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  • Shungin, Dmitry
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States of America.
    Deng, Wei Q.
    Varga, Tibor V.
    Luan, Jian'an
    Mihailov, Evelin
    Metspalu, Andres
    Morris, Andrew P.
    Forouhi, Nita G.
    Lindgren, Cecilia
    Magnusson, Patrik K. E.
    Pedersen, Nancy L.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Chu, Audrey Y.
    Justice, Anne E.
    Graff, Mariaelisa
    Winkler, Thomas W.
    Rose, Lynda M.
    Langenberg, Claudia
    Cupples, L. Adrienne
    Ridker, Paul M.
    Wareham, Nicholas J.
    Ong, Ken K.
    Loos, Ruth J. F.
    Chasman, Daniel I.
    Ingelsson, Erik
    Kilpeläinen, Tuomas O.
    Scott, Robert A.
    Mägi, Reedik
    Paré, Guillaume
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.
    Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 6, e1006812Article in journal (Refereed)
    Abstract [en]

    Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.

  • Tidehag, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Odontology, Prosthetic Dentistry. Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Iron absorption and iron status related to diet: an experimental and epidemiological study1995Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The absorption of iron from the diet is a major determinant of the iron status of an individual. Accuratemeasures of iron absorption are thus essential in the determination of the effects of diet composition on ironabsorption and status.

    The aim of these studies have firstly been to investigate different methods to measure iron absorptionand effects of diet in both rats and humans. Secondly to describe variations in iron status in a generalpopulation and to relate the variations to diet.

    Experimental studies in rats: The most important factors determining the availability of iron from thediet to growing rats appears to be the concentration of iron in the diet and the iron status of the rats. Thetype of cereal |rain in the diet and the diet phytate and fiber concentrations were of far less importance. Theabsorption of Fe from test meals, the iron balance over a period of a few days and the blood hemoglobinand serum and liver iron concentrations were in good general agreement on the effects of diet and iron statuson the bioavailability of iron from grain diets. The extent of coprophagy in rats is not affected by diet or ironstatus and did not affect iron absorption appreciably.

    Effect of dairy products on iron absorption in man: The effect of milk and fermented milk on ironabsorption was studied in nine ileostomy subjects. We found no decrease in iron absorption during twothree-week periods on a high calcium (milk) diet. The results of the present study differ from those studies inwhich the absorption of radioiron from test meals was measured, which have shown a pronounced effect ofhigh calcium levels. We believe that these differences in results were caused by differences in experimentaldesign and choice of measurement method. Our results support earlier findings that the iron status of thesubject rather than the bioavailability of dietary iron is the major factor determining absorption of dietarynon-heme iron.

    Measurement of iron absorption from single meals and daily diets in humans usingradioiron: Ten ileostomy subjects were given the same composite diet for all three meals each day for fiveconsecutive days (meal proportion ratio 1:2:4 for breakfast, lunch and dinner respectively). The ironabsorption from a low-fiber diet measured from the morning meals (55Fe) was almost 80% higher than theaverage iron absorption measured from all meals (59Fe) during the last two days on this diet. The ironabsorption from a high fiber diet eaten at breakfast was almost 50% higher than the daily average absorption.This suggests that all meals of the day should be labeled with radioiron and not just the morning meal.

    Population studies of diet and iron status: In a randomly selected population in Northern Sweden loweriron status was associated with a high intake of dairy products in women (25-44 yr.). The striking result washowever that iron status was not related to other major variations in dietary intake, particularly intake ofenergy and iron. No correlation could be demonstrated between iron status measured as ferritin, serum ironor TIBC and the estimated intakes of calcium, fiber, ascorbic acid, meat, tea or coffee, all of which are knownto be factors which influence the bioavailability of iron. On the population level, factors other than diet, e.g.menstruation and metabolic factors, were more important than diet as determinants of iron status.

  • Thorburn, William
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Recordings of applanating force at constant intraocular pressure: development of a new technique and results obtained from a study of human eyes1972Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This doctoral thesis is based on the following six papers, which will be referred to in the text by their Roman numerals:

    I. Linnér, E. and Thorburn, W. (1971) Applanation tonography at constant intraocular pressure. I. Basic considerations. Acta Ophthal. (Kbh*) 49, 165-169.

    II. Thorburn, W. Recordings of applanating force at constant intraocular pressure. Basic principle and apparatus description. Acta Ophthal. (Kbh.) In press.

    III. Thorburn, W. Recordings of applanating force at constant intraocular pressure. II. Procedures applied on living human eyes. Acta Ophthal. (Kbh.) In press.

    IV. Thorburn, W. Recordings of applanating force at constant intraocular pressure. III. Intraocular volume-pressure relationship studied in intact human eyes. Acta Ophthal. (Kbh.)In press.

    V. Thorburn, W. Recordings of applanating force at constant intraocular pressure. IV. Intraocular volume changes due to changes in blood content. Acta Ophthal. (Kbh*) In press.

    VI. Thorburn, W* Recordings of applanating force at constant intraocular pressure. V. Intraocular volume changes due to changes in the content of aqueous humour. Acta Ophthal. (Kbh.). In press.

  • Gylfe, Erik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Studies on free amino acids in the pancreatic ß-cells.1974Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is based on the following publicatipns, which will be referred to bytheir Roman numerals.

    I Gylfe, E: Changes of free amino acids in pancreatic ß-cells after starvation and substrate deprivation. Acta endocr (Kbh) 75, 105 (1974).

    II Gylfe, E and Heilman, B: Role of glucose as a regulator and precursor of amino acids in the pancreatic ß-cells. Endocrinology in press.

    III Gylfe, E: Glucose oxidation and contents of free amino acids in pancreatic ß-cells stimulated by a non-metabolizable leucine analogue. Biochim Biophys Acta in press.

    IV Gylfe, E, Heilman, B, Sehlin ] and Täljedal, l-B: Amino acid conversion into 5-hydroxytryptamine in pancreatic ß-cells. Endocrinology 93, 932 (1973).

  • Hassler, Ove
    et al.
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Angiographic abnormalities in the urinary bladder wall after irradiation1973Doctoral thesis, monograph (Other academic)
  • Mjörndal, Tom
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Thiothixene: a study on its pharmacokinetics and pharmacological effects in animal and man1976Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Thisthesis is based on the following publications:

    I    Mjörndal, T. and Oreland, L.: Determination of thioxan-thenes in plasma at therapeutic concentrations. Actapharmacol. et toxicol. 29, 295-302, 1971.

    II   Bergling, R., Mjörndal, T., Oreland, L., Rapp, W. andWold, S.: Plasma levels and clinical effects of thioridazine and thiothixene. J. Clin. Pharmacol. 15, 178-186, 1975.

    III  Mjörndal, T., Wiesel, F.A. and Oreland, L.: Biochemicaland behavioural effects of thiothixene. Relation totissue levels of the drug. Acta pharmacol. et toxicol.38, 490-496, 1976.J

    IV   Mjörndal, T.: A study on the effects of thiothixene,N-demethyl-thiothixene, thiothixene sulfoxide and barbital on the motor activity of the rat. Submitted toActa pharmacol. et toxicol.

    V    Mjörndal, T.: Effects of chlorpromazine and thiothixeneon hepatic microsomal enzymes. Submitted to Acta pharmacol. et toxicol.

    In the following discussion the papers will be referred to by their Roman numerals; other references are indicated by Arabic numerals.

  • Jeppsson, Jan-Olof
    Umeå University, Faculty of Medicine, Microbiology.
    Structural studies on human transferrin1967Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This review is a dissertation and contains a summary of the following publications:

    I. J.-O Jeppsson and J. Sjöquist: Separation of Normal Human Transferrin into Two Fractions. Biochim. Biophys. Actay 78 (1963) 658

    II. J.-O. Jeppsson: Isolation and Partial Characterization of Three Human Transferrin Variants. Biochim. Biophys. Acta, 1967, in press

    III. J.-O. Jeppsson: Subunits of Human Transferrin. Acta Chem. Scand.1967, in press

    IV. J.-O. Jeppsson and J. Sjöquist: Thin-layer Chromatography of PTH Amino Acids. Analyt. Biochem. 18 (1967) 264

    V. J.-O. Jeppsson: Structural Studies of Fragments Resulting from Cyanogen Bromide Degradation of Human Transferrin. Biochim. Biophys. Acta, 1967, in press.

    In addition the dissertation contains some hitherto unpublished results. In the text the above mentioned papers will be referred to by the Roman figures I — V, other references are indicated by Arabic figures.

  • Lernmark, Åke
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Studies on insulin release from the isolated mouse islet1971Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is a survey based on the following papers:

    I. The ß-cell capacity for insulin secretion in microdissected pancreatic islets from obese-hyperglycemic mice (in collaboration with B. Heilman). Life Sciences 8: 53, 1969.

    II. Effect of epinephrine and mannoheptulose on early and late phases of glucose-stimulated insulin release (in collaboration with B. Heilman). Metabolism 19: 614, 1970.

