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  • 1.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Geriatric Medicine in Norrköping.
    Nath, Sangeeta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Domert, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Proteasome Inhibition Induces Stress Kinase Dependent Transport Deficits – Implications for Alzheimer’s Disease2014In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 58, p. 29-39Article in journal (Refereed)
    Abstract [en]

    Alzheimer’s disease (AD) is characterized by accumulation of two misfolded and aggregated proteins, β-amyloid and hyperphosphorylated tau. Both cellular systems responsible for clearance of misfolded and aggregated proteins, the lysosomal and the proteasomal, have been shown to be malfunctioning in the aged brain and more so in AD patients. This malfunction could be the cause of β-amyloid and tau accumulation, eventually aggregating in plaques and tangles. We have investigated how decreased proteasome activity affects AD related pathophysiological changes of microtubule transport and stability, as well as tau phosphorylation. To do this, we used our recently developed neuronal model where human SH-SY5Y cells obtain neuronal morphology and function through differentiation. We found that exposure to low doses of the proteasome inhibitor MG-115 caused disturbed neuritic transport, together with microtubule destabilization and tau phosphorylation. Furthermore, reduced proteasome activity activated several kinases implicated in AD pathology, including JNK, c-Jun and ERK 1/2. Restoration of the microtubule transport was achieved by inhibiting ERK 1/2 activation, and simultaneous inhibition of both ERK 1/2 and c-Jun reversed the proteasome inhibition-induced tau phosphorylation. Taken together, this study suggests that a decrease in proteasome activity can, through activation of c-Jun and ERK 1/2, result in several events contributing to AD pathology. Restoring proteasome function or inhibiting ERK 1/2 and c-Jun could therefore be used as novel treatments against AD.

  • 2.
    Andersson, Lena B.
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Rehabilitation in Central County.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Health-related quality of life and activities of daily living in 85-year-olds in sweden2014In: Health and Social Care in the Community, ISSN 0966-0410, Vol. 22, no 4, p. 368-374Article in journal (Refereed)
    Abstract [en]

    Few studies have examined health-related quality of life (HRQoL) with respect to daily living and health factors for relatively healthy elderly individuals. To this end, this study examines 85-year-olds’ reported HRQoL in relation to social support, perceived health, chronic diseases, health care use and instrumental activities of daily living. Data were collected from 360 participants (55% response rate) between March 2007 and March 2008 using a postal questionnaire and a home visit interview.  HRQoL was assessed using the EQ-5D-3L. For the items in the EQ-5D-3L, more problems were related to lower HRQoL. Restricted mobility and occurrence of pain/discomfort was common.  Lower HRQoL was associated with increased risk for depression, increased use of medication, increased number of chronic diseases, and more problems with instrumental activities of daily living (IADL). Health care use and health care costs was correlated to lower HRQoL.  HRQoL is of importance to health care providers and must be considered together with IADL in the elderly population when planning interventions. These should take into account the specific needs and resources of the older individuals.

  • 3.
    Ansell, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Identification of Tumor Cell- and Stroma Derived Biomarkers of Treatment Response in Head and Neck Cancer2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Head and neck squamous cell carcinoma (HNSCC) poses a major health problem in the world with approximately 600 000 new cases yearly. Treatment resistance is a major problem within this patient group and despite advances in treatment strategies the overall survival rate has unfortunately not increased.

    One of the major components of the tumor microenvironment is the cancer associated fibroblasts (CAFs) which can modulate the treatment sensitivity, tumor growth, and the invasive potential of tumor cells.

    The aim of this thesis was to identify predictive markers for treatment response in HNSCC and to study the crosstalk between tumor cells and CAFs that may underlie treatment resistance.

    In paper I, we identified gene expression differences between one cisplatin sensitive cell line and two cisplatin resistant cell lines, by microarray analysis, and found that a high expression of matrix metalloproteinase (MMP) -7 was associated with resistance to cisplatin. In paper II, the epidermal growth factor (EGF) receptor ligands EGF, amphiregulin, and epiregulin were evaluated regarding their potential use as predictive biomarkers for cetuximab treatment response in tongue cancer cell lines and it was shown that EGF may serve as a marker for poor cetuximab response. In paper III and IV, we investigated the influence of CAFs on the proliferation, migration, gene expression, and cetuximab response of tumor cells. It was found that CAFs induced resistance to cetuximab in a MMP-dependent manner. In addition, a microarray analysis, comparing tumor cells co-cultured with CAFs and tumor cells cultured alone, revealed that CAFs induced multiple gene expression changes in tumor cells some of which are related to epithelial to mesenchymal transition. Some of these changes were found to be dependent on cell-cell contact.

    Taken together, we here suggest MMP-7 and EGF to be predictive markers of cisplatin and cetuximab response, respectively. We also show that CAFs protect HNSCC cells from cetuximab treatment; however, the factor responsible for the protective effect is yet to be discovered.

    List of papers
    1. Matrix metalloproteinase-7 and -13 expression associate to cisplatin resistance in head and neck cancer cell lines.
    Open this publication in new window or tab >>Matrix metalloproteinase-7 and -13 expression associate to cisplatin resistance in head and neck cancer cell lines.
    Show others...
    2009 (English)In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 45, no 10, p. 866-871Article in journal (Refereed) Published
    Abstract [en]

    Concomitant chemoradiotherapy is a common treatment for advanced head and neck squamous cell carcinomas (HNSCC). Cisplatin is the backbone of chemotherapy regimens used to treat HNSCC. Therefore, the aim of this study was to identify predictive markers for cisplatin treatment outcome in HNSCC. The intrinsic cisplatin sensitivity (ICS) was determined in a panel of tumour cell lines. From this panel, one sensitive and two resistant cell lines were selected for comparative transcript profiling using microarray analysis. The enrichment of Gene Ontology (GO) categories in sensitive versus resistant cell lines were assessed using the Gene Ontology Tree Machine bioinformatics tool. In total, 781 transcripts were found to be differentially expressed and 11 GO categories were enriched. Transcripts contributing to this enrichment were further analyzed using Ingenuity Pathway Analysis (IPA) for identification of key regulator genes. IPA recognized 20 key regulator genes of which five were differentially expressed in sensitive versus resistant cell lines. The mRNA level of these five genes was further assessed in a panel of 25 HNSCC cell lines using quantitative real-time PCR. Among these key regulators, MMP-7 and MMP-13 are implicated as potential biomarkers of ICS. Taken together, genome-wide transcriptional analysis identified single genes, GO categories as well as molecular networks that are differentially expressed in HNSCC cell lines with different ICS. Furthermore, two novel predictive biomarkers for cisplatin resistance, MMP-7 and MMP-13, were identified.

    Place, publisher, year, edition, pages
    Elsevier, 2009
    Keywords
    Predictive markers; Gene Ontology; Head and neck cancer; Cisplatin; Microarray; MMPs
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-21436 (URN)10.1016/j.oraloncology.2009.02.008 (DOI)000270022000005 ()19442568 (PubMedID)
    Available from: 2009-10-01 Created: 2009-10-01 Last updated: 2017-12-13Bibliographically approved
    2. Epidermal growth factor is a biomarker for poor cetuximab response in tongue cancer cells
    Open this publication in new window or tab >>Epidermal growth factor is a biomarker for poor cetuximab response in tongue cancer cells
    2016 (English)In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 45, no 1, p. 9-16Article in journal (Refereed) Published
    Abstract [en]

    Background: Epidermal growth factor receptor (EGFR) is a target for treatment in tongue cancer. Here, EGFR ligands were evaluated for their potential uses as predictive biomarkers of cetuximab treatment response.

    Methods: In three tongue cancer cell lines the influences of epidermal growth factor (EGF), amphiregulin (AR), and epiregulin (EPR) on tumour cell proliferation and cetuximab response were evaluated by the addition of recombinant human (rh) proteins or the siRNA-mediated downregulation of endogenous ligand production.

    Results: EGF or AR downregulation suppressed the proliferation of all investigated cell lines. Furthermore, all cell lines displayed increased cetuximab resistance upon the addition of rhEGF, whereas EGF silencing resulted in an improved cetuximab response in one cell line.

    Conclusions: Our data suggest that EGF and AR are critical components of the EGFR signalling network required for full proliferative potential. Moreover, EGF is a potential predictive biomarker of poor cetuximab response and a possible treatment target.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2016
    Keywords
    Head and neck cancer; Tongue cancer; Erbitux; EGFR ligands; treatment response
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-100675 (URN)10.1111/jop.12310 (DOI)000369990100003 ()
    Note

    Funding agencies: Foundation of Ake Wiberg; Swedish Cancer Society [2008/552, 2010/545]; County Council of Ostergotland; Linkoping University Hospital; Foundation of Magnus Bergvall; Cancer Foundation of Ostergotland

    Vid tiden för disputation förelåg publikationen endast som manuskript

    Available from: 2013-11-11 Created: 2013-11-11 Last updated: 2017-05-03
    3. Cancer-Associated Fibroblasts Induce Matrix Metalloproteinase-Mediated Cetuximab Resistance in Head and Neck Squamous Cell Carcinoma Cells
    Open this publication in new window or tab >>Cancer-Associated Fibroblasts Induce Matrix Metalloproteinase-Mediated Cetuximab Resistance in Head and Neck Squamous Cell Carcinoma Cells
    Show others...
    2012 (English)In: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 10, no 9, p. 1158-1168Article in journal (Refereed) Published
    Abstract [en]

    A growing body of evidence suggests that components of the tumor microenvironment, including cancer-associated fibroblasts (CAF), may modulate the treatment sensitivity of tumor cells. Here, we investigated the possible influence of CAFs on the sensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines to cetuximab, an antagonistic epidermal growth factor receptor (EGFR) antibody. Cetuximab treatment caused a reduction in the proliferation rate of HNSCC cell lines, whereas the growth of HNSCC-derived CAF cultures was unaffected. When tumor cells were cocultured with CAFs in a transwell system, the cetuximab-induced growth inhibition was reduced, and a complete protection from growth inhibition was observed in one of the tumor cell lines investigated. Media that had been conditioned by CAFs offered protection from cetuximab treatment in a concentration-dependent manner, suggesting that the resistance to treatment was mediated by CAF-derived soluble factors. The coculture of HNSCC cell lines with CAFs resulted in an elevated expression of matrix metalloproteinase-1 (MMP-1) in both the tumor cells and CAFs. Moreover, the CAF-induced resistance was partly abolished by the presence of an MMP inhibitor. However, CAFs treated with siRNA targeting MMP-1 still protected tumor cells from cetuximab treatment, suggesting that several MMPs may cooperate to facilitate resistance or that the protective effect is mediated by another member of the MMP family. These results identify a novel CAF-dependent modulation of cetuximab sensitivity and suggest that inhibiting MMPs may improve the effects of EGFR-targeted therapy.

    Place, publisher, year, edition, pages
    American Association for Cancer Research, 2012
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-86135 (URN)10.1158/1541-7786.MCR-12-0030 (DOI)000310648300003 ()
    Note

    Funding Agencies|Johan and Jakob Soderberg Foundation||Foundation Olle Engqvist Byggmastare||Swedish Laryng Foundation||Borgholm Rotary Club||Swedish National Board of Health and Welfare||Lions Research Foundation||Lars Hierta Memorial Foundation||Tore Nilsson Foundation for Medical Research||Swedish Society for medical research||County Council of Ostergotland||Cancer Foundation of Ostergotland||Merck Serono||Swedish Research Council|349-2008-6578|Swedish Cancer Society|CAN 2009/1136CAN 2010/545|

    Available from: 2012-12-07 Created: 2012-12-07 Last updated: 2017-12-07
    4. Molecular cross-talk between head and neck squamous cell carcinoma cells and cancer-associated fibroblasts
    Open this publication in new window or tab >>Molecular cross-talk between head and neck squamous cell carcinoma cells and cancer-associated fibroblasts
    Show others...
    2013 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Cancer-associated fibroblasts (CAFs) are one of the main components of the tumor stroma and are known to increase tumor growth and stimulate  invasion and metastasis. Increasing evidence suggests that CAFs may also be an important determinant of the response to various treatments. In this study we aimed to characterize the molecular cross-talk between CAFs and head and neck squamous cell carcinoma (HNSCC) cells.

