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  • Kozlowski, Piotr
    et al.
    Orebro Univ, Sch Med Sci, Dept Med, Orebro, Sweden..
    Lennmyr, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Ahlberg, Lucia
    Univ Hosp Linkoping, Dept Hematol, Linkoping, Sweden..
    Bernell, Per
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden..
    Hulegårdh, Erik
    Sahlgrens Univ Hosp, Dept Hematol & Coagulat, Gothenburg, Sweden..
    Karbach, Holger
    Univ Hosp Umea, Ctr Canc, Dept Hematol, Umea, Sweden..
    Karlsson, Karin
    Skane Univ Hosp, Dept Hematol & Oncol, Lund, Sweden..
    Tomaszewska-Toporska, Beata
    Skane Univ Hosp, Dept Hematol & Oncol, Lund, Sweden..
    Åström, Maria
    Orebro Univ, Sch Med Sci, Dept Med, Orebro, Sweden..
    Hallböök, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden2017Inngår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 99, nr 2, 141-149 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ObjectivesOlder/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials. MethodsUsing Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85years, diagnosed with ALL 2005-2012. ResultsOf 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype. Philadelphia chromosome positivity (Ph+) occurred in 35%. Of the 155 B- and T-ALL patients, 80% were treated with intensive protocols, and 20% with a palliative approach. Higher age and WHO performance status 2 influenced the choice of palliation. Intensive, palliative, and both approaches resulted in complete remission rate 83/16/70% and 3-year overall survival (OS) 32/3/26%. The age-adapted protocol did not improve outcome. With intensive treatment, platelet count 35x10(9)/L and age 75years were adverse prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor in the 55-64 year age-group. ConclusionsWe report a high frequency of Ph+ in older/elderly patients, with no evidence of poorer outcome compared to Ph-negative disease. Overall prognosis for elderly patients with ALL remains dismal, despite the use of age-adapted treatment.

  • Shungin, Dmitry
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. 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 universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. 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 interactions2017Inngår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, nr 6, e1006812Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • Glorieux, Emile
    et al.
    Högskolan Väst, Institutionen för ingenjörsvetenskap, Avdelningen för produktionssystem (PS).
    Franciosa, Pasquale
    Warwick Manufacturing Group, University of Warwick, CV4 7AL Coventry, UK.
    Ceglarek, Darek
    Warwick Manufacturing Group, University of Warwick, CV4 7AL Coventry, UK.
    End-effector design optimisation and multi-robot motion planning for handling compliant parts2017Inngår i: Structural and multidisciplinary optimization (Print), ISSN 1615-147X, E-ISSN 1615-1488, 1-14 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The deformation of compliant parts during material handling is a critical issue that can significantly affect the productivity and the parts' dimensional quality. There are multiple relevant aspects to consider when designing end-effectors to handle compliant parts, e.g. motion planning, holding force, part deformations, collisions, etc. This paper focuses on multi-robot material handling systems where the end-effector designs influence the coordination of the robots to prevent that these collide in the shared workspace. A multi-disciplinary methodology for end-effector design optimisation and multi-robot motion planning for material handling of compliant parts is proposed. The novelty is the co-adaptive optimisation of the end-effectors' structure with the robot motion planning to obtain the highest productivity and to avoid excessive part deformations. Based on FEA, the dynamic deformations of the parts are modelled in order to consider these during the collision avoidance between the handled parts and obstacles. The proposed methodology is evaluated for a case study that considers the multi-robot material handling of sheet metal parts in a multi-stage tandem press line. The results show that a substantial improvement in productivity can be achieved (up to 1.9%). These also demonstrate the need and contribution of the proposed methodology.

  • Tidehag, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Protetik. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Iron absorption and iron status related to diet: an experimental and epidemiological study1995Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

  • Samuelsson, Marcus
    et al.
    Högskolan Väst, Institutionen för individ och samhälle, Avd för utbildningsvetenskap och språk.
    Arvola, Mattias
    Linköpings universitet.
    Nordvall, Mathias
    Stenliden, Linnea
    Linköpings universitet.
    Simuleringsbaserad undervisning som ett kompletterande inslag i lärarutbildningen vid Linköpings universitet2017Rapport (Annet vitenskapelig)
  • Disputas: 2017-11-14 13:15 hall B42, Uppsala
    Singh, Kailash
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Regulatory T cells in type 1 diabetes: the role of IL-35 in counteracting the disease2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Type 1 diabetes (T1D) is etiologically considered as an autoimmune disease, where insulin-producing β-cells are damaged by autoimmune attacks. Regulatory T (Treg) cells are immune homeostasis cells. In the present thesis I aimed to investigate the role of Treg cells and other immune cells in the early development of T1D. In order to do that, we first determined which immune cells that are altered at an early stage of the T1D development. We found that dendritic cells and plasmacytoid dendritic cells induce the initial immune response.

    Next, we investigated the role of Treg cells in multiple low dose streptozotocin (MLDSTZ) induced T1D and in NOD mice. We found that the numbers of Treg cells were increased in both MLDSTZ and NOD mice when the MLDSTZ mice were hyperglycemic. However, the increased Treg cells showed a decreased production of anti-inflammatory cytokines (IL-10, IL-35 and TGF-β) and an increased expression of pro-inflammatory cytokines (IFN-γ and IL-17a). These results revealed that Treg cells switch their phenotype under T1D conditions.

    IL-35 administration effectively prevented the development of, and reversed established MLDSTZ induced T1D. Treg cells from IL-35 treated mice showed an increased expression of the Eos transcription factor, accompanied by an increased expression of IL-35 and a decreased expression of IFN-γ and IL-17a. These data indicate that IL-35 administration counteracted the early development of T1D by maintaining the phenotype of the Treg cells. Furthermore, IL-35 administration reversed established T1D in the NOD mouse model by maintaining the phenotype of Treg cells, seemingly by inducing the expression of Eos. Moreover, the circulating level of IL-35 was significantly lowered in both new onset and long-standing T1D patients compared to healthy controls. In addition, patients with T1D with remaining C-peptide had significantly higher levels of IL-35 than patients lacking C-peptide, suggesting that IL-35 might prevent the loss of β-cell mass. In line with this hypothesis, we found that LADA patients had a higher proportion of IL-35+ tolerogenic antigen presenting cells than T1D patients.