    III. Isolated mouse islets as a model for studying insulin release. Acta Diabet. Lat. 8:649, 1971.

    IV. The significance of 5-hydroxytryptamine for insulin secretion in the mouse. Horm. Metab. Res. 3: 305, 1971.

    V. Specificty of leucine-stimulation of insulin release. Hormones 3: 1972.

    VI. Effects of neutral and dibasic amino acids on the in vitro release of insulin. Hormones 3: 1972.

    These papers will be referred to in the text by their Roman numerals.4

  • Tjust, Anton E.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Danielsson, Adam
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Brännstrom, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Medical Biosciences. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Impact of Amyotrophic Lateral Sclerosis on Slow Tonic Myofiber Composition in Human Extraocular Muscles2017In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 58, no 9, 3708-3715 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To analyze the proportion and cross-sectional area of myofibers containing myosin heavy chain slow-twitch (MyHCI) and myosin heavy chain slow tonic (MyHCsto) in extraocular muscles of autopsied amyotrophic lateral sclerosis (ALS) patients with either spinal or bulbar site of disease onset. METHODS. Whole-muscle cross sections from the middle portion of the medial rectus were labeled with antibodies against MyHCI or MyHCsto and laminin. Myofibers labeled with the MyHC antibodies (MyHCI+sto) and the total number of myofibers were quantified in the orbital and global layer of 6 control individuals and 18 ALS patients. The cross-sectional area of myofibers labeled for either MyHC was quantified in 130 to 472 fibers/individual in the orbital and in 180 to 573 fibers/individual in the global layer of each specimen. RESULTS. The proportion of MyHCI+sto myofibers was significantly smaller in the orbital and global layer of ALS compared to control individuals. MyHCI+sto myofibers were significantly smaller in the global layer than in the orbital layer of ALS, whereas they were of similar size in control subjects. The decreased proportion of MyHCI+sto fibers correlated significantly with the age of death, but not disease duration, in patients who had the bulbar-onset variant of ALS but not in patients with spinal variant. CONCLUSIONS. ALS, regardless of site of onset, involves a loss of myofibers containing MyHCI+sto. Only in bulbar-onset cases did aging seem to play a role in the pathophysiological processes underlying the loss of MyHCI+sto fibers.

  • Björkstén, Bengt
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    The nitroblue tetrazolium (NBT) test: a methodological and clinical study1974Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This dissertation is based on the following six papers:

    I. Björksten, B.: The NBT Test Using Venous and Capillary Blood. Scand J Haemat, 11:270, 1973.

    II. Björksten, B.: The Influence of Technical Factors on the NBT test.Scand J Haemat, 12:46, 1974.

    III. Björkstén, B., Ekstrand, T., Gothefors, L. & Östberg, Y.: The Nitroblue Tétrazolium (NBT) Test and White Blood Cell Count in Acute Throat Infections. Submitted for publication.

    IV. Björkstén, B. & Wählby, L.: The Nitroblue Tétrazolium (NBT) Test and White Blood Cell Count in Patients with Acute Abdominal pain, with Special Reference to Acute Appendicitis. Acta Chir Scand. In press, 1974.

    V. Björkstén, B. & de Chateau, P.: Use of the Nitroblue Tétrazolium (NBT) Test in the Differentiation of Pyelonephritis from Cystitis. Submitted for publication.

    VI. Björkstén, B. & Lundmark, K.-M.: Abnormal Nitroblue Tétrazolium Test in Relatives of a Female with Chronic Granulomatous Disease. Scand J Infect Dis, 4:167, 1972.

    References to these papers will be made with the Roman numerals I - VI.

  • Schoultz, Bo von
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Studies on PZ, the pregnancy zone protein1974Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This dissertation is based on the following publications whichwill be referred to in the text by their Roman numerals:

    I Beckman, L., von Schoultz, B. & Stigbrand, T.: Induction of the "pregnancy zone" protein by ojral contraceptives.Acta Obstet. Gynec. Scand. 50: 369, 1971.

    II von Schoultz, B. & Stigbrand, T.: Purification of the "pregnancy zone" protein. Acta Obstet. Gynec. Scand.52: 51, 1973.

    III Beckman, L., von Schoultz, B. & Stigbrand, T.: Detection of the "pregnancy zone" protein by means of an immunodiffusion method. Acta Obstet. Gynec. Scand. 52: 157,1973.

    IV Beckman, L., von Schoultz, B. & Stigbrand, T.: "Pregnancy zone" protein in sera from patients with prostatic cancer treated with oestrogens. Urol. Res. 1: 67, 1973.

    V Beckman, G., von Schoultz, B. & Stigbrand, T.: The "pregnancy zone" protein and fetal welfare. Acta Obstet. Gynec. Scand. 53: 59, 1974.

    VI Beckman, G., Beckman, L., Magnusson, S.S. & von Schoultz, B.: The "pregnancy zone" protein and abortion. Acta Obstet. Gynec Scand. 53: 177, 1974.

    VII von Schoultz, B., Stigbrand, T., Carstensen, H., Södergård, R & Shanbhag, V.: Lack of steroid-binding by pregnancy zone protein. J. steroid. Biochem. 4: 483, 1973.

    VIII von Schoultz, B., Stigbrand, T. & Tärnvik, A.: Inhibition of PHA-induced lymphocyte stimulation by the pregnancy zone protein. FEBS Letters 38: 23, 1974.

    IXvon Schoultz, B.: A quantitative study of the pregnancy zone protein in the sera of pregnant and puerperal women. Amer. J. Obstet. Gynec. In press 1974.

    X von Schoultz, B. & Stigbrand, T.: Characterization of the"pregnancy zone protein" in relation to other Cfc^-Qlobulins of pregnancy. Submitted for publication.

  • Backman, Lars
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Counter-current distribution of interacting molecules: simulation of distribution behaviour and application to protein-protein interactions1981Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Associations of biological macromolecules with other macromolecules, with larger assemblies of macromolecules and with themselves are widely encountered phenomena. In principle, these interactions can be studied with any method able to differentiate between free molecules and complexes formed. The most extensively used techniques are sedimentation equilibrium and velocity, elastic light scattering and molecular sieve chromatography. This thesis describes an alternative technique; counter-current distribution in aqueous two-phase systems.

    The counter-current distribution behaviour of a solute depends on its size and surface properties including charge and hydrophobicity. Since the surface properties of a complex formed most probably differ from those of the solutes participating in the association, complex formation should lead to changes in the average distribution behaviour of each solute. Consequently, the presence of one solute should affect the counter-current distribution of another solute if they interact with each other.

    In order to establish the boundary conditions and the potential as well as limitations of the counter-current distribution technique, the distribution behaviour of homogeneous and heterogeneous association equilibria have been simulated.

    The model developed for describing the distribution behaviour of heterogeneous associations has been tested using the well characterized interaction between bovine serum albumin and L-tryptophan. It was demonstrated that the theoretical model could predict the experimental distribution behaviour of these two molecules.

    However, the primary aim of the counter-current distribution experiments has been to gain insight into protein-protein interactions. The metabolically linked enzymes, malate dehydrogenase and aspartate aminotransferase, have been studied in order to determine if there is also a physical link between these two enzymes. The results showed that the cytosolic enzymes as well as the mitochondrial forms associate while the cytoplasmic enzymes did not display any association with the mitochondrial forms. Thus, an organelle specific interaction between malate dehydrogenase and aspartate aminotransferase was demonstrated.

    Hemoglobin and carbonic anhydrase are functionally linked through the Bohr effect. Thus, the binding of oxygen by hemoglobin in the lung capillaries is associated with the binding of protons which are formed by the catalytic action of carbonic anhydrase. From the counter- current distribution experiments it was possible to conclude that humain carbonic anhydrase II, the high activity form, associates with human hemoglobin whereas carbonic anhydrase I, the low activity form, did not show any affinity for hemoglobin.

  • Wirell, Staffan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Binding of radiographic contrast media to serum proteins: a clinical and experimental investigation of their adverse effects through influence on active steroid hormone levels1982Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Summary of thesis based on the following papers:

    I Wirell S.: Adverse reactions at intravenous cholegraphy with ioglycamide. Correlation with the level of circulating sex hormones. Accepted for publication in Acta Radiol. Diagn. (1982)

    II Wirell S.: Effects of steroid hormones on the binding of ioglycamide (Bilivistan) to human blood serum. Acta Radiol. Diagn. 19 (1978), 289.

    III Wirell S.: Release of protein bound progesterone by ioglycamide in human serum. Accepted for publication in Acta Radiol. Diagn. (1982).

    IV Wirell S., Södergård R. and Selstam G.: Ioglycamide induced release of testosterone and estradiol from protein bound stores. Accepted for publication in Acta Radiol. Diagn. (1982).

    V Wirell S.: Binding of metrizamide to human serum proteins. Accepted for publication in Acta Radiol. Diagn. (1982).

    In a clinical study, Paper I, the highest incidence of adverse reactions at intra venous cholegraphy was recorded in young adults; especially in the luteal phase of the menstrual cycle.

    In Papers II, III and IV, the interplay between the protein binding of a bile- excreted contrast compound, ioglycamide, and steroid sex hormones was studied. Altered binding characteristics of the steroid hormone-protein binding indicated the possibility of a release of steroid hormones in the presence of ioglycamide. The significance of this finding was discussed in terms of clinical relevance.

    In Paper V, the binding of a non-ionic contrast compound to human serum proteins was studied with two different techniques. No, or only little, binding of metriz amide to human serum proteins was demonstrated.

  • Bucht, Gösta
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Clinical and etiological studies on dementia of Alzheimer type and multiinfarct dementia1983Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    1. Clinical studies. Clinical diagnosis of dementia has been made largely on the basis of clinical findings supported by appropriate radiological and laboratory investigations. A minority of patients have treatable or reversible underlying causes for their dementing syndrome. It is important to distinguish between the two main forms of dementia Alzheimer's disease, senile dementia of Alzheimer type (AD/SDAT) and MID so that advantage can be taken of any future progress in treatments.

    In the clinical study significant differences between several diagnostic procedures were found between patients with AD/SDAT and MID. Blood pressure was significantly lower in the AD/SDAT group and focal neurological signs were seen in 70% of the MID patients but only in 6% of patients with AD/SDAT. Electrocardiogram was normal in all patients with AD/SDAT but pathological in 75% of the MID patients. Electroencephalogram showed generalized slow frequencies in 79% of the AD/SDAT patients and localized changes in 65% of the MID patients. Computerized tomography showed a significantly greater dilation of the ventricular system in MID patients compared to AD/SDAT patients and controls. Monoamine metabolites in the cerebrospinal fluid were lower in AD/SDAT patients and normal in MID patients. Psychopathological signs were found to be more variable and more pronounced in the AD/SDAT group compared with MID patients.

