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  • 1.
    Aare, Magnus
    et al.
    KTH, School of Technology and Health (STH), Neuronic Engineering (Closed 20130701).
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Neuronic Engineering (Closed 20130701).
    Evaluation of head response to ballistic helmet impacts, using FEM2003Conference paper (Refereed)
  • 2.
    Aare, Magnus
    et al.
    KTH, School of Technology and Health (STH), Neuronic Engineering (Closed 20130701).
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Neuronic Engineering (Closed 20130701).
    Halldin, Peter
    KTH, School of Technology and Health (STH), Neuronic Engineering (Closed 20130701).
    Proposed global injury thresholds for oblique helmet impacts2003Conference paper (Refereed)
  • 3.
    Abedan Kondori, Farid
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Yousefi, Shahrouz
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Liu, Li
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Active human gesture capture for diagnosing and treating movement disorders2013Conference paper (Other academic)
    Abstract [en]

    Movement disorders prevent many people fromenjoying their daily lives. As with other diseases, diagnosisand analysis are key issues in treating such disorders.Computer vision-based motion capture systems are helpfultools for accomplishing this task. However Classical motiontracking systems suffer from several limitations. First theyare not cost effective. Second these systems cannot detectminute motions accurately. Finally they are spatially limitedto the lab environment where the system is installed. In thisproject, we propose an innovative solution to solve the abovementionedissues. Mounting the camera on human body, webuild a convenient, low cost motion capture system that canbe used by the patient in daily-life activities. We refer tothis system as active motion capture, which is not confinedto the lab environment. Real-time experiments in our labrevealed the robustness and accuracy of the system.

  • 4.
    Abtahi, Farhad
    KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems.
    Towards Heart Rate Variability Tools in P-Health: Pervasive, Preventive, Predictive and Personalized2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Heart rate variability (HRV) has received much attention lately. It has been shown that HRV can be used to monitor the autonomic nervous system and to detect autonomic dysfunction, especially vagal dysfunction. Reduced HRV is associated with several diseases and has also been suggested as a predictor of poor outcomes and sudden cardiac death. HRV is, however, not yet widely accepted as a clinical tool and is mostly used for research. Advances in neuroimmunity with an improved understanding of the link between the nervous and immune systems have opened a new potential arena for HRV applications. An example is when systemic inflammation and autoimmune disease are primarily caused by low vagal activity; it can be detected and prognosticated by reduced HRV. This thesis is the result of several technical development steps and exploratory research where HRV is applied as a prognostic diagnostic tool with preventive potential. The main objectives were 1) to develop an affordable tool for the effective analysis of HRV, 2) to study the correlation between HRV and pro-inflammatory markers and the potential degree of activity in the cholinergic anti-inflammatory pathway, and 3) to develop a biofeedback application intended for support of personal capability to increase the vagal activity as reflected in increased HRV. Written as a compilation thesis, the methodology and the results of each study are presented in each appended paper. In the thesis frame/summary chapter, a summary of each of the included papers is presented, grouped by topic and with their connections. The summary of the results shows that the developed tools may accurately register and properly analyse and potentially influence HRV through the designed biofeedback game. HRV can be used as a prognostic tool, not just in traditional healthcare with a focus on illness but also in wellness. By using these tools for the early detection of decreased HRV, prompt intervention may be possible, enabling the prevention of disease. Gamification and serious gaming is a potential platform to motivate people to follow a routine of exercise that might, through biofeedback, improve HRV and thereby health.

  • 5.
    Abtahi, Farhad
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems. Karolinska Institutet, Sweden.
    Hilderman, Marie
    Bruchfeld, Annette
    Seoane, Fernando
    KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems. University of Borås, Sweden.
    Janerot-Sjöberg, Birgitta
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden.
    Lindecrantz, Kaj
    KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems. Karolinska Institutet, Sweden.
    Pro-inflammatory Blood Markers and Heart Rate Variability in Apnoea as a Reflection of Basal Vagal ToneManuscript (preprint) (Other academic)
    Abstract [en]

    Pro-inflammatory cytokines play a crucial role in inflammatory response, which istightly regulated by the nervous system to avoid the damage caused by inflammation. There isevidence for a cholinergic anti-inflammatory pathway that includes afferent and efferent vagalnerves that sense the inflammation and stimulate the anti-inflammatory response. Non-functionalanti-inflammatory response might lead to excessive and chronic inflammation e.g., rheumatoidarthritis (RA), inflammatory bowel disease (IBD), and poor outcome. Heart rate variability(HRV) has been proposed as a potential tool to monitor the level of anti-inflammatory activitythrough the monitoring of vagal activity. In this paper, the association of pro-inflammatorymarkers with HRV indices is evaluated. We used a database called “Heart Biomarker Evaluationin Apnea Treatment (HeartBEAT)” that consists of 6±2 hours of Electrocardiogram (ECG)recordings during nocturnal sleep from 318 patients at baseline and 301of them at 3 monthsfollow-up. HRV indices are calculated from ECG recordings of 5-360 minutes. The results showa statistically significant correlation between heart rate (HR) and pro-inflammatory cytokines,independent of duration of ECG analysis. HRV indices e.g., standard deviation of all RRintervals (SDNN) show an inverse relation to the pro-inflammatory cytokines. Longer ECGrecordings show a higher potential to reflect the level of anti-inflammatory response. In light oftheories for the cholinergic anti-inflammatory pathway, a combination of HR and HRV as areflection of basal vagal activity might be a potential prognostic tool for interventional guidance.

  • 6.
    Abtahi, Farhad
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems.
    Seoane, Fernando
    KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems.
    Lindecrantz, Kaj
    KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems.
    Löfgren, Nils
    Elimination of ECG Artefacts in Foetal EEG Using Ensemble Average Subtraction and Wavelet Denoising Methods: A Simulation2014In: XIII Mediterranean Conference on Medical and Biological Engineering and Computing 2013, Springer, 2014, 551-554 p.Conference paper (Refereed)
    Abstract [en]

    Biological signals recorded from surface electrodes contain interference from other signals which are not desired and should be considered as noise. Heart activity is especially present in EEG and EMG recordings as a noise. In this work, two ECG elimination methods are implemented; ensemble average subtraction (EAS) and wavelet denoising methods. Comparison of these methods has been done by use of simulated signals achieved by adding ECG to neonates EEG. The result shows successful elimination of ECG artifacts by using both methods. In general EAS method which remove estimate of all ECG components from signal is more trustable but it is also harder for implementation due to sensitivity to noise. It is also concluded that EAS behaves like a high-pass filter while wavelet denoising method acts as low-pass filter and hence the choice of one method depends on application.

  • 7.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bélteky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Brain size is reduced by selectionfor tameness in Red Junglefowl–correlated effects in vital organs2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 3306Article in journal (Refereed)
    Abstract [en]

    During domestication animals have undergone changes in size of brain and other vital organs. We hypothesize that this could be a correlated effect to increased tameness. Red Junglefowl (ancestors of domestic chickens) were selected for divergent levels of fear of humans for five generations. The parental (P0) and the fifth selected generation (S5) were culled when 48–54 weeks old and the brains were weighed before being divided into telencephalon, cerebellum, mid brain and optic lobes. Each single brain part as well as the liver, spleen, heart and testicles were also weighed. Brains of S5 birds with high fear scores (S5 high) were heavier both in absolute terms and when corrected for body weight. The relative weight of telencephalon (% of brain weight) was significantly higher in S5 high and relative weight of cerebellum was lower. Heart, liver, testes and spleen were all relatively heavier (% of body weight) in S5 high. Hence, selection for tameness has changed the size of the brain and other vital organs in this population and may have driven the domesticated phenotype as a correlated response.

