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  • Public defence: 2019-04-26 10:15 TEMCAS, Hus T, Linköping
    Šafarič, Luka
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences.
    Anaerobic Digester Fluid Rheology and Process Efficiency: Interactions of Substrate Composition, Trace Element Availability, and Microbial Activity2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    As the anthropogenic greenhouse gas emissions continue imposing stress on our environment, it is becoming increasingly important to identify and implement new renewable technologies. Biogas production through anaerobic digestion has a great potential, since it links waste treatment with extraction of renewable energy, enabling circular bio-economies that are vital for a sustainable future.

    For biogas to have an important role as a renewable energy carrier in society, the scale of its production will need to be increased substantially. New substrates need to be introduced along with raising organic loading rates of the reactors to increase the rate of biogas production. This contributes to challenges in maintaining process stability, thus increasing the risk for process disturbances, including problems that were not commonly encountered before. These difficulties may be particularly pronounced when a broad range of new, largely untested substrates are introduced, leading to an increased heterogeneity of organic material entering the reactors. In the case of currently the most common reactor type; the continuous stirred-tank biogas reactor (CSTBR); such problems may include shifts in rheology (i.e. fluid behaviour) of the anaerobic digester sludge. This may lead to increased energy consumption and decreased digester mixing efficiencies, which in turn may lead to inefficient biogas processes, ultimately decreasing the economic and environmental viability of biogas production. Much is still unknown regarding how rheology shifts happen in biogas reactors, particularly when it comes to what role the substrate plays in rheological dynamics, as compared to the microbial community during varying levels of biogas process stability.

    This thesis elucidates the interactions between substrate type, microbial community and its metabolic activity, and anaerobic sludge rheology. A number of sludge samples from mesophilic and thermophilic CSTBRs digesting a broad range of substrates was analysed for their rheology. The specific effects of individual substrate types on CSTBR sludge rheology and the resulting implications for stirring power requirements and mixing efficiency were investigated. In order to also asses to which extent the microbial metabolism affects rheology at different levels of process disturbance, an experiment with a trace-element-induced inhibition of specific metabolic pathways under mesophilic reactor conditions was performed. This was used to identify the sequence of different interactions that occur in the reactor after the process begins to fail, and to evaluate how these interactions link to changes in digester sludge rheology. Finally, a case study of a disturbed thermophilic anaerobic digestion process was performed, including the monitoring of the response of rheology in relation to process stability, which was modified by changing trace element concentrations. The use of artificial substrate without polymeric compounds in both cases allowed for an evaluation of effects of the microbial community and its metabolic products on rheology without including the effects of complex substrates.

    The results showed that substrate type has a large effect on how different process parameters correlate with fluid behaviour. This was particularly apparent in the case of total solids and total volatile solids, which correlated well with rheological parameters for samples from reactors digesting agricultural waste, sewage sludge, paper mill waste, or food waste, but not for mesophilic co-digesters. Among the different substrates investigated, food waste was generally observed to lead to the highest limit viscosities (i.e. apparent viscosities at high shear rates, where it becomes linear and constant) of the anaerobic sludge, while digestion of paper mill waste and thermophilic co-digestion led to some of the lowest. No fluid type could be clearly coupled to a specific substrate, but it could be observed that increased solids content could generally be associated with more complex, non-Newtonian rheological behaviour. The differences in fluid characteristics between reactors corresponded to large differences in modelled stirring power requirements and mixing efficiency. The results indicated that fluids with high values of rheological parameters, such as the consistency index (K) or yield stress (τ0), would likely require more power or an adapted stirring system to achieve complete mixing. The substrates generally contributed more to the rheology characteristics of the anaerobic sludge than microbial cells on their own. Trace element-induced process disturbance initially led to the inhibition of specific microbial groups among methanogenic archaea or their syntrophic partners, which later escalated to broader inhibition of many microbial groups due to the accumulation of fermentation products. This resulted in microbial cell washout with a corresponding decrease of the contribution of the cells to anaerobic sludge rheology. A recovery of the thermophilic anaerobic digestion process was possible after the supplementation of selenium and tungsten was increased, resulting in increased propionate turnover rates, growing cell densities, and higher viscosity. Major shifts in the methanogenic community were observed, corresponding to the level of process stability. It could be concluded based on these experiments that the specific effect of microbial cells and their activity on sludge rheology were linked to cell density, which corresponded to process stability.

    A conceptual scheme was developed based on the studies in this thesis, defining complex interactions between substrate, microbial metabolism, and anaerobic sludge rheology in biogas processes. The possible causes of rheology shifts are visualised and discussed.

    List of papers
    1. Substrate and operational conditions as regulators of fluid properties in full-scale continuous stirred-tank biogas reactors - implications for rheology-driven power requirements
    Open this publication in new window or tab >>Substrate and operational conditions as regulators of fluid properties in full-scale continuous stirred-tank biogas reactors - implications for rheology-driven power requirements
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    2018 (English)In: Water Science and Technology, ISSN 0273-1223, E-ISSN 1996-9732, Vol. 78, no 4, p. 814-826Article in journal (Refereed) Published
    Abstract [en]

    Understanding fluid rheology is important for optimal design and operation of continuous stirred-tank biogas reactors (CSTBRs) and is the basis for power requirement estimates. Conflicting results have been reported regarding the applicability of total solid (TS) and/or total volatile solid (TVS) contents of CSTBR fluids as proxies for rheological properties. Thus, the present study investigates relationships between rheological properties of 12 full-scale CSTBR fluids, their substrate profiles, and major operational conditions, including pH, TS and TVS contents, organic loading rate, hydraulic retention time, and temperature. Rheology-driven power requirements based on various fluid characteristics were evaluated for a general biogas reactor setup. The results revealed a significant correlation only between the rheological fluid properties and TS or TVS contents for sewage sludge digesters and thermophilic co-digesters (CD), but not for mesophilic CD. Furthermore, the calculated power requirements for pumping and mixing, based on the various fluid characteristics of the studied CSTBRs, varied broadly irrespective of TS and TVS contents. Thus, this study shows that the TS and/or TVS contents of digester fluid are not reliable estimators of the rheological properties in CSTBRs digesting substrates other than sewage sludge.

    Place, publisher, year, edition, pages
    IWA PUBLISHING, 2018
    Keywords
    anaerobic digestion; biogas; continuous stirred-tank biogas reactor; power requirement; rheology; viscosity
    National Category
    Other Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:liu:diva-151955 (URN)10.2166/wst.2018.352 (DOI)000445519000010 ()30252659 (PubMedID)
    Note

    Funding Agencies|Innovation Agency (VINNOVA), Sweden [2008-139]; Scandinavian Biogas Fuels AB, Sweden; European Unions Seventh Framework ATBEST Marie-Curie ITN program [316838]; Biogas Research Center; Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS), Sweden; Linkoping University; Swedish Energy Agency [35624-2]

    Available from: 2018-10-16 Created: 2018-10-16 Last updated: 2019-04-02
    2. Dynamics of a Perturbed Microbial Community during Thermophilic Anaerobic Digestion of Chemically Defined Soluble Organic Compounds
    Open this publication in new window or tab >>Dynamics of a Perturbed Microbial Community during Thermophilic Anaerobic Digestion of Chemically Defined Soluble Organic Compounds
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    2018 (English)In: MICROORGANISMS, ISSN 2076-2607, Vol. 6, no 4, article id 105Article in journal (Refereed) Published
    Abstract [en]

    Knowledge of microbial community dynamics in relation to process perturbations is fundamental to understand and deal with the instability of anaerobic digestion (AD) processes. This study aims to investigate the microbial community structure and function of a thermophilic AD process, fed with a chemically defined substrate, and its association with process performance stability. Next generation amplicon sequencing of 16S ribosomal RNA (rRNA) genes revealed that variations in relative abundances of the predominant bacterial species, Defluviitoga tunisiensis and Anaerobaculum hydrogeniformans, were not linked to the process performance stability, while dynamics of bacterial genera of low abundance, Coprothermobacter and Defluviitoga (other than D. tunisiensis), were associated with microbial community function and process stability. A decrease in the diversity of the archaeal community was observed in conjunction with process recovery and stable performance, implying that the high abundance of specific archaeal group(s) contributed to the stable AD. Dominance of hydrogenotrophic Methanoculleus particularly corresponded to an enhanced microbial acetate and propionate turnover capacity, whereas the prevalence of hydrogenotrophic Methanothermobacter and acetoclastic Methanosaeta was associated with instable AD. Acetate oxidation via syntrophic interactions between Coprothermobacter and Methanoculleus was potentially the main methane-formation pathway during the stable process. We observed that supplementation of Se and W to the medium improved the propionate turnover by the thermophilic consortium. The outcomes of our study provided insights into the community dynamics and trace element requirements in relation to the process performance stability of thermophilic AD.

    Place, publisher, year, edition, pages
    MDPI, 2018
    Keywords
    Thermophilic Anaerobic Digestion; process perturbation; process stability; microbial community dynamics; trace elements
    National Category
    Microbiology
    Identifiers
    urn:nbn:se:liu:diva-154125 (URN)10.3390/microorganisms6040105 (DOI)000455073000010 ()30314333 (PubMedID)
    Note

    Funding Agencies|European Unions Seventh Framework ATBEST Marie-Curie ITN program [316838]; Linkoping University; Swedish Energy Agency [35624-2]; Biogas Research Center

    Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2019-04-02
  • Public defence: 2019-04-26 13:05 Originalet, Jönköping
    Gustafsson Bragde, Hanna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Laboratory Medicine, Region Jönköping County.
    Biomarkers of Inflammation and Intestinal Mucosa Pathology in Celiac Disease2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy triggered by gluten. The only currently available treatment is complying with a lifelong gluten-free diet, which should not be commenced before a CD diagnosis has been established by diagnostic test results (including histopathologic assessment of small intestinal biopsies and CD-specific antibody levels). This makes diagnostic swiftness and accuracy important. In cases with low CD-specific antibody levels and/or low-grade intestinal injuries the diagnosis can be difficult to establish. The main objective of this thesis was to complement and improve CD diagnostics by identifying and implementing new biomarkers, mainly based on gene expression, in small intestinal biopsies and blood. In paper I, genes were selected to reflect villous height, crypt elongation, immune response, and epithelial integrity. The results showed that a subset of those genes could discriminate active CD mucosa from mucosa without CD-related changes and grade the intestinal injury. In paper III, an unbiased investigation of gene expression in CD mucosa was performed using transcriptome analysis. Active CD and non-CD mucosa showed differential expression in a subset of genes, and some were differentially expressed in CD mucosa before histopathologic assessment could confirm intestinal alterations compatible with a CD diagnosis. Gene set analysis revealed that there are many biological processes affected in CD mucosa, including those associated with immune response, microbial infection, phagocytosis, intestinal barrier function, metabolism, and transportation.

    In parallel, gene expression was investigated in stabilised whole blood. Blood is a more accessible sampling material than intestinal biopsies, and stabilised blood is suitable for routine diagnostics since transcript levels are preserved at sampling. In paper II, expressions from a selection of genes were quantified in stabilised whole blood (RNA) and/or plasma (protein). Three genes with differential expression in CD were identified. Compared to the CD-specific autoantibodies against tissue transglutaminase (anti-TG2) alone, the addition of the information from the new potential markers resulted in a nonsignificant contribution to the diagnostic capacity of anti-TG2. An unbiased investigation using transcriptome analysis (paper IV) showed that gene level expression differences in stabilised whole blood were small between CD and non-CD. However, expression differences on a gene set level could potentially be used in CD diagnostics. CD-associated biological processes suggested by the results included a pro-inflammatory response, negative regulation of viral replication, proliferation, differentiation, cell migration, cell survival, translation, and haemostasis.

    Expression analysis using real-time polymerase chain reaction (PCR) is easy to perform, with instrumentation available at most clinical laboratories. Although select solitary biomarkers could be very useful in the diagnosis of CD, basing gene expression profiles on pathway information instead of single genes might also disclose disease heterogeneity between patients and add stability to a diagnostic method based on gene expressions. In conclusion, the results of this work demonstrate that analysing the expression of a few small intestinal genes can complement CD diagnostics. The application of gene expression analysis in cases with minor small intestine histopathological changes shows promising results, but needs further investigations. Additionally, gene expressions in other inflammatory diseases of the small intestine need to be investigated and compared with CD to complete the picture. Moreover, the findings from this work give clues about the biological contexts in which CD resides, and the potential of gene expression in blood at a gene set level is of interest for further investigations.

    List of papers
    1. Gene Expression Profiling of Duodenal Biopsies Discriminates Celiac Disease Mucosa From Normal Mucosa
    Open this publication in new window or tab >>Gene Expression Profiling of Duodenal Biopsies Discriminates Celiac Disease Mucosa From Normal Mucosa
    2011 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 69, no 6, p. 530-537Article in journal (Refereed) Published
    Abstract [en]

    Celiac disease (CD) is identified by histopathologic changes in the small intestine which normalize during a gluten-free diet. The histopathologic assessment of duodenal biopsies is usually routine but can be difficult. This study investigated gene expression profiling as a diagnostic tool. A total of 109 genes were selected to reflect alterations in crypt-villi architecture, inflammatory response, and intestinal permeability and were examined for differential expression in normal mucosa compared with CD mucosa in pediatric patients. Biopsies were classified using discriminant analysis of gene expression. Fifty genes were differentially expressed, of which eight (APOC3, CYP3A4, OCLN, MAD2L1, MKI67, CXCL11, IL17A, and CTLA4) discriminated normal mucosa from CD mucosa without classification errors using leave-one-out cross-validation (n = 39) and identified the degree of mucosal damage. Validation using an independent set of biopsies (n = 27) resulted in four discrepant cases. Biopsies from two of these cases showed a patchy distribution of lesions, indicating that discriminant analysis based on single biopsies failed to identify CD mucosa. In the other two cases, serology support class according to discriminant analysis and histologic specimens were judged suboptimal but assessable. Gene expression profiling shows promise as a diagnostic tool and for follow-up of CD, but further evaluation is needed.

    Place, publisher, year, edition, pages
    International Pediatrics Research Foundation, Inc. SN -, 2011
    National Category
    Medical Genetics
    Identifiers
    urn:nbn:se:liu:diva-156089 (URN)10.1203/PDR.0b013e318217ecec (DOI)
    Available from: 2019-04-03 Created: 2019-04-03 Last updated: 2019-04-03
    2. Potential blood-based markers of celiac disease
    Open this publication in new window or tab >>Potential blood-based markers of celiac disease
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    2014 (English)In: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 14, no 176Article in journal (Refereed) Published
    Abstract [en]

    Background: Blood-based diagnostics has the potential to simplify the process of diagnosing celiac disease (CD). Although high levels of autoantibodies against tissue transglutaminase (anti-TG2) are strongly indicative of active CD, several other scenarios involve a need for additional blood-based CD markers. Methods: We investigated the levels of messenger RNA (mRNA) in whole blood (n = 49) and protein in plasma (n = 22) from cases with active CD (n = 20), with confirmed CD and normalized histology (n = 15), and without a CD diagnosis (n = 14). Group differences were analyzed using Kruskal-Wallis one-way analysis of variance by ranks. We also investigated correlations between levels of potential markers, histopathology according to the modified Marsh scale, and CD risk gradient based on HLA type, using Spearman rank correlation. The relation between HLA-DQ2 gene dose effect and the expression levels of selected blood-based markers was investigated using the Mann-Whitney U test. Finally, the diagnostic performance of anti-TG2, potential blood-based CD markers, and logistic regression models of combined markers was evaluated using receiver operating characteristic (ROC) curve analysis. Results: CXCL11 protein levels and TNFRSF9 and TNFSF13B mRNA levels were identified as potential CD markers. These are all affected by or involved in the regulation of the NF-kappa B complex. CXCL11 protein levels and IL21 and IL15 mRNA levels were correlated with histopathology according to the modified Marsh scale, as were the established CD markers. HLA genotype risk and HLA-DQ2 gene dose effect did not show any significant relations with either the potential CD markers or the established CD markers. ROC curve analysis revealed a slight, non-significant increase in the area under the curve for the combined use of anti-TG2 and different constellations of potential blood-based CD markers compared to anti-TG2 alone. Conclusions: The CD markers identified in this study further emphasize the significance of components related to NF-kappa B regulation in relation to CD. However, the relevance of CXCL11, TNFSF13B, TNFRSF9, and other NF-kappa B interacting proteins recognized by pathway analysis, needs to be further investigated in relation to diagnosis and monitoring of CD.

