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  • 1.
    Jaque, Cassandra
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Johansson, Anders
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Kromatografi av polära läkemedel och metaboliter med HILIC-teknik2013Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    The purpose of this project was to investigate if retention of polar compounds that are given to treat tuberculosis, diabetes, inflammatory bowel disease and childhood leukemia could be obtained with HILIC separation. By varying different parameters for different types of columns the compounds were analyzed with the aim of finding guidelines for future method optimizations. To perform these analyzes three different columns were tested – ZIC-HILIC (silica-based with zwitterions), ZIC-pHILIC (polymer-based with zwitterions) and XBridge Amide (amide functions). The results were evaluated with selected quality measures. The parameters being varied were pH, temperature, flow rate, type of buffer and ionic strength. In addition, comparisons between isocratic and gradient separations were performed.

     

    Over 1 000 analyzes were conducted in which retention of 16 of total 18 substances were successfully obtained with HILIC. The columns that generated the best results in terms of greatest number of identified compounds were ZIC-HILIC and XBridge Amide. ZIC-pHILIC offered a wide pH range but generally gave inferior chromatography. The influence of the different parameters on the results has not been investigated in sufficient scope. This means that no specific methods for the different drug groups can be reported.

  • 2.
    Gustafsson, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology.
    Biophysical characterization of the *5 protein variant of human thiopurine methyltransferase by NMR spectroscopy2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Human thiopurine methyltransferase (TPMT) is an enzyme involved in the metabolism of thiopurine drugs, which are widely used in leukemia and inflammatory bowel diseases such as ulcerative colitis and Crohn´s disease. Due to genetic polymorphisms, approximately 30 protein variants are present in the population, some of which have significantly lowered activity. TPMT *5 (Leu49Ser) is one of the protein variants with almost no activity. The mutation is positioned in the hydrophobic core of the protein, close to the active site.

    Hydrogen exchange rates measured with NMR spectroscopy for N-terminally truncated constructs of TPMT *5 and TPMT *1 (wild type) show that local stability and hydrogen bonding patterns are changed by the mutation Leu49Ser. Most residues exhibit faster exchange rates and a lower local stability in TPMT *5 in comparison with TPMT *1. Changes occur close to the active site but also throughout the entire protein. Calculated overall stability is similar for the two constructs, so the measured changes are due to local stability.

    Protein dynamics measured with NMR relaxation experiments show that both TPMT *5 and TPMT *1 are monomeric in solution. Millisecond dynamics exist in TPMT *1 but not in TPMT *5, even though a few residues exhibit a faster dynamic. Dynamics on nanosecond to picosecond time scale have changed but no clear trends are observable.

  • 3.
    Ronquist, Gunnar
    et al.
    Avdelningen för klinisk kemi, institutionen för medicinska vetenskaper, Uppsala universitet, Uppsala, Sverige.
    Lötvall, Jan
    Krefting Research Center, Göteborgs universitet, Göteborg, Sverige.
    Gabrielsson, Susanne
    Enheten för translationell immunologi, medicinkliniken, Karolinska universitetssjukhuset; Karolinska institutet, Stockholm, Sverige.
    Mincheva-Nilsson, Lucia
    Avdelningen för klinisk immunologi, institutionen för klinisk mikrobiologi, Umeå universitet, Umeå, Sverige.
    Svanvik, Joar
    Transplantationscentrum Sahlgrenska universitetssjukhuset, Göteborg, Sverige.
    Telemo, Esbjörn
    Avdelningen för reumatologi och inflammationsforskning, Göteborgs universitet, Göteborg, Sverige.
    Waldenström, Anders
    Institutionen för folkhälsa och klinisk medicin, Umeå universitet, Umeå, Sverige.
    Exosomen – intercellulär signalbärare med framtids­potential [Exosomes - intercellular signal carriers with a future potential]: Kan ge nya diagnostiska och terapeutiska möjligheter [May provide new diagnostic and therapeutic opportunities]2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 46, no 110, 2050-2052 p.Article in journal (Other academic)
    Abstract [en]

    Small vesicles were first described in prostatic and seminal fluids more than 30 years ago [5]. They were called prostasomes and are members of the same family now called exosomes. All cells in the body can release extracellular vesicles that function as intercellular messengers. The smallest of these, exosomes, are produced by almost all types of cells in the body and exist in all body fluids. Exosomal signalling takes place in two different ways: either with a cargo of functional proteins and/or by transfection of functional RNA molecules from one cell to the cytoplasm of another, or by ligand-receptor mediated interactions between molecules of the exosome membrane and the cellular membrane of the target cell. The importance of exosomes both in health and disease is rapidly acknowledged and clinical applications in diagnosticts and therapy are under development. The content of proteins and nucleic acids of exosomes will soon be used as bio markers for different diseases such as cancer and cardiac disease. Clinical tests are ongoing where exosomes are used as natural vectors for cancer specific peptides in the treatment of cancer. Exosomes will most probably soon be used in therapy by using them as natural vectors for new  RNA based therapies and also for follow up of therapy.

  • 4.
    Zaigham, Mehreen
    et al.
    Department of Obstetrics and Gynecology Skåne University Hospital, Institution of Clinical Sciences, Lund University, Malmö, Sweden.
    Lundberg, Fredrik
    Department of Neonatology, Skåne University Hospital, Institution of Clinical Sciences, Lund University, Malmö, Sweden.
    Hayes, Ronald
    Banyan Biomarkers Inc., Alachua, FL, USA.
    Undén, Johan
    Department of Intensive Care and Perioperative Medicine, Skåne University Hospital, Institution of Clinical Sciences, Lund University, Malmö, Sweden.
    Olofsson, Per
    Department of Obstetrics and Gynecology Skåne University Hospital, Institution of Clinical Sciences, Lund University, Malmö, Sweden.
    Umbilical cord blood concentrations of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) in neonates developing hypoxic-ischemic encephalopathy.2015In: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 29, no 11, 1822-1828 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) concentrations in umbilical cord blood of neonates who develop Sarnat stage II-III hypoxic-ischemic encephalopathy (HIE) to healthy controls, and to relate the concentrations to the severity of neurology and long-time outcomes.

    MATERIAL AND METHODS: Cord sera of 15 neonates with HIE II-III and 31 matched controls were analyzed for UCH-L1 and GFAP. Comparisons were performed for cord artery pH, amplitude-integrated electroencephalography (aEEG), stage of HIE, and death or sequelae up to an age of 6 years. Parametric and non-parametric statistics were used with a two-sided p < 0.05 considered significant.

    RESULTS: Among controls no associations between biomarker concentrations and gestational age, birthweight, length of storage of cord sera and degree of hemolysis were found. No significant differences in biomarker concentrations were found between HIE neonates and controls, and no differences were found with regard to HIE stage, cord acidemia, severity of aEEG changes, or persistent sequelae or death.

    CONCLUSIONS: No differences in cord blood UCH-L1 and GFAP concentrations were found between HIE neonates and controls, and no associations were found between the biomarker concentrations and the severity of disease, or whether the condition developed into a permanent or fatal injury.

  • 5.
    Pettersson, Olivia
    et al.
    Linköping University, Department of Medical and Health Sciences.
    Wennfalk, Martina
    Linköping University, Department of Medical and Health Sciences.
    Patient education and adherence to tuberculosis treatment: - Indonesian nurses share their experiences2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Aim

    The aim of this qualitative study was to explore Indonesian nurses’ experiences of patient education and patients’ adherence to TB treatment.

    Background

    Tuberculosis (TB) is an infectious disease that 9.6 million people in the world suffer from. Indonesia is one of the world’s 22 high-burden countries with over 320.000 cases of TB in 2014. The UN’s (United Nation) goal is to have ended the TB epidemics by the year 2030. Nurses play a central role in accomplishing adherence to treatment and prevention of TB.

    Method

    To fulfil the aim a qualitative method using semi-structured interviews was used. The interviews were recorded and transcribed. The transcribed data was analysed by using a qualitative content analysis with a manifest approach.

    Findings

    The findings, based on the result of nine interviews, showed four themes: “Strategies for patient education”, “Factors affecting patient education and adherence to treatment”, ”Outcomes of patient education” and ”Feelings and opinions about patient education”.

    Conclusion

    This study showed that the nurses use different strategies when practicing patient education. It was also shown that the nurses are well aware about patient-related factors and how they affect patient education and adherence to TB treatment.

    Keywords

    Tuberculosis, nursing care, patient education, adherence 

  • 6.
    Galiè, Nazzareno
    et al.
    University of Bologna, Italy.
    Barberà, Joan A
    University of Barcelona and Biomedical Research Networking Center on Respiratory Diseases, Madrid, Spain.
    Frost, Adaani E
    Baylor College of Medicine, Houston, USA.
    Ghofrani, Hossein-Ardeschir
    University of Giessen and Marbury Lung Center, Giessen, Germany.
    Hoeper, Marius M
    Hanover Medical School and German Center of Lung Research, Hanover, Germany.
    McLaughlin, Vallerie V
    University of Michigan, USA.
    Peacock, Andrew J
    Regional Heart and Lung Center, Glasgow, Scotland.
    Simonneau, Gérald
    University Paris-Sud, Paris, France.
    Vachiery, Jean-Luc
    Hospital Erasme, Brussels, Belgium.
    Grünig, Ekkehard
    University Hospital Heidelberg, Heidelberg, Germany.
    Oudiz, Ronald J
    UCLA Medical Center, Torrance,USA.
    Vonk-Noordegraaf, Anton
    University Medical Center, Amsterdam, Netherlands.
    White, R James
    University of Rochester, NY, USA.
    Blair, Christiana
    Gilead Sciences, Foster City.
    Gillies, Hunter
    Gilead Sciences, Foster City.
    Miller, Karen L
    Gilead Sciences, Foster City.
    Harris, Julia H N
    GlaxoSmith Kline, Uxbridge, UK.
    Langley, Jonathan
    GlaxoSmith Kline, Uxbridge, UK.
    Rubin, Lewis J
    University of California at San Diego, USA.
    Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension2015In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 373, no 9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.

    METHODS: In this event-driven, double-blind study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response.

    RESULTS: The primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 [95% CI, 1.05 to 2.32]; P=0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia.