  • 8.
    Ahlström, Christer
    et al.
    Swedish National Road and Transport Research Institute, Traffic and road users, Human-vehicle-transport system interaction.
    Dukic, Tania
    Swedish National Road and Transport Research Institute, Traffic and road users, Human-vehicle-transport system interaction.
    Comparison of eye tracking systems with one and three cameras2011In: ACM International Conference Proceeding Series, 2011Conference paper (Refereed)
    Abstract [en]

    When using eye movements to determine the state of a car driver it is important that the eye tracker is robust, unobtrusive, inexpensive and fully automatic. The objectives of this study are to compare the performance of a one-camera system with a three-camera system and to investigate if the accuracy and availability of the one-camera system is sufficient to monitor driver state. Data from 53 subjects were evaluated and the results indicate that there is not much difference between a single-camera system and a multi-camera system as long as the driver is looking straight ahead. However, with more peripheral gaze directions, the larger coverage that is provided by the additional cameras works in favour of the multi-camera system. © ACM 2010.

  • 9.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Patient Dose Computation2014In: Comprehensive Biomedical Physics: Volume 9: Radiation Therapy Physics and Treatment Optimization / [ed] Anders Brahme, Amsterdam: Elsevier, 2014, 235-247 p.Chapter in book (Refereed)
    Abstract [en]

    Various dose calculation methods have been proposed to serve the needs in treatment planning of radiotherapy. Common to these are that they need a patient model to describe the interaction properties of the irradiated tissues, and a sufficiently accurate description of the incident radiation. This chapter starts with a brief review of the contexts in which patient dose calculations may serve, followed by a description of common methods for patient modelling and beam characterization. The focus is on external beam photon, but also partly covers particle beams like electrons and protons. The last section describes common approaches of varying complexity for dose calculations ranging from simple factor based models, more elaborate pencil and point kernel models, and finally summarizes some aspects of Monte Carlo and grid based methods.

  • 10.
    Akay, Altug
    KTH, School of Technology and Health (STH), Health Systems Engineering, Systems Safety and Management.
    A Novel Method to Intelligently Mine Social Media to Assess Consumer Sentiment of Pharmaceutical Drugs2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis focuses on the development of novel data mining techniques that convert user interactions in social media networks into readable data that would benefit users, companies, and governments. The readable data can either warn of dangerous side effects of pharmaceutical drugs or improve intervention strategies. A weighted model enabled us to represent user activity in the network, that allowed us to reflect user sentiment of a pharmaceutical drug and/or service. The result is an accurate representation of user sentiment. This approach, when modified for specific diseases, drugs, and services, can enable rapid user feedback that can be converted into rapid responses from consumers to industry and government to withdraw possibly dangerous drugs and services from the market or improve said drugs and services.

    Our approach monitors social media networks in real-time, enabling government and industry to rapidly respond to consumer sentiment of pharmaceutical drugs and services.

  • 11.
    Al-Absi, Thabit
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.
    Efficient Characterization of Short Anelloviruses Fragments Found in Metagenomic Samples2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Some viral metagenomic serum samples contain a huge amount of Anellovirus, which is a genetically diverse family with a few conserved regions making it hard to efficiently characterize. Multiple sequence alignment of the Anelloviruses found in the sample must be constructed to get a clear picture of Anellovirus diversity and to identify stable regions. Using available multiple sequence alignment software directly on these fragments results in an MSA of a very poor quality due to their diversity, misaligned regions and low-quality regions present in the sequence.

    An efficient MSA must be constructed in order to characterize these Anellovirus present in the samples. Pairwise alignment is used to align one fragment to the database sequences at a time. The fragments are then aligned to the database sequences using the start and end position from the pairwise alignment results. The algorithm will also exclude non-aligned portions of the fragments, as these are very hard to handle properly and are often products of misassembly or chimeric sequenced fragments. Other tools to aid further analysis were developed, such as finding a non-overlapping window that contains the most fragments, find consensus of the alignment and extract any regions from the MSA for further analysis.

    An MSA was constructed with a high percent of correctly aligned bases compared to an MSA constructed using MSA softwares. The minimal number of genomes found in the sampled sequence was found as well as a distribution of the fragments along the database sequence. Moreover, highly conserved region and the window containing most fragments were extracted from the MSA and phylogenetic trees were constructed for these regions. 

  • 12.
    Albano, Amanda
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Exploratory statistical study of long-term variability in echocardiographic indices (echocardiovariability) in healthy and diseased1987Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Heart rate variability, HRV, has been well researched for some decades. The oscillations of the heart rate is studied over a time period of some minutes up to 24 hours, it is measured with electrocardiography, ECG. From this one has concluded that the heart rate signal oscillates in accordance with the respiration, the resistance in the vessels etc.

    The most frequently used examination method of the heart is done with ultrasound, called echocardiography. One interesting variable at a time is measured and it is measured for a single heartbeat. With inspiration ofthe HRV studies this project focuses on some of the variables measured with ultrasound but over time andsimultaneously. The variables of interest are the myocardial motion and the blood flow in the left part ofthe heart, they are measured over two minutes. To complement these variables the well known variables HRand Resp are measured with ECG and added to the analysis.

    The methods used for analysing the variables are first of all descriptive statistics like mean and standard deviation. Secondly spectral analysis is performed to investigate in which frequencies the variables oscillates. Through coherence this is compared with the spectrum for HR where the three peaks have known origin. Finally principal component analysis, PCA, is performed as a method to compare all variables at the same time.

    The analyses are performed on seven measurements from five (5) healthy persons and five measurementsfrom four (4) patients with the disease FAP (“Skelleftesjukan”). The variables are investigated and described for the healthy persons first, then the healthy persons and patients are compared.

    The result from the study shows that most of the echo-variables oscillate in accordance with the respirationand the heart rate. For a healthy person the oscillations are within normal values and the relative deviation isaround 10%. The patients with FAP are most affected in the variables connected to the myocardium apartfrom HR, which is known since before.

    The coherence between the echo-variables and HR is low in one of VLF, very low frequency, or LF, lowfrequency, region and high in the other. In HF, high frequency, region the coherence is high for all variables.

    Finally the PCA was conducted on measurements from all healthy persons as one data set, from one ofthe healthy persons and from one of the patients with FAP. The analysis showed that for healthy personsrespiration is the process causing most variation and all of the echo-variables have a correlation to therespiration. For a patient with FAP the respiration is not as salient. A PCA over blocks of data at different time points however show that the signals are not oscillating in the same way multivariately over the wholetime series.

  • 13.
    Alonso, Fabiola
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Modeling and simulation of DBS – comparison between leads and stimulation modes2014Conference paper (Other academic)
  • 14.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Comparison of deep brain stimulation systems2014In: Poster Presentations, 2014, Vol. 29, 1173-1173 p., Suppl 1Conference paper (Other academic)
    Abstract [en]

    Objective: To quantitatively compare the electric field generated by voltage and current controlled deep brain stimulation systems.

    Background: Traditionally deep brain stimulation (DBS) systems have used voltage control however more recently, current controlled systems have been approved to treat Parkinson's disease and related movement disorders. In the endeavor of understanding the behavior of DBS systems a common approach is the use of computer models suitable to simulate the electric field, current density and other related electric parameters.

    Methods: 2D finite element models based on commercially available DBS systems have been built for each system: I. Model 3389, Medtronic Inc., USA for voltage control; and II. Model 6142, St Jude Medical Inc. USA for current control. The brain tissue has been simplified to homogeneous and isotropic medium. The electric settings correspond to a monopolar configuration, using one of the four contacts available as the active electrode and the outer boundary of the tissue as the reference. Three simulations were performed to mimic different stages of the leads implantation: a) an original stage where the brain tissue is considered as pure gray matter, b) an acute stage that simulates the leakage of cerebral spinal fluid immediately after the electrodes' insertion; and c) a chronic stage mimicking fibrous tissue created around the electrodes some weeks after implantation. Both systems were submitted to the same conditions using as active electrode the third contact from the tip of the lead. The comparison is based on the maximal distance reached by the isopotential of 0.2 V/mm.

    Results: The simulations showed that voltage controlled stimulation systems are more susceptible to changes in the electrical conductivity of the medium i.e. change over time of the tissue around the electrode. This agrees with the adjustment of the stimulation amplitude often necessary a few weeks postoperatively. Current controlled stimulation in turn, presented a linear behavior of the distance reached at different stimulation amplitudes at all stages.