    Place, publisher, year, edition, pages
    BioMed Central, 2014
    Keywords
    Celiac disease; Molecular diagnostics; Blood-based biological markers
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-112037 (URN)10.1186/1471-230X-14-176 (DOI)000342782900001 ()25298177 (PubMedID)
    Note

    Funding Agencies|Futurum - the Academy for Healthcare; Jonkoping County Council; Medical Research Council of Southeast Sweden

    Available from: 2014-11-17 Created: 2014-11-13 Last updated: 2019-04-03
    3. Celiac disease biomarkers identified by transcriptome analysis of small intestinal biopsies
    Open this publication in new window or tab >>Celiac disease biomarkers identified by transcriptome analysis of small intestinal biopsies
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    2018 (English)In: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 75, no 23, p. 4385-4401Article in journal (Refereed) Published
    Abstract [en]

    Establishing a celiac disease (CD) diagnosis can be difficult, such as when CD-specific antibody levels are just above cutoff or when small intestinal biopsies show low-grade injuries. To investigate the biological pathways involved in CD and select potential biomarkers to aid in CD diagnosis, RNA sequencing of duodenal biopsies from subjects with either confirmed Active CD (n=20) or without any signs of CD (n=20) was performed. Gene enrichment and pathway analysis highlighted contexts, such as immune response, microbial infection, phagocytosis, intestinal barrier function, metabolism, and transportation. Twenty-nine potential CD biomarkers were selected based on differential expression and biological context. The biomarkers were validated by real-time polymerase chain reaction of eight RNA sequencing study subjects, and further investigated using an independent study group (n=43) consisting of subjects not affected by CD, with a clear diagnosis of CD on either a gluten-containing or a gluten-free diet, or with low-grade intestinal injury. Selected biomarkers were able to classify subjects with clear CD/non-CD status, and a subset of the biomarkers (CXCL10, GBP5, IFI27, IFNG, and UBD) showed differential expression in biopsies from subjects with no or low-grade intestinal injury that received a CD diagnosis based on biopsies taken at a later time point. A large number of pathways are involved in CD pathogenesis, and gene expression is affected in CD mucosa already in low-grade intestinal injuries. RNA sequencing of low-grade intestinal injuries might discover pathways and biomarkers involved in early stages of CD pathogenesis.

    Place, publisher, year, edition, pages
    SPRINGER BASEL AG, 2018
    Keywords
    RNA-seq; RNA sequencing; Molecular biomarkers; Gene expression profiling; Gene ontology enrichment analysis
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-152799 (URN)10.1007/s00018-018-2898-5 (DOI)000449307300008 ()30097691 (PubMedID)
    Note

    Funding Agencies|Futurum-the Academy for Health and Care, Region Jonkoping County; Medical Research Council of Southeast Sweden; National Genomics Infrastructure - Swedish Research Council

    Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2019-04-10
  • Public defence: 2019-04-26 13:15 Domen, Visualiseringscenter C, Norrköping
    Grelsson, Bertil
    Linköping University, Department of Electrical Engineering, Computer Vision. Linköping University, Faculty of Science & Engineering.
    Vision-based Localization and Attitude Estimation Methods in Natural Environments2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Over the last decade, the usage of unmanned systems such as Unmanned Aerial Vehicles (UAVs), Unmanned Surface Vessels (USVs) and Unmanned Ground Vehicles (UGVs) has increased drastically, and there is still a rapid growth. Today, unmanned systems are being deployed in many daily operations, e.g. for deliveries in remote areas, to increase efficiency of agriculture, and for environmental monitoring at sea. For safety reasons, unmanned systems are often the preferred choice for surveillance missions in hazardous environments, e.g. for detection of nuclear radiation, and in disaster areas after earthquakes, hurricanes, or during forest fires. For safe navigation of the unmanned systems during their missions, continuous and accurate global localization and attitude estimation is mandatory.

    Over the years, many vision-based methods for position estimation have been developed, primarily for urban areas. In contrast, this thesis is mainly focused on vision-based methods for accurate position and attitude estimates in natural environments, i.e. beyond the urban areas. Vision-based methods possess several characteristics that make them appealing as global position and attitude sensors. First, vision sensors can be realized and tailored for most unmanned vehicle applications. Second, geo-referenced terrain models can be generated worldwide from satellite imagery and can be stored onboard the vehicles. In natural environments, where the availability of geo-referenced images in general is low, registration of image information with terrain models is the natural choice for position and attitude estimation. This is the problem area that I addressed in the contributions of this thesis.

    The first contribution is a method for full 6DoF (degrees of freedom) pose estimation from aerial images. A dense local height map is computed using structure from motion. The global pose is inferred from the 3D similarity transform between the local height map and a digital elevation model. Aligning height information is assumed to be more robust to season variations than feature-based matching.

    The second contribution is a method for accurate attitude (pitch and roll angle) estimation via horizon detection. It is one of only a few methods that use an omnidirectional (fisheye) camera for horizon detection in aerial images. The method is based on edge detection and a probabilistic Hough voting scheme. The method allows prior knowledge of the attitude angles to be exploited to make the initial attitude estimates more robust. The estimates are then refined through registration with the geometrically expected horizon line from a digital elevation model. To the best of our knowledge, it is the first method where the ray refraction in the atmosphere is taken into account, which enables the highly accurate attitude estimates.

    The third contribution is a method for position estimation based on horizon detection in an omnidirectional panoramic image around a surface vessel. Two convolutional neural networks (CNNs) are designed and trained to estimate the camera orientation and to segment the horizon line in the image. The MOSSE correlation filter, normally used in visual object tracking, is adapted to horizon line registration with geometric data from a digital elevation model. Comprehensive field trials conducted in the archipelago demonstrate the GPS-level accuracy of the method, and that the method can be trained on images from one region and then applied to images from a previously unvisited test area.

    The CNNs in the third contribution apply the typical scheme of convolutions, activations, and pooling. The fourth contribution focuses on the activations and suggests a new formulation to tune and optimize a piecewise linear activation function during training of CNNs. Improved classification results from experiments when tuning the activation function led to the introduction of a new activation function, the Shifted Exponential Linear Unit (ShELU).

    List of papers
    1. Efficient 7D Aerial Pose Estimation
    Open this publication in new window or tab >>Efficient 7D Aerial Pose Estimation
    2013 (English)In: 2013 IEEE Workshop on Robot Vision (WORV), IEEE , 2013, p. 88-95Conference paper, Published paper (Refereed)
    Abstract [en]

    A method for online global pose estimation of aerial images by alignment with a georeferenced 3D model is presented.Motion stereo is used to reconstruct a dense local height patch from an image pair. The global pose is inferred from the 3D transform between the local height patch and the model.For efficiency, the sought 3D similarity transform is found by least-squares minimizations of three 2D subproblems.The method does not require any landmarks or reference points in the 3D model, but an approximate initialization of the global pose, in our case provided by onboard navigation sensors, is assumed.Real aerial images from helicopter and aircraft flights are used to evaluate the method. The results show that the accuracy of the position and orientation estimates is significantly improved compared to the initialization and our method is more robust than competing methods on similar datasets.The proposed matching error computed between the transformed patch and the map clearly indicates whether a reliable pose estimate has been obtained.

    Place, publisher, year, edition, pages
    IEEE, 2013
    Keywords
    Pose estimation, aerial images, registration, 3D model
    National Category
    Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:liu:diva-89477 (URN)10.1109/WORV.2013.6521919 (DOI)000325279400014 ()978-1-4673-5646-6 (ISBN)978-1-4673-5647-3 (ISBN)
    Conference
    IEEE Workshop on Robot Vision 2013, Clearwater Beach, Florida, USA, January 16-17, 2013
    Available from: 2013-02-26 Created: 2013-02-26 Last updated: 2019-04-12
    2. Probabilistic Hough Voting for Attitude Estimation from Aerial Fisheye Images
    Open this publication in new window or tab >>Probabilistic Hough Voting for Attitude Estimation from Aerial Fisheye Images
    2013 (English)In: Image Analysis: 18th Scandinavian Conference, SCIA 2013, Espoo, Finland, June 17-20, 2013. Proceedings / [ed] Joni-Kristian Kämäräinen and Markus Koskela, Springer Berlin/Heidelberg, 2013, p. 478-488Conference paper, Published paper (Refereed)
    Abstract [en]

    For navigation of unmanned aerial vehicles (UAVs), attitude estimation is essential. We present a method for attitude estimation (pitch and roll angle) from aerial fisheye images through horizon detection. The method is based on edge detection and a probabilistic Hough voting scheme.  In a flight scenario, there is often some prior knowledge of the vehicle altitude and attitude. We exploit this prior to make the attitude estimation more robust by letting the edge pixel votes be weighted based on the probability distributions for the altitude and pitch and roll angles. The method does not require any sky/ground segmentation as most horizon detection methods do. Our method has been evaluated on aerial fisheye images from the internet. The horizon is robustly detected in all tested images. The deviation in the attitude estimate between our automated horizon detection and a manual detection is less than 1 degree.

    Place, publisher, year, edition, pages
    Springer Berlin/Heidelberg, 2013
    Series
    Lecture Notes in Computer Science, ISSN 0302-9743, E-ISSN 1611-3349 ; 7944
    National Category
    Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:liu:diva-98066 (URN)10.1007/978-3-642-38886-6_45 (DOI)000342988500045 ()978-3-642-38885-9 (ISBN)978-3-642-38886-6 (ISBN)
    Conference
    18th Scandinavian Conferences on Image Analysis (SCIA 2013), 17-20 June 2013, Espoo, Finland.
    Projects
    CIMSMAP
    Available from: 2013-09-27 Created: 2013-09-27 Last updated: 2019-04-12Bibliographically approved
    3. Highly Accurate Attitude Estimation via Horizon Detection
    Open this publication in new window or tab >>Highly Accurate Attitude Estimation via Horizon Detection
    2016 (English)In: Journal of Field Robotics, ISSN 1556-4959, E-ISSN 1556-4967, Vol. 33, no 7, p. 967-993Article in journal (Refereed) Published
    Abstract [en]

    Attitude (pitch and roll angle) estimation from visual information is necessary for GPS-free navigation of airborne vehicles. We propose a highly accurate method to estimate the attitude by horizon detection in fisheye images. A Canny edge detector and a probabilistic Hough voting scheme are used to compute an approximate attitude and the corresponding horizon line in the image. Horizon edge pixels are extracted in a band close to the approximate horizon line. The attitude estimates are refined through registration of the extracted edge pixels with the geometrical horizon from a digital elevation map (DEM), in our case the SRTM3 database, extracted at a given approximate position. The proposed method has been evaluated using 1629 images from a flight trial with flight altitudes up to 600 m in an area with ground elevations ranging from sea level up to 500 m. Compared with the ground truth from a filtered inertial measurement unit (IMU)/GPS solution, the standard deviation for the pitch and roll angle errors obtained with 30 Mpixel images are 0.04° and 0.05°, respectively, with mean errors smaller than 0.02°. To achieve the high-accuracy attitude estimates, the ray refraction in the earth's atmosphere has been taken into account. The attitude errors obtained on real images are less or equal to those achieved on synthetic images for previous methods with DEM refinement, and the errors are about one order of magnitude smaller than for any previous vision-based method without DEM refinement.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2016
    National Category
    Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:liu:diva-108212 (URN)10.1002/rob.21639 (DOI)000387925400005 ()
    Note

    At the date of the thesis presentation was this publication a manuscript.

    Funding agencies: Swedish Governmental Agency for Innovation Systems, VINNOVA [NFFP5 2013-05243]; Swedish Foundation for Strategic Research [RIT10-0047]; Swedish Research Council within the Linnaeus environment CADICS; Knut and Alice Wallenberg Foundation

    Available from: 2014-06-26 Created: 2014-06-26 Last updated: 2019-04-12Bibliographically approved
    4. Improved Learning in Convolutional Neural Networks with Shifted Exponential Linear Units (ShELUs)
    Open this publication in new window or tab >>Improved Learning in Convolutional Neural Networks with Shifted Exponential Linear Units (ShELUs)
    2018 (English)In: 2018 24th International Conference on Pattern Recognition (ICPR), IEEE, 2018, p. 517-522Conference paper, Published paper (Refereed)
    Abstract [en]

    The Exponential Linear Unit (ELU) has been proven to speed up learning and improve the classification performance over activation functions such as ReLU and Leaky ReLU for convolutional neural networks. The reasons behind the improved behavior are that ELU reduces the bias shift, it saturates for large negative inputs and it is continuously differentiable. However, it remains open whether ELU has the optimal shape and we address the quest for a superior activation function.We use a new formulation to tune a piecewise linear activation function during training, to investigate the above question, and learn the shape of the locally optimal activation function. With this tuned activation function, the classification performance is improved and the resulting, learned activation function shows to be ELU-shaped irrespective if it is initialized as a RELU, LReLU or ELU. Interestingly, the learned activation function does not exactly pass through the origin indicating that a shifted ELU-shaped activation function is preferable. This observation leads us to introduce the Shifted Exponential Linear Unit (ShELU) as a new activation function.Experiments on Cifar-100 show that the classification performance is further improved when using the ShELU activation function in comparison with ELU. The improvement is achieved when learning an individual bias shift for each neuron.

    Place, publisher, year, edition, pages
    IEEE, 2018
    Series
    International Conference on Pattern Recognition
    Keywords
    CNN, activation function
    National Category
    Other Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:liu:diva-151606 (URN)10.1109/ICPR.2018.8545104 (DOI)000455146800087 ()978-1-5386-3787-6 (ISBN)
    Conference
    24th International Conference on Pattern Recognition, ICPR 2018, Beijing, China, 20-24 Aug. 2018
    Funder
    Wallenberg Foundations
    Note

    Funding agencies:  Wallenberg AI, Autonomous Systems and Software Program (WASP) - Knut and Alice Wallenberg Foundation; Swedish Research Council [2014-6227]

    Available from: 2018-09-27 Created: 2018-09-27 Last updated: 2019-04-12
  • Public defence: 2019-05-03 10:00 Originalet, Qulturum, Hus B4, Jönköping
    Westerlind, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Geriatric Aspects of Frail Nursing Home Residents: A Swedish cohort study2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: The number and proportion of older people are increasing in Sweden as well as throughout the western world. Older people with increasing assistance needs that can no longer be met in their own home need institutional long-term care in nursing homes. A successive reduction of nursing home beds in combination with a future demographic development with a rapidly increasing number of older people will lead to higher demands on future medical care in nursing homes. Consequently, increased knowledge about the medical needs of nursing home residents is of great value.

    Objectives: This thesis explores some important geriatric aspects of frail nursing home residents. The specific aims was to characterise the population of nursing home residents, to explore the prevalence of anaemia, paying particular attention to risk factors and mortality, to investigate associations between falls and use of possible fall risk drug classes and to estimate the prevalence of diagnostic failure of cognitive impairment and to investigate whether diagnostic failure was associated with impaired medical care.

    Methods: All data originate from SHADES (the Study of Health and Drugs in Elderly nursing home residents in Sweden), a prospective cohort study that included nursing home residents at 12 nursing homes situated in three municipalities in southern Sweden between 2008 and 2011. The subjects were followed every six months with data collection from medical records concerning medications, diagnoses, hospital referrals and mortality, examinations including blood sample analyses, assessments with validated rating scales for cognitive evaluation, depression, risk of pressure ulcers, malnutrition or falls, and the need for care was rated through a questionnaire.

