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  • 3751.
    Ådemo, Ida
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Tid- och temperaturoptimering av lipoproteinlipas-aktivitet: -   en studie på Soleus och Vastus lateralis hos möss2012Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 3752.
    Ådén, Jörgen
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    NMR studies of protein dynamics and structure2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Enzymes are extraordinary molecules that can accelerate chemical reactions by several orders of magnitude. With recent advancements in structural biology together with classical enzymology the mechanism of many enzymes has become understood at the molecular level. During the last ten years significant efforts have been invested to understand the structure and dynamics of the actual catalyst (i. e. the enzyme). There has been a tremendous development in NMR spectroscopy (both hardware and pulse programs) that have enabled detailed studies of protein dynamics. In many cases there exists a strong coupling between enzyme dynamics and function. Here I have studied the conformational dynamics and thermodynamics of three model systems: adenylate kinase (Adk), Peroxiredoxin Q (PrxQ) and the structural protein S16. By developing a novel chemical shift-based method we show that Adk binds its two substrates AMP and ATP with an extraordinarily dynamic mechanism. For both substrate-saturated states the nucleotide-binding subdomains exchange between open and closed states, with the populations of these states being approximately equal. This finding contrasts with the traditional view of enzyme-substrate complexes as static low entropy states. We are also able to show that the individual subdomains in Adk fold and unfold in a non-cooperative manner. This finding is relevant from a functional perspective, since it allows a change in hydrogen bonding pattern upon substrate-binding without provoking global unfolding of the entire enzyme (as would be expected from a two-state folding mechanism). We also studied the structure and dynamics of the plant enzyme PrxQ in both reduced and oxidized states. Experimentally validated structural models were generated for both oxidation states. The reduced state displays unprecedented μs-ms conformational dynamics and we propose that this dynamics reflects local and functional unfolding of an α-helix in the active site. Finally, we solved the structure of S16 from Aquifex aeolicus and propose a model suggesting a link between thermostability and structure for a mesophilic and hyperthermophilic protein pair. A connection between the increased thermostability in the thermophilic S16 and residual structure in its unfolded state was discovered, persistent at high denaturant concentrations, thereby affecting the difference in heat capacity difference between the folded and unfolded state. In summary, we have contributed to the understanding of protein dynamics and to the coupling between dynamics and catalytic activity in enzymes.

  • 3753.
    Ådén, Jörgen
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wallgren, Marcus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Storm, Patrik
    Weise, Christoph
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Christiansen, Alexander
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Schröder, Wolfgang
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Funk, Christiane
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wolf-Watz, Magnus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Arabidopsis thaliana peroxiredoxin Q is extraordinarily dynamic on the μs-ms timescaleManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Peroxiredoxin Q (PrxQ) isolated from Arabidopsis thaliana belongs to a family of redox enzymes called peroxiredoxins, which are thioredoxin- or glutaredoxin dependent peroxidases acting to reduce peroxides and in particular hydrogen peroxide. PrxQ cycles between an active reduced state and an inactive oxidized state during its catalytic cycle. The catalytic mechanism involves a nucleophilic attack of the catalytic cysteine on hydrogen peroxide to generate a sulfonic acid intermediate with a concerted release of a water molecule. This intermediate is subsequently relaxed by the reaction of a second cysteine, denoted as the resolving cysteine, generating an intermolecular disulphide bond to expel a second water molecule into solution. PrxQ is finally recycled to the active state by a thioredoxin dependent reduction. Previous structural studies of PrxQ homologues have provided the structural basis for the switch between reduced and oxidized conformations. Here we have performed a detailed study of the structure and dynamics of PrxQ in both the oxidized and reduced state. Reliable and experimentally validated structural models of PrxQ in both oxidation states were generated using homology based modeling. Model-free analyses of NMR spin relaxation show that PrxQ is monomeric in both oxidation states. As evident from fast R2 relaxation rates the reduced form of PrxQ undergoes unprecedented dynamics on the slow μs-ms timescale. The ground state of the conformational dynamics is likely the stably folded reduced state as implied by circular dichroism spectroscopy. We speculate that the extensive dynamics is intimately related to the catalytic function of PrxQ.

  • 3754.
    Åhlén, Karina
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Collagen-binding integrin α2β1 activity in vivo and in vitro: Effects of platelet-derived growth factor-BB1998Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The expression of integrins by two cell clones from a rat colon carcinoma was investigated. Cloned cells that gave rise to regressive tumors, but not cells that gave rise to progressive, lethal, tumors, adhered to interstitial collagens through the integrin α2β1, although both cell types expressed it. These data suggest that the apparent activity of α2β1 is important for tumorinvasiveness.

    Inhibition of the α2β1 integrin in rat paw skin lead to a lowering of the interstitial fluid pressure (PIF). an effect that could be overcome by platelet-derived growth factor-BB (PDGF-BB).

    PDGF-BB could stimulate the synthesis of the α2, but not α1, α3 or β1 integrin chains in human AG1518 fibroblasts.

    PDGF-BB also stimulated cell spreading and induced a rapid and transientrelocalization of α2β1 in AG1518 fibroblasts. The relocalization was dependent on phosphatidylinositol 3-kinase (PI3-K) and protein kinase C (PKC), and involved disassembly of focal adhesions as seen in interference reflection microscopy (IRM). The mobility of β1-integrins in the cell membrane was increased in cells stimulated with PDGF-BB.

    PDGF-BB-stimulated collagen gel contraction, as well as the induction of a rise in cytoplasmic free calcium [Ca2+]i were shown to depend on PI3-K. The experimental anti-inflamatory drug α-trinositol induced an increase in [Ca2+]i and could restore PI3-K-dependent chemotaxis towards PDGF-BB as well as the lowering of PIF induced bv inhibitors of PI3K.

    In conclusion: α2β1 is implicated in invasiveness of tumor cells in vivo, and in the maintenance of interstitial fluid pressure (PIF). PDGF-BB is shown to regulate PIF, to stimulate synthesis of the integrin α2 chain, and to modulate cytoskeletal interactions of α1- integrins. The maintenance of PIF, as well as PDGF-BB-stimulation of collagen gel contraction, induction of integrin reorganization from focal adhesions, and induction of a calcium response, was dependent on an activation of PI3-K. PI3-K is hypothesized to mediate these effects at least in part through induction of a rise in [Ca2+]i.

  • 3755. Åkesson, Matilda
    The relationship between abdominal-height, energy consumption and glucose metabolism in obese children and adolescents.2016Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [en]

    Diabetes type-2 and cardiovascular diseases are some of the consequences of obesity. Body Mass Index (BMI) is the most common tool for defining obesity, but measurement of the abdominal-height is something new that might work better for definition of obesity. In this study, the aim was to find out whether there was a relationship between abdominal-height, glucose metabolism and resting energy expenditure in obese children and adolescents. Furthermore, to investigate if the abdominal-height was a more appropriate tool for the definition of obesity than BMI.A retrospective study was made on 43 obese children and adolescents. Several measurements of their body composition was obtained. They had also made an oral glucose tolerance test, an indirect respiratory calorimetry, had their abdominal-height measured and made a Bodpod analysis. The patients were divided into two groups (Group 1 and 2) based on their abdominal-height, and from the same patients, two other groups were made based on their BMI (Group A and B). The patients in Group 1, with the higher abdominal-height than those in Group 2, also in average had a higher age, weight, height, BMI, fat mass and larger waist circumference and hip circumference. Their resting energy expenditure, i.e. RMR and respiratory quotient (RQ) were lower, and so were their fat-free mass. The waist/hip-ratio was very similar in the two groups. During the oral glucose tolerance test, Group 1 had a statistically significant higher number of patients with impaired glucose tolerance than Group 2. Similar differences could be seen between Group A and Group B, where Group A was comparable to Group 1 and Group B to Group 2. However, no statistically significance could be seen comparing the two groups on the impaired glucose tolerance test.

