domains near surface.

  • Public defence: 2019-09-13 13:15 Sal IV, Uppsala
    Åhlman, Christoffer
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of History.
    Mötet med det skrivna ordet: Kvinnors läsande och skrivande under 1700-talet2019Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This thesis study how women in 18th century Sweden used reading and writing and how these skills could be a source of income. Historians have studied how many could read during this period or how writing was taught in the parish school. How these skills were used have, however, been overlooked. The main questions are: How, and in which circumstances, did women use reading and writing? Who were these women? What type of return did reading and writing have?

    To study how literacy was used is not without difficulty. The traces are often scattered in different types of source material. Several types of sources material have therefore been analyzed. Material like moving certificates, funeral sermons, personals, account books, verifications, church protocols, contracts, court records, recipes amongst others have been used.

    This thesis shows that women used reading and writing in different ways. There were not a question of one type of literacy but different types of literacies – it depended on the situation. A writing ability that was limited in one situation could be sufficient in another. By focus on social practice, this thesis argues that women´s reading and writing could have different types of return depending on individual and situation.

  • Public defence: 2019-09-20 09:00 T2, Huddinge
    Marlevi, David
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Non-invasive imaging for improved cardiovascular diagnostics: Shear wave elastography, relative pressure estimation, and tomographic reconstruction2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Throughout the last century, medical imaging has come to revolutionise the way we diagnose disease, and is today an indispensable part of virtually any clinical practice. In cardiovascular care imaging is extensively utilised, and the development of novel techniques promises refined diagnostic abilities: ultrasound elastography allows for constitutive tissue assessment, 4D flow magnetic resonance imaging (MRI) enables full-field flow mapping, and micro-Computed Tomography (CT) permits high-resolution imaging at pre-clinical level. However, following the complex nature of cardiovascular disease, refined methods are still very much needed to accurately utilise these techniques and to effectively isolate disease developments.

    The aim of this thesis has been to develop such methods for refined cardiovascular image diagnostics. In total eight studies conducted over three separate focus areas have been included: four on vascular shear wave elastography (SWE), three on non-invasive cardiovascular relative pressure estimations, and one on tomographic reconstruction for pre-clinical imaging.

    In Study I-IV, the accuracy and feasibility of vascular SWE was evaluated, with particular focus on refined carotid plaque characterisation. With confined arterial or plaque tissue restricting acoustic wave propagation, analysis of group and phase velocity was performed with SWE output validated against reference mechanical testing and imaging. The results indicate that geometrical confinement has a significant impact on SWE accuracy, however that a combined group and phase velocity approach can be utilised to identify vulnerable carotid plaque lesions in-vivo.

    In Study V-VII, a non-invasive method for the interrogation of relative pressure from imaged cardiovascular flow was developed. Using the concept of virtual work-energy, the method was applied to accurately assess relative pressures throughout complex, turbulence-inducing, branching vasculatures. The method was also applied on a dilated cardiomyopathy cohort, indicating arterial hemodynamic changes in cardiac disease.

    Lastly, in Study VIII a method for multigrid image reconstruction of tomographic data was developed, utilising domain splitting and operator masking to accurately reconstruct high-resolution regions-of-interests at a fraction of the computational cost of conventional full-resolution methods.

    Together, the eight studies have incorporated a range of different imaging modalities, developed methods for both constitutive and hemodynamic cardiovascular assessment, and utilised refined pre-clinical imaging, all with the same purpose: to refine current state cardiovascular imaging and to improve our ability to non-invasively assess cardiovascular disease. With promising results reached, the studies lay the foundation for continued clinical investigations, advancing the presented methods and maturing their usage for an improved future cardiovascular care.

  • Linda, Olsson
    RISE - Research Institutes of Sweden, ICT, Viktoria.
    The Role of Electric Vehicles in Reducing Climate Impact: Swedish Public Debate in 2010-20182019In: The International Journal of Climate Change, ISSN 1835-7156, Vol. 11, no 3, p. 1-13Article in journal (Refereed)
    Abstract [en]

    To meet the Paris agreement, CO2 emissions from road transport need to be severely lowered. In Sweden, as in many other countries, the number of electric vehicles (EVs) is increasing rapidly. This has led to a recurring debate on whether EVs will help reduce climate impact or not. The aim of this paper is to analyze the Swedish debate on the climate impact of EVs with respect to framing and validity of the arguments. Thirty-one opinion pieces published between 2010 and 2018 are studied. Two discourse coalitions are identified; supporters and opponents of EVs. The opponents’ main argument is that EVs use imported, coal-fired electricity with high CO2 emissions. The supporters argue that EVs use Swedish, fossil-free electricity, thereby causing no CO2 emissions. Neither coalition’s arguments are wholly valid, but nor are they wholly false. Swedish electricity production is largely fossil free, but, at times of high electricity demand, fossil-based electricity is imported. Thus, Swedish EVs often use fossil-free electricity, but sometimes they do not. This is likely to continue with a large-scale transition to electromobility. Both discourse coalitions motivate their positions with a desire to reduce climate impact. EV supporters are optimistic about technology development and frame EVs as fundamental for future carbon-neutral possibilities. While EV opponents are pessimistic, their framing of the issue implies a need for society to assume responsibility for sustainability in a wide system perspective. This should be acknowledged and used by policy-makers, to ensure that EVs’ full potential for climate change mitigation be realized.

  • Zhao, Wan-Yi
    et al.
    Fritsch, Peter W.
    Do, Van Truong
    Fan, Qiang
    Yin, Qiang-Yi
    Penneys, Darin S.
    Swenson, Ulf
    Swedish Museum of Natural History, Department of Botany.
    Liao, Wen-Bo
    Rehderodendron truongsonense (Styracaceae), a new species from Vietnam2019In: Journal of the Botanical Research Institute of Texas, ISSN 1934-5259, Vol. 13, no 1, p. 157-171Article in journal (Refereed)
    Abstract [en]

    Rehderodendron truongsonense, a new species from Vietnam, is described and illustrated. In the treatment of the Styracaceae for the Flore du Cambodge, du Laos, et du Viêtnam, specimens of this species were recognized as R. macrocarpum Hu. These specimens clearly differ from R. macrocarpum, however, as well as from all other species of Rehderodendron (where these characters are known) by, e.g., an evergreen ver- sus deciduous habit, fewer secondary veins of the leaf blade, shorter inflorescences and corolla lobes, large and conspicuous lowermost bracteoles, the presence of eight ovules per carpel, and a fruit with ca. 10 to 20 ribs that are indistinct. Phylogenetic analysis based on five chloroplast DNA regions (clpP-psbB, ndhD-psaC-ndhE-ndhG, rpl22-rps19, rps18-rpl20, and psbI-trnS-GCU) placed the new species as nested within Rehderodendron and sister to R. gongshanense. This new species is endemic to the Truong Son Mountain Range, from which the epi- thet is derived, and we assign it an IUCN Red List preliminary status as Near Threatened. 

  • Public defence: 2019-09-13 10:15 S 205 h, Samhällsvetarhuset, Umeå
    Enqvist, Lena
    Umeå University, Faculty of Social Sciences, Department of Law.
    En myndighet i samverkan: Försäkringskassans rättsliga förutsättningar att samverka med Arbetsförmedlingen samt hälso- och sjukvården2019Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This doctoral thesis investigates and analyzes the legal conditions under which the Swedish Social Insurance Agency may engage in cooperation with the Swedish Public Employment Service and Swedish Health Care Providers (both public and private), regarding rehabilitation, information exchange and investigation measures in individual sick leave insurance cases. It also presents an analysis of whether these legal conditions contribute to safeguarding legality and legal certainty when the Social Insurance Agency is involved in cooperation.