    Conclusions: Current controlled stimulation might be a good option due to its linear behavior over time, nevertheless more studies including a more realistic brain model, different designs of DBS electrodes and different electric parameter, are needed to encourage the use of this type of systems.

  • 15.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Latorre, Malcolm
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Neural Activation Compared to Electric Field Extension of Three DBS Lead Designs2015Conference paper (Refereed)
    Abstract [en]

    SINCE the introduction of deep brain stimulation (DBS) about 20 years ago, the stimulation technique has been dominated by Medtronic DBS-system setup. In recent years, new DBS systems have become available, of which some are in clinical trials or available to patients [1]. In the present study three different lead designs are investigated via computer simulation:

    Medtronic 3389, St. Jude 6148 and Sapiens SureStim. The aim was to compare the neural activation distance and the electric field (EF) maximum spatial extension for each lead.

    A 3D finite element method model was built using COMSOL Multiphysics 4.4a (COMSOL AB, Stockholm, Sweden) to simulate the electric potential around the DBS lead. Brain tissue was modelled as a homogeneous volume of grey matter (electric conductivity of 0.09 S/m). The electrode-tissue interface was modelled with a 250μm thick peri-electrode space mimicking the fibrous tissue which covers the lead at the chronic stimulation stage (σ = 0.06S/m, equivalent to white matter electric conductivity). The stimulation amplitude was set to 1V in monopolar configuration using C1 electrode or equivalent in all cases. Each simulated electric potential distribution was exported to MatLab (The MathWorks, USA) and used as input to a cable neuron simulation.

    An axon cable model with 21 nodes based on the concept by Åström et al., [2] was set up in MatLab and combined with the exported field distributions. The model considered a 5 μm thick neuron, a pulse width of 60 μs and a drive potential ranging from 0.5 V to 5 V in 0.5 V steps.

    The SureStim lead results showed a shorter neural activation distance and EF extension. The distance to the isolevel of 0.2 V/mm is close to the neural activation distance at each stimulation amplitude, and we conclude that the electric field is a suitable predictor to visualize the stimulated regions.

  • 16.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Latorre, Malcolm
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Comparison of Three Deep Brain Stimulation Lead Designs under Voltage and Current Modes2015In: WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2 / [ed] David A. Jaffray, Springer, 2015, Vol. 51, 1196-1199 p.Conference paper (Refereed)
    Abstract [en]

    Since the introduction of deep brain stimulation (DBS) the technique has been dominated by Medtronic sys-tems. In recent years, new DBS systems have become available for patients, and some are in clinical trials. The present study aims to evaluate three DBS leads operated in either voltage or current mode. 3D finite element method (FEM) models were built in combination with a neuron model for this purpose. The axon diameter was set to D = 5 μm and simulations performed in both voltage (0.5-5 V) and current (0.5-5 mA) mode. The evaluation was achieved based on the distance from the lead for neural activation and the electric field (EF) extension at 0.1 V/mm. The results showed that the neural activation distance agrees well between the leads with an activation distance dif-ference less than 0.5 mm. The shape of the field at the 0.1 V/mm isopotential surface in 3D is mostly spherical in shape around the activated section of the steering lead.

  • 17.
    Alrifaiy, Ahmed
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lab on a chip for electrophysiological measurements with control of the oxygen content: optical manipulation and spectroscopic analysis of biological cells2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Stroke affects nearly 20 million people around the world every year. Clinically, stroke is a result of brain damage due to the shortage of oxygen delivered to the nerve cells. To minimize suffering and costs related to the disease, extensive research is performed on different levels. The focus of our research is to achieve fundamental understanding on how the lack of oxygen in brain tissue activates intrinsic biomolecular defense mechanisms that may reduce brain damage. More knowledge may hopefully lead to new therapeutic and preventive strategies on the molecular level for individuals in the risk zone for stroke or those who have just suffered a stroke.The area of study is based on the discovery of a hemoprotein called neuroglobin (Ngb), which is found in various regions in the brain, in the islets of Langerhans, and in the retina. Several studies have shown that Ngb seems to have a protective function against hypoxia-related damage. However, until now, it has not been understood how Ngb affects the nerve system and protects neurons from damage.The well-established patch-clamp technique is routinely used to measure and analyze the electrophysiological activity of individual biological cells. To perform accurate patchclamp experiments, it is important to create well-controlled physiological conditions, i.e. different oxygen levels and fast changes of nutrients and other biochemical substances. A promising approach is to apply lab on a chip technologies combined with optical manipulation techniques. These give optimal control over fast changing environmental conditions and enable multiple readouts.The conventional open patch-clamp configuration cannot provide adequate control of the oxygen content. Therefore, the aim of the thesis was to design and test a multifunctional microfluidic system, lab on a chip (LOC), that can achieve normoxic, anoxic and hypoxic conditions. The conventional patch clamp configuration was substituted by a gas-tight LOC system with an integrated patch-clamp micropipette. The system was combined with optical tweezers, optical sensor and optical spectroscopy.Optical tweezers were used to trap and guide single cells through the LOC microchannels towards the fixed micropipette. Optical spectroscopy was essential to investigate the biochemical composition of the biological samples. The developed, gas-tight LOC acted as a multifunctional system for simultaneous electrophysiological and spectroscopic experiments with good control over the oxygen content in the liquid perifusing the cells. The system was tested in series of experiments: optically trapped cells (red blood cells from human and chicken and nerve cells) were steered to the fixed patch-clamp pipette within the LOC system. The oxygen content within the microfluidic channels was measured to ∼ 1% compared to the usual 4-7% found in open system. The trapping dynamics were monitored in real-time while the spectroscopic measurements were performed simultaneously to acquire absorption spectra of the trapped cell under varying environments. To measure the effect of the laser tweezers on the sample, neurons from rats in a Petri dish were optically trapped and steered towards the patch-clamp micropipette where electrophysiological investigations were performed. The optical tweezers had no effect on the electrophysiological measurements.The future aim is to perform complete protocols of patch-clamp electrophysiological investigations while simultaneously monitoring the biochemical composition of the sample by optical spectroscopy. The straightforwardness and stability of the microfluidic chip have shown excellent potential to be applied for various biomedical applications. The subsequent ambition is to use this system as a mini laboratory that has benefits in cell sorting, patch-clamp and fertilization experiments where the gaseous and the biochemical content is of importance.The long-term goal is to study the response of individual neurons and defense mechanisms under hypoxic conditions that may establish new ways to understand cell behavior related to Ngb for various diseases such as stroke, Alzheimer’s and Parkinson’s.

  • 18.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Bitaraf, Nazanin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Druzin, Michael
    Umeå universitet, Integrativ Medicinsk Biologi, Fysiologi.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Hypoxia on a chip: a novel approach for patch-clamp studies in a microfluidic system with full oxygen control2012In: World Congress on Medical Physics and Biomedical Engineering, May 26-31, 2012, Beijing, China / [ed] Mian Long, Berlin: Encyclopedia of Global Archaeology/Springer Verlag, 2012, 313-316 p.Conference paper (Refereed)
    Abstract [en]

    Here a new approach to perform patch-clamp investigations under anoxic and normoxic conditions on nerve cells from Sprague Dawley rats is presented. A patch-clamp micropipette is integrated within a poly-methyl methacrylate (PMMA) based microchip giving optimal control over the oxygen content and the biochemical environment. Nerve cells were trapped by optical tweezers and steered towards the patch-clamp micropipette within the micro-channels. Several experiments were performed to show proof of principle. The oxygen content within the microfluidic chamber was measured to 0.5-1.5 %. The photo-induced effect of the optical tweezers on the nerve cells was investigated in an open Petri dish. The optical trapping did not influence measurements. The microfluidic system was further tested in patch-clamp experiments. This approach showed significant advantages regarding the tuning of the oxygen content and may be used in various electrophysiological investigations of single cells demanding optimal control of the surroundings.