  • 3756.
    Ås, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Active dose selection and dose-response modeling for quantitative high-throughput screening (qHTS)2016Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    This master thesis studies the potential benefit of iterative selection of the concentrations

    evaluated when building mathematical dose-response curves (and response surfaces when

    there are two drugs) using experimental measurements. The reference alternative is to use

    a standard two-fold dilution series or ten-fold dilution series measured in replicates. The

    standard 4-parameter Hill dose-response model is used as a reference and for simulations.

    Models to screen for synergy between two different substances are also developed in this thesis.

  • 3757. Åsberg, Marie
    et al.
    Nygren, Åke
    Leopardi, Rosario
    Rylander, Gunnar
    Peterson, Ulla
    Karolinska Institutet.
    Wilczek, Lukas
    Källmén, Håkan
    Ekstedt, Mirjam
    Karolinska Institute.
    Åkerstedt, Torbjörn
    Lekander, Mats
    Ekman, Rolf
    Novel biochemical markers of psychosocial stress in women2009Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, nr 1, s. e3590-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women.

    METHODS: Plasma concentrations of interleukin (IL) 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women.

    RESULTS: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill.

    CONCLUSIONS: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.

  • 3758.
    Åstrand, Anders
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Andersson, Britt M
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Jalkanen, Ville
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    The first study on whole human prostate ex vivo using a tactile resonance sensor for cancer detectionArtikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Prostate cancer (PCa) is the most common form of cancer among males in Europe and the USA. A prostatectomy i.e. the removal of the prostate is the most common form of curative treatment. Prostate cancer can be suspected by a blood test for a prostate specific antigen (PSA) and a digital rectal examination (DRE) where a physician palpates the prostate through the rectum and where stiff nodules on the prostate is an indication for PCa. The final diagnosis of PCa is made by microscopic evaluation of ultrasound-guided biopsies taken from suspicious parts of the gland. After a prostatectomy the entire prostate is histopathologically analysed. One area of interest is the superficial part of the prostate gland as tumour growth on the surface suggests that the cancer has spread to other parts of the body.

     

    Tactile resonance sensors can be used to detect areas of different stiffness in soft tissue through a stiffness parameter. It is suggested that tactile resonance sensors can be used to detect prostate cancer since tumours in the human prostate usually is stiffer compared to surrounding healthy glandular tissue.

     

    The aim of the study was to detect tumours on, and beneath the surface, of whole human prostate glands ex vivo using a tactile resonance sensor system (TRSS). Model studies on spherical shaped tissue phantoms made of silicone and porcine tissue were performed to evaluate the ability of the TRSS to detect stiffer volumes at a distance beneath the surface. Finally two resected human prostate glands ex vivo from patients undergoing surgery for prostate cancer were studied.

     

    From the results it was concluded that the clamping force from the rotatable sample holder did not affect the magnitude of the stiffness parameter for the silicone samples. For the porcine muscle samples, the stiffness parameter showed to be affected by clamping forces larger than about 800 mN. The embedded stiff silicone nodules placed about 4 mm under the surface could be detected in both the silicone and biological tissue models with a sensor indentation distance of 0.6 mm. The measurements on resected whole human prostates showed that areas with elevated stiffness parameter values correlated (p < 0.05) with areas where cancer tumours were detected using histolopathological evaluation of the prostate. The tumours were significantly stiffer than the healthy tissue in the dorsal region. This is promising for the development of a clinically useful instrument to detect superficial prostate cancer.

  • 3759.
    Åstrand, Anders P
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Jalkanen, Ville
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Andersson, Britt M
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Lindahl, Olof A
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Detection of stiff nodules embedded in soft tissue phantoms, mimicking cancer tumours, using a tactile resonance sensor2014Inngår i: Journal of Biomedical Science and Engineering, ISSN 1937-6871, E-ISSN 1937-688X, Vol. 7, s. 181-193Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Prostate cancer (PCa) is the most common form of cancer among males in Europe and in the USA and the most common curative treatment is removal of the prostate, i.e. prostatectomy. After the removal, the prostate is histopathologically analysed. One area of interest is to examine the capsule of the prostate, as tumours on and near the surface can indicate that the PCa has spread to other parts of the body. There are no current methods to examine the surface of the prostate at the time of surgery. Tactile resonance sensors can be used for detecting areas of different stiffness in soft tissue. Human prostate tissue affected by cancer is usually stiffer than healthy tissue, and for this purpose a tactile resonance sensor was developed. The aim of this study was to investigate the depth at which embedded stiffer volumes could be detected, using soft tissue phantoms.

    Methods

    With the tactile resonance sensor used in this study, the shift of the resonance frequency and the force at contact with tissue can be measured, and combined into a tissue stiffness parameter. The detection sensitivity of the sensor at impression depths, 0.4 and 0.8 mm, was measured for detection of an inserted nodules of stiff silicone in softer silicone and in chicken muscle tissue, mimicking prostate tissue with cancer tumours.

    Results

    Measurements on the silicone samples detected the hidden stiffer object at a depth of 1-4 mm with a difference in the stiffness parameter of 80 – 900 mN/kHz (p < 0.028, n = 48). At the depth 5-6 mm the difference was smaller but still significant < 30 mN/kHz (p < 0.05, n = 24). For the measurements on chicken muscle, the detectable depth was 4 mm (p < 0.05, n = 24).

    Conclusion

    This model study suggests that, with only a small impression depth of ≤ 1 mm, the resonance sensor system described here can detect stiffness variations located at least 4 mm in silicone and chicken muscle, mimicking tumours in prostate tissue.

  • 3760.
    Åstrand, Bengt
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    ePrescribing: Studies in Pharmacoinformatics2007Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [sv]

    Det övergripande syftet med den här avhandlingen har varit att, inom området läkemedelsinformatik, studera utvecklingen av elektroniska stöd inom läkemedelsförskrivning; för klinisk praxis, uppföljning och forskning.

    Under århundraden har det handskrivna receptet varit det sätt, med vilket läkare förmedlat sina läkemedelsordinationer till apotekare, vilket också för patienten blivit en informationskälla för hur läkemedel ska användas för att göra bästa nytta. Nu genomgår receptet en förändring från pappersbaserat till elektroniskt meddelande och att anpassa en traditionell process till en ny elektronisk era innebär både möjligheter och utmaningar.

    Studierna som ingår i avhandlingen har visat att exponeringen av förskrivna läkemedel i en allmän befolkning har ökat under de senaste tre decennierna. Risken för potentiella interaktioner mellan läkemedel, varmed avses den risk som finns att olika läkemedel kan påverka varandras effekter och biverkningar, har också visat sig öka starkt desto fler läkemedel som används av en individ. Denna ökade samtidiga användning av flera olika läkemedel, så kallad polyfarmaci, medför att det finns en större anledning för förskrivare och farmacevter att uppmärksamma risken för potentiella interaktioner mellan läkemedel.

    De nyinrättade nationella receptregistren över uthämtad receptförskriven medicin bör användas bland annat för att upptäcka potentiella läkemedelsinteraktioner, såväl i vårdens utövning som inom läkemedelsepidemiologisk forskning. Den svenska läkemedelsförteckningen, som omfattar information om uthämtade receptförskrivna läkemedel för huvuddelen av den svenska befolkningen, bedöms ha en stor klinisk potential. Den enskilde individens historiska information om uthämtade läkemedel är tillgänglig för individen på Internet med hjälp av e-legitimation; även förskrivare och farmacevter på apotek kan ta del av informationen med den enskildes samtycke. Brist på tillgång till enhetliga och säkra autenticeringsmetoder inom hälso- och sjukvården kan dock fördröja tillgången på individuell läkemedelsinformation för förskrivare. I och med att de flesta recepten i Sverige nu skrivs och överförs elektroniskt är det viktigt att kvalitetsmässiga aspekter tas tillvara så att en iakttagen ökad risk för receptförskrivningsfel inte överförs i informationskedjan.