    HNSCC cell lines were co-cultured with their patient-matched CAFs for seven days, after which the gene expression of tumor cells was investigated by Affymetrix microarray. 58 protein coding genes were found to be differentially expressed (Q≤0.05) in tumor cells cocultured with CAFs when compared to tumor cells cultured alone. The top functions of these genes were cancer, cellular movement, and embryonic development as analyzed by Ingenuity Pathway Analysis. Nine genes were upregulated by ≥1.5-fold while the expression of 35 genes was found to be reduced by ≤ 0.67-fold. Several of the differentially expressed genes have been associated with epithelial-to-mesenchymal transition (EMT). The change in the expression of POSTN, GREM1, COL1A2, VIM, and MMP7 was verified by qPCR analysis. Moreover, the influence of CAFs on the proliferation, migration and cetuximab sensitivity of tumor cells was investigated, and was found to vary among the tumor cell-CAF pairs.

    In conclusion, we demonstrate that CAF-derived signals cause changes in the expression of multiple genes, several of which are associated with an EMT phenotype of tumor cells. Furthermore, CAFs modulate the proliferation, migration and cetuximab treatment response of tumor cells.

    Keywords
    Head and neck cancer; Tongue cancer; Erbitux; EGFR ligands; treatment response
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-100678 (URN)
    Available from: 2013-11-11 Created: 2013-11-11 Last updated: 2013-11-11Bibliographically approved
  • 4.
    Ansell, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Kankainen, M.
    Institute of Biomedicine, Medical Biochemistry and Developmental Biology, Genome-Scale Biology, Research Program, University of Helsinki, Helsinki, Finland.
    Jönsson, Jan-Ingvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Monni, O.
    Institute of Biomedicine, Medical Biochemistry and Developmental Biology, Genome-Scale Biology, Research Program, University of Helsinki, Helsinki, Finland.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Johansson, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Molecular cross-talk between head and neck squamous cell carcinoma cells and cancer-associated fibroblasts2013Manuscript (preprint) (Other academic)
    Abstract [en]

    Cancer-associated fibroblasts (CAFs) are one of the main components of the tumor stroma and are known to increase tumor growth and stimulate  invasion and metastasis. Increasing evidence suggests that CAFs may also be an important determinant of the response to various treatments. In this study we aimed to characterize the molecular cross-talk between CAFs and head and neck squamous cell carcinoma (HNSCC) cells.

    HNSCC cell lines were co-cultured with their patient-matched CAFs for seven days, after which the gene expression of tumor cells was investigated by Affymetrix microarray. 58 protein coding genes were found to be differentially expressed (Q≤0.05) in tumor cells cocultured with CAFs when compared to tumor cells cultured alone. The top functions of these genes were cancer, cellular movement, and embryonic development as analyzed by Ingenuity Pathway Analysis. Nine genes were upregulated by ≥1.5-fold while the expression of 35 genes was found to be reduced by ≤ 0.67-fold. Several of the differentially expressed genes have been associated with epithelial-to-mesenchymal transition (EMT). The change in the expression of POSTN, GREM1, COL1A2, VIM, and MMP7 was verified by qPCR analysis. Moreover, the influence of CAFs on the proliferation, migration and cetuximab sensitivity of tumor cells was investigated, and was found to vary among the tumor cell-CAF pairs.

    In conclusion, we demonstrate that CAF-derived signals cause changes in the expression of multiple genes, several of which are associated with an EMT phenotype of tumor cells. Furthermore, CAFs modulate the proliferation, migration and cetuximab treatment response of tumor cells.

  • 5.
    Asp, Filip
    et al.
    Karolinska Institutet.
    Mäki-Torkko, Elina
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Karltorp, Eva
    Karolinska Institutet.
    Harder, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience.
    Hergils, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Hur hör barn med bilaterala cochlea-implantat jämfört med normalhörande?2012Conference paper (Refereed)
  • 6.
    Austeng, Dordi
    et al.
    Uppsala University, Sweden University of Trondheim Hospital, Norway .
    Kallen, Karin
    Lund University, Sweden .
    Hellstrom, Ann
    University of Gothenburg, Sweden .
    Jakobsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lundgren, Pia
    Umeå University, Sweden .
    Tornqvist, Kristina
    University of Lund Hospital, Sweden .
    Wallin, Agneta
    St Eriks Eye Hospital, Sweden .
    Holmstrom, Gerd
    Uppsala University, Sweden .
    Regional differences in screening for retinopathy of prematurity in infants born before 27 weeks of gestation in Sweden - the EXPRESS study2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 4, p. 311-315Article in journal (Refereed)
    Abstract [en]

    Purpose: The primary aim was to analyse regional incidences of retinopathy of prematurity (ROP) and frequencies of treatment and their relation to perinatal risk factors during a 3-year period. A secondary aim was to study adherence to the study screening protocol in the different regions. Methods: A population-based study of neonatal morbidity in extremely preterm infants in Sweden (EXPRESS) was performed during 2004-2007. Screening for ROP was to start at postnatal age 5weeks and to continue weekly until the retina was completely vascularized or until regression of ROP. Logistic regression analyses were used for evaluation of differences in incidence of Any ROP, ROP 3 or more and ROP Type 1 between the seven regions of the country. Results: The regional incidence of ROP varied between 54% and 92% for Any ROP, between 25% and 43% for ROP stage 3 or more and between 8% and 23% of infants with ROP Type 1, all of whom were treated. There was no significant difference between the regions regarding ROP Type 1, even when adjusting for known risk factors for ROP. Conclusion: The heterogeneity between the regions regarding the incidence of ROP was reduced with increasing severity of ROP, and there was no heterogeneity regarding frequency of treatment for ROP, which is the most important issue for the children. We cannot exclude observer bias regarding mild ROP and ROP stage 3 in this study.

  • 7.
    Ball, Martin J
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    The rhaeadr effect in clinical phonology2014In: Clinical Linguistics & Phonetics, ISSN 0269-9206, E-ISSN 1464-5076, Vol. 28, no 7-8, p. 453-462Article in journal (Refereed)
    Abstract [en]

    A distinction is drawn between Crystals bucket theory of language processing and an overflow of effects between different linguistic levels in language production. Most of the examples are drawn from Welsh (a language of mutual interest to the author and the honoree of this issue). For that reason, it is proposed that this effect is termed the rhaeadr effect (from the Welsh for waterfall). The rhaeadr effect is illustrated with the initial consonant mutation systems of Welsh and Irish, and with data from both normal phonological (and morphophonological) development and disordered speech.

  • 8.
    Ball, Martin J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Granese, Angela
    University of Louisiana at Lafayette.
    Towards an evidence-base for /r/ therapy in English.2013In: Journal of Clinical Speech and Language Studies, ISSN 0791-5985, Vol. 20, p. 1-23Article in journal (Refereed)
  • 9.
    Ball, Martin J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Müller, Nicole
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Editorial Material2014In: Clinical Linguistics & Phonetics, ISSN 0269-9206, E-ISSN 1464-5076, Vol. 28, no 7-8, p. 451-452Article in journal (Other academic)
    Abstract [en]

    n/a

  • 10.
    Ball, Martin J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Müller, NicoleLinköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.Nelson, Ryan L.University of Louisiana at Lafayette, LA, USA.
    Handbook of qualitative research in communication disorders2014Collection (editor) (Other academic)
    Abstract [en]

    This volume provides a comprehensive and in-depth handbook of qualitative research in the field of communication disorders. It introduces and illustrates the wide range of qualitative paradigms that have been used in recent years to investigate various aspects of communication disorders.

    The first part of the Handbook introduces in some detail the concept of qualitative research and its application to communication disorders, and describes the main qualitative research approaches. The contributions are forward-looking rather than merely giving an overview of their topic. The second part illustrates these approaches through a series of case studies of different communication disorders using qualitative methods of research.

    This Handbook is an essential resource for senior undergraduate and graduate students, researchers and practitioners, in communication disorders and related fields.

  • 11.
    Ball, Martin J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Rutter, Ben
    University of Sheffield, UK.
    Kroll, Tobias
    Texas Tech University, USA.
    Interactional phonetics: background and examples.2014In: Handbook of qualitative research in communication disorders / [ed] Martin J. Ball, Nicole Müller, and Ryan L. Nelson, New York: Psychology Press, 2014, p. 311-328Chapter in book (Refereed)
  • 12.
    Bergdahl, Björn
    et al.
    Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences.
    Fyrenius, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences.
    Hultman, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Ledin, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    In the Forefront of Development:The New Undergraduate Medical Curriculu2006In: Celebrating the Past by Expanding the Future: The Faculty of Health Science, Linköping University 1986–2006 / [ed] Mats Hammar, Björn Bergdahl, Lena Öhman, Linköping: Linköping University Electronic Press, 2006, 1, p. 98-102Chapter in book (Other academic)
  • 13.
    Bergendal, Birgitta
    et al.
    Institute Postgrad Dent Educ, Sweden.
    Bakke, Merete
    University of Copenhagen, Denmark.
    McAllister, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Sjogreen, Lotta
    National Orofacial Resource Centre Rare Disease, Sweden.
    Asten, Pamela
    Lovisenberg Diakonale Hospital, Norway.
    Profiles of orofacial dysfunction in different diagnostic groups using the Nordic Orofacial Test (NOT-S)-A review2014In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 72, no 8, p. 578-584Article, review/survey (Refereed)
    Abstract [en]

    Objective. The Nordic Orofacial Test-Screening (NOT-S) was developed as a comprehensive method to assess orofacial function. Results from the screening protocol have been presented in 11 international publications to date. This study reviewed these publications in order to compile NOT-S screening data and create profiles of orofacial dysfunction that characterize various age groups and disorders. Materials and methods. NOT-S results of nine reports meeting the inclusion criteria were reviewed. Seven of these studies not only provided data on the mean and range of total NOT-S scores, but also on the most common domains of orofacial dysfunction (highest rate of individuals with dysfunction scores), allowing the construction of orofacial dysfunction profiles based on the prevalence of dysfunction in each domain of NOT-S. Results. The compiled data comprised 669 individuals, which included healthy control subjects (n = 333) and various patient groups (n = 336). All studies reported differences between individuals with diagnosed disorders and healthy control subjects. The NOT-S data could measure treatment effects and provided dysfunction profiles characterizing the patterns of orofacial dysfunction in various diagnoses. Conclusions. This review corroborates previous results that the NOT-S differentiates well between patients and healthy controls and can also show changes in individuals after treatment. NOT-S could be used as a standard instrument to assess orofacial dysfunction, evaluate the outcomes of oral habilitation and rehabilitation and improve comparability in clinical practice and research.