    Subsequently, we determined the proportions of IL-35+ Treg cells and IL-17a+ Treg cells in T1D patients with diabetic nephropathy (DN), which were age, sex and BMI matched with healthy controls and T1D patients. The proportion of IL-35+ Treg cells was decreased in DN and T1D patients, but IL-17a+ Treg cells were more abundant than in healthy controls. Furthermore, we found that the number of Foxp3+ Treg cells was increased in the kidneys of MLDSTZ mice. However, infiltration of mononuclear cells was seen in kidneys of these mice. In addition, kidney tissues of IL-35 treated MLDSTZ mice did not show any mononuclear cell infiltration. These results demonstrate that IL-35 may be used to prevent mononuclear cell infiltration in kidney diseases.

    Our findings indicate that the numbers of Foxp3+ Treg cells are increased in T1D, but that these Treg cells fail to counteract the ongoing immune assault in islets and kidneys of hyperglycemic mice. This could be explained by a phenotypic shift of the Treg cells under hyperglycemic conditions. IL-35 administration reversed established T1D in two different animal models of T1D and prevented mononuclear cell infiltration in the kidneys by maintaining the phenotype of Treg cells.

  • Burraco, Pablo
    et al.
    CSIC, Donana Biol Stn, Dept Wetland Ecol, Ecol Evolut & Dev Grp, E-41092 Seville, Spain..
    Valdes, Ana Elisa
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Fysiologisk botanik. Stockholm Univ, Dept Ecol Environm & Plant Sci, SE-10691 Stockholm, Sweden..
    Johansson, Frank
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik.
    Gomez-Mestre, Ivan
    CSIC, Donana Biol Stn, Dept Wetland Ecol, Ecol Evolut & Dev Grp, E-41092 Seville, Spain..
    Physiological mechanisms of adaptive developmental plasticity in Rana temporaria island populations2017Inngår i: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 17, 164Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Adaptive plasticity is essential for many species to cope with environmental heterogeneity. In particular, developmental plasticity allows organisms with complex life cycles to adaptively adjust the timing of ontogenetic switch points. Size at and time to metamorphosis are reliable fitness indicators in organisms with complex cycles. The physiological machinery of developmental plasticity commonly involves the activation of alternative neuroendocrine pathways, causing metabolic alterations. Nevertheless, we have still incomplete knowledge about how these mechanisms evolve under environments that select for differences in adaptive plasticity. In this study, we investigate the physiological mechanisms underlying divergent degrees of developmental plasticity across Rana temporaria island populations inhabiting different types of pools in northern Sweden. Methods: In a laboratory experiment we estimated developmental plasticity of amphibian larvae from six populations coming from three different island habitats: islands with only permanent pools, islands with only ephemeral pools, and islands with a mixture of both types of pools. We exposed larvae of each population to either constant water level or simulated pool drying, and estimated their physiological responses in terms of corticosterone levels, oxidative stress, and telomere length. Results: We found that populations from islands with only temporary pools had a higher degree of developmental plasticity than those from the other two types of habitats. All populations increased their corticosterone levels to a similar extent when subjected to simulated pool drying, and therefore variation in secretion of this hormone does not explain the observed differences among populations. However, tadpoles from islands with temporary pools showed lower constitutive activities of catalase and glutathione reductase, and also showed overall shorter telomeres. Conclusions: The observed differences are indicative of physiological costs of increased developmental plasticity, suggesting that the potential for plasticity is constrained by its costs. Thus, high levels of responsiveness in the developmental rate of tadpoles have evolved in islands with pools at high but variable risk of desiccation. Moreover, the physiological alterations observed may have important consequences for both short-term odds of survival and long term effects on lifespan.

  • Thorburn, William
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Recordings of applanating force at constant intraocular pressure: development of a new technique and results obtained from a study of human eyes1972Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

  • Carling, Kenneth
    Högskolan Dalarna, Akademin Industri och samhälle, Mikrodataanalys.
    A comment on outlier detection and skewed distributions2017Rapport (Annet vitenskapelig)
    Abstract [en]

    It seems that a paper of mine appearing in Computational Statistics & Data Analysis (Carling, 2000) has prompted the development of outlier detection methods for highly skewed data. However, I wrote the paper in the spirit of Exploratory Data Analysis (Tukey, 1977) and I shared Tukey’s opinion, and I still hold it, that skewed data are better to be transformed for approximate symmetry prior to detection of outliers (or other data analyses).

  • Gylfe, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Studies on free amino acids in the pancreatic ß-cells.1974Doktoravhandling, med artikler (Annet vitenskapelig)
    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 universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Angiographic abnormalities in the urinary bladder wall after irradiation1973Doktoravhandling, monografi (Annet vitenskapelig)
  • Mjörndal, Tom
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Thiothixene: a study on its pharmacokinetics and pharmacological effects in animal and man1976Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

  • Jogenfors, Jonathan
    et al.
    Linköpings universitet, Institutionen för systemteknik, Informationskodning. Linköpings universitet, Tekniska fakulteten.
    Adán, Cabello
    Departamento de Física Aplicada II, Universidad de Sevilla, Sevilla, Spain.
    Larsson, Jan-Åke
    Linköpings universitet, Institutionen för systemteknik, Informationskodning. Linköpings universitet, Tekniska fakulteten.
    Comment on "Franson Interference Generated by a Two-Level System"2017Annet (Annet vitenskapelig)
    Abstract [en]

    In a recent Letter [Phys. Rev. Lett. 118, 030501 (2017)], Peiris, Konthasinghe, and Muller report a Franson interferometry experiment using pairs of photons generated from a two-level semiconductor quantum dot. The authors report a visibility of 66% and claim that this visibility “goes beyond the classical limit of 50% and approaches the limit of violation of Bell’s inequalities (70.7%).” We explain why we do not agree with this last statement and how to fix the problem.

  • Disputas: 2017-11-10 13:15 Häggsalen, Ångströmlaboratoriet, Uppsala
    Grandin, Martina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Tribology of Metal-Graphite Composites: A Study of Sliding Electrical Contact Surfaces2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    An environmentally sustainable production of electrical power is important for preserving the earth’s natural resources. In order to utilize this power as efficiently as possible, it is of great importance to minimize the losses, for example in sliding electrical contacts. A sliding electrical contact is where current is transferred from one rotating to one stationary component and power is lost due to friction and contact resistance. Also in some signal applications, high performance sliding contacts are crucial to ensure stable signal transfer with low noise. Although sliding electrical contacts are primarily designed for good electrical performance, the system will benefit also from optimization of the tribological properties.

