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Jönsson, D., Bergström, A., Forsell, C., Simon, R., Engström, M., Ynnerman, A. & Hotz, I. (2019). A Visual Environment for Hypothesis Formation and Reasoning in Studies with fMRI and Multivariate Clinical Data. In: Eurographics Workshop on Visual Computing for Biology and Medicine: . Paper presented at Eurographics Workshop on Visual Computing for Biology and Medicine.
Open this publication in new window or tab >>A Visual Environment for Hypothesis Formation and Reasoning in Studies with fMRI and Multivariate Clinical Data
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2019 (English)In: Eurographics Workshop on Visual Computing for Biology and Medicine, 2019Conference paper, Published paper (Refereed)
Abstract [en]

We present an interactive visual environment for linked analysis of brain imaging and clinical measurements. The environment is developed in an iterative participatory design process involving neuroscientists investigating the causes of brain-related complex diseases. The hypotheses formation process about correlations between active brain regions and physiological or psychological factors in studies with hundreds of subjects is a central part of the investigation. Observing the reasoning patterns during hypotheses formation, we concluded that while existing tools provide powerful analysis options, they lack effective interactive exploration, thus limiting the scientific scope and preventing extraction of knowledge from available data.Based on these observations, we designed methods that support neuroscientists by integrating their existing statistical analysis of multivariate subject data with interactive visual explorationto enable them to better understand differences between patient groups and the complex bidirectional interplay between clinical measurement and the brain. These exploration concepts enable neuroscientists, for the first time during their investigations, to interactively move between and reason about questions such as ‘which clinical measurements are correlated with a specific brain region?’ or ‘are there differences in brain activity between depressed young and old subjects?’. The environment uses parallel coordinates for effective overview and selection of subject groups, Welch's t-test to filter out brain regions with statistically significant differences, and multiple visualizations of Pearson correlations between brain regions and clinical parameters to facilitate correlation analysis. A qualitative user study was performed with three neuroscientists from different domains. The study shows that the developed environment supports simultaneous analysis of more parameters, provides rapid pathways to insights, and is an effective support tool for hypothesis formation.

National Category
Media and Communication Technology
Identifiers
urn:nbn:se:liu:diva-160856 (URN)10.2312/vcbm.20191232 (DOI)978-3-03868-081-9 (ISBN)
Conference
Eurographics Workshop on Visual Computing for Biology and Medicine
Projects
Seeing Organ Function
Funder
Knut and Alice Wallenberg Foundation, 2013-0076Swedish Research Council, 2015-05462ELLIIT - The Linköping‐Lund Initiative on IT and Mobile CommunicationsSwedish e‐Science Research Center
Available from: 2019-10-10 Created: 2019-10-10 Last updated: 2019-10-10
Bednarska, O., Icenhour, A., Tapper, S., Witt, S. T., Tisell, A., Lundberg, P., . . . Walter, S. (2019). Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome. Pain, 160(9), 2004-2012
Open this publication in new window or tab >>Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome
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2019 (English)In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 160, no 9, p. 2004-2012Article in journal (Refereed) Published
Abstract [en]