    Avhandlingens slutsats är att e-förskrivning, med kommunikation och användning av lagrad information om receptexpeditioner, möjliggör att läkemedelsbehandling som process kan följas och studeras på ett helt nytt

  • 3761.
    Åstrand, Bengt
    et al.
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Hovstadius, Bo
    Antonov, Karolina
    Petersson, Göran
    Högskolan i Kalmar, eHälsoinstitutet, Högskolan i Kalmar.
    The Swedish National Pharmacy Register2007Inngår i: MEDINFO 2007: Proceedings of the 12th World Congress on Health (Medical) Informatics – Building Sustainable Health Systems, 2007, Vol. 12, nr 1, s. 345-349Konferansepaper (Fagfellevurdert)
  • 3762.
    Åstrand, Bengt
    et al.
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Montelius, Emelie
    Högskolan i Kalmar, Humanvetenskapliga institutionen.
    Petersson, Göran
    Högskolan i Kalmar, Humanvetenskapliga institutionen. Högskolan i Kalmar, eHälsoinstitutet, Högskolan i Kalmar.
    Ekedahl, Anders
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Assessment of ePrescription quality: an observational study at three mail-order pharmacies2009Inngår i: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 9, nr 1, s. Article number: 8-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The introduction of electronic transfer of prescriptions (ETP) or ePrescriptions in ambulatory health care has been suggested to have a positive impact on the prescribing and dispensing processes. Thereby, implying that ePrescribing can improve safety, quality, efficiency, and cost-effectiveness. In December 2007, 68% of all new prescriptions were transferred electronically in Sweden. The aim of the present study was to assess the quality of ePrescriptions by comparing the proportions of ePrescriptions and non-electronic prescriptions necessitating a clarification contact (correction, completion or change) with the prescriber at the time of dispensing.

    Methods: A direct observational study was performed at three Swedish mail-order pharmacies which were known to dispense a large proportion of ePrescriptions (38–75%). Data were gathered on all ePrescriptions dispensed at these pharmacies over a three week period in February 2006. All clarification contacts with prescribers were included in the study and were classified and assessed in comparison with all drug prescriptions dispensed at the same pharmacies over the specified period.

    Results: Of the 31225 prescriptions dispensed during the study period, clarification contacts were made for 2.0% (147/7532) of new ePrescriptions and 1.2% (79/6833) of new non-electronic prescriptions. This represented a relative risk (RR) of 1.7 (95% CI 1.3–2.2) for new ePrescriptions compared to new non-electronic prescriptions. The increased RR was mainly due to 'Dosage and directions for use', which had an RR of 7.6 (95% CI 2.8–20.4) when compared to other clarification contacts. In all, 89.5% of the suggested pharmacist interventions were accepted by the prescriber, 77.7% (192/247) as suggested and an additional 11.7% (29/247) after a modification during contact with the prescriber.

    Conclusion: The increased proportion of prescriptions necessitating a clarification contact for new ePrescriptions compared to new non-electronic prescriptions indicates the need for an increased focus on quality aspects in ePrescribing deployment. ETP technology should be developed towards a two-way communication between the prescriber and the pharmacist with automated checks of missing, inaccurate, or ambiguous information. This would enhance safety and quality for the patient and also improve efficiency and cost-effectiveness within the health care system.

  • 3763.
    Åstrand, Bengt
    et al.
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Åstrand, Emelie
    Uppsala universitet.
    Antonov, Karolina
    Apoteket AB, Stockholm.
    Petersson, Göran
    Högskolan i Kalmar, Humanvetenskapliga institutionen. Högskolan i Kalmar, eHälsoinstitutet, Högskolan i Kalmar.
    Detection of potential drug interactions: a model for a national pharmacy register2006Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 62, nr 9, s. 749-756Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective  The widespread use of pharmaceuticals prescribed by different physicians has caused the Swedish government to propose a new legislation with registration of all prescriptions dispensed at the Swedish pharmacies. In the present study, we wanted to examine the frequency, distribution and determinants of potential drug interactions.Methods  The prescriptions from all individuals (n=8,214) with two or more prescriptions during October 2003 to December 2004 were collected from the ongoing Jämtland cohort study of a total of about 11,000 individuals. Potential drug–drug interactions were detected with a computerized interaction detection system and classified according to clinical relevance (types A–D).Results  On average each individual filled 14.6 (men 14.3, women 14.8) prescriptions during the study period. 3.6% of the individuals used more than 15 different drugs. The number of detected potential drug interactions type A–D was 4,941 (men 1,949, women 2,992). The risk of receiving a potential interaction type A–D was estimated as the cumulative incidence 0.26 (2,116/8,214) overall, 0.22 (748/3,467) for men and 0.29 (1,368/4,747) for women during the 15-month study period. The age adjusted risk, RRadj, for women was estimated as 1.30. Excluding sex hormones and modulators of the genital system, the RRadj was 0.96, with no elevated risk for women. For potential interactions type D, that might have serious clinical consequences, 167 (cumulative incidence 0.0203) individuals (72 men, cumulative incidence 0.0208, 95 women cumulative incidence 0.0200) were detected. The risk of receiving a combination of potentially interacting drugs was positively correlated to age and polypharmacy. The cumulative incidence for elderly was estimated as 0.36 (65–84 years) and 0.39 (85 years and above). The relative risk for individuals with 15 drugs or more was estimated as 3.67 (95% CI 3.46–3.90).Conclusion  In a general population there were relatively few severe potential drug interactions. The new Swedish national pharmacy register will provide health care professionals with a powerful tool to systematically review all prescriptions. An alert system should focus on the more potential drug interactions, type C–D, with close monitoring of elderly and patients with polypharmacy.

  • 3764.
    Åstrand, Emelie
    et al.
    Högskolan i Kalmar.
    Åstrand, Bengt
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Antonov, Karolina
    The Association of Pharmaceutical Industry, Stockholm.
    Petersson, Göran
    Högskolan i Kalmar, Humanvetenskapliga institutionen. Högskolan i Kalmar, eHälsoinstitutet, Högskolan i Kalmar.
    Erratum: Potential drug interactions during a three-decade study2007Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 63, nr 11, s. 1095-Artikkel i tidsskrift (Fagfellevurdert)
  • 3765.
    Åstrand, Emelie
    et al.
    Högskolan i Kalmar, Naturvetenskapliga institutionen. Högskolan i Kalmar, eHälsoinstitutet, Högskolan i Kalmar.
    Åstrand, Bengt
    Högskolan i Kalmar, Naturvetenskapliga institutionen. Apoteket AB.
    Antonov, Karolina
    The Association of Pharmaceutical IndustryStockholm.
    Petersson, Göran
    Högskolan i Kalmar, Humanvetenskapliga institutionen. Högskolan i Kalmar, eHälsoinstitutet, Högskolan i Kalmar.
    Potential drug interactions during a three-decade study period: a cross-sectional study of a prescription register2007Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 63, nr 9, s. 851-859Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives  The increased risk of adverse events in patients receiving potentially interacting drugs has long been recognized. The purpose of the present study was to evaluate the change in the risk of receiving potentially interacting drugs during a period covering three decades and to examine the relative risk of actual drug combinations. Methods  The prescriptions from all individuals (about 8,000) with two or more prescriptions during three periods of 15 months, October to December 1983–1984, 1993–1994 and 2003–2004, were collected from an ongoing cohort study in the county of Jämtland, Sweden. The potential interactions were detected by a computerized system. Results  The relative risk (RR) of receiving potentially interacting drugs increased for type C interactions [RR: 1.177, 95% confidence interval (CI): 1.104–1.256] and decreased for type D interactions (RR: 0.714, 95% CI: 0.587–0.868) from the period 1983–1984 to 2003–2004. Polypharmacy for the participants increased by 61%, from 9.05 filled prescriptions per subject in 1983–1984 to 10.6 in 1993–1994 and 14.6 in 2003–2004. The RR was positively correlated to the pronounced increase in polypharmacy; in addition, an exponential relationship was found for the more severe type D interactions. Few interacting drug combinations were responsible for a large proportion of the risk. Conclusion  We conclude that the risk of receiving potentially interacting drugs was strongly correlated to the concomitant use of multiple drugs. The pronounced increase in polypharmacy over time implies a growing reason for prescribers and pharmacists to be aware of drug interactions. Recently established national prescription registers should be evaluated for drug interaction vigilance, both clinically and epidemiologically.