    Overall the thesis concludes that the legal conditions for such cooperation are good in terms of assistance regarding rehabilitation, information exchange and investigation measures. The designated assignment of the Social Insurance Agency relating to the distribution of sickness benefits is also such that any cooperation that helps the individual's rehabilitation or the investigation and assessment of entitlement to such benefits is encouraged. The legality and legal certainty in such cooperation is also found to be fundamentally safeguarded, since it follows from the principle of legality in Swedish administrative law that any measures taken by the Social Insurance Agency in cooperation with other bodies must be founded in the constitutional legal order. However, since the Social Insurance Agency's assignment pertains to the distribution of positive rights and benefits, the requirements governing how clearly stated and distinct such legal support must be are generally less stringent. This is reflected in the rules and principles identified as supporting or limiting the legal conditions for cooperation, as in many cases they lack detailed prerequisites for when they may be used or what should be done. Many of the legal rules or legal principles that limit the authority and power to freely design the possible content, aims and process practice of cooperation are also not specifically aimed at regulating such situations. Moreover, in many cases they are found in constitutional or general administrative law principles that are essentially abstract, and not usually applied by administrators in the handling of individual cases. This, in turn, affects the overall impact that the supporting factors of legality and legal certainty can have in the Social Insurance Agency's multi-party cooperation. These supporting factors include the Agency's duties to ensure independent decision-making (ideally) based on a clearly designated assignment, to comply with the legal principles of objectivity, equality before the law and foreseeability, and to respect the individual's personal integrity in multi-party cooperation.

  • Public defence: 2019-09-13 10:00 N 420, Naturvetarhuset, Umeå
    Ekman, Robin
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Quantum Kinetic Theory for Plasmas: spin, exchange, and particle dispersive effects2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is about developing and studying quantum mechanical models of plasmas. Quantum effects can be important at high densities, at low temperatures, and in strong electromagnetic fields, in various laboratory and astrophysical systems. The focus is on the electron spin, the intrinsic magnetic moment; exchange interactions, a purely quantum mechanical effect arising from particles being indistinguishable; and particle dispersive effects, essentially the Heisenberg uncertainty principle. The focus is on using phase-space formulations of quantum mechanics, namely Wigner and -functions. These methods allow carrying over techniques from classical plasma physics and identifying quantum as opposed to classical behavior.

    Two new kinetic models including the spin are presented, one fully relativistic and to first order in ħ, and one semi-relativistic but to all orders in ħ. Among other example calculations, for the former, conservation laws for energy, momentum, and angular momentum are derived and related to “hidden momentum” and the Abraham-Minkowski dilemma. Both models are discussed in the context of the existing literature.

    A kinetic model of exchange interactions, formally similar to a collision operator, is compared to a widely used fluid description based on density functional theory, for the case of electrostatic waves. The models are found to disagree significantly.

    A new, non-linear, wave damping mechanism is shown to arise from particle dispersive effects. It can be interpreted as the simultaneous absorption or emission of multiple wave quanta. This multi-plasmon damping is of particular interest for highly degenerate electrons, where it can occur on time scales comparable to or shorter than that of linear Landau damping.

  • Asprem, Egil
    Stockholm University, Faculty of Humanities, Department of Ethnology, History of Religions and Gender Studies.
    Aren't We Living in a Disenchanted World?2019In: Hermes Explains: Thirty Questions about Western Esotericism / [ed] Wouter J. Hanegraaff, Peter Forshaw, Marco Pasi, Amsterdam: Amsterdam University Press, 2019, p. 13-20Chapter in book (Other academic)
  • Mahmoud, Sara
    et al.
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Svensson, Henrik
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Self-driving cars learn by imagination2018In: Proceedings of the 14th SweCog Conference / [ed] Tom Ziemke, Mattias Arvola, Nils Dahlbäck, Erik Billing, Skövde: University of Skövde , 2018, p. 12-15Conference paper (Refereed)
  • Hammarlund-Larsson, Cecilia
    The Nordic Museum.
    Skärskådad samling: Samiskt kulturarv i Nordiska museet2008In: För Sápmi i tiden, Stockholm: Nordiska museets förlag, 2008, p. 85-106Chapter in book (Other academic)
  • Lantto, Patrik
    et al.
    Mörkenstam, Ulf
    Från "Lapprivilegier" till rättigheter som urfolk: Svensk samepolitik och samernas politiska mobilisering2008In: För Sápmi i tiden, Stockholm: Nordiska museets förlag, 2008, p. 58-84Chapter in book (Other academic)
  • Engvall, Tove
    et al.
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Information Systems and Technology.
    Samuelsson, Göran
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Information Systems and Technology.
    Ekonomiskt värde av information2017Report (Other academic)
    Abstract [sv]

    Information är en av Trafikverkets resurser och dess värde kan uttryckas på olika sätt och ha olika innebörd för olika aktörer vid olika tidpunkter. Informationen kan ha direkta ekonomiska värden, men värdet kan också uttryckas i dess betydelse för en långsiktig resursplanering och ekonomihantering.  Informationen  kan även bidra till arbetssätt som hushållar med skattemedel, och skapa  samhällseffekter inom t.ex  säkerhet och miljö. Vi har i den befintliga studien bland annat utgått ifrån standarden ISO 30300 som menar: 

    ”Att skapa och hantera verksamhetsinformation ingår i varje organisations aktiviteter, processer och system. Detta bidrar till effektivitet i verksamheten, ansvarstagande och riskhantering och till att verksamheten upprätthålls. Det gör det även möjligt för organisationer att se det värde som finns i informationsresurser som verksamhetstillgångar, kommersiella tillgångar och kunskapstillgångar, och bidra till att bevara det kollektiva minnet, som svar på utmaningar från den globala och digitala omvärlden” (ISO 30300, sid. iv). 

    I denna studie har vi valt att undersöka hur informationshanteringen, med fokus på ekonomirelaterad information, stödjer det pågående arbetet med ett livscykelperspektiv på anläggningen. Bakgrunden är Trafikverkets ambitioner att skapa en helhetssyn över anläggningens kostnader genom hela livscykeln. Och därmed också hur den ekonomiska redovisningen relaterar till annan information. Studien baseras på intervjuer med i huvudsak medarbetare på Trafikverket, men även vissa andra nyckelpersoner. Personer från följande funktioner och arbetsfält har intervjuats:  CoClass, BIM, ANDA/GUS, Öppna data, Informationsutbyten, Informationsförvaltning, Ekonomi, Ledningssystem, IT-strategi, Kontrakt och juridik, LCC, Internrevision, Riksrevisionen, Transportstyrelsen och Näringsdepartementet.

  • Engvall, Tove
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Information Systems and Technology.
    Fear, Greed and Lack of Trust in Online Financial Trade2017In: Journal of Administrative Sciences and Technology, ISSN 2165-9435, article id 106163Article in journal (Refereed)
    Abstract [en]

    Trust is a crucial component in business relations, and also a precondition for people’s adoption of electronic services. This study addresses challenges regarding trust in online financial trade. Results indicate that brokerage companies acting in a dishonest way, along with dominant patterns of fear, greed and lack of knowledge and awareness among clients, lead to frequent losses of money. Which leads to a lack of trust in brokers, brokerage companies and the business domain. The way technology is used increases the challenges of risk and an unequal relation between client and brokerage companies. Self-ethnography has been used as a method, where observations, interviews and conversations were performed. Suggestions are to do further research in order to identify how mechanisms for trustworthiness, accountability and transparency can be created in the business domain, in which management of records will play a central role.