Irritable bowel syndrome (IBS) is a visceral pain condition with psychological comorbidity. Brain imaging studies in IBS demonstratealtered function in anterior insula (aINS), a key hub for integration of interoceptive, affective, and cognitive processes. However,alterations in aINS excitatory and inhibitory neurotransmission as putative biochemical underpinnings of these functional changesremain elusive. Using quantitative magnetic resonance spectroscopy, we compared women with IBS and healthy women (healthycontrols [HC]) with respect to aINS glutamate 1 glutamine (Glx) and g-aminobutyric acid (GABA1) concentrations and addressedpossible associations with symptoms. Thirty-nine women with IBS and 21 HC underwent quantitative magnetic resonancespectroscopy of bilateral aINS to assess Glx and GABA1 concentrations. Questionnaire data from all participants and prospectivesymptom-diary data from patients were obtained for regression analyses of neurotransmitter concentrations with IBS-related andpsychological parameters. Concentrations of Glx were lower in IBS compared with HC (left aINS P , 0.05, right aINS P , 0.001),whereas no group differences were detected for GABA1concentrations. Lower right-lateralized Glx concentrations in patients weresubstantially predicted by longer pain duration, while less frequent use of adaptive pain‐coping predicted lower Glx in left aINS. Ourfindings provide first evidence for reduced excitatory but unaltered inhibitory neurotransmitter levels in aINS in IBS. The results alsoindicate a functional lateralization of aINS with a stronger involvement of the right hemisphere in perception of abdominal pain and ofthe left aINS in cognitive pain regulation. Our findings suggest that glutaminergic deficiency may play a role in pain processing in IBS.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
Keywords
Irritable bowel syndrome, Functional magnetic resonance imaging, Quantitative magnetic resonance spectroscopy, Insula, Visceral pain, Coping
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-160012 (URN)10.1097/j.pain.0000000000001589 (DOI)31045748 (PubMedID)
Available from: 2019-09-02 Created: 2019-09-02 Last updated: 2019-09-09Bibliographically approved
Jönsson, D., Bergström, A., Algström, I., Simon, R., Engström, M., Walter, S. & Hotz, I. (2019). Visual Analysis for Understanding Irritable Bowel Syndrome. In: Paul Rea (Ed.), Biomedical Visualisation: (pp. 111-122). Cham: Springer
Open this publication in new window or tab >>Visual Analysis for Understanding Irritable Bowel Syndrome
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2019 (English)In: Biomedical Visualisation / [ed] Paul Rea, Cham: Springer, 2019, p. 111-122Chapter in book (Refereed)
Abstract [en]

The cause of irritable bowel syndrome (IBS), a chronic disorder characterized by abdominal pain and disturbed bowel habits, is largely unknown. It is believed to be related to physical properties in the gut, central mechanisms in the brain, psychological factors, or a combination of these. To understand the relationships within the gut-brain axis with respect to IBS, large numbers of measurements ranging from stool samples to functional magnetic resonance imaging are collected from patients with IBS and healthy controls. As such, IBS is a typical example in medical research where research turns into a big data analysis challenge. In this chapter we demonstrate the power of interactive visual data analysis and exploration to generate an environment for scientific reasoning and hypothesis formulation for data from multiple sources with different character. Three case studies are presented to show the utility of the presented work.

Place, publisher, year, edition, pages
Cham: Springer, 2019
Series
Advances in Experimental Medicine and Biology ; 1156
Keywords
Explorative data analytics, Visualization in medicine, Irritable bowel syndrome
National Category
Media and Communication Technology
Identifiers
urn:nbn:se:liu:diva-160859 (URN)10.1007/978-3-030-19385-0_8 (DOI)9783030193843 (ISBN)9783030193850 (ISBN)
Funder
Knut and Alice Wallenberg Foundation, 2013-0076Swedish Research Council, 2015-05462ELLIIT - The Linköping‐Lund Initiative on IT and Mobile CommunicationsSwedish e‐Science Research Center
Available from: 2019-10-10 Created: 2019-10-10 Last updated: 2019-10-11Bibliographically approved
Witt, S. T., Drissi, N. M., Tapper, S., Wretman, A., Szakács, A., Hallböök, T., . . . Engström, M. (2018). Evidence for cognitive resource imbalance in adolescents with narcolepsy. Brain Imaging and Behavior, 12(2), 411-424
Open this publication in new window or tab >>Evidence for cognitive resource imbalance in adolescents with narcolepsy
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2018 (English)In: Brain Imaging and Behavior, ISSN 1931-7557, E-ISSN 1931-7565, Vol. 12, no 2, p. 411-424Article in journal (Refereed) Published
Abstract [en]