    The aim of this thesis is to increase the fundamental knowledge of the tribological and electrical performance of metal-graphite composite materials for sliding electrical contacts. The influence of mechanical and electrical load was investigated. Different stationary materials, from pure copper to nanocomposite coatings, were tested against copper- and silver-graphites. Two complementary test setups were used, one with reciprocating and one with unidirectional sliding. Surface analysis was essential to gain deepened understanding of the influence of the interaction on the surfaces. Especially my novel imaging of cross-sections has advanced the level on knowledge in this research field.

    On the stationary material surface, a tribofilm forms with constituents from the metal-graphite and the surrounding atmosphere. Cross-sectioning reveals a material flow that indicates turbulence. Furthermore, the presence of oxides in the tribofilm is not necessarily detrimental for the contact resistance as long as there is also pure metal available. The presence of graphite is vital for low friction and wear. It is shown that the tribological and electrical behaviour of this system is only marginally influenced by the material selection of the stationary contact. Increasing the metal content in the composite, on the other hand, greatly reduces the contact resistance while there is no significant impact on friction and wear. The mechanical load has to be optimized to compromise between low wear (achieved with low load) and low contact resistance (achieved with high load). Pure mechanical tests show a lower friction and higher wear rate in comparison to tests with a five ampere current.

  • Jeppsson, Jan-Olof
    Umeå universitet, Medicinska fakulteten, Mikrobiologi.
    Structural studies on human transferrin1967Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

  • Ekberg, Kerstin
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Bernfort, Lars
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Karlsson, Nadine
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Linderoth, Catharina
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Persson, Jan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Arbetsgivares kostnader, åtgärder och anpassningar för sjuknärvarande och sjukfrånvarande medarbetare: samband med återgång i arbete och produktion2017Rapport (Annet vitenskapelig)
    Abstract [sv]

    Studien syftade till att undersöka vilka åtgärder arbetsgivare gör för sjukskrivna medarbetare och vilka kostnader arbetsgivare och samhället har i samband med sjuknärvaro och sjukfrånvaro.

    Totalt 3000 sjukskrivna personer i AFA Försäkrings register med diagnoserna psykiska besvär eller besvär i rörelseorganen fick ett informationsbrev och förfrågan om samtycke till att forskarna skulle få skicka en enkät till deras arbetsledare; 393 sjukskrivna gav samtycke. En  webbenkät skickades till dessa arbetsledare. Totalt 198 arbetsledare (50 %) till sjukskrivna personer besvarade enkäten.

    Resultaten visar att arbetsgivare genomför en rad olika åtgärder och anpassningar när en medarbetare blir sjukskriven. Analyserna visade att dessa åtgärder och anpassningar i viss mån beror på vem den sjukskrivne medarbetaren är. Åtgärder och anpassningar var vanligare för sjukskrivna med psykiska diagnoser, för högutbildade och för sjukskrivna i högkvalificerade yrken. Kvinnor fick i högre grad anpassningar och åtgärder såsom ändrade arbetsuppgifter och psykosocialt stöd jämfört med män.

    Demografiska faktorer visade sig ha mindre betydelse för om den sjukskrivne återgick i arbete eller ej. Multipla logistiska regressionsanalyser visade att åtgärder och anpassningar på arbetsplatsen hade signifikanta samband med en ökad chans för återgång i arbete. Resultaten visade också att för sjukskrivna medarbetare vars arbetsledare hade tagit många kontakter med andra aktörer, som HR-avdelningen, företagshälsan och/eller Försäkringskassan var sannolikheten lägre att den sjukskrivne medarbetaren återgick i arbete. Arbetsledare tog fler kontakter, om den sjukskrivne medarbetaren hade en psykisk diagnos.

    Sjuknärvaro och produktionsförlust före, under och efter sjukskrivningen skattades av arbetsledarna. Sammanlagt beräknades produktionsförlusterna till cirka SEK 100 000 per sjukskrivningsfall. Härutöver lägger arbetsgivare tid på att ta kontakter, genomföra åtgärder och anpassningar och organisera om arbetet. Arbetsledare hade mycket oklar eller saknade helt uppfattning om vad tid, åtgärder och anpassningar kostar, varför detta inte har kunnat analyseras närmare. De beräknade genomsnittliga kostnaderna till följd av produktivitetsförluster är således en underskattning av de faktiska kostnaderna för arbetsgivare.

    Studien visar att arbetsledares kunskap om vad sjuknärvaro och sjukfrånvaro kostar för verksamheten och för samhället är begränsad. En ökad kostnadsmedvetenhet skulle kunna stimulera till att större resurser läggs på att implementera policys för hälsofrämjande åtgärder och att utbilda arbetsledare i att hantera frågor om hälsa och arbetsförmåga på arbetsplatsen.

  • Lernmark, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Studies on insulin release from the isolated mouse islet1971Doktoravhandling, med artikler (Annet vitenskapelig)
    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 universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Danielsson, Adam
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Brännstrom, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Impact of Amyotrophic Lateral Sclerosis on Slow Tonic Myofiber Composition in Human Extraocular Muscles2017Inngår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 58, nr 9, 3708-3715 s.Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • Nordström, Malin
    et al.
    Linköpings universitet, Institutionen för datavetenskap. Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Informatik. Linköpings universitet, Filosofiska fakulteten. Karolinska Institutet, Karolinska Universitetssjukhuset, Innovationslabbet för eHälsa.
    Lagsten, Jenny
    Örebro Universitet samt Karolinska Universitetssjukhuset, Innovationslabbet för eHälsa.
    Kliniska Beslutsstöd: En konceptualisering med IT-goverance implikationer2016Rapport (Annet vitenskapelig)
    Abstract [sv]

    Rapporten innehåller en konceptualisering av begreppet kliniska beslutsstöd. Fem centrala frågor diskuteras och besvaras; vilket är ursprunget för kliniska beslutsstöd?, vad är kliniska beslutsstöd?, var existerar kliniska beslutsstöd?, vilken funktion/syfte har kliniska beslutsstöd?, vad är kontexten för kliniska beslutsstöd?, hur pratar vi om kliniska beslutsstöd?. Resultatet används som avstam för vidare forskning kring IT-governance för kliniska beslutsstöd. 