  • Engvall, Tove
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Information Systems and Technology.
    In-equalities, Regulation, Ethics & Records - reflections from a case in Online Trade2018In: Archives of Business Research, ISSN 2054-7404, Vol. 6, no 8, p. 135-147Article in journal (Refereed)
    Abstract [en]

    In an ethnographic study in online trade at the financial market, different forms of inequalities in client-broker/business relations have been found. It takes expression in for example design of technology, control of and access to information, competence and misuse of trust. Trust is at the center of concern, since that is crucial both to success and a risk for being taken advantage of. This relates to power between actors, responsibilities and accountability. This is where records role as evidence of human acts and conducts have a central role, both in relation to regulation and business ethics. As established structures for ensuring rights and obligations throughout societies are challenged by digitalization and globalization, this has to be recreated in the online context. The article conclude that both regulation and ethics are crucial in forming common values, behaviours and understanding of trust. If not, trust is easily violated which set people in trouble.

    In order to ensure trust, accountability is an important factor to consider, as well as informal means for ensuring fair behaviours that promotes the building and maintenance of trust among actors. As the technological development challenge processes and means for trust and accountability, new tools ought to be developed. As well as people-related aspects at both personal, business and societal level have to be considered.

  • Jönses, Lars
    The Nordic Museum.
    Samerna i den kulturella konstruktionen av territoriet2008In: För Sápmi i tiden, Stockholm: Nordiska museets förlag, 2008, p. 43-57Chapter in book (Other academic)
  • Public defence: 2019-09-09 23:40
    Vu, Xuan-Son
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Privacy-awareness in the era of Big Data and machine learning2019Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Social Network Sites (SNS) such as Facebook and Twitter, have been playing a great role in our lives. On the one hand, they help connect people who would not otherwise be connected before. Many recent breakthroughs in AI such as facial recognition [49] were achieved thanks to the amount of available data on the Internet via SNS (hereafter Big Data). On the other hand, due to privacy concerns, many people have tried to avoid SNS to protect their privacy. Similar to the security issue of the Internet protocol, Machine Learning (ML), as the core of AI, was not designed with privacy in mind. For instance, Support Vector Machines (SVMs) try to solve a quadratic optimization problem by deciding which instances of training dataset are support vectors. This means that the data of people involved in the training process will also be published within the SVM models. Thus, privacy guarantees must be applied to the worst-case outliers, and meanwhile data utilities have to be guaranteed.

    For the above reasons, this thesis studies on: (1) how to construct data federation infrastructure with privacy guarantee in the big data era; (2) how to protect privacy while learning ML models with a good trade-off between data utilities and privacy. To the first point, we proposed different frameworks em- powered by privacy-aware algorithms that satisfied the definition of differential privacy, which is the state-of-the-art privacy-guarantee algorithm by definition. Regarding (2), we proposed different neural network architectures to capture the sensitivities of user data, from which, the algorithm itself decides how much it should learn from user data to protect their privacy while achieves good performance for a downstream task. The current outcomes of the thesis are: (1) privacy-guarantee data federation infrastructure for data analysis on sensitive data; (2) privacy-guarantee algorithms for data sharing; (3) privacy-concern data analysis on social network data. The research methods used in this thesis include experiments on real-life social network dataset to evaluate aspects of proposed approaches.

    Insights and outcomes from this thesis can be used by both academic and industry to guarantee privacy for data analysis and data sharing in personal data. They also have the potential to facilitate relevant research in privacy-aware representation learning and related evaluation methods.

  • Velders, Matthijs A
    et al.
    Calais, Fredrik
    Dahle, Nina
    Fall, Tove
    Hagström, Emil
    Leppert, Jerzy
    Nowak, Christoph
    Tenerz, Åke
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Karolinska institutet.
    Hedberg, Pär
    Cathepsin D improves the prediction of undetected diabetes in patients with myocardial infarction2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Background: Newer therapeutic agents for type 2 diabetes mellitus can improve cardiovascular outcomes, but diabetes remains underdiagnosed in patients with myocardial infarction (MI). We sought to identify proteomic markers of undetected dysglycaemia (impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) to improve the identification of patients at highest risk for diabetes. Materials and methods: In this prospective cohort, 626 patients without known diabetes underwent oral glucose tolerance testing (OGTT) during admission for MI. Proximity extension assay was used to measure 81 biomarkers. Multivariable logistic regression, adjusting for risk factors, was used to evaluate the association of biomarkers with dysglycaemia. Subsequently, lasso regression was performed in a 2/3 training set to identify proteomic biomarkers with prognostic value for dysglycaemia, when added to risk factors, fasting plasma glucose, and glycated haemoglobin A1c. Determination of discriminatory ability was performed in a 1/3 test set. Results: In total, 401/626 patients (64.1%) met the criteria for dysglycaemia. Using multivariable logistic regression, cathepsin D had the strongest association with dysglycaemia. Lasso regression selected seven markers, including cathepsin D, that improved prediction of dysglycaemia (area under the receiver operator curve [AUC] 0.848 increased to 0.863). In patients with normal fasting plasma glucose, only cathepsin D was selected (AUC 0.699 increased to 0.704). Conclusions: Newly detected dysglycaemia, including manifest diabetes, is common in patients with acute MI. Cathepsin D improved the prediction of dysglycaemia, which may be helpful in the a priori risk determination of diabetes as a motivation for confirmatory OGTT.

  • Public defence: 2019-09-13 09:15 Siegbahnsalen, Uppsala
    Espadas Escalante, Juan José
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics. Uppsala University.
    On numerical analyses of woven composite laminates: Homogenization, damage and fracture2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This dissertation analyzes various mechanical properties of textile reinforced composite laminates.

    The dissertation is based on a total of six published works, which are essentially numerical, although experimental elements are available. The numerical methods used are based on high-resolution finite element models in combination with sophisticated phase-field theories for brittle fracture. A key result is that important mechanical properties in engineering applications, such as fracture or damage resistance, can be substantially affected by the arrangement of the constituent materials at the meso level.

  • Giacometti, Alberto
    et al.
    Nordic Council of Ministers, Nordregio.
    Teräs, Jukka
    Nordic Council of Ministers, Nordregio.
    Aalto, Heikki
    Social and Economic Resilience in the Bothnian Arc Cross-Border Region2019Report (Other academic)
    Abstract [en]

    What global and local risks and long-term challenges is the Bothnian Arc cross-border area exposed to? And how can societies and economies in this area anticipate and respond to them to ensure resilient long-term development paths? Answering these questions was the challenge of Nordregio together with the Bothnian Arc association on behalf of the Nordic Thematic Group on Innovative and Resilient regions, set by the Nordic Council of Ministers from 2017 to 2020. For this purpose, an exploratory study was conducted in a participative manner in 2018-2019, including key experts from across the region to provide input on challenges and potential threats as well as factors driving resilience in the Bothnian Arc cross-border area.

  • Public defence: 2019-09-19 13:00 Kollegiesalen, Stockholm
    Prästings, Anders
    KTH, School of Architecture and the Built Environment (ABE), Civil and Architectural Engineering, Soil and Rock Mechanics.
    Managing uncertainties in geotechnical parameters: From the perspective of Eurocode 72019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Geotechnical engineering is strongly associated with large uncertainties. Geotechnical site investigations are made only at discrete points and most of a soil volume is never tested. A major issue is therefore how to cost effectively reduce geotechnical uncertainties with respect to structural performance. Managing the geotechnical uncertainties is thus an important aspect of the design process. Guidance on this subject is given in the European design code for geotechnical design, Eurocode 7 (EN 1997), which advocates the use of the partial-factor method, with the added possibility to use the observational method if the uncertainties are large and difficult to assess.This thesis aims to highlight, develop and improve methods to assess the quality and value of geotechnical site investigations through reliability-based design. The thesis also discusses the limitations of the deterministic partial-factor method, according to its EN 1997 definition, and how to better harmonise this design methodology with the risk-based approach of reliability-based design. The main research contributions are: (1) a presented case study showing the importance of and potential gains with a robust framework for statistical evaluation of geotechnical parameters, (2) the discussion on the limitations of the partial-factor method in EN 1997, and (3) the discussion on how to harmonise the EN 1997 definition of the partial-factor method with the risk-based approach of reliability-based design.

