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  • 25351.
    Falk, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Prevention of skin cancer in primary health care: an evaluation of three different prevention effort levels and the applicability of a phototest2008In: European Journal of General Practice, ISSN 1381-4788, E-ISSN 1751-1402, Vol. 14, no 2, p. 68-75Article in journal (Refereed)
    Abstract [en]

    Background/objective: The high skin cancer incidence in western society, and its known association with sun exposure habits, makes the area an important target for prevention. We investigated, in a primary healthcare setting, differentiated levels of prevention efforts directed at the propensity of the patient to change his/her sun habits, sun protection behaviour, and attitudes, after information intervention. Additionally, the impact of the performance of a phototest to determine individual sun sensitivity was evaluated. Methods: 308 patients visiting a primary healthcare centre in southern Sweden completed a questionnaire concerning sun habits, sun protection behaviour, and attitudes, and were randomized into one of three groups, representing increasing levels of prevention effort in terms of resources. Feedback on their questionnaire and general preventive sun protection advice was given, in the first group by means of a letter, and in the second and third groups by a doctor's consultation. Group 3 also underwent a phototest, with a self-reading assessment and a written follow-up of the phototest result. Change of sun habits, behaviour, and attitudes, based on the Transtheoretical Model of Behaviour Change and on Likert scale scorings, was evaluated after 6 months, by a repeated questionnaire. Results: Prevention mediated by a doctor's consultation had a clearly better impact on the subjects. The addition of a phototest did not further reinforce this effect in the group as a whole, but it did for a subgroup of individuals with high ultraviolet (UV) sensitivity, as determined by the phototest itself, suggesting that this might actually be a tool to improve outcome in this high-risk group. Conclusion: A personal doctor's consultation is a valuable tool in the effective delivery of preventive information in the general practice setting. In individuals with high UV-sensitivity and thus high risk for skin cancer the performance of a photo-test reinforces a positive outcome in habits, behaviour and attitudes.

  • 25352.
    Falk, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care Centres. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Reliability of self-assessed reading of skin tests: A possible approach in research and clinical practice?2010In: Dermatologi Online, ISSN 1087-2108, E-ISSN 1087-2108, Vol. 16, no 2Article in journal (Refereed)
    Abstract [en]

    In the investigation and management of skin disease, various testing protocols are of importance. The extent to which clinical judgments and decisions on therapy are supported by the performance of such testing can be affected negatively by the lack of time and resources for the performance of tests. In the present study, the possibility of utilizing self-reporting by subjects is investigated. Determination of irritation threshold for sodium lauryl sulphate (SLS) and minimal erythema dose for ultraviolet B were chosen as suitable self-reading protocols. Test reading by 26 subjects instructed in "present" or "absent" reporting of test reactions were compared to trained observer reading. Absolute agreement was found in 76.9 percent of the SLS reactions and in 85 percent of the UVB reactions. Weighted Kappa for the agreement between observations showed values of 0.76 for the SLS reactions and 0.83 for UVB reactions. We conclude that use of the protocols here studied, and other test protocols modified to accommodate a binomial assessment outcome ("+" or "-"), could well lead to an increase in the performance of skin testing. This could be a qualitative advantage for diagnosis and management of skin diseases. Additionally, population studies and even prevention initiatives could be facilitated. © 2010 Dermatology Online Journal.

  • 25353.
    Falk, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Bradley, Thomas
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Edström, Morgan
    Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Johansson-Fredin, Solveig
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County.
    Tärning, Eva
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Carlsson, Per
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Från evidens till praktik: utvärdering av ett nytt arbetssätt för att använda evidens i vårdens förbättringsarbete2014Report (Other academic)
    Abstract [sv]

    Att hälso- och sjukvården ska bedrivas utifrån vetenskap och beprövad erfarenhet är allmänt vedertaget. Ett snabbt ökande kunskapsflöde innebär dock höga krav på såväl behandlande enheter som på den enskilda läkaren, som i sitt vardagsarbete ska fatta medicinska beslut utifrån bästa möjliga kunskap. Att på ett strukturerat och effektivt sätt underlätta spridningen av, och tillgången till, evidensbaserad kunskap utgör en stor utmaning för hela samhället, inklusive forskarsamhället. För vården är det en utmaning att använda kunskapen.

    Syftet med projektet var att utveckla, pröva och utvärdera en lokalt anpassad modell för implementering av evidensbaserad kunskap i klinisk verksamhet, baserad på ett arbetssätt som tidigare prövats i Kanada (Alberta Ambassador Programme), och som modifierades för att passa de lokala förutsättningarna i Östergötland, där projektet genomfördes. Som kliniskt beslutsproblem att studera valdes förskrivning av läkemedlet pregabalin, som används vid epilepsi, generaliserat ångestsyndrom (GAD) och neuropatisk smärta. Valet grundades på att läkemedlet är dyrt i förhållande till alternativen, på en  ökande förskrivning med stor variationinom länet, samt på rapporter om  förskrivning utanför rekommenderadesjukdomstillstånd. Sammantaget pekade detta på osäkerhet i hur läkemedlet skulle användas och därmed utrymme för förbättring.

    Projektet genomfördes i fyra steg: 1) Framtagning av ett övergripande evidensdokument för pregabalin, 2) Expertgruppsmöten (uppdelade på psykiatri/smärta) där det utifrån evidensdokumentet arbetades fram ett sammanfattande evidensunderlag/expertrekommendation, 3) Dialogmöten på ett antal sjukhuskliniker/vårdcentraler, samt 4) Uppföljning och utvärdering. En webbenkät skickades till deltagarna direkt efter genomförda dialogmöten, samt efter tio veckor. Resultatet visade att deltagarna till övervägande del var nöjda med innehållet i och formerna för dialogen. En majoritet bedömde innehållet som värdefullt för kliniska ställningstaganden, och att det vid tioveckorsuppföljningen fått spridning på den egna enheten. Statistik över receptförskrivningen av pregabalin tio månader före och efter interventionen, visade för länets tre psykiatriska kliniker (vilka före interventionen skilt sig drastiskt åt i fråga om förskrivning per 1000 patienter) en tydlig utjämning i förskrivning mellan klinikerna. För övriga sjukhuskliniker och vårdcentraler gick det däremot inte att se någon tydlig förändring i detta avseende.

    Sammanfattningsvis bedöms den prövade modellen för implementering av evidensbaserad kunskap ha fungerat väl utifrån det praktiska genomförandet och baserat på deltagarnas omdömen, och bör därav kunna prövas även inom andra områden.

  • 25354.
    Falk, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Hagesund, Elisabet
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    CBT-based group intervention for insomnia – a non-randomized trial in primary care2016In: Journal of Sleep Disorders and Therapy, E-ISSN 2167-0277, Vol. 5, no 230Article in journal (Refereed)
    Abstract [en]

    Abstract

    Insomnia is a major health problem, commonly leading to pharmacological treatment. During recent years, behavioural therapies have gained stronger therapeutic position, not least cognitive behavioural therapy (CBT). The aim was to investigate the effect of a CBT-based group intervention for insomnia in primary care, by means of self-reported sleep quality and duration. In addition, cortisol in saliva, as a biological marker of stress was tested. Methods: Fifty participants with primary insomnia, attending primary care, were enrolled, 35 receiving the intervention, and 15 serving as control. The intervention group was recruited during the first two study years, and controls during a following third year, without randomization. The intervention included eight CBT-based group sessions, each two-hour long and led by a psychologist, with 4-6 participants in each group. Controls were handled in accordance with ordinary clinical routine, including pharmacological intervention. Sleep onset time, duration and quality were assessed before and after the intervention, by patients filling-out the Pittsburgh Sleep Quality Index (PSQI). Insomnia severity was assessed by the Insomnia Severity Index (ISI). Also, cortisol in saliva levels were monitored. Results: In the intervention group, significant shortening of mean sleep onset time, from 60-27 min (p<0.05) was observed, and a prolongation of mean sleep duration time, from 298-358 min (p<0.05), in neither case seen in the control group, although between-group difference was not statistically significant. Both PSQI and ISI means scores were significantly improved in the intervention group, from 12.1 to 7.9 (p<0.05) and from 19.4 to 12.5 (p<0.01), respectively, in the latter case significantly more so than in the control group (p<0.05). No effect on cortisol levels was detected, in either group. In conclusion, the tested eight-session CBT-based group intervention for insomnia appears to reduce severity and duration of insomnia, and to shorten time before falling asleep, when provided in primary care.

  • 25355.
    Falk, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care Centres. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Ilias, Michail
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Inter-observer variability in reading of phototest reactions with sharply or diffusely delineated borders2008In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 14, no 4, p. 397-402Article in journal (Refereed)
    Abstract [en]

    Background: In both clinical and experimental phototesting, naked eye assessment of erythema has been the main assessment parameter. As with all subjective assessment, variability in recorded results due to variable circumstances around the performance and reading of tests influences reliability and utility of data whether they be interpreted for an individual patient or for a group of research subjects.

    Methods: In the present study, variability in the reporting of diameter of ultraviolet B (UVB) erythema has been studied. The erythematous reactions were assessed by the naked eye and with the help of a millimetre-graded ruler by a group of dermatologists and dermatological trainees. Reaction size, objectively quantified by means of laser Doppler perfusion imaging (LDPI) using thresholding of the reaction perfusion, and known size of UVB provocation were used as yardsticks in order to quantify this variability.

    Results: Agreement between observers, against known size, was excellent for reactions with a sharp border, but for reactions with a diffuse or indistinct border there was a substantial inter-observer variability. This was also true for the comparison between naked-eye reading and LDPI assessment of the reaction size.

    Conclusion: It is concluded that if naked-eye readings are to be the outcome measurement, then provocations/protocols producing distinct borders are an advantage. If borders between provoked and unprovoked skin can be expected to be diffuse, i.e. part of a continuum of response, the use of objective, bioengineering techniques such as LDPI is required. Quantitative methods are also the basis for more detailed presentation and interpretation of test results including information on dose response above the minimal erythema dose.

  • 25356.
    Falk, Magnus
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Ilias, Michail
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Phototesting with a divergent UVB beam in the investigation of anti-inflammatory effects of topically applied substances2003In: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 19, no 4, p. 195-202Article in journal (Refereed)
    Abstract [en]

    Background: Phototesting based on a single exposure to a divergent ultraviolet B (UVB) beam with radially decreasing UVB doses can be used to determine an individual's minimal erythema dose (MED). Laser Doppler perfusion imaging (LDPI) data can be combined with dosimetry data to produce objective dose–response plots in addition to the MED. The aim of this study was to investigate whether the divergent beam protocol could be used to demonstrate and quantify the anti-inflammatory effects of clobetasol diproprionate (Dermovate®), pharmaceutical-grade acetone and a gel vehicle, applied after skin provocation by UVB.