  • 3766.
    Åstrand, Mikael
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Engineering strategies for ABD-derived affinity proteins for therapeutic and diagnostic applications2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Small stable protein domains are attractive scaffolds for engineering affinity proteins due to their high tolerance to mutagenesis without loosing structural integrity. The albuminbinding domain is a 5 kDa three-helix bundle derived from the bacterial receptor Protein G with low-nanomolar affinity to albumin. In this thesis, the albumin-binding domain is explored as a scaffold for engineering novel affinity proteins with the possible benefit of combining a prolonged serum half-life with specific targeting in a single small scaffold protein. Previously, a library was created by randomizing surface-exposed residues in order to engineer affinity to a new target antigen in addition to the inherent albumin affinity. Here, phage display selections were separately performed against the tumor antigens ERBB2 and ERBB3. The ERBB3 selection resulted in a panel of candidates that were found to have varying affinities to ERBB3 in the nanomolar range, while still retaining a high affinity to albumin. Further characterization concluded that the clones also competed for binding to ERBB3 with the natural activating ligand Heregulin. The selections against ERBB2 resulted in sub-nanomolar affinities to ERBB2 where the binding site was found to overlap with the antibody Trastuzumab. The binding sites on ABD to albumin and either target were found in both selections to be mutually exclusive, as increased concentrations of albumin reduced the level of binding to ERBB2 or ERBB3. An affinity-matured ERBB2 binder, denoted ADAPT6, which lacked affinity to albumin was evaluated as a radionuclide-labeled imaging tracer for diagnosing ERBB2-positive tumors. Biodistribution studies in mice showed a high renal uptake consistent with affinity proteins in the same size range and the injected ADAPT quickly localized to the implanted tumor. High contrast images could be generated and ERBB2-expressing tissue could be distinguished from normal tissue with high contrast, demonstrating the feasibility of the scaffold for use as diagnostic tool. In a fourth study, affinity maturation strategies using staphylococcal cell-surface display were evaluated by comparing two replicate selections and varying the stringency. A sub-nanomolar target concentration was concluded to be inappropriate for equilibrium selection as the resulting output was highly variable between replicates. In contrast, equilibrium sorting at higher concentrations followed by kinetic-focused off-rate selection resulted in high output overlap between attempts and a clear correlation between affinity and enrichment.

  • 3767.
    Åström, Jeanette
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Att särskilja en stickblödning från subaraknoidal blödning vid likvoranalys: Ett underlag för en korrektionsformel som kan kompensera för bilirubinökning i likvor till följd av en stickblödning2019Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 3768.
    Åström, Maria
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden; Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tajeddinn, Walid
    iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine.
    Linder, Olle
    Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Palmblad, Jan
    Division of Hematology, Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Lindblad, Per
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma2018Inngår i: Biomarker Insights, ISSN 1177-2719, E-ISSN 1177-2719, Vol. 13, artikkel-id UNSP 1177271918792246Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explained by cytokine production from the cancer cells.

    CASE PRESENTATIONS: A 64-year-old man was referred for hematology workup due to pronounced leukocytosis. While being evaluated for a possible hematologic malignancy as the cause, he was found to have a metastasized renal cell carcinoma, and hyperleukocytosis was classified as a leukemoid reaction. A multiplex panel for measurement of 25 serum cytokines/chemokines showed highly elevated levels of granulocyte colony-stimulating factor (G-CSF) and CXCL8 (C-X-C-motif chemokine ligand 8, previously known as interleukin [IL]-8). By immunohistochemistry it was shown that the renal carcinoma cells expressed both these cytokines. Two additional, consecutive patients with renal cell carcinoma with paraneoplastic leukocytosis also showed elevated serum levels of CXCL8, but not of G-CSF. Nonparametric statistical evaluation showed significantly higher serum concentrations of CXCL8, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor, but lower interferon gamma (IFN-gamma) and IL-1 alpha, for the 3 renal cell carcinoma cases compared with healthy blood donors.

    CONCLUSIONS: In suspected paraneoplastic leukocytosis, multiplex serum cytokine analyses may facilitate diagnosis and provide an understanding of the mechanisms for the reaction. In the index patient, combined G-CSF and CXCL8 protein expression by renal carcinoma cells was uniquely documented. A rapidly fatal course was detected in all 3 cases, congruent with the concept that autocrine/paracrine growth signaling in renal carcinoma cells may induce an aggressive tumor phenotype. Immune profiling studies could improve our understanding for possible targets when choosing therapies for patients with metastatic renal cell carcinoma.

  • 3769.
    Åström, Mattias
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan. Sapiens Steering Brain Stimulation BV, NL-5656 Eindhoven, Netherlands.
    Diczfalusy, Elin
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Martens, Hubert
    Sapiens Steering Brain Stimulation B.V., Eindhoven, The Netherlands.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Relationship between Neural Activation and Electric Field Distribution during Deep Brain Stimulation2015Inngår i: IEEE Transactions on Biomedical Engineering, ISSN 0018-9294, E-ISSN 1558-2531, Vol. 62, nr 2, s. 664-72Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Models and simulations are commonly used to study deep brain stimulation (DBS). Simulated stimulation fields are often defined and visualized by electric field isolevels or volumes of tissue activated (VTA). The aim of the present study was to evaluate the relationship between stimulation field strength as defined by the electric potential V, the electric field E, and the divergence of the electric field ∇(2) V, and neural activation. Axon cable models were developed and coupled to finite-element DBS models in three-dimensional (3-D). Field thresholds ( VT , ET, and ∇(2) VT ) were derived at the location of activation for various stimulation amplitudes (1 to 5 V), pulse widths (30 to 120 μs), and axon diameters (2.0 to 7.5 μm). Results showed that thresholds for VT and ∇(2) VT were highly dependent on the stimulation amplitude while ET were approximately independent of the amplitude for large axons. The activation field strength thresholds presented in this study may be used in future studies to approximate the VTA during model-based investigations of DBS without the need of computational axon models.

  • 3770.
    Åström, Mattias
    et al.
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Johansson, Johannes
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Hariz, Marwan
    Institute of Neurology London.
    Eriksson, Ola
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Wårdell, Karin
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    The effect of cystic cavities on deep brain stimulation in the basal ganglia: A simulation-based study2006Inngår i: Journal of Neural Engineering, ISSN 1741-2560, E-ISSN 1741-2552, Vol. 3, nr 2, s. 132-138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Although the therapeutic effect of deep brain stimulation (DBS) is well recognized, a fundamental understanding of the mechanisms responsible is still not known. In this study finite element method (FEM) modelling and simulation was used in order to study relative changes of the electrical field extension surrounding a monopolar DBS electrode positioned in grey matter. Due to the frequently appearing cystic cavities in the DBS-target globus pallidus internus, a nucleus of grey matter with and without a cerebrospinal fluid filled cystic cavity was modelled. The position, size and shape of the cyst were altered in relation to the electrode. The simulations demonstrated an electrical field around the active element with decreasing values in the radial direction. A stepwise change was present at the edge between grey and white matters. The cyst increased the radial extension and changed the shape of the electrical field substantially. The position, size and shape of the cyst were the main influencing factors. We suggest that cystic cavities in the DBS-target may result in closely related unexpected structures or neural fibre bundles being stimulated and could be one of the reasons for suboptimal clinical effects or stimulation-induced side effects. © 2006 IOP Publishing Ltd.