  • Al-Mashhadi, Ammar Nadhom Farman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Dukic, Milena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Engstrand Lilja, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Rhabdomyomatous mesenchymal hamartoma presenting in a child as a perineal mass2019In: Journal of Pediatric Surgery Case Reports, ISSN 0022-3476, E-ISSN 2213-5766, Vol. 47, article id 101242Article in journal (Refereed)
    Abstract [en]

    Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare hamartomatous lesion in the dermis and subcutaneous tissue. It is mostly found in the face and neck region of children. We report a case of solitary RMH located in the perineum of an 8-month-old boy. Microscopic examination of specimen showed a disordered collection of mature adipose tissue, skeletal muscle, adnexal elements and nerve bundles, and immunohistochemistry confirmed a RMH. This case emphasizes the possibility of RMH in the perineum of the children. Even if RMH is a rare condition in the perineum it should be considered as a differential diagnosis of a perineal mass in children.

  • Svonni, Mikael
    Samerna i språkhistorien2008In: För Sápmi i tiden, Stockholm: Nordiska museets förlag, 2008, p. 32-42Chapter in book (Other academic)
  • Baer, Lars-Anders
    Tolkning av ett förflutet2008In: För Sápmi i tiden, Stockholm: Nordiska museets förlag, 2008, p. 16-31Chapter in book (Other academic)
  • Urdaneta, Veronica
    et al.
    Hernandez, Sara B.
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Departamento de Genética, Facultad de Biología, Universidad de Sevilla, Sevilla, Spain.
    Casadesus, Josep
    Mutational and non mutational adaptation of Salmonella enterica to the gall bladder2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 5203Article in journal (Refereed)
    Abstract [en]

    During systemic infection of susceptible hosts, Salmonella enterica colonizes the gall bladder, which contains lethal concentrations of bile salts. Recovery of Salmonella cells from the gall bladder of infected mice yields two types of isolates: (i) bile-resistant mutants; (ii) isolates that survive lethal selection without mutation. Bile-resistant mutants are recovered at frequencies high enough to suggest that increased mutation rates may occur in the gall bladder, thus providing a tentative example of stress-induced mutation in a natural environment. However, most bile-resistant mutants characterized in this study show defects in traits that are relevant for Salmonella colonization of the animal host. Mutation may thus permit short-term adaptation to the gall bladder at the expense of losing fitness for transmission to new hosts. In contrast, non mutational adaptation may have evolved as a fitness-preserving strategy. Failure of RpoS(-) mutants to colonize the gall bladder supports the involvement of the general stress response in non mutational adaptation.

  • Fugelstad, Anna
    et al.
    Karolinska Inst, Dept Clin Neurosci, Gotgatan 83E, SE-I1662 Stockholm, Sweden.
    Thiblin, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Johansson, Lars Age
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Ågren, Gunnar
    Former Natl Inst Publ Hlth, Gotgatan 83E, SE-17662 Stockholm, Sweden.
    Sidorchuk, Anna
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden.
    Opioid-related deaths and previous care for drug use and pain relief in Sweden2019In: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 201, p. 253-259Article in journal (Refereed)
    Abstract [en]

    Aim: In 2006-2014, the rate of drug-related deaths, typically opioid poisonings, more than doubled in Sweden. Opioid prescriptions for pain control or opioid agonist therapy also increased. In this retrospective study, we compared death rates between individuals whose first recorded contact with prescribed opioids was for pain control and individuals that had received substance use disorder (SUD) treatment before their first recorded opioid prescription.

    Methods: We included 2834 forensically examined individuals (ages 15-64 years) that died of poisoning in Sweden in 2006-2014. For each death we acquired data on previous opioid prescriptions and SUD treatments. We compared three study groups: pain control (n = 788); a SUD treatment group (n = 1629); and a group with no prescription for pain control or SUD treatment (n = 417).

    Results: Overall fatal poisonings increased from 2.77 to 7.79 (per 100,000 individuals) from 2006 to 2014 (relative 181% increase). Fatal poisoning increased from 2006 to 2014 by 269% in the pain control group (0.64 to 2.36 per 100,000) and by 238% in the SUD treatment group (1.35 to 4.57 per 100,000). Heroin-related deaths remained constant; consequently, the increase was likely attributable to prescription opioids.

    Conclusion: A rapid increase in deaths attributable mainly to prescription opioids for pain control, was reported previously in the United States. Our study indicated that increased access to prescription opioids might contribute to higher death rates also in Sweden among patients seeking pain control and individuals with an established SUD; however, deaths related to prescription opioids mainly occurred among those with SUDs.

  • Zsoter, Ervin
    et al.
    European Ctr Medium Range Weather Forecasts, Reading, Berks, England;Univ Reading, Dept Geog & Environm Sci, Reading, Berks, England.
    Cloke, Hannah L.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL. Univ Reading, Dept Geog & Environm Sci, Reading, Berks, England;Univ Reading, Dept Meteorol, Reading, Berks, England;Ctr Nat Hazards & Disaster Sci, Uppsala, Sweden.
    Stephens, Elisabeth
    Univ Reading, Dept Geog & Environm Sci, Reading, Berks, England.
    de Rosnay, Patricia
    European Ctr Medium Range Weather Forecasts, Reading, Berks, England.
    Munoz-Sabater, Joaquin
    European Ctr Medium Range Weather Forecasts, Reading, Berks, England.
    Prudhomme, Christel
    European Ctr Medium Range Weather Forecasts, Reading, Berks, England.
    Pappenberger, Florian
    European Ctr Medium Range Weather Forecasts, Reading, Berks, England.
    How Well Do Operational Numerical Weather Prediction Configurations Represent Hydrology?2019In: Journal of Hydrometeorology, ISSN 1525-755X, E-ISSN 1525-7541, Vol. 20, no 8, p. 1533-1552Article in journal (Refereed)
    Abstract [en]

    Land surface models (LSMs) have traditionally been designed to focus on providing lower-boundary conditions to the atmosphere with less focus on hydrological processes. State-of-the-art application of LSMs includes a land data assimilation system (LDAS), which incorporates available land surface observations to provide an improved realism of surface conditions. While improved representations of the surface variables (such as soil moisture and snow depth) make LDAS an essential component of any numerical weather prediction (NWP) system, the related increments remove or add water, potentially having a negative impact on the simulated hydrological cycle by opening the water budget. This paper focuses on evaluating how well global NWP configurations are able to support hydrological applications, in addition to the traditional weather forecasting. River discharge simulations from two climatological reanalyses are compared: one "online" set, which includes land-atmosphere coupling and LDAS with an open water budget, and an "offline" set with a closed water budget and no LDAS. It was found that while the online version of the model largely improves temperature and snow depth conditions, it causes poorer representation of peak river flow, particularly in snowmelt-dominated areas in the high latitudes. Without addressing such issues there will never be confidence in using LSMs for hydrological forecasting applications across the globe. This type of analysis should be used to diagnose where improvements need to be made; considering the whole Earth system in the data assimilation and coupling developments is critical for moving toward the goal of holistic Earth system approaches.