    CONCLUSIONS: Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).

  • 7.
    Söderquist, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Proteus: A new predictor for protean segments2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The discovery of intrinsically disordered proteins has led to a paradigm shift in protein science. Many disordered proteins have regions that can transform from a disordered state to an ordered. Those regions are called protean segments.

    Many intrinsically disordered proteins are involved in diseases, including Alzheimer's disease, Parkinson's disease and Down's syndrome, which makes them prime targets for medical research. As protean segments often are the functional part of the proteins, it is of great importance to identify those regions.

    This report presents Proteus, a new predictor for protean segments. The predictor uses Random Forest (a decision tree ensemble classifier) and is trained on features derived from amino acid sequence and conservation data.

    Proteus compares favourably to state of the art predictors and performs better than the competition on all four metrics: precision, recall, F1 and MCC.

    The report also looks at the differences between protean and non-protean regions and how they differ between the two datasets that were used to train the predictor.

  • 8.
    Björkroth, Jennie
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Effekter av naturvårdsgallring på förekomsten av lunglav på ädellövträd2015Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    Sun-exposed broad leaved deciduous trees have a great species diversity of epiphytic lichens. In Europe, these trees have decreased dramatically in number as wooded pastures have become overgrown with trees and bushes, and broad leaved deciduous stands have been replaced by planted coniferous trees. These are the main reasons for many lichens depending on deciduous trees being red-listed. Epiphytic lichens in overgrown areas could benefit from conservation thinning, but few studies have been performed on how this type of cutting affects the lichens. In a previous study, the presence of red-listed epiphytic lichens in a broad leaved deciduous forest was examined. After the study, thinning of trees and bushes was made. Here we study the effects of this thinning on Lobaria pulmonaria. We tested possible factors that may affect the growth of L. pulmonaria, and if there were any differences in incidence and vitality of the lichen between managed and unmanaged stands. Since Dutch elm disease and ash dieback are well spread in the area, we wanted to see if they also affected the growth of L. pulmonaria. There were no differences in incidence and growth between managed and unmanaged stands. The results were unexpected since other studies show that, for instance, increased sun exposure often has a great effect on the growth of lichens. Many elms and ashes were dead or dying and had a significant negative effect on the change of number of lobes and the lobe surface. The diseases of the trees can thus be assumed to be the greatest cause of why the lichens in the managed stand did not benefit from thinning.

  • 9.
    Hongxing, Li
    et al.
    Department of Clinical Dentistry – Prosthodontics, University of Bergen, Bergen, Norway.
    List, Thomas
    Orofacial pain and Jaw Function, Malmö University, Malmö, Sweden.
    Nilsson, Ing-Marie
    Specialist Center for Oral Rehabilitation, Norrköping, Sweden .
    Johansson, Anders
    Department of Clinical Dentistry – Prosthodontics, University of Bergen, Bergen, Norway.
    Nordrehaug Astrom, Anne
    Department of Clinical Dentistry – Community Dentistry, University of Bergen, Bergen, Norway.
    Validity and reliability of OIDP and OHIP-14: a survey of Chinese high school students2014In: BMC Oral Health, ISSN 1472-6831, Vol. 14, no 158, 1-10 p.Article in journal (Refereed)
    Abstract [en]

    Background: To determine the impact of oral diseases on everyday life, measures of oral quality of life are needed. In complementing traditional disease-based measures, they assess the need for oral care to evaluate oral health care programs and management of treatment. To assess the reliability and validity of the Oral Impact of Daily Performance (OIDP) and the short-form Oral Health Impact Profile (OHIP-14) among high school students in Xian, the capital of Shanxi province, China. Methods: Cross-sectional one-stage stratified random cluster sample using high schools as the primary sampling unit. Students completed self-administered questionnaires at school. The survey included the OHIP-14 and OIDP inventories, translated and culturally adapted for China, and global oral health and socio-behavioral measures. Results: A total of 5,608 students participated in the study, with a 93% response rate (mean age 17.2, SD 0.8, 52% females, 45.3% urban residents). The proportion experiencing at least one impact (at any frequency) during the previous six months was 62.9% for the OHIP-14 and 45.8% for the OIDP. Cronbachs alpha measured internal consistency at 0.85 for OHIP-14 and 0.75 for OIDP while Cohens kappa varied between 0.27 and 0.58 for OHIP-14 items and between 0.23 and 0.65 for OIDP items. Kappa scores for the OHIP-14 and OIDP additive scores were 0.52 and 0.66, respectively. Both measures varied systematically and in the expected direction, with global oral health measures showing criterion validity. The correlation between OIDP and OHIP-14 was r(s) + 0.65. That both measures varied systematically with socio-behavioral factors indicates construct validity. Conclusion: Both the OIDP and OHIP-14 inventories had reasonable reliability and construct validity in relation to subjective global oral health indicators among adolescents attending high schools in China and thus appear to be useful oral health -related quality of life measures in this context. Overall, the OHIP-14 and OIDP performed equally well, although OHIP-14 had superior content validity due to its sensitivity towards less severe impacts.

  • 10.
    Larsson, Elias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Isaksson, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Avgörande faktorer för talnaturlighet hos personer med Parkinsons sjukdom: Korrelationsstudie mellan naiva lyssnares bedömning och akustisk analys2015Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Speech and voice changes are common in Parkinson’s disease. These changes can affect the speaker’s intelligibility but can also have a negative impact on the perceived naturalness of speech. The research available regarding the different factors that affect speech naturalness is scarce, which was the motivation behind this study.

    The aim of the present study was to investigate whether the level of perceived speech naturalness could derive from any specific aspects of speech. This was accomplished by recording speech samples from eight people with Parkinson’s disease using a test battery with various speech tasks. These samples were presented to a group of 27 naive listeners whose task was to judge the level of intelligibility as well as the level of speech naturalness. Correlations were then made between their assessments and various acoustic measurements.

    The main finding of the present study was that speech and articulation rate seemed to have the greatest impact on the perceived level of naturalness, where the people who had the slowest rate were judged to be the least natural sounding. Furthermore there were strong indications that the level of intelligibility correlated with the level of speech naturalness. In this study there were no other acoustic correlates found with statistical significance.

  • 11.
    Romanos, J.
    et al.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, PO Box 30001, Groningen 9700 RB, Netherlands; School of Medicine, Lebanese American University, Beirut, Lebanon.
    Rosen, A.
    Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden; Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden.
    Kumar, V.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Trynka, G.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, PO Box 30001, Groningen 9700 RB, Netherlands; Division of Genetics and Division of Rheumatology, Harvard Medical School, Brigham and Womens Hospital, Boston, MA, United States.
    Franke, L.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Szperl, A.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Gutierrez-Achury, J.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Van, Diemen C.C.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Kanninga, R.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Jankipersadsing, S.A.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Steck, A.
    Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States.
    Eisenbarth, G.
    Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States.
    Van, Heel D.A.
    Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, United Kingdom.
    Cukrowska, B.
    Department of Pathology, Childrens Memorial Health Institute, Warsaw, Poland.
    Bruno, V.
    European Laboratory for Food-Induced Disease, University of of Naples Federico II, Naples, Italy.
    Mazzilli, M.C.
    Department of Molecular Medicine, Sapienza University of of Rome, Rome, Italy.
    Nunez, C.
    Clinical Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos IdISSC, Madrid, Spain.
    Bilbao, J.R.
    Immunogenetics Research Laboratory, Hospital de Cruces, Bizkaia, Spain.
    Mearin, M.L.
    Department of Paediatrics, Leiden University of Medical Centre, Leiden, Netherlands.
    Barisani, D.
    Department of Experimental Medicine, Faculty of Medicine, University of of Milano- Bicocca, Monza, Italy.
    Rewers, M.
    Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States.
    Norris, J.M.
    Epidemiology Department, Colorado School of Public Health, Aurora, United States.
    Ivarsson, A.
    Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden.
    Boezen, H.M.
    Department of Epidemiology, University of of Groningen, University of Medical Centre Groningen, Groningen, Netherlands.
    Liu, E.
    Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States.
    Wijmenga, C.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, PO Box 30001, Groningen 9700 RB, Netherlands.
    Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants2014In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 3, 415-422 p.Article in journal (Refereed)
    Abstract [en]

    Background The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. Objective We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. Design We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case-control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. Results Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. Conclusions Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD.

  • 12.
    Seki, Satomi
    et al.
    University of Tokyo.
    Kato, Naoko
    University of Tokyo.
    Ito, Naomi
    University of Tokyo.
    Kinugawa, Koichiro
    University of Tokyo.
    Ono, Minoru
    University of Tokyo.
    Motomura, Noboru
    University of Tokyo.
    Yao, Atsushi
    University of Tokyo.
    Watanabe, Masafumi
    University of Tokyo.
    Imai, Yasushi
    University of Tokyo.
    Takeda, Norihiko
    University of Tokyo.
    Inoue, Masashi
    University of Tokyo.
    Hatano, Masaru
    University of Tokyo.
    Kazuma, Kazuma
    University of Tokyo.
    Validity and reliability of Seattle angina questionnaire Japanese version in patients with coronary artery disease2010In: Asian Nurs Res (Korean Soc Nurs Sci), Vol. 4, no 2, 57-63 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to evaluate the validity and reliability of the Seattle Angina Questionnaire, Japanese version (SAQ-J) as a disease-specific health outcome scale in patients with coronary artery disease. METHODS: Patients with coronary artery disease were recruited from a university hospital in Tokyo. The patients completed self-administered questionnaires, and medical information was obtained from the subjects' medical records. Face validity, concurrent validity evaluated using Short Form 36 (SF-36), known group differences, internal consistency, and test-retest reliability were statistically analyzed. RESULTS: A total of 354 patients gave informed consent, and 331 of them responded (93.5%). The concurrent validity was mostly supported by the pattern of association between SAQ-J and SF-36. The patients without chest symptoms showed significantly higher SAQ-J scores than did the patients with chest symptoms in 4 domains. Cronbach's alpha ranged from .51 to .96, meaning that internal consistency was confirmed to a certain extent. The intraclass correlation coefficient of most domains was higher than the recommended value of 0.70. The weighted kappa ranged from .24 to .57, and it was greater than .4 for 14 of the 19 items. CONCLUSIONS: The SAQ-J could be a valid and reliable disease-specific scale in some part for measuring health outcomes in patients with coronary artery disease, and requires cautious use.