  • 3771.
    Åström, Mattias
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Tripoliti, Elina
    University College, London.
    Hariz, Mawan I.
    University Hospital, Umeå .
    Zrinzo, Ludvig U.
    University College, London.
    Martinez-Torres, Irene
    University College, London.
    Limousin, Patricia
    University College, London.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Patient-Specific Model-Based Investigation of Speech Intelligibility and Movement during Deep Brain Stimulation2010Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 88, nr 4, s. 224-233Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/Aims: Deep brain stimulation (DBS) is widely used to treat motor symptoms in patients with advanced Parkinson’s disease. The aim of this study was to investigate the anatomical aspects of the electric field in relation to effects on speech and movement during DBS in the subthalamic nucleus. Methods: Patient-specific finite element models of DBS were developed for simulation of the electric field in 10 patients. In each patient, speech intelligibility and movement were assessed during 2 electrical settings, i.e. 4 V (high) and 2 V (low). The electric field was simulated for each electrical setting. Results: Movement was improved in all patients for both high and low electrical settings. In general, high-amplitude stimulation was more consistent in improving the motor scores than low-amplitude stimulation. In 6 cases, speech intelligibility was impaired during high-amplitude electrical settings. Stimulation of part of the fasciculus cerebellothalamicus from electrodes positioned medial and/or posterior to the center of the subthalamic nucleus was recognized as a possible cause of the stimulation-induced dysarthria. Conclusion: Special attention to stimulation-induced speech impairments should be taken in cases when active electrodes are positioned medial and/or posterior to the center of the subthalamic nucleus.

  • 3772.
    Åström, Mattias
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Zrinzo, Ludvic U
    University College London.
    Tisch, Stephen
    Linköpings universitet, Tekniska högskolan.
    Tripoliti, Elina
    University College London.
    Hariz, Marwan I
    University College London.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Method for patient-specific finite element modeling and simulation of deep brain stimulation2009Inngår i: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 47, nr 1, s. 21-28Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Deep brain stimulation (DBS) is an established treatment for Parkinsons disease. Success of DBS is highly dependent on electrode location and electrical parameter settings. The aim of this study was to develop a general method for setting up patient-specific 3D computer models of DBS, based on magnetic resonance images, and to demonstrate the use of such models for assessing the position of the electrode contacts and the distribution of the electric field in relation to individual patient anatomy. A software tool was developed for creating finite element DBS-models. The electric field generated by DBS was simulated in one patient and the result was visualized with isolevels and glyphs. The result was evaluated and it corresponded well with reported effects and side effects of stimulation. It was demonstrated that patient-specific finite element models and simulations of DBS can be useful for increasing the understanding of the clinical outcome of DBS.

  • 3773.
    Öberg, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    EKG-avvikelser hos ungdomar i relation till kön, ålder och aktivitetsnivå2019Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 3774.
    Öberg, Åke
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Medicinsk teknik i Japan1973Rapport (Annet (populærvitenskap, debatt, mm))
  • 3775.
    Ödin, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Internalisering av yttermembranvesiklar från Aggregatibacter actinomycetemcomitans i humana celler2013Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 3776.
    Ögren, Jessica
    et al.
    Division of Medical Diagnostics, Clinical Microbiology Laboratory, County Hospital Ryhov, Region Jönköping County, Sweden.
    Van Nguyen, Song
    Department of Medical Laboratory, Da Nang University of Medical Technology and Pharmacy, Da Nang, Vietnam.
    Dimberg, Jan
    Högskolan i Jönköping, Hälsohögskolan, HHJ, Avd. för naturvetenskap och biomedicin. Högskolan i Jönköping, Hälsohögskolan, HHJ. Biomedicinsk plattform.
    Matussek, Andreas
    Division of Medical Diagnostics, Clinical Microbiology Laboratory, County Hospital Ryhov, Region Jönköping County, Sweden.
    Prevalence of Dientamoeba fragilis, Giardia duodenalis, Entamoeba histolytica/dispar, and Cryptosporidium spp inDa Nang, Vietnam, detected by a multiplex real-time PCR2016Inngår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, nr 6, s. 529-533Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We surveyed the prevalence of Dientamoeba fragilis, Giardia duodenalis, Entamoeba histolytica, Entamoeba dispar, and Cryptosporidium spp in individuals with and without gastrointestinal (GI) symptoms residing in and around Da Nang city, Vietnam. Fecal samples were collected from children (n = 100) and adults (n = 80) with GI symptoms and from healthy individuals (n = 88) reporting no GI symptoms. Parasite detection was performed by multiplex real-time PCR. Overall, except for G. duodenalis, we found a low prevalence (<5%) of D. fragilis and E. dispar and no detection of E. histolytica and C. spp in all participants with GI symptoms. Specifically for D. fragilis this contrasts with findings in European populations of children with GI symptoms showing prevalence up to 73%. Moreover, our results indicate that the prevalence of G. duodenalis is higher in patients with GI symptoms compared to asymptomatic individuals and this difference is most obvious in young patients.

  • 3777.
    Öhberg, Fredrik
    Högskolan i Gävle, Centrum för belastningsskadeforskning.
    Biomechanical methods and error analysis related to chronic musculoskeletal pain2009Doktoravhandling, monografi (Annet vitenskapelig)
    Abstract [en]

    Background Spinal pain is one of humanity’s most frequent complaints with high costs for the individual and society, and is commonly related to spinal disorders. There are many origins behind these disorders e.g., trauma, disc hernia or of other organic origins. However, for many of the disorders, the origin is not known. Thus, more knowledge is needed about how pain affects the neck and neural function in pain affected regions. The purpose of this dissertation was to improve the medical examination of patients suffering from chronic whiplash-associated disorders or other pain related neck-disorders.

    Methods A new assessment tool for objective movement analysis was developed. In addition, basic aspects of proprioceptive information transmission, which can be of relevance for muscular tension and pain, are investigated by studying the coding of populations of different types of sensory afferents by using a new spike sorting method. Both experiments in animal models and humans were studied to accomplish the goals of this dissertation. Four cats where were studied in acute animal experiments. Mixed ensembles of afferents were recorded from L7-S1 dorsal root filaments when mechanical stimulating the innervated muscle. A real-time spike sorting method was developed to sort units in a multi-unit recording. The quantification of population coding was performed using a method based on principal component analysis. In the human studies, 3D neck movement data were collected from 59 subjects with whiplash-associated disorders (WAD) and 56 control subjects. Neck movement patterns were identified by processing movement data into parameters describing the rotation of the head for each subject. Classification of neck movement patterns was performed using a neural network using processed collected data as input. Finally, the effect of marker position error on the estimated rotation of the head was evaluated by computer simulations.

    Results Animal experiments showed that mixed ensembles of different types of afferents discriminated better between different muscle stimuli than ensembles of single types of these afferents. All kinds of ensembles showed an increase in discriminative ability with increased ensemble size. It is hypothesized that the main reason for the greater discriminative ability might be the variation in sensitivity tuning among the individual afferents of the mixed ensemble will be larger than that for ensembles of only one type of afferent. In the human studies, the neural networks had a predictivity of 0.89, a sensitivity of 0.90 and a specificity of 0.88 when discriminating between control and WAD subjects. Also, a systematic error along the radial axis of the rigid body added to a single marker had no affect on the estimated rotation of the head.

    Conclusion The developed spike sorting method, using neural networks, was suitable for sorting a multiunit recording into single units when performing neurophysiological experiments. Also, it was shown that neck movement analysis combined with a neural network could build the basis of a decision support system for classifying suspected WAD or other pain related neck-disorders.