    Results: SHADES included a total of 428 subjects with a mean age of 85 years, of whom 71% were women. They demonstrated comorbidity with a mean of three registered medical diagnoses, and polypharmacy with a mean of seven regularly used drugs. More than half of the sample (60%) were at risk of malnutrition and one third were at risk of developing pressure ulcers. A set of single items from the performed risk assessments was found to be important in understanding frailty and need for care. One third of the women and half of the men had anaemia. For the men, anaemia was associated with significantly higher mortality. Haemoglobin decline was also associated with higher mortality. Almost everyone (93%) had an increased fall risk and 62% had fallen during the last year. There was an association between falls during the last year and regular use of non-benzodiazepine hypnotics. In the older age group there was also an association between these drugs and serious falls the next 6 months. Dementia was previously diagnosed in 42%. However, among subjects without a dementia diagnosis, 72% were cognitively impaired (Mini Mental State Examination <24). These subjects were significantly older, did not get anti-dementia treatment and had higher levels of brain natriuretic peptide compared to the diagnosed dementia group, possibly indicating heart failure. Their risks of malnutrition and pressure ulcers were similar to the dementia group.

    Conclusions: Nursing home residents are generally frail. Anaemia is associated with higher mortality among men. The fall risk is generally high and use of non-benzodiazepine hypnotics is associated with a higher occurrence of falls. Cognitive impairment is undiagnosed in half of the cases and may indicate underlying heart failure. Consequently, regular medical follow-ups in this population are proposed to include blood count, drug review, and cognitive evaluation. In the case of cognitive impairment, exclusion of underlying disease such as heart failure should be considered.

    List of papers
    1. How to assess frailty and the need for care? Report from the Study of Health and Drugs in the Elderly (SHADES) in community dwellings in Sweden
    Open this publication in new window or tab >>How to assess frailty and the need for care? Report from the Study of Health and Drugs in the Elderly (SHADES) in community dwellings in Sweden
    Show others...
    2011 (English)In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 53, no 1, p. 40-45Article in journal (Refereed) Published
    Abstract [en]

    Abstract

    Knowledge about the need for care of elderly individuals in community dwellings and the factors affecting their needs and support is limited. The aim of this study was to characterize the frailty of a population of elderly individuals living in community dwellings in Sweden in relation to co-morbidity, use of drugs, and risk of severe conditions such as malnutrition, pressure ulcers, and falls. In 2008, 315 elderly individuals living in community dwellings were interviewed and examined as part of the SHADES-study. The elderly demonstrated co-morbidity (a mean of three diseases) and polypharmacy (an average of seven drugs). More than half the sample was at risk for malnutrition, one third was at risk for developing pressure ulcers, and nearly all (93%) had an increased risk of falling and a great majority had cognitive problems. Age, pulse pressure, body mass index, and specific items from the modified Norton scale (MNS), the Downton fall risk index (DFRI), and the mini nutritional assessment (MNA-SF) were related to different outcomes, defining the need for care and frailty. Based on the results of this study, we suggest a single set of items useful for understanding the need for care and to improve individual based care in community dwellings.

     

    Place, publisher, year, edition, pages
    Elsevier, 2011
    Keywords
    Frailty; Community dwellings; Risk-assessments; Cognitive function
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-66914 (URN)10.1016/j.archger.2010.06.011 (DOI)
    Available from: 2011-03-21 Created: 2011-03-21 Last updated: 2019-03-21Bibliographically approved
    2. Prevalence and predictive importance of anemia in Swedish nursing home residents - a longitudinal study
    Open this publication in new window or tab >>Prevalence and predictive importance of anemia in Swedish nursing home residents - a longitudinal study
    2016 (English)In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 16, article id 206Article in journal (Refereed) Published
    Abstract [en]

    Background: Anemia is common in elderly people and especially in nursing home residents. Few studies have been performed on the consequences of anemia in a nursing home population. This study explored the prevalence of anemia in nursing homes in Sweden, including risk factors and mortality associated with anemia or hemoglobin (Hb) decline. Methods: Three hundred ninety patients from 12 nursing homes were included during 2008-2011. Information about medication, blood samples, questionnaire responses and information about physical and social activities was recorded. The baseline characteristics of the patients were compared for subjects with and without anemia. Vital status was ascertained during the following 7 years from baseline to compare the survival. Hb levels amp;lt;120 g/L in women and amp;lt;130 g/L in men were used to define anemia. For 220 of the subjects Hb change during one year was registered and the quartiles in Hb change were compared in terms of baseline characteristics and mortality. Results: The prevalence of anemia at baseline was 52% among men and 32% among women. The men with anemia had a two-year mortality significantly higher (61%) than the men without anemia (29%, p = 0.001) but there was no statistical difference in two- year survival in women. In anemic men there was a higher mortality (Hazard Ratio = 1.58) during a total follow-up period of up to 7 years after adjustment for age, increased B-type natriuretic peptide (BNP) and decreased estimated Glomerular Filtration Rate (eGFR). Among men, but not women, we found baseline correlations between anemia and elevated BNP (amp;gt;100 ng/L) and severely reduced eGFR (amp;lt;30 ml/min). When the lowest quartile of Hb change (decline amp;gt;9 g/L) was compared with the highest (improvement amp;gt;6 g/L) the mortality was higher in the lowest quartile (p = 0.03). Conclusions: Anemia is common in nursing home residents in Sweden, especially among men for whom it is related to higher mortality. A rapid Hb drop is associated with higher mortality. Regardless of earlier Hb values, monitoring Hb regularly in a nursing home population seems important for catching rapid Hb decline correlated with higher mortality.

    Place, publisher, year, edition, pages
    BIOMED CENTRAL LTD, 2016
    Keywords
    Anemia; Mortality; Elderly; Nursing homes; Longitudinal study
    National Category
    Geriatrics
    Identifiers
    urn:nbn:se:liu:diva-133780 (URN)10.1186/s12877-016-0375-2 (DOI)000389385600001 ()27912734 (PubMedID)
    Note

    Funding Agencies|Medical Research Council of Southeast Sweden (FORSS); Futurum - academy of health and care, Region Jonkoping county; Swedish Society of Medicine; Fromma Foundation; ALF funding from Region Skane

    Available from: 2017-01-09 Created: 2017-01-09 Last updated: 2019-03-21
    3. Use of non-benzodiazepine hypnotics is associated with falls in nursing home residents: a longitudinal cohort study
    Open this publication in new window or tab >>Use of non-benzodiazepine hypnotics is associated with falls in nursing home residents: a longitudinal cohort study
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    2018 (English)In: Aging Clinical and Experimental Research, ISSN 1594-0667, E-ISSN 1720-8319, p. 1-9Article in journal (Refereed) Published
    Abstract [en]

    Background

    Falls and related injuries are common among older people, and several drug classes are considered to increase fall risk.

    Aims

    This study aimed to investigate the association between the use of certain drug classes and falls in older nursing home residents in Sweden, and relate these to different age groups.

    Methods

    Information on falls that occurred in the previous year and regular use of possible fall risk drugs including non-benzodiazepine hypnotics (zopiclone and zolpidem) was collected from 331 nursing home residents during 2008–2011. Over the following 6 months, the occurrence of serious falls, requiring a physician visit or hospital care, was registered. Association between serious falls and drug use was compared between an older (≥ 85 years) and a younger group.

    Results

    An increased fall risk (Downton Fall Risk Index ≥ 3) was found in 93% of the study subjects (aged 65–101 years). Baseline data indicated an association between falls that occurred in the previous year and regular use of non-benzodiazepine hypnotics (p = 0.005), but not with the other studied drug classes. During the following 6 months, an association between use of non-benzodiazepine hypnotics and serious falls in the older group (p = 0.017, odds ratio 4.311) was found. No association was found between the other studied drug classes and serious falls.

    Discussion

    These results indicate an association between falls and the use of non-benzodiazepine hypnotics, compounds that previously have been considered generally well-tolerated in older people.

    Conclusions

    Caution is advocated when using non-benzodiazepine hypnotics regularly in older people living in nursing homes.

    Place, publisher, year, edition, pages
    Springer, 2018
    Keywords
    Accidental falls, Frail elderly, Nursing homes, Hypnotics and sedatives, Adverse effects, Longitudinal study
    National Category
    Rheumatology and Autoimmunity Geriatrics Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:liu:diva-156240 (URN)10.1007/s40520-018-1056-0 (DOI)30341643 (PubMedID)2-s2.0-85055751099 (Scopus ID)
    Available from: 2019-04-09 Created: 2019-04-09 Last updated: 2019-04-16Bibliographically approved
  • Public defence: 2019-05-08 09:15 ACAS, Linköping
    Matschewsky, Johannes
    Linköping University, Department of Management and Engineering, Environmental Technology and Management. Linköping University, Faculty of Science & Engineering.
    Effective and efficient design and provision of product-service systems: challenges, opportunities, and solutions2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The world manufacturing companies operate in is changing. In the past, these companies relied on the design and sale of products. Today, this linear model of business is becoming increasingly insufficient. As customers are more and more focused on their core business, buying and operating machinery and other goods becomes unattractive to them. In response to this, manufacturing companies are expanding their value capture into additional stages of the product lifecycle by providing integrated offerings of products and services — Product-Service Systems (PSSs).

    Designing and providing PSSs is fundamentally different from traditional product sales. Expanding to become a PSS provider is, therefore, challenging for companies with a history of designing and selling products. Departing from this, it is the aim of this thesis to support manufacturing companies in their expansion to effective and efficient design and provision of PSSs. The research reported has both descriptive and prescriptive properties, reflecting the goals of understanding the status quo in manufacturing companies’ practice and providing support based on this.

    To establish a point of departure, the current design and provision of two manufacturing companies expanding their business towards PSSs was investigated. From this, an in-depth understanding of the status quo and a number of challenges emerged.

    Based on this, the research had the goal to contribute to identifying and developing solutions to these challenges, with an initial focus on methods supporting PSS design and provision. However, although methods fitting to the challenges identified exist, they appear to receive limited uptake in manufacturing companies’ practice. In order to improve their practical utility, a structured method is proposed to assist users in both academia and practice in developing methods in a requirements-oriented fashion. The utility of methods in improving the efficiency and effectiveness of PSS design and provision is thereby to be enhanced.

    A particular challenge for manufacturing companies expanding to become PSS providers is the change in how value is captured: Resulting from the extensive involvement throughout the lifecycle, a need for a broader, multidimensional understanding of value capture was identified. However, the manufacturing companies investigated have been found to experience challenges in grasping this change, with a focus on a product sales-centric understanding of value capture remaining prevalent. To support companies towards reaping the benefits of the expansion to PSS design and provision, methods to explore how value is currently created and captured in the use phase and how to enhance the future value capture based on that information in the design phase have been developed and applied. As a result, broadly relevant value dimensions were attained, aiming to facilitate a lifecycle-focused, effective, and efficient design and provision of PSSs.

    Eventually, to broaden the understanding of effective and efficient design and provision of PSSs in practice today, the potential contributions of real-world PSSs to a circular economy were investigated based on an existing framework. The result was ambiguous, indicating both advancements compared to traditional sales and substantial room for improvement, particularly with a focus on the absolute decoupling of economic activity and resource use.

    Based on the synthesis of the research results, manufacturing companies are supported in their expansion to effective and efficient design and provision of PSSs — and towards a promising future.

    List of papers
    1. PSS without PSS design: possible causes, effects and solutions
    Open this publication in new window or tab >>PSS without PSS design: possible causes, effects and solutions
    2016 (English)In: Sustainability Through Innovation in Product Life Cycle Design: Part III / [ed] Mitsutaka Matsumoto, Keijiro Masui, Shinichi Fukushige and Shinsuke Kondoh, Singapore: Springer, 2016, 1, p. 233-248Chapter in book (Refereed)
    Abstract [en]

    Product-Service Systems (PSS) are seen as a cornerstone of a future circular economy. However, in order to achieve the desired environmental benefits, the industrial implementation of PSS design is key. This chapter discusses the apparent lack of an adaptation of design processes to PSS or adoption of PSS design methods within companies, which are nevertheless successfully offering PSS. Based on experiences at two companies and under close regard of the relevant literature, possible causes of this lack of method adaptation/adoption are discussed, and the effects this may have are deliberated. Lastly, potential solutions to this issue and ways forward are introduced and reflected upon focusing on the companies.

    Place, publisher, year, edition, pages
    Singapore: Springer, 2016 Edition: 1
    Series
    EcoProduction, ISSN 2193-4614 ; 2016
    Keywords
    Method Adoption; Process Adaptation; EcoDesign; Integrated Product Service Offerings;
    National Category
    Environmental Management Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-130909 (URN)10.1007/978-981-10-0471-1_16 (DOI)9789811004698 (ISBN)9789811004711 (ISBN)
    Available from: 2016-08-30 Created: 2016-08-30 Last updated: 2019-04-10Bibliographically approved
    2. Designing and providing integrated product-service systems: challenges, opportunities and solutions resulting from prescriptive approaches in two industrial companies
    Open this publication in new window or tab >>Designing and providing integrated product-service systems: challenges, opportunities and solutions resulting from prescriptive approaches in two industrial companies
    2018 (English)In: International Journal of Production Research, ISSN 0020-7543, E-ISSN 1366-588X, Vol. 56, no 6, p. 2150-2168Article in journal (Refereed) Published
    Abstract [en]

    Due to customer pressure and growing competition, industrial companies are increasingly moving towards providing integrated offerings of products and services (PSS). Despite this trend, literature providing a deep understanding of the challenges associated with this transition is limited, while publications discussing approaches that focus on overcoming these challenges are particularly lacking. This article is based on a multi-case study of two Swedish industrial companies undergoing the transition to designing and providing PSS. It reports on the challenges identified at the case companies as well as opportunities arising from and solutions to these challenges. Subsequent to initial research on the challenges, prescriptive approaches such as a life cycle costing method and a PSS design method were applied in the case companies over an extended time frame. On the one hand, these prescriptive approaches provided both a deeper understanding of the challenges, which include a persistent product centred mindset, a lack of adjustment to changed incentive structures and the separation of product and service design. On the other hand, they also led to effective solutions such as focusing on customer value and introducing a PSS transition facilitator for the design team. These solutions were adapted to the situations in the respective companies and they partly went beyond the prescriptive measures first introduced. Therefore, the article shows the applicability of prescriptive approaches and methods to detect, understand and alleviate the challenges of PSS design and provision. Further, the article provides broadly applicable learning for industrial companies undergoing this process.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2018
    Keywords
    PSS, servitisation, design method, implementation, product–service integration
    National Category
    Other Mechanical Engineering
    Identifiers
    urn:nbn:se:liu:diva-137904 (URN)10.1080/00207543.2017.1332792 (DOI)000433967100005 ()2-s2.0-85020232003 (Scopus ID)
    Funder
    Mistra - The Swedish Foundation for Strategic Environmental Research, 2014/16Vinnova, Strategic Innovation
    Note

    Funding agencies: Mistra REES (Resource Efficient and Effective Solutions) programme - Mistra (The Swedish Foundation for Strategic Environmental Research) [2014/16]; programme for Strategic Innovation - Vinnova (Swedish Governmental Agency for Innovation Systems)

    Available from: 2017-06-16 Created: 2017-06-16 Last updated: 2019-04-10Bibliographically approved
    3. Capturing and enhancing provider value in product-service systems throughout the lifecycle: A systematic approach
    Open this publication in new window or tab >>Capturing and enhancing provider value in product-service systems throughout the lifecycle: A systematic approach
    2018 (English)In: CIRP - Journal of Manufacturing Science and Technology, ISSN 1755-5817, E-ISSN 1878-0016Article in journal (Refereed) Published
    Abstract [en]

    Although the transition from product seller to product-service system (PSS) provider implies fundamental changes in both value creation for customers and value capture by the provider, prior research has largely focused on the investigation and enhancement of customer value through PSSs. In contrast, a discussion of the changes in how providers attain value and support to enhance this in industrial practice is lacking at this time. This article presents a systematic, empirically-based approach to analyze and enhance PSS providers’ value capture throughout the lifecycle. This is achieved by two methods provider value analysis (PVA) facilitates a structured assessment of the value capture during the provision of PSSs in the use phase of the lifecycle, while provider value evaluation (ProVa) operationalizes the results of this analysis in the design phase to facilitate an improved value capture in the coming iteration. As the approach was developed in close collaboration with a large-scale PSS provider, the article further reports the results of its application in a case study spanning two years. As a result of using PVA, value dimensions of broad relevance for PSS providers are presented, supported by findings of applying the method at an additional PSS provider. Through the approach presented and case study results attained, the article points out how the design and management of a PSS, focusing on the provider’s value and available benefits throughout the lifecycle, can be enhanced in industry, while extending the academic body of knowledge on the value capture of PSS providers and its implications for PSS design and provision.