  • Lindholm, Daniel
    et al.
    AstraZeneca R&D, Gothenburg, Sweden.
    Sarno, Giovanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Erlinge, David
    Lund Univ, Dept Cardiol, Lund, Sweden.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hasvold, Lars Pal
    AstraZeneca, Dept Med, Sodertalje, Sweden.
    Janzon, Magnus
    Linkoping Univ, Dept Med & Hlth Sci, Dept Cardiol, Linkoping, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Combined association of key risk factors on ischaemic outcomes and bleeding in patients with myocardial infarction2019In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 105, no 15, p. 1175-1181Article in journal (Refereed)
    Abstract [en]

    Objective: In patients with myocardial infarction (MI), risk factors for bleeding and ischaemic events tend to overlap, but the combined effects of these factors have scarcely been studied in contemporary real-world settings. We aimed to assess the combined associations of established risk factors using nationwide registries.

    Methods: Using the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry, patients with invasively managed MI in 2006-2014 were included. Six factors were assessed in relation to cardiovascular death (CVD)/MI/stroke, and major bleeding: age >= 65, chronic kidney disease, diabetes, multivessel disease, prior bleeding and prior MI.

    Results: We studied 100 879 patients, of whom 20 831 (20.6%) experienced CVD/MI/stroke and 5939 (5.9%) major bleeding, during 3.6 years median follow-up. In adjusted Cox models, all factors were associated with CVD/MI/stroke, and all but prior MI were associated with major bleeding. The majority (53.5%) had >= 2 risk factors. With each added risk factor, there was a marked but gradual increase in incidence of the CVD/MI/stroke. This was seen also for major bleeding, but to a lesser extent, largely driven by prior bleeding as the strongest risk factor.

    Conclusions: The majority of patients with MI had two or more established risk factors. Increasing number of risk factors was associated with higher rate of ischaemic events. When excluding patients with prior major bleeding, bleeding incidence rate increased only minimally with increasing number of risk factors. The high ischaemic risk in those with multiple risk factors highlights an unmet need for additional preventive measures.

  • Agbo, Mathias Jr
    et al.
    Makuwira, Jonathan
    Malawi University of Science and Technology, Limbe, Malawi.
    Cruelty by design: how African cities discriminate against people with disabilities2019Report (Other academic)
    Abstract [en]

    Africa is currently home to some 78 million people with disabilities. Meanwhile, recent years have seen the size and populations of the continent’s major cities increasing at a startling rate. As a result, there is a pressing need to consider issues of urban design and accessibility, and how they affect people with disabilities.

  • Public defence: 2019-09-25 13:15 Planck, Linköping
    Kargén, Ulf
    Linköping University, Department of Computer and Information Science, Database and information techniques. Linköping University, Faculty of Science & Engineering.
    Scalable Dynamic Analysis of Binary Code2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In recent years, binary code analysis, i.e., applying program analysis directly at the machine code level, has become an increasingly important topic of study. This is driven to a large extent by the information security community, where security auditing of closed-source software and analysis of malware are important applications. Since most of the high-level semantics of the original source code are lost upon compilation to executable code, static analysis is intractable for, e.g., fine-grained information flow analysis of binary code. Dynamic analysis, however, does not suffer in the same way from reduced accuracy in the absence of high-level semantics, and is therefore also more readily applicable to binary code. Since fine-grained dynamic analysis often requires recording detailed information about every instruction execution, scalability can become a significant challenge. In this thesis, we address the scalability challenges of two powerful dynamic analysis methods whose widespread use has, so far, been impeded by their lack of scalability: dynamic slicing and instruction trace alignment. Dynamic slicing provides fine-grained information about dependencies between individual instructions, and can be used both as a powerful debugging aid and as a foundation for other dynamic analysis techniques. Instruction trace alignment provides a means for comparing executions of two similar programs and has important applications in, e.g., malware analysis, security auditing, and plagiarism detection. We also apply our work on scalable dynamic analysis in two novel approaches to improve fuzzing — a popular random testing technique that is widely used in industry to discover security vulnerabilities.

    To use dynamic slicing, detailed information about a program execution must first be recorded. Since the amount of information is often too large to fit in main memory, existing dynamic slicing methods apply various time-versus-space trade-offs to reduce memory requirements. However, these trade-offs result in very high time overheads, limiting the usefulness of dynamic slicing in practice. In this thesis, we show that the speed of dynamic slicing can be greatly improved by carefully designing data structures and algorithms to exploit temporal locality of programs. This allows avoidance of the expensive trade-offs used in earlier methods by accessing recorded runtime information directly from secondary storage without significant random-access overhead. In addition to being a standalone contribution, scalable dynamic slicing also forms integral parts of our contributions to fuzzing. Our first contribution uses dynamic slicing and binary code mutation to automatically turn an existing executable into a test generator. In our experiments, this new approach to fuzzing achieved about an order of magnitude better code coverage than traditional mutational fuzzing and found several bugs in popular Linux software. The second work on fuzzing presented in this thesis uses dynamic slicing to accelerate the state-of-the-art fuzzer AFL by focusing the fuzzing effort on previously unexplored parts of the input space.

    For the second dynamic analysis technique whose scalability we sought to improve — instruction trace alignment — we employed techniques used in speech recognition and information retrieval to design what is, to the best of our knowledge, the first general approach to aligning realistically long program traces. We show in our experiments that this method is capable of producing meaningful alignments even in the presence of significant syntactic differences stemming from, for example, the use of different compilers or optimization levels.

  • Adegun, Olumuyiwa
    The Nordic Africa Institute, Research Unit. Federal University of Technology, Akure, Akure, Nigeria ; University of the Witwatersrand, Johannesburg, South Africa.
    Community engagement key for upgrading informal settlements2019Report (Other academic)
    Abstract [en]

    Several African countries are tackling the issue of slums and informal settlements by building completely new housing developments. However, many residents view these new areas as less habitable because of poor social conditions. Drawing on three case studies, this policy note argues that community engagement is crucial when planning to replace informal settlements with modern housing in African cities.

  • Honigs, Katrina
    et al.
    Lombardi, Luigi
    Tirabassi, Sofia
    Stockholm University, Faculty of Science, Department of Mathematics. University of Bergen.
    Derived equivalences of canonical covers of hyperelliptic and Enriques surfaces in positive characteristic2019In: Mathematische Zeitschrift, ISSN 0025-5874, E-ISSN 1432-1823Article in journal (Refereed)
    Abstract [en]

    We prove that any Fourier–Mukai partner of an abelian surface over an algebraically closed field of positive characteristic is isomorphic to a moduli space of Gieseker-stable sheaves. We apply this fact to show that the set of Fourier–Mukai partners of a canonical cover of a hyperelliptic or Enriques surface over an algebraically closed field of characteristic greater than three is trivial. These results extend earlier results of Bridgeland–Maciocia and Sosna to positive characteristic.