  • 19.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Bitaraf, Nazanin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Druzin, Michael
    Umeå universitet, Integrativ Medicinsk Biologi, Fysiologi.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Patch-clamp measurements on a chip with full control over the oxygen content2012In: Journal of Biochips & Tissue Chips, ISSN 2153-0777, Vol. 2, no 1, 1-5 p.Article in journal (Refereed)
  • 20.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Patch-clamp electrophysiological measurements on single cells under hypoxic conditions in microfluidic systems2012Conference paper (Refereed)
  • 21.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Polymer-based microfluidic devices for pharmacy, biology and tissue engineering2012In: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 4, no 3, 1349-1398 p.Article in journal (Refereed)
    Abstract [en]

    This paper reviews microfluidic technologies with emphasis on applications in the fields of pharmacy, biology, and tissue engineering. Design and fabrication of microfluidic systems are discussed with respect to specific biological concerns, such as biocompatibility and cell viability. Recent applications and developments on genetic analysis, cell culture, cell manipulation, biosensors, pathogen detection systems, diagnostic devices, high-throughput screening and biomaterial synthesis for tissue engineering are presented. The pros and cons of materials like polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA), polystyrene (PS), polycarbonate (PC), cyclic olefin copolymer (COC), glass, and silicon are discussed in terms of biocompatibility and fabrication aspects. Microfluidic devices are widely used in life sciences. Here, commercialization and research trends of microfluidics as new, easy to use, and cost-effective measurement tools at the cell/tissue level are critically reviewed.

  • 22.
    Andersson, Matilda
    Halmstad University, School of Business, Engineering and Science.
    Analysis of Changes in Running Technique Between a Shod and Barefoot Running Condition.2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Lately, barefoot running has become popular and there is a debate on the pros and cons of barefoot running with regards to running injuries. Many factors are causing injuries and one of the factors discussed is the fact that we run in shoes. When we run in shoes the biomechanics of the running technique may and therefore be a possible cause to injury. Aim: The aim of the study was to assess how the foot strike pattern, angle of the knee and ankle joint at time of initial contact, as well as the step length changes between a shod and barefoot running condition in habitually shod runners when running in a pace equivalent to their running pace over ten kilometers. Method: Twenty-seven healthy runners (18 male, 9 female) were included in the study. The study took place at the fitness center of Halmstad University. Subjects ran on a treadmill, in an individual pace equivalent to their running pace over ten km, both in a shod and barefoot running condition. Two-dimensional analysis of the sagittal plane kinematics of the knee joint, ankle joint and foot position to horizontal, foot strike pattern and step length was done. Participants ran for ten minutes with shoes and for five minutes barefoot. Running technique was videotaped using an Iphone 6 camera and landmarks were marked with white tape to ease the analysis. Results: Changes in foot strike pattern was observed. When running barefoot 63% of the subjects adopted a non-heel strike pattern compared to 18.5% when shod (p=0.001). Knee flexion was increased at IC for the barefoot condition, with 164°±6 relative knee angle compared to 167°±6 when shod (p=0.001). Ankle angle at IC did not show a statistical significant difference between conditions (p=0.657). When barefoot the angle was 117°±8 compared to 115°±8 when shod. Foot angle to horizontal showed a flatter foot placement at IC with a less dorsiflexed foot for the barefoot condition (-4°±8) compared to shod (-12°±8), (p=0.001). Step length was decreased for the barefoot condition (0.82m ±0.15)   compared to shod (0.85m ±0.13), (p=0.008). Conclusion: Results are consistent with previous findings that barefoot running in some cases change the running technique with a flatter foot placement, an increased knee flexion at IC and a decreased step length. However, caution must be taken when habitually shod runners transition to barefoot running in regards to the biomechanical changes that may occur. To benefit from barefoot running a non-heel strike pattern is required. Further, the running technique may be the more important factor, regardless of wearing shoes or not.

  • 23.
    Angelopoulos, Angelos
    et al.
    -.
    Aslanides, E.
    -.
    Backenstoss, G.
    -.
    Bargassa, P.
    -.
    Behnke, O.
    -.
    Benelli, A.
    -.
    Bertin, V.
    -.
    Blanc, F.
    -.
    Bloch, P.
    -.
    Carlson, P.
    -.
    Danielsson, Mats
    KTH, Superseded Departments, Physics.
    K0⇋ K̄0 transitions monitored by strong interactions: a new determination of the K L–K S mass difference2001In: Physics Letters B, ISSN 0370-2693, E-ISSN 1873-2445, Vol. 503, no 1, 49-57 p.Article in journal (Refereed)
    Abstract [en]

    The CPLEAR set-up (modified) has been used to determine the KL–KS mass difference by a method where neutral-kaon strangeness oscillations are monitored through kaon strong interactions, rather than semileptonic decays, thus requiring no assumptions on CPT invariance for the decay amplitudes. The result, Δm=(0.5343±0.0063stat±0.0025syst)×1010ℏ/s, provides a valuable input for CPT tests.

  • 24.
    Angland, Erik
    et al.
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Karlsson, Henrik
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Gustafsson, Agnetha
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Pettersson, Håkan
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Luftmätningar av  inhalerat 99mTc till BMA vid ventilationsundersökningar med Technegas.2006Conference paper (Other academic)
  • 25.
    Antonsson, Jacob
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Motion Tracking Using a Permanent Magnet2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In this project the possibility of using a network of magnetometers sensing a permanent magnet for tracking has been investigated. Both the orientation and the position of the magnet have been considered. A dipole approximation of the magnetic field is used to develop two models. One of the models parametrizes the orientation with the magnetic moment vector, while the other parametrizes the orientation with a unit quaternion. An extended Kalman filter have been used to estimate position and orientation.

    Several calibration algorithms have been developed to calibrate for sensor errors, differences in sensor coordinate frame orientations and also for the estimation of the magnetic moment norm of a permanent magnet. The models have been tested using an optical reference system for position and orientation estimation. Initial results are ambiguous and further testing is necessary. One conclusion is that the model using the magnetic moment vector as orientation parametrization is less sensitive to the accuracy of the initial guesses of the filter recursions and also less sensitive to possible model errors.

    A mathematical result of the possibility of using a non stationary sensor network to track the magnet is also given.

  • 26.
    Athanasiou, Vasileios
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Estimation and modelling of fMRI BOLD response2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    One of the current topics of research in neuroimaging techniques is related to explaining and modelling the Blood Oxygen Level Dependent (BOLD) responses. BOLD responses are estimated by processing functional Magnetic Resonance Imaging (fMRI) data. BOLD responses are caused by hemodynamic responses to neural activity which alter the levels of blood oxygenation at local brain regions. The main aims of the current thesis were to i) develop and examine methods regarding BOLD response estimation from the visual cortex and the frontal cortex of human brain and to ii) develop a model in order to explain the physiological mechanisms which cause the estimated BOLD responses.

    In order to satisfy the main aims, fMRI data were provided by the Center of Medical Imaging and Visualization (CMIV). The provided fMRI data consist of fMRI brain measurements of twelve healthy human subjects who were subjected to visual stimulation. By processing the fMRI data, Regions Of Interest (ROIs) were extracted at the anatomical sites of the visual cortex and the frontal cortex. Afterwards, the fMRI data were manipulated in order to extract BOLD responses from the visual cortex and the frontal cortex. Various methods were developed and compared in terms of which technique provided well representative BOLD responses.       

    Subsequently, a model was developed by using software Wolfram Mathematica 9 in order to explain the physiological mechanisms of the estimated BOLD responses at the visual and the frontal cortex. The model aimed to solve for oxygen concentration in blood plasma as blood flows from the arterial part to the venous part of the blood circulation system through a capillary. Oxygen outward diffusion through the capillary wall and oxygen concentration at the extravascular environment were modelled as well. Blood plasma oxygen concentration was turned into hemoglobin oxygen saturation (Sa ) through hemoglobin oxygen dissociation curve and Henry’s law for gases. As a result, the Sa  was estimated through modelling for oxygen concentration in blood plasma. Finally, the developed model ended to a system with input the fractional change of Cerebral Blood Flow (CBF) velocity and Cerebral Metabolic Rate of Oxygen (CMR ) and as output a proportional signal to the BOLD response. By simulating for different scenarios of fractional changes of CBF velocity and CMR  and by comparing the resulted BOLD responses to the estimated ones, it was attempted to explain for the physiological mechanisms which caused the BOLD responses at the anatomical sites of the visual and frontal cortex.