    Place, publisher, year, edition, pages
    Elsevier, 2018
    Keywords
    Servitization; PSS design; PSS evaluation; PSS value; Provider value; PSS implementation; PSS management
    National Category
    Environmental Management
    Identifiers
    urn:nbn:se:liu:diva-152879 (URN)10.1016/j.cirpj.2018.08.006 (DOI)2-s2.0-85053313953 (Scopus ID)
    Funder
    Mistra - The Swedish Foundation for Strategic Environmental Research, REES
    Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2019-04-10Bibliographically approved
  • Public defence: 2019-05-09 09:15 Planck, Fysikhuset, Linköping
    Sundman, Ann-Sofie
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Dog behaviour: Intricate picture of genetics, epigenetics, and human-dog relations2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Dogs, Canis familiaris, share the lives of humans all over the world. That dogs, and the behavior of dogs, are of interest to many is therefore no surprise. In this thesis, the main aim has been to identify factors that affect dogs’ behaviours.

    The dog, Canis familiaris, is our first domesticated animal. Since domestication, various types of dogs have developed through adaptation to an environment shared with humans and through our selective breeding, resulting in a unique variation in morphology and behaviour. Although there is an individual variation in the behaviour of dogs, there is also a difference between breeds. Moreover, selection during the last decades has split some breeds into divergent types. Labrador and golden retrievers are divided into a common type, for show and companionship, and a field type, for hunting. By comparing the breed types, we can study the effects of recent selection. In Paper I, we investigate differences in general behavioural traits between Labrador and golden retriever and between common and field type within the two breeds by using results from the standardized behaviour test Dog Mentality Assessment. There were differences between breeds and types for all behavioural traits. However, there was also an interaction between breed and type. Thus, a common/field-type Labrador does not behave like a common/field-type golden retriever. Even though they have been selected for similar traits, the selection has affected the general behavioural traits differently in the two breeds.

    In paper II, we were interested in dogs’ human-directed social skills. Dogs have a high social competence when it comes to humans. Two experiments commonly used to study these skills are the problem-solving test, where dogs’ human-directed behaviours when faced with a problem are measured, and the pointing test, where dogs are tested on how well they understand human gestures. We compared the social skills of German shepherds and Labrador retrievers, and of common- and field-type Labradors. Labradors were more successful in the pointing test and German shepherds stayed closer to their owners during the problem solving. Among Labrador types, the field type had more human eye contact than the common type. Importantly, when comparing the two experiments, we found no positive correlations between the problem-solving test and the pointing test, suggesting that the two tests measure different aspects of human-directed social behaviour in dogs.

    A previous study has identified two suggestive genetic regions for human-directed social behaviours during the problem-solving test in beagles. In paper III, we show that these SNPs are also associated to social behaviours in Labrador and golden retrievers. Moreover, the Labrador breed types differed significantly in allele frequencies. This indicates that the two SNPs have been affected by recent selection and may have a part in the differences in sociability between common and field type.

    The behaviour of dogs cannot simply be explained by genetics, there is also an environmental component. In paper IV, we study which factors that affect long-term stress in dogs. Long-term cortisol can be measured by hair samples. We found a clear synchronization in hair cortisol concentrations between dogs and their owners. Neither dogs’ activity levels nor their behavioural traits affected the cortisol, however, the personality of the owners did. Therefore, we suggest that dogs mirror the stress level of their owners.

    The mediator between genes and the environment is epigenetics, and one epigenetic factor is DNA methylation. In paper V, we compared methylation patterns of wolves and dogs as well as dog breeds. Between both wolves and dogs and among dogs there were substantial differences in methylated DNA regions, suggesting that DNA methylation is likely to contribute to the vast variation among canines. We hypothesize that epigenetic factors have been important during domestication and in breed formation.

    In this thesis, I cover several aspects on how dogs’ behaviours can be affected, and paint an intricate picture on how genetics, epigenetics, and human-dog relations forms dog behaviour.

    List of papers
    1. Similar recent selection criteria associated with different behavioural effects in two dog breeds
    Open this publication in new window or tab >>Similar recent selection criteria associated with different behavioural effects in two dog breeds
    2016 (English)In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 15, no 8, p. 750-756Article in journal (Refereed) Published
    Abstract [en]

    Selection during the last decades has split some established dog breeds into morphologically and behaviourally divergent types. These breed splits are interesting models for behaviour genetics since selection has often been for few and well-defined behavioural traits. The aim of this study was to explore behavioural differences between selection lines in golden and Labrador retriever, in both of which a split between a common type (pet and conformation) and a field type (hunting) has occurred. We hypothesized that the behavioural profiles of the types would be similar in both breeds. Pedigree data and results from a standardized behavioural test from 902 goldens (698 common and 204 field) and 1672 Labradors (1023 and 649) were analysed. Principal component analysis revealed six behavioural components: curiosity, play interest, chase proneness, social curiosity, social greeting and threat display. Breed and type affected all components, but interestingly there was an interaction between breed and type for most components. For example, in Labradors the common type had higher curiosity than the field type (F1,1668 = 18.359; P < 0.001), while the opposite was found in goldens (F1,897 = 65.201; P < 0.001). Heritability estimates showed considerable genetic contributions to the behavioural variations in both breeds, but different heritabilities between the types within breeds was also found, suggesting different selection pressures. In conclusion, in spite of similar genetic origin and similar recent selection criteria, types behave differently in the breeds. This suggests that the genetic architecture related to behaviour differs between the breeds.

    Place, publisher, year, edition, pages
    Wiley-Blackwell Publishing Inc., 2016
    Keywords
    Behavioural genetics, behavioural test, dog behaviour, dogs, golden retriever, heritability, Labrador retriever, selection
    National Category
    Evolutionary Biology Zoology Behavioral Sciences Biology Genetics
    Identifiers
    urn:nbn:se:liu:diva-132746 (URN)10.1111/gbb.12317 (DOI)000393079000007 ()27520587 (PubMedID)
    Note

    Funding agencies: research council, Formas; Advanced Research Grant from the European Research Council (ERC) [322206]

    Available from: 2016-11-22 Created: 2016-11-22 Last updated: 2019-04-17Bibliographically approved
    2. Understanding of human referential gestures is not correlated to human-directed social behaviour in Labrador retrievers and German shepherd dogs
    Open this publication in new window or tab >>Understanding of human referential gestures is not correlated to human-directed social behaviour in Labrador retrievers and German shepherd dogs
    Show others...
    2018 (English)In: Applied Animal Behaviour Science, ISSN 0168-1591, E-ISSN 1872-9045, Vol. 201, p. 46-53Article in journal (Refereed) Published
    Abstract [en]

    Dogs are known to excel in interspecific communication with humans and both communicate with humans and follow human communicative cues. Two tests commonly used to test these skills are, firstly, the problem-solving paradigm, and, secondly, following human referential signals, for example pointing. The aim of the present study was to investigate whether dogs that seek more human contact in an unsolvable problem-solving paradigm also better understand human communicative cues in a pointing test. We also assessed between- and within-breed variation in both tests. 167 dogs were tested and were of the breeds German shepherd dog and Labrador retriever. The Labradors were separated into the two selection lines: common type (bred for show and pet) and field type (bred for hunting). A principal component analysis of behaviours during the problem solving revealed four components: Passivity, Experimenter Contact, Owner Contact and Eye Contact. We analysed the effect of these components on success rate in the pointing test and we found no effect for three of them, while a negative correlation was found for Owner Contact (F(1,147) = 6.892; P = 0.010). This was only present in common-typed Labradors. We conclude that the ability to follow a pointing cue does not predict the propensity for human-directed social behaviour in a problem-solving situation and suggest that the two tests measure different aspects of human-directed social behaviour in dogs.

    Place, publisher, year, edition, pages
    Elsevier, 2018
    Keywords
    Human-dog communication, Human-directed social behaviour, Pointing test, Problem-solving test, German shepherd dogs. Labrador retrievers
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:liu:diva-145542 (URN)10.1016/j.applanim.2017.12.017 (DOI)000430774800007 ()2-s2.0-85039704233 (Scopus ID)
    Note

    Funding agencies: European Research Council (ERC) [322206]

    Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2019-04-17Bibliographically approved
    3. Sociality genes are associated with human-directed social behaviour in golden and Labrador retriever dogs
    Open this publication in new window or tab >>Sociality genes are associated with human-directed social behaviour in golden and Labrador retriever dogs
    Show others...
    2018 (English)In: PeerJ, ISSN 2167-8359, E-ISSN 2167-8359, Vol. 6, article id e5889Article in journal (Refereed) Published
    Abstract [en]

    Background: Dogs have human-directed social skills that allow them to communicate and cooperate with humans. We have previously identified two loci on chromosome 26 associated with human contact-seeking behaviors during an unsolvable problem task in laboratory beagles (Persson et A, 2016). The aim of the present study was to verify the single nucleotide polymorphisms (SNPs) in additional dog breeds. We also studied how the allele frequencies have changed during domestication and recent selection. Methods: Dogs of two breeds, 61 golden retrievers and 100 Labrador retrievers, were phenotyped and genotyped, and 19 wolves were genotyped. The Labrador retrievers were divided into common and field type by pedigree data to make it possible to study the effects of recent selection. All dogs were tested in an unsolvable problem task where human-directed social behaviors were scored. DNA from dogs (buccal swabs) and wolves (blood or brain tissue) was analyzed for genotype on two of the previously identified SNP markers, BICF2G630798942 (SNP1) and BICF2S23712114 (SNP2), by pyrosequencing. Results: There was genetic variation for SNP1 in both dog breeds whereas the wolves were fixed for this polymorphism, and for SNP2 there was variation in both dogs and wolves. For both SNPs, Labrador retriever types differed significantly in allele frequencies. We found associations between SNPs and human-directed social behavior in both dog breeds. In golden retrievers, SNP I was associated with physical contact variables, for example, with the duration of physical contact with the owner (F-2,F-56 = 4.389, p = 0.017). SNP2 was associated with several behavioral variables in both breeds, among others owner gazing frequency in both golden retrievers (F-2,F-55 = 6.330, p = 0.003) and Labradors (F-1,F-93 = 5.209, p = 0.025). Discussion: Our results verify the association between the previously identified SNPs and human-directed social behavior scored in an unsolvable problem task. Differences in allele frequencies suggest that these loci have been affected by selection. The results indicate that these genomic regions are involved in human-directed social behavior in not only beagles but in other dog breeds as well. We hypothesize that they may have been important during dog domestication.

    Place, publisher, year, edition, pages
    PEERJ INC, 2018
    Keywords
    Genetics; Dog genetics; Dog behavior; Human-dog communication; Human-directed social behavior; Golden retrievers; Labrador retrievers; Wolf; Domestication; Behavior genetics
    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:liu:diva-153536 (URN)10.7717/peerj.5889 (DOI)000452327000008 ()30416887 (PubMedID)
    Note

    Funding Agencies|European Research Council (ERC) [322206]

    Available from: 2018-12-20 Created: 2018-12-20 Last updated: 2019-04-17
  • Public defence: 2019-05-09 10:15 Nobel (BL32), B-huset, Linköping
    Ghosh, Arpan
    Linköping University, Department of Mathematics, Mathematics and Applied Mathematics. Linköping University, Faculty of Science & Engineering.
    Mathematical modelling of flow through thin curved pipes with application to hemodynamics2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The problem of mathematical modelling of incompressible flows with low velocities through narrow curvilinear pipes is addressed in this thesis. The main motivation for this modelling task is to eventually model the human circulatory system in a simple way that can facilitate the medical practitioners to efficiently diagnose any abnormality in the system. The thesis comprises of four articles.

    In the first article, a two-dimensional model describing the elastic behaviour of the wall of a thin, curved,  exible pipe is presented. The wall is assumed to have a laminate structure consisting of several anisotropic layers of varying thickness. The width of the channel is allowed to vary along the pipe. The two-dimensional model takes the interactions of the wall with any surrounding material and the  fluid  flow into account and is obtained through a dimension reduction procedure. Examples of canonical shapes of pipes and their walls are provided with explicit systems of differential equations at the end.

    In the second article, a one-dimensional model describing the blood flow through a moderately curved, elastic blood vessel is presented. The two-dimensional model presented in the first paper is used to model the vessel wall while linearized Navier-Stokes equations are used to model the  flow through the channel. Surrounding muscle tissues and presence of external forces other than gravity are taken into account. The model is again obtained via a dimension reduction procedure based on the assumption of thinness of the vessel relative to its length. Results of numerical simulations are presented to highlight the influence of different factors on the blood flow.

    The one-dimensional model described in the second paper is used to derive a simplified one-dimensional model of a false aneurysm which forms the subject of the third article. A false aneurysm is an accumulation of blood outside a blood vessel but confined by the surrounding muscle tissue. Numerical simulations are presented which demonstrate different characteristics associated with a false aneurysm.

    In the final article, a modified Reynolds equation, along with its derivation from Stokes equations through asymptotic methods, is presented. The equation governs the steady flow of a fluid with low Reynolds number through a narrow, curvilinear tube. The channel considered may have large curvature and torsion. Approximations of the velocity and the pressure of the fluid inside the channel are constructed. These approximations satisfy a modified Poiseuille equation. A justification for the approximations is provided along with a comparison with a simpler case.

    List of papers
    1. A TWO-DIMENSIONAL MODEL OF THE THIN LAMINAR WALL OF A CURVILINEAR FLEXIBLE PIPE
    Open this publication in new window or tab >>A TWO-DIMENSIONAL MODEL OF THE THIN LAMINAR WALL OF A CURVILINEAR FLEXIBLE PIPE
    2018 (English)In: Quarterly Journal of Mechanics and Applied Mathematics, ISSN 0033-5614, E-ISSN 1464-3855, Vol. 71, no 3, p. 349-367Article in journal (Refereed) Published
    Abstract [en]

    We present a two-dimensional model describing the elastic behaviour of the wall of a curved flexible pipe. The wall has a laminate structure consisting of several anisotropic layers of varying thickness and is assumed to be much smaller in thickness than the radius of the channel which itself is allowed to vary. Our two-dimensional model takes the interaction of the wall with any surrounding or supporting material and the fluid flow into account and is obtained via a dimension reduction procedure. The curvature and twist of the pipes axis as well as the anisotropy of the laminate wall present the main challenges in applying the dimension reduction procedure so plenty of examples of canonical shapes of pipes and their walls are supplied with explicit systems of differential equations at the end.

    Place, publisher, year, edition, pages
    OXFORD UNIV PRESS, 2018
    National Category
    Other Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:liu:diva-150869 (URN)10.1093/qjmam/hby009 (DOI)000441808700006 ()
    Note

    Funding Agencies|Russian Foundation of Basic Research [18-01-00325]

    Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2019-04-16
    2. A one dimensional model of blood flow through a curvilinear artery
    Open this publication in new window or tab >>A one dimensional model of blood flow through a curvilinear artery
    2018 (English)In: Applied Mathematical Modelling, ISSN 0307-904X, E-ISSN 1872-8480, Vol. 63, p. 633-643Article in journal (Refereed) Published
    Abstract [en]

    We present a one-dimensional model describing the blood flow through a moderately curved and elastic blood vessel. We use an existing two dimensional model of the vessel wall along with Navier-Stokes equations to model the flow through the channel while taking factors, namely, surrounding muscle tissue and presence of external forces other than gravity into account. Our model is obtained via a dimension reduction procedure based on the assumption of thinness of the vessel relative to its length. Results of numerical simulations are presented to highlight the influence of different factors on the blood flow. (C) 2018 Elsevier Inc. All rights reserved.