  • 13. Kato, Naoko
    et al.
    Kinugawa, Koichiro
    Ito, Naomi
    Yao, Atsushi
    Watanabe, Masafumi
    Imai, Yasushi
    Takeda, Norihiko
    Hatano, Masaru
    Kazuma, Keiko
    Adherence to self-care behavior and factors related to this behavior among patients with heart failure in Japan2009In: Heart & Lung, ISSN 0147-9563, E-ISSN 1527-3288, Vol. 38, no 5, 398-409 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adherence to self-care behavior is important for patients with heart failure (HF) to prevent exacerbation of HF. The aim of this study was to evaluate adherence, identify associated factors, and clarify the impact of previous HF hospitalizations on adherence in outpatients with HF. METHODS: A total of 116 outpatients completed a questionnaire, including the Japanese version of the European Heart Failure Self-Care Behavior Scale, to assess adherence. RESULTS: Regardless of previous hospitalizations, adherence to seek help if HF worsened was poor. Multivariate analysis adjusted for age and brain natriuretic peptide showed that diabetes mellitus and being employed were independent predictors of poorer adherence to self-care behavior (P = .03, P = .02, respectively), but the experience of previous HF hospitalizations was not a predictor. CONCLUSIONS: Self-care strategies for HF should target patients with diabetes mellitus and employed patients. Further study is necessary to develop effective programs for such patients.

  • 14.
    Knip, Mikael
    et al.
    University of Helsinki, Helsinki, Finland.
    Åkerblom, Hans K
    University of Helsinki, Helsinki, Finland.
    Becker, Dorothy
    University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
    Dosch, Hans-Michael
    University of Toronto, Toronto, Ontario, Canada.
    Dupre, John
    University of Western Ontario, London, Canada.
    Fraser, William
    University of Montréal, Montréal, Québec, Canada.
    Howard, Neville
    Children’s Hospital of Westmead, Sydney, Australia.
    Ilonen, Jorma
    University of Turku, Turku, Finland.
    Krischer, Jeffrey P
    University of South Florida, Tampa, USA.
    Kordonouri, Olga
    Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.
    Lawson, Margaret L
    Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada .
    Palmer, Jerry P
    University of Washington, Seattle, USA.
    Savilahti, Erkki
    University of Helsinki, Helsinki, Finland.
    Vaarala, Outi
    National Institute for Health and Welfare, Helsinki, Finland.
    Virtanen, Suvi M
    National Institute for Health and Welfare, Helsinki, Finland.
    Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial.2014In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 311, no 22, 2279-2287 p.Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.

    OBJECTIVE: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children.

    DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013.

    INTERVENTIONS: The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate.

    MAIN OUTCOMES: AND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years).

    RESULTS: The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups.

    CONCLUSIONS AND RELEVANCE: Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777.

  • 15.
    Ringdahl, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Familjen i cancervården - när en förälder är sjuk2014Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This study describes how the whole family with its various family members are affected in different ways when a parent suffers a cancer disease. Parents ' experience includes both their vision of how parenting and relationship are affected and how they see that the children, teenagers and young adults is affected when one parent is ill, and the significance of any talks had offered.  Even the children, teenagers and young adults as dependents between the ages of 10-25 years, have given their views on how they perceive themselves and parents affected by that one parent has/had a cancerous disease and the significance of any talks had offered. This study shows, among other things, that partner describes a much higher impact for themselves and their children than parents who are patient, and that young adults are more affected by the parent's cancer than what parents think.

  • 16.
    Prieto-Velasco, Mario
    et al.
    Complejo Asistencial Universitario de León, León, Spain .
    Isnard Bagnis, Corinne
    Université Pierre et Marie Curie, Paris France .
    Dean, Jessica
    Department of Clinical Health Psychology, Salford Royal Hospital, Salford, UK.
    Goovaerts, Tony
    Cliniques Universitaires St. Luc, Brussels, Belgium .
    Melander, Stefan
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Mooney, Andrew
    St James’s University, Leeds, UK .
    Nilsson, Eva-Lena
    Skåne Universitetssjukhus, Malmö .
    Rutherford, Peter
    Baxter-Gambro Renal, Zurich, Switzerland.
    Trujillo, Carmen
    Hospital Regional Carlos Haya, Malaga, Spain.
    Zambon, Roberto
    Unità Operativa di Nefrologia, Dialisi e Trapianto, Ospedale San Bortolo,Vicenza, Italy.
    Crepaldi, Carlo
    Unità Operativa di Nefrologia, Dialisi e Trapianto, Ospedale San Bortolo,Vicenza, Italy.
    Predialysis education in practice: a questionnaire survey of centres with established programmes.2014In: BMC research notes, ISSN 1756-0500, Vol. 7, 730- p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is growing evidence that renal replacement therapy option education (RRTOE) can result in enhanced quality of life, improved clinical outcomes, and reduced health care costs. However, there is still no detailed guidance on the optimal way to run such programmes. To help address this knowledge gap, an expert meeting was held in March 2013 to formulate a position statement on optimal ways to run RRTOE. Experts were selected from units that had extensive experience in RRTOE or were performing research in this field. Before the meeting, experts completed a pilot questionnaire on RRTOE in their own units. They also prepared feedback on how to modify this questionnaire for a large-scale study.

    METHODS: A pilot, web-based questionnaire was used to obtain information on: the renal unit and patients, the education team, RRTOE processes and content, how quality is assessed, and funding.

    RESULTS: Four nurses, 5 nephrologists and 1 clinical psychologist (9 renal units; 6 EU countries) participated. Nurses were almost always responsible for organising RRTOE. Nephrologists spent 7.5% (median) of their time on RRTOE. Education for the patient and family began several months before dialysis or according to disease progression. Key topics such as the 'impact of the disease' were covered by every unit, but only a few units described all dialysis modalities. Visits to the unit were almost always arranged. Materials came in a wide variety of forms and from a wide range of sources. Group education sessions were used in 3/9 centres. Expectations on the timing of patients' decisions on modality and permanent access differed substantially between centres. Common quality assurance measures were: patient satisfaction, course attendance, updated materials. Only 1 unit had a dedicated budget.

    CONCLUSIONS: There were substantial variations in how RRTOE is run between the units. A modified version of this questionnaire will be used to assess RRTOE at a European level.

  • 17.
    Goovaerts, Tony
    et al.
    Cliniques Universitaires St Luc, Brussels, Belgium .
    Bagnis Isnard, Corinne
    Université Pierre et Marie Curie, Paris France.
    Crepaldi, Carlo
    Unità Operativa di Nefrologia, Dialisi e Trapianto, Ospedale San Bortolo, Vicenza, Italy.
    Dean, Jessica
    Salford Royal Hospital, Salford, UK.
    Melander, Stefan
    Mooney, Andrew
    St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
    Prieto-Velasco, Mario
    Unidad de Nefrología, Complejo Asistencial Universitario de León, León, Spain.
    Trujillo, Carmen
    Unidad clínica de Gestión de Nefrología, Hospital Regional Carlos Haya, Malaga, Spain.
    Zambon, Roberto
    Dialisi e Trapianto, Ospedale San Bortolo, Vicenza, Italy.
    Nilsson, Eva-Lena
    Skåne University Hospital .
    Continuing education: preparing patients to choose a renal replacement therapy.2015In: Journal of Renal Care, ISSN 1755-6678, E-ISSN 1755-6686, Vol. 41, no 1, 62-75 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with progressive chronic kidney disease face a series of treatment decisions that will impact the quality of life of themselves and their family. Renal replacement therapy option education (RRTOE), generally provided by nurses, is recommended by international guidelines

    OBJECTIVES: To provide nurses with advice and guidance on running RRTOE.

    DESIGN: A consensus conference.

    PARTICIPANTS: Four nurses, 5 nephrologists and 1 clinical psychologist (9 renal units; 6 European countries) from units that had extensive experience in RRTOE or were performing research in this field.

    APPROACH: Experts brainstormed and discussed quality standards for the education team, processes, content/topics, media/material/funding and quality measurements for RRTOE.

    RESULTS: Conclusions and recommendations from these discussions that are particularly pertinent to nurses are presented in this paper.

    CONCLUSIONS: Through careful planning and smooth interdisciplinary cooperation, it is possible to implement an education and support programme that helps patients choose a form of RRT that is most suited to their needs. This may result in benefits in quality of life and clinical outcomes.

    APPLICATION TO PRACTICE: There are large differences between renal units in terms of resources available and the demographics of the catchment area. Therefore, nurses should carefully consider how best to adapt the advice offered here to their own situation. Throughout this process, it is crucial to keep in mind the ultimate goal - providing patients with the knowledge and skill to make a modality choice that will enhance their quality of life to the greatest degree.

  • 18.
    Skarphagen, Richard
    et al.
    Linköping University, Department of Electrical Engineering. Linköping University, The Institute of Technology.
    Suu, Albin
    Linköping University, Department of Electrical Engineering. Linköping University, The Institute of Technology.
    Utveckling av prototyp för utläsning av sensorvärden från enkortsdator via NFC2014Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    The use of phone to check if you are sick or not has just begun, one example of this is that Apple recently released its new ios that contains the app “Health” where you can check how many steps you have taken on a day, check your pulse rate or how many calories you have burnt during the day.

    We simply want to check our health at home with ease so we don’t have to go to the hospital, this requires that our product has to be small and cellpowered and of course cheap.

    This report describes our examwork where we investigate if we can build a blood flow measurement/measuring prototype, it has to be cheap, cellpowered, small and it must have theability to send its information via the protocol NFC.

    We were given a Raspberry Pi, this to keep the price down, and for the NFCsending issue wehad to use Androidphones/tablets with NFC on them. To reach the goal we had to program the Raspberry Pi in C to take care of the information, and make an app for Android in Java that reads the information wirelessly and can show the information on display.

    Late in the project we noticed that our ADC couldn’t handle the probe, wich made us unable to realise the blood flow probe measurements. Therefore our finished product is not the complete product we were hiping for.