The study investigated brain activity changes during performance of a verbal working memory task in a population of adolescents with narcolepsy. Seventeen narcolepsy patients and twenty healthy controls performed a verbal working memory task during simultaneous fMRI and EEG acquisition. All subjects also underwent MRS to measure GABA and Glutamate concentrations in the medial prefrontal cortex. Activation levels in the default mode network and left middle frontal gyrus were examined to investigate whether narcolepsy is characterized by an imbalance in cognitive resources. Significantly increased deactivation within the default mode network during task performance was observed for the narcolepsy patients for both the encoding and recognition phases of the task. No evidence for task performance deficits or reduced activation within the left middle frontal gyrus was noted for the narcolepsy patients. Correlation analyses between the spectroscopy and fMRI data indicated that deactivation of the anterior aspect of the default mode in narcolepsy patients correlated more with increased concentrations of Glutamate and decreased concentrations of GABA. In contrast, deactivation in the default mode was correlated with increased concentrations of GABA and decreased concentrations of Glutamate in controls. The results suggested that narcolepsy is not characterized by a deficit in working memory but rather an imbalance of cognitive resources in favor of monitoring and maintaining attention over actual task performance. This points towards dysregulation within the sustained attention system being the origin behind self-reported cognitive difficulties in narcolepsy.

Place, publisher, year, edition, pages
Springer-Verlag New York, 2018
Keywords
EEG, GABA, MRS, Narcolepsy, Working memory, fMRI
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-145535 (URN)10.1007/s11682-017-9706-y (DOI)000429029000011 ()28321606 (PubMedID)2-s2.0-85015625386 (Scopus ID)
Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2019-05-01Bibliographically approved
Simon, R., Pihlsgård, J., Berglind, U., Söderfeldt, B. & Engström, M. (2017). Mantra meditation suppression of default mode beyond an active task: a pilot study. Journal of Cognitive Enhancement, 1(2), 219-227
Open this publication in new window or tab >>Mantra meditation suppression of default mode beyond an active task: a pilot study
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2017 (English)In: Journal of Cognitive Enhancement, ISSN 2509-3290, Vol. 1, no 2, p. 219-227Article in journal (Refereed) Published
Abstract [en]

Within the field of neuroimaging, the discovery of a constellation of brain regions silently active when we are “resting” has provided a new view into the elusive effects of meditative practice. This network, called the default mode network (DMN), has been shown by functional neuroimaging to be active when an individual is at rest. Meta-analyses of the fMRI neurocorrelates of meditation have shown that across diverse practices, the most common general effect appears to be modulation of regions within the DMN. The specific ...

Place, publisher, year, edition, pages
Springer, 2017
Keywords
Meditation, Mantra, Attention, Default mode network, Anterior cingulate cortex, Posterior cingulate cortex, Precuneus, Functional magnetic resonance imaging (fMRI), Deactivation, Kundalini yoga
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-139581 (URN)10.1007/s41465-017-0028-1 (DOI)
Available from: 2017-08-09 Created: 2017-08-09 Last updated: 2018-01-13Bibliographically approved
Van Ettinger-Veenstra, H., Mcallister, A., Lundberg, P., Karlsson, T. & Engström, M. (2016). Higher Language Ability is Related to Angular Gyrus Activation Increase During Semantic Processing, Independent of Sentence Incongruency. Frontiers in Human Neuroscience, 10(110)
Open this publication in new window or tab >>Higher Language Ability is Related to Angular Gyrus Activation Increase During Semantic Processing, Independent of Sentence Incongruency
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2016 (English)In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 10, no 110Article in journal (Refereed) Published
Abstract [en]

This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task which tapped language comprehension and inference, and modulated sentence congruency employing functional magnetic resonance imaging (fMRI). We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, there was a significant increase of activation in the inferior frontal gyrus (IFG) bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing, is opposed to what the neural efficiency hypothesis would predict. We can conclude that no evidence is found for an interaction between semantic congruency related brain activation and highlevel language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2016
Keywords
fMRI; semantic processing; congruency; sentence reading; language ability; inferior frontal gyrus; angular gyrus
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-126805 (URN)10.3389/fnhum.2016.00110 (DOI)000371873000001 ()27014040 (PubMedID)
Note