    Place, publisher, year, edition, pages
    ELSEVIER SCIENCE INC, 2018
    Keywords
    Blood flow; Curvilinear vessel; Asymptotic analysis; Dimension reduction; Numerical simulation
    National Category
    Fluid Mechanics and Acoustics
    Identifiers
    urn:nbn:se:liu:diva-151627 (URN)10.1016/j.apm.2018.07.019 (DOI)000444362800034 ()
    Note

    Funding Agencies|Russian Foundation of Basic Research [18-01-00325]

    Available from: 2018-10-09 Created: 2018-10-09 Last updated: 2019-04-16
  • Public defence: 2019-05-10 09:00 Hasselquistsalen, Växthuset, Linköping
    Zajdel, Joanna
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Interactions between the brain and the immune system in pain and inflammation2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Reciprocal interactions between the nervous and immune systems have gained a lot of attention in the last two decades, especially after demonstrating that cytokine immunotherapies can induce depression and after describing the inflammatory reflex. A lot of effort has been dedicated to understanding how the signals from the immune system reach the brain and vice versa, and on their role in health and disease. However, it is not well-known which of the brain circuits, receptors and signalling molecules give rise to behavioural and affective changes induced by inflammation, such as reduced food intake and induction of negative mood. Moreover, although it is well established that early life stress leads to an increased risk of developing inflammatory diseases in adulthood, the acute effects of stress on the inflammatory response in childhood are not well described. Using mouse models of systemic and local inflammation, I studied (1) how inflammatory pain elicits negative affect, (2) if CGRPα is necessary for parabrachial-amygdaloid pathway-mediated behaviours associated with pain and inflammation, and finally, (3) what are the effects of stress on the inflammatory process during early life. The results indicate that (1) the negative affect of inflammatory pain is triggered by inhibition of serotonergic neurons of the dorsal raphe nucleus, as a result of prostaglandin E2 binding to EP3 receptors; (2) CGRPα is dispensable for most pain- and inflammation-related protective behaviours; (3) acute stress potentiates the pro-inflammatory cytokine expression after an inflammatory challenge in mouse pups. The phenomena studied here can contribute to understanding how immune system activation induces changes in mood and behaviour common for inflammation and depression.

    List of papers
    1. Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain
    Open this publication in new window or tab >>Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain
    Show others...
    2017 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 127, no 4, p. 1370-1374Article in journal (Refereed) Published
    Abstract [en]

    Pain is fundamentally unpleasant and induces a negative affective state. The affective component of pain is mediated by circuits that are distinct from those mediating the sensory-discriminative component. Here, we have investigated the role of prostaglandins in the affective dimension of pain using a rodent pain assay based on conditioned place aversion to formalin injection, an inflammatory noxious stimulus. We found that place aversion induced by inflammatory pain depends on prostaglandin E-2 that is synthesized by cyclooxygenase 2 in neural cells. Further, mice lacking the prostaglandin E-2 receptor EP3 selectively on serotonergic cells or selectively in the area of the dorsal raphe nucleus failed to form an aversion to formalininduced pain, as did mice lacking the serotonin transporter. Chemogenetic manipulations revealed that EP3 receptor activation elicited conditioned place aversion to pain via inhibition of serotonergic neurons. In contrast to their role in inflammatory pain aversion, EP3 receptors on serotonergic cells were dispensable for acute nociceptive behaviors and for aversion induced by thermal pain or a kappa opioid receptor agonist. Collectively, our findings show that prostaglandin-mediated modulation of serotonergic transmission controls the affective component of inflammatory pain.

    Place, publisher, year, edition, pages
    AMER SOC CLINICAL INVESTIGATION INC, 2017
    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:liu:diva-136568 (URN)10.1172/JCI90678 (DOI)000398183300026 ()28287401 (PubMedID)
    Note

    Funding Agencies|European Research Council; Swedish Medical Research Council; Knut and Alice Wallenberg Foundation; Swedish Brain Foundation; County Council of Ostergotland; National Institute of Neurological Disorders and Stroke (NINDS)

    Available from: 2017-04-24 Created: 2017-04-24 Last updated: 2019-04-08
    2. Acute maternal separation potentiates the gene expression and corticosterone response induced by inflammation
    Open this publication in new window or tab >>Acute maternal separation potentiates the gene expression and corticosterone response induced by inflammation
    Show others...
    2019 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 77, p. 141-149Article in journal (Refereed) Published
    Abstract [en]

    Maternal care is crucial for infants and profoundly affects their responses to different kinds of stressors. Here, we examined how maternal separation affects inflammatory gene expression and the corticosterone response to an acute immune challenge induced by lipopolysaccharide (LPS; 40 µg/kg ip) in mouse pups, 8–9 days old. Maternal separation initially attenuated LPS-induced hypothalamic pro-inflammatory gene expression, but later, at 3 h after immune challenge, robustly augmented such gene expression and increased serum corticosterone levels. Providing the pups with a warm and soft object prevented the separation-induced augmented hypothalamic-pituitary-adrenal (HPA)-axis response. It also prevented the potentiated induction of some, but not all, inflammatory genes to a similar extent as did the dam. Our results show that maternal separation potentiates the inflammatory response and the resulting HPA-axis activation, which may have detrimental effects if separation is prolonged or repeated.

    Place, publisher, year, edition, pages
    Elsevier, 2019
    Keywords
    Lipopolysaccharide, Hypothalamus, Cytokines, Inflammation, Maternal separation, Corticosterone
    National Category
    Pharmacology and Toxicology Developmental Biology Medical Biotechnology Immunology
    Identifiers
    urn:nbn:se:liu:diva-154886 (URN)10.1016/j.bbi.2018.12.016 (DOI)30590109 (PubMedID)2-s2.0-85059128986 (Scopus ID)
    Available from: 2019-03-04 Created: 2019-03-04 Last updated: 2019-04-08Bibliographically approved
  • Public defence: 2019-05-10 10:15 ACAS, Linköping
    Lawrence, Akvile
    Linköping University, Department of Management and Engineering, Energy Systems. Linköping University, Faculty of Science & Engineering.
    Energy Management for Improving Energy Efficiency in the Pulp and Paper Industry: Success Factors for Strengthening Drivers and Overcoming Barriers2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Industrial energy efficiency improves the profit and competitive advantage of companies. The pulp and paper industry (PPI) being one of the five most energy-intensive industries uses 5.6% of global industrial energy, according to the International Energy Agency. It is one of the key sectors that is faced with the challenge of improving energy efficiency. The PPI is not less important in Sweden where it uses ~52% of the total industrial energy, employing >20000 people and where improvement of the energy end-use by 1% corresponds to estimated savings of ~218 MSEK annually. Energy management (EnM) is a means for improving energy efficiency (EE). However, despite research showing the possibility for annual improvement of the energy end-use by e.g. 5.5-19.4%, EnM is not always used to its full potential or often hardly implemented, resulting in an EE gap, i.e. the difference between the optimal and actual energy efficiency. Why then does this EE gap exist? What are the drivers and barriers for practicing EnM to its full potential and thus improving energy efficiency? What are the success factors for encouraging the drivers and overcoming the barriers? What practical recommendations can be made that could lead to the improvement of energy efficiency? After extracting information from historical and current information using tools from multivariate data analysis (MDA), this PhD dissertation presents new knowledge that intends to contribute to overcome the challenges of improving energy efficiency in the PPI. Specifically, international research primarily addressing EnM in the PPI showed that EnM in the PPI is perceived as EnM via technology, despite that EnM contains other aspects than EnM via technology, e.g. proactive EnM practices. This result indicates the presence of a knowledgegap on how to deploy EnM in the PPI. Studies of the PPI in Sweden showed different EnM practices among the individual types of mills, i.e. pulp mills, paper mills and integrated-pulp and paper mills. Integrated mills seemed to measure the energy-related performance more than pulp mills and paper mills. However, the results also suggested that the Swedish PPI worked continuously and regularly with EnM. Further, aside from the top ranked perceived drivers being economical and the barriers being organizational, knowledge related drivers and barriers were amongst the most important. High ranking of the knowledge related drivers and barriers together with the results that commonly only selected employees were trained in EnM indicated that communication between the trained employees and operations personnel and the absorptive capacity for energy issues could potentially be improved. Additionally, research showed that by using MDA, previously unstudied/unidentified connections were discovered such as that during the ten-year voluntary agreement policy program known as PFE (Program for improved energy efficiency in energy-intensive industry), companies less financially stable and less experienced with EnM tended to save electricity more than the more financially stable and more EnM experienced mills. Furthermore, results also demonstrate that the specific energy use, also known as specific energy consumption (SEC), that is commonly used as the energy key performance indicator for energy efficiency needs to be used with more clarity and caution for assuring validity of the benchmarking of energy efficiency. Altogether, the success factors for EnM for improving energy efficiency could be summarized in the versatile 4M memory tool - The “4M for energy efficiency”: mind, measure, monitor and manage. The “4M for energy efficiency” suggests that all the four “Ms” should be practiced simultaneously in order to maximize the achievement of goals of EnM in the PPI and as well as in other sectors.

    List of papers
    1. Drivers, Barriers, and Success Factors for Improving Energy Management in the Pulp and Paper Industry
    Open this publication in new window or tab >>Drivers, Barriers, and Success Factors for Improving Energy Management in the Pulp and Paper Industry
    2018 (English)In: Sustainability, ISSN 2071-1050, E-ISSN 2071-1050, Vol. 10, no 6, article id 1851Article, review/survey (Refereed) Published
    Abstract [en]

    Successful energy management is a way to achieve energy efficiency in the pulp and paper industry (PPI), which is important for assuring energy supply security, for increasing economic competitiveness, and for mitigating greenhouse gases. However, research shows that although energy use within PPI can be reduced by 5.5-19.4% per year, some of this by energy management practices, energy management is not always implemented. Why is this so? What are the barriers to, and drivers of implementation? How can the barriers be overcome? A systematic review of barriers and drivers in energy management in the PPI within peer-reviewed scientific articles suggests that the world-wide events that affect energy supply, volatility, and use seemingly also affect the number and frequency of research articles on energy management in the PPI. The perception of energy management in the PPI seems to be dominated by the understanding that it can mostly be achieved through technological improvements aiming to improve energy efficiency. The main driver of energy management was shown to be economic conditions: high and unstable energy prices, followed by drivers such as the need to remain internationally competitive, collaboration and energy management systems. Meanwhile, examples of the most important barriers are technical risks, lack of access to capital, lack of time and other priorities, and slim organization. The success factors for enhancing drivers and overcoming barriers were continuous energy accounting, energy-related collaboration, energy-efficiency programmes, and benchmarking. Altogether, success factors for energy management for improved energy efficiency could be summarized in the 4M frameworkthe 4M for energy efficiency: mind, measure, monitor, and managethat could be used as the energy management memory-tool that could lead to improved energy efficiency in other sectors as well.

    Place, publisher, year, edition, pages
    MDPI, 2018
    Keywords
    energy management; energy efficiency; pulp and paper industry; barriers; drivers; ISO 50001; success factors
    National Category
    Energy Systems
    Identifiers
    urn:nbn:se:liu:diva-151523 (URN)10.3390/su10061851 (DOI)000436570100163 ()
    Note

    Funding Agencies|Swedish Energy Agency [2015-002143]; Division of Energy Systems in the Department of Management and Engineering at Linkoping University

    Available from: 2018-09-24 Created: 2018-09-24 Last updated: 2019-04-12
    2. Effects of firm characteristics and energy management for improving energy efficiency in the pulp and paper industry
    Open this publication in new window or tab >>Effects of firm characteristics and energy management for improving energy efficiency in the pulp and paper industry
    2018 (English)In: Energy, ISSN 0360-5442, E-ISSN 1873-6785, Vol. 153, p. 825-835Article in journal (Refereed) Published
    Abstract [en]

    The Swedish pulp and paper industry (PPI) must increase energy efficiency to remain competitive on the global market, which has experienced entries from countries with cheaper energy and raw material supplies. Interactions among variables for energy use, production, energy management, electricity price and firm characteristics (FC), in different types of mills, i.e., pulp, paper and integrated mills, in Sweden from 2006 to 2015 indicate that correlations among the studied variables were different in different types of mills. This difference between types of mills seemed to originate partly from varying accessibility to production residue that could be used for energy. For all types of mills, variation of electricity prices did not correlate significantly with energy efficiency during the study period. The studied FC were firms age, number of employees, number of companies in company group, net sales and profit for the year. Energy efficiency was more affected by the variables characterizing energy and production compared to the variables representing FC. This study also suggested presence of possible discrepancies between FC that were perceived as barriers to energy management towards energy efficiency, according to previous studies, and what was shown by the data combining variables representing energy use, production and FC. (C) 2018 Elsevier Ltd. All rights reserved.

    Place, publisher, year, edition, pages
    PERGAMON-ELSEVIER SCIENCE LTD, 2018
    Keywords
    Energy efficiency; Specific energy; Pulp and paper industry; Firm characteristics; Energy intensive industry; Energy management
    National Category
    Energy Systems
    Identifiers
    urn:nbn:se:liu:diva-150880 (URN)10.1016/j.energy.2018.04.092 (DOI)000436651100074 ()
    Note

    Funding Agencies|Swedish Energy Agency

    Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2019-04-12
    3. Drivers, barriers and success factors for energy management in the Swedish pulp and paper industry
    Open this publication in new window or tab >>Drivers, barriers and success factors for energy management in the Swedish pulp and paper industry
    Show others...
    2019 (English)In: Journal of Cleaner Production, ISSN 0959-6526, E-ISSN 1879-1786, Vol. 223, p. 67-82Article in journal (Refereed) Published
    Abstract [en]

    Research has revealed the existence of an energy-efficiency gap – the difference between optimal and actual energy end-use, suggesting that energy efficiency can be improved. Energy management (EnM) is a means for improving industrial energy efficiency. However, due to various barriers, the full potential of EnM is not realised. Several studies have addressed drivers and barriers to energy efficiency but few to EnM. This study aims to identify EnM practices, the most important perceived drivers and barriers for EnM, and relations among them in the energy-intensive Swedish pulp and paper industry (PPI), which has the longest experience internationally of practising EnM systems, and has worked according to the standards since 2004. Our results show that, altogether, the PPI works regularly and continuously with EnM, with a clear division of responsibilities. The highest maturity for EnM practices was for energy policy, followed by organization, investments, and performance measurement. The study also shows that communication between middle management and operations personnel has potential for improvement. The most important categories of drivers were economic, whereas for barriers they were organizational. Nevertheless, knowledge-related barriers and drivers were amongst the most important, suggesting that the absorptive capacity for energy issues could be improved.

    Keywords
    Barriers, Drivers, Success factors, Energy management, Energy efficiency, Pulp and paper industry
    National Category
    Energy Systems
    Identifiers
    urn:nbn:se:liu:diva-156271 (URN)10.1016/j.jclepro.2019.03.143 (DOI)
    Available from: 2019-04-10 Created: 2019-04-10 Last updated: 2019-04-12
    4. Effects of monetary investment, payback time and firm characteristics on electricity saving in energy-intensive industry
    Open this publication in new window or tab >>Effects of monetary investment, payback time and firm characteristics on electricity saving in energy-intensive industry
    2019 (English)In: Applied Energy, ISSN 0306-2619, E-ISSN 1872-9118, Vol. 240, p. 499-512Article in journal (Refereed) Published
    Abstract [en]

    Our study looked at the extent to which firm characteristics such as total firm capital affect electricity saving in energy-intensive industry in Sweden from 2007 to 2015. Specifically, the most influential variables for systematic variation in electricity saving in the energy-intensive companies participating in Sweden’s voluntary programme for improving energy efficiency in energy-intensive industry (the PFE) were studied by analysing monetary investment, payback time and firm characteristics. Monetary investment and payback time influenced electricity savings during the PFE more than firm characteristics, with monetary investment being most influential. Nevertheless, the total systematic variation in firm characteristics may account for ∼16% of the systematic variation in electricity saving, where ∼74% (32 of 43) of the studied firm characteristics seemed to merit further investigation and where ∼49% (21 of 43) of firm characteristics appeared most influential. The most influential firm characteristics were total firm capital, stock turnover ratio, machinery, short-term liabilities per turnover ratio and goodwill. The overall results showed that firm characteristics can influence a firm’s energy-saving activities and indicated a tendency for more energy savings in companies that were financially weaker or had done less work to improve energy efficiency prior to the PFE.