    2. Etiological studies. Immunoglobulin and albumin were found changed in serum and CSF of both AD/SDAT and MID, indicating a more active immune response in MID and a less dense cerebrospinal fluid barrier in both MID and AD/SDAT. There appears to be a consumption of IgG in the central nervous system in patients with AD/SDAT.

    Abnormal chromosomes appearing as acentric fragments, i.e. without visible centromeres, were found in 90% of patients with AD/SDAT, 30% of patients with MID, and not at all in the control group. Increased aneuploidy was also seen both in patients with MID and AD/SDAT.

    Diabetes mellitus in old age and AD/SDAT do not seem to ’ coexist. Furthermore, patients with AD/SDAT have changed carbohydrate metabolism with decreased fasting blood sugar concentrations, increased glucose tolerance and higher concentration of insulin during an oral glucose tolerance test.

  • Freij, Lennart
    et al.
    Wall, Stig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Nyström, Lennarth
    Exploring child health and its ecology: the Kirkos study in Addis Ababa. An evaluation of community utilization of a mother and child health clinic1977Doctoral thesis, monograph (Other academic)
  • Samuelson, Gösta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    An epidemiological study of child health and nutrition in a northern Swedish county1971Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is a summary of the following original papers:

    I. An epidemiological study of child health and nutrition in a northern Swedish county. I. Food consumption survey. Acta Paediat Scand, 60: Suppl. 214, 1971.

    II. An epidemiological study of child health and nutrition in a northern Swedish county. II. Methodological study of the recall technique. Nutr Metabol, 12: 321, 1970.

    III. An epidemiological study of child health and nutrition in a northern Swedish county. III. Medical and anthropometrical examinations. Acta Paediat Scand, 60, 1971. In press.

    IV. An epidemiological study of child health and nutrition in a northern Swedish county. IV. Haematological investigations, especially in regard to iron deficiency anaemia. Acta Paediat Scand, 60, 1971. In press. In collaboration with S. Sjölin.

    V. An epidemiological study of child health and nutrition in a northern Swedish county. V. Oral health studies. Odont. Rev, 22, 1971. In press. In collaboration with H. Grahnén and G. Lindström.

    VI. An epidemiological study of child health and nutrition in a northern Swedish county. VI. Relationship between general and oral health, food habits and socio-economic conditions. In collaboration with H. Grahnén and E. Arvidsson. To be published, 1971.

  • Maaroufi, Nadia I.
    et al.
    Nordin, Annika
    Palmqvist, Kristin
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Gundale, Michael J.
    Nitrogen enrichment impacts on boreal litter decomposition are driven by changes in soil microbiota rather than litter quality2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 4083Article in journal (Refereed)
    Abstract [en]

    In nitrogen (N) limited boreal forests, N enrichment can impact litter decomposition by affecting litter quality and by changing the soil environment where litter decomposes. We investigated the importance of litter quality and soil factors on litter decomposition using a 2-year reciprocal transplant experiment for Picea abies needle litter, derived from plots subjected to 17 years of N addition, including control, low and high N treatments (ambient, 12.5 and 50 kg N ha(-1) yr(-1), respectively). Our data show that changes in soil factors were the main pathway through which N impacted litter decomposition, with rates reduced by approximate to 15% when placed in high N relative to control plots, regardless of litter origin. Litter decomposition was correlated to soil microbiota, with Picea abies litter decomposition positively correlated with gram negative and fungal functional groups. Our results suggest that previous findings of increase soil C accumulation in response to N deposition is likely to occur as a result of changes in soil microbiota rather than altered litter quality.

  • Kristoffer, Karlsson
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Arvid, Horned
    Icon based Indoor Navigation: Is icon based navigation a good method for indoor wayfinding?2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Humans today rely heavily on navigational aids on their smartphones to find their way. These aids have shown to be decreasing our ability to learn routes since the interaction with the environment is minimal. Technology assisting indoor navigation is getting more common, and the same approach, which has shown to impair spatial ability, is used, and will most likely result in the same problems. In the current study an application was developed that uses landmarks represented as icons to guide the users. The application was tested in a wayfinding task and compared to a control group using text instructions. Time for completing the route, wayfinding errors and route knowledge were measured and compared between groups. The results show that the text group had a faster walking time, but no significant difference was found in the other measurement. The route knowledge test turned out to be too difficult for the participants. The conclusion of the study is that icon based indoor navigation works but more research needs to be done to test if it facilitates spatial learning

  • Janunger, Karl-Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Benign and malignant gastric mucosal changes after partial gastrectomy1978Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    anunger, Karl-Gunnar. Benign and malignant gastric mucosal changes after partial gastrectomy.

    The development of benign and malignant mucosal changes in the gastric remnant were studied early (1-3 years) postoperatively in 55 patients and late (10-24 years) postoperatively in 336 of 676 patients subjected to partial gastrectomy for ulcer disease.

    Chronic gastritis with atrophy, intestinal metaplasia and cystic dilatation of the gastric glands was found early postoperatively with the same prevalence in gastric and duodenal ulcer patients. Wiereas the prevalence of atrophy, and of acute and chronic gastritis was the same both early and late postoperatively, the prevalence of intestinal metaplasia, cystic dilatation and lipid islands increased with time. The prevalence of inflammatory changes late postoperatively was not correlated to sex, age or type of anastomotic procedure.

    A significantly increased risk for stump carcinoma was found in male patients more than 12 years postoperatively. No difference correlated to type of ulcer disease or anastomotic procedure could be demonstrated. In duodenal ulcer patients the time interval between operation and diagnosis of carcinoma was independent of age at operation, while in gastric ulcer patients the interval was shorter with increasing age at operation.

    Gastric stump carcinomas were found in 12 of the 336 (3.6?£) patients examined gastroscopically; four of these were early carcinomas. In four patients with stump carcinoma the correct diagnosis could not be established at the first examination.

    Gastric polyps and precancerous mucosal changes were the only macro- or microscopical findings in some cases with already existing non-visible carcinoma.

    The CEA immunohistochemical study of the gastric mucosa showed a positive reaction in 10 of 49 patients; 6 of the 10 had carcinoma, precancerous changes or adenomatous polyp. Three patients with diagnosed or later discovered carcinoma had CEA negative reactions. However, the results indicate that there is a correlation between demonstrated CEA content and increased risk for development of stump carcinoma. To evaluate whether this method can be used to identify patients at special risk for development of gastric carcinoma requires further study.

    Because of increased risk for stump carcinoma, gastric ulcer patients ought to be examined with gastroscopy from about 10 years after partial gastrectomy, and duodenal ulcer patients from about 15 years, irrespective of the type of anastomotic procedure. Rç-examinations ought to be performed every two to four years. In patients with gastric polyps or precancerous mucosal changes re-examinations should be performed earlier, within 6-12 months.

  • Christianson, Sven-Åke
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Amnesia and emotional arousal1984Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The purpose of the present thesis was twofold. First, to study the role of emotional arousal in memory processes, and secondly, to relate this concept to empirical findings of amnesia. In both clinical and experimental settings it has been observed that remembering is impaired for events occurring prior to, and after a traumatic critical event. This memory impairment is also demonstrated for the traumatic event per se. In relation to these phenomena an interaction is commonly observed such that remembering of events aquired in a state of high emotionality, or arousal, is inferior to events aquired in neutral low arousal conditions at short test intervals, but superior at delayed test intervals. The general notion to be tested was how and to what extent these phenomena are mediated by an increase in emotional arousal. In order to test this hypothesis a series of experiments was designed so that retrograde and anterograde amnesia, and amnesia for the traumatic event, could be studied so as to evaluate the locus of the emotional arousal and amnesia effects with respect to encoding (attention), storage (consolidation), and retrieval (reconstruction). Emotional arousal was induced by sources associated with the to-be-remembered (TBR) material (traumatic pictures), and by sources not associated with the TBR-material (injections of adrenalin). Memory performance was measured by recall and recognition techniques. Amnesia was obtained only when the source of arousal was associated with the TBR-items. It was concluded that amnesia in connection to hightened emotional arousal depends on attention demanding characteristics of the traumatic event, rather than physiological properties of hightened arousal per se. An interaction between factors at encoding and retrieval was proposed as an explanation for the amnesia effects obtained. An interpretation in terms of consolidation has, throughout this thesis, been shown to be invalid in explaining the memory phenomena referred to.

  • Holmlund, Dan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ureteral stones: an experimental and clinical study of the mechanism of the passage and arrest of ureteral stones1968Doctoral thesis, monograph (Other academic)
  • Public defence: 2017-11-10 09:00 Sal A, byggnad 23, Umeå
    Löfgren, Hans O.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Preventive psychosocial parental and school programmes in a general population2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction Numerous preventive programmes have emerged, and need to be investigated to determine their effects on the normal population. Earlier studies have shown a decrease in depressive symptoms, positive effects on children’s disruptive behaviour problems, and an improvement in parental competence. About a fifth of the parents in previous studies had problem-oriented (targeted) reasons for enrolment, whereas the rest of the parents had general (universal) reasons. The results of those studies suggest that the programmes are cost effective in terms of Quality-Adjusted Life Years.

    Aim Four sub-studies were performed, and their aims were to investigate the effect of parental training programmes (PTPs) in a naturalistic setting on parents’ mental health in the general population, to investigate how PTPs affect parents’ sense of parental competence, to investigate how PTPs affect parental stress and analyse the parents open questions about the PTPs, and to investigate the feasibility and to measure the effect on depression, anxiety, and social problems of two preventive school programmes for pupils in grade 7.