Funding Agencies|Linkoping University; Linkoping University Hospital local funds

Available from: 2016-04-07 Created: 2016-04-05 Last updated: 2018-01-10
Lundengård, K., Cedersund, G., Sten, S., Leong, F., Smedberg, A., Elinder, F. & Engström, M. (2016). Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI. PloS Computational Biology, 12(6), Article ID e1004971.
Open this publication in new window or tab >>Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI
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2016 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 12, no 6, article id e1004971Article in journal (Refereed) Published
Abstract [en]

Functional magnetic resonance imaging (fMRI) measures brain activity by detecting the blood-oxygen-level dependent (BOLD) response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neuronal activity. The exact mechanisms behind this neurovascular coupling are not yet fully investigated. There are at least three different ways in which these mechanisms are being discussed. Firstly, mathematical models involving the so-called Balloon model describes the relation between oxygen metabolism, cerebral blood volume, and cerebral blood flow. However, the Balloon model does not describe cellular and biochemical mechanisms. Secondly, the metabolic feedback hypothesis, which is based on experimental findings on metabolism associated with brain activation, and thirdly, the neurotransmitter feed-forward hypothesis which describes intracellular pathways leading to vasoactive substance release. Both the metabolic feedback and the neurotransmitter feed-forward hypotheses have been extensively studied, but only experimentally. These two hypotheses have never been implemented as mathematical models. Here we investigate these two hypotheses by mechanistic mathematical modeling using a systems biology approach; these methods have been used in biological research for many years but never been applied to the BOLD response in fMRI. In the current work, model structures describing the metabolic feedback and the neurotransmitter feed-forward hypotheses were applied to measured BOLD responses in the visual cortex of 12 healthy volunteers. Evaluating each hypothesis separately shows that neither hypothesis alone can describe the data in a biologically plausible way. However, by adding metabolism to the neurotransmitter feed-forward model structure, we obtained a new model structure which is able to fit the estimation data and successfully predict new, independent validation data. These results open the door to a new type of fMRI analysis that more accurately reflects the true neuronal activity.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2016
National Category
Bioinformatics (Computational Biology)
Identifiers
urn:nbn:se:liu:diva-130437 (URN)10.1371/journal.pcbi.1004971 (DOI)000379349700045 ()27310017 (PubMedID)
Note

Funding Agencies|Swedish Research council [2014-6249]; Knut and Alice Wallenbergs foundation, KAW [2013.0076]; Research council of Southeast Sweden [FORSS-481691]; Linkoping University

Available from: 2016-08-06 Created: 2016-08-05 Last updated: 2018-03-19
Warntjes, M. J., Engström, M., Tisell, A. & Lundberg, P. (2016). Modeling the Presence of Myelin and Edema in the Brain Based on Multi-Parametric Quantitative MRI. Frontiers in Neurology, 7(16)
Open this publication in new window or tab >>Modeling the Presence of Myelin and Edema in the Brain Based on Multi-Parametric Quantitative MRI
2016 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 7, no 16Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to present a model that uses multi-parametric quantitative MRI to estimate the presence of myelin and edema in the brain. The model relates simultaneous measurement of R-1 and R-2 relaxation rates and proton density to four partial volume compartments, consisting of myelin partial volume, cellular partial volume, free water partial volume, and excess parenchymal water partial volume. The model parameters were obtained using spatially normalized brain images of a group of 20 healthy controls. The pathological brain was modeled in terms of the reduction of myelin content and presence of excess parenchymal water, which indicates the degree of edema. The method was tested on spatially normalized brain images of a group of 20 age-matched multiple sclerosis (MS) patients. Clear differences were observed with respect to the healthy controls: the MS group had a 79 mL smaller brain volume (1069 vs. 1148 mL), a 38 mL smaller myelin volume (119 vs. 157 mL), and a 21 mL larger excess parenchymal water volume (78 vs. 57 mL). Template regions of interest of various brain structures indicated that the myelin partial volume in the MS group was 1.6 +/- 1.5% lower for gray matter (GM) structures and 2.8 +/- 1.0% lower for white matter (WM) structures. The excess parenchymal water partial volume was 9 +/- 10% larger for GM and 5 +/- 2% larger for WM. Manually placed ROls indicated that the results using the template ROls may have suffered from loss of anatomical detail due to the spatial normalization process. Examples of the application of the method on high-resolution images are provided for three individual subjects: a 45-year-old healthy subject, a 72-year-old healthy subject, and a 45-year-old MS patient. The observed results agreed with the expected behavior considering both age and disease. In conclusion, the proposed model may provide clinically important parameters, such as the total brain volume, degree of myelination, and degree of edema, based on a single qMRI acquisition with a clinically acceptable scan time.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2016
Keywords
quantitative magnetic resonance imaging; brain tissue modeling; myelin; edema; T-1 relaxation; T-2 relaxation; proton density
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126132 (URN)10.3389/fneur.2016.00016 (DOI)000370433200002 ()26925030 (PubMedID)
Note