    Method: Sixteen Caucasian subjects were illuminated with the divergent beam on three areas close together on the left side of their upper backs. Two of the provoked areas on each subject were treated with acetone, gel vehicle or Dermovate®, and one area was left untreated as a control. Skin blood perfusion was assessed 6 and 24 h after UVB illumination using LDPI. The reaction diameter, the mean perfusion, and the average dose–response plots for each group and treatment were extracted from the LDPI data.

    Results: Application of the topical steroid clobetasol diproprionate after UVB provocation markedly decreased the inflammatory response. Acetone and the gel vehicle also showed mild anti-inflammmatory effects in two of the parameters but not for the mean perfusion response. The mean diameter differences between controls and treated reactions had predominantly positive 99% confidence intervals. Analysis of the dose–response data at doses higher than the MED showed a linear relationship (0.89≤R2≤0.98) for all reactions but with lower gradients in treated reactions, mostly marked for clobetasol diproprionate.

    Conclusions:  The divergent beam protocol can be used to demonstrate and quantify the effects of topical agents on the UVB reaction, in terms of reaction diameter, mean perfusion and changes in dose–response characteristics. The dose–response approach seems to be applicable even in diagnostic testing of an individual patient's response to UVB.

  • 25357.
    Falk, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care Centres. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Magnusson, Henrik
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Sun protection advice mediated by the general practitioner: An effective way to achieve long-term change of behaviour and attitudes related to sun exposure?2011In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 29, no 3, p. 135-143Article in journal (Refereed)
    Abstract [en]

    Objective. To investigate, in primary health care, differentiated levels of prevention directed at skin cancer, and how the propensity of the patients to change sun habits/sun protection behaviour and attitudes towards sunbathing were affected, three years after intervention. Additionally, the impact of the performance of a phototest as a complementary tool for prevention was evaluated. Design. Randomized controlled study. Setting and subjects. During three weeks in February, all patients andgt;= 18 years of age registering at a primary health care centre in southern Sweden were asked to fill in a questionnaire mapping sun exposure habits, attitudes towards sunbathing, and readiness to increase sun protection according to the Transtheoretical Model of Behaviour Change (TTM) (n = 316). They were randomized into three intervention groups, for which sun protection advice was given, in Group 1 by means of a letter, and in Groups 2 and 3 orally during a personal GP consultation. Group 3 also underwent a phototest to demonstrate individual skin UV sensitivity. Main outcome measures. Change of sun habits/sun protection behaviour and attitudes, measured by five-point Likert scale scores and readiness to increase sun protection according to the TTM, three years after intervention, by a repeated questionnaire. Results. In the letter group, almost no improvement in sun protection occurred. In the two doctors consultation groups, significantly increased sun protection was demonstrated for several items, but the difference compared with the letter group was significant only for sunscreen use. The performance of a phototest did not appear to reinforce the impact of intervention. Conclusion. Sun protection advice, mediated personally by the GP during a doctors consultation, can lead to improvement in sun protection over a prolonged time period.

  • 25358.
    Falk, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Olsen Faresjö, Åshild
    Linköping University, Department of Medical and Health Sciences, Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Sun Exposure Habits and Health Risk-related Behaviours Among Individuals with Previous History of Skin Cancer2013In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 33, no 2, p. 631-638Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to investigate possible associations between UV exposure and other health risk behaviours in different social environments and in regard to previous history of skin cancer. Patients and Methods: In two closely-located, equally-sized cities in Sweden, representing different social environments (blue collar and white collar), patients aged 55-69 years, diagnosed with skin cancer (study group, n=489) or seborrhoeic keratosis (control group, n=664), were identified through a regional Health Care Register, and were given a questionnaire mapping for sun habits, tobacco smoking, alcohol use, and physical activity. Results: A previous history of skin cancer was associated with reduced UV exposure (pandlt;0.01) and increased UV protection (pandlt;0.00.1), higher alcohol consumption (pandlt;0.05), and higher level of physical activity (pandlt;0.05). Smoking was more common among subjects frequently sunbathing and rarely using sunscreen, but frequent sunbathing was positively associated with physical activity (pandlt;0.05). Daily smoking and risky drinking habits were more common in the blue collar social environment, while no differences were seen for sun habits in this respect. Conclusion: A previous history of skin cancer appears to promote increased UV protection. In contrast to alcohol/smoking habits, no association between social environment and sun habits was found.

  • 25359.
    Falk, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Region Östergötland, Center for Health and Developmental Care, Patient Safety.
    Wiréhn, Ann-Britt
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis.
    Lagerfelt, Marie
    Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Woisetschläger, Mischa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Ahlström, Ulla
    Vårdcentralen Kungsgatan Linköping, Sweden Region Östergötland, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Modifierad brittisk modell kortade ledtid till datortomografi av kolon2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112Article in journal (Refereed)
    Abstract [en]

    The British national Institute for Health and Care Excellence (NICE) has presented guidelines based on signs and symptoms which should raise a suspicion of colorectal cancer. A slightly modified version of these guidelines, adapted to Swedish conditions, named Swedish NICE (sNICE) criteria, was implemented at eight primary care centres. By following the sNICE criteria, cases with higher degree of suspicion of colorectal cancer were advised for computer tomography (CT) of the colon, whereas cases of low degree of suspicion were advised for the considerably less time and patient demanding CT of the abdomen. For patients with isolated anal symptoms without presence of sNICE criteria, active expectancy for six weeks was recommended, followed by renewed consideration. Results showed that the ratio between CT colon and CT abdomen was reduced from 2.2 to 1.1 after introduction of the sNICE criteria. Also, the proportion of patients undergoing CT colon within two weeks from admittance was increased from 3 to 25 %. We conclude that the sNICE criteria may be a useful supportive tool for the primary care physician.

  • 25360. Falk, Martin
    Visualization and mesoscopic simulation in systems biology2013Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Biological cells appear everywhere on earth. They might live on their own as unicellular organism, like bacteria, or might form complex organisms consisting of several thousands or millions of cells. Despite their small size of only a few micrometers, they are complex little miracles. A better understanding of the internal mechanisms and interplays within a single cell is the key to the understanding of life. In the context of this thesis, the mechanism of cellular signal transduction, i.e. relaying a signal from outside the cell by different means of transport toward its target inside the cell, is employed. Understanding and adjusting parts of the cellular signaling mechanism will eventually lead to the design of new drugs with less or even without any side-effects. Besides experiments, understanding can also be achieved by numerical simulations of cellular behavior. This is where systems biology closely relates and depends on recent research results in computer science in order to deal with the modeling, the simulation, and the analysis of the computational results.

    Since a single cell can consist of billions of molecules, the simulation of intracellular processes requires a simplifiedmodel. Typically, mesoscopic models are used containing only parts that are believed to be necessary for the processes. The simulation domain has to be three dimensional to consider the spatial, possibly asymmetric, intracellular architecture filled with individual particles representing signaling molecules. In contrast to continuous models defined by systems of partial differential equations, a particle-based model allows tracking individual molecules moving through the cell. This particle-based approach, however, demands for a higher computational effort than, e.g., non-spatial models that can be solved with ordinary differential equations. The overall process of signal propagation usually requires between minutes and hours to complete, but the movement of molecules and the interactions between them have to be computed in the range of microseconds. Hence, the computation of thousands of consecutive time steps is necessary, requiring several hours or even days of computational time for a sequential simulation. The need for several simulation runs with different parameter settings, a higher level of detail including more particles, or a generally more precise simulation, i.e. smaller time steps, demands for short execution times of the simulation. To speed up the simulation, the parallel hardware of current central processing units (CPUs) and graphics processing units (GPUs) can be employed. The parallelization of interacting particles, however, is non-trivial and requires special care when utilizing modern manycore architectures like the GPU. Finally, the resulting data has to be analyzed by domain experts and, therefore, has to be represented in meaningful ways. Typical prevalent analysis methods include the aggregation of the data in tables or simple 2D graph plots, sometimes 3D plots for continuous data. Despite the fact that techniques for the interactive visualization of data in 3D are well-known, so far none of the methods have been applied to the biological context of single cell models and specialized visualizations fitted to the experts’ need are missing. Another issue is the hardware available to the domain experts that can be used for the task of visualizing the increasing amount of time-dependent data resulting from simulations. Exa-scale visualization still seems to be a long way off, but even the data sets available today are pushing the rendering capability of current graphics hardware to its limits. However, it is important that the visualization keeps up with the simulations to ensure that domain experts can still analyze their data sets. To deal with the massive amount of data to come, compute clusters will be necessary with specialized hardware dedicated to data visualization. It is, thus, important, to develop visualization algorithms for this dedicated hardware, which is currently available as GPU.

    In this thesis, the computational power of recent many-core architectures (CPUs as well as GPUs) is harnessed for both the simulation and the visualizations. Novel parallel algorithms are introduced to parallelize the spatio-temporal, mesoscopic particle simulation to fit the architectures of CPU and GPU in a similar way, easing the portability between both. Besides molecular diffusion, the simulation considers extracellular effects on the signal propagation as well as the import of molecules into the nucleus and a dynamic cytoskeleton. An extensive comparison between different configurations is performed leading to the conclusion that the usage of GPUs is not always beneficial. Depending on the simulation setup, however, the GPU implementation can be up to ten times faster than the parallel simulation on the CPU. For the visual data analysis, novel interactive visualization techniques were developed to visualize the 3D simulation results. Existing glyph-based approaches are combined in a new way facilitating the visualization of the individual molecules in the interior of the cell as well as their trajectories. A novel implementation of the depth of field effect, as known from photography, combined with additional depth cues and coloring aid the visual perception and reduce visual clutter. To obtain a continuous signal distribution from the discrete particles, techniques known from volume rendering are employed. The visualization of the underlying atomic structures provides new detailed insights and can be used for educational purposes besides showing the original data. The proposed technique allows for the interactive visualization of data sets containing several billion atoms per time step. A microscope-like visualization allows for the first time to generate images of synthetic data similar to images obtained in wet lab experiments. The simulation and the visualizations are merged into a prototypical framework, thereby supporting the domain expert during the different stages of model development, i.e. design, parallel simulation, and analysis.

    Although the proposed methods for both simulation and visualization were developed with the study of single-cell signal transduction processes in mind, they are also applicable to models consisting of several cells and other particle-based scenarios. Examples in this thesis include the diffusion of drugs into a tumor, the detection of protein cavities, and molecular dynamics data from laser ablation simulations, among others.