    Method In a longitudinal quantitative study in a real-world setting, 279 parents from the general population in northern Sweden participated in five PTPs. A comparison group of 702 parents without intervention was included. Simultaneously, a community sample of 59 pupils in grade 7 participated in two preventive school programmes. Both studies were conducted from 2010 to 2013. Parents were assigned to professionally supported interventions that included 5-10 two-hour sessions. Respondents filled in a web-based questionnaire with the General Health Questionnaire (GHQ), the Parents Sense of Competence (PSOC) for parents who had children aged 0-17 years, and the Swedish Parenthood Stress Questionnaire (SPSQ) for parents who had children aged 0-10 years. The intervention groups’ results were compared to comparison group of 702 parents from northern Sweden that had not participated in any parental training programme. In the school study, one of the preventive programmes was an ongoing programme called “Life-Skills”, and the other was an implemented Canadian programme called “Choosing Healthy Actions and Thoughts” (CHAT). The pupils completed a test battery including the Sense of Coherence (SOC), the Children’s Depression Inventory (CDI), and the Youth Self-Report (YSR) instruments. Follow up of the parental programme study was done six months after the post-intervention measure, and follow up of the school study was at one year.

    Results The improvements in GHQ were statistically significant for the mean of the 279 parents in the intervention group compared to the mean of a comparison group of the 702 parents who did not receive any intervention. This suggests that evidence-based PTPs enhance parental well-being even for parents without problems. The intervention group showed a statistically significant improvement in parental competence compared to the comparison group over time. The intervention itself had a significant effect on parental satisfaction, but the efficacy effect was not sustained when taking into account potential confounders. In the SPSQ, the intervention group was smaller due to the fact that the instrument was not validated for children over the age of 10 and one of the parental training groups was only for parents of teenagers. A reduction of stress in the sub-scale of health problems was detected, but no other subscale showed the intervention to have a significant effect when controlling for confounding variables. In the school study, both programmes had good feasibility according to the stake- holders and had several positive mental health outcomes over time. Compared to Life-Skills, CHAT had more significant positive effects on reducing anxious/depressive symptoms and girls experienced significant positive effects on reduced anxious/depressive behaviour, while boys reduced their aggressive behaviours.

    Conclusions Earlier studies indicate that PTPs enhance perceived parental competence among referred parents. The present study shows that PTPs applied in the general population might also enhance perceived parental benefits such as improved health and satisfaction, suggesting that PTPs can be an important preventive strategy to enhance parenthood. The results suggest that parents who feel a need to increase their parenting competence might participate in PTPs based on lower scores than the comparison control group both before and after the intervention. The school-based programme shows that schools may be a suitable arena for preventive programmes because there was a significant short-term improvement in depression symptoms. Further studies need to explore how parents’ participation in PTPs affects children’s mental health in the general population in quantitative longitudinal studies in real-word settings. There is also a need for bigger studies and RCTs on school preventions and on how children’s health develops naturally in the population.

  • Davoine, Celine
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Abreu, Ilka N.
    Khajeh, Khalil
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Blomberg, Jeanette
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Kidd, Brendan N.
    Kazan, Kemal
    Schenk, Peer M.
    Gerber, Lorenz
    Nilsson, Ove
    Moritz, Thomas
    Björklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Functional metabolomics as a tool to analyze Mediator function and structure in plants2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, e0179640Article in journal (Refereed)
    Abstract [en]

    Mediator is a multiprotein transcriptional co-regulator complex composed of four modules; Head, Middle, Tail, and Kinase. It conveys signals from promoter-bound transcriptional regulators to RNA polymerase II and thus plays an essential role in eukaryotic gene regulation. We describe subunit localization and activities of Mediator in Arabidopsis through metabolome and transcriptome analyses from a set of Mediator mutants. Functional metabolomic analysis based on the metabolite profiles of Mediator mutants using multivariate statistical analysis and heat-map visualization shows that different subunit mutants display distinct metabolite profiles, which cluster according to the reported localization of the corresponding subunits in yeast. Based on these results, we suggest localization of previously unassigned plant Mediator subunits to specific modules. We also describe novel roles for individual subunits in development, and demonstrate changes in gene expression patterns and specific metabolite levels in med18 and med25, which can explain their phenotypes. We find that med18 displays levels of phytoalexins normally found in wild type plants only after exposure to pathogens. Our results indicate that different Mediator subunits are involved in specific signaling pathways that control developmental processes and tolerance to pathogen infections.

  • Chatzittofis, Andreas
    et al.
    Savard, Josephine
    Arver, Stefan
    Görts Öberg, Katarina
    Hallberg, Jonas
    Nordström, Peter
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men2017In: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 6, no 2, 187-193 p.Article in journal (Refereed)
    Abstract [en]

    Background and aims: There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods: This case-control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire-Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery-Asberg Depression Rating Scale - Self-rating. Results: Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion: Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion: Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men.

  • Li, Zhen
    et al.
    De La Torre, Amanda R.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Plant Sciences, University of California-Davis, Davis, CA.
    Sterck, Lieven
    Cánovas, Francisco M.
    Avila, Concepción
    Merino, Irene
    Antonio Cabezas, Jose
    Teresa Cervera, Maria
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Plant Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Van de Peer, Yves
    Single-Copy Genes as Molecular Markers for Phylogenomic Studies in Seed Plants2017In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 9, no 5, 1130-1147 p.Article in journal (Refereed)
    Abstract [en]

    Phylogenetic relationships among seed plant taxa, especially within the gymnosperms, remain contested. In contrast to angio-sperms, for which several genomic, transcriptomic and phylogenetic resources are available, there are few, if any, molecular markers that allow broad comparisons among gymnosperm species. With few gymnosperm genomes available, recently obtained transcriptomes in gymnosperms are a great addition to identifying single-copy gene families as molecular markers for phylogenomic analysis in seed plants. Taking advantage of an increasing number of available genomes and transcriptomes, we identified single-copy genes in a broad collection of seed plants and used these to infer phylogenetic relationships between major seed plant taxa. This study aims at extending the current phylogenetic toolkit for seed plants, assessing its ability for resolving seed plant phylogeny, and discussing potential factors affecting phylogenetic reconstruction. In total, we identified 3,072 single-copy genes in 31 gymnosperms and 2,156 single-copy genes in 34 angiosperms. All studied seed plants shared 1,469 single-copy genes, which are generally involved in functions like DNA metabolism, cell cycle, and photosynthesis. A selected set of 106 single-copy genes provided good resolution for the seed plant phylogeny except for gnetophytes. Although some of our analyses support a sister relationship between gnetophytes and other gymnosperms, phylogenetic trees from concatenated alignments without 3rd codon positions and amino acid alignments under the CAT + GTR model, support gnetophytes as a sister group to Pinaceae. Our phylogenomic analyses demonstrate that, in general, single-copy genes can uncover both recent and deep divergences of seed plant phylogeny.

  • Sahu, Sanjaya Kumar
    et al.
    Kumar, Manish
    Chakraborty, Sohini
    Banerjee, Srijon Kaushik
    Kumar, Ranjeet
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Department of Chemistry, Bose Institute, Kolkata, India.
    Gupta, Pushpa
    Jana, Kuladip
    Gupta, Umesh D.
    Ghosh, Zhumur
    Kundu, Manikuntala
    Basu, Joyoti
    MicroRNA 26a (miR-26a)/KLF4 and CREB-C/EBP beta regulate innate immune signaling, the polarization of macrophages and the trafficking of Mycobacterium tuberculosis to lysosomes during infection2017In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 13, no 5, e1006410Article in journal (Refereed)
    Abstract [en]

    For efficient clearance of Mycobacterium tuberculosis (Mtb), macrophages tilt towards M1 polarization leading to the activation of transcription factors associated with the production of antibacterial effector molecules such as nitric oxide (NO) and proinflammatory cytokines such as interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha). At the same time, resolution of inflammation is associated with M2 polarization with increased production of arginase and cytokines such as IL-10. The transcriptional and post-transcriptional mechanisms that govern the balance between M1 and M2 polarization, and bacteria-containing processes such as autophagy and trafficking of Mtb to lysosomes, are incompletely understood. Here we report for the first time, that the transcription factor KLF4 is targeted by microRNA-26a (miR-26a). During Mtb infection, downregulation of miR-26a (observed both ex vivo and in vivo) facilitates upregulation of KLF4 which in turn favors increased arginase and decreased iNOS activity. We further demonstrate that KLF4 prevents trafficking of Mtb to lysosomes. The CREB-C/EBP beta signaling axis also favors M2 polarization. Downregulation of miR-26a and upregulation of C/ebpbeta were observed both in infected macrophages as well as in infected mice. Knockdown of C/ebpbeta repressed the expression of selected M2 markers such as Il10 and Irf4 in infected macrophages. The importance of these pathways is substantiated by observations that expression of miR-26a mimic or knockdown of Klf4 or Creb or C/ebpbeta, attenuated the survival of Mtb in macrophages. Taken together, our results attribute crucial roles for the miR-26a/KLF4 and CREB-C/EBP beta signaling pathways in regulating the survival of Mtb in macrophages. These studies expand our understanding of how Mtb hijacks host signaling pathways to survive in macrophages, and open up new exploratory avenues for host-targeted interventions.