  • 3778.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Biomechanical methods and error analysis related to chronic musculoskeletal pain2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background Spinal pain is one of humanity’s most frequent complaints with high costs for the individual and society, and is commonly related to spinal disorders. There are many origins behind these disorders e.g., trauma, disc hernia or of other organic origins. However, for many of the disorders, the origin is not known. Thus, more knowledge is needed about how pain affects the neck and neural function in pain affected regions. The purpose of this dissertation was to improve the medical examination of patients suffering from chronic whiplash-associated disorders or other pain related neck-disorders.

    Methods A new assessment tool for objective movement analysis was developed. In addition, basic aspects of proprioceptive information transmission, which can be of relevance for muscular tension and pain, are investigated by studying the coding of populations of different types of sensory afferents by using a new spike sorting method. Both experiments in animal models and humans were studied to accomplish the goals of this dissertation. Four cats where were studied in acute animal experiments. Mixed ensembles of afferents were recorded from L7-S1 dorsal root filaments when mechanical stimulating the innervated muscle. A real-time spike sorting method was developed to sort units in a multi-unit recording. The quantification of population coding was performed using a method based on principal component analysis. In the human studies, 3D neck movement data were collected from 59 subjects with whiplash-associated disorders (WAD) and 56 control subjects. Neck movement patterns were identified by processing movement data into parameters describing the rotation of the head for each subject. Classification of neck movement patterns was performed using a neural network using processed collected data as input. Finally, the effect of marker position error on the estimated rotation of the head was evaluated by computer simulations.

    Results Animal experiments showed that mixed ensembles of different types of afferents discriminated better between different muscle stimuli than ensembles of single types of these afferents. All kinds of ensembles showed an increase in discriminative ability with increased ensemble size. It is hypothesized that the main reason for the greater discriminative ability might be the variation in sensitivity tuning among the individual afferents of the mixed ensemble will be larger than that for ensembles of only one type of afferent. In the human studies, the neural networks had a predictivity of 0.89, a sensitivity of 0.90 and a specificity of 0.88 when discriminating between control and WAD subjects. Also, a systematic error along the radial axis of the rigid body added to a single marker had no affect on the estimated rotation of the head.

    Conclusion The developed spike sorting method, using neural networks, was suitable for sorting a multiunit recording into single units when performing neurophysiological experiments. Also, it was shown that neck movement analysis combined with a neural network could build the basis of a decision support system for classifying suspected WAD or other pain related neck-disorders.

  • 3779.
    Öhman, Caroline
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Carlsson, Elin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Ginebra, Maria Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Dept. of Materials Science and Metallurgy, Technical University of Catalonia.
    Persson, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Porosity prediction of calcium phosphate cements2013Konferansepaper (Fagfellevurdert)
  • 3780.
    Öhman, Caroline
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Carlsson, Elin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Ginebra, Maria Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Dept. of Materials Science and Metallurgy, Technical University of Catalonia.
    Persson, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Prediction of porosity in hydroxyapatite and brushite cements2013Konferansepaper (Fagfellevurdert)
  • 3781.
    Öhman, Caroline
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Hulsart-Billström, Gry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Particelli, Francesca
    Laboratorio di Tecnologia Medica, Istituto Ortopedico Rizzoli, Italy.
    Baruffaldi, Fabio
    Laboratorio di Tecnologia Medica, Istituto Ortopedico Rizzoli, Italy.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Premixed calcium phosphate cement as a carrier of bone morphogenetic protein2013Konferansepaper (Fagfellevurdert)
  • 3782.
    Öhman, Caroline
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Nouhi, Shirin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Hulsart-Billström, Gry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Facilitating separation of bone from bonelike materials in micro-computed tomography images2014Konferansepaper (Fagfellevurdert)
  • 3783.
    Öhman, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    RNA uttryck av KIF23 i humana vävnader2013Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 3784.
    Ölvebo, Isabelle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Leukotoxinproduktion i isolat från Aggregatibacter actinomycetemcomitans: En parodontitpatogen med stor genetisk variation2012Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 3785. Önnerfjord, Patrik
    et al.
    Khabut, Areej
    Reinholt, Finn P
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Heinegård, Dick
    Quantitative proteomic analysis of eight cartilaginous tissues reveals characteristic differences as well as similarities between subgroups2012Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, nr 23, s. 18913-18924Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human synovial joints display a characteristic anatomic distribution of arthritis, e.g. rheumatoid arthritis primarily affects the metacarpophalangeal and proximal finger joints, but rarely the distal finger joints, whereas osteoarthritis occurs in the distal and proximal finger joints. Pelvospondylitis has a selective localization to the spine and sacroiliac joints. Is this tropism due to differences between the cartilages at the molecular level? To substantiate this concept the present study provides a background detailed compositional analysis by relative quantification of extracellular matrix proteins in articular cartilages, meniscus, intervertebral disc, rib, and tracheal cartilages on samples from 5-6 different individuals using an optimized approach for proteomics. Tissue extraction followed by trypsin digestion and two-dimensional LC separations coupled to tandem mass spectrometry, relative quantification with isobaric labeling, iTRAQ (TM), was used to compare the relative abundance of about 150 proteins. There were clear differences in protein patterns between different kinds of cartilages. Matrilin-1 and epiphycan were specific for rib and trachea, whereas asporin was particularly abundant in the meniscus. Interestingly, lubricin was prominent in the intervertebral disc, especially in the nucleus pulposus. Fibromodulin and lumican showed distributions that were mirror images of one other. Analyses of the insoluble residues from guanidine extraction revealed that a fraction of several proteins remained unextracted, e.g. asporin, CILP, and COMP, indicating cross-linking. Distinct differences in protein patterns may relate to different tissue mechanical properties, and to the intriguing tropism in different patterns of joint pathology.

  • 3786.
    Örnborg, Madelene
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för hälsovetenskaper.
    Basal expression i Mo, M1 och M2 makrofager samt bakterien Propionibacterium acnes påverkan på M0 makrofagers uttryck av CCL2,CCR2,CSF-1 och CSF-1R mRNA2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 3787.
    Östberg, Linus J.
    et al.
    Karolinska Inst, Sci Life Lab, Dept Med Biochem & Biophys, Stockholm, Sweden..
    Persson, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik. Karolinska Inst, Sci Life Lab, Dept Med Biochem & Biophys, Stockholm, Sweden..
    Höög, Jan-Olov
    Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden..
    Computational studies of human class V alcohol dehydrogenase - the odd sibling2016Inngår i: BMC Biochemistry, ISSN 1471-2091, E-ISSN 1471-2091, Vol. 17, artikkel-id 16Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: All known attempts to isolate and characterize mammalian class V alcohol dehydrogenase (class V ADH), a member of the large ADH protein family, at the protein level have failed. This indicates that the class V ADH protein is not stable in a non-cellular environment, which is in contrast to all other human ADH enzymes. In this report we present evidence, supported with results from computational analyses performed in combination with earlier in vitro studies, why this ADH behaves in an atypical way. Results: Using a combination of structural calculations and sequence analyses, we were able to identify local structural differences between human class V ADH and other human ADHs, including an elongated beta-strands and a labile a-helix at the subunit interface region of each chain that probably disturb it. Several amino acid residues are strictly conserved in class I-IV, but altered in class V ADH. This includes a for class V ADH unique and conserved Lys51, a position directly involved in the catalytic mechanism in other ADHs, and nine other class V ADH-specific residues. Conclusions: In this study we show that there are pronounced structural changes in class V ADH as compared to other ADH enzymes. Furthermore, there is an evolutionary pressure among the mammalian class V ADHs, which for most proteins indicate that they fulfill a physiological function. We assume that class V ADH is expressed, but unable to form active dimers in a non-cellular environment, and is an atypical mammalian ADH. This is compatible with previous experimental characterization and present structural modelling. It can be considered the odd sibling of the ADH protein family and so far seems to be a pseudoenzyme with another hitherto unknown physiological function.