  • 27. Augustine, Robin
    Near-field dosimetry for the millimeter-wave exposure of human cells in vitro2012In: Bioelectromagnetics, ISSN 0197-8462, E-ISSN 1521-186X, 55-64 p.Article in journal (Refereed)
    Abstract [en]

    Due to the expected mass deployment of millimeter-wave wireless technologies, thresholds of potential millimeter-wave-induced biological and health effects should be carefully assessed. The main purpose of this study is to propose, optimize, and characterize a near-field exposure configuration allowing illumination of cells in vitro at 60 GHz with power densities up to several tens of mW/cm(2) . Positioning of a tissue culture plate containing cells has been optimized in the near-field of a standard horn antenna operating at 60 GHz. The optimal position corresponds to the maximal mean-to-peak specific absorption rate (SAR) ratio over the cell monolayer, allowing the achievement of power densities up to 50 mW/cm(2) at least. Three complementary parameters have been determined and analyzed for the exposed cells, namely the power density, SAR, and temperature dynamics. The incident power density and SAR have been computed using the finite-difference time-domain (FDTD) method. The temperature dynamics at different locations inside the culture medium are measured and analyzed for various power densities. Local SAR, determined based on the initial rate of temperature rise, is in a good agreement with the computed SAR (maximal difference of 5%). For the optimized exposure setup configuration, 73% of cells are located within the ±3 dB region with respect to the average SAR. It is shown that under the considered exposure conditions, the maximal power density, local SAR, and temperature increments equal 57 mW/cm(2) , 1.4 kW/kg, and 6 °C, respectively, for the radiated power of 425 mW.

  • 28.
    Balkanyi, Laszlo
    et al.
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Schulz, Stefan
    Medizinische Universität Graz, Austria and Freiburg University Medical Center, Freiburg, Germany.
    Cornet, Ronald
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Bodenreider, Olivier
    National Library of Medicine, Bethsheda, USA.
    Medical concept representation: the years beyond 2000.2013In: Proceedings of Studies in Health Technology & Informatics, vol. 192, IOS Press, 2013, Vol. 192, 1011-1011 p.Conference paper (Refereed)
    Abstract [en]

    This work aims at understanding the state of the art in the broad contextual research area of "medical concept representation". Our data support the general understanding that the focus of research has moved toward medical ontologies, which we interpret as a paradigm shift. Both the opinion of socially active groups of researchers and changes in bibliometric data since 1988 support this opinion. Socially active researchers mention the OBO foundry, SNOMED CT, and the UMLS as anchor activities.

  • 29. Belfrage, Sara
    Without informed consent2013In: Moral, Ethical, and Social Dilemmas in the Age of Technology: Theories and Practice, IGI Global, 2013, 291-305 p.Chapter in book (Other academic)
    Abstract [en]

    The requirement of always obtaining participants' informed consent in research with human subjects cannot always be met, for a variety of reasons. This paper describes and categorises research situations where informed consent is unobtainable. Some of these kinds of situations, common in biomedicine and psychology, have been previously discussed, whereas others, for example, those more prevalent in infrastructure research, introduce new perspectives. The advancement of new technology may lead to an increase in research of these kinds. The paper also provides a review of methods intended to compensate for lack of consent, and their applicability and usefulness for the different categories of situations are discussed. The aim of this is to provide insights into one important aspect of the question of permitting research without informed consent, namely, how well that which informed consent is meant to safeguard can be achieved by other means.

  • 30. Bergström, Mattias
    et al.
    Ericson, Åsa
    Larsson, Madelene
    Nergård, Henrik
    Larsson, Tobias
    Luleå Technical University.
    Renström, Boo
    Needs as a basis for design rationale2008In: / [ed] Dorian Marjanovic, Mario Storga, Neven Pavkovic, Nenad Bojcetic, University of Zagreb, Dubrovnik, Croatia: University of Zagreb , 2008Conference paper (Refereed)
    Abstract [en]

    A basic principle for Needfinding [Faste, 1987; Patnaik & Becker, 1999] is that designers and engineers should interact directly with users to get direct insights into the user domain. Needfinding is not a new phenomena, it is almost forty years ago since the process was adopted at Stanford University’s product design program [Patnaik & Becker, 1999]. As the name, Need-finding, implies, this is an intertwined approach to find needs which are not readily articulated by users. The application of a Needfinding process offers qualitative methods to make those needs visible early on in product development. In fact, the process has become more interesting during recent time, since qualitative methods have gained more acceptance outside the academic realm [ibid.].The word qualitative indicates that what are sought for are qualities such as people’s experiences, what they perceive or interpret into a situation [Miles & Huberman, 1994; Patton, 2002]. Such data is contextually dependent, i.e., it must be generated in the context in which the phenomena occur. Besides context, people’s activities, behaviours and goals are important to observe and learn from. The objectives, for applying Needfinding, are to make the identification of needs and design a seamless effort, as well as an interest to identify opportunities to innovations. Needs last longer than any solution [Patnaik & Becker, 1999], since they are grounded in people’s activities. The solution and product that might meet such needs change over time. One example is how to store computer data, the products which satisfy the need has changed from, e.g., punch cards, magnetic tape, floppy discs [ibid.] to USB-flash memories. A guiding methodology in Needfinding is a flexible process, which is adapted to the task at hand [Kelley, 2001]. Such a process is conveyed in a few basic steps and, builds on a ‘philosophy’ which permeates all activities in order to adapt the process according to the project. Therefore, the designer’s ability to rely on such a process depends on familiarity with a number of methods for observations and interviews, as well as an aptitude for socio-technical skills. Hence, the purpose in this paper is to present and reflect on methods used in a running development project to identify needs in a product development project. This is done to contribute to the advancement of a need driven product development process. The disposition of this paper is as follows. First, our approach in studying the need identification activities is presented. Second, a theoretical frame for need identification and design is presented, i.e., Needfinding [Patnaik & Becker, 1999]. Third, the practice of finding needs is outlined and discussed.

  • 31.
    Bitaraf, Nazanin
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Alrifaiy, Ahmed
    Luleå tekniska universitet.
    Druzin, Mikhail
    Umeå University, Department of Integrative Medical Biology, Physiology.
    Ramser, Kerstin
    Development of a multifunctional microfluidic system for studies of nerve cell activity during hypoxic and anoxic conditions2009In: World Congress on Medical Physics and Biomedical Engineering: September 7 - 12, 2009, Munich, Germany, Berlin: Springer Science+Business Media B.V., 2009, Vol. 8, 176-179 p.Conference paper (Refereed)
  • 32.
    Bleser, Gabriele
    et al.
    German Research Center for Artificial Intelligence (DFKI), Kaiserslautern, Germany.
    Steffen, Daniel
    German Research Center for Artificial Intelligence (DFKI), Kaiserslautern, Germany.
    Reiss, Attila
    ACTLab, University of Passau, 94032, Passau, Germany.
    Weber, Markus
    German Research Center for Artificial Intelligence (DFKI), Kaiserslautern, Germany.
    Hendeby, Gustaf
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Fradet, Laetitia
    Université de Poitiers, 86000, Poitiers, France.
    Personalized Physical Activity Monitoring Using Wearable Sensors2015In: Smart Health: Open Problems and Future Challenges / [ed] Andreas Holzinger, Carsten Röcker, Martina Ziefle, Springer International Publishing , 2015, 99-124 p.Chapter in book (Refereed)
    Abstract [en]

    It is a well-known fact that exercising helps people improve their overall well-being; both physiological and psychological health. Regular moderate physical activity improves the risk of disease progression, improves the chances for successful rehabilitation, and lowers the levels of stress hormones. Physical fitness can be categorized in cardiovascular fitness, and muscular strength and endurance. A proper balance between aerobic activities and strength exercises are important to maximize the positive effects. This balance is not always easily obtained, so assistance tools are important. Hence, ambient assisted living (AAL) systems that support and motivate balanced training are desirable. This chapter presents methods to provide this, focusing on the methodologies and concepts implemented by the authors in the physical activity monitoring for aging people (PAMAP) platform. The chapter sets the stage for an architecture to provide personalized activity monitoring using a network of wearable sensors, mainly inertial measurement units (IMU). The main focus is then to describe how to do this in a personalizable way: (1) monitoring to provide an estimate of aerobic activities performed, for which a boosting based method to determine activity type, intensity, frequency, and duration is given; (2) supervise and coach strength activities. Here, methodologies are described for obtaining the parameters needed to provide real-time useful feedback to the user about how to exercise safely using the right technique.