  • Ding, Ming
    et al.
    Huang, Tao
    Bergholdt, Helle K. M.
    Nordestgaard, Borge G.
    Ellervik, Christina
    Qi, Lu
    Frazier-Wood, Alexis C.
    Aslibekyan, Stella
    North, Kari E.
    Voortman, Trudy
    Graff, Mariaelisa
    Smith, Caren E.
    Lai, Chao-Qiang
    Varbo, Anette
    Lemaitre, Rozenn N.
    de Jonge, Ester A. L.
    Fumeron, Frederic
    Corella, Dolores
    Wang, Carol A.
    Tjonneland, Anne
    Overvad, Kim
    Sorensen, Thorkild I. A.
    Feitosa, Mary F.
    Wojczynski, Mary K.
    Kahonen, Mika
    Ahmad, Shafqat
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Psaty, Bruce M.
    Siscovick, David S.
    Barroso, Ines
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hernandez, Dena
    Ferrucci, Luigi
    Bandinelli, Stefania
    Linneberg, Allan
    Sandholt, Camilla Helene
    Pedersen, Oluf
    Hansen, Torben
    Schulz, Christina-Alexandra
    Sonestedt, Emily
    Orho-Melander, Marju
    Chen, Tzu-An
    Rotter, Jerome I.
    Allison, Mathew A.
    Rich, Stephen S.
    Sorli, Jose V.
    Coltell, Oscar
    Pennell, Craig E.
    Eastwood, Peter R.
    Hofman, Albert
    Uitterlinden, Andre G.
    Zillikens, MCarola
    van Rooij, Frank J. A.
    Chu, Audrey Y.
    Rose, Lynda M.
    Ridker, Paul M.
    Viikari, Jorma
    Raitakari, Olli
    Lehtimaki, Terho
    Mikkila, Vera
    Willett, Walter C.
    Wang, Yujie
    Tucker, Katherine L.
    Ordovas, Jose M.
    Kilpelainen, Tuomas O.
    Province, Michael A.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA; Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Arnett, Donna K.
    Tanaka, Toshiko
    Toft, Ulla
    Ericso, Ulrika
    Franco, Oscar H.
    Mozaffarian, Dariush
    Hu, Frank B.
    Chasman, Daniel I.
    Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study2017In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 356, j1000Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. DESIGN Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. SETTING CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. PARTICIPANTS Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. MAIN OUTCOME MEASURES The instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. RESULTS Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). CONCLUSION The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.

  • Löfstrand, Tord
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Determination of gestational age and lung maturity: phospholipids, creatinine and phosphatase in amniotic fluid1976Doctoral thesis, comprehensive summary (Other academic)
  • Boquist, Lennart
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    The endocrine pancreas in the Chinese hamster: studies on non-diabetic, alloxan-treated, zinc-deficient, and spontaneously diabetic animals1969Doctoral thesis, comprehensive summary (Other academic)
  • Perris, Hjördis
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    A multifactorial study of life events in depressed patients1982Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this study was an attempted elucidation of the possible pathogenic role of life events in the onset and development of depression. Although several authors seem to agree that the impact of life events should be seen in relation to the person experiencing them, no comprehensive studies have been published so far where life events have been analysed in relation to the vulnerability of the individual who becomes depressed. The present study was inspired by Freud’s concept of ”Ergänzungsreihe”, and was based on the general assumption that biological as well as psychological and social factors contribute greatly to modifying an individual’s vulnerability to external events.

    To test this hypothesis the occurrence of life events was studied by means of a semistructured interview in a consecutive series of 206 depressed patients of both sexes treated as in- or outpatients* and the results have been analysed in relation to a series of variables which could be assumed to be of importance in modifying the vulnerability of the patients. The main hypothesis was that the more vulnerable the individual was in relation to each of the investigated factors, the fewer events would be necessary to produce a depressive breakdown and the more negative would be the experience of such events. Biological, psychological and clinical variables were taken into account in different parts of the present study.

    The results support the view that the impact of life events should be seen idiosyncratically and in relation to the specific vulnerability of each individual. Furthermore the study illustrates a fruitful approach for further studies aimed at a closer understanding of the role of external events in the development of a depressive illness.

  • Näsman, Birgitta
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    The limbic-hypothalamic-pituitary-adrenal axis in Alzheimer's disease1994Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Dysfunction of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis is a common finding in advanced dementia. In this study, the function of the LHPA axis at different levels was investigated in patients with dementia and in healthy elderly.

    A subtle disturbance in the feedback regulation of the LHPA axis was found in patients with early (i.e., mild to moderate) Alzheimer’s disease (AD). After 0.5 mg dexamethasone, serum cortisol levels were less suppressed in AD patients and plasma adrenocorticotropin (ACTH) levels were lower as compared with healthy elderly. After stimulation with human corticotropin-releasing hormone a blunted ACTH response was found in AD patients while relative serum cortisol, déhydroépiandrostérone, and androstenedione responses were increased. Significant correlations were found between low plasma ACTH levels and temporal lobe atrophy and between low peak plasma ACTH levels and hippocampal atrophy measured with computer tomography. Patients with advanced AD and multi-infarct dementia had lower basal levels of déhydroépiandrostérone sulphate in combination with no difference in cortisol levels, resulting in a high cortisol/DHAS ratio. The difference persisted after adjustments for age and sex in a multivariate analysis. In patients with early AD, basal serum levels of dehydroepiandrosterone and androstenedione were increased, and this increase was accentuated after stimulation with ACTH. Peripheral glucocorticoid sensitivity was examined by skin vasoconstrictor blanching tests. Patients with AD and patients treated with glucocorticoids showed skin blanching at higher clobetasol concentrations than healthy elderly.

    These findings justify further investigations on the role of LHPA axis dysfunction in Alzheimer’s disease and its possible importance for the pathophysiology of the disease.

  • Korsman, Tom
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Acidification trends in Swedish lakes: an assessment of past water chemistry conditions using lake sediments1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis presents temporal perspectives of lake acidification in Sweden. Sediment records have been used to study timing, trends and causes of acidification, and two different techniques for assessing past lake-water acidity are presented.

    A new technique for pH prediction, based on near-infrared (NIR) spectroscopy of surface sediments, is developed. This study shows that there is a pH related fraction of lake sediments that can be recorded by NIR analysis. Relationships between NIR spectra of surface sediment samples and measured lake-water pH values, and between NIR spectra of sediment cores and historical pH values inferred by diatom analysis, are modelled by partial least squares regression. The prediction errors of the models are comparable to those obtained by modelling of diatom and lake-water pH data. By further development NIR spectroscopy can become useful for inferring past pH, as well as several other lake-water parameters, from sediment cores.

    Diatom-based predictive models, using multivariate calibration methods, are developed for inferences of lake-water pH, alkalinity and colour. These models are used to provide a regional assessment of recent lake acidification in the provinces of Västerbotten and Norrbotten, northern Sweden. The study shows that a pH decline has occurred in some southeastern lakes, but that most of the lakes have not faced significant changes in lake-water pH, alkalinity and colour. The inferred water chemistiy changes are discussed in relation to atmospheric deposition and land-use.

    In a study of eight acid-sensitive Swedish boreal-forest lakes a past-analogue approach is used to test whether contemporary expansion of conifers could cause lake acidification. Water chemistry changes associated with the natural pre-historic colonization and expansion of spruce in Sweden (—3000 years B.P.), at times of background atmospheric acidity, are inferred to evaluate the acidification ability of spruce per se on surface waters. This study shows that under natural, unpolluted conditions spruce colonization and expansion did not cause lake acidification.

    In a synthesis of palaeolimnological acidification research in Sweden a general model for pH- development for acid clear-water lakes in southern Sweden is presented. The pH-development from the last déglaciation to present time can be divided into four different periods; (i) a natural long-term acidification period (12000 B.P. - 2300 B.P., or later), with a gradual decrease in pH resulting from declining fluxes of base cations from catchment soils; (ii) a human induced alkalization period (2300 B.P. - 1900 A.D.), with a pH increase due to human activities in the catchments; (iii) the recent acidification period (about 1900 A.D. - present), when pH decreased towards 4.5 due to acid deposition and possibly ceased land-use; and (iv) the liming period (1970s - present), when pH often increases to values above 7 following lime treatment to counteract acidification. The implications of these past pH changes for the concept of contemporary lake acidification and for liming policy are outlined.

  • Bergman, Maud
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Chemical and thermodynamic studies of dental gold alloys with special reference to homogenization, electrochemical corrosion and cluster formation1976Doctoral thesis, comprehensive summary (Other academic)
  • Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Distribution of puumala virus in Sweden1997Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Puumala virus, belonging to the genus hantavirus, is the causative agent of nephropathia epidemica (NE), a relatively mild form of hemorrhagic fever with renal syndrome. Puumala virus occurs endemically in Central and Northern Europe and Western Russia. In Sweden, NE is reported from the northern and central parts but virtually not at all from the southern part of the country. The bank vole (Clethrionomys glareolus) is the main reservoir of Puumala virus and humans are infected by inhalation of aerosolized animal secreta. In northern Sweden, the density of the bank vole population varies cyclically in intervals of 3-4 years and the incidence of NE shows a covariation.

    The prevalence of serum antibodies to hantaviruses in northern Sweden was studied in a stratified and randomly selected adult population sample comprising 1538 subjects. As expected, the prevalence increased with age. There was no difference between men and women, which was unexpected based on a male:female ratio of > 2:1 in clinical reports. By use of an immunofiuorescent assay, a seroprevalence of 5.4% and by a newly developed enzyme-linked immunosorbent assay (ELISA) with recombinant Puumala virus nucleocapsid protein as antigen, a prevalence of 8.9% was recorded. This is about or more than ten times higher than what would be calculated from clinical reports.

    By use of the ELISA, an occupational risk of acquisition of Puumala virus infection was demonstrated. Serum samples from 910 farmers and 663 referent subjects living in various rural parts of Sweden were tested. Among farmers from the Puumala virus-endemic northern and central parts of the country, the seroprevalence (12.9%) was higher (p=0.01) than in referents (6.8%). In the southern part of Sweden, only 2/459 persons had antibodies. Only a limited number of children with NE had been previously reported. In a separate study, 32 children with Puumala virus infection were identified and the clinical picture of NE in children was found to be similar to that of adult cases.