Funding Agencies|Linkoping University; County Council Ostergotland

Available from: 2016-03-15 Created: 2016-03-15 Last updated: 2017-11-30
Källman, U., Bergstrand, S., Ek, A.-C., Engström, M. & Lindgren, M. (2016). Nursing staff induced repositionings and immobile patients' spontaneous movements in nursing care.. International Wound Journal, 13(6), 1168-1175
Open this publication in new window or tab >>Nursing staff induced repositionings and immobile patients' spontaneous movements in nursing care.
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2016 (English)In: International Wound Journal, ISSN 1742-4801, E-ISSN 1742-481X, Vol. 13, no 6, p. 1168-1175Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate nursing staff induced repositionings and the patients' spontaneous movements during the day and night among older immobile patients in nursing care. Furthermore, the aim was to identify factors associated with the nursing staff induced repositionings and the patients' spontaneous movement frequency. An observational cross-sectional design was used. Spontaneous movements among patients (n = 52) were registered continuously using the MovinSense monitoring system. The nursing staff documented each time they repositioned the patient. Patients spontaneous movements were compared with nursing staff induced repositionings. There were large variations in the patients' spontaneous repositioning frequency during both days and nights, which shows that, although immobilised, some patients frequently reposition themselves. Analgesics were positively related to the movement frequency and psycholeptics were negatively related. The nursing staff more often repositioned the patients who were assessed as high risk than those assessed as low risk, but the patients' spontaneous movement frequency was not correlated to the risk score. This may be important when planning repositioning schedules. A monitoring system may be useful in decision making with regard to planning repositioning and positions used in the prevention of pressure ulcers among elderly immobile patients.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keywords
Nursing home residents, patient repositioning, pressure ulcer, interface pressure, skin temperature, tissue blood flow
National Category
Nursing
Identifiers
urn:nbn:se:liu:diva-117445 (URN)10.1111/iwj.12435 (DOI)000387664400011 ()25779932 (PubMedID)
Note

Funding agencies: Research Council Sodra Alvsborg Boras Sweden; Research Council ostergotland Linkoping Sweden; SwedBank Sjuharad foundation for research at the Sodra Alvsborg Hospital Boras Sweden; Sodra Alvsborgs Hospital Boras Sweden; King Gustaf V and Queen Victorias F

Available from: 2015-04-27 Created: 2015-04-27 Last updated: 2017-12-04Bibliographically approved
Walter, S. A., Forsgren, M., Lundengård, K., Simon, R., Torkildsen Nilsson, M., Söderfeldt, B., . . . Engström, M. (2016). Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex. PLoS ONE, 11(3)
Open this publication in new window or tab >>Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3Article in journal (Refereed) Published
Abstract [en]

Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms.

Place, publisher, year, edition, pages
San Francisco, CA, United States: Public Library of Science, 2016
Keywords
quantitative magnetic resonance imaging; brain tissue modeling; myelin; edema; T-1 relaxation; T-2 relaxation; proton density
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-126192 (URN)10.1371/journal.pone.0148737 (DOI)000371434500011 ()26930498 (PubMedID)
Note

Funding agencies: Linkoping University; County Council of Ostergotland

Available from: 2016-03-18 Created: 2016-03-18 Last updated: 2018-01-10Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2167-2450

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