  • 14.
    Bernstein, Joshua G
    et al.
    National Military Audiology and Speech Pathology Center Walter Reed National Military Medical Center, Bethesda, MD, USA.
    Danielsson, Henrik
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Hällgren, Mathias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linnaeus Centre HEAD.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Rönnberg, Jerker
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Lunner, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Spectrotemporal modulation sensitivity as a predictor of speech intelligibility in noise with hearing aids2014In: Spectrotemporal modulation sensitivity as a predictor of speech intelligibility in noise with hearing aids, 2014Conference paper (Refereed)
    Abstract [en]

    The audiogram predicts less than a third of the variance in speech reception thresholds (SRTs) for hearing-impaired (HI) listeners properly fit with individualized frequency-dependent gain. The remaining variance is often attributed to a combination of su-prathreshold distortion in the auditory pathway and non-auditory factors such as cogni-tive processing. Distinguishing between these factors requires a measure of suprathresh-old auditory processing to account for the non-cognitive contributions. Preliminary re-sults in 12 HI listeners identified a correlation between spectrotemporal modulation (STM) sensitivity and speech intelligibility in noise presented over headphones. The cur-IHCON 2014 27 August 13-17, 2014rent study assessed the effectiveness of STM sensitivity as a measure of suprathreshold auditory function to predict free-field SRTs in noise for a larger group of 47 HI listeners with hearing aids.SRTs were measured for Hagerman sentences presented at 65 dB SPL in stationary speech-weighted noise or four-talker babble. Pre-recorded speech and masker stimuli were played through a small anechoic chamber equipped with a master hearing aid pro-grammed with individualized gain. The output from an IEC711 Ear Simulator was played binaurally through insert earphones. Three processing algorithms were examined: linear gain, linear gain plus noise reduction, or fast-acting compressive gain.STM stimuli consist of spectrally-rippled noise with spectral-peak frequencies that shift over time. STM with a 2-cycle/octave spectral-ripple density and a 4-Hz modulation rate was applied to a 2-kHz lowpass-filtered pink-noise carrier. Stimuli were presented over headphones at 80 dB SPL (±5-dB roving). The threshold modulation depth was estimated adaptively in a two-alternative forced-choice task.STM sensitivity was strongly correlated (R2=0.48) with the global SRT (i.e., the SRTs averaged across masker and processing conditions). The high-frequency pure-tone aver-age (3-8 kHz) and age together accounted for 23% of the variance in global SRT. STM sensitivity accounted for an additional 28% of the variance in global SRT (total R2=0.51) when combined with these two other metrics in a multiple-regression analysis. Correla-tions between STM sensitivity and SRTs for individual conditions were weaker for noise reduction than for the other algorithms, and marginally stronger for babble than for sta-tionary noise.The results are discussed in the context of previous work suggesting that STM sensitivity for low rates and low carrier frequencies is impaired by a reduced ability to use temporal fine-structure information to detect slowly shifting spectral peaks. STM detection is a fast, simple test of suprathreshold auditory function that accounts for a substantial pro-portion of variability in hearing-aid outcomes for speech perception in noise.

  • 15.
    Bjørnevik, Kjetil
    et al.
    University of Bergen, Norway; Haukeland Hospital, Norway .
    Riise, Trond
    University of Bergen, Norway; Haukeland Hospital, Norway .
    Casetta, Ilaria
    University of Ferrara, Italy .
    Drulovic, Jelena
    University of Belgrade, Serbia .
    Granieri, Enrico
    University of Ferrara, Italy .
    Holmoy, Trygve
    University of Oslo, Norway; Akershus University Hospital, Norway .
    Kampman, Margitta T.
    University of Tromsø, Norway; University Hospital North Norway.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Lauer, Klaus
    Griesheim, Darmstadt, Germany.
    Lossius, Andreas
    University of Oslo, Norway; National Hospital Norway.
    Magalhaes, Sandra
    McGill University, Canada .
    Myhr, Kjell-Morten
    Haukeland Hospital, Norway; University of Bergen, Norway .
    Pekmezovic, Tatjana
    University of Belgrade, Serbia .
    Wesnes, Kristin
    University of Bergen, Norway; Haukeland Hospital, Norway .
    Wolfson, Christina
    McGill University, Canada .
    Pugliatti, Maura
    University of Bergen, Norway; University of Sassari, Italy .
    Sun exposure and multiple sclerosis risk in Norway and Italy: The EnvIMS study2014In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no 8, p. 1042-1049Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    The objective of this paper is to estimate the association between multiple sclerosis (MS) and measures of sun exposure in specific age periods in Norway and Italy.

    METHODS:

    A total of 1660 MS patients and 3050 controls from Italy and Norway who participated in a multinational case-control study (EnvIMS) reported sun habits during childhood and adolescence.

    RESULTS:

    A significant association between infrequent summer outdoor activity and increased MS risk was found in Norway and in Italy. The association was strongest between the ages of 16 and 18 years in Norway (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.30-2.59), and between birth and age 5 years in Italy (OR 1.56, 95% CI 1.16-2.10). In Italy a significant association was also found during winter (OR 1.42, 95% CI 1.03-1.97). Frequent sunscreen use between birth and the age of 6 years was associated with MS in Norway (OR 1.44, 95% CI 1.08-1.93) after adjusting for outdoor activity during the same period. Red hair (OR 1.67, 95% CI 1.06-2.63) and blonde hair (OR 1.36, 95% CI 1.09-1.70) were associated with MS after adjusting for outdoor activity and sunscreen use.

    CONCLUSION:

    Converging evidence from different measures underlines the beneficial effect of sun exposure on MS risk.

  • 16.
    Blumenthal, Cecilia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Lundeborg Hammarström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    LINUS. LINköpingsUnderSökningen: Ett fonologiskt testmaterial från 3 år2014Report (Other academic)
    Abstract [sv]

    När ett barn med misstänkta tal‐ och språkavvikelser kommer till logoped för bedömning är det viktigt att samtliga aspekter av tal och språk beaktas. Under de år som svensk logopedi har vuxit fram, har ett flertal instrument för bedömning av barn tal‐ och språk tagits fram. Ett av dessa, Stora fonemtestet, som skapades i mitten av 1980‐talet, har länge varit det enda vitt spridda testet av barns fonologi i landet. Testet fanns under flera år inte att beställa på förlag, vilket var ett av motiven till arbetet med att ta fram ett nytt fonologiskt bedömningsmaterial. Ett annat var att Enheten för logopedi vid Linköpings universitet sedan 2010 ingår i en större multicenterstudie av avvikande fonologi i olika språk. Inom ramen för detta projekt och genom några magisterarbeten i logopedi har ett nytt fonologiskt bedömningsmaterial, LINUS, skapats. Vår förhoppning är att materialet skall vara ett användbart verktyg för att samla in data vid utredning av tal‐ och språkförmåga hos barn.

  • 17.
    Bolin, K.
    et al.
    University of Gothenburg, Sweden; University of Gothenburg, Sweden.
    Berggren, F.
    UCB Pharma, Denmark.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Regional variation in prevalence and healthcare utilization due to epilepsy in Sweden2014In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 130, no 6, p. 354-359Article in journal (Refereed)
    Abstract [en]

    ObjectiveTo estimate the regional differences in the prevalence of epilepsy and the associated costs due to inpatient and outpatient care and anti-epileptic drug (AED) utilization for the years 2005 and 2011 in Sweden. MethodsRegion-specific estimates of the prevalence of epilepsy were obtained using a method based on a linkage of the healthcare and pharmaceutical registries and the cause of death registry. Regional cost components were estimated using registry data by region on inpatient and outpatient care utilization, AED sales, and mortality. Per-patient utilization and monetary costs were calculated. ResultsEstimated prevalence of epilepsy varied substantially across the regions in 2011, from 0.76% in Jamtland to 1.08% in Gotland. The national prevalence was 0.88%. The average number of hospitalizations per patient and year decreased at the national level between 2005 and 2011. At the national level, the per-patient specialized care (outpatient) utilization also decreased between 2005 and 2011. However, at the regional level, the decrease was not uniform, and in some counties, the per-patient utilization increased during the period studied. The per-patient utilization of AEDs increased in all counties, except Kronoberg, between 2005 and 2011. Moreover, between-region differences in healthcare and AED utilization, and significant differences between regions and national averages were revealed. Similarly, regional per-patient costs were shown to deviate from the national average in 13 of 21 regions. ConclusionsThere is significant variation in the prevalence of epilepsy and the provision of health care for patients with epilepsy across the different regions of Sweden.

  • 18. Borch Petersen, E
    et al.
    Wöstmann, M
    Obleser, J
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Lunner, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Health Sciences. Linköping University, The Swedish Institute for Disability Research. Eriksholm Research Centre, Snekkersten, Denmark.
    Compensated hearing loss predicts generation of auditory evoked potentials.2014Conference paper (Refereed)
  • 19.
    Boström, Inger
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Stawiarz, Leszek
    Karolinska Institute, Sweden .
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Age-specific sex ratio of multiple sclerosis in the National Swedish MS Register (SMSreg)2014In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no 4, p. 513-514Article in journal (Other academic)
  • 20.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    An in Vivo Method for Visualizing Flow Dynamics of Cells within Corneal Lymphatics2013In: Lymphatic Research and Biology, ISSN 1539-6851, E-ISSN 1557-8585, Vol. 11, no 2, p. 93-100Article in journal (Refereed)
    Abstract [en]

    Background: Monitoring the trafficking of specific cell populations within lymphatics could improve our understanding of processes such as transplant rejection and cancer metastasis. Current methods, however, lack appropriate image resolution for single-cell analysis or are incompatible with in vivo and longitudinal monitoring of lymphatics in their native state. We therefore sought to achieve high-resolution live imaging of the dynamic behavior of cells within lymph vessels in the rat cornea.

    Methods/Results: Inflammatory angiogenesis was induced by suture placement in corneas of Wistar rats. Pre- and up to 3 weeks post-induction, corneas were noninvasively examined by laser-scanning in vivo corneal confocal microscopy (IVCM) using only endogenous contrast. Lymph vessels and the cells harbored therein were documented by still images, real-time video, and 3D confocal stack reconstruction of live tissue. In vivo, conjunctival and corneal lymphatics were morphologically distinct, those with corneal location being one-quarter the diameter of those in the conjunctiva (p<0.001). Cells were recruited to initially empty pre-existing lymph vessels during the first day of inflammation and maintained a dense occupation of vessels for up to 7 days. A diverse population of cells (diameter range: 1.5–27.5 μm) with varying morphology was observed, and exhibited variable flow patterns and were transported singly and in clusters of at least 2–9 adherent cells.

    Conclusions: The in vivo microscopic technique presented enables lymph vessels and cell trafficking to be studied in high resolution in a minimally-perturbed physiologic milieu.

  • 21.
    Burman, Joachim
    et al.
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Iacobaeus, Ellen
    Karolinska Institute Solna, Sweden.
    Svenningsson, Anders
    Umeå University, Sweden; University Hospital Northern Sweden, Sweden.
    Lycke, Jan
    Sahlgrens University Hospital, Sweden.
    Gunnarsson, Martin
    Örebro University Hospital, Sweden; University of Örebro, Sweden.
    Nilsson, Petra
    Skåne University Hospital Lund, Sweden.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Fredrikson, Sten
    Karolinska Institute Huddinge, Sweden.
    Martin, Claes
    Karolinska Institute, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences.
    Uggla, Bertil
    University of Örebro, Sweden; Örebro University Hospital, Sweden.
    Lenhoff, Stig
    Skåne University Hospital, Sweden.
    Johansson, Jan-Erik
    Sahlgrens University Hospital, Sweden.
    Isaksson, Cecilia
    Umeå University, Sweden.
    Hagglund, Hans
    University of Uppsala Hospital, Sweden.
    Carlson, Kristina
    University of Uppsala Hospital, Sweden.
    Fagius, Jan
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience2014In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, no 10, p. 1116-1121Article in journal (Refereed)
    Abstract [en]

    Background Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS. Methods Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months. Results At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%). Conclusions HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.

  • 22.
    Classon, Elisabet
    et al.
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Ng, Hoi Ning Elaine
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, The Swedish Institute for Disability Research. Linköping University, Faculty of Arts and Sciences. Linnaeus Centre HEAD.
    Arlinger, Stig
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Kilman, Lisa
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Larsby, Birgitta
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Lyxell, Björn
    Linköping University, The Swedish Institute for Disability Research. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping. Linköping University, Faculty of Health Sciences.
    Lunner, Thomas
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Mishra, Sushmit
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Rudner, Mary
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Rönnberg, Jerker
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Reading span performance in 339 Swedish 50-89 year old individuals with hearing impairment: Effects of test version and age, and relation to speech recognition in noise2013Manuscript (preprint) (Other academic)
    Abstract [en]

    The Swedish reading span test (Rönnberg, Lyxell, Arlinger, & Kinnefors, 1989) is often used to assess working memory capacity (WMC) in the field of cognitive hearing science. The test has proven useful as a predictor of speech recognition in noise in adverse conditions. It has been used in a wide range of experimental studies and has been translated to several languages. The purpose of this paper was to provide reference data for the Swedish reading span test (Rönnberg et al., 1989) in a large sample of adults with hearing impairment aged 50-89 years that are representative of patients seeking rehabilitation at audiological clinics. Data from finished and ongoing projects were collated and reanalyzed for this purpose. The original full version and a shortened version of the test were compared, in terms of percentage correct. In addition, performance on the full version was compared across two different age-cohorts, 50-69 year olds and 70-89 year olds. Frequency distributions and percentile scores are reported, as well as relations with demographic variables, and speech recognition in noise. Results showed that reading span performance was related to age, but not sex, with lower scores in older participants. Pure tone hearing thresholds accounted for a small but significant amount of the variance such that higher reading span scores were related to better hearing. The frequency distributions of scores did not differ across the two versions of the test, but the long version seemed to be more sensitive to age. Performance in both versions was significantly correlated with speech recognition in noise. Regression analyses however showed that reading span explained additional variance in speech in noise recognition, after the effects of age and pure tone hearing thresholds were accounted for, only in the 50-69 year olds. These findings are discussed in relation to  age-related differences in the ability to recruit cognitive resources in the service of speech communication.