  • 25361.
    Falk, Martin
    et al.
    VISUS - Visualization Research Center, University of Stuttgart, Germany.
    Daub, Markus
    Institute of Analysis, Dynamics, and Modeling, University of Stuttgart, Germany.
    Schneider, Guido
    Institute of Analysis, Dynamics, and Modeling, University of Stuttgart, Germany.
    Ertl, Thomas
    VISUS - Visualization Research Center, University of Stuttgart, Germany.
    Modeling and Visualization of Receptor Clustering on the Cellular Membrane2011In: IEEE Symposium on Biological Data Visualization (BioVis 2011), IEEE, 2011, p. 9-15Conference paper (Refereed)
    Abstract [en]

    In cell biology, apopotosis is a very important cellular process. Apopotosis, or programmed cell death, allows an organism to remove damaged or unneeded cells in a structured manner in contrast to necrosis. Ligands bind to the death receptors located on the cellular membrane forming ligand-receptor clusters. In this paper, we develop a novel mathematical model describing the stochastic process of the ligand-receptor clustering. To study the structure and the size of the receptor clusters, a stochastic particle simulation is employed. Besides the translation of the particles on the plasma membrane, we also take the particle rotation into account as we model binding sites explicitly. Glyph-based visualization techniques are used to validate and analyze the results of our in-silico model. Information on the individual clusters as well as particle-specific data can be selected by the user and are mapped to colors to highlight certain properties of the data. The preliminary results of our model look very promising. The visualization supports the process of model development by visual data analysis containing the identification of cluster components as well as the illustration of particle trajectories.

  • 25362.
    Falk, Martin
    et al.
    VISUS – Visualization Research Center, University of Stuttgart, Germany.
    Grottel, S.
    VISUS – Visualization Research Center, University of Stuttgart, Germany.
    Ertl, T.
    VISUS – Visualization Research Center, University of Stuttgart, Germany.
    Interactive Image-Space Volume Visualization for Dynamic Particle Simulations2010In: Proceedings of SIGRAD 2010: Content Aggregation and Visualization / [ed] Kai-Mikael Jää-Aro Thomas Larsson, Linköping University Electronic Press, 2010, p. 35-43Conference paper (Refereed)
    Abstract [en]

    Particle-based simulation plays an important role in many different fields of science and engineering. Two common visualization approaches for the resulting data are glyph-based rendering and density sampling employing volume rendering. Fine geometric features are inherently captured by glyph-based methods. However, they might suffer from aliasing and the global structure is often poorly conveyed. Volume rendering preserves the global structure but is limited due to the sampling resolution. To avoid aliasing artifacts and large memory footprints, we propose a direct volume rendering technique with on-demand density sampling of the particle data, as combination of splatting, texture slicing, and ray casting. We optimized our system with a novel ray cast termination employing early-z-test culling and hardware occlusion queries utilizing inter-frame coherency. Our system contains a fully-featured volume renderer and captures all geometric features of the data set representable at the available display resolution. Since no pre-computation is required, the proposed method can be used easily to visualize time-dependent data sets. The effectiveness of our approach is shown with examples from different application fields.

  • 25363.
    Falk, Martin
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Grottel, Sebastian
    Technische Universität Dresden, Germany.
    Krone, Michael
    University of Stuttgart, Germany.
    Reina, Guido
    University of Stuttgart, Germany.
    Interactive GPU-based Visualization of Large Dynamic Particle Data2016Book (Refereed)
    Abstract [en]

    Prevalent types of data in scientific visualization are volumetric data, vector field data, and particle-based data. Particle data typically originates from measurements and simulations in various fields, such as life sciences or physics. The particles are often visualized directly, that is, by simple representants like spheres. Interactive rendering facilitates the exploration and visual analysis of the data. With increasing data set sizes in terms of particle numbers, interactive high-quality visualization is a challenging task. This is especially true for dynamic data or abstract representations that are based on the raw particle data.

    This book covers direct particle visualization using simple glyphs as well as abstractions that are application-driven such as clustering and aggregation. It targets visualization researchers and developers who are interested in visualization techniques for large, dynamic particle-based data. Its explanations focus on GPU-accelerated algorithms for high-performance rendering and data processing that run in real-time on modern desktop hardware. Consequently, the implementation of said algorithms and the required data structures to make use of the capabilities of modern graphics APIs are discussed in detail. Furthermore, it covers GPU-accelerated methods for the generation of application-dependent abstract representations. This includes various representations commonly used in application areas such as structural biology, systems biology, thermodynamics, and astrophysics.

  • 25364.
    Falk, Martin
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Hotz, Ingrid
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Ljung, Patric
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Treanor, Darren
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Leeds Teaching Hospitals NHS Trust, United Kingdom.
    Ynnerman, Anders
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundström, Claes
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Sectra AB.
    Transfer Function Design Toolbox for Full-Color Volume Datasets2017In: 2017 IEEE PACIFIC VISUALIZATION SYMPOSIUM (PACIFICVIS), IEEE, IEEE, 2017, p. 171-179Conference paper (Refereed)
    Abstract [en]

    In this paper, we tackle the challenge of effective Transfer Function (TF) design for Direct Volume Rendering (DVR) of full-color datasets. We propose a novel TF design toolbox based on color similarity which is used to adjust opacity as well as replacing colors. We show that both CIE L*u*v* chromaticity and the chroma component of YCbCr are equally suited as underlying color space for the TF widgets. In order to maximize the area utilized in the TF editor, we renormalize the color space based on the histogram of the dataset. Thereby, colors representing a higher share of the dataset are depicted more prominently, thus providing a higher sensitivity for fine-tuning TF widgets. The applicability of our TF design toolbox is demonstrated by volume ray casting challenging full-color volume data including the visible male cryosection dataset and examples from 3D histology.

  • 25365.
    Falk, Martin
    et al.
    VISUS - Visualization Research Center, Universität Stuttgart, Germany.
    Klann, Michael
    Institute of Biochemical Engineering and Center Systems Biology, Universität Stuttgart, Germany.
    Reuss, Matthias
    Institute of Biochemical Engineering and Center Systems Biology, Universität Stuttgart, Germany.
    Ertl, Thomas
    VISUS - Visualization Research Center, Universität Stuttgart, Germany.
    3D Visualization of Concentrations from Stochastic Agent-based Signal Transduction Simulations2010In: Biomedical Imaging: From Nano to Macro, 2010 IEEE International Symposium on: From Nano to Macro (ISBI 2010), IEEE, 2010, p. 1301-1304Conference paper (Refereed)
    Abstract [en]

    Cellular signal transduction involves a transport step from the plasma membrane towards the nucleus, during which the signaling molecules are partly deactivated in control loops. This leads to a gradient in the concentration of active signaling molecules. The low number of molecules introduces spatio-temporal fluctuations and the asymmetric cellular architecture further increases the complexity. We propose a technique to represent this pattern in a continuous three-dimensional concentration map. The local concentration is computed and visualized with volume rendering techniques at interactive frame rates and is therefore well-suited for time-dependent data. Our approach allows the transition from the nano-scale of single and discrete signaling proteins to a continuous signal on the cell level. In the application context of this paper, we employ an agent-based Monte Carlo simulation to calculate the actual particle positions depending on reaction and transport parameters in the cell. The applicability of the proposed technique is demonstrated by an investigation of the effects of different transport parameters in Mitogen-activated protein kinase (MAPK) signaling.

  • 25366.
    Falk, Martin
    et al.
    VISUS - Visualization Research Center, Universität Stuttgart, Germany.
    Klann, Michael
    Institute of Biochemical Engineering and Center Systems Biology, Universität Stuttgart, Germany.
    Reuss, Matthias
    Institute of Biochemical Engineering and Center Systems Biology, Universität Stuttgart, Germany.
    Ertl, Thomas
    VISUS - Visualization Research Center, Universität Stuttgart, Germany.
    Visualization of Signal Transduction Processes in the Crowded Environment of the Cell2009In: IEEE Pacific Visualization Symposium (PacificVis 2009), 2009, p. 169-176Conference paper (Refereed)
    Abstract [en]

    In this paper, we propose a stochastic simulation to model and analyze cellular signal transduction. The high number of objects in a simulation requires advanced visualization techniques: first to handle the large data sets, second to support the human perception in the crowded environment, and third to provide an interactive exploration tool. To adjust the state of the cell to an external signal, a specific set of signaling molecules transports the information to the nucleus deep inside the cell. There, key molecules regulate gene expression. In contrast to continuous ODE models we model all signaling molecules individually in a more realistic crowded and disordered environment. Beyond spatiotemporal concentration profiles our data describes the process on a mesoscopic, molecular level, allowing a detailed view of intracellular events. In our proposed schematic visualization individual molecules, their tracks, or reactions can be selected and brought into focus to highlight the signal transduction pathway. Segmentation, depth cues and depth of field are applied to reduce the visual complexity. We also provide a virtual microscope to display images for comparison with wet lab experiments. The method is applied to distinguish different transport modes of MAPK (mitogen-activated protein kinase) signaling molecules in a cell. In addition, we simulate the diffusion of drug molecules through the extracellular space of a solid tumor and visualize the challenges in cancer related therapeutic drug delivery.

  • 25367.
    Falk, Martin
    et al.
    Visualization Research Center (VISUS), University of Stuttgart, Germany..
    Krone, Michael
    Visualization Research Center (VISUS), University of Stuttgart, Germany..
    Ertl, Thomas
    Visualization Research Center (VISUS), University of Stuttgart, Germany..
    Atomistic Visualization of Mesoscopic Whole-Cell Simulations2012In: VCBM 12: Eurographics Workshop on Visual Computing for Biology and Medicine / [ed] Timo Ropinski and Anders Ynnerman and Charl Botha and Jos Roerdink}, The Eurographics Association , 2012, Vol. 2, p. 123-130Conference paper (Refereed)
    Abstract [en]

    Molecular visualizations are a principal tool for analyzing the results of biochemical simulations. With modern GPU ray casting approaches it is only possible to render several millions of atoms at interactive frame rates unless advanced acceleration methods are employed. But even simplified cell models of whole-cell simulations consist of at least several billion atoms. However, many instances of only a few different proteins occur in the intracellular environment, which is beneficial in order to fit the data into the graphics memory. One model is stored for each protein species and rendered once per instance. The proposed method exploits recent algorithmic advances for particle rendering and the repetitive nature of intracellular proteins to visualize dynamic results from mesoscopic simulations of cellular transport processes. We present two out-of-core optimizations for the interactive visualization of data sets composed of billions of atoms as well as details on the data preparation and the employed rendering techniques. Furthermore, we apply advanced shading methods to improve the image quality including methods to enhance depth and shape perception besides non-photorealistic rendering methods.