  • Alerby, Eva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Hagström, Erica
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Förhandlingar, uppgivenhet och blåbärets area: en studie av gymnasieelevers upplevelser av skolan i Nacka kommun2019Report (Other academic)
  • Santoni, Giola
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden.
    Meinow, Bettina
    Karolinska Inst, Aging Res Ctr, Dept Neurobiol Care Sci & Soc, Tomtebodavagen 18A,Floor 10, S-17165 Solna, Sweden;Stockholm Univ, Stockholm, Sweden;Stockholm Gerontol Res Ctr, Stockholm, Sweden.
    Wimo, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Ctr Alzheimer Res, Solna, Sweden.
    Marengoni, Alessandra
    Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden;Univ Brescia, Dept Clin & Expt Sci, Brescia, Italy.
    Fratiglioni, Laura
    Karolinska Inst, Aging Res Ctr, Dept Neurobiol Care Sci & Soc, Tomtebodavagen 18A,Floor 10, S-17165 Solna, Sweden;Stockholm Univ, Stockholm, Sweden;Stockholm Gerontol Res Ctr, Stockholm, Sweden.
    Calderon-Larranaga, Amaia
    Karolinska Inst, Aging Res Ctr, Dept Neurobiol Care Sci & Soc, Tomtebodavagen 18A,Floor 10, S-17165 Solna, Sweden;Stockholm Univ, Stockholm, Sweden.
    Using an Integrated Clinical and Functional Assessment Tool to Describe the Use of Social and Medical Care in an Urban Community-Dwelling Swedish Older Population2019In: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 20, no 8, p. 988-994Article in journal (Refereed)
    Abstract [en]

    Objectives: To describe the use of social and medical care services in a community-dwelling older population from Stockholm, Sweden, using an integrated clinical and functional assessment tool.

    Design: Study based on data from the longitudinal community-based Swedish National Study on Aging and Care in Kungsholmen.

    Setting and Participants: Random sample of people >65 years of age living in the community in central Stockholm between March 2001 and June 2004 (N = 2368).

    Measures: Health status was measured with a health assessment tool (HAT), which combines 5 indicators (gait speed, cognitive function, chronic multimorbidity, mild disability, severe disability) collected during Swedish National Study on Aging and Care in Kungsholmen clinical examinations. The amount of formal and informal social care was self-reported in hours per month and recorded by trained nurses at baseline and the 3-year follow-up for those >= 78 years of age at baseline. Data on hospital admissions, 30-day readmissions, days spent in the hospital, primary care visits, and specialist visits were obtained from Stockholm County Council registers (2001-2007).

    Results: At baseline, 10% of the sample received formal social care and 11% received informal care. Annually between baseline and the 3-year follow-up, 15% were admitted to the hospital, 5% were readmitted, 78% visited a specialist, and 89% visited primary care. Those with the best HAT scores received 0.02 hours/month of formal care; those with the worst, 34 h/mo. The corresponding numbers for other variables were 0.02 vs 73 h/mo of informal care, 2 vs 11 hospital admissions per 10 persons/year, 44 vs 226 hospital days per 10 persons/y, 0.4 vs 2 30-day readmissions per 10 persons/y, 37 vs 78 specialist visits per 10 persons/y, and 50 vs 327 primary care visits per 10 persons/y.

    Conclusions/Implications: Because of its high discriminative power, the easy-to-use HAT index could help decision makers to plan medical and social care services.

  • Westergren, Christina
    et al.
    The Nordic Museum.
    Silvén, Eva
    The Nordic Museum.
    Inledning2008In: För Sápmi i tiden, Stockholm: Nordiska museets förlag, 2008, p. 7-15Chapter in book (Other academic)
  • Public defence: 2019-09-13 09:15 B42, Uppsala
    Wegler, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Proteomics-informed analysis of drug disposition in the human liver and small intestine2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Orally administered drugs are absorbed in the intestine and generally metabolized in the liver. Therefore, understanding factors determining drug distribution and elimination in these tissues is important. This thesis aimed at using mass spectrometry (MS)-based proteomics and functional studies to better understand in vitro model systems used for drug clearance predictions. Further, it aimed at understanding the changes in drug disposition caused by obesity and gastric bypass surgery (GBP).

    The study was initiated by investigating factors influencing MS-based protein quantification by comparing results from different proteomics methods, and by studying protein distribution during subcellular fractionation. The largest variability in protein quantification was ascribed to insufficient enrichment from subcellular fractionation, most likely due to collection of the majority of the proteins in the initial fraction of the fractionation protocols.

    Proteomics and metabolic activity analyses were then used to investigate differences in intrinsic clearance from two commonly used in vitro systems, human liver microsomes and hepatocytes. For some compounds, the faster microsomal metabolism could be explained by a higher available unbound drug concentration and CYP content in the microsomes as compared to in the hepatocytes.

    Next, inter-individual protein expression variability in human liver and jejunum was explored. This showed that proteins covered a wide inter-individual variability spectrum, in which proteins with low variabilities were associated with essential cellular functions, while many proteins with high variabilities were disease-related.

    Further, the effects of obesity, GBP, and weight loss on the proteomes of human liver and jejunum were analyzed. After GBP and subsequent weight loss, patients showed lower levels of jejunal proteins involved in inflammatory response and drug metabolism.

    Finally, proteomics data from patients with and without obesity was combined with parameters from in vitro transport kinetics, and a mechanistic model to predict drug disposition was developed. The model successfully predicted rosuvastatin plasma concentrations in the patients.

    In conclusion, this thesis has provided insights into factors influencing protein quantification and function in vitro. Furthermore, this thesis demonstrates how proteomics contributes to improved understanding of inter-individual and physiological differences, and how it can be used for in vitro-in vivo scaling of drug clearance.

  • Jacob, Pierre
    et al.
    Harvard University, USA.
    Lindsten, Fredrik
    Uppsala universitet, Avdelningen för systemteknik, Sweden.
    Schön, Thomas B.
    Uppsala universitet, Avdelningen för systemteknik, Sweden.
    Retracted article: Smoothing with Couplings of Conditional Particle Filters2018In: Journal of the American Statistical Association, ISSN 0162-1459, E-ISSN 1537-274XArticle in journal (Refereed)
    Abstract [en]

    In state space models, smoothing refers to the task of estimating a latent stochastic process given noisy measurements related to the process. We propose an unbiased estimator of smoothing expectations. The lack-of-bias property has methodological benefits: independent estimators can be generated in parallel, and confidence intervals can be constructed from the central limit theorem to quantify the approximation error. To design unbiased estimators, we combine a generic debiasing technique for Markov chains, with a Markov chain Monte Carlo algorithm for smoothing. The resulting procedure is widely applicable and we show in numerical experiments that the removal of the bias comes at a manageable increase in variance. We establish the validity of the proposed estimators under mild assumptions. Numerical experiments are provided on toy models, including a setting of highly-informative observations, and for a realistic Lotka-Volterra model with an intractable transition density.

  • Bjønness, Kathrine
    et al.
    Jónsson, Kári
    Danielsson, Helena
    Gustafsson, Tomas
    Sander Poulsen, Tomas
    Forsberg, Tommi
    Keller, Nicole
    Stefani, Martina
    Skyrudsmoen, Lene
    F-gas methodologies and measurements in the Nordic Countries2019Other (Other (popular science, discussion, etc.))
    Abstract [en]

    This project report is a part of the NMR KOL project Nordic Policy Cluster for F-gases with the purpose of comparing the Nordic countries’ methodologies and regulations related to the use of F-gases.Fluorinated gases (F-gases, including HFCs, PFCs, SF6 and NF3) are a range of potent greenhouse gases that are used in a number of different applications and products for refrigeration, foams, aerosols, and technical installations.The report contains a survey and an overview of F-gas methodologies used for UNFCCC reporting, as well as an account of emissions and regulations in the Nordic countries.The objective with the analysis was to provide an overview of differences and similarities within the Nordic countries in relation to F-gases. The analysis shall enable harmonization of data collection, emission factors, choice of methods, and regulatory instruments.

  • Ericsson, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Advanced Neutron Spectroscopy in Fusion Research2019In: Journal of fusion energy, ISSN 0164-0313, E-ISSN 1572-9591, Vol. 38, no 3-4, p. 330-355Article in journal (Refereed)
    Abstract [en]

    This paper presents a review of the current state-of-the-art neutron spectroscopy in fusion research. The focus is on the fundamental nuclear physics and measurement principles. A brief introduction to relevant nuclear physics concepts is given and also a summary of the basic properties of neutron emission from a fusion plasma. Compact monitors/spectrometers like diamond, CLYC and the liquid scintillator are discussed. A longer section describes in some detail the more advanced, designed systems like those based on the thin-foil proton recoil and time-of-flight techniques. Examples of spectroscopy systems installed at JET and planned for ITER are given.