  • Björkstén, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    The nitroblue tetrazolium (NBT) test: a methodological and clinical study1974Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

  • Nordström, Malin
    et al.
    Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Informatik. Linköpings universitet, Filosofiska fakulteten.
    Lagsten, Jenny
    Karolinska Universitetssjukhuset och Örebro Universitet.
    Permert, Johan
    Karolinska Institutet.
    Klinisk IT-governance: Principer och språkbruk för klinisk verksamhet och informationssystem i samklang2016Rapport (Annet vitenskapelig)
    Abstract [sv]

    Vården befinner sig i en dynamisk transformeringsfas där ökad patientinvolvering, värdebaserad vård och personaliserad vård snabbt växer i betydelse. Detta kräver en förbättrad informationsbehandling i klinisk verksamhet, kvalitetsarbete, management samt för innovation och klinisk forskning. Rapporten visar att samma information idag hanteras i flera separata strukturer, vilket i framtiden skall kunna undvikas om vi, genom god organisering, kan skapa ändamålsenliga informationssystem för klinisk verksamhet.

    Vi delar problembilden med utredningen ”Nästa fas i e-hälsoarbetet”, men medan den utredningen fokuserar på statens roll som samordnare och normerare, fokusera vi på vårdgivarnas roll och vad dessa kan göra för att förbättra strukturer och processer mellan klinisk verksamhet och IT-verksamhet.

    Rapporten genomsyras av perspektivet informatik (informationssystem). Detta område har fått ökad uppmärksamhet i och med behovet av ökad semantisk interoperabilitet, då patienter vårdas i kedjor och nätverk av många vårdgivare, och det förväntas att informationen följer patienten. Den här rapporten handlar dock inte om semantisk interoperabilitet eller teknik/arkitektur, utan om hur vårdgivarna kan och bör organisera fram adekvata informationssystem. Samtidigt som man säkrar stabilitet i de cirka 12 500 informationssystem som används i Sverige i vården idag. Vi etiketterar detta klinisk IT-governance, för att betona det kritiska i behovet av samverkan mellan klinisk verksamhet och IT-verksamhet, för att dessa mål ska uppnås. I rapporten påvisas en komplexitet som kan förefalla avskräckande, men som vi menar är en realitet som måste hanteras. Det finns tyvärr inga Silver Bullets för att lösa behovet av informationsförsörjning. Det handlar om enträgenhet, systematiskt och hårt arbete.

    Rapporten bygger på tre studier där vi har undersökt; IT-governance hos vårdgivare i hela landet (L-ITG), hur det informatiska gapet kan överbryggas vid utveckling av kliniska beslutsstöd (BIG), samt behov av strukturer och arbetssätt för digital innovation i Innovationslabbet för eHälsa (Innovationslabbet) vid Karolinska Universitetssjukhuset. Vi som har skrivit rapporten har alla mångårig erfarenhet som forskare, praktiker och lärare inom medicin och/eller informatik.

    L-ITG visar att IT-governancefrågan har beaktats runt om i landet den senaste 10årsperioden. Befintliga informationssystem har kartlagts och 90 procent av landstingen har valt att införa en IT-governancemodell för att organisera samverkan mellan klinisk verksamhet och IT-verksamhet. Detta bör betraktas som en form av transformation, där den traditionella modellen med decentraliserat beslutsfattande kring informationssystem, är på väg att utvecklas till en modell för samverkan mellan klinisk verksamhet och IT-verksamhet. Med hjälp av modellen kan avvägningar göras mellan vårdgrenar, för att använda begränsade resurser på bästa sätt. Medan vissa landsting precis har börjat resan, är andra inne på 7-8 årscykeln, där införandet har övergått till regelrätt kvalitetsarbete. Vi ser dock att införandet av samverkansmodellen har brustit på en central punkt: Den delen av arbetet med informationssystem som ligger nära den kliniska verksamheten (användarstöd, utbildning, förbättringsarbete genom mallar/formulär, deltagande i upphandling osv.) har i många fall organiserats i IT-verksamheten istället för, som sig bör, i den kliniska verksamheten. Forskning och erfarenheter visar samstämmigt att en sådan organisering leder till lägre användaracceptans och lägre nytta av de investeringar som är gjorda i befintliga informationssystem. Användarmedverkan har en central betydelse för kvalitet och acceptans både vid utveckling och vid förvaltning av informationssystem. Detta i kombination med att det skett en intresseglidning från kliniker och forskare mot andra typer av informationssystem, t.ex. kvalitetsregister, gör att en samlad kraftansträngning krävs får att återerövra klinikernas engagemang för vårdgivarnas informationssystem. Dessa andra informationssystem innehåller ofta data som genomgått en valideringsprocess, ger en möjlighet att påverka systemen i kortare cykler samt förenar professionsgrenar över vårdgivargränser. Klinikerna och forskarnas engagemang krävs också för att utveckla och förvalta vårdgivarnas kliniska informationssystem. Vi föreslår därför ett antal konkreta åtgärder som bör genomföras för att öka det kliniska engagemanget, och därmed nyttan, av vårdgivarnas informationssystem. Dessa kan sammanfattas i följande fyra punkter;

    1. Positionera klinisk informatik som ett kompetensområde och utbilda hälsoinformatiker (kan både ha klinisk och/eller informatikbakgrund).
    2. Inrätta en CMIO-roll som får det yttersta ansvaret för klinisk informatik och som blir en ”speaking partner” till CIO avseende informatikfrågor.
    3. Återför den verksamhetsnära förvaltningen till de kliniska verksamheterna. Klinikerna ska inte ”sugas ifrån” den kliniska verksamheten, för att arbeta med IT.
    4. Använd ett språkbruk som är mer anpassat till klinisk verksamhet än traditionella IT-governancetermer.

    Studien av Innovationslabbet, visar att det finns ett behov av att skapa innovationsarenor där kliniska professioner, forskare, innovationsaktörer och IT-professioner kan mötas och utveckla idéer. Innovationslabbet för eHälsa, präglades av ett ”själv-tryck”, där en stor mängd idéer strömmade in från olika delar av SLL. Innovationslabbets idé var från början att finnas som en virtuell resurs, mot bakgrund av att innovation uppstår i den kliniska verksamheten. Vår studie visar dock att en sådan fysisk arena har en funktion och måste ges legitimitet och organisatorisk struktur om det ska vara görligt att stimulera och ta tillvara medarbetarnas innovationsidéer. Behovet av systemutvecklingskompetens hos landstingen är en fråga som får anses belagd via studien av Innovationslabbet, men också via LITG där de flesta pekade på behovet av egen utvecklingsförmåga. Inte nödvändigtvis för att utveckla informationssystem från grunden, utan för att göra t.ex. prototyper som grund för kravställning vid upphandling. Sammanfattningsvis föreslår vi införandet av en dynamisk förmåga hos vårdgivarna bestående av tre agila (lättrörliga) IT-governancemekanismer:

    1. Analytiska system för att uppfatta, filtrera, och kalibrera idéer, behov och möjligheter.
    2. Organisatoriska strukturer och processer för att eskalera idéer, behov och möjligheter till utveckling i Trippel Helix konstellationer (klinisk verksamhet, akademi och industri).
    3. Mekanismer för kontinuerlig sammansmältning av det nya med det befintliga genom kunskapshantering, överföringsarenor samt utbildning och systematiskt lärande.