    Variations in the prevalence of Puumala virus in the bank vole population within an endemic region are not well known. Here, a higher mean rodent density and a higher prevalence of Puumala virus-specific serum antibodies were recorded in the vicinity of households afflicted with NE than in rural control areas. The data indicated that the risk of exposure locally within an endemic region may vary widely and tentatively suggested that a threshold density of bank voles might be necessary to achieve before effective spread of Puumala virus within the rodent population may occur.

    There is no firm evidence of the occurrence of Puumala virus among wild living animals other than rodents. A study of Swedish moose, an animal which is ecologically well characterized, was performed. Convincing evidence of past Puumala virus infection was found in 5/260 moose originating from Puumala virus-endemic areas but in none of 167 animals from nonendemic areas. Based on the low seroprevalence recorded, moose seemed to serve as endstage hosts rather than being active parts of the enzootic circle of transmission.

    In conclusion, the present investigations confirmed that the exposure to Puumala virus is geographically well restricted in Sweden. Seroprevalence studies indicated that only a minor proportion of individuals infected with Puumala virus are clinically reported, with a bias in favour of men. NE was confirmed to occur in children, with a clinical picture similar to that of adults. An occupational risk was defined for acquisition of Puumala virus infection. Studies in rodents suggested that there may be wide local variations within a limited area in the risk of exposure to Puumala virus. The studies validated the usefulness of a newly developed ELISA based on recombinant nucleocapsid peptides of hantaviruses and finally, methodological progress was reached when Puumala virus was, for the first time, successfully isolated from a Scandinavian patient.

  • Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Dialysis Procedures Alter Metabolic Conditions2017In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 9, no 6, 548Article, review/survey (Refereed)
    Abstract [en]

    A progressive chronic kidney disease results in retention of various substances that more or less contribute to dysfunction of various metabolic systems. The accumulated substances are denominated uremic toxins. Although many toxins remain undetected, numerous newly defined toxins participate in the disturbance of food breakdown. In addition, toxic effects may downregulate other pathways, resulting in a reduced ability of free fatty acid breakdown by lipoprotein lipase (LPL) and hepatic lipase (HL). Dialysis may even worsen metabolic functions. For LPL and HL, the use of heparin and low molecular weight heparin as anticoagulation during hemodialysis (HD) initiate a loss of these enzymes from their binding sites and degradation, causing a temporary dysregulation in triglyceride breakdown. This lack of function will cause retention of the triglyceride containing lipids for at least 8 h. In parallel, the breakdown into free fatty acids is limited, as is the energy supply by them. This is repeated thrice a week for a normal HD patient. In addition, dialysis will cause a loss of amino acids and disturb glucose metabolism depending on the dialysates used. The addition of glucose in the dialysate may support oxidation of carbohydrate and the retention of Amadori products and subsequent tissue alterations. To avoid these effects, it seems necessary to further study the effects of anticoagulation in HD, the extent of use of glucose in the dialysate, and the supplementation of amino acids.

  • Mutie, Pascal M.
    et al.
    Giordano, Giuseppe N.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Lund Univ, Skane Univ Hosp, Dept Clin Sci, Harvard Sch Publ Hlth, Univ Oxford, Radcliff Dept Med.
    Lifestyle precision medicine: the next generation in type 2 diabetes prevention?2017In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 15, 171Article, review/survey (Refereed)
    Abstract [en]

    The driving force behind the current global type 2 diabetes epidemic is insulin resistance in overweight and obese individuals. Dietary factors, physical inactivity, and sedentary behaviors are the major modifiable risk factors for obesity. Nevertheless, many overweight/obese people do not develop diabetes and lifestyle interventions focused on weight loss and diabetes prevention are often ineffective. Traditionally, chronically elevated blood glucose concentrations have been the hallmark of diabetes; however, many individuals will either remain 'prediabetic' or regress to normoglycemia. Thus, there is a growing need for innovative strategies to tackle diabetes at scale. The emergence of biomarker technologies has allowed more targeted therapeutic strategies for diabetes prevention (precision medicine), though largely confined to pharmacotherapy. Unlike most drugs, lifestyle interventions often have systemic health-enhancing effects. Thus, the pursuance of lifestyle precision medicine in diabetes seems rational. Herein, we review the literature on lifestyle interventions and diabetes prevention, describing the biological systems that can be characterized at scale in human populations, linking them to lifestyle in diabetes, and consider some of the challenges impeding the clinical translation of lifestyle precision medicine.

  • Loeb, Stacy
    et al.
    Ventimiglia, Eugenio
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Division of Experimental Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Universita Vita-Salute San Raffaele, Milan, Italy.
    Salonia, Andrea
    Folkvaljon, Yasin
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden .
    Meta-Analysis of the Association Between Phosphodiesterase Inhibitors (PDE5Is) and Risk of Melanoma2017In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 109, no 8, djx086Article in journal (Refereed)
    Abstract [en]

    The US Food and Drug Administration recently announced the need to evaluate the association between PDE5is and melanoma. We performed a meta-analysis on the association between PDE5i and melanoma using random effects models and examined whether it met Hill's criteria for causality. A systematic search of Medline, EMBASE, and the Cochrane Library from 1998 to 2016 identified three case-control studies and two cohort studies, including a total of 866 049 men, of whom 41 874 were diagnosed with melanoma. We found a summary estimate indicating an increased risk of melanoma in PDE5i users (relative risk = 1.12, 95% confidence interval = 1.02 to 1.23). However, there was no difference in risk between men with low and high exposure to PDE5i, and risk was higher for in situ melanoma than localized and high-risk melanoma, suggesting a lack of dose response and biological gradient. PDE5i use was also associated with basal cell cancer, suggesting a lack of specificity and likely confounding by ultraviolet exposure. Thus, although this meta-analysis found a statistically significant association between PDE5i and melanoma, it did not satisfy Hill's criteria for causality.

  • Persson, Emilia
    et al.
    Gustafsson, Christian
    Nordström, Fredrik
    Sohlin, Maja
    Gunnlaugsson, Adalsteinn
    Petruson, Karin
    Rintelä, Niina
    Hed, Kristoffer
    Blomqvist, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Olsson, Lars E.
    Siversson, Carl
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    MR-OPERA: a multicenter/multivendor validation of magnetic resonance imaging–only prostate treatment planning using synthetic computed tomography images2017In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 99, no 3, 692-700 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To validate the dosimetric accuracy and clinical robustness of a commercially available software for magnetic resonance (MR) to synthetic computed tomography (sCT) conversion, in an MR imaging–only workflow for 170 prostate cancer patients.

    Methods and Materials: The 4 participating centers had MriPlanner (Spectronic Medical), an atlas-based sCT generation software, installed as a cloud-based service. A T2-weighted MR sequence, covering the body contour, was added to the clinical protocol. The MR images were sent from the MR scanner workstation to the MriPlanner platform. The sCT was automatically returned to the treatment planning system. Four MR scanners and 2 magnetic field strengths were included in the study. For each patient, a CT-treatment plan was created and approved according to clinical practice. The sCT was rigidly registered to the CT, and the clinical treatment plan was recalculated on the sCT. The dose distributions from the CT plan and the sCT plan were compared according to a set of dose-volume histogram parameters and gamma evaluation. Treatment techniques included volumetric modulated arc therapy, intensity modulated radiation therapy, and conventional treatment using 2 treatment planning systems and different dose calculation algorithms.

    Results: The overall (multicenter/multivendor) mean dose differences between sCT and CT dose distributions were below 0.3% for all evaluated organs and targets. Gamma evaluation showed a mean pass rate of 99.12% (0.63%, 1 SD) in the complete body volume and 99.97% (0.13%, 1 SD) in the planning target volume using a 2%/2-mm global gamma criteria.

    Conclusions: Results of the study show that the sCT conversion method can be used clinically, with minimal differences between sCT and CT dose distributions for target and relevant organs at risk. The small differences seen are consistent between centers, indicating that an MR imaging–only workflow using MriPlanner is robust for a variety of field strengths, vendors, and treatment techniques.

  • Rösblad, Birgit
    Visual and proprioceptive control of arm movements: studies of development and dysfunction1994Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this dissertation was to examine the role of sensory information for control of goal-directed arm movements in children. The role of visual and proprioceptive information on the target for end point accuracy was examined in normal 4- to 12-year- old children (Study I), and in children with motor impairments (Study II). Accuracy in pointing with the unseen hand was found to improve rapidly during the age period tested, with the most pronounced development taking place in the preschool years. Visual specification of the target was superior to proprioceptive specification for all age groups tested. The performance of children with motor impairments was more variable than that of the non-impaired children, and this effect was most pronounced when visual information about the target was unavailable. The importance of visual information for controlling the transport and handling part of reaching movements were examined in normal 6- to 8-year-old children (Study III), and in children with developmental coordination disorders (Study IV). Object handling required visual information on both target and hand. For the transport phase of the movement visual information on target was sufficient, and sight of hand did not improve performance. The young children were relatively more impaired than the older children when lacking adequate visual information. The children with developmental coordination disorders responded to the withdrawal of visual information in a similar way to that of the normally developed children. A discontinuity at 7 years of age in the development of perceptual control of pointing movements, observed in Study I, was further investigated and confirmed in study V. In this study the ability to control movements visually and prorioceptively was also investigated and found to develop in parallel rather than one being a prerequisite for the other.