    We had to change the probe to a IRdistance sensor, wich we chose because then we would still be able to show that we can send information from a sensor via ADC to Raspberry Pi and then to the phone/tablet.

    Our finished product became a small, cheap and cellpowered distance measurer. This showed us that we have the knowledge to make a small, cheap and cellpowered hospital gear.

    In the future there are big possibilites with what you can do with this  technique for example, check for disease, blood flow, lung capacity just by reading via moving your phone over for example a watch.

  • 19.
    Perkiö, Mattias
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Assessment of Pulse Wave Velocity in the Aorta by using 4D Flow MRI2014Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The purpose of this master thesis was to evaluate the estimation of pulse wave velocity (PWV) in the aorta using 4D flow MRI. PWV is the velocity of the pressure wave generated by the heart during systole and is a marker of arterial stiffness and a predictor of cardiovascular disease (CVD). PWV can in principle be estimated based on the time (travel-time) it takes for the pulse wave to travel a fixed distance (travel-distance), or based on the distance the pulse wave travels during a fixed time. In the commonly used time-to-travel-a-fixed-distance approach, planes are placed at two or more locations along the aorta. The travel-time is found by studying velocity waveforms at these pre-defined locations over time and thereby by estimating the time-difference for the pressure wave to reach each of these locations. In the distance-travelled-in-a-fixed-time approach, the pulse wave is located by studying at the velocity along the aorta at pre-defined instances in time. The travel-distance for the pulse wave between two instances in time is set as the difference in location of the pulse wave, where the location is identified as the location when the velocity has reached a predefined baseline. The specific aims of this thesis was to investigate the effect of using multiple locations as well as the effects of temporal and spatial resolution in the time-to-travel-a-fixed-distance approach, and to evaluate the possibility of using the distance-travelled-in-a-fixed-time approach. Additionally, the possibility of combining the two approaches was investigated. The study of using multiple locations revealed that more planes reduces the uncertainty of PWV estimation. Temporal resolution was found to have a major impact on PWV estimation, whereas spatial resolution had a more minor effect. A method for estimating PWV using 4D flow MRI using the distance-travelled-in-a-fixed-time approach was presented. Values obtained were compared favourably against previous findings and reference values, in the case of healthy young volunteers. The combination of the time-to-travel-a-fixed-distance and distance-travelled-in-a-fixed-time approaches appears feasible.

  • 20.
    Bäckman, Lisa
    et al.
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences.
    Karlsson, Malin
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences.
    Arbetsterapeutiska åtgärder som främjar delaktighet i dagliga aktiviteter hos personer med demenssjukdom2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The number of older people in society is increasing, and along with it so is the prevalence of dementia. Activity is of great importance for people with dementia, but the disease has negative effects on the ability to perform everyday occupations. The purpose of this study was therefore to describe occupational therapy interventions that promote participation in daily activities in persons with dementia. Data was collected through a systematic search using five databases, and through a manual search. Altogether, 14 articles were included in the study. The data were analyzed using a qualitative content analysis. Patterns were identified and later analyzed. The study proposes compensatory and remedial interventions, such as modifying the physical environment to accommodate the disability, simplifying activities and improving cognitive functioning to facilitate performance in daily activities. By making individualized modifications of the physical environment, coaching caregivers, and adapting activities to personal requirements and interests, people with dementia are given a greater opportunity to be independent and to experience participation in daily activities. This study shows that occupational therapy interventions can have positive effects on persons with dementia and on their possibilities to participate in daily activities.

  • 21.
    Karlsson, Lise-Lott
    Linköping University, Department of Culture and Communication, Centre for Applied Ethics. Linköping University, Faculty of Arts and Sciences.
    Prenatal Testing and Reproductive Freedom: A Mother´s Right to Choose2014Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of this thesis is to analyse and examine the debate on prenatal testing in Western countries, with a special focus on my own country, Sweden. In the near future it might be possible for a pregnant woman to profile the DNA of her foetus with a simple blood test early in pregnancy. This method of prenatal testing – Non Invasive Prenatal Diagnosis (NIPD) – could potentially detect the genetic causes of almost every disease. I will argue that prenatal testing should be offered by society to all pregnant women, not only to those at highest risk of giving birth to children with severe conditions. I will do that from a perspective of reproductive freedom. Furthermore, I will argue that offering prenatal testing for some conditions (such as Downs’s syndrome) and not for others, is conflicting with the autonomous choice of the pregnant woman.

  • 22.
    Westergren, Samuel
    Linköping University, Faculty of Health Sciences.
    Nivåer av det lysosomala systemets proteiner i hjärnvävnad från Alzheimerpatienter2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Alzheimer's disease is the most common cause of dementia, and when the population becomes larger and older also the number of patients increase. A cerebral atrophy and microscopic findings of extracellular plaques of β-amyloid, intracellular neurofibrillary of phosphorylated tau and loss of nerve cell protrusions, axons, synapses and dendrites are seen during the disease. One of the early pathological changes is the disruption of the neuronal lysosomal network that plays an important role in the degradation of macromolecules. In a previous study elevated levels of proteins of the lysosomal network in cerebrospinal fluid from Alzheimer’s disease patients was demonstrated. The purpose of this study was to measure levels of the lysosomal network system in the brain. The six proteins EEA1, PICALM, LAMP-1, LAMP -2, LC3 and TFEB were analyzed in human brain tissue from five Alzheimer's disease cases and five control cases by Western blot. The results show a significant increase in the temporal cortex of LAMP-1 and LAMP -2 and a significant decrease of LC3 and EEA1 in patients with Alzheimer's disease. In order to draw proper conclusions about how the increased levels in cerebrospinal fluid reflect the different disease mechanisms in the brain it requires further analysis of more patient samples and from other areas of the brain.

  • 23.
    Azadi, Sahar
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Alternativ splicing: Mutationer i BRCA1 och BRCA2 orsakar bröstcancer2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    During the past decade it has been shown that alternative splicing is a important mechanism for the proteome diversity. AS is a mechanism that generates a large amount of protein isoforms from a low number of human genes. Alternative splicing is regulated by four groups of cis-regulatory elements and different splicing factors. Even though AS is important for the diversity and complexity of different organisms it is also a source for different genetic diseases like cancer. This review article will focus on breast cancer and its connection to the mechanism of alternative splicing. Breast cancer is a common disease in women. In recent years many studies have shown an important relationship between mutations in the alternative splicing mechanism and the two most important genes involved in breast cancer BRCA1 and BRCA2. This article will also present different efforts against this disease. 

  • 24.
    Sandsveden, Li
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Evaluation of the Robustness of the Brain Parenchymal Fraction for Brain Atrophy Measurements2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In certain diseases, like Multiple Sklerosis and Alzheimer's disease, the progression of the disease can be measured by whole brain atrophy. A difficulty with this is that all people have very different scull sizes, thus also very different brain sizes. This makes it almost impossible to establish "normal values" for brain size. The spread is very large and the method is not practical to use for individual patients. A method with less spread in healthy persons is to use the ratio of the Brain Parenchymal Fraction (BPF). The use of Brain Parenchymal Fraction has increased steadily since it was first introduced in 1999. 

    BPF = BPV/ICV

    This study was performed to increase the knowledge of what is normal and to evaluate the robustness of the BPF as a measurement for brain atrophy. Among other things, the change in the BPF when calculated from incomplete volumes (parts of the scull missing in the set of MR images) was evaluated. 

    The results show that when parts are missing from the top (superior) of the scull the resulting BPF is strictly higher than the correct PBF and when parts are missing from the lower (inferior) part of teh scull the resulting BPF is stritly lower than teh correct value. 

    Two different methods where tried to compensate for missing parts. The first method was to find a variable factor to compensate with, the size of this factor was depending on how much of the scull that was missing. The second method was to interpolate the ICV and BPV curves and from the new interpolated curves, calculate a new BPF.

    The method of compensating incomplete volumes using a factor calculated as a function of the intercranial volume of the first/last available slice turned out to be the better. 

  • 25.
    Sandberg, Alexander
    Linköping University, Department of Physics, Chemistry and Biology, Biochemistry. Linköping University, The Institute of Technology.
    Interaction studies of luminescent conjugated oligothiophenes with aggregated Amyloid β2013Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Alzheimer’s disease is the most common cause of dementia and was responsible for over 2% of all deaths in Sweden 2012. One of the pathological hallmarks is amyloid plaques built by fibrillated Amyloid β. Luminescent conjugated oligothiophenes are known to stain and give characteristic fluorescence spectra when staining amyloid fibrils. Little is however known about the interactions between LCOs and fibrils. Studies have been performed on molecules more traditionally known to stain amyloid fibrils. Studies have also been performed on fibrils using limited proteolysis. So far no studies have been performed using LCOs combined with limited proteolysis in order to study the interaction pattern between LCOs and fibrils.

    Amyloid β is expressed and purified using a simple few step purification protocol. The amyloid β peptide was then fibrillated in several generations in order to select for a homogenous fibril structure. This purification protocol also has the ability to purify different oligomers of Amyloid β that are interesting from a toxicity point of view. In this thesis optical characteristics and limited proteolysis with mass spectrometry are being used to studies the interactions between LCOs and fibrillated amyloid β. The proteolytic pattern was suggestive of an accessible N-terminal and a hidden C-terminal of Amyloid β M1-42 in the fibril. It was also shown that the proteolysis cleavage pattern of Chymotrypsin is not disrupted when the LCO pKTAA was used to stain fibrils. The emission spectra from the two LCOs pATAA and pKTAA changes differently when subjected to continuous excitation indicative of conformational changes or chemical modification.

  • 26.
    Gudmann Knutsson, Sophie
    et al.
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Stenbeck, David
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Subject SexIQ - An improved sexual education for students in Jr. high school2010Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Communication is steadily becoming more and more important in human beings everyday life. All around us, companies, advertisement agencies and regular people are working hard to find proper channels to communicate their information. With this abundance of information around us, problems in sorting which information is important and correct vs. what is pure reflection are bound to arise. We face a increasing difficulty in reaching a certain target group.

    This report accounts for a project started by two students in cooperation with Landstinget i Östergötland, Ungdomshälsan i Norrköping and Victoriaskolan in Norrköping. The project investigates proper methods for communicating sex education to younger teenagers. The project began as a theoretical project but developed into an actual project.