    I denna miljö kan den kliniska informatiken som kompetensområde initialt ges möjlighet att formas, växa och ta ett större ansvar för semantisk interoperabilitet på olika nivåer samt utveckla kliniska informationsmodeller och kliniska beslutsstöd. Våra tre studier pekar alla mot att kliniska beslutsstöd är det som klinikerna efterfrågar. Av de cirka 30 innovationsprojekt vi studerat, utgjorde de allra flesta någon typ av beslutsstöd som integrerar kunskap från olika källor för att förmedla kunskap, och på sikt även ge individuella rekommendationer.

    I föreliggande rapport har vi sammanfattningsvis tre bidrag;

    1. Principer för att hantera stabilitet (mode 1-förmåga) och dynamik (mode 2-förmåga)
      • a. En övergripande bimodal modell för att hantera stabilitet respektive förändring i två skilda strukturer.
      • b. Principer och åtgärder för stärkt mode 1 förmåga
      • c. Förslag till indelning och innehåll i mode 2 förmåga
    2. Förslag till begrepp för området klinisk IT-governance som kan vara professionsöverskridande (kliniska professioner, forskare och IT-professioner)
    3. Positionering av klinisk informatik som kompetensområde.

    Vi pekar dessutom på att IT-governance är ett etablerat kunskapsområde, och det bör vara naturligt att detta kunskapsområde, påverkar fortsatt utveckling av ITgovernance i praktiken, på samma sätt som forskning inom medicin påverkar klinisk verksamhet.

    Med dessa principer, åtgärder och förslag till gemensamt språkbruk är det vår förhoppning att gemensamma informationssystem kan användas för klinisk verksamhet, klinisk forskning, för innovation samt i managementsyfte.

    Rapporten vänder sig till beslutsfattare hos vårdgivare, som har ansvar över kliniska informationssystem, såväl ur kliniskt som IT-mässigt perspektiv.

  • Schoultz, Bo von
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Studies on PZ, the pregnancy zone protein1974Doktoravhandling, med artikler (Annet vitenskapelig)
    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 universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Counter-current distribution of interacting molecules: simulation of distribution behaviour and application to protein-protein interactions1981Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

  • Disputas: 2017-10-26 09:00 Hugo Theorell, Norra entrén, Linköping
    Klintström, Eva
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Image Analysis for Trabecular Bone Properties on Cone-Beam CT Data2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Trabecular bone structure as well as bone mineral density (BMD) have impact on the biomechanical competence of bone. In osteoporosis-related fractures, there have been shown to exist disconnections in the trabecular network as well as low bone mineral density. Imaging of bone parameters is therefore of importance in detecting osteoporosis. One available imaging device is cone-beam computed tomography (CBCT). This device is often used in pre-operative imaging of dental implants, for which the trabecular network also has great importance.

    Fourteen or 15 trabecular bone specimens from the radius were imaged for conducting this in vitro project.

    The imaging data from one dual-energy X-ray absorptiometry (DXA), two multi-slice computed tomography (MSCT), one high-resolution peripheral quantitative computed tomography (HR-pQCT) and four CBCT devices were segmented using an in-house developed code based on homogeneity thresholding. Seven trabecular microarchitecture parameters, as well as two trabecular bone stiffness parameters, were computed from the segmented data. Measurements from micro-computed tomography (micro-CT) data of the same bone specimens were regarded as gold standard.

    Correlations between MSCT and micro-CT data showed great variations, depending on device, imaging parameters and between the bone parameters. Only the bone-volume fraction (BV/TV) parameter was stable with strong correlations. Regarding both HR-pQCT and CBCT, the correlations to micro-CT were strong for bone structure parameters as well as bone stiffness parameters. The CBCT device 3D Accuitomo showed the strongest correlations, but overestimated BV/TV more than three times compared to micro-CT. The imaging protocol most often used in clinical imaging practice at our clinic demonstrated strong correlations as well as low radiation dose.

    CBCT data of trabecular bone can be used for analysing trabecular bone properties, like bone microstructure and bone biomechanics, showing strong correlations to the reference method of micro-CT. The results depend on choice of CBCT device as well as segmentation method used. The in-house developed code based on homogeneity thresholding is appropriate for CBCT data. The overestimations of BV/TV must be considered when estimating bone properties in future clinical dental implant and osteoporosis research.

  • Wirell, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Binding of radiographic contrast media to serum proteins: a clinical and experimental investigation of their adverse effects through influence on active steroid hormone levels1982Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