  • Nilsson, Per A.
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History. International Office.
    The Swedish Experience of International Student Mobility2017In: On the verge of a new era: value, viability and visibility of international education / [ed] Riikka Vanhanen, Jyrki Holappa, Jyväskylä: JAMK University of Applied Sciences Library , 2017, 25-31 p.Chapter in book (Other academic)
    Abstract [en]

    The internationalisation of education started in the late 1970s when the wording in the Swedish Higher Education Act was changed, emphasising that higher education institutions (HEI) should promote understanding of other countries and of international circumstances. This also opened the door for other changes in Swedish regulations, such as the study aid system, allowing more students to study abroad. However, the greatest boost to international student mobility was when Sweden entered the Erasmus Programme in 1992 (Lundgren & Nilsson, 2009).

    It is clear that there are political ambitions when it comes to international student mobility. Politicians set the roles for mobility through political decisions about studying in a foreign country, regulations for migration, student loans, recognition for foreign degrees, etc. There is also a global education market being developed outside Sweden. More countries have an interest in the business of international education and the commodification of education due to a decrease of public HEI funding (Knight, 2012). This means that market solutions have entered the global scene, which countries around the world have to adjust to, including Sweden. The aim with this article is to highlight some of the Swedish experiences in regard to international student mobility.

  • Niklasson, Urban
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Spectral analysis of the heart rate variability: a methodological study1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Heart rate and other cardiovascular variables are not steady but fluctuate over time. The evolution of computer technology the last 2 decades has made detailed analysis of the fluctuations possible and has focused the attention to the information content of the variability.

    Autonomic nervous influence on the heart can be assessed by measuring the heart rate variability from R-R intervals in the electrocardiogram. Applications have been developed in many fields where the pathophysiological features of the patients include autonomic dysfunction.

    This thesis is based on clinical studies and model studies compared with results from healthy volunteers. Two patient groups, with familial amyloidosis and with myotonic dystrophy, were evaluated using simple indexes of heart rate variability. Signs of autonomic dysfunction which is a dominant clinical feature in familial amyloidosis with polyneuropathy was confirmed by abnormal heart rate variability indexes. In myotonic dystrophy heart rate variability was normal but recumbent and standing plasma catecholamines were elevated. Reassessment of the heart rate variability with spectral analysis confirmed the results.

    The integral pulse frequency modulation (IPFM) model can be used as a simple analogy of the interface between autonomic activity and the cardiac pacemaker. Computer simulations using the IPFM model revealed marked differences in the estimated modulating variability depending on whether the intervals between simulated beats or the frequency of beats was analyzed. Comparison with data from healthy volunteers indicated that the IPFM model was valid and that heart rate should be preferred instead of R-R intervals for variability measurements.

    Beat-by-beat heart rate can be viewed as an irregular sample of the underlying autonomic activity. Spectral analysis of simulated heart rate variability data using the IPFM model showed attenuation of high frequency variability with decreasing mean heart rate and with increasing variability mean frequency. Application of these results on data from healthy volunteers suggest that the effects can be significant in actual variability measurements.

    Cholinergic blockade resulted in reduced heart rate variability at all spectral frequencies. Adrenergic beta-blockade reduced high-frequency variability in standing position indicating that high-frequency variability might partly be sympathetically mediated.

  • Wikman, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    To desire and to choose: aspects of women's and men's urge to have children1994Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this study was to increase available knowledge about women's and men’s desire for pregnancy and for a child/children to serve as a basis for further studies of problems and inconsistencies in the reproductive sphere. The motivation to become a parent was hypothesized as being not only of an existential, social, interpersonal and intrapsychic character but also a biologically anchored personality trait.

    The first part of the study deals with the development of a method for collecting valid information concerning this intimate and personal sphere of life and to categorize this information into measurable dimensions. A questionnaire was constructed and factor analysis was used as a statistical tool. There are two versions of the final instrument, one for women and one for men. Interviews were used as a means of testing the validity of the instrument. Experiences from the methodological development process revealed that it was meaningful to deal with the issue though suitable wording was not easily found.

    In the main part of the study, two large populations, one reference group of 416 women and 329 men of fertile ages and one group of expecting parents, 369 women and 345 men, were investigated by means of the questionnaire. Attitudes were dominated by two opposing views of children: 'Children mean existential satisfaction' and 'Children mean restriction of freedom'. This confirmed the findings of earlier studies and clinical experience that ambivalence is a natural phenomenon, that may be associated with feelings of guilt. The view of one's own parents as models in parenthood was a third important dimension. The view of the child's sex was a fourth important and complex dimension.

    The similarities between women and men were striking. There were only subtle differences between reference women and pregnant women. Reference men and child-expecting men had different response patterns, child-expecting men emphasizing more the advantages of having children.

    In the last part of the study 48 women were followed during pregnancy and after childbirth using the questionnaire and determination of levels of the intestinal peptide gastrin. Gastrin may be a marker of energy-storing characteristics, thus influencing reproductive capacity. There were some attitudinal differences between 0-parous women and parous women, the latter agreeing less with the view of 'children as restriction of freedom'. The view of 'children as existential satisfaction' was agreed with more after childbirth than during pregnancy. The view of one’s own parents as models in parenthood correlated with the levels of gastrin during this period.

  • Gustafsson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Mattsson, Sofia
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Gallego, Gisselle
    Students' satisfaction with a web-based pharmacy program in a re-regulated pharmacy market2017In: Pharmacy, ISSN 2226-4787, E-ISSN 1913-4711, Vol. 5, no 3, E47Article in journal (Refereed)
    Abstract [en]

    In response to the shortage of pharmacists in Northern Sweden, a web-based Bachelor of Science in Pharmacy program was established at Umeå University in 2003. In 2009, the Swedish pharmacy market was re-regulated from a state monopoly to an open market, but it is unknown what impact this has had on education satisfaction. The objectives of this study were to examine the level of satisfaction among graduates from a web-based pharmacy program and to describe what subjects and skills students would have liked more or less of in their education. A secondary objective was to compare the level of satisfaction before and after the Swedish pharmacy market was re-regulated. A cross-sectional survey was conducted in 2015 with all alumni who had graduated from the pharmacy program between 2006 and 2014 (n = 511), and responses to questions about graduates' satisfaction with the program were analyzed (n = 200). Most graduates (88%) agreed or strongly agreed that the knowledge and skills acquired during their education were useful in their current job. The graduates stated that they would have wanted more applied pharmacy practice and self-care counselling, and fewer social pharmacy and histology courses. Further, 82% stated that they would start the same degree program if they were to choose again today, and 92% agreed or strongly agreed that they would recommend the program to a prospective student. Graduates were more likely to recommend the program after the re-regulation (p = 0.007). In conclusion, pharmacy graduates were very satisfied with their education, and no negative effects of the re-regulation could be observed on program satisfaction.

  • Kristensen, Bo Traberg
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stroke in young adults in northern Sweden1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Objectives. To study different aspects of cerebral venous and arterial occlusive disease including cerebrospinalfluid hydrodynamics, epidemiology, aetiology, genetics, metabolic and haemostatic disorders, andcognitive function in young adults in Northern Sweden.

    Methods. Cerebrospinal fluid hydrodynamics were investigated with a constant pressure infusion methodin patients with superior sagittal sinus thrombosis. Ten patients were studied with serial examinations, upto 15 years after the onset of the disease.

    Epidemiological data on ischaemic stroke in young adults aged 18 to 44 years were collected to calculateincidence and mortality based on the WHO Northern Sweden MONICA register of acute strokeevents. One hundred and seven consecutive patients aged 18-44 years with ischaemic stroke referred toUmeå university hospital were studied prospectively during a five-year period and were extensively evaluatedaccording to a standardized protocol. During follow-up at least three months after onset 102 and 80patients, respectively, were evaluated for disturbances in the fibrinolytic system and in the metabolism ofhomocysteine. A comprehensive neuropsychological battery was performed in a subset of 20 patients withinfratentorial infarcts.

    Results and conclusions. All patients with superior sagittal sinus thrombosis demonstrated a marked increasein intracranial pressure due to raised pressure in the sagittal sinus. A striking feature was the persistentintracranial pressure increase with only a slow decline over time.

    The incidence rate for ischaemic stroke was higher than previously reported from most countries inWestern Europe. The higher incidence was not explained by a higher prevalence of atherosclerotic vasculopathy. In spite of extensive evaluation, including advanced cardiac imaging, the cause of ischaemic strokein young adults still remains uncertain or unknown in most cases.

    Patients had lowered tissue plasminogen activator activity and increased plasminogen activator inhibitortype 1 activity. Increased fibrinogen levels and tissue plasminogen activator mass concentration wereindependently associated with ischaemic stroke. Metabolic perturbations were closely interrelated with tissueplasminogen activator and plasminogen activator inhibitor type 1 activity. Elevated plasma fibrinogenlevels and abnormalities in the fibrinolytic system in conjunction with metabolic perturbations may be importantcontributors to an increased stroke risk among young adults.

    Stroke patients had an exaggerated increase in total homocysteine levels after methionine loading.Abnormal responsivity to methionine loading was associated with higher tissue plasminogen activatormass concentration, plasminogen activator inhibitor 1 levels and lower tissue plasminogen activator activity. Abnormal homocysteine metabolism may provide an additional thrombogenetic risk, partly mediatedby interactions with the fibrinolytic system.

    Circumscribed infratentorial lesions (mainly cerebellar) impaired central aspects of attention andworking memory, and inflicted damage upon visuospatial skills. In contrast, these patients may not sufferfrom global intellectual impairment and difficulties with respect to memory for previous events. The prognosisis favorable in terms of neurological deficits and handicap, but cognitive disability may be the mostsignificant problem in adapting to their former occupations.Key w ords. Cerebral venous thrombosis, cerebrospinal fluid dynamics, ischaemic stroke, young adults, epidemiology,fibrinolysis, homocysteine, cerebellar infarct, neuropsychology.