  • 23.
    Classon, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, The Swedish Institute for Disability Research.
    Rudner, Mary
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Rönnberg, Jerker
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Working memory compensates for hearing related phonological processing deficit2013Conference paper (Refereed)
    Abstract [en]

    Acquired hearing impairment is associated with gradually declining phonological representations. According to the Ease of Language Understanding (ELU) model, poorly defined representations lead to mismatch in phonologically challenging tasks. To resolve the mismatch, reliance on working memory capacity (WMC) increases. This study investigated whether WMC modulated performance in a phonological task in individuals with hearing impairment. A visual rhyme judgment task with congruous or incongruous orthography, followed by an incidental episodic recognition memory task, was used. In participants with hearing impairment, WMC modulated both rhyme judgment performance and recognition memory in the orthographically similar non-rhyming condition; those with high WMC performed exceptionally well in the judgment task, but later recognized few of the words. For participants with hearing impairment and low WMC the pattern was reversed; they performed poorly in the judgment task but later recognized a surprisingly large proportion of the words. Results indicate that good WMC can compensate for the negative impact of auditory deprivation on phonological processing abilities by allowing for efficient use of phonological processing skills. They also suggest that individuals with hearing impairment and low WMC may use a non-phonological approach to written words, which can have the beneficial side effect of improving memory encoding.

    LEARNING OUTCOMES:

    Readers will be able to: (1) describe cognitive processes involved in rhyme judgment, (2) explain how acquired hearing impairment affects phonological processing and (3) discuss how reading strategies at encoding impact memory performance.

  • 24.
    Classon, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, The Swedish Institute for Disability Research.
    Rönnberg, Jerker
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Rudner, Mary
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Johansson, M
    Hearing impairment, Linguistic processing and access to verbal long-term memory:: In search of electrophysiological indices2011Conference paper (Refereed)
  • 25.
    Czajka, Marcin Piotr
    et al.
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Frajdenberg, Agata
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Johansson, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. St. Erik Eye Hospital, Stockholm, Sweden.
    Outcomes after combined 1.8-MM microincision cataract surgery and 23-gauge transconjunctival vitrectomy for posterior segment disease: a retrospective study2014In: Retina, ISSN 0275-004X, E-ISSN 1539-2864, Vol. 34, no 1, p. 142-148Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    The aim of the study was to retrospectively review indications, intraoperative and postoperative complications, and outcomes of combined coaxial microincision cataract surgery and 23-gauge vitrectomy for posterior segment disease.

    METHODS:

    The outcomes and findings of surgery in 50 patients (50 eyes) who underwent coaxial microincision cataract surgery and foldable intraocular lens implantation combined with 23-gauge vitrectomy for a variety of indications between January 2010 and March 2012.

    RESULTS:

    No posterior capsule tear was observed during surgery. Intraoperatively, a retinal break was found in 9 eyes (18%), which were successfully treated with laser and/or cryotherapy. Corneal suture was done in 6 eyes (12%), 5 of them left and 1 right. Sclerotomy was sutured in 2 left and 2 right eyes, respectively, a total of 4 eyes (8%). In 1 case, 23-gauge vitrectomy was converted to 20-gauge vitrectomy. The postoperative intraocular pressure (millimeters of mercury, mean ± standard deviation) was 16.7 ± 9.8. Hypotony (intraocular pressure < 9 mmHg) occurred in 9 eyes (18%). In 1 eye (2%) posterior iris synechia were observed 2 weeks after surgery, and intraocular pressure was >40 mmHg. Intraocular pressure was normalized after Nd:YAG laser iridotomy. Fibrin reaction in the anterior chamber was observed in 1 eye (2%) Day 1 after surgery. Posterior capsule opacification, which required Nd:YAG laser capsulotomy, was observed in 11 eyes (22%) during the follow-up.

    CONCLUSION:

    Combined sutureless coaxial microincision cataract surgery and 23-gauge vitrectomy offers the advantages of both coaxial microincision cataract surgery (less wound leakage, good anterior chamber stability, and safety) and 23-gauge vitrectomy (decreased inflammation and faster rehabilitation after surgery).

  • 26.
    Danbolt, Christina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Hult, Peter
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Arts and Sciences.
    Grahn, Lita Tibbling
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Validation and characterization of the computerized laryngeal analyzer (CLA) technique.1999In: Dysphagia (New York. Print), ISSN 0179-051X, E-ISSN 1432-0460, Vol. 14, no 4, p. 191-195Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the response characteristics of the Computerized Laryngeal Analyzer (CLA) and the validity of the noninvasive CLA method to detect swallowing-induced laryngeal elevation correctly. Two healthy adults and two experimental models were used in the study. The CLA technique identified all swallowing events but was unable to discriminate between swallowing and other movements of the tongue or the neck. The computer program produced a derivated response to a square wave signal. Stepwise bending increments of the sensor displayed a linear amplitude response. The degree of laryngeal elevation could not be estimated with the CLA technique, and it was not possible to draw any reliable conclusions from the recordings as to whether the larynx was moving upward or downward.

  • 27.
    Davidsson, Anette
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Georgiopoulos, Charalampos
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Granerus, Göran
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Zachrisson, Helene
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Comparison between visual assessment of dopaminergic degeneration pattern and semi-quantitative ratio calculations in patients with Parkinsons disease and Atypical Parkinsonian syndromes using DaTSCAN (R) SPECT2014In: Annals of Nuclear Medicine, ISSN 0914-7187, E-ISSN 1864-6433, Vol. 28, no 9, p. 851-859Article in journal (Refereed)
    Abstract [en]

    Objective To verify if I-123-FP-CIT, DaTSCAN (R) can differentiate early stages of Parkinsons disease (PD) as well as patients with Atypical Parkinsonian syndromes (APS) from manifest Parkinsons disease. Methods 128 consecutive patients were investigated with I-123-FP-CIT SPECT during a 4-year period. All patients were diagnosed according to the established consensus criteria for diagnosis of PD (n = 53) and APS (n = 19). Remaining patients were grouped early PD (before onset of L-DOPA medication), (n = 20), vascular PD (n = 6), and non-PD syndromes (n = 30) and SWEDD (n = 1). SPECT images were analyzed visually according to a predefined ranking scale of dopaminergic nerve cell degeneration, distinguishing a posterior-anterior degeneration pattern (egg shape) from a more global and severe degeneration pattern (burst striatum). Striatum uptake ratios were quantitatively analyzed with the 3D software, EXINI. Results In the group of APS patients, the burst striatum pattern was most frequent and found in 61 % (11/18 patients). In PD patients, the egg shape pattern was dominating, especially in early PD where it was present in 95 % (19/20 patients). The positive predictive value for the egg shape pattern to diagnose PD was 92 % in this material (APS and all PD patients) and the specificity 90 % for the burst striatum pattern to exclude APS. The uptake ratios were reduced in both PD and APS patients and closely related to the image ranking. Conclusion In this study, we found that in more than half of the patients it was possible to differentiate between PD and APS by visual interpretation only. Similar results were obtained using semi-quantitative uptake ratios. Combining visual assessment with uptake ratios did not add to the discriminating power of DaTSCAN (R) SPECT in this material.

  • 28.
    Davidsson, Anette
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Georgiopoulos, Charalampos
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Granerus, Göran
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Zachrisson, Helene
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Comparison between visual assessment of dopaminergic degeneration pattern and semi-quantitative ratio calculations in patients with Parkinson's disease and Atypical Parkinsonian snydromes using DaTSCAN SPECT2014Conference paper (Other academic)
    Abstract [en]

    Background: Parkinson's disease (PD) is a degenerative disorder characterized by the progressive degeneration of dopamine-containing cells in substantia nigra, and it is the second most common neurodegenerative disorder worldwide. It can be difficult to differentiate between idiopathic PD and Atypical Parkinsonian syndromes (APS). In a high percentage of APS patients, the right diagnosis is not established even during late stages of the disease. Currently there is no specific test to verify PD, especially in the early stages of the disease.

    The aim was to verify if 123I-FP-CIT, DaTSCAN ® can differentiate early stages of Parkinson's disease as well as patients with Atypical Parkinsonian syndromes from manifest Parkinson's disease.

    Materials and methods: 121 consecutive patients were investigated with 123I-FP-CIT SPECT, during a four year period. All patients were diagnosed according to the established consensus criteria for diagnosis of Parkinson's disease (PD), (n=53), Atypical Parkinsonian syndromes (APS) (n=18). Remaining patients were grouped early PD (before onset the of L-dopa medication), (n=20), and non-PD syndromes (n=30). SPECT images were analysed visually according to a predefined ranking scale of dopaminergic degeneration, distinguishing a posterior-anterior degeneration pattern (egg shape) to a more global and severe degeneration pattern (burst striatum). Striatum ratios were quantitatively analysed with the 3D software, EXINI.

    Results: In the group of APS patients the burst striatum pattern was most frequent and found in 61% (11/18 patients). In PD patients the egg shape pattern was dominating, especially in early PD where it was present in 95% (19/20 patients). The sensitivity of burst striatum degeneration pattern was 61% (95%-CI 36-83%), specificity 90% (95%-CI 81-96%). The sensitivity of egg shape pattern was 74% (95%-CI 62-84%), specificity 90% (95%-CI 47-90%). The uptake ratios were reduced in both PD and APS patients and closely related to the image pattern. The lowest putamen/caudate ratio was found in early PD.

    Conclusion: In this study we found that in more than half of the patients it was possible to differentiate between PD and APS by visual interpretation only. Similar results were obtained using semi-quantitative uptake ratios, but combining visual assessment with uptake ratios did not add to the discriminating power of DATSCAN ® SPECT in this material

    References: Kahraman D, Eggers C, Schicha H, Timmermann L, Schmidt M. Visual assessment of dopaminergic degeneration pattern in 123I-FP-CIT SPECT differentiates patients with atypical parkinsonian syndromes and idiopathic Parkinson's disease. J Neurol. 2012;259:251-60

  • 29.
    Domert, Jakob
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Rao, Sahana Bhima
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Agholme, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Brorsson, Ann-Christin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nath, Sangeeta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Spreading of Amyloid-β Peptides via Neuritic Cell-to-cell Transfer Is Dependent on Insufficient Cellular Clearance2014In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 65, p. 82-92Article in journal (Refereed)
    Abstract [en]

    The spreading of pathology through neuronal pathways is likely to be the cause of the progressive cognitive loss observed in Alzheimer's disease (AD) and other neurodegenerative diseases. We have recently shown the propagation of AD pathology via cell-to-cell transfer of oligomeric amyloid beta (Aβ) residues 1-42 (oAβ1-42) using our donor-acceptor 3-D co-culture model. We now show that different Aβ-isoforms (fluorescently labeled 1-42, 3(pE)-40, 1-40 and 11-42 oligomers) can transfer from one cell to another. Thus, transfer is not restricted to a specific Aβ-isoform. Although different Aβ isoforms can transfer, differences in the capacity to clear and/or degrade these aggregated isoforms result in vast differences in the net amounts ending up in the receiving cells and the net remaining Aβ can cause seeding and pathology in the receiving cells. This insufficient clearance and/or degradation by cells creates sizable intracellular accumulations of the aggregation-prone Aβ1-42 isoform, which further promotes cell-to-cell transfer; thus, oAβ1-42 is a potentially toxic isoform. Furthermore, cell-to-cell transfer is shown to be an early event that is seemingly independent of later appearances of cellular toxicity. This phenomenon could explain how seeds for the AD pathology could pass on to new brain areas and gradually induce AD pathology, even before the first cell starts to deteriorate, and how cell-to-cell transfer can act together with the factors that influence cellular clearance and/or degradation in the development of AD.