    A lot of effort has gone into building a foundation for what types of information is relevant for the students and which method this information should be conveyed to the students in. From this a proposition for how sexual education in Swedish schools can be changed and improved from a student’s perspective compared to what it is today.

    The purpose of this degree project has been to explore what the current sexual´education today consists of and how students feel about it. Further the purpose has been to find out what information that as of today is available but isn’t conveyed to the students, and to from this material and some additions present a basis for all teachers to use as a support for sexual education in Sweden.

    Qualitative studies have been made through interviews with teachers and students at two schools with differing prior experience with sexual education. A lot of information has been gathered from RFSU and there has been an open dialogue with Ungdomshälsan in Norrköping and the Center for Disease Control at Landstinget i Östergötland. In other words, the project has been conducted with assistance from teachers, students and specialists in the area who also work with conveying information to youths. To ensure a arbitrary result a evaluation of the project by students and teachers has also been performed at the school that hosted the Theme-week. The conclusion of these can be found as an appendix in this report.

  • 27.
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Detection of Neurotransmitters in the Human Brain Using Magnetic Resonance Spectroscopy2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    There is an increasing interest in studying the concentration of the inhibitory neurotransmitter γ-Amino Butyric Acid (GABA), both in the healthy and diseased brain by using Magnetic Resonance Spectroscopy (MRS). Recent studies have shown correlations between an abnormal GABA concentration in certain regions of the brain and disorders as e.g. Parkinson’s disease and depressive disorders. There are presently many technical difficulties with the absolute quantification of GABA and the method MEGA-PRESS is currently the standard technique used in data acquisitions and processing of spectra. In this thesis, different techniques of GABA quantification have been evaluated and the most important aspect was to explore the precision of the method for further usage as a clinical tool. This project involved the exploration of data acquisitions by using a MEGA-PRESS sequence on a 3 T MR-system, processing of the resulting datasets using different methodologies, GABA quantification by using linear combination of model spectra (LCModel), and interpretation of the results by performing statistical analyses. The thesis resulted in a low resolution GABA-atlas of the brain which did not indicate any significant differences in the GABA concentration within the healthy subject group. However, a significant regional difference was observed in the brain. The main uncertainties arose mainly due to the relatively small subject groups and the large measurement error. Future measurements will require improvements both in the data acquisition and in analyzing these with an improved method of processing. The final conclusion was that the GABA quantification sequence MEGA-PRESS is useful both in diagnosis and as a research tool, although further improvements are required.

  • 28.
    Enetoft, Daniel
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Automating analysis of two-dimensional liquid chromatography data2008Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    A biomarker is a cellular or molecular indicator of exposure, disease, or susceptibility to disease. Ones a biomarker has been confirmed, it can be used to diagnose disease risk or to tailor treatment for it.

    A protein is a possible biomarker. These proteins can be found by several methods, where two-dimensional liquid chromatography (2DLC) is one of the newer approaches. This technique is capable of separating thousands of proteins. To find the proteins whose abundance differs in different groups, the data must be carefully analyzed. Due to the amount of proteins that can be found by the method and difficulties in preparation of the data, this is not a simple problem to solve.

    In this thesis a workflow for finding differences between groups of samples analyzed with 2DLC is presented.

    The workflow has been separated into three parts. The first part is background subtraction, to remove the parts of the signals that originate from noise. After that comes alignment of the signals. The difficulties to prepare the 2DLC data makes the signal unpredictably distorted in a non linear way. The last part is the essence of the analysis process. First determine that differences do exist between the groups of data being analyzed and then identify where it differs.

    Several methods for each part have been evaluated and are presented in this thesis.

  • 29.
    Strömberg, Jan-Erik
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Babić, Ankica
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Krusinska, Ewa
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Extraction of Diagnostic Rules using Recursive Partitioning Systems: A Comparision of Two Approaches1992In: Artificial Intelligence in Medicine, ISSN 0933-3657, E-ISSN 1873-2860, Vol. 4, no 5, 373-387 p.Article in journal (Refereed)
    Abstract [en]

    There are several empirical systems based on principles of learning from examples that can be used as a tool for decision support by medical experts in medicine. We are comparing two systems of this kind, one based on Quinlan's ID3 algorithm, and the other based on Breiman's CART (Classification And Regression Trees) algorithm. Both of these methods represent the extracted knowledge in form of binary tree structured diagnostic rules. In this paper we present the most important features of the two systems and discuss important differences between the two; all this in a uniform framework. We then study the implications these differences and similarities make when applied to clinical data. The empirical study includes two medical data sets: the first one concerning patients with highly selective vagotomy (HSV) for duodenal ulcer surgery, and the second one concerning patients with non-specified liver disease.

  • 30.
    Karlsson, Cecilia
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Studies of unspecific interaction between the Aβ antibody 6E10 and blood coagulation protein factor X2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Alzheimer’s disease is neurodegenerative with amyloid plaque and neurofibrillary tangles as pathological hallmarks. The most abundant component in the amyloid plaque is the amyloid-β (Aβ) peptide, with presence of both isoform Aβ40 and Aβ42. In immunological methods studying the Aβ peptide a specific monoclonal antibody, 6E10, is routinly being used. In this master thesis work unspecific binding of 6E10 antibody to the blood coagulating protein factor X has been investigated. Factor X is a protein in the blood coagulation cascade where it forms protein complex that activates thrombin. Non-hemostatic functions with connections to nerves and Aβ peptide are also known. Studies with Western blot show clear binding of 6E10 to denatured factor X. Interaction studies with ELISA gives uncertain results, where binding is found but no clear binding curve is obtained. Studies with native factor X in real time measurements with SPR gave no binding at all. These results suggest binding to denatured factor X. Immunohistochemistry studies of colocalisation of factor X and Aβ peptide gave clear evidence that factor X and Aβ are found near each other in mouse brain tissue. Factor X is located outside the blood vessels and Aβ is located at the inside. 

  • 31.
    Andersson Naesseth, Christian
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Nowcasting using Microblog Data2012Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    The explosion of information and user generated content made publicly available through the internet has made it possible to develop new ways of inferring interesting phenomena automatically. Some interesting examples are the spread of a contagious disease, earth quake occurrences, rainfall rates, box office results, stock market fluctuations and many many more. To this end a mathematical framework, based on theory from machine learning, has been employed to show how frequencies of relevant keywords in user generated content can estimate daily rainfall rates of different regions in Sweden using microblog data.

    Microblog data are collected using a microblog crawler. Properties of the data and data collection methods are both discussed extensively. In this thesis three different model types are studied for regression, linear and nonlinear parametric models as well as a nonparametric Gaussian process model. Using cross-validation and optimization the relevant parameters of each model are estimated and the model is evaluated on independent test data. All three models show promising results for nowcasting rainfall rates.

  • 32.
    Graflund, Marianne
    et al.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro.
    Sorbe, B.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro.
    Bryne, M.
    Department of Pathology, Institute of Cancer Research, Norwegian Radium Hospital, Oslo, Norway.
    Karlsson, M.
    Department of Pathology, Örebro University Hospital, Örebro.
    The prognostic value of a histologic grading system, DNA profile, and MIB-1 expression in early stages of cervical squamous cell carcinomas2002In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 2, 149-157 p.Article in journal (Refereed)
    Abstract [en]

    This study evaluated the prognostic importance of a new grading system focusing on the invasive tumor front, DNA profile, and the proliferation marker MIB-1. A complete geographic series of 172 women treated with radical hysterectomy (Wertheim–Meigs) for FIGO stage I–II cervical carcinomas was the target population. The analyses were performed on 141 (82%) squamous cell carcinomas of the complete series. During the period of observation (mean 222 months), 17 recurrences (12.1%) were encountered. Prognostic factors for disease-free survival were lymph node status (P < 0.000001), radical surgical margins (P = 0.00004), and tumor size (P = 0.002). The complete score of the invasive front grading system (IFG), and the individual scores of two variables—pattern of invasion and host response—were all significantly (P = 0.002, P = 0.007, P = 0.0001) associated with pelvic lymph node metastases. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting lymph node metastases. The total IFG score was also a significant (P = 0.003) prognostic factor for disease-free survival. DNA ploidy, S-phase fraction, and MIB-1 expression were nonsignificant factors in predicting pelvic lymph node metastases and disease-free survival of the patient. The IFG in the original or modified versions could predict low- and high-risk groups of tumors and therefore be of value in treatment planning for these patients.

  • 33.
    Graflund, Marianne
    et al.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro.
    Sorbe, B.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro.
    Karlsson, M.
    Department of Pathology, Örebro University Hospital, Örebro.
    Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma: Correlation with clinical outcome2002In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 3, 290-298 p.Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to assess the value of p53, bcl-2, and p21WAF1/CIP1 immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21WAF1/CIP1. None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21WAF1/CIP1 appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.

  • 34.
    Unge, Peter
    et al.
    Sandviken.
    Gad, Adel
    Falun.
    Eriksson, Karin
    Astra Hässle AB.
    Bergman, Börje
    Ludvika.
    Carling, Lasse
    Bollnäs.
    Ekström, Per
    Sandviken.
    Glise, Hans
    Trollhättan.
    Gnarpe, Håkan
    Gävle.
    Ljunghard, Ola
    Astra Hässle AB.
    Lindholmer, Christer
    Stockholm.
    Sandzén, Birger
    Umeå.
    Strandberg, Lars
    Avesta.
    Stubberöd, Arild
    Värnamo.
    Weywadt, Lars
    Borås.
    Amoxicillin added to omeprazole prevents relapse in the treatment of duodenal ulcer patients1993In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 5, no 5, 325-332 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate two different therapies, omeprazole/amoxicillin versus omepra-zole alone, in the treatment of duodenal ulcer patients with respect to eradication of Helicobacter pylori and time in remission during a 6-month follow-up after cessation of therapy.

    Design: Double-blind, randomized, parallel groups.

    Setting: Outpatient referrals in nine Swedish centres.

    Patients: This study included 248 patients with active duodenal ulcer.

    Main outcome measures: Endoscopic and symptomatic evaluation of time in remission. Culture, histology and serology for determination of H. pylori status.