  • Gärling, Anita
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Parents' perceptions of children's accident risk1988Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The purpose of the present thesis was, first, to study how parents and other adults percieve or judge children’s accident risk, and, secondly, to relate such judgements to the subjects’ preferences for and satisfaction with different residential conditions.

    A theoretical framework is proposed which assumes that judgements of children’s accident risk are based on beliefs about what causes accidents to children. Such beliefs are furthermore assumed to be acquired more often from indirect sources than from own direct experiences. Nevertheless, because of parents’ higher motivation to protect their children, they are assumed to differ from other adults who are not parents with respect to their causal models and, as a consequence, their risk perceptions.

    To test some implications of the theoretical framework, three empirical studies were carried out in which parents and nonparents were requested to judge the risk children run of having accidents under different circumstances and to judge the strengths of five causes of such accidents, the parent, the child, the environment, other people, and chance. In two of the studies the subjects were also requested to express their preferences for different residential neighborhoods varying in traffic conditions, or satisfaction with their own residential conditions either as it is or if changed in different ways.

    Support for the implications of the theoretical framework was obtained in that causal explanations of accidents were shown to play a decisive role for judgements of accident risk. However, very slight differences were found between parents’ and nonparents’ causal models and risk perceptions. The results furthermore indicated that accident risk was of importance for parents’ satisfaction with their residential conditions if changes with perceived accident consequences were implemented. In this respect parents differed from nonparents. For the latter other things than children’s accident risk tended to be more important.

  • Hoffman, Victoria
    et al.
    Söderström, Lars
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Self-management of stress urinary incontinence via a mobile app: two-year follow-up of a randomized controlled trial2017In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 96, no 10, 1180-1187 p.Article in journal (Refereed)
    Abstract [en]

    Introduction. We investigated the long-term effects of using a mobile app to treat stress urinary incontinence with a focus on pelvic floor muscle training. Material and methods. A previous randomized controlled trial of 123 women aged 27-72 years found that three months of self-managing stress urinary incontinence with support from the Tat((R)) app was effective. We followed up the women in the app group (n=62) two years after the initial trial with the same primary outcomes for symptom severity (International Consultation on Incontinence Questionnaire Short Form) and condition-specific quality of life (ICIQ-Lower Urinary Tract Symptom Quality of Life) and compared the scores with those at baseline. Results. Of the 62 women, 61 and 46 (75.4%), respectively, participated in three-month and two-year follow-ups. Baseline data did not differ between responders and non-responders at follow-up. The mean decreases in International Consultation on Incontinence Questionnaire Short Form and ICIQ-Lower Urinary Tract Symptom Quality of Life scores after two years were 3.1 (95% confidence interval 2.0-4.2) and 4.0 (95% confidence interval 2.1-5.9), respectively. Of the 46 women, four (8.7%) rated themselves as very much better, nine (19.6%) as much better, and 16 (34.8%) as a little better. The use of incontinence protection products decreased significantly (p=0.04), and the proportion of women who felt they could contract their pelvic muscles correctly increased from 14/46 (30.4%) at baseline to 31/46 (67.4%) at follow-up (p<0.001). Conclusions. Self-management of stress urinary incontinence with support from the Tat((R)) app had significant and clinically relevant long-term effects and may serve as first-line treatment.

  • Troiano, Giuseppe
    et al.
    Caponio, Vito Carlo Alberto
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Gu, Xiaolian
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Lo Muzio, Lorenzo
    Sgaramella, Nicola
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Wang, Lixiao
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Expression of the long non-coding RNA HOTAIR as a prognostic factor in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 42, 73029-73036 p.Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Long noncoding RNAs (lncRNAs) are often dysregulated in cancer tissue and seem to play an important role in neoplastic processes. Recent studies have shown that the HOX transcript antisense intergenic RNA (HOTAIR) may play a role as a marker of prognosis in squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to perform a meta-analysis of studies focused on the prognostic role of HOTAIR in SCCHN.

    Results: At the end of the selection process, four studies were considered eligible for inclusion in the meta-analysis, comprising a total of 271 patients. Meta-analysis revealed that high expression of HOTAIR was associated with poor overall survival (HR, 1.90; 95% CI: [1.42, 2.53]; p < 0,0001), advanced tumor stage (OR, 3.44; 95% CI: [1.84, 6.43]; p < 0,001) and lymph-node metastasis (OR, 3.31; 95% CI: [1.24, 8.79]; p = 0,02).

    Materials and Methods: The literature search was performed in the following databases: PUBMED, SCOPUS, EMBASE and Web of Science, in order to find studies that met the inclusion criteria.

    Conclusions: Findings from this systematic review and meta-analysis revealed that HOTAIR represents a potential biomarker of prognosis in patients with squamous cell carcinoma of the head and neck.

  • Niklasson, André
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Dialogue Systems Using Web-based Language Tools2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Chatbots in commercial environments are on the rise with the release of several web-based language understanding tools. The vast majority of the dialogue systems deployed today uses very primitive state-machine architectures to model their interactions. These primitive approaches are reliable and easy to implement but the dialogue becomes very unnatural and the system always has the initiative in the conversation. The positive features of being easy to build, and the ability to easily retain control over the system normally supersedes the shortcomings.This thesis proposes a dialogue model that utilizes new approaches for dialogue modeling but aims to be easy to congure. The proposed dialogue management strategy is implemented in a prototype dialogue system. Developers are able to model their dialogues using an XML dialogue description. The system utilizes LUIS.ai, a recently launched web-based language tool for sentence analysis. LUIS.ai is evaluated together with the prototype dialogue system.i

  • Thomson, Suzanne E.
    et al.
    Charalambous, Chloe
    Smith, Carol-Anne
    Tsimbouri, Penelope M.
    Déjardin, Theophile
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Hart, Andrew M.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). The Centre for Cell Engineering, College of Medical, Veterinary and Life Sciences, University of Glasgow, University Avenue, Hillhead, Glasgow G128QQ, UK; Canniesburn Plastic Surgery Unit, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, UK.
    Riehle, Mathis O.
    Microtopographical cues promote peripheral nerve regeneration via transient mTORC2 activation2017In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 60, 220-231 p.Article in journal (Refereed)
    Abstract [en]

    Despite microsurgical repair, recovery of function following peripheral nerve injury is slow and often incomplete. Outcomes could be improved by an increased understanding of the molecular biology of regeneration and by translation of experimental bioengineering strategies. Topographical cues have been shown to be powerful regulators of the rate and directionality of neurite regeneration, and in this study we investigated the downstream molecular effects of linear micropatterned structures in an organotypic explant model. Linear topographical cues enhanced neurite outgrowth and our results demonstrated that the mTOR pathway is important in regulating these responses. mTOR gene expression peaked between 48 and 72 h, coincident with the onset of rapid neurite outgrowth and glial migration, and correlated with neurite length at 48 h. mTOR protein was located to glia and in a punctate distribution along neurites. mTOR levels peaked at 72 h and were significantly increased by patterned topography (p < 0.05). Furthermore, the topographical cues could override pharmacological inhibition. Downstream phosphorylation assays and inhibition of mTORC1 using rapamycin highlighted mTORC2 as an important mediator, and more specific therapeutic target. Quantitative immunohistochemistry confirmed the presence of the mTORC2 component rictor at the regenerating front where it co-localised with F-actin and vinculin. Collectively, these results provide a deeper understanding of the mechanism of action of topography on neural regeneration, and support the incorporation of topographical patterning in combination with pharmacological mTORC2 potentiation within biomaterial constructs used to repair peripheral nerves.

    Statement of Significance: Peripheral nerve injury is common and functionally devastating. Despite microsurgical repair, healing is slow and incomplete, with lasting functional deficit. There is a clear need to translate bioengineering approaches and increase our knowledge of the molecular processes controlling nerve regeneration to improve the rate and success of healing. Topographical cues are powerful determinants of neurite outgrowth and represent a highly translatable engineering strategy. Here we demonstrate, for the first time, that microtopography potentiates neurite outgrowth via the mTOR pathway, with the mTORC2 subtype being of particular importance. These results give further evidence for the incorporation of microtopographical cues into peripheral nerve regeneration conduits and indicate that mTORC2 may be a suitable therapeutic target to potentiate nerve regeneration.

  • Chen, Genqiang
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China.
    Wu, Guochao
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Alriksson, Björn
    Wang, Wei
    Hong, Feng F.
    Jönsson, Leif J.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bioconversion of waste fiber sludge to bacterial nanocellulose and use for reinforcement of CTMP paper sheets2017In: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 9, no 9, 458Article in journal (Refereed)
    Abstract [en]

    Utilization of bacterial nanocellulose (BNC) for large-scale applications is restricted by low productivity in static cultures and by the high cost of the medium. Fiber sludge, a waste stream from pulp and paper mills, was enzymatically hydrolyzed to sugar, which was used for the production of BNC by the submerged cultivation of Komagataeibacter xylinus. Compared with a synthetic glucose-based medium, the productivity of purified BNC from the fiber sludge hydrolysate using shake-flasks was enhanced from 0.11 to 0.17 g/(L x d), although the average viscometric degree of polymerization (DPv) decreased from 6760 to 6050. The cultivation conditions used in stirred-tank reactors (STRs), including the stirring speed, the airflow, and the pH, were also investigated. Using STRs, the BNC productivity in fiber-sludge medium was increased to 0.32 g/(L x d) and the DPv was increased to 6650. BNC produced from the fiber sludge hydrolysate was used as an additive in papermaking based on the chemithermomechanical pulp (CTMP) of birch. The introduction of BNC resulted in a significant enhancement of the mechanical strength of the paper sheets. With 10% (w/w) BNC in the CTMP/BNC mixture, the tear resistance was enhanced by 140%. SEM images showed that the BNC cross-linked and covered the surface of the CTMP fibers, resulting in enhanced mechanical strength.