  • 30.
    Dong, Huan-Ji
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Health Maintenance in Very Old Age: Medical Conditions, Functional Outcome and Nutritional Status2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall aim of this thesis was to provide better understanding of the underlying factors related to health maintenance in very old people, with a focus on medical conditions, functional outcome and nutritional status. Data were gathered from the ELSA 85 project (Elderly in Linköping Screening Assessment). The ELSA 85 project was started in 2007 with a population-based survey of 85-year-old individuals (n = 650) residing in Linköping municipality, Sweden. During the study period from 2007 to 2010, we conducted surveys by postal questionnaire, home visits, geriatric clinic visits, and reviews of electronic medical records as well as the database of health service consumption. A series of cross-sectional analyses were performed on multimorbidity, health service consumption, activities of daily living (ADLs), physical functioning and nutritional status.

    Of 650 eligible individuals, 496 (78% of those alive) completed the questionnaire (Paper I). Despite the prevalence of multimorbidity (68%) and frequent use of assistive technology for mobility (40%), the majority managed self-care (85%), usual activities (74%) and had high self-rated health (>60/100, visual analogue scale). Factors associated with in-patient care were an increased number of general practitioner visits, more use of assistive technology, community assistance, multimorbidity (≥2 chronic diseases) and/or heart failure and arrhythmia.

    Cluster analyses (n = 496, Paper II) revealed five clusters: vascular, cardiopulmonary, cardiac (only for men), somatic–mental (only for men), mental disease (only for women), and three other clusters related to ageing (one for men and two for women). Heart failure in men (odds ratio [OR], 2.4; 95% confidence interval [CI], 1–5.7) and women (OR, 3; 95% CI, 1.3–6.9) as a single morbidity explained more variance than morbidity clusters in models of emergency room visits. Men’s cardiac cluster (OR, 1.6; 95% CI, 1–2.7) and women’s cardiopulmonary cluster (OR, 1.7; 95% CI, 1.2–2.4) were significantly associated with hospitalization. The combination of the cardiopulmonary cluster with the men’s cardiac cluster (OR, 1.6; 95% CI, 1–2.4) and one of the women’s ageing clusters (OR, 0.5; 95% CI, 0.3–0.8) showed interaction effects on hospitalization.

    In Paper III, overweight (body mass index [BMI], 25–29.9 kg/m2) and obese (BMI, ≥30 kg/m2) individuals (n = 333) perceived more difficulty performing instrumental ADL (IADL) and had more comorbidities than their normal weight counterparts (BMI, 18.5–24.9 kg/m2). After controlling for socio-demographic factors, obese but not overweight individuals were more likely to perceive increased difficulty in performing outdoor activities (OR, 2.1; 95% CI, 1.1–4) and cleaning (OR, 2.2; 95% CI, 1.2–4.2) than their normal weight counterparts. Although obesity was also associated with multimorbidity (OR, 3; 95% CI, 1.2–8), the health service cost of each case of multimorbidity (n = 251) was highest in individuals of normal weight and nearly three times as much as in obese individuals (ratio, 2.9; 95% CI, 1.1–8.1).

    In Paper IV, 88-year-old obese women (n = 83) had greater absolute waist circumference, fat mass (FM) and fat-free mass (FFM), and lower handgrip strength (HS) corrected for FFM and HS-based ratios (HS/weight (Wt), HS/BMI, HS/FFM and HS/FM) than their normal weight and overweight counterparts. After adjusting for physical activity levels and the number of chronic diseases, the HS-based ratios explained more variance in physical functioning in Short Form-36 (R2, 0.52–0.54) than other single anthropometric or body composition parameters (R2, 0.45–0.51). Waist circumference, HS, and two HS-based ratios (HS/Wt and HS/FFM) were also associated with the number of IADL with no difficulty.

    In conclusion, the ELSA 85 population showed a fairly positive image of healthy perception, good functional ability as well as low use of health care among the majority of participants. Patterns of cardiac and pulmonary conditions were better associated than any single morbidity with hospitalization. Heart failure as a single morbidity was better associated than multimorbidity patterns with emergency room visits. For 85-year-olds, being obese, as opposed to overweight, was associated with self-reported activity limitations and comorbidities. Overweight elderly living in their own homes in this population had similar well-being to those of normal weight. In the cohort of 88-year-olds, obese women had high waist circumference, but their HS was relatively low in relation to their Wt and FFM. These parameters were better than BMI for predicting physical function and independent daily living.

    List of papers
    1. Health-related factors associated with hospitalization for old people: Comparisons of elderly aged 85 in a population cohort study
    Open this publication in new window or tab >>Health-related factors associated with hospitalization for old people: Comparisons of elderly aged 85 in a population cohort study
    Show others...
    2012 (English)In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 54, no 2, p. 391-397Article in journal (Refereed) Published
    Abstract [en]

    The aim of this population-based study was to (1) describe living conditions and actual health care utilization among 85 year olds; (2) determine factors that affect hospital admissions in this age. The study was conducted on 85-year-old residents in Linkoping municipality, Sweden. The data collected included medical records, health care utilization during the preceding 12 months and a postal questionnaire on assistance, assistive technology, functional impairment, feelings of loneliness, worries and health-related quality of life measured by the EQ-5D. Out of 650 eligible individuals, 496 (78% of those alive) participated. Despite the prevalence of multi-morbidity (68%) and mental discomfort, the majority managed self-care (85%), usual activities (74%) and had high (andgt;60/100) self-rated health evaluated by a visual analog scale (VAS). The non-hospitalized group reported a better health status than the hospitalized group in terms of medical aspects, living conditions and subjective estimation. Factors associated with in-patient care were an increased number of general practitioner visits, more assistive technology, community assistance, multimorbidity and/or diagnosed congestive heart failure and arrhythmia.

    Place, publisher, year, edition, pages
    Elsevier, 2012
    Keywords
    Population study, Hospitalization, Health care service, postal questionnaire
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-76812 (URN)10.1016/j.archger.2011.04.023 (DOI)000301647400064 ()
    Note

    Funding Agencies|Health Research Council of the South-East of Sweden|FORSS-8888FORSS-11636FORSS-31811|County of Ostergotland|LIO-11877LIO-31321LIO-79951|Janne Elgqvist Family Foundation||

    Available from: 2012-04-20 Created: 2012-04-20 Last updated: 2017-12-07
    2. Multimorbidity patterns of and use of health services by Swedish 85-year-olds: an exploratory study
    Open this publication in new window or tab >>Multimorbidity patterns of and use of health services by Swedish 85-year-olds: an exploratory study
    2013 (English)In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 13, no 120Article in journal (Refereed) Published
    Abstract [en]

    Background

    As life expectancy continues to rise, more elderly are reaching advanced ages (≥80 years). The increasing prevalence of multimorbidity places additional demands on health-care resources for the elderly. Previous studies noted the impact of multimorbidity on the use of health services, but the effects of multimorbidity patterns on health-service use have not been well studied, especially for very old people. This study determines patterns of multimorbidity associated with emergency-room visits and hospitalization in an 85-year-old population.

    Methods

    Health and living conditions were reported via postal questionnaire by 496 Linköping residents aged 85 years (189 men and 307 women). Diagnoses of morbidity were reviewed in patients’ case reports, and the local health-care register provided information on the use of health services. Hierarchical cluster analysis was applied to evaluate patterns of multimorbidity with gender stratification. Factors associated with emergency-room visits and hospitalization were analyzed using logistic regression models.

    Results

    Cluster analyses revealed five clusters: vascular, cardiopulmonary, cardiac (only for men), somatic–mental (only for men), mental disease (only for women), and three other clusters related to aging (one for men and two for women). Heart failure in men (OR = 2.4, 95% CI = 1–5.7) and women (OR = 3, 95% CI = 1.3–6.9) as a single morbidity explained more variance than morbidity clusters in models of emergency-room visits. Men's cardiac cluster (OR = 1.6; 95% CI = 1–2.7) and women's cardiopulmonary cluster (OR = 1.7, 95% CI = 1.2–2.4) were significantly associated with hospitalization. The combination of the cardiopulmonary cluster with the men’s cardiac cluster (OR = 1.6, 95% CI = 1–2.4) and one of the women’s aging clusters (OR = 0.5, 95% CI = 0.3–0.8) showed interaction effects on hospitalization.

    Conclusion

    In this 85-year-old population, patterns of cardiac and pulmonary conditions were better than a single morbidity in explaining hospitalization. Heart failure was superior to multimorbidity patterns in explaining emergency-room visits. A holistic approach to examining the patterns of multimorbidity and their relationships with the use of health services will contribute to both local health care policy and geriatric practice.

    Place, publisher, year, edition, pages
    BioMed Central, 2013
    Keywords
    Multimorbidity, 85-year-old, Emergency-room visit, Hospitalization
    National Category
    Geriatrics
    Identifiers
    urn:nbn:se:liu:diva-102219 (URN)10.1186/1471-2318-13-120 (DOI)000328479800001 ()
    Available from: 2013-12-04 Created: 2013-12-04 Last updated: 2017-12-06Bibliographically approved
    3. Health Consequences Associated with Being Overweight or Obese: A Swedish Population-Based Study of 85-Year-Olds
    Open this publication in new window or tab >>Health Consequences Associated with Being Overweight or Obese: A Swedish Population-Based Study of 85-Year-Olds
    2012 (English)In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 60, no 2, p. 243-250Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: To determine whether being overweight or obese is associated with significant health outcomes in an 85-year-old population. less thanbrgreater than less thanbrgreater thanDESIGN: A cross-sectional population-based study. less thanbrgreater than less thanbrgreater thanSETTING: Linkoping, Sweden. less thanbrgreater than less thanbrgreater thanPARTICIPANTS: Three hundred thirty-eight people born in 1922 were identified using the local authoritys register. less thanbrgreater than less thanbrgreater thanMEASUREMENTS: Data related to sociodemographic characteristics, health-related quality of life (HRQoL), assistance use, and the presence of diseases were collected using a postal questionnaire. Anthropometry and functional status were assessed during home and geriatric clinic visits. Diseases were double-checked in the electronic medical records, and information about health service consumption was obtained from the local healthcare register. less thanbrgreater than less thanbrgreater thanRESULTS: Overweight (body mass index (BMI) 25.0-29.9 kg/m(2)) and obese (BMI andgt;= 30.0 kg/m(2)) participants perceived more difficulty performing instrumental activities of daily living (IADLs) and had more comorbidity than their normal-weight counterparts (BMI 18.5-24.9 kg/m(2)), but their overall HRQoL and health service costs did not differ from those of normal-weight participants. After controlling for sociodemographic factors, being overweight did not influence IADLs or any comorbidity, but obese participants were more likely to perceive greater difficulty in performing outdoor activities (odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.1-4) and cleaning (OR = 2.2, 95% CI = 1.2-4.2) than their normal-weight counterparts. Although obesity was also associated with multimorbidity (OR = 3, 95% CI = 1.2-8), the health service cost of each case of multimorbidity (n = 251) was highest in normalweight participants and nearly three times as much as in obese participants (ratio: 2.9, 95% CI = 1.1-8.1). less thanbrgreater than less thanbrgreater thanCONCLUSION: For 85-year-olds, being obese, as opposed to overweight, is associated with self-reported activity limitations and comorbidities. Overweight older adults living in their own homes in this population had well-being similar to that of those with normal weight.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2012
    Keywords
    health consequences, overweight, obesity, 85-year-olds
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-76197 (URN)10.1111/j.1532-5415.2011.03827.x (DOI)000300677400007 ()
    Note

    Funding Agencies|Health Research Council of the South-East of Sweden||County of Ostergotland||Janne Elgqvist Family Foundation||

    Available from: 2012-03-31 Created: 2012-03-30 Last updated: 2017-12-07
    4. Obese very old women have low relative handgrip strength, poor physical function, and difficulty in daily living
    Open this publication in new window or tab >>Obese very old women have low relative handgrip strength, poor physical function, and difficulty in daily living
    2015 (English)In: The Journal of Nutrition, Health & Aging, ISSN 1279-7707, E-ISSN 1760-4788, Vol. 19, no 1, p. 20-25Article in journal (Refereed) Published
    Abstract [en]

    Objectives: To investigate how anthropometric and body composition variables, and handgrip strength (HS) affect physical function and independent daily living in 88-year-old Swedish women.