  • 25368.
    Falk, Martin
    et al.
    Visualization Research Center (VISUS), University of Stuttgart, Germany.
    Krone, Michael
    Visualization Research Center (VISUS), University of Stuttgart, Germany.
    Ertl, Thomas
    Visualization Research Center (VISUS), University of Stuttgart, Germany.
    Atomistic Visualization of Mesoscopic Whole-Cell Simulations Using Ray-Casted Instancing2013In: Computer graphics forum (Print), ISSN 0167-7055, E-ISSN 1467-8659, Vol. 32, no 8, p. 195-206Article in journal (Refereed)
    Abstract [en]

    Molecular visualization is an important tool for analysing the results of biochemical simulations. With modern GPU ray casting approaches, it is only possible to render several million of atoms interactively unless advanced acceleration methods are employed. Whole-cell simulations consist of at least several billion atoms even for simplified cell models. However, many instances of only a few different proteins occur in the intracellular environment, which can be exploited to fit the data into the graphics memory. For each protein species, one model is stored and rendered once per instance. The proposed method exploits recent algorithmic advances for particle rendering and the repetitive nature of intracellular proteins to visualize dynamic results from mesoscopic simulations of cellular transport processes. We present two out-of-core optimizations for the interactive visualization of data sets composed of billions of atoms as well as details on the data preparation and the employed rendering techniques. Furthermore, we apply advanced shading methods to improve the image quality including methods to enhance depth and shape perception besides non-photorealistic rendering methods. We also show that the method can be used to render scenes that are composed of triangulated instances, not only implicit surfaces.

  • 25369.
    Falk, Martin
    et al.
    VISUS - Visualization Research Center, University of Stuttgart, Germany.
    Ott, Michael
    VISUS - Visualization Research Center, University of Stuttgart, Germany.
    Ertl, Thomas
    VISUS - Visualization Research Center, University of Stuttgart, Germany.
    Klann, Michael
    Automatic Control Laboratory, BISON Group, ETH Zürich,Switzerland.
    Koeppl, Heinz
    Automatic Control Laboratory, BISON Group, ETH Zürich,Switzerland.
    Parallelized Agent-based Simulation on CPU and Graphics Hardware for Spatial and Stochastic Models in Biology2011In: Proceedings of the 9th International Conference on Computational Methods in Systems Biology, CMSB'112011, ACM Press, 2011, p. 73-82Conference paper (Refereed)
    Abstract [en]

    The complexity of biological systems is enormous, even when considering a single cell where a multitude of highly parallel and intertwined processes take place on the molecular level. This paper focuses on the parallel simulation of signal transduction processes within a cell carried out solely on the graphics processing unit (GPU). Each signaling molecule is represented by an agent performing a discretetime continuous-space random walk to model its diffusion through the cell. Since the interactions and reactions between the agents can be competitive and are interdependent, we propose spatial partitioning for the reaction detection to overcome the data dependencies in the parallel execution of reactions. In addition, we present a simple way to simulate the Michaelis-Menten kinetics in our particle-based method using a per-particle delay. We apply this agent-based simulation to model signal transduction in the MAPK (Mitogen-Activated Protein Kinase) cascade both with and without cytoskeletal filaments. Finally, we compare the speed-up of our GPU simulation with a parallelized CPU version resulting in a twelvefold speedup.

  • 25370.
    Falk, Martin
    et al.
    VISUS – Visualization Research Center, Universitat Stuttgart, Germany .
    Schafhitzel, Tobias
    Graphical Systems, Institut VIS, Universitat Stuttgart, Germany .
    Weiskopf, Daniel
    VISUS – Visualization Research Center, Universitat Stuttgart, Germany .
    Ertl, Thomas
    Graphical Systems, Institut VIS, Universitat Stuttgart, Germany .
    Panorama maps with non-linear ray tracing2007In: GRAPHITE '07: Proceedings of the 5th international conference on Computer graphics and interactive techniques in Australia and Southeast Asia, ACM Digital Library, 2007, p. 9-16Conference paper (Refereed)
    Abstract [en]

    We present a framework for the interactive generation of 3D panorama maps. Our approach addresses the main issue that occurs during panorama map construction: non-linear projection or deformation of the terrain in order to minimize the occlusion of important information such as roads and trails. Traditionally, panorama maps are hand-drawn by skilled illustrators. In contrast, our approach provides computer support for the rendering of non-occluded views of 3D panorama maps, where deformations are modeled by nonlinear ray tracing. The deflection of rays is influenced by 2D and 3D force fields that directly consider the shape of the terrain. In addition, our framework allows the user to further modify the force fields to have fine control over the deformations of the panorama map. User interaction is facilitated by our real-time rendering system in terms of linked multiple views of both linear and non-linear projected terrain and the deformed view rays. Fast rendering is achieved by GPU-based non-linear ray tracing. We demonstrate the usefulness of our modeling and visualization method by several examples.

  • 25371.
    Falk, Martin
    et al.
    VISUS – Visualization Research Center, Universität Stuttgart.
    Seizinger, A.
    VISUS – Visualization Research Center, Universität Stuttgart.
    Sadlo, F.
    VISUS – Visualization Research Center, Universität Stuttgart.
    Üffinger, M.
    VISUS – Visualization Research Center, Universität Stuttgart.
    Weiskopf, D.
    VISUS – Visualization Research Center, Universität Stuttgart.
    Trajectory-Augmented Visualization of Lagrangian Coherent Structures in Unsteady Flow2010In: International Symposium on Flow Visualization (ISFV14), 2010Conference paper (Other academic)
    Abstract [en]

    The finite-time Lyapunov exponent (FTLE) field can be used for many purposes, from the analysis of the predictability in dynamical systems to the topological analysis of timedependent vector fields. In the topological context, the topic of this work, FTLE ridges represent Lagrangian coherent structures (LCS), a counterpart to separatrices in vector field topology. Since the explicit vector field behavior cannot be deduced from these representations, they may be augmented by line integral convolution patterns, a computational flow visualization counterpart to the surface oil flow method. This is, however, strictly meaningful only in stationary vector fields. Here, we propose an augmentation that visualizes the LCS-inducing flow behavior by means of complete trajectories but avoids occlusion and visual clutter. For this we exploit the FTLE for both the selection of significant trajectories as well as their individual representation. This results in 3D line representations for 2D vector fields by treating 2D time-dependent vector fields in 3D space-time. We present two variants of the approach, one easing the choice of the finite advection time for FTLE analysis and one for investigating the flow once the time is chosen.

  • 25372.
    Falk, Martin
    et al.
    Visualization Res. Center (VISUS), Univ. Stuttgart, Stuttgart.
    Weiskopf, Daniel
    Visualization Res. Center (VISUS), Univ. Stuttgart, Stuttgart.
    Output-Sensitive 3D Line Integral Convolution2008In: IEEE Transactions on Visualization and Computer Graphics, ISSN 1077-2626, E-ISSN 1941-0506, Vol. 14, no 4, p. 820-834Article in journal (Refereed)
    Abstract [en]

    We propose a largely output-sensitive visualization method for 3D line integral convolution (LIC) whose rendering speed is mainly independent of the data set size and mostly governed by the complexity of the output on the image plane. Our approach of view-dependent visualization tightly links the LIC generation with the volume rendering of the LIC result in order to avoid the computation of unnecessary LIC points: early-ray termination and empty-space leaping techniques are used to skip the computation of the LIC integral in a lazy-evaluation approach; both ray casting and texture slicing can be used as volume-rendering techniques. The input noise is modeled in object space to allow for temporal coherence under object and camera motion. Different noise models are discussed, covering dense representations based on filtered white noise all the way to sparse representations similar to oriented LIC. Aliasing artifacts are avoided by frequency control over the 3D noise and by employing a 3D variant of MlPmapping. A range of illumination models is applied to the LIC streamlines: different codimension-2 lighting models and a novel gradient-based illumination model that relies on precomputed gradients and does not require any direct calculation of gradients after the LIC integral is evaluated. We discuss the issue of proper sampling of the LIC and volume-rendering integrals by employing a frequency-space analysis of the noise model and the precomputed gradients. Finally, we demonstrate that our visualization approach lends itself to a fast graphics processing unit (GPU) implementation that supports both steady and unsteady flow. Therefore, this 3D LIC method allows users to interactively explore 3D flow by means of high-quality, view-dependent, and adaptive LIC volume visualization. Applications to flow visualization in combination with feature extraction and focus-and-context visualization are described, a comparison to previous methods is provided, and a detailed performance analysis is included.

  • 25373.
    Falk, Martin
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Ynnerman, Anders
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Treanor, Darren
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Leeds Teaching Hospitals NHS Trust, United Kingdom.
    Lundström, Claes
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Sectra, Linköping, Sweden.
    Interactive Visualization of 3D Histopathology in Native Resolution2019In: IEEE Transactions on Visualization and Computer Graphics, ISSN 1077-2626, E-ISSN 1941-0506, Vol. 25, no 1, p. 1008-1017Article in journal (Refereed)
    Abstract [en]

    We present a visualization application that enables effective interactive visual analysis of large-scale 3D histopathology, that is, high-resolution 3D microscopy data of human tissue. Clinical work flows and research based on pathology have, until now, largely been dominated by 2D imaging. As we will show in the paper, studying volumetric histology data will open up novel and useful opportunities for both research and clinical practice. Our starting point is the current lack of appropriate visualization tools in histopathology, which has been a limiting factor in the uptake of digital pathology. Visualization of 3D histology data does pose difficult challenges in several aspects. The full-color datasets are dense and large in scale, on the order of 100,000 x 100,000 x 100 voxels. This entails serious demands on both rendering performance and user experience design. Despite this, our developed application supports interactive study of 3D histology datasets at native resolution. Our application is based on tailoring and tuning of existing methods, system integration work, as well as a careful study of domain specific demands emanating from a close participatory design process with domain experts as team members. Results from a user evaluation employing the tool demonstrate a strong agreement among the 14 participating pathologists that 3D histopathology will be a valuable and enabling tool for their work.