  • 33.
    Blom, Hans
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    STED microscopy: increased resolution for medical research?2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 276, no 6, 560-578 p.Article, review/survey (Refereed)
    Abstract [en]

    Optical imaging is crucial for addressing fundamental problems in all areas of life science. With the use of confocal and two-photon fluorescence microscopy, complex dynamic structures and functions in a plethora of tissue and cell types have been visualized. However, the resolution of classical' optical imaging methods is poor due to the diffraction limit and does not allow resolution of the cellular microcosmos. On the other hand, the novel stimulated emission depletion (STED) microscopy technique, because of its targeted on/off-switching of fluorescence, is not hampered by a diffraction-limited resolution barrier. STED microscopy can therefore provide much sharper images, permitting nanoscale visualization by sequential imaging of individual-labelled biomolecules, which should allow previous findings to be reinvestigated and provide novel information. The aim of this review is to highlight promising developments in and applications of STED microscopy and their impact on unresolved issues in biomedical science.

  • 34.
    Brantefors, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Department of Physics. Karolinska Institutet, Department of Clinical Neuroscience.
    Dynamic fMRI brain connectivity: A study of the brain’s large-scale network dynamics2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Approximately 20% of the body’s energy consumption is ongoingly consumed by the brain, where the main part is due to the neural activity, which is only increased slightly when doing a demanding task. This ongoingly neural activity are studied with the so called resting-state fMRI, which mean that the neural activity in the brain is measured for participants with no specific task. These studies have been useful to understand the neural function and how the neural networks are constructed and cooperate. This have also been helpful in several clinical research, for example have differences been identified between bipolar disorder and major depressive disorder. Recent research has focused on temporal properties of the ongoing activity and it is well known that neural activity occurs in bursts. In this study, resting-state fMRI data and temporal graph theory is used to develop a point based method (PBM) to quantify these bursts at a nodal level. By doing this, the bursty pattern can be further investigated and the nodes showing the most bursty pattern (i.e hubs) can be identified. The method developed shows a robustness regarding several different aspects. In the method is two different variance threshold algorithms suggested. One local variance threshold (LVT) based on the individual variance of the edge time-series and one global variance threshold (GVT) based on the variance of all edges time-series, where the GVT shows the highest robustness. However, the choice of threshold needs to be adapted for the aims of the current study. Finally, this method ends up in a new measure to quantify this bursty pattern named bursty centrality. The derived temporal graph theoretical measure was correlated with traditional static graph properties used in resting state and showed a low but significant correlation. By applying this method on resting-state fMRI data for 32 young adults was it possible to identify regions of the brain that showed the most dynamic properties, these regions differed between the two thresholding algorithms

  • 35.
    Broomé, Michael
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Frenckner, Björn
    Broman, Mikaeö
    Bjällmark, Anna
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Recirculation during veno-venous extra-corporeal membrane oxygenation: a simulation study2015In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 38, no 1, 23-30 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    Veno-venous ECMO is indicated in reversible life-threatening respiratory failure without life-threatening circulatory failure. Recirculation of oxygenated blood in the ECMO circuit decreases efficiency of patient oxygen delivery but is difficult to measure. We seek to identify and quantify some of the factors responsible for recirculation in a simulation model and compare with clinical data.

    METHODS:

    A closed-loop real-time simulation model of the cardiovascular system has been developed. ECMO is simulated with a fixed flow pump 0 to 5 l/min with various cannulation sites - 1) right atrium to inferior vena cava, 2) inferior vena cava to right atrium, and 3) superior+inferior vena cava to right atrium. Simulations are compared to data from a retrospective cohort of 11 consecutive adult veno-venous ECMO patients in our department.

    RESULTS:

    Recirculation increases with increasing ECMO-flow, decreases with increasing cardiac output, and is highly dependent on choice of cannulation sites. A more peripheral drainage site decreases recirculation substantially.

    CONCLUSIONS:

    Simulations suggest that recirculation is a significant clinical problem in veno-venous ECMO in agreement with clinical data. Due to the difficulties in measuring recirculation and interpretation of the venous oxygen saturation in the ECMO drainage blood, flow settings and cannula positioning should rather be optimized with help of arterial oxygenation parameters. Simulation may be useful in quantification and understanding of recirculation in VV-ECMO.

  • 36. Brown, Shannon
    et al.
    Ortiz-Catalan, Max
    Petersson, Joel
    Rodby, Kristian
    Seoane, Fernando
    KTH, School of Technology and Health (STH), Medical Engineering, Computer and Electronic Engineering. University of Borås, Sweden.
    Intarsia-Sensorized Band and Textrodes for Real-Time Myoelectric Pattern Recognition2016In: Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS / [ed] Patton, J Barbieri, R Ji, J Jabbari, E Dokos, S Mukkamala, R Guiraud, D Jovanov, E Dhaher, Y Panescu, D Vangils, M Wheeler, B Dhawan, AP, Institute of Electrical and Electronics Engineers (IEEE), 2016, 6074-6077 p., 7592114Conference paper (Refereed)
    Abstract [en]

    Surface Electromyography (sEMG) has applications in prosthetics, diagnostics and neuromuscular rehabilitation. Self-adhesive Ag/AgCl are the electrodes preferentially used to capture sEMG in short-term studies, however their long-term application is limited. In this study we designed and evaluated a fully integrated smart textile band with electrical connecting tracks knitted with intarsia techniques and knitted textile electrodes. Real-time myoelectric pattern recognition for motor volition and signal-to-noise ratio (SNR) were used to compare its sensing performance versus the conventional Ag-AgCl electrodes. After a comprehending measurement and performance comparison of the sEMG recordings, no significant differences were found between the textile and the Ag-AgCl electrodes in SNR and prediction accuracy obtained from pattern recognition classifiers.

  • 37.
    Budde, Kiran Kumar
    Linköping University, Department of Electrical Engineering, Computer Vision.
    A Matlab Toolbox for fMRI Data Analysis: Detection, Estimation and Brain Connectivity2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Functional Magnetic Resonance Imaging (fMRI) is one of the best techniques for neuroimaging and has revolutionized the way to understand the brain functions. It measures the changes in the blood oxygen level-dependent (BOLD) signal which is related to the neuronal activity. Complexity of the data, presence of different types of noises and the massive amount of data makes the fMRI data analysis a challenging one. It demands efficient signal processing and statistical analysis methods.  The inference of the analysis is used by the physicians, neurologists and researchers for better understanding of the brain functions.

         The purpose of this study is to design a toolbox for fMRI data analysis. It includes methods to detect the brain activity maps, estimation of the hemodynamic response (HDR) and the connectivity of the brain structures. This toolbox provides methods for detection of activated brain regions measured with Bayesian estimator. Results are compared with the conventional methods such as t-test, ordinary least squares (OLS) and weighted least squares (WLS). Brain activation and HDR are estimated with linear adaptive model and nonlinear method based on radial basis function (RBF) neural network. Nonlinear autoregressive with exogenous inputs (NARX) neural network is developed to model the dynamics of the fMRI data.  This toolbox also provides methods to brain connectivity such as functional connectivity and effective connectivity.  These methods are examined on simulated and real fMRI datasets.