  • Benzelstierna, Lars
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Teologiska fakulteten.
    Dissertatio historico-theologica, historiolam fratrum Bohemorum eorvmqve dissensvm a Zinzendorffianis exponens, quam cum consensu venerandæ facultatis theologicæ, in regia academia Upsaliensi, præside ... Laurentio Benzelstierna ... publico examini modeste submittit Gunnarus Follén Sv. filius, Ostro-Gothus. In audit. Carol. maj. die I. Julii, anni MDCCLII. horis ante meridiem solitis.1752No name for locale no (Annet vitenskapelig)
  • Benzelstierna, Lars
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Teologiska fakulteten.
    Dissertatio theologica, de peccato in spiritum sanctum, quam, cum consensu ... facultatis theologicæ, in regia academia Upsaliensi præside ... Laurentio Benzelstjerna ... publico examini modeste submittit Gabriel Lyrberg V. Gothus. In audit. Carol. maj. die [XI] Junii anni MDCCLII. horis ante meridiem solitis.1752No name for locale no (Annet vitenskapelig)
  • Benzelstierna, Lars
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Teologiska fakulteten.
    Dissertationem hist.-theologicam, de cognitione historiæ ecclesiasticæ ecclesiæ ministro necessaria, ex consensu ... facult. theol. in reg. acad. Ups. præside ... Laurentio Benzelstierna ... publico examini submittit Ioannes Fryksell Wermelandus. In audit. Car. maj. d. [27] Nov. MDCCLI. horis a. m. solitis.1751No name for locale no (Annet vitenskapelig)
  • Benzelstierna, Lars
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Teologiska fakulteten.
    Dissertatio theologica, munera ministerii ecclesiastici foeminis abjudicata evincens, quam, consent. max. venerand. fac. theol. in reg. acad. Upsal. præside ... Laurentio Benzelstierna ... publico examini offert, stipendiarius Zedritzianus, Johannes Wenström, Uplandus. In audit. Carol. maj. die [XVI] Nov. MDCCLI. h. a. m. s.1751No name for locale no (Annet vitenskapelig)
  • Benzelstierna, Lars
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Teologiska fakulteten.
    Specimine academico discrimen inter confessionem Augustanam invariatam et variatam, consentiente ... facult. theolog. in reg. acad. Upsaliensi, præside ... Laurentio Benzelstierna ... publice ventilandam sistit Nicolaus Ascher, Vermelandus, in aud. Carol. maj. die [I.] Julii. anni MDCCLI. H. A. M. S.1751No name for locale no (Annet vitenskapelig)
  • Benzelstierna, Lars
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Teologiska fakulteten.
    Specimine academico necessitatem reformationis Lutheranæ, ex consensu ven. facult. theol. in reg. acad. Ups. præside ... Laurentio Benzelstierna ... publice examinandam sistit Petrus Arrhenius Larsson, Uplandus, in audit. Carol. maj. die [III Octobr.] anni MDCCL.1750No name for locale no (Annet vitenskapelig)
  • Benzelstierna, Lars
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Teologiska fakulteten.
    Exercitium academicum, de symbolo Athanasiano, ex consensu ven. facult. theol. in regia academia Upsaliensi, præside ... Laur. Benzelstierna ... publico examini modeste submittit, Johannes Hamberg, v. d. m. Medelpadus, in audit. Carol. maj. die VI. Junii, anni MDCCXLIX, horis, ante meridiem, solitis.1749No name for locale no (Annet vitenskapelig)
  • Benzelstierna, Lars
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Filosofiska fakulteten.
    Diatriba philologica, de pentathlou, seu certaminum gymnicorum apud Græcos, origine, cum adplicatione ad res patrias, cujus partem primam, indulg. ampliss. Facult. Philos. in illustri athenæo Upsalensi, præside, ... Laur. Benzelstierna, ... publico examini modeste subjicit ... Christianus Rosbeck, Uplandus. in audit. Carol. maj. die V. Nov. MDCCXLVIII1748No name for locale no (Annet vitenskapelig)
  • Benzelstierna, Lars
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Teologiska fakulteten.
    Dissertatio historico-theologica, de symbolo apostolico, quam, consent. vener. facult. theol. in regia academia Upsaliensi, præside ... Laurentio Benzelstierna ... publico examini modeste subjicit Petrus Wastenius, Cuprimontano-Dalekarlus. In audit. Carol. maj. ad d. XXX Junii. anni MDCCXLVIII. H. a. m. s.1748No name for locale no (Annet vitenskapelig)
  • Benzelstierna, Lars
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Teologiska fakulteten.
    Schediasma de Juliano imperatore vere apostata contra Arnoldum et observatores Halenses quod, consentiente vener. facult. theol. in incluta academia Upsaliensi, præside ... Laur. Benzelstierna ... stipendiarius Helmfeldianus, Ulricus D. Voltemat, in audit. Carol major. d. XVIII. Maji. anni MDCCXLVIII.1748No name for locale no (Annet vitenskapelig)
  • Bucht, Gösta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Clinical and etiological studies on dementia of Alzheimer type and multiinfarct dementia1983Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

  • Disputas: 2017-11-10 09:15 B41, Uppsala
    Åkerbladh, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Palladium(0)-Catalysed Carbonylative Multicomponent Reactions: Synthesis of Heterocycles and the Application of Quinolinyl Pyrimidines as Enzyme Inhibitors2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Palladium-catalysed carbonylative multicomponent reactions have proven useful for the synthesis of structurally diverse compounds. Carbon monoxide serves as an atom-efficient, one-carbon building block, which allows for further structural elaboration of the carbonyl compound. By varying the components of the carbonylative multicomponent reaction, considerable product diversity can readily be attained. However, due to the reluctance to use toxic CO gas, considerable efforts have been directed at exploring non-gaseous approaches. The work described in this thesis has mainly focused on the development of palladium(0)-catalysed, carbonylative multicomponent synthetic methodology, using the non-gaseous CO source molybdenum hexacarbonyl, in the synthesis of heterocycles and other biologically relevant functional groups.

    The first part of this work describes the development of a non-gaseous carbonylative Sonogashira cross-coupling of bifunctional ortho-iodoanilines and terminal alkynes. Where 4-quinolones were synthesised via a carbonylation/cyclisation sequence. Using a similar synthetic strategy, three different N-cyanobenzamide intermediates were prepared by palladium-catalysed carbonylative couplings of various aryl halides and bromides and cyanamide. The formed intermediates provided a basis for further chemical transformations. First, ortho-iodoanilines were carbonylatively coupled with cyanamide and subsequently cyclised to yield heterocyclic 2-aminoquinazolinones. Next, building on those findings, the same synthetic strategy was applied to ortho-halophenols to provide a highly convenient domino carbonylation/cyclisation method for the preparation of benzoxazinones. The developed method was used to evaluate the efficiency of various non-gaseous CO sources. Third, the palladium-catalysed carbonylative synthesis of N-cyanobenzamides, was used to produce biologically relevant N-acylguanidines with considerable product diversity. Finally, one of the developed carbonylative methodologies was used in the preparation of potential NDH-2 inhibitors based on a quinolinyl pyrimidine scaffold. The prepared compounds were biologically evaluated in terms of inhibition of oxidoreductase NDH-2 and antibacterial activity on Gram-negative bacteria, S. aureus and Mtb. The biological evaluation revealed that some of the quinolinyl pyrimidines exerted inhibitory activity on the NDH-2 enzyme and possessed antibacterial properties.

    The work described in this thesis has been devoted to the development of non-gaseous one-pot, multicomponent carbonylation/cyclisation and carbonylation/amination reactions. The described methods offer highly attractive synthetic strategies that can be of great value to synthetic and medicinal chemists.

  • Abelsson, Anna
    Karlstads universitet, Institutionen för hälsovetenskaper.
    Simulering som lärande inom prehospital akutsjukvård2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [sv]

    Den prehospitala akutsjukvården är ett komplext kunskapsfält som innebär att vårdaren skall kunna bemöta patient och närstående, bedöma skada, sjukdom och den aktuella situationen samt avgöra vilka vårdåtgärder som skall prioriteras.