  • Wigren, Anna
    et al.
    Uppsala universitet, Avdelningen för systemteknik, Sweden.
    Murray, Lawrence
    Uppsala universitet, Avdelningen för systemteknik, Sweden.
    Lindsten, Fredrik
    Uppsala universitet, Avdelningen för systemteknik, Sweden.
    Improving the particle filter in high dimensions using conjugate artificial process noise2018In: 18th IFAC Symposium on System IdentificationSYSID 2018 Proceedings, Elsevier, 2018, Vol. 51, p. 670-675Conference paper (Refereed)
    Abstract [en]

    The particle filter is one of the most successful methods for state inference and identification of general non-linear and non-Gaussian models. However, standard particle filters suffer from degeneracy of the particle weights, in particular for high-dimensional problems. We propose a method for improving the performance of the particle filter for certain challenging state space models, with implications for high-dimensional inference. First we approximate the model by adding artificial process noise in an additional state update, then we design a proposal that combines the standard and the locally optimal proposal. This results in a bias-variance trade-off, where adding more noise reduces the variance of the estimate but increases the model bias. The performance of the proposed method is empirically evaluated on a linear-Gaussian state space model and on the non-linear Lorenz'96 model. For both models we observe a significant improvement in performance over the standard particle filter.

  • Cecconello, Marco
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Liquid Scintillators Neutron Response Function: A Tutorial2019In: Journal of fusion energy, ISSN 0164-0313, E-ISSN 1572-9591, Vol. 38, no 3-4, p. 356-375Article in journal (Refereed)
    Abstract [en]

    This tutorial is devoted to the understanding of the different components that are present in the neutron light output pulse height distribution of liquid scintillators in fusion relevant energy ranges. The basic mechanisms for the generation of the scintillation light are briefly discussed. The different elastic collision processed between the incident neutrons and the hydrogen and carbon atoms are described in terms of probability density functions and the overall response function as their convolution. The results from this analytical approach is then compared with those obtained from simplified and full Monte Carlo simulations. Edge effect, finite energy resolution, light output and transport and competing physical processes between neutron and carbon and hydrogen atoms and their impact on the response functions are discussed. Although the analytical treatment here presented allows only for a qualitative comparison with full Monte Carlo simulations it enables an understanding of the main features present in the response function and therefore provides the ground for the interpretation of more complex response functions such those measured in fusion plasmas. Although the main part of this tutorial is focused on the response function to mono-energetic 2.45 MeV neutrons a brief discussion is presented in case of broad neutron energy spectra and how these can be used to infer the underlying properties of fusion plasmas via the application of a forward modelling method.

  • Calafat, Francisco M.
    et al.
    Natl Oceanog Ctr, Joseph Proudman Bldg,6 Brownlow St, Liverpool L3 5DA, Merseyside, England.
    Wahl, Thomas
    Univ Cent Florida, Natl Ctr Integrated Coastal Res, 12800 Pegasus Dr,Suite 211, Orlando, FL 32816 USA;Univ Cent Florida, Dept Civil Environm & Construct Engn, USA.
    Lindsten, Fredrik
    Uppsala universitet, Reglerteknik, Sweden.
    Williams, Joanne
    Natl Oceanog Ctr, England.
    Frajka-Williams, Eleanor
    Univ Southampton, Ocean & Earth Sci, European Way, England.
    Coherent modulation of the sea-level annual cycle in the United States by Atlantic Rossby waves2018In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 2571Article in journal (Refereed)
    Abstract [en]

    Changes in the sea-level annual cycle (SLAC) can have profound impacts on coastal areas, including increased flooding risk and ecosystem alteration, yet little is known about the magnitude and drivers of such changes. Here we show, using novel Bayesian methods, that there are significant decadal fluctuations in the amplitude of the SLAC along the United States Gulf and Southeast coasts, including an extreme event in 2008-2009 that is likely (probability = 68%) unprecedented in the tide-gauge record. Such fluctuations are coherent along the coast but decoupled from deep-ocean changes. Through the use of numerical and analytical ocean models, we show that the primary driver of these fluctuations involves incident Rossby waves that generate fast western-boundary waves. These Rossby waves project onto the basin-wide upper mid-ocean transport (top 1000 m) leading to a link with the SLAC, wherein larger SLAC amplitudes coincide with enhanced transport variability.

  • Åkerstedt, Torbjorn
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden;Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Schwarz, Johanna
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden;Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Gruber, Georg
    Siesta Grp, Vienna, Austria.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Short sleep-poor sleep?: A polysomnographic study in a large population-based sample of women2019In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 28, no 4, article id e12812Article in journal (Refereed)
    Abstract [en]

    There is a lack of studies on the association between total sleep time (TST) and other polysomnographical parameters. A key question is whether a short sleep is an expression of habitual short sleep, or whether it reflects temporary impairment. The purpose of the present study was to investigate the association between TST and amount of sleep stages and sleep continuity measures, in a large population-based sample of women (n = 385), sleeping at home in a normal daily life setting. The results show that sleep efficiency, N1 (min), N2 (min), REM (min), REM% and proportion of long sleep segments, increased with increasing TST, whereas the number of awakenings/hr, the number of arousals/hr, N1% and REM intensity decreased. In addition, longer sleep was more associated with TST being perceived as of "usual" duration and with better subjective sleep quality. TST was not associated with habitual reported sleep duration. It was concluded that short TST of a recorded sleep in a real-life context may be an indicator of poor objective sleep quality for that particular sleep episode. Because individuals clearly perceived this reduction, it appears that self-reports of poor sleep quality often may be seen as indicators of poor sleep quality. It is also concluded that PSG-recorded sleep duration does not reflect habitual reported sleep duration in the present real-life context.

  • Alvarez, Laura
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid- Consejo Superior de Investigaciones Científicas, Madrid, Spain.
    Sanchez-Hevia, Dione
    Sanchez, Mercedes
    Berenguer, Jose
    A new family of nitrate/nitrite transporters involved in denitrification2019In: International Microbiology, ISSN 1139-6709, E-ISSN 1618-1905, Vol. 22, no 1, p. 19-28Article in journal (Refereed)
    Abstract [en]

    Denitrifying bacteria carry out nitrate and nitrite respiration inside and outside the cell, respectively. In Thermus thermophilus, nitrate and nitrite transport processes are carried out by major facilitator superfamily (MFS) transporters. The sequence of the nar operon of nitrate-only respiring strains of T. thermophilus includes two tandemly organized MFS transporter genes (narK and narT) of the NarK1 and NarK2 families. Both can function as nitrate/nitrite antiporters, but NarK has been proposed as more specific for nitrate whereas NarT more specific for nitrite. In some nitrate- and nitrite-respiring strains of the same species, a single MFS transporter (NarO) belonging to a different MFS subfamily appears. To analyze the role of this single MFS in the same genetic context, we transferred the two types of nar operon to the aerobic strain HB27, and further included in both of them the ability to respire nitrite. The new denitrifying strains HB27dn, with two MFS, and HB27dp, with a single one, were used to isolate mutants devoid of transporters. Through in trans complementation experiments, we demonstrate that the NarO single MFS works efficiently in the transport of both nitrate and nitrite.