  • 38.
    Buendia, Ruben
    et al.
    University of Borås, Sweden.
    bogonez-franco, Paco
    Technical University of Catalonia.
    Nescolarde, Lexa
    Technical University of Catalonia.
    Seoane, Fernando
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS).
    Influence of electrode mismatch on Cole parameter estimation from Total Right Side Electrical Bioimpedance Spectroscopy measurements2012In: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 34, no 7, 1024-1028 p.Article in journal (Refereed)
    Abstract [en]

    Applications based on measurements of Electrical Bioimpedance (EBI) spectroscopy analysis, like assessment of body composition, have proliferated in the past years. Currently Body Composition Assessment (BCA) based in Bioimpedance Spectroscopy (BIS) analysis relays on an accurate estimation of the Cole parameters R-0 and R-infinity. A recent study by Bogonez-Franco et al. has proposed electrode mismatch as source of remarkable artefacts in BIS measurements. Using Total Right Side BIS measurements from the aforementioned study, this work has focused on the influence of electrode mismatch on the estimation of R-0 and R-infinity using the Non-Linear Least Square curve fitting technique on the modulus of the impedance. The results show that electrode mismatch on the voltage sensing electrodes produces an overestimation of the impedance spectrum leading to a wrong estimation of the parameters R-0 and R-infinity, and consequently obtaining values around 4% larger that the values obtained from BIS without electrode mismatch. The specific key factors behind electrode mismatch or its influence on the analysis of single and spectroscopy measurements have not been investigated yet, no compensation or correction technique is available to overcome the deviation produced on the EBI measurement. Since textile-enabled EBI applications using dry textrodes, i.e. textile electrodes with dry skin-electrode interfaces and potentially large values of electrode polarization impedance are more prone to produce electrode mismatch, the lack of a correction or compensation technique might hinder the proliferation of textile-enabled EBI applications for personalized healthcare monitoring.

  • 39.
    Bujtar, Peter
    et al.
    Southern General Hospital, Glasgow.
    Simonovics, Janos
    Southern General Hospital, Glasgow.
    Koptyug, Andrey
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Ecotechnology and Sustainable Building Engineering.
    George, Sandor
    Southern General Hospital, Glasgow.
    Varadi, Karoly
    Southern General Hospital, Glasgow.
    Emerging manufacturing bioengineering technologies 2: Scaffold designing experiment using titanium scaffolds2014In: British Journal of Oral & Maxillofacial Surgery, ISSN 0266-4356, E-ISSN 1532-1940, Vol. 52, no 8, e60-e61 p.Article in journal (Refereed)
    Abstract [en]

    Substantial volume defects of the head and neck oftenrequire customized solutions to improve quality of life likefree flap transfers.Titanium and its alloys are versatile materialsproviding the feature of osteointegration. The conditionswhich facilitate the deposition of lamellar bone are underextensive research. Our project aimed to determine whethertitanium can function as a scaffold - unlike simple plates - toenhance bone regeneration for load bearing structures. Thereaction of stem cells to scaffolds with varying stiffness willbe presented.Additive manufacturing were used to produce a variety ofscaffolds to optimize titanium structures. Electric beam melting(EBM) manufacturing allowed us to optimize the elasticmodulus (Young) of the titanium to match with cadaveric 

    bone from a previous project. Multidirectional mechanicaltests were performed on the various designs of titanium cellstructures (n=80). The predictability and quality of manufacturingwas assessed statistically and also with scanningelectron microscope (SEM).The results demonstrated structures matching the mechanicalproperties of bone and even anisotropy as our resultssuggest 3GPa elasticity. This allows the possibility to buildregenerating bone with predictable properties. In addition,predictable patterning - unlike etching and sandblasting - ofmicroscopic (nano) features found to be significant and nonhomogenous simple repetitive patterns provide better cellularresponse.The benefit that tissue engineering techniques offer isdecreased morbidity, relative independence from donor site,with a highly specific and customized shape. Titanium basedreconstruction constructs seems to offer an alternative futurefor bony reconstruction.

  • 40.
    Candefjord, Stefan
    et al.
    Chalmers University of Technology.
    Murayama, Yoshinobu
    College of Engineering, Nihon University.
    Nyberg, Morgan
    Hallberg, Josef
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Ljungberg, Börje
    Umeå University, Department of Surgical and Perioperative Science, Urology and Andrology.
    Bergh, Anders
    Department of Medical Biosciences Pathology, Umeå University.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Combining scanning haptic microscopy and fibre optic Raman spectroscopy for tissue characterisation2012In: Journal of Medical Engineering & Technology, ISSN 0309-1902, E-ISSN 1464-522X, Vol. 36, no 6, 319-327 p.Article in journal (Refereed)
    Abstract [en]

    The tactile resonance method (TRM) and Raman spectroscopy (RS) are promising for tissue characterisation in vivo. Our goal is to combine these techniques into one instrument, to use TRM for swift scanning, and RS for increasing the diagnostic power. The aim of this study was to determine the classification accuracy, using support vector machines, for measurements on porcine tissue and also produce preliminary data on human prostate tissue. This was done by developing a new experimental setup combining micro-scale TRM — scanning haptic microscopy (SHM) — for assessing stiffness on a micro-scale, with fibre optic RS measurements for assessing biochemical content. We compared the accuracy for using SHM alone versus SHM combined with RS, for different degrees of tissue homogeneity. The cross-validation classification accuracy for healthy porcine tissue types using SHM alone was 65–81%, and when RS was added it was increased to 81–87%. The accuracy for healthy and cancerous human tissue was 67–70% when only SHM was used, and increased to 72–77% for the combined measurements. This shows that the potential for swift and accurate classification of healthy and cancerous prostate tissue is high. This is promising for developing a tool for probing the surgical margins during prostate cancer surgery.

  • 41. Capece, Sabrina
    et al.
    Chiessi, Ester
    Cavalli, Roberta
    Giustetto, Pierangela
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Paradossi, Gaio
    A general strategy for obtaining biodegradable polymer shelled microbubbles as theranostic devices2013In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 49, no 51, 5763-5765 p.Article in journal (Refereed)
    Abstract [en]

    Fabrication of multifunctional ultrasound contrast agents (UCAs) has been recently addressed by several research groups. A versatile strategy for the synthesis of UCA precursors in the form of biodegradable vesicles with a biocompatible crosslinked polymer shell is described. Upon ultrasound irradiation, acoustic droplet vaporization transforms such particles into microbubbles behaving as UCAs. This proof of concept entails the features of a potential theranostic microdevice.

  • 42.
    Cedersund, Gunnar
    et al.
    Linköping University, Department of Electrical Engineering. Linköping University, The Institute of Technology.
    Knudsen, C.
    Technical University of Denmark.
    Improved parameter estimation for systems with an experimentally located Hopf bifurcation2005In: IEE Proceedings - Systems Biology, ISSN 1741-2471, E-ISSN 1741-248X, Vol. 152, no 3, 161-168 p.Article in journal (Refereed)
    Abstract [en]

    When performing system identification, we have two sources of information: experimental data and prior knowledge. Many cell-biological systems are oscillating, and sometimes we know an input where the system reaches a Hopf bifurcation. This is the case, for example, for glycolysis in yeast cells and for the Belousov-Zhabotinsky reaction, and for both of these systems there exist significant numbers of quenching data, ideal for system identification. We present a method that includes prior knowledge of the location of a Hopf bifurcation in estimation based on time-series. The main contribution is a reformulation of the prior knowledge into the standard formulation of a constrained optimisation problem. This formulation allows for any of the standard methods to be applied, including all the theories regarding the methods properties. The reformulation is carried out through an over-parametrisation of the original problem. The over-parametrisation allows for extra constraints to be formed, and the net effect is a reduction of the search space. A method that can solve the new formulation of the problem is presented, and the advantage of adding the prior knowledge is demonstrated on the Brusselator.