  • 25374.
    Falk, Matilda
    et al.
    Linköping University, Department of Science and Technology, Communications and Transport Systems. Linköping University, The Institute of Technology.
    Hedkrok, Sabina
    Linköping University, Department of Science and Technology, Communications and Transport Systems. Linköping University, The Institute of Technology.
    Coordination of the information and material flow of lego products - A case study at Siemens Industrial Turbomachinery AB2015Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Studien betraktar informations- och materialflödet för legomaterial på Siemens Industrial Turbomachinery AB i Finspång. Det studerade problemet gäller att det finns en dålig uppfattning bland de anställda om hur flödet och arbetet med lego ser ut, samt dålig kommunikation mellan de inblandade avdelningarna. Genom intervjuer med ansvariga för legomaterialsamt granskning av tidigare dokument har legoflödet kunnat beskrivas. Problematiken på företaget har studerats utifrån teori kring processer och flöden samt kommunikation, integration och koordinering Rapporten presenterar en samordnad bild över arbetet med legomaterial genom en kartläggning med tillhörande flödesschema över informations- och materialflödet för lego inom företaget. I studien har problem med koordination och samarbetet mellan de inblandade avdelningarna identifierats. Rapporten följs upp med förslag på åtgärder och vidare arbete för att lösa problemen.

  • 25375.
    Falk, Oscar
    et al.
    Linköping University, Department of Management and Engineering, Business Administration. Linköping University, Faculty of Arts and Sciences.
    Svallingson, Gabriel
    Linköping University, Department of Management and Engineering, Business Administration. Linköping University, Faculty of Arts and Sciences.
    Att nå målkongruens inom detaljhandeln: En tvåfallstudie om hur organisationer med hög personalomsättning använder sig av incitamentsprogram för att nå målkongruens2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    An organization exists for individuals to work together and reach a common goal. In times of high personal turnover rate, it is a challenge for many organizations to achieve goal congruence and the purpose with this study is to examine how companies work to achieve goal congruence in line with increasing personal turnover rate with the aid of incentive plans.

    In the theoretical reference frame theories are described regarding the relationship between superior and subordinate, different types of incentive plans and motivational theories. To be able to answer the purpose of this essay, interviews have been conducted on two different companies in retail with individuals who works with incentive plans and a survey has been conducted in one of the companies© stores. The empirical result shows that the incentive plans are used in the researched organizations to achieve goal congruence, increase employee retention and improve the commitment with the employees. The results showed that incentive plans apply to reach different types of goals and that personal development was the primary motivational factor.

  • 25376.
    Falk, Pia
    et al.
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Olsson, Emil
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Implementation of an Image Quality Rating System2010Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    As the digital camera surveillance business expands, much eort is put into optimizing the quality of the captured images. There is a need for a image quality rating system when specifying and developing new cameras. This system can be used to compare new technology to old cameras as well as competitor cameras in order to locate the dierences. The rating should be based on technical measurements and resemble human perception of image quality.

    This thesis has focused on measuring and rating resolution and noise since these are important parts of perceived image quality. Images of a predetermined target (both stationary and rotating) were captured by the camera in three illuminations. An application was developed to facilitate input of the captured images as well as performing the required calculations. The application then returns one calculated image quality rating per illumination.

  • 25377.
    Falk, Stina
    et al.
    Linköping University, Department of Behavioural Sciences and Learning.
    Norén, Veronika
    Linköping University, Department of Behavioural Sciences and Learning.
    Utvecklingssamtal - en del av performance?2008Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    I denna kvalitativa studie har utvecklingssamtal och dess betydelse för performance undersökts. De frågeställningar som studien utgår ifrån rör hur chefer ser på utvecklingssamtal, vilka möjligheter och hinder som finns kopplade till dem, hur de kan utvecklas samt om det finns faktorer som kan ha betydelse för att påverka företagets strävan mot performance. För att besvara frågeställningarna intervjuades nio chefer och resultatet presenteras utifrån frågeställningarna.

    Utvecklingssamtal kopplat till performance var inte självklart för cheferna att resonera om, då många inte funderat kring detta tidigare. Det framkommer att samtliga chefer är positivt inställda till utvecklingssamtal. Cheferna ger också uttryck för olika möjligheter och hinder i utvecklingssamtalen. Det finns viss överensstämmelse mellan det undersökta företagets direktiv för utvecklingssamtal och chefernas hantering och syn på utvecklingssamtal. Dessutom menar de flesta av cheferna att den mall som är grundläggande för hur utvecklingssamtalen hålls på företaget har brister. Cheferna anser att det finns skillnader mellan produktionsarbetare och tjänstemän i flera aspekter gällande utvecklingssamtal.

    I analysen framkommer att det finns olika förutsättningar i utvecklingssamtalen utifrån tre faktorer; hantering, direktiv och kontext. Det finns förutsättningar som kan vara positiva för utvecklingssamtalens påverkan på performance och det förekommer även förutsättningar som kan innebära svårigheter för denna påverkan.

    Utifrån resultatet har två slutsatser framkommit. Den första är att utvecklingssamtalens förutsättningar kan verka avgörande för deras påverkan på performance. Den andra slutsatsen är att utvecklingssamtalen torde prioriteras utifrån ett mer långsiktigt perspektiv i organisationen för att de ska kunna ha betydelse för performance.

  • 25378.
    Falk, Stina
    et al.
    Linköping University, Department of Behavioural Sciences and Learning.
    Norén, Veronika
    Linköping University, Department of Behavioural Sciences and Learning.
    Vilken betydelse har en facklig organisation för intern rörlighet?2007Independent thesis Basic level (degree of Bachelor), 10 points / 15 hpStudent thesis
    Abstract [sv]

    Detta är en kvalitativ studie som fokuserar på en facklig organisations betydelse för intern rörlighet. Syftet är att bidra med kunskap om och studera vilken roll en facklig organisation har för intern rörlighet av personal inom en kommun.

    Frågeställningarna rör fackliga företrädares och medlemmar i den fackliga organisationens uppfattningar om hantering av intern rörlighet, samt den fackliga organisationens främjande eller försvårande av denna.

    För att besvara frågeställningarna utifrån den kvalitativa ansats som tillämpas har empiri insamlats genom intervjuer med fyra personer från varje aktörsgrupp vilket resulterade i att åtta intervjuer genomfördes.

    Resultatet presenteras i två delar, en för varje aktörsgrupp. Av resultatet framkommer att den fackliga organisationen på många sätt uppfattas främja intern rörlighet för medlemmarna inom kommunen genom sitt arbete med att underlätta förutsättningarna för intern rörlighet. Resultatet visar också att det finns möjligheter för den fackliga organisationen att inom vissa områden förbättra sitt främjande arbete för medlemmarnas interna rörlighet inom kommunen.

    Studien har två slutsatser. Den ena är att den fackliga organisationen måste prioritera intern rörlighet som arbetsområde inom hela organisationen. Den andra är att den fackliga organisationen endast har egentligt inflytande på negativ intern rörlighet.

  • 25379.
    Falk, Thomas
    Linköping University, The Institute of Technology. Linköping University, Department of Computer and Information Science, EISLAB - Economic Information Systems.
    Påverkar IT-investeringarna produktiviteten?2006In: Ekonomiska informationssystem: där ekonomi och IT möts / [ed] Fredrik Nilsson & Nils-Göran Olve, Lund: Studentlitteratur , 2006, p. 147-163Chapter in book (Other academic)
    Abstract [sv]

    Hur styr vi IT och hur tar vi vara på dess möjligheter? Boken sammanfattar tjugo års debatt om nyttan av IT och vad som behövs för att förverkliga den. Införande av nya system kan vara svårt nog. Men det är i regel förändringarna av verksamheten som är den stora utmaningen - och som har störst potential att skapa nytta.I snart 20 år har forskare vid EIS, ämnesområdet Ekonomiska informationssystem inom Institutionen för datavetenskap vid Linköpings universitet, studerat bl a strategisk ekonomistyrning och IT:s betydelse för nya organisationslösningar under ledning av Birger Rapp, Sveriges första professor i ämnet. Samspelet mellan IT-ansvariga och andra (linjechefer, controllers, affärsutvecklare m fl) är nyckeln till framgång och strategi, ansvar, styrning och ekonomi är nyckelord i de flesta bidrag i boken. Den vänder sig till studenter, forskare och praktiker - alla som vill ha en överskådlig sammanfattning av vad företag bör göra för att få god nytta av sina informationssystem. Bland praktiker är controllers och IT-ansvariga - i synnerhet de som deltar i strategiutveckling - särskilt viktiga målgrupper. I boken medverkar ytterligare elva forskare: Leif Appelgren, Lars Engwall, Thomas Falk, Göran Goldkuhl, Anna Moberg, Anders G. Nilsson, Jan Olhager, Tomas Ohlin, Carl-Johan Petri, Vivian Vimarlund och Alf Westelius.

  • 25380.
    Falk, Thomas
    et al.
    Linköping University, Department of Management and Engineering, Industrial Economics. Linköping University, Faculty of Science & Engineering.
    Petri, Carl-Johan
    Linköping University, Department of Management and Engineering, Industrial Economics. Linköping University, Faculty of Science & Engineering.
    Roy, Jan
    Mittuniversitetets forskningsgrupp Etour.
    Walldius, Åke
    Kungliga Tekniska högskolan, Stockholm.
    Att beskriva en organisations strategi som en karta2016In: Strategisk ekonomistyrning: med dialog i fokus / [ed] Fredrik Nilsson, Carl-Johan Petri, Alf Westelius, Lund: Studentlitteratur AB, 2016, p. 23-61Chapter in book (Other academic)
  • 25381.
    Falk, Thomas
    et al.
    Linköping University, Department of Management and Engineering, Industrial Economics. Linköping University, Faculty of Science & Engineering.
    Petri, Carl-Johan
    Linköping University, Department of Management and Engineering, Industrial Economics. Linköping University, Faculty of Science & Engineering.
    Roy, Jan
    Mitthögskolan, Sweden.
    Walldius, Åke
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Illustrating an organisation's strategy as a map2016In: Strategic management control: with focus on dialogue / [ed] Fredrik Nilsson, Carl-Johan Petri, Alf Westelius, Lund: Studentlitteratur, 2016, p. 27-65Chapter in book (Other academic)
  • 25382.
    Falk, Urban
    et al.
    Linköping University, Department of Management and Economics.
    Theding, Ebba
    Linköping University, Department of Management and Economics.
    Brands- invaluable assets?2001Independent thesis Advanced level (degree of Magister)Student thesis
    Abstract [en]

    Background: In order to make financially logical decisions it is important to know the real value of all assets in a company. Brands are intangible assets that are often said to be of great value in the context of mergers and acquisitions. Despite this fact, they are rarely given an exact financial figure.

    Purpose: The purpose of this paper is to investigate the significance and value of brands in M&A. By this we aim to contribute to the understanding of brands in the context of M&A and try to find out if brands are invaluable assets in both respects.