    Patientens lidande kan lindras genom att vårdaren tränar färdigheter i ett prehospitalt kontext. Detta främjar en god och säker vård samt stärker patientens möjligheter till överlevnad.

    Resultatet visar på behovet av simulering inom prehospital akutsjukvård. Med simulering lär sig vårdaren att hantera realistiska, dynamiska och komplexa vårdsituationer, vilket skapar kunskaper, färdigheter och erfarenheter av omhändertagande av patient drabbad av högenergitrauma. Simuleringens utformning och miljö skapar förutsättningar för lärandet vilket framkommer i interventionsstudien.

    Utifrån resultatet i föreliggande forskning utvecklas en modell för lärande med hjälp av simulering.

  • Berg, Jessica
    et al.
    Statens väg- och transportforskningsinstitut, Samhälle, miljö och transporter, SAMT, Mobilitet, aktörer och planering, MAP.
    Ihlström, Jonas
    Statens väg- och transportforskningsinstitut, Trafik och trafikant,TRAF, Trafikanttillstånd, TIL.
    Kollektivtrafikens betydelse för mobilitet och vardagsaktiviteter hos hushåll på landsbygd: intervjustudie2017Rapport (Annet vitenskapelig)
    Abstract [sv]

    VTI har fått i uppdrag av regeringen att genomföra en studie om effektiva och innovativa lösningar som kan öka medborgarnas vilja och möjlighet att utnyttja kollektivtrafiken på landsbygd. Denna studie är en delstudie inom uppdraget och syftar till att synliggöra lokala exempel på hur tillgången till transporter tillgodoser behov av mobilitet och deltagande i vardagsaktiviteter hos personer som bor på landsbygd. Följande frågor ska besvaras:

    1) Vilka för- och nackdelar beskrivs med att bo på landsbygd?

    2) Hur används olika transportsätt?

    3) I vilket mån kan kollektivtrafik möta deras mobilitetsbehov?

    Det empiriska materialet består av intervjuer med personer från 14 hushåll boende i landsbygder som kan definieras som tätortsnära enligt före detta Glesbygdsverkets definition. Landsbygderna ligger i Kinda kommun i Östergötland, Falun i Dalarna och Östersunds i Jämtland. Resultatet presenterar positiva och negativa aspekter med att bo på landsbygd, användandet av olika transportmedel, upplevda begränsningar och fördelar med att använda kollektivtrafik, bilens betydelse och informanternas förslag på lösningar som kan öka användningen av kollektivtrafik. Utifrån resultatet föreslås ett antal åtgärder och förbättringar som skulle kunna öka möjligheten att resa med kollektivtrafik och minska bilresor: Kollektivtrafik som binder ihop landsbygder med knutpunkter för att öka tillgängligheten till starka stråk; samordning mellan skolresor och allmän kollektivtrafik; tillgång till service och handel vid knutpunkter; samordning mellan län för att kunna erbjuda effektiv kollektivtrafik till huvudorter med hänsyn till geografisk närhet snarare än administrativa gränser; integrera ett brett utbud av olika former av mobilitet; bilpool, samåkning, allmän- och efterfrågestyrd kollektivtrafik och hyrcykelsystem för att hela reskedjan ska fungera.

  • Freij, Lennart
    et al.
    Wall, Stig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    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 clinic1977Doktoravhandling, monografi (Annet vitenskapelig)
  • Samuelson, Gösta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    An epidemiological study of child health and nutrition in a northern Swedish county1971Doktoravhandling, med artikler (Annet vitenskapelig)
    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 universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Gundale, Michael J.
    Nitrogen enrichment impacts on boreal litter decomposition are driven by changes in soil microbiota rather than litter quality2017Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 4083Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • Roos, Anna
    Utförare miljöövervakning, Naturhistoriska riksmuseet, NRM.
    Fiskgjuse - Miljögiftsbelastning i ägg insamlade i Sverige2013Rapport (Annet vitenskapelig)
    Abstract [sv]

    Inom ramen för Projekt fiskgjuse har ägg från Sverige, framför allt södra Sverige, analyserats med avseende på klorerade, bromerade och fluorerade ämnen samt tungmetaller, metylkvicksilver och selen. Dessutom har äldre analysdata avseende kvicksilver datalags och inkorporerats i denna rapport.

    Resultat:

    Sju ägg som tidigare analyserats för Hg analyserades på nytt för att se om analysresultaten är jämförbara, vilket de var. Därmed kunde gamla och nya resultat avseende kvicksilver läggas ihop i en trendanalys. Halterna av kvicksilver i de analyserade äggen (n=211) har minskat med ca 2,1% årligen sedan 1960-talet. Halter överstigande 500 ng/g våtvikt (v.v.) i ägg kan förknippas med negativa effekter på reproduktionen hos vissa rovfåglar. Elva procent av äggen år 1964-1986 hade halter överskridande 500 ng/g v.v., men inget av de 20 ägg som analyserats från 2008-2013 överskred detta värde.

    Halterna av selen vs kvicksilver (n=29) på molviktsbasis visar på ett överskott av selen. En jämförelse mellan metylkvicksilver och totalkvicksilver visade att så gott som allt kvicksilver i äggen är av formen metylkvicksilver. Även halterna av koppar, zink och mangan har minskat i de analyserade äggen (mellan 0,9-2,2% årligen, n=29). Selen visade på en tendens till minskning, dock inte statistiskt signifikant.

    Samtliga analyserade pesticider har också minskat över tid, med ca 6-10% årligen (HCB, transnonaklordan, transklordan, cis-klordan, p,p´-DDE, p,p´-DDE och p,p´-DDD, n=60). Även 22 analyserade CB-kongener minskade i halt över tid, med mellan 3-8% årligen (n=60).

    De sex BDEs som fanns i mätbara halter i samtliga ägg (BDE-28, -47, -99, -100, -153, och -154) ökade i halt fram till 2001 och därefter sågs en minskning för tre av dem (BDE-47, -99 och -100). BDE-28, -153 och -154 har inte minskat i halt sedan 2001 (n=60). Trots en minskning av tre kongener sedan 2001 så är medelhalten ΣBDE i äggen från 2013 högre än de från början av tidsserien (1960-talet).