    Participants: A cross-sectional analysis of 83 community-dwelling women, who were 88 years old with normal weight (n=30), overweight (n=29), and obesity (n=24) in Linköping, Sweden, was performed.

    Measures: Assessments of body weight (Wt), height, waist circumference (WC), and arm circumference were performed by using an electronic scale and measuring tape. Tricep skinfold thickness was measured by a skinfold calliper. Fat mass (FM) and fat-free mass (FFM) were measured by bioelectrical impedance analysis, and HS was recorded with an electronic grip force instrument. Linear regression was used to determine the contributions of parameters as a single predictor or as a ratio with HS to physical function (Short Form-36, SF-36PF) and instrumental activities of daily living (IADL).

    Results: Obese women had greater absolute FM and FFM, and lower HS corrected for FFM and HS-based ratios (i.e., HS/Wt, HS/body mass index [BMI]) than their normal weight and overweight counterparts. After adjusting for physical activity levels and the number of chronic diseases, HS-based ratios explained more variance in SF-36PF scoring (R2: 0.52–0.54) than single anthropometric and body composition variables (R2: 0.45–0.51). WC, HS, and HS-based ratios (HS/Wt and HS/FFM) were also associated with the number of IADL with no difficulty.

    Conclusion: Obese very old women have a high WC, but their HS is relatively low in relation to their Wt and FFM. These parameters are better than BMI for predicting physical function and independent daily living.

    Place, publisher, year, edition, pages
    Springer, 2015
    Keywords
    Very old; Handgrip strength; Body composition; Physical function; Instrumental activities of daily living
    National Category
    Geriatrics
    Identifiers
    urn:nbn:se:liu:diva-105215 (URN)10.1007/s12603-014-0512-6 (DOI)000348024800003 ()
    Available from: 2014-03-13 Created: 2014-03-13 Last updated: 2017-12-05Bibliographically approved
  • 31.
    Dong, Huan-Ji
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Multimorbidity patterns of and use of health services by Swedish 85-year-olds: an exploratory study2013In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 13, no 120Article in journal (Refereed)
    Abstract [en]

    Background

    As life expectancy continues to rise, more elderly are reaching advanced ages (≥80 years). The increasing prevalence of multimorbidity places additional demands on health-care resources for the elderly. Previous studies noted the impact of multimorbidity on the use of health services, but the effects of multimorbidity patterns on health-service use have not been well studied, especially for very old people. This study determines patterns of multimorbidity associated with emergency-room visits and hospitalization in an 85-year-old population.

    Methods

    Health and living conditions were reported via postal questionnaire by 496 Linköping residents aged 85 years (189 men and 307 women). Diagnoses of morbidity were reviewed in patients’ case reports, and the local health-care register provided information on the use of health services. Hierarchical cluster analysis was applied to evaluate patterns of multimorbidity with gender stratification. Factors associated with emergency-room visits and hospitalization were analyzed using logistic regression models.

    Results

    Cluster analyses revealed five clusters: vascular, cardiopulmonary, cardiac (only for men), somatic–mental (only for men), mental disease (only for women), and three other clusters related to aging (one for men and two for women). Heart failure in men (OR = 2.4, 95% CI = 1–5.7) and women (OR = 3, 95% CI = 1.3–6.9) as a single morbidity explained more variance than morbidity clusters in models of emergency-room visits. Men's cardiac cluster (OR = 1.6; 95% CI = 1–2.7) and women's cardiopulmonary cluster (OR = 1.7, 95% CI = 1.2–2.4) were significantly associated with hospitalization. The combination of the cardiopulmonary cluster with the men’s cardiac cluster (OR = 1.6, 95% CI = 1–2.4) and one of the women’s aging clusters (OR = 0.5, 95% CI = 0.3–0.8) showed interaction effects on hospitalization.

    Conclusion

    In this 85-year-old population, patterns of cardiac and pulmonary conditions were better than a single morbidity in explaining hospitalization. Heart failure was superior to multimorbidity patterns in explaining emergency-room visits. A holistic approach to examining the patterns of multimorbidity and their relationships with the use of health services will contribute to both local health care policy and geriatric practice.

  • 32.
    Duits, Flora H.
    et al.
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands.
    Teunissen, Charlotte E.
    Vrije University of Amsterdam, Netherlands.
    Bouwman, Femke H.
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands.
    Visser, Pieter-Jelle
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands; University of Maastricht, Netherlands.
    Mattsson, Niklas
    Centre Imaging Neurodegenerat Disease, CA USA.
    Zetterberg, Henrik
    UCL Institute Neurol, England.
    Blennow, Kaj
    University of Gothenburg, Sweden.
    Hansson, Oskar
    Lund University, Sweden.
    Minthon, Lennart
    Lund University, Sweden.
    Andreasen, Niels
    Karolinska University Hospital, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Wallin, Anders
    University of Gothenburg, Sweden.
    Olde Rikkert, Marcel
    Donders Institute Brain Cognit and Behav, Netherlands.
    Tsolaki, Magda
    Aristotle University of Thessaloniki, Greece.
    Parnetti, Lucilla
    University of Perugia, Italy.
    Herukka, Sanna-Kaisa
    University of Eastern Finland, Finland; Kuopio University Hospital, Finland.
    Hampel, Harald
    University of Paris 06, France; University of Paris 06, France.
    De Leon, Mony J.
    NYU, NY USA.
    Schroeder, Johannes
    Heidelberg University, Germany.
    Aarsland, Dag
    Stavanger University Hospital, Norway.
    Blankenstein, Marinus A.
    Vrije University of Amsterdam, Netherlands.
    Scheltens, Philip
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands.
    van der Flier, Wiesje M.
    Vrije University of Amsterdam, Netherlands.
    The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?2014In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 10, no 6, p. 713-723Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-beta(1-42) (A beta(42)), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimers disease (AD). Methods: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). Results: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/A beta(42) ratio and 0.08 for the p-tau/A beta(42) ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of greater than0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.

  • 33.
    Edfeldt, Lennart
    et al.
    University of Uppsala Hospital, Sweden .
    Stromback, Karin
    University of Uppsala Hospital, Sweden .
    Grendin, Joakim
    Umeå University Hospital, Sweden .
    Bunne, Marie
    Oslo University Hospital, Norway .
    Harder, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Peebo, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Eeg-Olofsson, Mans
    Sahlgrens University Hospital, Sweden .
    Petersson, Carl-Magnus
    Skåne University Hospital, Sweden .
    Konradsson, Konrad
    University of Uppsala Hospital, Sweden .
    Evaluation of cost-utility in middle ear implantation in the Nordic School: a multicenter study in Sweden and Norway2014In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 134, no 1, p. 19-25Article in journal (Refereed)
    Abstract [en]

    Conclusion: Hearing restoration using an active middle ear implant (AMEI) is a highly cost-effective treatment for a selected group of patients with no other possibilities for auditory rehabilitation. Objectives: To evaluate the cost-utility of using an AMEI for hearing rehabilitation. Methods: This was a prospective, multicenter, single-subject repeated study in six tertiary referral centers. Twenty-four patients with sensorineural (SNHL), conductive (CHL), and mixed hearing loss (MHL) were implanted with the AMEI Vibrant Soundbridge (R) (VSB) for medical reasons. All patients were previously rehabilitated with conventional hearing aids. Multiple validated quality of life patient questionnaires, Health Utilities Index (HUI 2 and 3), and Glasgow Hearing Aid Benefit Profile (GHABP) were used to determine the utility gain and quality adjusted life years (QALY). Directly related treatment costs for the implantation were calculated and related to utility gain and QALY. Results: The cost/QALY for patients with SNHL was estimated at (sic)7260/QALY, and for patients with C/MHL at (sic)12 503/QALY.

  • 34.
    Edström, Måns
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Huddinge University Hospital.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Regulatory T cells in Multiple Sclerosis – Indications of impaired function of suppressive capacity and a role for chemokines2014Manuscript (preprint) (Other academic)
    Abstract [en]

    BACKGROUND Regulatory T cells (Treg) are critical for immune regulation and homeostasis. In multiple sclerosis (MS), the function of these cells has been shown to be impaired, although the underlying mechanism has yet to be shown. In the current study, we aimed to characterize and assess the phenotypical, functional and transcriptional characteristics of memory and naïve Treg in MS patients and controls.

    MATERIAL AND METHODS 27 patients with relapsing-remitting disease were included, along with 29 healthy controls. Flow cytometry was used for detailed phenotyping of Treg subpopulations CD4+CD45RA+/- and CD4dimCD25++ and their expression of FOXP3, CD39 and HELIOS. CFSE (proliferation marker) and CD69 (activation marker) were used to investigate the functional capacity of Treg. A microarray was employed for genome-wide transcriptional characterization of isolated Treg.

    RESULTS CD4+CD45RA–CD25++ activated Treg displayed a higher expression of FOXP3 and CD39 than resting CD4+CD45RA+CD25+ Treg, while no significant phenotypical differences were observed in Treg subpopulations between patients and controls. However, a lower anti-proliferative capacity was observed in activated Treg of MS patients compared with those of controls (p<0.05), while suppression of activation was similar to controls. Gene set enrichment analysis (GSEA) of microarray data revealed enrichment for the GO gene set ‘chemokine receptor binding’ in MS Treg.

    CONCLUSION Although numerical phenotypical assessment of resting and activated Tregs did not reveal any significant difference between patients and controls, functional co-culturing experiments showed an impaired function in activated Treg of MS patients. Furthermore, GSEA revealed immune-related gene sets overexpressed in Treg of MS patients, possibly containing clues to the functional impairment. In particular over-activity in chemokine signalling in Treg would be of interest for further investigation.

  • 35.
    Edén, Ulla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Dellby, Anette
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Utheim, Tor P.
    Oslo University Hospital, Norway Harvard University, MA 02114 USA .
    Riise, Ruth
    Innland Hospital, Norway .
    Chen, Xiangjun
    Synslaser Kirurgi AS, Norway .
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Letter: Cataract development in Norwegian patients with congenital aniridia2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 2, p. E165-E167Article in journal (Other academic)
    Abstract [en]

    n/a

  • 36.
    Eklund, Robert
    et al.
    Linköping University, Department of Culture and Communication, Language and Culture. Linköping University, Faculty of Arts and Sciences.
    McAllister, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Fanny, Pehrson
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping. Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience.
    An acoustic comparison of voice characteristics in ‘kulning’, head and modal registers.2013In: Robert Eklund (ed.), Proceedings of Fonetik 2013, the XXVIth Swedish Phonetics Conference, Studies in Language and Culture, no. 21, ISBN 978-91-7519-582-7, eISBN 978-91-7519-579-7, ISSN 1403-2570, pp. 21–24. / [ed] Robert Eklund, 2013, p. 21-24Conference paper (Other academic)
    Abstract [en]

    The Swedish folk singing style ‘kulning’ issurprisingly understudied, despite its almostmythical status in Swedish folklore. While somephysiological–productive aspects of kulninghave been treated in previous work, acousticproperties are still much lacking description.This paper compares kulning, head (‘falsetto’)and modal voice from an acoustic perspective.

  • 37.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bertus Warntjes, Marcel, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. SyntheticMR AB, Linkoping, Sweden.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Multi-Parametric Representation of Voxel-Based Quantitative Magnetic Resonance Imaging2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, p. e111688-Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to explore the possibilities of multi-parametric representations of voxel-wise quantitative MRI data to objectively discriminate pathological cerebral tissue in patients with brain disorders. For this purpose, we recruited 19 patients with Multiple Sclerosis (MS) as benchmark samples and 19 age and gender matched healthy subjects as a reference group. The subjects were examined using quantitative Magnetic Resonance Imaging (MRI) measuring the tissue structure parameters: relaxation rates, R-1 and R-2, and proton density. The resulting parameter images were normalized to a standard template. Tissue structure in MS patients was assessed by voxel-wise comparisons with the reference group and with correlation to a clinical measure, the Expanded Disability Status Scale (EDSS). The results were visualized by conventional geometric representations and also by multi-parametric representations. Data showed that MS patients had lower R-1 and R-2, and higher proton density in periventricular white matter and in wide-spread areas encompassing central and sub-cortical white matter structures. MS-related tissue abnormality was highlighted in posterior white matter whereas EDSS correlation appeared especially in the frontal cortex. The multi-parameter representation highlighted disease-specific features. In conclusion, the proposed method has the potential to visualize both high-probability focal anomalies and diffuse tissue changes. Results from voxel-based statistical analysis, as exemplified in the present work, may guide radiologists where in the image to inspect for signs of disease. Future clinical studies must validate the usability of the method in clinical practice.