    Results: Eradication of H. pylori was 54 compared with 4% and the proportion of patients in remission at 6 months was 70 compared with 36% in the omeprazole/amoxicillin treated group versus the group treated with omeprazole alone. Of the patients who became H. pylori-negative, 84% were in remission throughout the study.

    Conclusion: H. pylori is an almost obligate prerequisite for duodenal ulcer disease. Amoxicillin added to omeprazole nearly doubled the proportion of patients in remission at 6 months follow-up. The eradication rate of H. pylori in patients with excellent compliance was 74%.

  • 35.
    Graflund, Marianne
    et al.
    Department of Gynecologic Oncology, Medical Center Hospital, Örebro, Sweden.
    Sorbe, B.
    Department of Gynecologic Oncology, Medical Center Hospital, Örebro, Sweden.
    Hussein, A.
    Department of Pathology, Medical Center Hospital, Örebro, Sweden.
    Bryne, M.
    Department of Pathology, Institute of Cancer Research, the Norwegian Radium Hospital, Oslo, Norway.
    Karlsson, M.
    Department of Pathology, Medical Center Hospital, Örebro, Sweden.
    The prognostic value of histopathologic grading parameters and microvessel density in patients with early squamous cell carcinoma of the uterine cervix2002In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 1, 32-41 p.Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate the prognostic importance of clinical and histopathologic factors, including malignancy grading systems (MGS), partial index (PI), invasive front grading (IFG), and microvessel density. A complete geographic series of 172 early stage (FIGO I–II) cervical carcinomas treated by Wertheim-Meigs surgery during the period 1965–1990 was studied. The patients were followed up for at least 10 years. Significant prognostic factors for disease-free survival were lymph node status (P < 0.0000001), radical surgical margins (P = 0.00003), and tumor size (P = 0.008). In a multivariate Cox analysis it was shown that lymph node status was the single most important prognostic factor with regard to disease-free survival. The total MGS and the PI scores were highly significantly (P = 0.0001) associated with pelvic lymph node metastases and disease-free survival rate in squamous cell carcinomas. The MGS and the PI systems were superior to the IFG system in predicting lymph node metastases. The total IFG score was also a statistically highly significant (P = 0.003) prognostic factor with regard to disease-free survival in both univariate and multivariate analyses. Microvessel density was a nonsignificant prognostic factor. There was a highly significant (P = 0.002) association between vascular space invasion of tumor cells and the presence of lymph node metastases. In conclusion, histopathologic malignancy grading systems provide valuable prognostic information in patients with early stage squamous cell carcinomas of the uterine cervix.

  • 36.
    Lind, Tore
    et al.
    Department of Surgery, Kärnsjukhuset, Skövde, Sweden.
    Veldhuyzen van Zanten, Sander
    Department of Medicine, Victoria General Hospital, Halifax, Nova Scotia, Canada.
    Unge, Peter
    Department of Internal Medicine, Sandvikens Hospital, Sandviken, Sweden.
    Spiller, Robin
    Department of Therapeutics, Queen's Medical Center, Nottingham, UK.
    Bayerdörffer, Ekkehard
    Klinikum Grosshadern, Universität München, Munich, Germany.
    O'Morain, Colm
    Department of Gastroenterology, Meath/Adelaide Hospital, Trinity College Dublin, Ireland.
    Dev Bardhan, Karna
    Rotherham General Hospitals, Rotherham, UK.
    Bradette, Marc
    Department of Gastroenterology, Hôpital Christ-Roi Vanier, PQ, Canada.
    Chiba, Naoki
    Surrey GI Clinic, Guelph, Ontario, Canada.
    Wrangestadh, Michael
    Astra Hässle, Mölndal, Sweden.
    Cederberg, Christer
    Astra Hässle, Mölndal, Sweden.
    Idström, Jan-Peter
    Astra Hässle, Mölndal, Sweden.
    Eradication of Helicobacter pylori Using One-week Triple Therapies Combining Omeprazole with Two Antimicrobials: The MACH I Study1996In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 1, no 3, 138-144 p.Article in journal (Refereed)
    Abstract [en]

    Background.Eradication of Helicobacter pylori provides potential cure in the majority of patients with peptic ulcer disease, and eradication rates of more than 90% have been reported, using omeprazole in combination with two antimicrobials. The choice of antimicrobials, dose regimen and duration of treatment have varied between studies, however, and an optimal treatment still has to be established.

    Materials and Methods.We conducted an international, randomized, double-blind, placebo-controlled study involving more than 100 patients in each of six treatment groups in 43 hospital gastrointestinal units in Canada, Germany, Ireland, Sweden, and the United Kingdom. Patients (n=787) with proved duodenal ulcer disease were randomized to treatment twice daily for 1 week with omeprazole, 20 mg (O), plus either placebo (P) or combinations of two of the following anti-microbials: amoxicillin, 1 gm (A), clarithromycin, 250 or 500 mg (C250, C500), or metronidazole, 400 mg (M). Eradication of H. pylori was evaluated by 13C-UBT, performed before and 4 weeks after treatment cessation.

    Results.The eradication rates for the all-patients-treated analysis were 96%. OAC500; 95%, OMC250; 90%, OMC500; 84%, OAC250; 79%, OAM; and 1%, OP. OAC500 and OMC250 achieved eradication rates with lower 95% confidence interval limits exceeding 90%. All regimens were well-tolerated, 96% of patients complied with their dose regimen, and 2.3% of the patients discontinued treatment owing to adverse events.

    Conclusions.Omeprazole triple therapies given twice daily for 1 week produce high eradication rates, are well-tolerated, and are associated with high patient compliance. The two most effective therapies were those combining omeprazole, 20 mg, with either amoxicillin, 1 gm, plus clarithromycin, 500 mg, or metronidazole, 400 mg, plus clarithromycin, 250 mg, all given twice daily.

  • 37.
    Graflund, Marianne
    et al.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro.
    Sorbe, Bengt
    Department of Gynecological Oncology, Örebro University Hospital, Örebro.
    Karlsson, Mats
    Department of Pathology, Örebro University Hospital, Örebro.
    MIB-1, p53, bcl-2 and WAF-1 expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas: Correlation with clinical outcomeManuscript (preprint) (Other academic)
    Abstract [en]

    A complete series of 40 cervical carcinomas with pelvic lymph node rnetastases were analysed immunohistochemically for prognostic markers. The aims of this study were to examine whether the detection of MIB-1, p53, bcl-2, and WAF-1 could be used as a prognostic marker for tumor recurrence and survival rate. During the period of observation (mean 222, range 72-360 months) 22 (55%) recurrences were encountered and 20 patients died of the disease. There were 35 squamous cell carcinomas (87.5%), 2 adenosquamouscarcinomas (5.0%), and 3 pure adenocarcinomas (7.5%). One tumor (2.5%) was well differentiated, 12 twnors (30%) were moderately differentiated, and 27 tumors (67 .5%) were poorly differentiated. The primary tumor grade (P=0.037) and radicality of the surgical margins (P=0.021) were significant prognostic factors with regard to tumor recurrence. The site and number of lymph nodes with metastases had no prognostic value. P53, bcl-2, and WAF-1 were not predictive factors for recurrences or the cancer-specific survival rate. The concordant expression of WAF-1 in the primary tumor and in lymphnode metastases was lower than for p53 and bcl-2. The proliferative activity (MIB-1) seemed to be lower in tumor cells metastasized to the pelvic lymph nodes than in cells of the primary tumor. Expression of MIB-1 in lymph nodes was predictive of disease-free survival in both univariate and mu!tivariate proportional hazard Cox analyses.

  • 38.
    Ros, Axel
    et al.
    Department of Surgery, County Hospital of Ryhov, Jönköping, Sweden.
    Gustafsson, Lennart
    Motala Hospital, Motala, Sweden.
    Krook, Hans
    Vrinnevi Hospital, Norrköping, Sweden.
    Nordgren, Carl-Eric
    County Hospital, Kalmar, Sweden.
    Thorell, Anders
    Karolinska Hospital, Stockholm, Sweden.
    Wallin, Göran
    Karolinska Hospital, Stockholm, Sweden.
    Nilsson, Erik
    Motala Hospital, Motala, Sweden.
    Laparoscopic cholecystectomy versus mini-laparotomy cholecystectomy: a prospective, randomized, single-blind study2001In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 234, no 6, 741-749 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To analyze outcomes after open small-incision surgery (minilaparotomy) and laparoscopic surgery for gallstone disease in general surgical practice.

    Methods: This study was a randomized, single-blind, multicenter trial comparing laparoscopic cholecystectomy (LC) to minilaparotomy cholecystectomy (MC). Both elective and acute patients were eligible for inclusion. All surgeons normally performing cholecystectomy, both trainees under supervision and consultants, operated on randomized patients. LC was a routine procedure at participating hospitals, whereas MC was introduced after a short training period. All nonrandomized cholecystectomies at participating units during the study period were also recorded to analyze the external validity of trial results. The randomization period was from March 1, 1997, to April 30, 1999.

    Results: Of 1,705 cholecystectomies performed at participating units during the randomization period, 724 entered the trial and 362 patients were randomized to each of the procedures. The groups were well matched for age and sex, but there were fewer acute operations in the LC group than the MC group. In the LC group 264 and in the MC group 150 operations were performed by surgeons who had done more than 25 operations of that type. Median operating times were 100 and 85 minutes for LC and MC, respectively. Median hospital stay was 2 days in each group, but in a nonparametric test it was significantly shorter after LC. Median sick leave and time for return to normal recreational activities were shorter after LC than MC. Intraoperative complications were less frequent in the MC group, but there was no difference in the postoperative complication rate between the groups. There was one serious bile duct injury in each group, but no deaths.

    Conclusions: Operating time was longer and convalescence was smoother for LC compared with MC. Further analyses of LC versus MC are necessary regarding surgical training, surgical outcome, and health economy.