  • 3788.
    Österberg, Marie
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    What’s in? What’s out? And how did it get there?: Studies on topologies and insertion of membrane proteins2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Because of their hydrophobic and hydrophilic nature and the need for a lipid bilayer for retaining the native structure, membrane proteins are hard to study. Nevertheless, they are important, as many of our diseases are related to membrane proteins and around 60% of the different pharmaceutical drugs are directed against a membrane proteins [1]. There are many ways to study a protein, you can study function, structure, how the protein is targeted and inserted into its specific organelle, the interactions with other proteins or ligands etc. In the absence of a high-resolution structure, a topology model for a membrane protein is often useful. We have obtained reliable topologies for 546 of the membrane proteins going through the secretory pathways in S. cerevisiae by combining experimental data with topology prediction programs. In addition we have produced topology models for over 15,000 membrane proteins from 38 sequenced eukaryotic genomes using homology to the experimentally determined group.

    We also examined the growth rates and tolerance to certain stress conditions for our large set of clones that over-express membrane proteins. This provides important information both for structural studies of membrane proteins where large amounts of protein is needed for further studies, and for getting some insight in the function of specific proteins. Finally we have studied the integration of membrane proteins by the Tim23 translocon in the inner membrane of mitochondria. We have investigated the hydrophobicity required for efficient integration of transmembrane (TM) helices by Tim23. From this data we have derived an in vivo hydrophobicity scale for the insertion of different amino acids into the inner membrane of the mitochondria, and have made a comparison with a previously determined hydrophobicity scale for the ER translocon Sec61. We concluded that charged residues flanking the TM segment are of major importance for insertion into the membrane.

    We therefore further investigated the importance of charged residues flanking the first, weakly hydrophobic, TM segment in the mitochondrial inner membrane protein Mgm1p with regard to membrane insertion by the Tim23 complex.

  • 3789.
    Östergren, Tiolina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Identification of MYCN and SOX9 target genes and a study of drug treatment effects in medulloblastoma2015Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Medulloblastoma (MB) is the most common malignant brain tumor affecting children. The transcription factors MYCN and SOX9 are associated with initiation, maintenance and recurrence of MB and are also connected to more aggressive tumors. In this study, a ChIP was performed to isolate DNA from genes that are transcriptionally regulated by these proteins. Identification of these target genes will reveal new potential drug targets and help us better understand the functions of MYCN and SOX9. The ChIP was not fully optimized during this project and the target genes were not sent for sequencing and identified. To study the connection between SOX9 and recurrence, cells with different levels of SOX9 were treated with drugs, after which cell viability was measured. No significant difference in resistance could be measured. Change in expression level of MYCN, SOX9 and other relevant genes after drug treatment was also studied. The results show an increase in SOX9 and HES1, suggesting that these genes are involved in tumor recurrence.

  • 3790.
    Österman, Marie
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Utvärdering av kapillärt protrombinkomplex i EDTA-microtainerrör2010Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Blodcirkulationen är essentiell för människans överlevnad. När blodets koagulation- och antikoagulationssystem kommer i obalans kan koagelbildning orsaka venös tromboembolism, blodpropp. Patienter som har haft en blodpropp behandlas med antivitamin K-läkemedel (Waran®) för att förebygga recidiv. Dosen är individanpassad och för att erhålla rätt terapeutisk verkan krävs övervakning genom mätning av protrombinkomplex i plasma.

    Syftet med studien var att utföra en utvärdering samt göra en hållbarhetsstudie på en ny provtagningsrutin för kapillära protrombinkomplex.I studien ingick 48 personer varav 33 män och 15 kvinnor. Åldersfördelning var 22-88 år och medianålder var 62 år. I samband med ordinarie provtagning, vilken användes som referensmetod, för P-protrombinkomplex togs ca 350 μL blod kapillärt i EDTA-microtainerrör. Genom spädning (1:4) av EDTA-blod i citratbuffert möjliggjordes analys av kapillärt P-protrombinkomplex efter 1, 8 och 24 timmar. Samtliga prover analyserades med turbidimetrisk detektion i instrumentet ACL Top 500. Studiens analysresultat jämfördes mot referensmetoden.Studien visar att protrombinkomplexaktiviteten är stabil i blod med EDTA-tillsats i upp till 8 timmar efter provtagning. Dock kan stabiliteten inte garanteras hos individer med hereditära koagulationsrubbningar.

  • 3791.
    Östling, Jonas
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Function and regulation of the Yeast Mig1 repressor1998Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Glucose repression is a global regulatory response in the yeast Saccharomyces cerevisiae. Thus, in the presence of glucose, the preferred carbon source, expression of many genes encoding proteins required for metabolism of other carbon sources are turned off.

    An important mediator of glucose repression is the Mig1 repressor. It is a DNA binding transcription factor that has two zinc fingers of the C2H2 type. When glucose is available, Mig1 binds to the promotors of glucose repressed genes and is then thought to recruit a large co-repressor complex, consisting of the Cyc8/Ssn6 and Tup1 proteins. Mig1 is negatively regulated by the Snf1 protein kinase, a protein which is essential for the expression of all glucose repressed genes in yeast.

    In this work, domains within the Mig1 repressor were characterized that mediate its carbon source regulation and its function as a repressor. An extensive deletion analysis of Mig1 revealed that an effector domain of 24 amino acid residues in the extreme C-terminus of the protein is important for repression. The C-terminal effector domain is structurally and functionally conserved also in the Mig1 homologues from the distantly related yeasts Kluyveromyces lactis and K. marxianus. A combined deletion analysis and alanine scanning mutagenesis of the effector domain in K. marxianus revealed that three leucines and one isoleucine are particularly important for its function in vivo.

    The deletion analysis of the Mig1 from S. cerevisiae also revealed that two internal domains, R1 and R2, are important for the regulation of Mig1 by glucose. Thus, a deletion of either R1 or R2 converts Mig1 to a constitutive repressor. Further experiments were conducted with a Mig1-VP16 hybrid activator in which the C-terminal effector domain was replaced by the activating, domain from the viral protein VP16 The analysis revealed that this hybrid activator is negatively regulated by Snf1. We further found that Mig1-VP16 is phosphorylated in the absence of glucose, and that this phosphorylation is dependent on Snf1. Point mutations in Mig1 -VP16 identified three serines that are important both for Snf1 control of Mig1-VP16 activity and for phosphorylation in the absence of glucose. Two of the serines are located in the R1 domain within sequence motifs similar to a consensus in vitro target site for Snf1. The third serine, which does not resemble the Snf1 consensus target site, is located near the zinc fingers adjacent to a basic domain, the B-domain, which is essential both for the function of Mig1-VP16 as an activator and for the function of Mig1 as a repressor.

  • 3792.
    Östlund, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Evaluating the Congo red staining method with the aim to solve problematics in the work process and optimize amyloidosis diagnostics2017Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Some diagnostic methods have been used for a very long time. Congo red stain saw the light of day in 1883, and quickly became important in many fields of use. Nowadays we recognize the importance of Congo red in diagnose of amyloid diseases. However, the technique and experience needed throughout the process from a suspected case to the diagnose is of greate importance. When diagnostic difficulties appeared in a few patient cases at the local hospital in Gävle, Sweden, a solution was needed. A delayed diagnose could have a potential devastating outcome seen in the perspective of the patient. Therefore it is crucial to have both sensitive and specific diagnostic methods that are optimized against the sought pathogenesis. This study aspired to find the solution to the difficulties in diagnostic work, brought to light by a pathology doctor at the hospital. Several different methodical procedures are used throughout the process, and were evaluated with focus lying on the thickness of the tissue, the staining method and the microscopes used in diagnostics. Different thickness of the tissue was cut and stained. The results demonstrated the importance of proper techniques and methods in preparing the tissue, and the tools to analyse it with. The thickness of tissue and the lightsource in the microscope played a cruicial role in diagnostics. Additionally it showed the importance to continue to raise the quality of work and make progress in the diagnostic and scientific field, possibly by finding new applications for old methods.