    Realisation: We have studied theoretical findings on the subject and thereafter made our own study of two cases of acquisitions; the acquistition of Candelia by Cloetta and that of NK Cityfastigheter by Hufvudstaden.

    Results: We have found that brands represent a real financial value to companies. Financial evaluations however seem to be of lesser importance in the context of M&A. In these situations it appears as if valuation of brands mainly serves as an arbitrary basis for negotiations. The question of the good fit between companies and other brands is seem to be the most important issue in M&A.

  • 25383.
    Falkcrona, Jerry
    Linköping University, Department of Electrical Engineering.
    Role-based access control and single sign-on for Web services2008Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Nowadays, the need for sharing information between different systems in a secure manner is common, not only in the corporate world but also in the military world. This information often resides at different locations, creating a distributed system. In order to share information in a secure manner in a distributed system, credentials are often used to attain authorization.

    This thesis examines how such a distributed system for sharing information can be realized, using the technology readily available today. Accounting to the results of this examination a basic system is implemented, after which the overall security of the system is evaluated. The thesis then presents possible extensions and improvements that can be done in future implementations.

    The result shows that dynamic roles do not easily integrate with a single sign-on system. Combining the two technologies leads to several synchronization issues, where some are non-trivial to solve.

  • 25384.
    Falke, Björn
    Linköping University, Department of Computer and Information Science. Linköping University, The Institute of Technology.
    Replacing a physical console with an iPad2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This thesis report presents an iPad application built for replacing a physical display console on an indoor exercise-bike. The paper attempts to answer whether it's possible to do this sort of replacement and what possible consequences it could have.

    The paper details the actual implementation and important design decisions such as Wi-Fi vs Bluetooth or iOS vs Android are discussed. The class structure and coding philosophy of the project are presented as well as choice of IDE and language.

    Part of the purpose behind replacing the old console is to improve the user experience. This papers describes in detail the user interface of the developed application as well as guidelines for how such an application should be constructed.

    The paper concludes that it is possible to replace the console on the EB200 exercise-bike with a tablet application and that it has the potential to be a superior solution.

  • 25385.
    Falkeborg, Rikard
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Löfberg, Johan
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Hansson, Anders
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Low-Rank Exploitation in Semidefinite Programming for Control2010In: Proceedings of Reglermöte 2010, 2010Conference paper (Other academic)
    Abstract [en]

    Many control related problems can be cast as semidefinite programs but, even though there exist polynomial time algorithms and good publicly available solvers, the time it takes to solve these problems can be long. Something many of these problems have in common, is that some of the variables enter as matrix valued variables. This leads to a low-rank structure in the basis matrices which can be exploited when forming the Newton equations. In this paper, we describe how this can be done, and show how our code can be used when using SDPT3. The idea behind this is old and is implemented in LMI Lab, but we show that when using a modern algorithm, the computational time can be reduced. Finally, we describe how the modeling language YALMIP is changed in such a way that our code can be interfaced using standard YALMIP commands, which greatly simplifies for the user.

  • 25386.
    Falkeborn, Rikard
    Linköping University, Department of Electrical Engineering.
    Evaluation of Differential Algebraic Elimination Methods for Deriving Consistency Relations from an Engine Model2006Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    New emission legislations introduced in the European Union and the U.S. have made truck manufacturers face stricter requirements for low emissions and on-board diagnostic systems. The on-board diagnostic system typically consists of several tests that are run when the truck is driving. One way to construct such tests is to use so called consistency relations. A consistency relation is a relation with known variables that in the fault free case always holds. Calculation of a consistency relation typically involves eliminating unknown variables from a set of equations.

    To eliminate variables from a differential polynomial system, methods from differential algebra can be used. In this thesis, the purely algebraic Gröbner basis algorithm and the differential Rosenfeld-Gröbner algorithm implemented in the Maple package Diffalg have been compared and evaluated. The conclusion drawn is that there are no significant differences between the methods. However, since using Gröbner basis requires differentiations to be made in advance, the recommendation is to use the Rosenfeld-Gröbner algorithm.

    Further, attempts to calculate consistency relations using the Rosenfeld-Gröbner algorithm have been made to a real application, a model of a Scania diesel engine. These attempts did not yield any successful results. It was only possible to calculate one consistency relation. This can be explained by the high complexity of the model.

  • 25387.
    Falkeborn, Rikard
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Structure Exploitation in Semidefinite Programming for Control2010Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Many control problems can be cast as semidefinite programs. However, since the size of these problems grow quite quickly, the computational time to solve them can be quite substantial. In order to reduce the computational time, many proposals of how to tailormake algorithms to various types of control problems can be found in the literature. In this thesis, two papers with similar ambitions are presented.

    The first paper deals with the case where the constraints of the optimization problem are of the type that stems from the Kalman-Yakubovic-Popov lemma, and where some of these constraints are so called complicating constraints. This means the optimization problem will be greatly simplified if these constraints were not present. By the use of Lagrangian relaxation, the optimization problem is decomposed into smaller ones, which can be solved independently of each other. Computational results show that for some classes of problems, this algorithm can reduce the computational time compared to using a solver which does not take into account the nature of the complicating constraints.

    In the second paper, the fact that many control-related semidefinite programs have matrix-valued variables is utilized to speed up computations. This implies that the corresponding basis matrices have a certain low-rank structure which can be exploited when formulating the equations for the search directions, something that was discovered in the 90s and is implemented in LMI Lab. However, much has happened in the area of semidefinite programming since the release of LMI Lab, and new, faster algorithms have been developed. However, the idea of using the lowrank structure in the basis matrices can still be used. We implement this, using the publicly available solver SDPT3 in combination with our code for formulating the system of equations for the search directions. In order to facilitate for potential users, we also describe how the modeling language YALMIP is changed so that this lowrank structure can be tracked, and how the code can be easily interfaced. Computational results show that the computational time is decreased.

    List of papers
    1. A Decomposition Algorithm for KYP-SDPs
    Open this publication in new window or tab >>A Decomposition Algorithm for KYP-SDPs
    2009 (English)In: Proceedings of the 10th European Control Conference (ECC), 2009, p. 3202-3207Conference paper, Published paper (Refereed)
    Abstract [en]

    In this paper, a structure exploiting algorithm for semidefinite programs derived from the Kalman-Yakubovich-Popov lemma, where some of the constraints appear as complicating constraints is presented. A decomposition algorithm is proposed, where the structure of the problem can be utilized. In a numerical example, where a controller that minimizes the sum of the H2-norm and the H-norm is designed, the algorithm is shown to be faster than SeDuMi and the special purpose solver KYPD.

    Keywords
    Optimization, Optimization Algorithms
    National Category
    Computational Mathematics Engineering and Technology Control Engineering
    Identifiers
    urn:nbn:se:liu:diva-21937 (URN)10.3166/EJC.18.249-256 (DOI)
    Conference
    10th European Control Conference (ECC), Budapest, Hungary, August, 2009
    Available from: 2009-10-07 Created: 2009-10-06 Last updated: 2013-10-09
    2. Low-Rank Exploitation in Semidefinite Programming for Control
    Open this publication in new window or tab >>Low-Rank Exploitation in Semidefinite Programming for Control
    2010 (English)Report (Other academic)
    Abstract [en]

    Many control related problems can be cast as semidefinite programs but, even though there exist polynomial time algorithms and good publicly available solvers, the time it takes to solve these problems can be long. Something many of these problems have in common, is that some of the variables enter as matrix valued variables. This leads to a low-rank structure in the basis matrices which can be exploited when forming the Newton equations. In this paper, we describe how this can be done, and show how our code can be used when using SDPT3. The idea behind this is old and is implemented in LMI Lab, but we show that when using a modern algorithm, the computational time can be reduced. Finally, we describe how the modeling language YALMIP is changed in such a way that our code can be interfaced using standard YALMIP commands, which greatly simplifies for the user.

    Place, publisher, year, edition, pages
    Linköping: Linköping University Electronic Press, 2010. p. 7
    Series
    LiTH-ISY-R, ISSN 1400-3902 ; 2927
    Keywords
    Semidefinite programming, Structure exploitation, Mathematical programming, Matrix algebra
    National Category
    Control Engineering
    Identifiers
    urn:nbn:se:liu:diva-56215 (URN)LiTH-ISY-R-2927 (ISRN)
    Available from: 2010-04-30 Created: 2010-04-30 Last updated: 2014-06-19Bibliographically approved
  • 25388.
    Falkeborn, Rikard
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Hansson, Anders
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    A Decomposition Algorithm for KYP-SDPs2009In: Proceedings of the 10th European Control Conference (ECC), 2009, p. 3202-3207Conference paper (Refereed)
    Abstract [en]

    In this paper, a structure exploiting algorithm for semidefinite programs derived from the Kalman-Yakubovich-Popov lemma, where some of the constraints appear as complicating constraints is presented. A decomposition algorithm is proposed, where the structure of the problem can be utilized. In a numerical example, where a controller that minimizes the sum of the H2-norm and the H-norm is designed, the algorithm is shown to be faster than SeDuMi and the special purpose solver KYPD.

  • 25389.
    Falkeborn, Rikard
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Hansson, Anders
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    A Decomposition Algorithm for KYP-SDPs2009Report (Other academic)
    Abstract [en]

    In this paper, a structure exploiting algorithm for semidefinite programs derived from the Kalman-Yakubovich-Popov lemma, where some of the constraints appear as complicating constraints is presented. A decomposition algorithm is proposed, where the structure of the problem can be utilized. In a numerical example, where a controller that minimizes the sum of the H2-norm and the H-norm is designed, the algorithm is shown to be faster than SeDuMi and the special purpose solver KYPD.

  • 25390.
    Falkeborn, Rikard
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Hansson, Anders
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    A Decomposition Algorithm for KYP-SDPs2012In: European Journal of Control, ISSN 0947-3580, E-ISSN 1435-5671, Vol. 18, no 3, p. 249-256Article in journal (Refereed)
    Abstract [en]

    In this paper, a structure exploiting algorithm for semidefinite programs derived from the Kalmatz-Yakubovich-Popov lemma, where some of the constraints appear as complicating constraints is presented. A decomposition algorithm is proposed, where the structure of the problem can be utilized. In a numerical example, where a controller that minimizes the stun of the H-2-norm and the H-infinity-norm is designed, the algorithm, is shown to be faster than SeDuMi and the special purpose solver KYPD.