  • 39.
    Persson, Gunnar E.
    et al.
    Department of Surgery, Ryhov Hospital in Jönköping, Sweden.
    Ros, Axel G. B.
    Department of Surgery, Ryhov Hospital in Jönköping, Sweden.
    Thulin, Anders J. G.
    Department of Surgery, Ryhov Hospital in Jönköping, Sweden.
    Surgical treatment of gallstones: changes in a defined population during a 20-year period2002In: European Journal of Surgery, ISSN 1102-4151, Vol. 168, no 1, 13-17 p.Article in journal (Refereed)
    Abstract [en]

    Objective:

    To study developments in routine gallstone surgery in a defined population over a 20-year period with regard to incidence of operations, implementation of new methods, postoperative complications, and postoperative duration of hospital stay.

    Design:

    Retrospective study of medical records.

    Setting:

    County hospital, Sweden.

    Subjects:

    All patients who were residents of Jönköping during one of the three-year periods 1976–1978, 1986–1988, or 1996–1998 and had their first surgical treatment, either cholecystectomy/choledochotomy or therapeutic endoscopy for gallstone disease.

    Results:

    The overall annual incidence of operations for gallstones decreased from 2.01 to 1.13/1000 inhabitants between the first and second period (p < 0.001). This is explained by a significant reduction in the number of elective operations while the number of urgent operations increased between the first and second periods from 0.39 to 0.53/1000 (p < 0.05) and continued to increase and reached 0.75/1000 during the third period (p < 0.001). New methods were introduced for the treatment of gallstones that gradually made this type of operation more varied and complex in routine practice. The postoperative hospital stay decreased from 7.0 days during the 1970s to 3.9 days during the 1990s. Postoperative morbidity was unchanged.

    Conclusions:

    The decreasing rate of gallstone surgery noted between the 1970s and 1980s did not continue through the 1990s. Urgent surgery for gallstone disease has gradually become more common and now predominates over elective surgery in routine practice. The introduction of less traumatic surgical techniques contributed to the significant decrease in hospital stay after gallstone surgery. However, morbidity has not decreased and the diversification of surgical techniques used for treatment of gallstones requires continuous evaluation in routine practice.

  • 40.
    Alonso Orozco, Fabiola
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Finite Element Method Modelling and Simulations for Comparisonbetween Deep Brain Stimulation Electrodes2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The Deep Brain Stimulation (DBS) is an invasive therapy that alleviates the symptoms of several neurological disorders by electrically stimulating specific regions of the brain, generally within the basal ganglia. Until now Medtronic DBS system is the only approved by the Food and Drug Administration, nevertheless European and Australian countries  have recently approved St. Jude DBS systems to treat Parkinson’s disease and related movement disorders.

         Traditionally, voltage-controlled stimulation (the type of systems provided by Medtronic) has been used and clinicians are familiar with its settings; however the knowledge about systems based in current-controlled stimulation (St. Jude systems) is rather scarce. One of the key factors for a successful therapy is the optimal selection of the electrical parameters for stimulation. Due to the critical zone where the surgery is performed, modeling and simulations of DBS systems have been extensively used to observe how the electric field is distributed in the brain tissue and ultimately to help the clinicians to select the best parameters.

         In this thesis two finite element models of the DBS systems mentioned above have been developed; five examinations were designed, based on the physical and electrical differences between the systems, to observe and quantitatively compare the electric field distribution.

        The aim of this thesis was to investigate the differences between two representative models of each company but moreover to contribute with information regarding current-controlled stimulation.

    The results obtained are expected to be useful for further investigations where the magnitude and distribution of the electric field generated by this type of electrodes are needed.

  • 41.
    Wåhlin, Monica
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Granberg, Lotta
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Betydelsefulla faktorer i överföringsprocessen från barn– till vuxensjukvård hos unga med kronisk sjukdom2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Allt fler barn och ungdomar överlever idag en kronisk sjukdom och behöver överföras till vuxensjukvård. Idag är inte denna transition/överföringsprocess tillfredsställande utan en förbättring behöver ske.

    Syfte: Syftet var att identifiera faktorer som är betydelsefulla i samband med överföringsprocessen från barn- till vuxensjukvård hos unga med kronisk sjukdom.

    Metod: En systematisk litteraturstudie genomfördes. Efter urval och granskning genomfördes analys och tolkning. Studien omfattade 23 artiklar som besvarade studiens syfte.

    Resultat: Efter analys av artiklarna kunde fyra faktorer urskiljas. Information och förberedelse, samarbete mellan barn- och vuxensjukvård, psykosociala faktorer samt vårdgivarnas kompetens och egenskaper.

    Konklusion: Överföringsprocessen måste förberedas bättre. Den ska starta tidigt, individualiseras och involvera både patienten och föräldrar. Fokus ska ligga på att stärka ungdomarnas oberoende och att förändra föräldrarollen. Vårdgivarnas främsta uppgift är att bygga broar genom en förbättrad kommunikation och ett ökat samarbete mellan barn- och vuxensjukvård. Vårdgivarna måste känna sig trygga i sin kunskap om patienten när det gäller tidigare sjukhistoria och kunskap om sjukdomen samt bli bättre på ungdomsmedicinska frågor för att bemöta ungdomarna på ett bra sätt.

  • 42.
    Djupdalen, Rhiannon
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Sömn, depressionssymtom, livskvalitet och Alzheimers sjukdom2012Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Sleep-disturbances in persons with Alzheimer´s disease are prevalent. They are characterized as increased frequency and duration of awakenings, decreased slow-wave sleep, REM-sleep and increase of day-time napping. Depression and lower quality of life are associated with sleep-disturbances. Altogether a significant source of stress for caregivers and an important factor in institutionalization. Non-pharmacological treatment alternatives are rare.

    Method: Single-case A-B-C design, with non-concurrent multiple baselines, a pilotstudy.

    Aim: To explore if an educational program on sleep, sleep disturbances and behavioural change directed towards caregivers improved sleep, depression and quality of life in persons with Alzheimer´s disease living at home. A second aim was to test program and method.

    Result: Three patients/cases were included and in one case sleep was improved. Depression and quality of life outcome varied in all cases. The program and method has the potential of being useful after some adjustments.

    Conclusion: Non-pharmacological treatments are needed and this study shows that a behavioural program is a feasible way to improve sleep in patients with Alzheimer´s disease. More research is needed to develop method and increase overall knowledge within the area. Knowledge of sleep and non-pharmacological treatments for sleep problems are scarce in clinical environment and nurses have an important task.

  • 43.
    Forsgren, Mikael Fredrik
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Human Whole Body Pharmacokinetic Minimal Model for the Liver Specific Contrast Agent Gd-EOB-DTPA2011Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Magnetic resonance imaging (MRI) of the liver is an important non-invasive tool for diagnosing liver disease. A key application is dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). With the use of the hepatocyte specific contrast agent (CA) Gd-EOB-DTPA it is now possible to evaluate the liver function. Beyond traditional qualitative evaluation of the DCE-MRI images, parametric quantitative techniques are on the rise which yields more objective evaluations. Systems biology is a gradually expanding field using mathematical modeling to gain deeper mechanistic understanding in complex biological systems. The aim of this thesis to combine these two fields in order to derive a physiologically accurate minimal whole body model that can be used to quantitatively evaluate liver function using clinical DCE-MRI examinations. 

    The work is based on two previously published sources of data using Gd-EOB-DTPA in healthy humans; i) a region of interest analysis of the liver using DCE-MRI ii) a pre-clinical evaluation of the contrast agent using blood sampling.  The modeling framework consists of a system of ordinary differential equations for the contrast agent dynamics and non-linear models for conversion of contrast agent concentrations to relaxivity values in the DCE-MRI image volumes.

    Using a χ2-test I have shown that the model, with high probability, can fit the experimental data for doses up to twenty times the clinically used one, using the same parameters for all doses. The results also show that some of the parameters governing the hepatocyte flux of CA can be numerically identifiable. Future applications with the model might be as a basis for regional liver function assessment. This can lead to disease diagnosis and progression evaluation for physicians as well as support for surgeons planning liver resection.

  • 44.
    Sorbe, Bengt
    et al.
    University Hospital, Örebro.
    Graflund, Marianne
    University Hospital, Örebro.
    Nygren, Lisa
    University Hospital, Örebro.
    Horvath, Gyorgy
    Sahlgrenska University Hospital.
    Swahn, Marie
    Sahlgrenska University Hospital.
    Boman, Karin
    Umeå University Hospital.
    Bangshoj, Rene
    Central Hospital Karlstad.
    Lood, Margareta
    Central Hospital Karlstad.
    Malmström, Henric
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    A phase II study of docetaxel weekly in combination with carboplatin every three weeks as first line chemotherapy in stage IIB-IV epithelial ovarian cancer: Neurological toxicity and quality-of-life evaluation2012In: International Journal of Oncology, ISSN 1019-6439, Vol. 40, no 3, 773-781 p.Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to assess the response rate, toxicity, progression-free survival (PFS) and overall survival (OS) in a series of advanced stage ovarian carcinoma patients treated with a first-line weekly docetaxel and three weekly carboplatin regimens. All eligible patients were treated with intravenous docetaxel (30 mg/m(2)) on Days 1, 8 and 15, and carboplatin (area under the curve, 5) on Day 1; Q21 days for at least 6 cycles. Neurological tests, questionnaires, and the EORTC QLQ-C30 and OV28 were used for quality-of-life assessments. One hundred and six patients received at least one cycle of primary chemotherapy (median 6.0; range, 1-9) and they were evaluable for toxicity assessment. Eighty-five patients had evaluable disease and received at least 3 courses of chemotherapy and were evaluable for clinical response rate. The overall response rate was 78.8% (95% CI 70.1-87.5%) and the biochemical response was 92.8% (95% CI 87.2-98.4%). The median PFS was 12.0 months and the median OS was 35.3 months. Thirty-six patients (34.0%) experienced grades 3 and 4 neutropenia, which resulted in the removal of 3 patients. Six patients (5.7%) experienced grades 3 or 4 thrombocytopenia. No patients experienced grade 3-4 sensory neuropathy. Epiphora, nail changes and fatigue were frequently recorded non-hematological side effects. The tolerable hematological toxicity (no need for colony-stimulating factors) and the low rate of severe neurotoxicity (only grade 1-2) and response rates in line with the standard 3-week paclitaxel-carboplatin regimen for advanced primary ovarian carcinoma after suboptimal cytoreductive surgery make this regimen an interesting alternative in selected patients.