  • 43.
    Cervin, Ida
    et al.
    Sectra AB, Chalmers University of Technology, Sectra AB, Gothenburg, Sweden.
    Molin, Jesper
    Center for Medical Image Science and Visualization, Chalmers University of Technology, Sectra AB, Gothenburg, Sweden.
    Lundström, Claes
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Improving the creation and reporting of structured findings during digital pathology review2016In: Journal of Pathology Informatics, ISSN 2229-5089, E-ISSN 2153-3539, Vol. 7, no 1, 32-32 p.Article in journal (Refereed)
    Abstract [en]

    Background: Today, pathology reporting consists of many separate tasks, carried out by multiple people. Common tasks include dictation during case review, transcription, verification of the transcription, report distribution, and report the key findings to follow-up registries. Introduction of digital workstations makes it possible to remove some of these tasks and simplify others. This study describes the work presented at the Nordic Symposium on Digital Pathology 2015, in Linköping, Sweden. Methods: We explored the possibility to have a digital tool that simplifies image review by assisting note-taking, and with minimal extra effort, populates a structured report. Thus, our prototype sees reporting as an activity interleaved with image review rather than a separate final step. We created an interface to collect, sort, and display findings for the most common reporting needs, such as tumor size, grading, and scoring. Results: The interface was designed to reduce the need to retain partial findings in the head or on paper, while at the same time be structured enough to support automatic extraction of key findings for follow-up registry reporting. The final prototype was evaluated with two pathologists, diagnosing complicated partial mastectomy cases. The pathologists experienced that the prototype aided them during the review and that it created a better overall workflow. Conclusions: These results show that it is feasible to simplify the reporting tasks in a way that is not distracting, while at the same time being able to automatically extract the key findings. This simplification is possible due to the realization that the structured format needed for automatic extraction of data can be used to offload the pathologists' working memory during the diagnostic review.

  • 44.
    Chu, Jiangtao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Koudriavtsev, Vitali
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Flourescence imaging of molecule transport in high molecular weight cut-off microdialysis2014Conference paper (Refereed)
  • 45.
    Chu, Jiangtao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Koudriavtsev, Vitali
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Fluorescence imaging of macromolecule transport in high molecular weight cut-off microdialysis2014In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 406, no 29, 7601-7609 p.Article in journal (Refereed)
    Abstract [en]

    When microdialysis (MD) membrane exceeds molecular weight cut-off (MWCO) of 100 kDa, the fluid mechanics are in the ultrafiltration regime. Consequently, fluidic mass transport of macromolecules in the perfusate over the membrane may reduce the biological relevance of the sampling and cause an inflammatory response in the test subject. Therefore, a method to investigate the molecular transport of high MWCO MD is presented. An in vitro test chamber was fabricated to facilitate the fluorescent imaging of the MD sampling process, using fluoresceinylisothiocyanate (FITC) dextran and fluorescence microscopy. Qualitative studies on dextran behavior inside and outside the membrane were performed. Semiquantitative results showed clear dextran leakage from both 40 and 250 kDa dextran when 100 kDa MWCO membranes were used. Dextran 40 kDa leaked out with an order of magnitude higher concentration and the leakage pattern resembled more of a convective flow pattern compared with dextran 250 kDa, where the leakage pattern was more diffusion based. No leakage was observed when dextran 500 kDa was used as a colloid osmotic agent. The results in this study suggest that fluorescence imaging could be used as a method for qualitative and semiquantitative molecular transport and fluid dynamics studies of MD membranes and other hollow fiber catheter membranes.

  • 46.
    Chu, Jiangtao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Koudriavtsev, Vitali
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Flourescence imaging of molecule transport in high molecular weight cut-off microdialysis2014Conference paper (Refereed)
  • 47.
    Cloots, Rudy J.H.
    et al.
    Eindhoven University of Technology, Department of Mechanical Engineering.
    van Dommelen, J.A.W.
    Eindhoven University of Technology, Department of Mechanical Engineering.
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Neuronic Engineering.
    Geers, Marc
    Eindhoven University of Technology, Department of Mechanical Engineering.
    Multi-scale mechanics of traumatic brain injury: predicting axonal strains from head loads2013In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 12, no 1, 137-150 p.Article in journal (Refereed)
    Abstract [en]

    The length scales involved in the development of diffuse axonal injury typically range from the head level (i.e., mechanical loading) to the cellular level. The parts of the brain that are vulnerable to this type of injury are mainly the brainstem and the corpus callosum, which are regions with highly anisotropically oriented axons. Within these parts, discrete axonal injuries occur mainly where the axons have to deviate from their main course due to the presence of an inclusion. The aim of this study is to predict axonal strains as a result of a mechanical load at the macroscopic head level. For this, a multi-scale finite element approach is adopted, in which a macro-level head model and a micro-level critical volume element are coupled. The results show that the axonal strains cannot be trivially correlated to the tissue strain without taking into account the axonal orientations, which indicates that the heterogeneities at the cellular level play an important role in brain injury and reliable predictions thereof. In addition to the multi-scale approach, it is shown that a novel anisotropic equivalent strain measure can be used to assess these micro-scale effects from head-level simulations only.

  • 48.
    Cloots, Rudy J.H.
    et al.
    Eindhoven University of Technology, Department of Mechanical Engineering.
    van Dommelen, JAW
    Eindhoven University of Technology, Department of Mechanical Engineering.
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Neuronic Engineering.
    Geers, Marc
    Eindhoven University of Technology, Department of Mechanical Engineering.
    Traumatic Brain Injury at Multiple Length Scales: Relating Diffuse Axonal Injury to Discrete Axonal Impairment2010In: 2010 INTERNATIONAL IRCOBI CONFERENCE ON THE BIOMECHANICS OF INJURY PROCEEDINGS, 2010, 119-130 p.Conference paper (Refereed)
  • 49.
    Cornet, Ronald
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Dentler, Kathrin
    Dept. of Computer Science, VU University Amsterdam, The Netherlands and Dept. of Medical Informatics, Academic Medical Center, University of Amsterdam, The Netherlands.
    Redundant Elements in SNOMED CT Concept Definitions2013In: proceedings of AIME 2013, Lecture Notes in ComputerScience 2013, Vol. 7885, Springer , 2013, 186-195 p.Conference paper (Refereed)
    Abstract [en]

    While redundant elements in SNOMED CT concept definitions are harmless from a logical point of view, they unnecessarily make concept definitions of typically large ontologies such as SNOMED CT hard to construct and to maintain. In this paper, we apply a fully automated method to detect intra-axiom redundancies in SNOMED CT. We systematically analyse the completeness and soundness of the results of our method by examining the identified redundant elements. In absence of a gold standard, we check whether our method identifies concepts that are likely to contain redundant elements because they become equivalent to their stated subsumer when they are replaced by a fully defined concept with the same definition. To evaluate soundness, we remove all identified redundancies, and test whether the logical closure is preserved by comparing the concept hierarchy to the one of the official SNOMED CT distribution. We found that 35,010 of the 296,433 SNOMED CT concepts (12%) contain redundant elements in their definitions, and that the results of our method are sound and complete with respect to our partial evaluation. We recommend to free the stated form from these redundancies. In future, knowledge modellers should be supported by being pointed to newly introduced redundancies.

  • 50.
    Cornet, Ronald
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. University of Amsterdam, The Netherlands.
    Nyström, Mikael
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Karlsson, Daniel
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    User-Directed Coordination in SNOMED CT2013In: MedInfo 2013: Proceedings of the 14th World Congress on Medical and Health Informatics / [ed] Lehmann, C.U., Ammenwerth, E., Nøhr, C., Amsterdam: IOS Press, 2013, 72-76 p.Conference paper (Refereed)
    Abstract [en]

    The possibility of post-coordination of SNOMED CT concepts, especially by clinical users, is both an asset and a challenge for SNOMED CT implementation. To get insight in the applicability of post-coordination, we analyzed scenarios for user-directed coordination that are described in the documentation of SNOMED CT. The analyses were based on experiences from previous and ongoing research and implementation work, including national mapping projects, and investigations on collection of data for multiple uses. These scenarios show various usability and representation problems: high number of relationships for refinement and qualification, improper options for refinement, incorrect formal definitions, and lack of support for applying editorial rules. Improved user-directed coordination in SNOMED CT in real practice requires advanced sanctioning, increased consistency of definitions of concepts in SNOMED CT, and real-time analysis of the post-coordinate expression.

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