  • 25391.
    Falkeborn, Rikard
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Löfberg, Johan
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Hansson, Anders
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Low-Rank Exploitation in Semidefinite Programming for Control2010In: Proceedings of the 2010 IEEE International Symposium on Computer-Aided Control System Design, 2010, p. 24-28Conference paper (Refereed)
    Abstract [en]

    Many control related problems can be cast as semidefinite programs but, even though there exist polynomial time algorithms and good publicly available solvers, the time it takes to solve these problems can be long. Something many of these problems have in common, is that some of the variables enter as matrix valued variables. This leads to a low-rank structure in the basis matrices which can be exploited when forming the Newton equations. In this paper, we describe how this can be done, and show how our code can be used when using SDPT3. The idea behind this is old and is implemented in LMI Lab, but we show that when using a modern algorithm, the computational time can be reduced. Finally, we describe how the modeling language YALMIP is changed in such a way that our code can be interfaced using standard YALMIP commands, which greatly simplifies for the user.

  • 25392.
    Falkeborn, Rikard
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Löfberg, Johan
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Hansson, Anders
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Low-Rank Exploitation in Semidefinite Programming for Control2010Report (Other academic)
    Abstract [en]

    Many control related problems can be cast as semidefinite programs but, even though there exist polynomial time algorithms and good publicly available solvers, the time it takes to solve these problems can be long. Something many of these problems have in common, is that some of the variables enter as matrix valued variables. This leads to a low-rank structure in the basis matrices which can be exploited when forming the Newton equations. In this paper, we describe how this can be done, and show how our code can be used when using SDPT3. The idea behind this is old and is implemented in LMI Lab, but we show that when using a modern algorithm, the computational time can be reduced. Finally, we describe how the modeling language YALMIP is changed in such a way that our code can be interfaced using standard YALMIP commands, which greatly simplifies for the user.

  • 25393.
    Falkeborn, Rikard
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Löfberg, Johan
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Hansson, Anders
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Low-Rank Exploitation in Semidefinite Programming for Control2011In: International Journal of Control, ISSN 0020-7179, E-ISSN 1366-5820, Vol. 84, no 12, p. 1975-1982Article in journal (Refereed)
    Abstract [en]

    Many control-related problems can be cast as semidefinite programs. Even though there exist polynomial time algorithms and excellent publicly available solvers, the time it takes to solve these problems can be excessive. What many of these problems have in common, in particular in control, is that some of the variables enter as matrix-valued variables. This leads to a low-rank structure in the basis matrices which can be exploited when forming the Newton equations. In this article, we describe how this can be done, and show how our code, called STRUL, can be used in conjunction with the semidefinite programming solver SDPT3. The idea behind the structure exploitation is classical and is implemented in LMI Lab, but we show that when using a modern semidefinite programming framework such as SDPT3, the computational time can be significantly reduced. Finally, we describe how the modelling language YALMIP has been changed in such a way that our code, which can be freely downloaded, can be interfaced using standard YALMIP commands. This greatly simplifies modelling and usage.

  • 25394.
    Falkeborn, Tina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Nasal vaccination using novel mucosal adjuvants: with main focus on influenza A virus2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Influenza viruses have sporadically caused pandemics during the last century, with the most severe occurring in 1918 when the “Spanish flu”, an A/H1N1 influenza virus, passed around the globe killing about 20-100 million people. Today 250 000-500 000 deaths occur annually due to influenza virus or secondary infection after influenza, e.g. pneumonia. Influenza viruses cause severe infections in susceptible age groups like children and elderly and in individuals with impaired immune response due to other medical conditions. The best way to prevent an influenza epidemic is by vaccination. Since the 1950´s we have vaccines against seasonal flu, but vaccine efficacy is not 100 % and there is a need to develop better and more effective vaccines, especially for the risk groups. Since the virus enters the host through the nasal cavity, nasal vaccination is a good approach. By stimulating a mucosal immune response already in the nasal cavity, the goal with nasal vaccination is to stop the virus before it enters the host. Nasal vaccination also reduces the risk of transmission of blood-borne diseases, and is less painful and easier to administer, compared to injectable vaccines.

    In order to be able to use less immunogenic antigens, like split and subunit antigens, as nasal vaccine components, an adjuvant is needed to enhance the immune response. At the moment there is no licensed mucosal adjuvant for human use. Several studies are ongoing, but it is a complicated and long way to reach the market. In this thesis nasal vaccination with influenza antigen together with the mucosal adjuvant Endocine™ and other mucosal adjuvants has been evaluated. The Endocine™ adjuvant has been shown to be safe and well tolerated in clinical trials. Depending on the pathogen of interest, different approaches are necessary. For HIV, DNA-vaccination has been evaluated together with a plasmid encoding Salmonella typhimurium flagellin C and the mucosal adjuvant N3. The results found in paper I-IV show that by adding adjuvant to the antigen enhances the protective immune response towards the antigen. Enhanced systemic, mucosal and cell-mediated immunity were observed. Hopefully in the future these adjuvants evaluated in this thesis, will be used in vaccines for humans.

    List of papers
    1. Endocine™, N3OA and N3OASq; Three Mucosal Adjuvants That Enhance the Immune Response to Nasal Influenza Vaccination
    Open this publication in new window or tab >>Endocine™, N3OA and N3OASq; Three Mucosal Adjuvants That Enhance the Immune Response to Nasal Influenza Vaccination
    Show others...
    2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8Article in journal (Refereed) Published
    Abstract [en]

    Annual outbreaks of seasonal influenza are controlled or prevented through vaccination in many countries. The seasonal vaccines used are either inactivated, currently administered parenterally, or live-attenuated given intranasally. In this study three mucosal adjuvants were examined for the influence on the humoral (mucosal and systemic) and cellular influenza A-specific immune responses induced by a nasally administered vaccine. We investigated in detail how the anionic Endocine™ and the cationic adjuvants N3OA and N3OASq mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses as compared to the vaccine alone after intranasal immunization. The study showed that nasal administration of a split virus vaccine together with Endocine™ or N3OA induced significantly higher humoral and cell-mediated immune responses than the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated immune response. Furthermore, nasal administration of the influenza vaccine in combination with any of the adjuvants; Endocine™, N3OA or N3OASq, significantly enhanced the mucosal immunity against influenza HA protein. Thus the addition of these mucosal adjuvants leads to enhanced immunity in the most relevant tissues, the upper respiratory tract and the systemic circulation. Nasal influenza vaccination with an inactivated split vaccine can therefore provide an important mucosal immune response, which is often low or absent after traditional parenteral vaccination.

    Place, publisher, year, edition, pages
    Public Library of Science, 2013
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-97667 (URN)10.1371/journal.pone.0070527 (DOI)000323124000019 ()
    Note

    Funding Agencies|Eurocine Vaccines||Vinnova Research funds||Halsofonden||

    Available from: 2013-09-19 Created: 2013-09-19 Last updated: 2017-12-06
    2. DNA-Encoded Flagellin Activates Toll-Like Receptor 5 (TLR5), Nod-like Receptor Family CARD Domain-Containing Protein 4 (NRLC4), and Acts as an Epidermal, Systemic, and Mucosal-Adjuvant
    Open this publication in new window or tab >>DNA-Encoded Flagellin Activates Toll-Like Receptor 5 (TLR5), Nod-like Receptor Family CARD Domain-Containing Protein 4 (NRLC4), and Acts as an Epidermal, Systemic, and Mucosal-Adjuvant
    Show others...
    2013 (English)In: Vaccines, ISSN 2076-393X, Vol. 1, no 4, p. 415-443Article in journal (Refereed) Published
    Abstract [en]

    Eliciting effective immune responses using non-living/replicating DNA vaccines is a significant challenge. We have previously shown that ballistic dermal plasmid DNA-encoded flagellin (FliC) promotes humoral as well as cellular immunity to co-delivered antigens. Here, we observe that a plasmid encoding secreted FliC (pFliC(-gly)) produces flagellin capable of activating two innate immune receptors known to detect flagellin; Toll-like Receptor 5 (TLR5) and Nod-like Receptor family CARD domain-containing protein 4 (NRLC4). To test the ability of pFliC(-gly) to act as an adjuvant we immunized mice with plasmid encoding secreted FliC (pFliC(-gly)) and plasmid encoding a model antigen (ovalbumin) by three different immunization routes representative of dermal, systemic, and mucosal tissues. By all three routes we observed increases in antigen-specific antibodies in serum as well as MHC Class I-dependent cellular immune responses when pFliC(-gly) adjuvant was added. Additionally, we were able to induce mucosal antibody responses and Class II-dependent cellular immune responses after mucosal vaccination with pFliC(-gly). Humoral immune responses elicited by heterologus prime-boost immunization with a plasmid encoding HIV-1 from gp160 followed by protein boosting could be enhanced by use of pFliC(-gly). We also observed enhancement of cross-clade reactive IgA as well as a broadening of B cell epitope reactivity. These observations indicate that plasmid-encoded secreted flagellin can activate multiple innate immune responses and function as an adjuvant to non-living/replicating DNA immunizations. Moreover, the capacity to elicit mucosal immune responses, in addition to dermal and systemic properties, demonstrates the potential of flagellin to be used with vaccines designed to be delivered by various routes.

    Place, publisher, year, edition, pages
    Basel, Switzerland: MDPI AG, 2013
    Keywords
    adaptive immunity; DNA adjuvant; flagellin; NLRC4; TLR5
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-99352 (URN)10.3390/vaccines1040415 (DOI)
    Available from: 2013-10-16 Created: 2013-10-16 Last updated: 2015-05-19Bibliographically approved
    3. Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants: cholera toxin and alum
    Open this publication in new window or tab >>Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants: cholera toxin and alum
    Show others...
    2015 (English)In: Jacobs Journal of Vaccine and Vaccination, ISSN 2381-2664, Vol. 1, no 1, article id 006Article in journal (Refereed) Published
    Abstract [en]

    To enable efficient mucosal vaccination with split or subunit antigens, an adjuvant is often needed. To date, no mucosal adjuvants are approved for human use, however, there are a variety of mucosal adjuvants in development, including the liposome-based adjuvant Endocine™. The aim of this study was to evaluate split influenza antigens together with Endocine™ and in order to assess the potency of Endocine™, the induction of humoral immune responses were compared to those following influenza vaccination with cholera toxin (CT) or aluminum salt (alum). We show that Endocine™ significantly enhances influenza-specific immune responses in intranasally immunized mice compared to nonadjuvanted vaccine. Furthermore, vaccines adjuvanted with Endocine™ evoked comparable serum IgG and virus neutralizing (VN) antibody titers as nasal vaccines adjuvanted with CT. Compared to parenteral vaccination with alum, Endocine™ triggered significantly higher mucosal and serum IgA titers, and similar VN titers. Taken together, these results support further development of Endocine™ as a mucosal adjuvant and as part of a nasal influenza vaccine candidate.