  • 38.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Hallböök, Tove
    Sahlgrenska Academy, University of Gothenburg, Sweden.
    Szakacs, Attila
    Sahlgrenska Academy, University of Gothenburg. Sweden; Halmstad County Hospital, Sweden.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Functional magnetic resonance imaging in narcolepsy and the Kleine–Levin syndrome2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, no 105Article in journal (Refereed)
    Abstract [en]

    This work aims at reviewing the present state of the art when it comes to understanding the pathophysiology of narcolepsy and the Kleine–Levin syndrome (KLS) from a neuroimaging point of view. This work also aims at discussing future perspectives of functional neuroimaging in these sleep disorders. We focus on functional magnetic resonance imaging (fMRI), which is a technique for in vivo measurements of brain activation in neuronal circuitries under healthy and pathological conditions. fMRI has significantly increased the knowledge on the affected neuronal circuitries in narcolepsy and the Kleine–Levin syndrome. It has been shown that narcolepsy is accompanied with disturbances of the emotional and the closely related reward systems. In the Kleine Levin syndrome, fMRI has identified hyperactivation of the thalamus as a potential biomarker that could be used in the diagnostic procedure. The fMRI findings in both narcolepsy and the Kleine–Levin syndrome are in line with previous structural and functional imaging studies. We conclude that fMRI in combination with multi-modal imaging can reveal important details about the pathophysiology in narcolepsy and the Kleine–Levin syndrome. In the future, fMRI possibly gives opportunities for diagnostic support and prediction of treatment response in individual patients.

  • 39.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jan Bertus Warntje, Marcel
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Multi-Parametric Representation of Voxel-Based Quantitative Magnetic Resonance Imaging2014Conference paper (Other academic)
    Abstract [en]

    The aim of the study was to explore the possibilities of multi-parametric representations of voxel-wise quantitative MRI data to objectively discriminate pathological cerebral tissue in patients with brain disorders. For this purpose, we recruited 19 patients with Multiple Sclerosis (MS) as benchmark samples and 19 age and gender matched healthy subjects as a reference group. The subjects were examined using quantitative Magnetic Resonance Imaging (MRI) measuring the tissue structure parameters: relaxation rates, R and R, and proton density. The resulting parameter images were normalized to a standard template. Tissue structure in MS patients was assessed by voxel-wise comparisons with the reference group and with correlation to a clinical measure, the Expanded Disability Status Scale (EDSS). The results were visualized by conventional geometric representations and also by multi-parametric representations. Data showed that MS patients had lower R and R, and higher proton density in periventricular white matter and in wide-spread areas encompassing central and sub-cortical white matter structures. MS-related tissue abnormality was highlighted in posterior white matter whereas EDSS correlation appeared especially in the frontal cortex. The multi-parameter representation highlighted disease-specific features. In conclusion, the proposed method has the potential to visualize both high-probability focal anomalies and diffuse tissue changes. Results from voxel-based statistical analysis, as exemplified in the present work, may guide radiologists where in the image to inspect for signs of disease. Future clinical studies must validate the usability of the method in clinical practice.

  • 40.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Reduced thalamic and pontine connectivity in Kleine–Levin syndrome2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, no 42Article in journal (Refereed)
    Abstract [en]

    The Kleine–Levin syndrome (KLS) is a rare sleep disorder, characterized by exceptionally long sleep episodes. The neuropathology of the syndrome is unknown and treatment is often inadequate. The aim of the study was to improve understanding of the underlying neuropathology, related to cerebral networks, in KLS during sleep episodes. One patient with KLS and congenital nystagmus was investigated by resting state functional magnetic resonance imaging during both asymptomatic and hypersomnic periods. Fourteen healthy subjects were also investigated as control samples. Functional connectivity was assessed from seed regions of interest in the thalamus and the dorsal pons. Thalamic connectivity was normal in the asymptomatic patient whereas the connectivity between the brain stem, including dorsal pons, and the thalamus was diminished during hypersomnia. These results suggest that the patient’s nystagmus and hypersomnia might have their pathological origin in adjacent dorsal pontine regions. This finding provides additional knowledge of the cerebral networks involved in the neuropathology of this disabling disorder. Furthermore, these findings regarding a rare syndrome have broad implications, and results could be of interest to researchers and clinicians in the whole field of sleep medicine.

  • 41.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Thalamic Activation in the Kleine-Levin Syndrome2014In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 37, no 2, p. 379-386Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES:

    The objective of this study was to investigate if combined measures of activation in the thalamus and working memory capacity could guide the diagnosis of Kleine-Levin Syndrome (KLS). A second objective was to obtain more insight into the neurobiological causes of KLS.

    DESIGN:

    Matched group and consecutive recruitment.

    SETTING:

    University hospital neurology department and imaging center.

    PATIENTS OR PARTICIPANTS:

    Eighteen patients with KLS diagnosed according to the International Classification of Sleep Disorders and 26 healthy controls were included.

    INTERVENTIONS:

    N/A.

    MEASUREMENTS AND RESULTS:

    Working memory capacity was assessed by the listening span task. A version of this task (reading span) was presented to the participants during functional magnetic resonance imaging (fMRI). Activation in the thalamus was measured in a region of interest analysis. A combination of the working memory capacity and the thalamic activation measures resulted in 80% prediction accuracy, 81% sensitivity, and 78% specificity regarding the ability to separate KLS patients from healthy controls. The controls had an inverse relation between working memory capacity and thalamic activation; higher performing participants had lower thalamic activation (r = -0.41). KLS patients showed the opposite relationship; higher performing participants had a tendency to higher thalamic activation (r = -0.35).

    CONCLUSIONS:

    This study shows that functional neuroimaging of the thalamus combined with neuropsychological assessment of working memory function provides a means to guide diagnosis of Kleine-Levin Syndrome. Results in this study also indicate that imaging of brain function and evaluation of cognitive capacity can give insights into the neurobiological mechanisms of Kleine-Levin Syndrome.

  • 42.
    Ericsson, Elisabeth
    et al.
    Örebro University, Sweden .
    Graf, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Lundeborg Hammarström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Hultcrantz, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Tonsillotomy versus tonsillectomy on young children: 2 year post surgery follow-up2014In: Journal of Otolaryngology - Head & Neck Surgery, ISSN 1916-0216, Vol. 43, article id 26Article in journal (Refereed)
    Abstract [en]

    Objectives: To study the long-term effect of tonsillotomy and tonsillectomy in young children after two years in comparison to the results after six months. Method: Children, age 4-5 with Sleep Disordered Breathing (SDB) and tonsil hyperplasia, were randomized to TE (32) or TT (35). TT was performed ad modum Hultcrantz with radiofrequency technique (Ellman). An adenoidectomy with cold steel was performed in the same session for 80% of cases. The patients were assessed prior to surgery, at six and 24 months postoperatively. Effects of surgery were evaluated clinically, through questionnaire (general health/snoring/ENT-infections), Quality of Life (QoL), survey of pediatric obstructive sleep apnea with OSA-18, and childrens behavior with the Child Behavior Checklist. Results: After two years there was still no difference between the groups with respect to snoring and frequency or severity of upper airway infections. Both TT and TE had resulted in large improvement in short and long term QoL and behavior. Three TT-children and one TE child had been re-operated due to recurrence of obstructive problems, the TE-child and one of the TT-children with adenoidectomy and two of the TT-children with tonsillectomy. Three of the TT-children had tonsil tissue protruding slightly out of the tonsil pouch and twelve TE-children had small tonsil remnants within the tonsil pouches, but with no need for surgery. Conclusion: Younger children have a small risk of symptom-recurrence requiring re-surgery within two years after TT. For the majority, the positive effect on snoring, infections, behavior and quality of life remain and is similar to TE.

  • 43.
    Ericsson, Elisabeth
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Lundeberg, Stefan
    Smärtbehandlingsenheten, Astrid Lindgrens Barnsjukhus, Stockholm.
    Brattwall, Metha
    An/Op/IVA/Sc Sahlgrenska Universitetssjukhuset, Mölndal.
    Stalfors, Joacim
    ÖNH-Kliniken, Sahlgrenska Universitetssjukhuset, Göteborg.
    Hemlin, Claes
    ÖNH-Kliniken, Aleris Specialistvård Sabbatsberg, Stockholm.
    Hessén-Söderman, Anne-Charlotte
    ÖNH-Kliniken, Aleris Specialistvård Sabbatsberg, Stockholm.
    Hultcrantz, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Sunnergren, Ola
    ÖNH- Kliniken, Länssjukhuset Ryhov, Jönköping.
    Odhagen, Erik
    ÖNH-Kliniken, Södra Älvsborgs Sjukhus, Borås.
    Nationella riktlinjer för farmakologisk behandling av smärta och illamående i samband med tonsillotomi och tonsillektomi på barn och ungdomar (<18 år)2013In: Svensk ÖNH-tidskrift, ISSN 1400-0121, Vol. 30, no 3, p. 4p. 1-5Article in journal (Refereed)
    Abstract [sv]

    Riktlinjerna är framtagna av referensgruppen för Tonsilloperation. Syftet med dessa riktlinjer är att optimera det perioperativa omhändertagandet (premedicinering - peroperativt - postoperativt smärtomhändertagande) i samband med tonsilloperationer på barn och ungdomar. Bakgrund och referenser till riktlinjerna finns i ett separat dokument.

    Riktlinjerna gäller för friska barn. Finns det riskfaktorer som ex grav sömnapné, kraftig övervikt, komplicerande sjukdomstillstånd eller organpåverkan behöver den farmakologiska behandlingen anpassas efter situationen.

    Tonsillkirurgi medför svår och långvarig smärta samt hög frekvens av illamående. Smärtan är ofta värst dag 3 till 5 efter tonsillektomi. Tonsillotomi ger generellt upphov till mindre smärta än tonsillektomi. För att uppnå effekt behöver den farmakologiska smärtbehandlingen påbörjas redan vid premedicineringen och fortlöpa under själva anestesin/ingreppet. En multimodal behandling ska eftersträvas och målsättningen är att uppnå en för individen acceptabel smärtnivå i det postoperativa skedet och i hemmet.

    Den farmakologiska behandlingen ska kombineras med preoperativ information om ingreppet till patienten och vårdnadshavare. En lugn och trygg situation före anestesistart ökar chanserna för ett lugnt postoperativt förlopp.