    Keywords
    Energy efficiency, Energy saving, Energy intensive industry, Energy management, Firm characteristics, Voluntary agreement
    National Category
    Energy Systems
    Identifiers
    urn:nbn:se:liu:diva-156280 (URN)10.1016/j.apenergy.2019.02.060 (DOI)
    Available from: 2019-04-11 Created: 2019-04-11 Last updated: 2019-04-12
    5. Specific Energy Consumption/Use (SEC) in Energy Management for Improving Energy Efficiency in Industry: Meaning, Usage and Differences
    Open this publication in new window or tab >>Specific Energy Consumption/Use (SEC) in Energy Management for Improving Energy Efficiency in Industry: Meaning, Usage and Differences
    2019 (English)In: Energies, ISSN 1996-1073, E-ISSN 1996-1073, Vol. 12, no 2, article id 247Article in journal (Refereed) Published
    Abstract [en]

    Although several research studies have adopted specific energy consumption (SEC) as an indicator of the progress of improved energy efficiency, publications are scarce on critical assessments when using SEC. Given the increasing importance of monitoring improved industrial energy efficiency and the rising popularity of SEC as an energy key performance indicator (e-KPI), an in-depth analysis and problematization on the pros and cons of using SEC would appear to be needed. The aim of this article is to analyse SEC critically in relation to industrial energy efficiency. By using SEC in the pulp and paper industry as an example, the results of this exploratory study show that although SEC is often used as an e-KPI in industry, the comparison is not always straightforward. Challenges emanate from a lack of information about how SEC is calculated. It is likely that SEC is an optimal e-KPI within the same study, when all deployed SECs are calculated in the same way, and with the same underlying assumptions. However, before comparing SEC with other studies, it is recommended that the assumptions on which calculations are based should be scrutinized in order to ensure the validity of the comparisons. The paper remains an important contribution in addition to the available handbooks.

    Place, publisher, year, edition, pages
    MDPI, 2019
    Keywords
    specific energy consumption; specific energy use; specific energy; SEC; energy management; energy efficiency; industry; energy use; manufacturing
    National Category
    Energy Systems
    Identifiers
    urn:nbn:se:liu:diva-155606 (URN)10.3390/en12020247 (DOI)000459743700048 ()
    Note

    Funding Agencies|Swedish Energy Agency [40537-1]; Swedish Environmental Protection Agency [802-0082-17]; Division of Energy Systems at the Department of Management and Engineering, Linkoping University

    Available from: 2019-03-21 Created: 2019-03-21 Last updated: 2019-04-12
  • Public defence: 2019-05-10 13:00 Granitsalen, Linköping
    Bahlmann, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Goal-directed fluid therapy during major abdominal surgery2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Both hypo- and hypervolemia increase the risk for postoperative complications after major abdominal surgery. Fluid needs vary amongst patients depending on differences in preoperative dehydration, intraoperative physiology and surgical characteristics. Goal-directed fluid therapy (GDFT) aims to target the right amount of fluid administration in each patient by evaluating the effect of fluid boluses on haemodynamic parameters such as stroke volume. It has been shown to reduce postoperative morbidity and is generally recommended for high-risk surgery. The overall aim of this thesis was to evaluate whether more simple devices for GDFT result in clinical benefit, thus facilitating the application of GDFT in more patients.

    Aim: To compare performance and clinical benefit of pleth variability index (PVI), a noninvasive, easy-to-use device for GDFT, with the reference method of oesophageal Doppler; to evaluate methods for measuring preoperative dehydration and its effect on fluid handling by the body; and to confirm the expected clinical benefits of GDFT in patients undergoing oesophageal resection, a high risk procedure.

    Methods: In Studies I-III 150 patients scheduled for open abdominal surgery of at least 2 hrs were randomised to GDFT with either PVI or oesophageal Doppler. In the first half of the cohort, both monitors were connected to compare intraoperative performance. In 30 patients preoperative dehydration was analysed. In study IV 64 patients undergoing oesophageal resection were randomised to GDFT using pulse contour analysis or standard treatment.

    Results: The concordance between PVI and oesophageal Doppler for indicating the need for and effect of a fluid bolus was low, and both had only limited capacity to predict the effect of a fluid bolus. Both methods resulted in comparable amounts of fluid being administered and similar clinical outcome. Preoperative dehydration was limited but did impact on fluid handling. Patients receiving GDFT during oesophageal resection received more fluid and more dobutamine compared to controls, but this did not result in any clinical benefit.

    Conclusions: There are methodological issues as well as uncertainties about the clinical benefit of GDFT. We cannot recommend a strict application of any GDFT strategy, but suggest that its components should be incorporated in a more encompassing assessment of a patient’s fluid needs. The measurement, impact and treatment of preoperative dehydration need to be further clarified.

    List of papers
    1. Agreement between Pleth Variability Index and oesophageal Doppler to predict fluid responsiveness
    Open this publication in new window or tab >>Agreement between Pleth Variability Index and oesophageal Doppler to predict fluid responsiveness
    2016 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 2, p. 183-192Article in journal (Refereed) Published
    Abstract [en]

    Background: Optimisation of stroke volume using oesophageal Doppler is an established technique to guide intraoperative fluid therapy. The method has practical limitations and therefore alternative indices of fluid responsiveness, such as ventilator-induced variation in the pulse oximetric signal (Pleth Variability Index (PVI)) could be considered. We hypothesised that both methods predict fluid responsiveness in a similar way. Methods: Seventy-five patients scheduled for open major abdominal surgery were randomised to fluid optimisation using fluid bolus algorithms based on either PVI (n = 35) or Doppler (n = 39). All patients were monitored with both methods; the non-guiding method was blind. Primary endpoint was the concordance between the methods to predict fluid responsiveness. We also analysed the ability of each method to predict a stroke volume increase &gt;= 10% after a fluid bolus, as well as the accumulated intraoperative bolus fluid volume. Results: PVI indicated a need for fluid in one-third of the situations when Doppler did so, Cohens kappa = 0.03. A fluid bolus indicated by the PVI algorithm increased stroke volume by &gt;= 10% in half the situations. The same was found for the Doppler algorithm. The mean total bolus volume given was 878 ml when the fluid management was governed by PVI compared to 826 ml with Doppler (P = 0.71). Conclusion: PVI-and Doppler-based stroke volume optimisations agreed poorly, which did not affect the amount of fluid administered. None of the algorithms showed a good ability to predict fluid responsiveness. Our results do not support the fluid responsiveness concept.

    Place, publisher, year, edition, pages
    WILEY-BLACKWELL, 2016
    National Category
    Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-124622 (URN)10.1111/aas.12632 (DOI)000368139700006 ()26373826 (PubMedID)
    Note

    Funding Agencies|Department of Anaesthesiology and Intensive Care, Linkoping University Hospital; County Council of Ostergotland

    Available from: 2016-02-09 Created: 2016-02-08 Last updated: 2019-04-10
    2. Dehydration and fluid volume kinetics before major open abdominal surgery
    Open this publication in new window or tab >>Dehydration and fluid volume kinetics before major open abdominal surgery
    2014 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 10, p. 1258-1266Article in journal (Refereed) Published
    Abstract [en]

    Introduction: Assessment of dehydration in the preoperative setting is of potential clinical value. The present study uses urine analysis and plasma volume kinetics, which have both been validated against induced changes in body water in volunteers, to study the incidence and severity of dehydration before open abdominal surgery begins. Methods: Thirty patients (mean age 64 years) had their urine analysed before major elective open abdominal surgery for colour, specific weight, osmolality and creatinine. The results were scored and the mean taken to represent a dehydration index. Thereafter, the patients received an infusion of 5ml/kg of Ringers acetate intravenously for over 15min. Blood was sampled for 70min and the blood haemoglobin concentration used to estimate the plasma volume kinetics. Results: Distribution of fluid occurred more slowly (Pless than0.01) and the elimination half-life was twice as long (median 40min, not significant) in the 11 patients (37%) diagnosed to be moderately dehydrated as compared with euhydrated patients. The dehydration index indicated that the fluid deficit in these patients corresponded to 2.5% of the body weight, whereas the deficit in the others was 1%. In contrast, the 11 patients who later developed postoperative nausea and vomiting had a very short elimination half-life, only 9min (median, Pless than0.01). These patients were usually euhydrated but had microalbuminuria (Pless than0.03) and higher natriuresis (Pless than0.01). Conclusions: The degree of dehydration before major surgery was modest as evidenced both by urine sampling and volume kinetic analysis.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2014
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:liu:diva-112464 (URN)10.1111/aas.12416 (DOI)000343826500010 ()25307711 (PubMedID)
    Note

    Funding Agencies|County Council of Ostergotland [LiO-314271, LiO-357621]

    Available from: 2014-11-28 Created: 2014-11-28 Last updated: 2019-04-10Bibliographically approved
    3. Pleth variability index or stroke volume optimization during open abdominal surgery: a randomized controlled trial
    Open this publication in new window or tab >>Pleth variability index or stroke volume optimization during open abdominal surgery: a randomized controlled trial
    2018 (English)In: BMC Anesthesiology, ISSN 1471-2253, E-ISSN 1471-2253, Vol. 18, article id 115Article in journal (Refereed) Published
    Abstract [en]

    Background: The impact of Goal Directed Fluid Therapy (GDFT) based on the non-invasive Pleth Variability Index (PVI) on clinical outcome after abdominal surgery has only sparingly been explored. The purpose of this study was to compare the effect of intraoperative GDFT guided by PVI to a control group using esophageal Doppler on the incidence of complications and length of hospital stay after major abdominal surgery. We hypothesized that there would be no difference between the groups. Methods: This was a randomized controlled trial in a Swedish university hospital between November 2011 and January 2015; 150 patients scheduled for open abdominal surgery lasting 2 h or more were included. Exclusion criteria included hepatic resection or severe cardiac arrhythmia. The patients were randomized 1: 1 to either the intervention group or the control group. The intervention group received intraoperative GDFT by administering fluid boluses of 3 ml/kg tetrastarch aiming at a PVI value below 10%, while GDFT in the control group aimed for optimization of stroke volume as assessed with esophageal Doppler. Blinded observers assessed complications until postoperative day 30 using pre-defined definitions, as well as length of hospital stay. Results: One hundred and-fifty patients were randomized and 146 patients were available for the final data analysis. Median duration of surgery was 3 h. A total of 64 complications occurred in the PVI group (N = 74) and 70 in the Doppler group (N = 72) (p = 0.93). Median (IQR) length of stay was 8.0 (8.0) days in the PVI group and 8.0 (9.5) in the Doppler group (P = 0.57). Conclusions: No difference in clinical outcome, as defined by number of postoperative complications, and length of hospital stay, was found when goal directed fluid therapy was applied using PVI as an alternative to esophageal Doppler. PVI appears to be an acceptable alternative to esophageal Doppler for goal directed fluid therapy during major open abdominal surgery.

    Place, publisher, year, edition, pages
    BMC, 2018
    Keywords
    Doppler ultrasonography; Fluid therapy; Laparotomy; Photoplethysmography; Stroke volume; Complications
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:liu:diva-150857 (URN)10.1186/s12871-018-0579-4 (DOI)000442038200002 ()30121072 (PubMedID)
    Note

    Funding Agencies|Department of Anesthesiology and Intensive Care, University Hospital Linkoping, Sweden; Region Ostergotland

    Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2019-04-10
    4. Goal-directed therapy during transthoracic oesophageal resection does not improve outcome: Randomised controlled trial
    Open this publication in new window or tab >>Goal-directed therapy during transthoracic oesophageal resection does not improve outcome: Randomised controlled trial
    2019 (English)In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 36, no 2, p. 153-161Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Goal-directed therapy (GDT) is expected to be of highest benefit in high-risk surgery. Therefore, GDT is recommended during oesophageal resection, which carries a high risk of postoperative complications.

    OBJECTIVES: The aim of this study was to confirm the hypothesis that GDT during oesophageal resection improves outcome compared with standard care.

    DESIGN: A randomised controlled study.

    SETTING: Two Swedish university hospitals, between October 2011 and October 2015.

    PATIENTS: Sixty-four patients scheduled for elective transthoracic oesophageal resection were randomised. Exclusion criteria included colonic interposition and significant aortic or mitral valve insufficiency.

    INTERVENTION: A three-step GDT protocol included stroke volume optimisation using colloid boluses as assessed by pulse-contour analysis, dobutamine infusion if cardiac index was below 2.5 l min m and norepinephrine infusion if mean arterial blood pressure was below 65 mmHg.

    MAIN OUTCOME MEASURE: The incidence of complications per patient at 5 and 30 days postoperatively as assessed using a predefined list.

    RESULTS: Fifty-nine patients were available for analysis. Patients in the intervention group received more colloid fluid (2190 ± 875 vs. 1596 ± 759 ml, P < 0.01) and dobutamine more frequently (27/30 vs. 9/29, P < 0.01). The median [interquartile range, IQR] incidence of complications per patient 5 days after surgery was 2 [0 to 3] in the intervention group and 1 [0 to 2] in the control group (P = 0.10), and after 30 days 4 [2 to 6] in the intervention group and 2 [1 to 4] in the control group (P = 0.10).

    CONCLUSION: Goal-directed therapy during oesophageal resection did not result in a reduction of the incidence of postoperative complications.

    TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01416077.

    Place, publisher, year, edition, pages
    Lippincott Williams & Wilkins, 2019
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:liu:diva-156264 (URN)10.1097/EJA.0000000000000908 (DOI)000462763800010 ()30431499 (PubMedID)2-s2.0-85059795456 (Scopus ID)
    Note

    Funding agencies: Linkoping Medical Society

    Available from: 2019-04-10 Created: 2019-04-10 Last updated: 2019-04-18Bibliographically approved
  • Public defence: 2019-05-17 09:00 Hasselquistsalen, Linköping
    Ward, Liam
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Sex differences in atherosclerosis and exercise effects2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cardiovascular disease (CVD) is the leading cause of death globally, with atherosclerosis being the main cause of cardiovascular diseases. Atherosclerosis is an inflammatory disease of the blood vessel wall, which over time will cause thickening and hardening of the vessel wall. Atherosclerosis can result in catastrophic vascular events, such as myocardial infarction and stroke. There are distinct sex differences in CVD mortality at different ages, before menopause women have a lower mortality of CVD in comparison to men, which equalises after menopause. In addition to sex differences in the incidence of CVD, there are also distinct sex differences in the phenotype of atherosclerotic plaques, with men generally developing more severe and vulnerable plaques that are at risk of rupture.

    This thesis aimed to investigate the sex differences in atherosclerosis, in particular how the proteome and pathophysiology differs. In addition, we sought to investigate the potential benefit of an exercise programme, in reducing CVD risks, using a randomised controlled trial including postmenopausal women.