  • 3793.
    Öystilä Sjödin, Madelen
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Kronisk behandling med allopregnanolon påverkar inte mängden beta-amyloida plack i AβPPSwePSEN1E9 AD-möss2012Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 3794.
    Öz, Diana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Investigating distribution of DIO2 and MOT8 mRNA with quantitative reverse transcription-PCR and immunohistochemistry staining of endometrial and fallopian tube tissue2018Independent thesis Advanced level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [en]

    Infertility is defined as not being able to conceive after 1 year of regular intercourse without use of contraception. Unexplained infertility is a diagnosis given to couples where the reason to infertility cannot be clarified even after the routine examination. Undefined infertility is a common and growing problem because most people are not aware of the fact that fertility decreases after the age of 35. Hyper- and hypothyroidism has been known to affect the menstrual cycle as well as increased risk of miscarriage. However, the specific effect of thyroid hormones on infertility has not yet been clarified. This study aims to compare the gene expression of two thyroid hormone receptors DIO2 and MOT8 in human endometrium and fallopian tube tissue from two phases of the menstruation cycle, follicular phase and lutheal phase. The methods used were RT-qPCR and immunohistochemistry, which showed a statistically significant difference in the expression of DIO2 and MOT8 between fallopian tube tissue and endometrium, but not between follicular and lutheal phase. However, MOT8 seemed to have a tendency to be down-regulated in the follicular phase but the results need to be validated with different endogenous controls and larger study groups.

  • 3795.
    Özarslan, Evren
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Yolcu, Cem
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Herberthson, Magnus
    Linköpings universitet, Matematiska institutionen, Matematik och tillämpad matematik. Linköpings universitet, Tekniska fakulteten.
    Knutsson, Hans
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Westin, Carl-Fredrik
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Laboratory for Mathematics in Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
    Influence of the Size and Curvedness of Neural Projections on the Orientationally Averaged Diffusion MR Signal2018Inngår i: Frontiers in Physics, E-ISSN 2296-424X, Vol. 6, s. 1-10, artikkel-id 17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuronal and glial projections can be envisioned to be tubes of infinitesimal diameter as far as diffusion magnetic resonance (MR) measurements via clinical scanners are concerned. Recent experimental studies indicate that the decay of the orientationally-averaged signal in white-matter may be characterized by the power-law, Ē(q) ∝ q−1, where q is the wavenumber determined by the parameters of the pulsed field gradient measurements. One particular study by McKinnon et al. [1] reports a distinctively faster decay in gray-matter. Here, we assess the role of the size and curvature of the neurites and glial arborizations in these experimental findings. To this end, we studied the signal decay for diffusion along general curves at all three temporal regimes of the traditional pulsed field gradient measurements. We show that for curvy projections, employment of longer pulse durations leads to a disappearance of the q−1 decay, while such decay is robust when narrow gradient pulses are used. Thus, in clinical acquisitions, the lack of such a decay for a fibrous specimen can be seen as indicative of fibers that are curved. We note that the above discussion is valid for an intermediate range of q-values as the true asymptotic behavior of the signal decay is Ē(q) ∝ q−4 for narrow pulses (through Debye-Porod law) or steeper for longer pulses. This study is expected to provide insights for interpreting the diffusion-weighted images of the central nervous system and aid in the design of acquisition strategies.

  • 3796.
    Joint Nordic Registers and Biobanks: A goldmine for health and welfare research2014Rapport (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    This report is based on the work of the NORIA-net on Registers and Biobanks (NRB), a Nordic working group of key actors involved in Nordic research and research policy at the national level. This NORIA-net has focused its activities on how to overcome existing obstacles that impede Nordic data sharing and has proposed ways of enhancing coordination to strengthen Nordic register-based research.

    Register-based research within the field of health and wellbeing has great potential for producing knowledge that can be used to improve the capacity of the Nordic welfare states.

    Nordic register-based research has the potential to attract international interest and to enable the Nordic research community to take the international lead in this field.

  • 3797.
    Legislation on biotechnology in the Nordic countries: – an overview 20162016Annet (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    The current report is an update of the reports on Legislation onbiotechnology in the Nordic countries published in 2014 and 2015. Given the clear need for such overviews, the Nordic Committee on Bioethics decided to update the tables to reflect recent legal amendments. The aim of this report is to give the reader information on the current status in the different countries and a chance to compare the legal situation.

    Sixteen important areas of biotechnology have been chosen for this overview:

    • Assisted reproduction
    • Preimplantation genetic diagnosis (PGD)
    • Preimplantation genetic screening (PGS)
    • Abortion• Prenatal Diagnosis and/or screening
    • Organ and tissue transplantation
    • Embryo research
    • Cloning
    • Clinical research on humans
    • Human biobanks
    • Ethical committees
    • Genetic testing
    • Advanced therapy medicinal products
    • Genetically modified organisms
    • Animal experimentation
    • Legal status of Council of Europe Biomedicine Conventionand its additional protocols
  • 3798.
    Legislation on biotechnology in the Nordic countries: – an overview 20172017Annet (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    The current report is an update of the reports on Legislation on biotechnology in the Nordic countries published annually since 2014. Given the clear need for such overviews, the Nordic Committee on Bioethics decided to update the tables to reflect recent legal amendments. The aim of this report is to give the reader information on the current status in the different countries and a chance to compare the legal situation.

    Sixteen important areas of biotechnology have been chosen for this overview:

    • Assisted reproduction
    • Preimplantation genetic diagnosis (PGD)
    • Preimplantation genetic screening (PGS)
    • Abortion
    • Prenatal Diagnosis and/or screening
    • Organ and tissue transplantation
    • Embryo research
    • Cloning
    • Clinical research on humans
    • Human biobanks
    • Ethical committees
    • Genetic testing
    • Advanced therapy medicinal products
    • Genetically modified organisms
    • Animal experimentation
    • Legal status of Council of Europe Biomedicine Convention and its additional protocols
  • 3799.
    Legislation on biotechnology in the Nordic countries: an overview 20142014Rapport (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    The legislation on biotechnology varies markedly from one Nordic country to another. The aim of this report is to give the reader information of the current status in the different countries and a chance to compare the legal situations. Sixteen important areas of biotechnology have been chosen for this overview:

    • Assisted reproduction
    • Preimplantation genetic diagnosis (PGD)
    • Preimplantation genetic screening (PGS)
    • Abortion
    • Prenatal Diagnosis and/or screening
    • Organ and tissue transplantation
    • Embryo research
    • Cloning
    • Clinical research on humans
    • Human biobanks
    • Ethical committees
    • Genetic testing
    • Advanced therapy medicinal products
    • Genetically modified organisms
    • Animal experimentation
    • Legal status of Council of Europe Biomedicine Convention and its additional protocols
  • 3800.
    Palmgren, Juni ()
    Karolinska Institutet.
    Nordic biobanks and registers: A basis for innovative research on health and welfare2017Rapport (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    The report describes a knowledge base for cross-border development of research that uses Nordic registers, biobanks and clinical studies, and offers suggestions for policy implications. Separate reports are provided on the Nordic Trial Alliance (NTA), the Nordic eScience Action Plan 2.0 and Open Access to research data from a Nordic perspective.

    This report focuses on registers and biobanks as research infrastructures for innovative research on health and welfare. The Nordic countries have very similar and unique healthcare and welfare systems. The personal identification number (PIN) for each citizen makes it possible to carry out longitudinal research and research based on a combination of health registers (e.g. healthcare data, biobanks, register on the prevalence of different diseases and causes of death) and social registers (e.g. education, employment, migration, gender representation in democratic decision-making). In contrast to the rest of the world, the Nordic countries have very long time series at the population level, considered to be a unique “goldmine” for research. The proposed longitudinal data infrastructure is particularly well suited to studying changes in the Nordic welfare model over time and for setting up a unique basis for personalised medicine/precision medicine that could guide medical practice in real time, including social and behavioural aspects.

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