  • 44.
    Fagerholm, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Carlsson, David J.
    National Research Council of Canada, Ottawa, Ontario; University of Ottawa Eye Institute, Ontario, Canada.
    Merrett, Kimberley
    University of Ottawa Eye Institute, Ontario, Canada.
    Griffith, May
    University of Ottawa Eye Institute, Ontario, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Canada.
    Corrigendum to “Corneal Regeneration Following Implantation of a Biomimetic Tissue-Engineered Substitute”  [vol 2, Issue 2, pg 162-164, 2009]2014In: Clinical and Translational Science, ISSN 1752-8054, E-ISSN 1752-8062, Vol. 7, no 4, p. 347-347Article in journal (Other academic)
    Abstract [en]

    n/a

  • 45.
    Fagerholm, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Ong, Jeb A.
    Maisonneuve Rosemont Hospital, Montreal, Canada .
    Merrett, Kimberley
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Ottawa Hospital Research Institute, Canada.
    Jackson, W. Bruce
    Ottawa Hospital Research Institute, Canada .
    Polarek, James W.
    FibroGen Inc, San Francisco, CA, USA.
    Suuronen, Erik J.
    University of Ottawa Heart Institute, Canada .
    Liu, Yuwen
    CooperVision Inc, Pleasanton, CA, USA.
    Brunette, Isabelle
    Maisonneuve Rosemont Hospital, Montreal, Canada .
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 8, p. 2420-2427Article in journal (Refereed)
    Abstract [en]

    We developed cell-free implants, comprising carbodiimide crosslinked recombinant human collagen (RHC), to enable corneal regeneration by endogenous cell recruitment, to address the worldwide shortage of donor corneas. Patients were grafted with RHC implants. Over four years, the regenerated neo-corneas were stably integrated without rejection, without the long immunosuppression regime needed by donor cornea patients. There was no recruitment of inflammatory dendritic cells into the implant area, whereas, even with immunosuppression, donor cornea recipients showed dendritic cell migration into the central cornea and a rejection episode was observed. Regeneration as evidenced by continued nerve and stromal cell repopulation occurred over the four years to approximate the micro-architecture of healthy corneas. Histopathology of a regenerated, clear cornea from a regrafted patient showed normal corneal architecture. Donor human cornea grafted eyes had abnormally tortuous nerves and stromal cell death was found. Implanted patients had a 4-year average corrected visual acuity of 20/54 and gained more than 5 Snellen lines of vision on an eye chart. The visual acuity can be improved with more robust materials for better shape retention. Nevertheless, these RHC implants can achieve stable regeneration and therefore, represent a potentially safe alternative to donor organ transplantation.

  • 46.
    Farnebo, Lovisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Tiefenböck, Katharina
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ansell, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Thunell, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Garvin, Stina
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Strong expression of survivin is associated with positive response to radiotherapy and improved overall survival in head and neck squamous cell carcinoma patients2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 133, no 8, p. 1994-2003Article in journal (Refereed)
    Abstract [en]

    Head and neck squamous cell carcinoma (HNSCC) is a malignancy that is associated with severe mortality despite advances in therapy. Todays standard treatment most commonly includes radiotherapy, often combined with chemotherapy or surgery. There are so far no established biomarkers to predict response to radiation, and thus the aim of this study was to investigate a series of markers that could potentially identify HNSCC patients who would benefit from radiotherapy. The selected markers, both proteins (epidermal growth factor receptor, survivin and p53), and single nucleotide polymorphisms (SNPs) in the genes of XRCC3, XRCC1, XPC, XPD, MDM2, p53 and FGFR4 were correlated to the response to radiotherapy and overall survival. Investigations were performed on pretreatment tumor biopsies from patients classified as responders or nonresponders to radiotherapy. Protein expression was examined using immunohistochemistry and the genotyping of specific SNPs was analyzed using PCR-RFLP or pyrosequencing. We found that survivin expression was significantly stronger in the responder group (p = 0.003) and that patients with a strong survivin expression had a significantly better overall survival (p andlt; 0.001). Moreover, downregulation of survivin by siRNA in two HNSCC cell lines significantly decreased their sensitivity to radiation. Among the SNPs analyzed, patients with the XPD Lys751Gln SNP had a significantly shorter overall survival (p = 0.048), and patients with the FGFR4 Gly388Arg SNP had a significantly longer overall survival (p = 0.010). In conclusion, our results suggest that survivin plays an important role in the response to radiotherapy and may be a useful marker for predicting radiotherapy response in patients with HNSCC. less thanbrgreater than less thanbrgreater thanWhats new? Resistance to radiation therapy is a significant problem in the treatment of head and neck squamous cell carcinoma (HNSCC) and has created a need for the discovery of markers predictive of radiotherapy response. One promising marker is survivin, an inhibitor of apoptosis. Here, in pre-treatment biopsies from 40 patients with HNSCC, strong survivin expression was significantly associated with response to radiotherapy and increased overall survival. The data also indicate that single nucleotide polymorphisms in the genes XPD and FGFR4 are other possible predictors of overall survival after radiotherapy.

  • 47.
    Fisher, James L.
    et al.
    Ohio State University, OH 43201 USA Ohio State University, OH 43201 USA Ohio State University, OH 43201 USA .
    Pettersson, David
    Karolinska Institute, Sweden .
    Palmisano, Sadie
    Ohio State University, OH 43201 USA .
    Schwartzbaum, Judith A.
    Ohio State University, OH 43201 USA Ohio State University, OH 43201 USA Ohio State University, OH 43201 USA Ohio State University, OH 43201 USA .
    Edwards, Colin G.
    Mt Carmel Health Syst, OH USA .
    Mathiesen, Tiit
    Karolinska Hospital, Sweden .
    Prochazka, Michaela
    Karolinska Institute, Sweden .
    Bergenheim, Tommy
    Umeå University, Sweden .
    Florentzson, Rut
    Sahlgrenska University Hospital, Sweden .
    Harder, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Nyberg, Gunnar
    University of Uppsala Hospital, Sweden .
    Siesjo, Peter
    Skåne University Hospital, Sweden .
    Feychting, Maria
    Karolinska Institute, Sweden .
    Loud Noise Exposure and Acoustic Neuroma2014In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 180, no 1, p. 58-67Article in journal (Refereed)
    Abstract [en]

    The results from studies of loud noise exposure and acoustic neuroma are conflicting. A population-based case-control study of 451 acoustic neuroma patients and 710 age-, sex-, and region-matched controls was conducted in Sweden between 2002 and 2007. Occupational exposure was based on historical measurements of occupational noise (321 job titles summarized by a job exposure matrix) and compared with self-reported occupational noise exposure. We also evaluated self-reported noise exposure during leisure activity. Conditional logistic regression was used to estimate odds ratios. There was no statistically significant association between acoustic neuroma and persistent occupational noise exposure, either with or without hearing protection. Exposure to loud noise from leisure activity without hearing protection was more common among acoustic neuroma cases (odds ratio = 1.47, 95% confidence interval: 1.06, 2.03). Statistically significant odds ratios were found for specific leisure activities including attending concerts/clubs/sporting events (odds ratio = 1.82, 95% confidence interval: 1.09, 3.04) and participating in workouts accompanied by loud music (odds ratio = 2.84, 95% confidence interval: 1.37, 5.89). Our findings do not support an association between occupational exposure to loud noise and acoustic neuroma. Although we report statistically significant associations between leisure-time exposures to loud noise without hearing protection and acoustic neuroma, especially among women, we cannot rule out recall bias as an alternative explanation.

  • 48.
    Forsgren, Mikael
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlström, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Karlsson, Markus
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Cedersund, Gunnar
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Whole Body Mechanistic Minimal Model for Gd-EOB-DTPA Contrast Agent Pharmacokinetics in Evaluation of Diffuse Liver Disease2014Conference paper (Other academic)
    Abstract [en]

    Purpose: Aiming for non-invasive diagnostic tools to decrease the need for biopsy in diffuse liver disease and to quantitatively describe liver function, we applied a mechanistic pharmacokinetic modelling analysis of liver MRI with Gd-EOB-DTPA. This modelling method yields physiologically relevant parameters and was compared to previously developed methods in a patient group with diffuse liver disease. Materials and Methods: Using data from healthy volunteers undergoing liver MRI, an identifiable mechanistic model was developed, based on compartments described by ordinary differential equations and kinetic expressions, and validated with independent data including Gd-EOB-DTPA concentration measurements in blood samples. Patients (n=37) with diffuse liver disease underwent liver biopsy and MRI with Gd-EOB-DTPA. The model was used to derive pharmacokinetic parameters which were then compared with other quantitative estimates in their ability to separate mild from severe liver fibrosis. Results: The estimations produced by the mechanistic model allowed better separation between mild and severe fibrosis than previously described methods for quantifying hepatic Gd-EOB-DTPA uptake. Conclusions: With a mechanistic pharmacokinetic modelling approach, the estimation of liver uptake function and its diagnostic information can be improved compared to current methods.

  • 49.
    Frennesson, Christina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Nilsson, Sven Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    A three-year follow-up of ranibizumab treatment of exudative AMD: impact on the outcome of carrying forward the last acuity observation in drop-outs2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 3, p. 216-220Article in journal (Refereed)
    Abstract [en]

    Abstract. Purpose: To analyse a 3-year clinical patient cohort of ranibizumab treatment of exudative age-related macular degeneration (AMD), to investigate the impact on visual outcome of carrying forward the last acuity observation in drop-outs and to explore possible differences between the early and the late phase of the study. Methods: A retrospective study of 312 eyes with neovascular AMD. The patients were followed up monthly, received three initial monthly injections of 0.5 mg ranibizumab and were re-treated pro re nata (PRN). Time-domain optical coherence tomography (TD-OCT) was used until spectral-domain (SD)-OCT was introduced during the last year of enrolment. Sixty-five patients were discontinued from the study. Primary outcome: change in best corrected visual acuity (BCVA). Results: Best corrected visual acuity was 58.4 (CI 56.9-59.9) ETDRS (Early Treatment Diabetic Retinopathy Study) letters. At three months, it had increased by 4.1 letters (p = 0.0004), at 12 months by 1.8 letters, at 24 months by 1.0 letter and at 36 months by 0.1 letter. However, if the last available acuity of drop-outs was carried forward one step and included, acuity had increased by 3.9 letters at 3 months (p less than 0.0001) and by 1.0 letter at 12 months but had decreased by 3.8 letters at 24 months (p = 0.019) and by 4.1 letters (p = 0.003) at 36 months. At 24 months, the result was significantly (p = 0.030) less favourable when drop-outs were included. In patients enrolled during the late phase, BCVA was 59.3 (CI 56.7-62.0). It had increased by 5.7 letters (p less than 0.0001) at three months and by 5.8 letters at 12 months (p = 0.0016). In patients enrolled during the early phase, BCVA was 57.9 (CI 55.0-60.8). At three months, it had increased by 3.5 letters (p = 0.0008), but at 12 months, it had decreased by 2.3 letters (ns). The result at 12 months was significantly (p = 0.0033) better for the late than for the early phase. The number of injections was also significantly (p = 0.011) higher in the late phase. Adverse events were similar to those in earlier clinical trials. Conclusions: The results of this 3-year cohort showed that the initial average acuity could be maintained over 36 months, which was comparable to those of many other clinical cohorts. However, if the last available acuity of drop-outs was carried forward one step and included, the acuity figures would have fallen significantly. The results in patients enrolled during the late phase of the study were fairly similar to those in clinical trials.

  • 50.
    Frennesson, Christina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Wadelius, Claes
    Uppsala University, Sweden .
    Nilsson, Sven Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Best vitelliform macular dystrophy in a Swedish family: genetic analysis and a seven-year follow-up of photodynamic treatment of a young boy with choroidal neovascularization2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 3, p. 238-242Article in journal (Refereed)
    Abstract [en]

    Abstract. Purpose: To determine the mutation in a Swedish family with Best disease (vitelliform macular dystrophy; VMD) and to investigate the short- and long-term effects of photodynamic treatment (PDT) on subretinal neovascularization in a young boy. Methods: The five members of three generations of a family with VMD underwent a thorough ophthalmological examination, including best-corrected visual acuity (VA), visual field, colour vision, biomicroscopy of the posterior segment (dilated), fundus photography and electro-oculography (EOG). For the proband, an eleven-year-old boy, his father and grandfather, dark adaptation test, angiography and electroretinography (ERG) were also performed. After PCR amplification, the genotype was determined by cleavage with restriction enzyme, specific for the W93C allele. Results: Four family members had an abnormal EOG response. All showed the W93C mutation in the VMD2 gene. Visual acuity ranged from 20/20 to 20/250. The fundus manifestations varied from minor pigmentary changes over egg yolk-like lesions to chorioretinal atrophy, and fluorescein angiography showed corresponding pathology. In the proband, VA decreased during follow-up from 0.5 (20/40) to 0.08 (20/250) due to a subfoveal neovascularization with haemorrhage, and PDT with visudyne was begun. The haemorrhage resolved within 2 months, and after three treatments, VA had increased to 0.25 (20/80). One year later, acuity had improved to 0.5 (20/40), and this result was stable throughout the 7 years of the follow-up. Conclusion: The mutation was determined to be W93C, the most common mutation in VMD in Sweden. In an eleven-year-old boy with subretinal neovascularization, PDT seemed to be beneficial also in a long-term follow-up.

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