    Sex differences in atherosclerosis were first investigated via proteomic analysis of human carotid endarterectomy samples. Initially, five intraplaque biopsies were taken from distinct atheroma regions, including; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Protein extracts from these biopsies were subjected to analysis by mass spectrometry. The novel sampling method was successful in reducing the effect of plaque heterogeneity, a limitation in previous proteomic studies of atherosclerosis, and a number of previously unreported proteins were identified in human carotid atheroma. In addition to this, with the inclusion of multivariate statistical modelling, it was found that 43 proteins significantly discriminated the carotid atheroma between men and women. These proteins were grouped by function, and it was found that atheroma from men was associated with the increased abundance of inflammatory response proteins, including phospholipase-A2 membrane associated and lysozyme C, and atheroma from women was associated with increased abundance of blood coagulation, complement activation, and transport proteins, notably including; antithrombin-III, coagulation factor XII, and afamin. In addition, differences were also ii observed in the abundance of iron metabolism related proteins. These sex differences were further expanded upon from a pathophysiological perspective. Immunohistochemistry stainings of ferritin and transferrin receptor 1 were found significantly increased in the atheroma from men. Moreover, the levels of plasma haemoglobin were also significantly increased in men and were associated with the development of more vulnerable and severe plaque types. The more vulnerable and severe plaque types were also associated with significantly greater macrophage infiltration. In summary, these results are indicative of men developing atheroma with greater inflammation that are more vulnerable, due to increased iron and inflammatory proteins and macrophage infiltration, whereas atheroma from women develop with less inflammation and a more stable phenotype.

    The randomised controlled clinical trial aimed at investigating the effects of resistance training (RT), over a 15-week period, in postmenopausal women. Plasma samples were obtained at week-0 and week-15 of the study period, and analyses were performed primarily using a series of immunoassays. Results showed that women participating in RT, with good compliance, were associated with significant decreases in plasma levels of ferritin, lipids, and inflammatory adipokines. These results suggest that the use of regular RT may be a beneficial intervention in reducing the levels of body iron, lipids, and inflammation, all of which are risk factors for the development of CVD. However, validation studies are required in a larger cohort of postmenopausal women, in addition to the inclusion or complementary studies in middle-aged men.

    In summary, the works included in this thesis further expand on the current knowledge of sex differences in atherosclerosis, and also provides information on the potential of an exercise intervention to beneficially reduces the effects of known risk factors of CVD.

    List of papers
    1. Distinctive proteomic profiles among different regions of human carotid plaques in men and women
    Open this publication in new window or tab >>Distinctive proteomic profiles among different regions of human carotid plaques in men and women
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    2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 26231Article in journal (Refereed) Published
    Abstract [en]

    The heterogeneity of atherosclerotic tissue has limited comprehension in proteomic and metabolomic analyses. To elucidate the functional implications, and differences between genders, of atherosclerotic lesion formation we investigated protein profiles from different regions of human carotid atherosclerotic arteries; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Proteomic analysis was performed using 2-DE with MALDI-TOF, with validation using nLC-MS/MS. Protein mapping of 2-DE identified 52 unique proteins, including 15 previously unmapped proteins, of which 41 proteins were confirmed by nLC-MS/MS analysis. Expression levels of 18 proteins were significantly altered in plaque regions compared to the internal control region. Nine proteins showed site-specific alterations, irrespective of gender, with clear associations to extracellular matrix remodelling. Five proteins display gender-specific alterations with 2-DE, with two alterations validated by nLC-MS/MS. Gender differences in ferritin light chain and transthyretin were validated using both techniques. Validation of immunohistochemistry confirmed significantly higher levels of ferritin in plaques from male patients. Proteomic analysis of different plaque regions has reduced the effects of plaque heterogeneity, and significant differences in protein expression are determined in specific regions and between genders. These proteomes have functional implications in plaque progression and are of importance in understanding gender differences in atherosclerosis.

    Place, publisher, year, edition, pages
    NATURE PUBLISHING GROUP, 2016
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-129495 (URN)10.1038/srep26231 (DOI)000376554600001 ()27198765 (PubMedID)
    Note

    Funding Agencies|Swedish Heart Lung Foundation; Linkoping University Hospital Research foundation; Swedish Institute; China Scholarship Council

    Available from: 2016-06-20 Created: 2016-06-20 Last updated: 2019-04-17
    2. Proteomics and multivariate modelling reveal sex-specific alterations in distinct regions of human carotid atheroma
    Open this publication in new window or tab >>Proteomics and multivariate modelling reveal sex-specific alterations in distinct regions of human carotid atheroma
    2018 (English)In: Biology of Sex Differences, ISSN 2042-6410, Vol. 9, article id 54Article in journal (Refereed) Published
    Abstract [en]

    BackgroundAtherosclerotic lesions are comprised of distinct regions with different proteomic profiles. Men and women develop differences in lesion phenotype, with lesions from women generally being more stable and less prone to rupture. We aimed to investigate the differences in proteomic profiles between sexes, including distinct lesion regions, to identify altered proteins that contribute to these differences observed clinically.MethodsCarotid endarterectomy samples (ten men/ten women) were obtained, and intraplaque biopsies from three distinct regions (internal control, fatty streak and plaque) were analysed by tandem-mass spectrometry. Multivariate statistical modelling, using orthogonal partial least square-discriminant analysis, was used to discriminate the proteomes between men and women.ResultsMultivariate discriminant modelling revealed proteins from 16 functional groups that displayed sex-specific associations. Additional statistics revealed ten proteins that display region-specific alterations when comparing sexes, including proteins related to inflammatory response, response to reactive oxygen species, complement activation, transport and blood coagulation. Transport protein afamin and blood coagulation proteins antithrombin-III and coagulation factor XII were significantly increased in plaque region from women. Inflammatory response proteins lysozyme C and phospholipase A2 membrane-associated were significantly increased in plaque region from men. Limitations with this study are the small sample size, limited patient information and lack of complementary histology to control for cell type differences between sexes.ConclusionsThis pilot study, for the first time, utilises a multivariate proteomic approach to investigate sexual dimorphism in human atherosclerotic tissue, and provides an essential proteomic platform for further investigations to help understand sexual dimorphism and plaque vulnerability in atherosclerosis.

    Place, publisher, year, edition, pages
    BMC, 2018
    Keywords
    Afamin; Atherosclerosis; Lysozyme C; Mass spectrometry; Serine protease inhibitors; Vulnerability
    National Category
    Medical Genetics
    Identifiers
    urn:nbn:se:liu:diva-153822 (URN)10.1186/s13293-018-0217-3 (DOI)000454616000001 ()30594242 (PubMedID)
    Note

    Funding Agencies|Swedish Heart Lung Foundation; Torsten and Ragnar Soderbergs Foundation; Stroke Foundation; Olle Engkvist Foundation; Swedish Gamla Tjanarinnor Foundation; Linkoping University Hospital Research Fund

    Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-04-17
    3. Carotid Atheroma From Men Has Significantly Higher Levels of Inflammation and Iron Metabolism Enabled by Macrophages
    Open this publication in new window or tab >>Carotid Atheroma From Men Has Significantly Higher Levels of Inflammation and Iron Metabolism Enabled by Macrophages
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    2018 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, no 2, p. 419-425Article in journal (Refereed) Published
    Abstract [en]

    Background and Purpose-Men differ from women in the manifestation of atherosclerosis and iron metabolism. Intraplaque hemorrhage and hemoglobin (Hb) catabolism by macrophages are associated with atherosclerotic lesion instability. The study aims were to investigate sex differences in (1) lesion severity in relation to blood Hb, (2) iron homeostasis in human carotid plaques, and (3) macrophage polarization within atheroma. Methods-The carotid artery samples from 39 men and 23 women were immunostained with cell markers for macrophages, smooth muscle cells, ferritin, and TfR1 (transferrin receptor 1), which were further analyzed according to sex in relation to iron, Hb, and lipids in circulation. Additionally, samples of predefined regions from human carotid atherosclerotic lesions, including internal controls, were used for proteomic analysis by mass spectrometry. Results-Male patients, compared with women, had larger necrotic cores and more plaque rupture, which were associated with higher levels of Hb. Atheroma of male patients had significantly higher levels of Hb in circulation and CD68 macrophages, ferritin, and TfR1 in lesions. CD68 macrophages were significantly correlated with ferritin and TfR1. Plaques from male patients comparatively possessed higher levels of inflammatory macrophage subsets, CD86 (M1) and CD163 (M2), but lower levels of STF (serotransferrin) and HPX (hemopexin). Conclusions-Male patients with carotid atheroma had more advanced and ruptured lesions associated with significantly higher levels of inflammatory macrophage infiltration and high iron stores in the blood and in their plaques. These findings help to understand sex differences and iron metabolism in atherosclerosis and factors related to atheroma progression.

    Place, publisher, year, edition, pages
    LIPPINCOTT WILLIAMS & WILKINS, 2018
    Keywords
    atherosclerosis; ferritins; hemoglobins; hemopexin; macrophages; male
    National Category
    Neurology
    Identifiers
    urn:nbn:se:liu:diva-144876 (URN)10.1161/STROKEAHA.117.018724 (DOI)000422928000035 ()29284736 (PubMedID)
    Note

    Funding Agencies|Swedish Heart-Lung Foundation; Torsten and Ragnar Soderbergs Foundation; Stroke Foundation; Olle Engkvist Foundation; Swedish Gamla Tjanarinnor Foundation; Linkoping University; Linkoping University Hospital Research Fund

    Available from: 2018-02-09 Created: 2018-02-09 Last updated: 2019-04-17
  • Public defence: 2019-05-24 13:00 Aulan, Jönköping
    Neshro, Barmano
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Structured management, Symptoms, Health-related Quality of Life and Alcohol in Patients with Atrial Fibrillation2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting at least 2.9 % of the Swedish population. Although AF is associated with increased risk of ischaemic stroke, there have been many reports on the underuse of oral anticoagulants (OAC) and non-adherence to guidelines in other areas as well. AF is also associated with disabling symptoms and decreased health-related quality of life (HRQoL), but some patients are asymptomatic. The reasons for the great variation of symptoms remain unclear. Furthermore, although research on AF has increased, studies have mainly focused on treatment, while studies on risk factors, such as alcohol consumption, have only recently gained attention.

    The aim of this thesis was to investigate whether structured care of patients with AF could improve guideline adherence and HRQoL compared to standard care, and to determine which factors affect symptoms and HRQoL prior to treatment with radiofrequency catheter ablation (RFA), as well as improvement after RFA. Furthermore, we aimed to examine the associations of alcohol consumption with cardiac biomarkers, the size of the left atrium (LA), and re-ablation.

    This thesis is based on two studies. In the ‘Structured Management and Coaching – Patients with Atrial Fibrillation’ (SMaC-PAF) study, 176 patients were recruited to the intervention group, receiving a structured follow-up programme, and 146 patients were recruited to the control group, receiving standard care. The two groups were compared in regard to adherence to guidelines and patient-reported outcome measures (PROMs) assessing symptoms and HRQoL.

    In the ‘Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation’ (SMURF) study, 192 patients referred for their first RFA of AF were included. PROMs questionnaires were filled out, echocardiography was performed, and cardiac biomarkers were analysed. Alcohol consumption was assessed through interview and through analysis of ethyl glucuronide in hair (hEtG). AF recurrence and re-ablation within 12 months were examined.

    In the first study, after one year, 94% (n=112) and 74% (n=87) of patients with indication for OAC in the intervention and the control groups, respectively, actually received treatment with OAC (p <0.01). Both groups improved in anxiety and HRQoL scores over the year, but in the intervention group, arrhythmia-specific symptoms were less frequently experienced and the SF-36 scores were more similar to the norm population.

    In the second study, the most important predictors of arrhythmia-related symptoms and HRQoL prior to RFA were anxiety, depression and low-grade inflammation, while frequent AF attacks prior to RFA, freedom from AF recurrence after RFA, female gender, no enlarged LA, absence of diabetes, and the presence of heart failure were significant predictors of improvement in symptoms and HRQoL after RFA. Men with hEtG ≥7 pg/mg had higher levels of cardiac biomarkers, larger LA volumes and a higher re-ablation rate than men with hEtG <7 pg/mg, while no such findings were present in women.

    In conclusion, structured management was superior to standard care in patients with AF, emphasising the importance of structured care, adjusted to local requirements, in order to improve the care and well-being of patients with AF. Although the reasons for the great variety of symptoms in patients with AF still are not yet fully understood, it seems that psychological factors and inflammation play a role, and that improvement in symptoms and HRQoL after RFA is influenced by gender, diabetes, heart failure, LA size and the frequency of attacks before, as well as freedom from AF after, RFA. Finally, alcohol consumption corresponding to hEtG ≥7 pg/mg was associated with higher levels of cardiac biomarkers, larger LA size and a higher rate of re-ablation in men, implying that men with an hEtG-value ≥7 pg/mg have a higher risk for LA remodelling that could potentially lead to a deterioration of the AF situation.

  • Public defence: 2019-05-24 13:00 Berzeliussalen, Linköping
    Tobieson, Lovisa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Surgically Treated Intracerebral Haemorrhage: Pathophysiology and Clinical Aspects2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Mortality and morbidity of intracerebral haemorrhage (ICH) is excessively high, and the case fatality rate has not improved in the last decades. Although surgery for ICH can be life-saving, no positive effect on functional outcome has been found in large cohorts of ICH patients. Increased understanding of the pathophysiology of ICH is needed to develop improved treatment strategies.

    In 17 ICH patients, paired cerebral microdialysis (CMD) catheters were inserted in the perihaemorrhagic zone (PHZ) and in normal uninjured cortex at time of surgery. Despite normalisation of cerebral blood flow, a persistent metabolic crisis indicative of mitochondrial dysfunction was detected in the PHZ. This metabolic pattern was not observed in the uninjured cortex.

    CMD was also used to sample proteins for proteomic analysis. A distinct proteome profile that changed over time was found in the PHZ when compared to the seemingly normal, uninjured cortex. However, protein adsorption to CMD membranes, which may interfere with concentration measurements, was substantial.

    Surgical treatment of 578 ICH patients was analysed in a nation-wide retrospective multi-centre study in Sweden over five years. Patients selected for surgery had similar age, pre-operative level of consciousness and co-morbidity profiles, but ICH volume and the proportion of deep-seated ICH differed among the six neurosurgical centres. Furthermore, there was variability in the post-operative care, including the use and duration of intracranial pressure monitoring, cerebrospinal fluid drainage and mechanical ventilation.

    In conclusion, the results of this thesis show that:

    (i) Despite surgical removal of an ICH a metabolic crisis caused by mitochondrial dysfunction, a potential future therapeutic target, persists in the perihaemorrhagic zone.

    (ii-iii) CMD is a valuable tool in ICH research for sampling novel biomarkers using proteomics, which may aid in the development of improved therapeutic interventions. However, caveats of the technique, such as protein adsorption to the CMD membrane, must be considered.

    (iv) The nation-wide study illustrates similar clinical features in patients selected for ICH surgery, but substantial variability in ICH volume and location as well as neurocritical care strategies among Swedish neurosurgical centres. Development of refined clinical guidelines may reduce such intercentre variability and lead to improved functional outcome for ICH patients.  

    List of papers
    1. Persistent Metabolic Disturbance in the Perihemorrhagic Zone Despite a Normalized Cerebral Blood Flow Following Surgery for Intracerebral Hemorrhage.
    Open this publication in new window or tab >>Persistent Metabolic Disturbance in the Perihemorrhagic Zone Despite a Normalized Cerebral Blood Flow Following Surgery for Intracerebral Hemorrhage.
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    2018 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    BACKGROUND: We hypothesized that reduced cerebral blood flow (CBF) and/or energy metabolic disturbances exist in the tissue surrounding a surgically evacuated intracerebral hemorrhage (ICH). If present, such CBF and/or metabolic impairments may contribute to ongoing tissue injury and the modest clinical efficacy of ICH surgery.

    OBJECTIVE: To conduct an observational study of CBF and the energy metabolic state in the perihemorrhagic zone (PHZ) tissue and in seemingly normal cortex (SNX) by microdialysis (MD) following surgical ICH evacuation.

    METHODS: We evaluated 12 patients (median age 64; range 26-71 yr) for changes in CBF and energy metabolism following surgical ICH evacuation using Xenon-enhanced computed tomography (n = 10) or computed tomography perfusion (n = 2) for CBF and dual MD catheters, placed in the PHZ and the SNX at ICH surgery.