  • 45.
    Nnamani, Christian
    Linköping University, Department of Culture and Communication, Centre for Applied Ethics.
    Professional Confidentiality and HIV: Duty to Warn Third Parties and its Social Implications to Public Health in Nigeria2008Independent thesis Advanced level (degree of Master (Two Years)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Confidentiality is considered an integral component of medical practise, yet there has been debate within the medical community as to whether there should be exceptions to the obligation to protect patient’s confidences. In the cases involving medical patients with deadly sexually transmittable disease like HIV/AIDS, physicians feel caught between two basic principles – keeping of medical confidentiality and public safety. Bioethicists would favour breaking of confidentiality when the public safety and the life of someone are endangered. However, considering the complexities and discrimination in connection with HIV/AIDS in Nigerian context, many would be tempted to discourage the notification of partners who risk being infected, through the moral obligation of 'duty to warn', but some others would argue that not notifying people of such threat to life would only help in spreading the virus to ignorant partners of an index patient. I argued that there is an overridden utilitarian principle to save others from harm, but some others cite the negative effects the breaking of medical confidentiality would have on the healthcare system as a reason not to favour partner notification. Nevertheless, people would appreciate the value of breaching confidentiality in HIV/AIDS related cases when various forms of discrimination and stigmatisations are criminalised and policies to protect the fundamental rights of people living with HIV/AIDS (PLWHA) are strictly adhered to.

  • 46.
    Hirbod, Sam
    et al.
    Linköping University, Department of Management and Engineering. Linköping University, Faculty of Arts and Sciences.
    Lindqvist, Cecilia
    Linköping University, Department of Management and Engineering. Linköping University, Faculty of Arts and Sciences.
    Improving health promotional workplace programs: A study of HIV/AIDS workplace programs in Kenya2011Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Background: HIV/AIDS is believed to be one of the largest threats to the general business climates in Sub-Saharan Africa. The private sector has, in response, taken initiatives to reduce the impact of the epidemic by developing so called HIV/AIDS workplace programmes. The programs aim to create awareness regarding HIV/AIDS through the education and treatment of the disease. We want to examine the programs and discover the factors that may inhibit their implementation and progress, this, in order to improve the stability of the HIV/AIDS workplace programs.

    Aim: The overall aim of this thesis is to examine and investigate HIV/AIDS workplace programs, with the purpose of disclosing the primary factors that may affect their progress.

    Completion and results: This thesis demonstrates that the implementation and progress of HIV/AIDS workplace programs are highly affected by leadership, management, motivation and stigma. Managers, acting as role models, increase the employees’ motivation to participate in the workplace programs. In addition, their involvement helps to ensure the stability and progress of the workplace programs.

    The systematization of activities and allocation of resources, such as money and time, also play a significant part, regarding employee motivation. This in turn results in a higher level of employee participation. Due to tough market conditions and lack of clarity, concerning the relation between HIV/AIDS and productivity, managers often fail to invest the necessary resources needed, to ensure the stability of the HIV/AIDS workplace program. The involvement of managers and spread of information has a significant effect on stigma, decreasing the many false beliefs prevalent due to religion and culture. Based on the findings, theoretical as well as empirical, the lack of leadership and management, decrease in motivation and HIV/AIDS-related stigma are referred to as the three main obstacles which hinder the progress of HIV/AIDS workplace programs.

    HIV/AIDS is one of the world’s largest health problems, around 16 million children died, in 2009, due to the illness (The World Factbook 2011). 32 million individuals are infected, of which the majority live in Sub-Saharan Africa (The World Factbook 2011). Kenya is one of the most affected countries in the world. The lack of coordination of resources has resulted in a staggering limitation, only 5 percent of the Kenyan population receives sufficient aid (United States Agency International Development 2010). With the help of the workplace programs, instituted by the companies themselves, a new channel of reaching out to those in need has been opened.

    In this thesis, focus is laid upon HIV/AIDS workplace programs, which aim to spread information and treat HIV/AIDS. Attention has especially been given to the factors which affect the implementation and progress of the HIV/AIDS workplace programs.

    The found factors, especially those which affect the workplace programs negatively, are used in order to form proposals regarding how to overcome the obstacles. The proposals are based on empirical findings and theoretical framework. These are later developed further, by the authors, in order to reach congruence with the main purpose of the thesis; to examine and investigate HIV/AIDS workplace programs, with the purpose of disclosing the primary factors that may affect their progress.

  • 47.
    Eriksson, Elina
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Wärdig, Frida
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Utan karta - med kompass: Sjuksköterskors erfarenheter av omvårdnad när patienten vårdas för alkoholrelaterad skada eller sjukdom2011Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Alkohol leder till hälsoproblem i befolkningen. Slutenvården är en aktör för att identifiera individer med riskfylld alkoholkonsumtion, missbruk eller beroende. Kort rådgivning vid hög alkoholkonsumtion är effektivt. Sjuksköterskans roll inom kort rådgivning är ännu relativt odefinierad. Syfte: Syftet med studien var att belysa sjuksköterskors erfarenheter och upplevelser av omvårdnad då patienten vårdas inom somatisk slutenvård för alkoholrelaterad skada eller sjukdom. Metod: Kvalitativ ansats valdes. Åtta semistrukturerade intervjuer genomfördes med sjuksköterskor verksamma inom somatisk slutenvård. Materialet analyserades genom konventionell innehållsanalys. Resultat: Studiens huvudfynd sammanfattades av: Vårdmötet, Den professionella relationen och Kommunikation. Mötet beskrevs som den ram inom vilken sjuksköterskan gav omvårdnad till patienten. En professionell relation skapade närhet till patienten och möjliggjorde omvårdnad. Kommunikation om alkohol upplevdes som känsligt. Sjuksköterskorna förde olika typer av samtal där de använde sig av olika strategier för att bibehålla en god relation till patienten. Konklusion: Sjuksköterskan i den somatiska slutenvården mötte patienter där skada eller sjukdom var alkoholrelaterad. Etisk medvetenhet har tolkats som grundläggande för det professionella förhållningssättet. Viljan att hjälpa patienter till bättre hälsa fanns beskriven, så även osäkerhet om hur sjuksköterskan bäst hjälper patienten inom ramen för den somatiska slutenvården. Sjuksköterskan i slutenvården har möjlighet att genom relationen och kommunikationen med patienten initiera förändring av alkoholvanor.  

  • 48.
    Svensson, Jakob
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Epidemiologisk fall-kontroll studie av reumatoid artrit: betydelsen av genotyp och omgivningsfaktorer2004Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aim of this study was to evaluate the effects of some environmental and genetic predisposing factors of Rheumatoid Arthritis (RA). RA is an inflammatory disease where the immune system decomposes body tissue. A significant increased risk of RA was shown when exposed to grain and smoking. The genes that were studied were GSTM1, GSTT1 and Fcgamma- RII. The genes themselves were no predisposing factors of RA, but smoking showed to be a significant greater riskfactor for RA for individuals having a deletion of the GSTM1 or the Fc-gamma-RII gene, or not having a deletion of the GSTT1 gene. Exposure to grain showed to be a significant greater riskfactor for RA for individuals not having a deletion of the GSTM1, GSTT1 or the Fc-gamma-RII gene. Also individuals not having a deletion of the Fc-gamma-RII gene showed an increased risk for RA when exposed to stonedust.

  • 49.
    Samuelsson, Johanna
    Linköping University, Department of Medical and Health Sciences.
    Visualization of Regional Liver Function with Hepatobiliary Contrast Agent Gd-EOB-DTPA2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Liver biopsy is a very common, but invasive procedure for diagnosing liver disease. However, such a biopsy may result in severe complications and in some cases even death. Therefore, it would be highly desirable to develop a non-invasive method which would provide the same amount of information on staging of the disease and also the location of pathologies. This thesis describes the implementation of such a non-invasive method for visualizing and quantifying liver function by the combination of MRI (Magnetic Resonance Imaging), image reconstruction, and image analysis, and pharmacokinetic modeling. The first attempt involved automatic segmentation, functional clustering (k-means) and classification (kNN) of in-data (liver, spleen and blood vessel segments) in the pharmacokinetic model. However, after implementing and analyzing this method some important issues were identified and the image segmentation method was therefore revised. The segmentation method that was subsequently developed involved a semi-automatic procedure, based on a modified image forest transform (IFT). The data were then simulated and optimized using a pharmacokinetic model describing the pharmacokinetics of the liver specific contrast agent Gd-EOB-DTPA in the human body. The output from the modeling procedure was then further analyzed, using a least-squares method, in order to assess liver function by estimating the fractions of hepatocytes, extracellular extravascular space (EES) and blood plasma in each voxel of the image. The result were in fair agreement with literature values, although further analyses and developments will be required in order to validate and also to confirm the accuracy of the method.

  • 50.
    Eriksson, Sabina
    Linköping University, Department of Physics, Chemistry and Biology, Molecular genetics .
    Studies of peripheral tolerance in AIRE deficient mice2011Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    Autoimmune Polyendocrine Syndrome Type 1(APS I) is a monogenic autosomal recessive autoimmune disorder which is the result of mutations in the autoimmune regulator (AIRE) gene. Symptoms of the disease include circulation of multiple organ specific autoantibodies, which leads to the breakdown of several tissues, including the adrenal cortex and the parathyroid glands. The patients also develop a number of non-endocrine disorders. This study has investigated the peripheral tolerance mechanisms controlled by the AIRE gene in Aire deficient mice, an animal model of the disease. The B cell Activating Factor (BAFF), which is a cytokine involved in B cell survival and growth, is elevated in Aire-/- mice, resulting in an increased release of autoantibodies and B cell proliferation. Therefore the BAFF level differences between TCR-/- and B6 mice was studied, and the results showed significantly higher levels of BAFF in TCR-/- mice. This is not in accordance with earlier studies. ICOS and ICOSL are involved in the activation of follicular T helper cells. The expression of ICOSL on different subpopulations of DC from mice was studied to evaluate the possible influence of AIRE expression on the T cells in the spleen. The results showed that ICOSL is significantly higher expressed in peripheral 33D1+ DCs in Aire-/- mice, showing that AIRE has a role in the over-activation of the follicular T helper cells, which can lead to autoantibody production and inflammation. These results show that AIRE is involved in peripheral tolerance.

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