    Trettio ägg från 1997-2013 har analyserats för 16 perfluorerade/högfluorerade ämnen (PFAS) inom projektet: de perfluorerade karboxylsyrorna (PFCA) PFBA, PFPePA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA, PFHxDA och PFOcDA samt de perfluorerade sulfonsyrorna (PFSA) PFHxS, PFOS och PFDS Nio föregångarämnen (s.k. prekursorer) analyserats, 5:3 FTCA, 6:2 FTUCA, 7:3 FTCA, 8:2 FTUCA, 10:2 FTUCA, N-MeFOSA, N-EtFOSA, N-MeFOSE och N-EtFOSE. Nästan alla ägg hade halter under detektionsgränsen avseende de kortkedjiga karboxylaterna PFBA, PFPePA, PFHxA, PFHpA, samt PFOA liksom samtliga prekursorer förutom 7:3 FTCA. PFOS var det mest dominerande ämnet, andelen PFOS vs PFAS var i snitt 72% (43-95%). Halterna PFOS låg mellan 12-632 ng/g v.v. Det finns rapport om att 100 ng PFOS/g ägg är den lägsta halt (LOEL) som ger negativ påverkan på häckningsresultatet hos höns. I denna studie hade 40% av fiskgjuseäggen från 2013 halter över 100 ng/g v.v. och fortsatt övervakning av dessa ämnen är önskvärt.

    Halterna av ΣPFCA visade på en tendens till ökning, dock inte statistiskt signifikant (p<0,08) medan ΣPFSA låg stabilt över tidsperioden 1997-2013 och fortsatt övervakning av dessa ämnen är önskvärt liksom PBDEs mf

  • Janunger, Karl-Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Benign and malignant gastric mucosal changes after partial gastrectomy1978Doktoravhandling, med artikler (Annet vitenskapelig)
    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 universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Amnesia and emotional arousal1984Doktoravhandling, monografi (Annet vitenskapelig)
    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 universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ureteral stones: an experimental and clinical study of the mechanism of the passage and arrest of ureteral stones1968Doktoravhandling, monografi (Annet vitenskapelig)
  • Disputas: 2017-11-15 13:00 Visualization Studio VIC, Stockholm
    Saikia, Himangshu
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Comparison and Tracking Methods for Interactive Visualization of Topological Structures in Scalar Fields2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Scalar fields occur quite commonly in several application areas in both static and time-dependent forms. Hence a proper visualization of scalar fieldsneeds to be equipped with tools to extract and focus on important features of the data. Similarity detection and pattern search techniques in scalar fields present a useful way of visualizing important features in the data. This is done by isolating these features and visualizing them independently or show all similar patterns that arise from a given search pattern. Topological features are ideal for this purpose of isolating meaningful patterns in the data set and creating intuitive feature descriptors. The Merge Tree is one such topological feature which has characteristics ideally suited for this purpose. Subtrees of merge trees segment the data into hierarchical regions which are topologically defined. This kind of feature-based segmentation is more intelligent than pure data based segmentations involving windows or bounding volumes. In this thesis, we explore several different techniques using subtrees of merge trees as features in scalar field data. Firstly, we begin with a discussion on static scalar fields and devise techniques to compare features - topologically segmented regions given by the subtrees of the merge tree - against each other. Second, we delve into time-dependent scalar fields and extend the idea of feature comparison to spatio-temporal features. In this process, we also come up with a novel approach to track features in time-dependent data considering the entire global network of likely feature associations between consecutive time steps.The highlight of this thesis is the interactivity that is enabled using these feature-based techniques by the real-time computation speed of our algorithms. Our techniques are implemented in an open-source visualization framework Inviwo and are published in several peer-reviewed conferences and journals.

  • Disputas: 2017-11-14 10:00 sal 14, hus 5, Kräftriket, Stockholm
    Neuner, Christoph
    Stockholms universitet, Naturvetenskapliga fakulteten, Matematiska institutionen.
    On Supersingular Perturbations2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis consists of four papers and deals with supersingular rank one perturbations of self-adjoint operators and their models in Hilbert or Pontryagin spaces. Here, the term supersingular describes perturbation elements that are outside the underlying space but still obey a certain regularity conditions.

    The first two papers study certain Sturm-Liouville differential expressions that can be realised as Schrödinger operators. In Paper I we show that for the potential consisting of the inverse square plus a comparatively well-behaved term we can employ an existing model due to Kurasov to describe these operators in a Hilbert space. In particular, this approach is in good agreement with ODE techniques.

    In Paper II we study the inverse fourth power potential.While it is known that the ODE techniques still work, we show that the above model fails and thus that there are limits to the above operator theoretic approach.

    In Paper III we concentrate on generalising Kurasov's model. The original formulation assumes that the self-adjoint operator is semi-bounded, whereas we drop this requirement. We give two models with a Hilbert and Pontryagin space structure, respectively, and study the connections between the resulting constructions.

    Finally, in Paper IV, we consider the concrete case of the operator of multiplication by the independent variable, a self-adjoint operator whose spectrum covers the real line, and study its perturbations. This illustrates some of the formalism that was developed in the previous paper, and a number of more explicit results are obtained, especially regarding the spectra of the appearing perturbed operators.

  • Disputas: 2017-11-14 10:00 William-Olssonsalen, Geovetenskapens hus, Stockholm
    Uzdavinys, Povilas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Establishing the molecular mechanism of sodium/proton exchangers2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Sodium/proton exchangers are ubiquitous secondary active transporters that can be found in all kingdoms of life. These proteins facilitate the transport of protons in exchange for sodium ions to help regulate internal pH, sodium levels, and cell volume. Na+/H+ exchangers belong to the SLC9 family and are involved in many physiological processes including cell proliferation, cell migration and vesicle trafficking. Dysfunction of these proteins has been linked to physiological disorders, such as hypertension, heart failure, epilepsy and diabetes.

    The goal of my thesis is to establish the molecular basis of ion exchange in Na+/H+ exchangers. By establishing how they bind and catalyse the movement of ions across the membrane, we hope we can better understand their role in human physiology.

    In my thesis, I will first present an overview of Na+/H+ exchangers and their molecular mechanism of ion translocation as was currently understood by structural and functional studies when I started my PhD studies. I will outline our important contributions to this field, which were to (i) obtain the first atomic structures of the same Na+/H+ exchanger (NapA) in two major alternating conformations, (ii) show how a transmembrane embedded lysine residue is essential for carrying out electrogenic transport, and (iii) isolate and recorde the first kinetic data of a mammalian Na+/H+ exchanger (NHA2) in an isolated liposome reconstitution system.

  • Disputas: 2017-11-10 09:00 Sal A, byggnad 23, Umeå
    Löfgren, Hans O.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Preventive psychosocial parental and school programmes in a general population2017Doktoravhandling, med artikler (Annet vitenskapelig)
    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.