    RESULTS: CBF was evaluated at a mean of 21 and 58 h postsurgery. In the hemisphere ipsilateral to the ICH, CBF improved between the investigations (36.6 ± 20 vs 40.6 ± 20 mL/100 g/min; P < .05). In total, 1026 MD samples were analyzed for energy metabolic alterations including glucose and the lactate/pyruvate ratio (LPR). The LPR was persistently elevated in the PHZ compared to the SNX region (P < .05). LPR elevations in the PHZ were predominately type II (pyruvate normal-high; indicating mitochondrial dysfunction) as opposed to type I (pyruvate low; indicating ischemia) at 4 to 48 h (70% vs 30%) and at 49 to 84 h (79% vs 21%; P < .05) postsurgery.

    CONCLUSION: Despite normalization of CBF following ICH evacuation, an energy metabolic disturbance suggestive of mitochondrial dysfunction persists in the perihemorrhagic zone.

    Place, publisher, year, edition, pages
    Oxford University Press, 2018
    National Category
    Neurology
    Identifiers
    urn:nbn:se:liu:diva-150994 (URN)10.1093/neuros/nyy179 (DOI)29788388 (PubMedID)
    Available from: 2018-09-10 Created: 2018-09-10 Last updated: 2019-04-17
    2. Dynamic protein changes in the perihaemorrhagic zone of Surgically Treated Intracerebral Haemorrhage Patients
    Open this publication in new window or tab >>Dynamic protein changes in the perihaemorrhagic zone of Surgically Treated Intracerebral Haemorrhage Patients
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    2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 3181Article in journal (Refereed) Published
    Abstract [en]

    The secondary injury cascades exacerbating the initial brain injury following intracerebral haemorrhage (ICH) are incompletely understood. We used dual microdialysis (MD) catheters placed in the perihaemorrhagic zone (PHZ) and in seemingly normal cortex (SNX) at time of surgical ICH evacuation in ten patients (range 26-70 years). Routine interstitial MD markers (including glucose and the lactate/pyruvate ratio) were analysed and remaining microdialysate was analysed by two-dimensional gel electrophoresis (2-DE) and nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS). Two time intervals were analysed; median 2-10 hours post-surgery (time A) and median 68-76 hours post-ICH onset (time B). Using 2-DE, we quantified 232 +/- 31 different protein spots. Two proteins differed between the MD catheters at time A, and 12 proteins at time B (p amp;lt; 0.05). Thirteen proteins were significantly altered between time A and time B in the SNX and seven proteins in the PHZ, respectively. Using nLC-MS/MS ca 800 proteins were identified out of which 76 were present in all samples. At time A one protein was upregulated and two downregulated, and at time B, seven proteins were upregulated, and four downregulated in the PHZ compared to the SNX. Microdialysis-based proteomics is feasible for study of secondary injury mechanisms and discovery of biomarkers after ICH.

    Place, publisher, year, edition, pages
    NATURE PUBLISHING GROUP, 2019
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-155569 (URN)10.1038/s41598-019-39499-2 (DOI)000459897600115 ()30816204 (PubMedID)
    Note

    Funding Agencies|Swedish Stroke Association (STROKE-Riksforbundet); ALF Grants of Region Ostergotland

    Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-04-17
    3. Differences in neurosurgical treatment of intracerebral haemorrhage: a nation-wide observational study of 578 consecutive patients
    Open this publication in new window or tab >>Differences in neurosurgical treatment of intracerebral haemorrhage: a nation-wide observational study of 578 consecutive patients
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    2019 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    Background

    Supratentorial intracerebral haemorrhage (ICH) carries an excessive mortality and morbidity. Although surgical ICH treatment can be life-saving, the indications for surgery in larger cohorts of ICH patients are controversial and not well defined. We hypothesised that surgical indications vary substantially among neurosurgical centres in Sweden.

    Objective

    In this nation-wide retrospective observational study, differences in treatment strategies among all neurosurgical departments in Sweden were evaluated.

    Methods

    Patient records, neuroimaging and clinical outcome focused on 30-day mortality were collected on each operated ICH patient treated at any of the six neurosurgical centres in Sweden from 1 January 2011 to 31 December 2015.

    Results

    In total, 578 consecutive surgically treated ICH patients were evaluated. There was a similar incidence of surgical treatment among different neurosurgical catchment areas. Patient selection for surgery was similar among the centres in terms of patient age, pre-operative level of consciousness and co-morbidities, but differed in ICH volume, proportion of deep-seated vs. lobar ICH and pre-operative signs of herniation (p < .05). Post-operative patient management strategies, including the use of ICP-monitoring, CSF-drainage and mechanical ventilation, varied among centres (p < .05). The 30-day mortality ranged between 10 and 28%.

    Conclusions

    Although indications for surgical treatment of ICH in the six Swedish neurosurgical centres were homogenous with regard to age and pre-operative level of consciousness, important differences in ICH volume, proportion of deep-seated haemorrhages and pre-operative signs of herniation were observed, and there was a substantial variability in post-operative management. The present results reflect the need for refined evidence-based guidelines for surgical management of ICH.

    Place, publisher, year, edition, pages
    Springer, 2019
    Keywords
    Intracerebral haemorrhage, Surgery, Guidelines, Craniotomy, External ventricular drain, Intraventricular haemorrhage
    National Category
    Surgery
    Identifiers
    urn:nbn:se:liu:diva-156370 (URN)10.1007/s00701-019-03853-0 (DOI)
    Available from: 2019-04-17 Created: 2019-04-17 Last updated: 2019-04-17
  • Public defence: 2019-05-31 13:00 Hugo Theorell, Norra Entrén, Linköping
    Ziegler, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Improving Assessments of Hemodynamics and Vascular Disease2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Blood vessels are more than simple pipes, passively enabling blood to pass through them. Their form and function are dynamic, changing with both aging and disease. This process involves a feedback loop wherein changes to the shape of a blood vessel affect the hemodynamics, causing yet more structural adaptation. This feedback loop is driven in part by the hemodynamic forces generated by the blood flow, and the distribution and strength of these forces appear to play a role in the initiation, progression, severity, and the outcome of vascular diseases.

    Magnetic Resonance Imaging (MRI) offers a unique platform for investigating both the form and function of the vascular system. The form of the vascular system can be examined using MR-based angiography, to generate detailed geometric analyses, or through quantitative techniques for measuring the composition of the vessel wall and atherosclerotic plaques. To complement these analyses, 4D Flow MRI can be used to quantify the functional aspect of the vascular system, by generating a full time-resolved three-dimensional velocity field that represents the blood flow.

    This thesis aims to develop and evaluate new methods for assessing vascular disease using novel hemodynamic markers generated from 4D Flow MRI and quantitative MRI data towards the larger goal of a more comprehensive non-invasive examination oriented towards vascular disease. In Paper I, we developed and evaluated techniques to quantify flow stasis in abdominal aortic aneurysms to measure this under-explored aspect of aneurysmal hemodynamics. In Paper II, the distribution and intensity of turbulence in the aorta was quantified in both younger and older men to understand how aging changes this aspect of hemodynamics. A method to quantify the stresses generated by turbulence that act on the vessel wall was developed and evaluated using simulated flow data in Paper III, and in Paper V this method was utilized to examine the wall stresses of the carotid artery. The hemodynamics of vascular disease cannot be uncoupled from the anatomical changes the vessel wall undergoes, and therefore Paper IV developed and evaluated a semi-automatic method for quantifying several aspects of vessel wall composition. These developments, taken together, help generate more valuable information from imaging data, and can be pooled together with other methods to form a more comprehensive non-invasive examination for vascular disease.

    List of papers
    1. Visualizing and quantifying flow stasis in abdominal aortic aneurysms in men using 4D flow MRI
    Open this publication in new window or tab >>Visualizing and quantifying flow stasis in abdominal aortic aneurysms in men using 4D flow MRI
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    2019 (English)In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 57, p. 103-110Article in journal (Refereed) Published
    Abstract [en]

    Purpose: To examine methods for visualizing and quantifying flow stasis in abdominal aortic aneurysms (AAA) using 4D Flow MRI. Methods: Three methods were investigated: conventional volumetric residence time (VRT), mean velocity analysis (MVA), and particle travel distance analysis (TDA). First, ideal 4D Flow MRI data was generated using numerical simulations and used as a platform to explore the effects of noise and background phase-offset errors, both of which are common 4D Flow MRI artifacts. Error-free results were compared to noise or offset affected results using linear regression. Subsequently, 4D Flow MRI data for thirteen (13) subjects with AAA was acquired and used to compare the stasis quantification methods against conventional flow visualization. Results: VRT (R-2 = 0.69) was more sensitive to noise than MVA (R-2 = 0.98) and TDA (R-2 = 0.99) at typical noncontrast signal-to-noise ratio levels (SNR = 20). VRT (R-2 = 0.14) was more sensitive to background phase-offsets than MVA (R-2 = 0.99) and TDA (R-2 = 0.96) when considering a 95% effective background phase-offset correction. Qualitatively, TDA outperformed MVA (Wilcoxon p amp;lt; 0.005, mean score improvement 1.6/5), and had good agreement (median score 4/5) with flow visualizations. Conclusion: Flow stasis can be quantitatively assessed using 4D Flow MRI. While conventional residence time calculations fail due to error accumulation as a result of imperfect measured velocity fields, methods that do not require lengthy particle tracking perform better. MVA and TDA are less sensitive to measurement errors, and TDA generates results most similar to those obtained using conventional flow visualization.

    Place, publisher, year, edition, pages
    ELSEVIER SCIENCE INC, 2019
    Keywords
    Abdominal aortic aneurysm; Hemodynamics; 4D flow MRI; Flow stasis
    National Category
    Medical Laboratory and Measurements Technologies
    Identifiers
    urn:nbn:se:liu:diva-154524 (URN)10.1016/j.mri.2018.11.003 (DOI)000458096100012 ()30445146 (PubMedID)
    Available from: 2019-02-20 Created: 2019-02-20 Last updated: 2019-04-17
    2. Age-Related Vascular Changes Affect Turbulence in Aortic Blood Flow
    Open this publication in new window or tab >>Age-Related Vascular Changes Affect Turbulence in Aortic Blood Flow
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    2018 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 36Article in journal (Refereed) Published
    Abstract [en]

    Turbulent blood flow is implicated in the pathogenesis of several aortic diseases but the extent and degree of turbulent blood flow in the normal aorta is unknown. We aimed to quantify the extent and degree of turbulece in the normal aorta and to assess whether age impacts the degree of turbulence. 22 young normal males (23.7 +/- 3.0 y.o.) and 20 old normal males (70.9 +/- 3.5 y.o.) were examined using four dimensional flow magnetic resonance imaging (4D Flow MRI) to quantify the turbulent kinetic energy (TKE), a measure of the intensity of turbulence, in the aorta. All healthy subjects developed turbulent flow in the aorta, with total TKE of 3-19 mJ. The overall degree of turbulence in the entire aorta was similar between the groups, although the old subjects had about 73% more total TKE in the ascending aorta compared to the young subjects (young = 3.7 +/- 1.8 mJ, old = 6.4 +/- 2.4 mJ, p amp;lt; 0.001). This increase in ascending aorta TKE in old subjects was associated with age-related dilation of the ascending aorta which increases the volume available for turbulence development. Conversely, age-related dilation of the descending and abdominal aorta decreased the average flow velocity and suppressed the development of turbulence. In conclusion, turbulent blood flow develops in the aorta of normal subjects and is impacted by age-related geometric changes. Non-invasive assessment enables the determination of normal levels of turbulent flow in the aorta which is a prerequisite for understanding the role of turbulence in the pathophysiology of cardiovascular disease.

    Place, publisher, year, edition, pages
    FRONTIERS MEDIA SA, 2018
    Keywords
    turbulent kinetic energy (TKE); turbulent blood flow; aortic blood flow; aortic dilation; normal values; 4D flow MRI; phase contrast MRI
    National Category
    Physiology
    Identifiers
    urn:nbn:se:liu:diva-145129 (URN)10.3389/fphys.2018.00036 (DOI)000423400000001 ()29422871 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council [2013-6077, 2014-6191]; Swedish Heart and Lung foundation [20140398]; Kangwon National University [D1001179-01-01]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2016R1A6A3A03006337]

    Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2019-04-17
    3. Assessment of Turbulent Flow Effects on the Vessel Wall Using Four-Dimensional Flow MRI
    Open this publication in new window or tab >>Assessment of Turbulent Flow Effects on the Vessel Wall Using Four-Dimensional Flow MRI
    2017 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 77, no 6, p. 2310-2319Article in journal (Refereed) Published
    Abstract [en]

    Purpose: To explore the use of MR-estimated turbulence quantities for the assessment of turbulent flow effects on the vessel wall. Methods: Numerical velocity data for two patient-derived models was obtained using computational fluid dynamics (CFD) for two physiological flow rates. The four-dimensional (4D) Flow MRI measurements were simulated at three different spatial resolutions and used to investigate the estimation of turbulent wall shear stress (tWSS) using the intravoxel standard deviation (IVSD) of velocity and turbulent kinetic energy (TKE) estimated near the vessel wall. Results: Accurate estimation of tWSS using the IVSD is limited by the spatial resolution achievable with 4D Flow MRI. TKE, estimated near the wall, has a strong linear relationship to the tWSS (mean R(2=)0.84). Near-wall TKE estimates from MR simulations have good agreement to CFD-derived ground truth (mean R-2=0.90). Maps of near-wall TKE have strong visual correspondence to tWSS. Conclusion: Near-wall estimation of TKE permits assessment of relative maps of tWSS, but direct estimation of tWSS is challenging due to limitations in spatial resolution. Assessment of tWSS and near-wall TKE may open new avenues for analysis of different pathologies. (C) 2016 International Society for Magnetic Resonance in Medicine

    Place, publisher, year, edition, pages
    WILEY, 2017
    Keywords
    phase contrast magnetic resonance imaging; wall shear stress; turbulence; turbulent kinetic energy; aorta
    National Category
    Medical Image Processing
    Identifiers
    urn:nbn:se:liu:diva-138232 (URN)10.1002/mrm.26308 (DOI)000401270900022 ()27350049 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council; National Supercomputer Centre [SNIC2014-11-22]

    Available from: 2017-06-14 Created: 2017-06-14 Last updated: 2019-04-17
  • Public defence: 2019-06-05 10:15 Planck, Fysikhuset, Linköping
    Pilemalm, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Theoretical and experimental studies of ternary and quaternary nitrides for machining and thermoelectric materials2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Nitrides are used as coatings and thin films for a wide range of applications. The study and use of nitrides in the recent decades have shifted towards ternary, quaternary or even higher order (complex) nitrides. There is an interest to use ternary and quaternary nitrides for machining and thermoelectric materials, because it gives the possibility to choose composition and thereby design the materials properties. This thesis presents research results on TiAlN and and TiAlN-based coatings that are used as hard coatings for machining and on ternary scandium nitrides that are of interest for thin films for thermoelectric applications. The high-pressure high-temperature behavior of cubic TiAlN deposited on cubic boron nitride has been experimentally studied. It has been shown that the spinodal decomposition, which means decomposition into cubic domains enriched in TiN and AlN, is delayed as a result of high pressure compared to ambient pressure. No chemical interaction between coating and substrate occurs. TiZrAlN has been theoretically and experimentally studied at high temperature. The results show that the when Zr-content is decreased and the Al-content is increased the decomposition route changes from nucleation and growth to spinodal decomposition. The microstructure evolution with temperature depends on the initial composition. In the case where the decompositon starts with only spinodal decomposition the microstructure at 1100 °C consists of domains that are larger than in the case where the decomposition occurs by nucleation and growth. ScMN2 (M=V, Nb, Ta) phases have been experimentally demonstrated for M=Nb and Ta in a few studies, but have not been much investigated. In this theseis, their crystal structure, stability, elastic properties, electronic structure and thermoelectric properties have been studied. At 0 K and 0 GPa it has been shown that these three phases are thermodynamically and elastically stable. Additionally, these are narrow bandgap semiconductors and their thermoelectric properties can be tuned by doping. Pressure has a stabilizing effect on these structures. When pressure increases from 0-150 GPa the elastic constants and moduli increases in the range 53-317 %.