  • Singh, S. S.
    et al.
    Univ Cambridge, Dept Engn, Trumpington St, Cambridge CB2 1PZ, England.
    Lindsten, Fredrik
    Uppsala universitet, Reglerteknik, Sweden.
    Moulines, E.
    Ecole Polytech, Ctr Math Appl, Route Saclay, F-91128 Palaiseau, France.
    Blocking strategies and stability of particle Gibbs samplers2017In: Biometrika, ISSN 0006-3444, E-ISSN 1464-3510, Vol. 104, no 4, p. 953-969Article in journal (Refereed)
    Abstract [en]

    Sampling from the posterior probability distribution of the latent states of a hidden Markov model is nontrivial even in the context of Markov chain Monte Carlo. To address this, Andrieu et al. (2010) proposed a way of using a particle filter to construct a Markov kernel that leaves the posterior distribution invariant. Recent theoretical results have established the uniform ergodicity of this Markov kernel and shown that the mixing rate does not deteriorate provided the number of particles grows at least linearly with the number of latent states. However, this gives rise to a cost per application of the kernel that is quadratic in the number of latent states, which can be prohibitive for long observation sequences. Using blocking strategies, we devise samplers that have a stable mixing rate for a cost per iteration that is linear in the number of latent states and which are easily parallelizable.

  • Public defence: 2019-09-13 10:00 E1405
    Kallin, Sara
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Rehabilitation.
    Deformation of human soft tissues: Experimental and numerical aspects2019Licentiate thesis, monograph (Other academic)
  • Aaboud, M.
    et al.
    Asimakopoulou, Eleni M.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Bergeås Kuutmann, Elin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Bokan, Petar
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Brenner, Richard
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ekelöf, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellajosyula, Venugopal
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellert, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ferrari, Arnaud
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Gradin, P. O. Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Isacson, Max
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Mårtensson, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Sales De Bruin, Pedro H.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zwalinski, L.
    Searches for third-generation scalar leptoquarks in √s = 13 TeV pp collisions with the ATLAS detector2019In: Journal of High Energy Physics (JHEP), ISSN 1126-6708, E-ISSN 1029-8479, no 6, article id 144Article in journal (Refereed)
    Abstract [en]

    Limits are set on the pair production of scalar leptoquarks, where all possible decays of the leptoquark into a quark (t, b) and a lepton (, ) of the third generation are considered. The limits are presented as a function of the leptoquark mass and the branching ratio into charged leptons for up-type (LQ<sub ) and down-type (/t) leptoquarks. Many results are reinterpretations of previously published ATLAS searches. In all cases, LHC proton-proton collision data at a centre-of-mass energy of = 13 TeV recorded by the ATLAS detector in 2015 and 2016 are used, corresponding to an integrated luminosity of 36.1 fb(-1). Masses below 800 GeV are excluded for both LQu and LQd independently of the branching ratio, with masses below about 1 TeV being excluded for the limiting cases of branching ratios equal to zero or unity.

  • Public defence: 2019-09-16 09:00 sal FB42 AlbaNova universitetscentrum, Stockholm
    Mohamed El Hassan, Ashraf
    Stockholm University, Faculty of Science, Department of Physics.
    Multiparty Quantum Communication and fs-laser Written Integrated Optics Circuits2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Quantum information science, the rapidly developing interdisciplinary field,  gives power to the information and communications technologies (ICT) by  providing secure communication, precision measurements, ultra-powerful simulation and ultimately computation. It is well known that photons are an ideal candidate for encoding the quantum bit, or "qubit", in quantum information and specially for quantum communication. This thesis consists of two main parts. In the first part, realization of quantum security tasks using optical fibers has been implemented. Bell tests are a cornerstone of quantum key distribution and are necessary for device-independent security. Device-independent Bell inequality test must be performed with care to avoid loopholes. Time-energy entanglement has a distinct advantage over polarization as it is easier transmitted over longer distances, therefore, it may be preferable as a quantum resource to perform reliable key distribution. Novel multi-party communication protocols: secret sharing, detectable Byzantine agreement, clock synchronization, and reduction of communication complexity, all these quantum protocols has been realized without compromising on detection efficiency or generating extremely complex many-particle entangled states. These protocols are realized in an optical fiber setup with sequential phase modulation on single photons. In recent years there has been great interest in fabricating ICT optical setups in low scale in glass chips, which would replace the bulk setups on tables used today. In the second part of the thesis, realization of photonic waveguides in glass has been implemented. Using femtosecond laser inscription of waveguides in glass, photonic quantum technologies and integrated optical circuits are becoming more and more important in miniaturization of optical circuits written in different glass samples for the quantum optics and quantum information processing. These platforms offer stability over the time-scales required for multi-photon coincidence based measurements. The study and optimization the different building blocks for integrated photonic quantum circuits, for instance the directional coupler and Mach-Zehnder interferometer is very important. The principal goal is to develop a method for design, fabrication and characterization of integrated optics circuits for further applications in quantum information. Incorporation of photon sources, detectors, and circuits integrating waveguides technology can be used to produce integrated photonics devices.

  • Zambrano, Jesus
    et al.
    Malardalen Univ, Sch Business Soc & Engn, POB 883, S-72123 Vasteras, Sweden.
    Samuelsson, Oscar
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. IVL Swedish Environm Res Inst, POB 210, S-10031 Stockholm, Sweden.
    Carlsson, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control.
    Machine learning techniques for monitoring the sludge profile in a secondary settler tank2019In: Applied water science, ISSN 2190-5487, E-ISSN 2190-5495, Vol. 9, no 6, article id 146Article in journal (Refereed)
    Abstract [en]

    The aim of this paper is to evaluate and compare the performance of two machine learning methods, Gaussian process regression (GPR) and Gaussian mixture models (GMMs), as two possible methods for monitoring the sludge profile in a secondary settler tank (SST). In GPR, the prediction of the response variable is given as a Gaussian probability density function, whereas in the GMM the probability density function is built as a weighted sum of Gaussian distributions. In both approaches, a residual is calculated and a fault detection criterion is implemented via a recursive decision rule. As case study, GMM and GPR were tested using real data from a sensor measuring the suspended solids concentration as a function of the SST level in a wastewater treatment plant in Bromma, Sweden. Results suggest that GMM gives a faster response but is also more sensitive than GPR to changes during normal conditions.

  • Public defence: 2019-09-13 13:00 Room E22, VisbyNorberg, Monica
    Engagerat ledarskap för att skapa förutsättningar för allas delaktighet: Utgångspunkter i kvalitetsarbetet2019Doctoral thesis, monograph (Other academic)
    Abstract [en]

    According to increased demands on continuous improvements for organizations, they choose different strategies for improvements such as the use of systematic quality systems to structure the progresses in the business. However, studies have shown that improvement projects often fail due to the leadership and commitment within the organization. Research points out weak or missing techniques and tools connected to committed leadership and let everybody be committed, two important principles in systematic quality systems like Total Quality Management, in Sweden mentioned as the cornerstone model.

    Based on six different studies, this doctoral thesis deepens the knowledge about managers’ prerequisites to use leadership, which can enable commitment to an organization’s quality work in a Swedish context. First, five smaller studies were conducted, mainly focused on diversity, inclusion, and leadership in different kinds of organizations. The results from these five studies created a foundation for the sixth and main study, a case study within an organization dealing with Fast-Moving Consumer Goods. The case study included observations, both non-participation and participation, interviews with CEO, the management group, employees, but included also group measurement and document studies during a year with follow-up interviews.

    In conclusion, the doctoral thesis results have contributed to the development of techniques and tools connected to how a committed leadership can give prerequisites to let everybody be committed. The results have also given the possibility to complement the model Principles-Practices-Tools (PAV) with additional principles, concrete techniques and tools