    Place, publisher, year, edition, pages
    Jacobs Publishers, 2015
    Keywords
    Mucosal adjuvant; nasal immunization; vaccine; Endocine; influenza; neutralizing antibodies
    National Category
    Clinical Laboratory Medicine Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-117979 (URN)
    Available from: 2015-05-19 Created: 2015-05-19 Last updated: 2018-01-11Bibliographically approved
    4. The mucosal adjuvant 1 Endocine™ increases immune responses to influenza antigen in aged mice
    Open this publication in new window or tab >>The mucosal adjuvant 1 Endocine™ increases immune responses to influenza antigen in aged mice
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    More effective influenza vaccines for the elderly population is needed. The vaccines used today are less effective in elderly compared to in adults. It is more difficult to stimulate a protective immune response in elderly due to immunosenescence. Elderly people have a decline in both humoral and cell mediated immunity, which make them more susceptible to viral infections. The aim of this study was to evaluate the mucosal adjuvant Endocine™ together with split influenza antigen in different ages of BALB/c mice (15, 20 and 25 months old). The results from this study show that a nasal influenza vaccine  formulated with Endocine™ enhanced both systemic and mucosal immune responses compared to an unadjuvanted vaccine delivered subcutaneously or intra nasal in aged mice. However, in the 25 months old mice only a very modest immune response was detected. Although the influenza-specific immune responses in aged mice were not induced to the same levels as achieved in young mice, the results show that nasal vaccine formulated with Endocine™ could provide benefits for the elderly.

    National Category
    Clinical Laboratory Medicine Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-117980 (URN)
    Available from: 2015-05-19 Created: 2015-05-19 Last updated: 2018-01-11Bibliographically approved
  • 25395.
    Falkeborn, Tina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Asahara, Naomi
    Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Japan.
    Hayashi, Masayuki
    Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Japan.
    Arai, Masaaki
    Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Japan.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Maltais, Anna-Karin
    Eurocine Vaccines AB, Karolinska Institutet Science Park, Solna, Sweden.
    Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants: cholera toxin and alum2015In: Jacobs Journal of Vaccine and Vaccination, ISSN 2381-2664, Vol. 1, no 1, article id 006Article in journal (Refereed)
    Abstract [en]

    To enable efficient mucosal vaccination with split or subunit antigens, an adjuvant is often needed. To date, no mucosal adjuvants are approved for human use, however, there are a variety of mucosal adjuvants in development, including the liposome-based adjuvant Endocine™. The aim of this study was to evaluate split influenza antigens together with Endocine™ and in order to assess the potency of Endocine™, the induction of humoral immune responses were compared to those following influenza vaccination with cholera toxin (CT) or aluminum salt (alum). We show that Endocine™ significantly enhances influenza-specific immune responses in intranasally immunized mice compared to nonadjuvanted vaccine. Furthermore, vaccines adjuvanted with Endocine™ evoked comparable serum IgG and virus neutralizing (VN) antibody titers as nasal vaccines adjuvanted with CT. Compared to parenteral vaccination with alum, Endocine™ triggered significantly higher mucosal and serum IgA titers, and similar VN titers. Taken together, these results support further development of Endocine™ as a mucosal adjuvant and as part of a nasal influenza vaccine candidate.

  • 25396.
    Falkeborn, Tina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Brave, Andreas
    Swedish Institute Communicable Disease Control SMI, Sweden.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Åkerlind, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Microbiology.
    Schroder, Ulf
    Eurocine Vaccines AB, Sweden.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Endocine™, N3OA and N3OASq; Three Mucosal Adjuvants That Enhance the Immune Response to Nasal Influenza Vaccination2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8Article in journal (Refereed)
    Abstract [en]

    Annual outbreaks of seasonal influenza are controlled or prevented through vaccination in many countries. The seasonal vaccines used are either inactivated, currently administered parenterally, or live-attenuated given intranasally. In this study three mucosal adjuvants were examined for the influence on the humoral (mucosal and systemic) and cellular influenza A-specific immune responses induced by a nasally administered vaccine. We investigated in detail how the anionic Endocine™ and the cationic adjuvants N3OA and N3OASq mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses as compared to the vaccine alone after intranasal immunization. The study showed that nasal administration of a split virus vaccine together with Endocine™ or N3OA induced significantly higher humoral and cell-mediated immune responses than the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated immune response. Furthermore, nasal administration of the influenza vaccine in combination with any of the adjuvants; Endocine™, N3OA or N3OASq, significantly enhanced the mucosal immunity against influenza HA protein. Thus the addition of these mucosal adjuvants leads to enhanced immunity in the most relevant tissues, the upper respiratory tract and the systemic circulation. Nasal influenza vaccination with an inactivated split vaccine can therefore provide an important mucosal immune response, which is often low or absent after traditional parenteral vaccination.

  • 25397.
    Falkeborn, Tina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Lindberg, Alf
    Eurocine Vaccines AB, Karolinska Institutet Science Park, Solna, Sweden.
    Maltais, Anna-Karin
    Eurocine Vaccines AB, Karolinska Institutet Science Park, Solna, Sweden.
    The mucosal adjuvant 1 Endocine™ increases immune responses to influenza antigen in aged miceManuscript (preprint) (Other academic)
    Abstract [en]

    More effective influenza vaccines for the elderly population is needed. The vaccines used today are less effective in elderly compared to in adults. It is more difficult to stimulate a protective immune response in elderly due to immunosenescence. Elderly people have a decline in both humoral and cell mediated immunity, which make them more susceptible to viral infections. The aim of this study was to evaluate the mucosal adjuvant Endocine™ together with split influenza antigen in different ages of BALB/c mice (15, 20 and 25 months old). The results from this study show that a nasal influenza vaccine  formulated with Endocine™ enhanced both systemic and mucosal immune responses compared to an unadjuvanted vaccine delivered subcutaneously or intra nasal in aged mice. However, in the 25 months old mice only a very modest immune response was detected. Although the influenza-specific immune responses in aged mice were not induced to the same levels as achieved in young mice, the results show that nasal vaccine formulated with Endocine™ could provide benefits for the elderly.

  • 25398.
    Falkeborn, Tina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Olliver, Marie
    Karolinska Institute, Sweden.
    Lindberg, Alf
    Karolinska Institute, Sweden.
    Maltais, Anna-Karin
    Karolinska Institute, Sweden.
    The intranasal adjuvant Endocine((TM)) enhances both systemic and mucosal immune responses in aged mice immunized with influenza antigen2017In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 14, article id 44Article in journal (Refereed)
    Abstract [en]

    Despite availability of annual influenza vaccines, influenza causes significant morbidity and mortality in the elderly. This is at least in part a result of immunosenescence; the age-dependent decrease in immunological competence that results in greater susceptibility to infections and reduced responses to vaccination. To improve protective immune responses in this age group, new vaccines strategies, such as the use of adjuvants, are needed. Here, we evaluated the mucosal vaccine adjuvant Endocine(TM), formulated with split influenza antigen and administered intranasally in aged (20-month old) mice. Humoral immune responses were assessed and compared to unadjuvanted intranasal and subcutaneous vaccines. We show that formulation with Endocine(TM) significantly enhances hemagglutination inhibition (HI) titers, as well as serum IgG and mucosal IgA antibody titers, compared to both types of unadjuvanted vaccines. Thus, our results indicate that intranasal vaccination with Endocine(TM) is a possible approach for the development of mucosal influenza vaccines for the elderly.

  • 25399.
    Falkeholm, L
    et al.
    Vrinnevi Hosp, Pathol & Cytol Lab, Norrkoping, Sweden Linkoping Univ, Fac Hlth Sci, Div Environm & Occupat Med, Linkoping, Sweden Ryhov Hosp, Dept Pathol, Jonkoping, Sweden.
    Grant, CA
    Vrinnevi Hosp, Pathol & Cytol Lab, Norrkoping, Sweden Linkoping Univ, Fac Hlth Sci, Div Environm & Occupat Med, Linkoping, Sweden Ryhov Hosp, Dept Pathol, Jonkoping, Sweden.
    Magnusson, A
    Moller, E
    Vrinnevi Hosp, Pathol & Cytol Lab, Norrkoping, Sweden Linkoping Univ, Fac Hlth Sci, Div Environm & Occupat Med, Linkoping, Sweden Ryhov Hosp, Dept Pathol, Jonkoping, Sweden.
    Xylene-free method for histological preparation: A multicentre evaluation2001In: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 81, no 9, p. 1213-1221Article in journal (Refereed)
    Abstract [en]

    The backbone of daily pathological diagnostic work is the paraffin section. Paraffin sections are still prepared by methods largely unchanged for over 150 years. A xylene-free method has been developed that excludes xylene, not only as the intermediate step before the paraffin baths, but also for deparaffinizing of the cut sections, which also eliminates the need for rehydration and dehydration for the staining and mounting steps. Elimination of xylene from tissue processing cuts costs, saves time, and improves the laboratory environment. Experience with xylene-free sections since 1995 at the Vrinnevi Hospital is favorable. Our opinion is that the xylene-free sections are equivalent to conventionally processed sections. To test this hypothesis, nine pathologists from three hospitals participated in an evaluation trial. Paired tissue blocks from 10 consecutively submitted samples each of breast, intestine, and skin were processed by either the xylene-free or the conventional method. Sections from each block were deparaffinized and stained with hematoxylin-eosin (H&E), with periodic acid-Schiff (PAS), and with van Gieson's method. A randomized mix of 180 sections (10 samples x 3 tissues x 3 stains x 2) gave 90 matched pairs. Each section was blindly examined and scored by nine pathologists to give 810 paired observations for statistical evaluation. The xylene-free sections were ranked as good as or better than their conventional counterparts in 74% of the comparisons, and poorer in 26%. The major discriminating factor was the staining method. H&E and PAS sections were equivalent. The xylene-free van Gieson sections, cut from the same blocks and randomly assigned to this stain, tended to be downgraded. This could be traced to a faulty stain solution used for this batch. The overall results have demonstrated professional acceptance for the xylene-free method of processing histological sections.

  • 25400.
    Falkenberg, Melcher
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice.
    Avoiding lower leg amputation. Diabetes in the new millenium.2000In: Proceedings Fourth International Conference St Vincent Declaration Primary care Diabetes Goup Prague, october 13&14 2000,2000, St Vincent Declaration Primary Care Diabetes Group , 2000, p. 21-22Conference paper (Refereed)
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