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Sökning: WFRF:(Nilsson Mikael 1967)

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4.
  • Aleksandrov, D., et al. (författare)
  • Halo excitations in fragmentation of He-6 at 240 MeV/u on carbon and lead targets
  • 2000
  • Ingår i: Nuclear Physics A. - 0375-9474. ; 669:1-2, s. 51-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Dissociation of a 240 MeV/u beam of He-6, incident on carbon and lead targets, has been studied in kinematically complete experiments to investigate low-lying excitation modes in the halo nucleus He-6. It is shown that alignment effects characterize the inelastic scattering and allow an unambiguous assignment of the spin of a narrow resonance observed in the excitation energy spectrum. The differential cross sections for the He-6 inelastic scattering on carbon and lead targets were deduced from the measured moments of the two neutrons and the a-particle. An analysis of these distributions shows that quadrupole and, possibly, monopole excitations characterize the hadronic interaction, while the dipole mode is dominating in Coulomb dissociation. Neither theoretically predicted new resonance states in He-6 nor nuclear excitation of a dipole mode were found. Direct evidence has been obtained for strong suppression of Coulornb post-acceleration in direct Coulomb breakup in a lead target.
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5.
  • Allard, Christina, et al. (författare)
  • Rasbiologiskt språkbruk i statens rättsprocess mot sameby
  • 2015
  • Ingår i: Dagens Nyheter. - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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6.
  • Andéhn, Mikael, et al. (författare)
  • Facets of country image and brand equity : Revisiting the role of product categories in country-of-origin effect research
  • 2016
  • Ingår i: Journal of Consumer Behaviour. - : Wiley. - 1472-0817 .- 1479-1838. ; 15:3, s. 225-238
  • Tidskriftsartikel (refereegranskat)abstract
    • The country-of-origin effect is a topic central to the field of international marketing. Country of origin has been found to exert a particularly potent effect on consumer evaluation in situations where there is a strong link between a country and a particular product category. The present study provides further insight into how this particular effect can be understood. Drawing on a novel conceptualization of how country image and product categories interact, this study tested the relative evaluative relevance of product category with respect to estimates of brand equity across a variety of product categories. The findings suggest that facets of a country's image that are more closely related to the evaluation situation exert a greater influence on the evaluation of brands. This result encourages scholars as well as practitioners to re-evaluate which situations might cause the country of origin effect to hold managerial relevance and paves the way for new paths toward a more comprehensive understanding of the effect. 
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10.
  • Andersson, Sofie, 1976, et al. (författare)
  • Study of nitrate complex formation with Pm, Eu, Am and Cm using a solvent extraction technique
  • 2004
  • Ingår i: Radiochimica Acta. - : Walter de Gruyter GmbH. - 0033-8230 .- 2193-3405. ; 92:12, s. 863-867
  • Tidskriftsartikel (refereegranskat)abstract
    • The separation of actinides and lanthanides is an important question in the treatment of spent nuclear fuel in the transmutation concept. To find an efficient and well functioning separation process it is necessary to study the chemistry of the elements in the two groups in different aqueous media. The stability constants of the nitrate complex formation with Pm, Eu, Am and Cm were determined using solvent extraction. The extraction was studied using the synergistic system of 2,6-bis-(benzoxazolyl)-4-dodecyloxylpyridine and 2-bromodecanoic acid in tert-butyl benzene. As the nitrate ion concentration in the aqueous phase was increased, a decrease in separation between actinides and lanthanides was seen owing to complex formation between the different elements and the nitrate ions.
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  • Arildsson, Mikael, 1967-, et al. (författare)
  • Critical design parameters in laser Doppler perfusion imaging
  • 1996
  • Ingår i: <em>Proc. SPIE</em> 2678. - : SPIE Proceedings Series. - 9780819420527 ; , s. 401-408
  • Konferensbidrag (refereegranskat)abstract
    • Laser Doppler Perfusion Imaging (LDPI) is a method for visualization of tissue blood perfusion. A low power laser beam is used to step-wise scan a tissue area of interest and a perfusion estimate based on the backscattered, partially Doppler broadened, light is generated. Although the basic operating principle of LDPI is the same as that of conventional Laser Doppler Perfusion Monitoring (LDPM), significant differences exist between the implementation of the methods which must be taken into account in order to generate high quality perfusion images. The purpose of this study is to investigate the relevance of a number of LDPI design parameters, such as:(1) The influence of artifact noise when using a continuously moving laser beam instead of a step-wise moving beam to scan the image.(2) The signal processor output's dependency on the distance between the measurement object and the scanner head when using collimated laser light.(3) The speed and mode of the scanning.The results show a substantial rise in the noise level when using a continuously moving beam as opposed to a step-wise. Skin measurements using a collimated laser beam demonstrated an amplification factor dependency on the distance between the skin surface and the scanner head not present when using a divergent laser beam. The scanning speed is limited by the trade-off between the Doppler signal lower cut-off frequency and the image quality.
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13.
  • Arildsson, Mikael, 1967-, et al. (författare)
  • Effects on skin blood flow by provocation during local analgesia
  • 2000
  • Ingår i: Microvascular Research. - : Elsevier BV. - 0026-2862 .- 1095-9319. ; 59:1, s. 122-130
  • Tidskriftsartikel (refereegranskat)abstract
    • Although topical analgesia cream has been used for several years, little is known about its effects on the microcirculation. Previous studies have shown a vasoconstrictive effect after short application times and a vasodilatation after longer application. It has also been shown that vasomotion does not occur in the analgesized skin. The present study was undertaken to investigate the alterations in skin blood perfusion following local cooling, local heating and pin-pricking after the establishment of analgesia. In 11 healthy volunteers, skin analgesia was attained by use of a eutectic mixture of lidocaine and prilocaine (EMLA, Astra Pain Control AB, Sweden) applied to the skin three hours prior to provocation. The changes in skin blood perfusion, after applying three different provocation methods, were studied using the laser Doppler technique. Local cooling and heating to temperatures of +10 and +45°C, respectively, were applied for 9 s by use of a copper probe (Ø12 mm). In the pin-prick provocation method, a combined effect of deflection and penetration of the skin to in total 3 mm was attained. Identical provocation methods were applied to placebo treated and untreated skin areas. After heat provocation, significant differences in the perfusion response between the treatments were seen (P < 0.0001). Skin areas treated with analgesia cream responded with a slow increase in perfusion that persisted beyond the four minute measurement period. Placebo and untreated areas decreased their perfusion over time. After cooling a significant reduction in skin perfusion was seen, irrespective of the treatment. Similarly, after pin-pricking a perfusion increase was seen for all treatments. The findings indicate that topical analgesia influences the myogenic control of the blood flow in those vascular plexa measured by laser Doppler following heat provocation. No differences could be seen in the response to pin-pricking and cooling for the different treatments.
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14.
  • Arildsson, Mikael, 1967-, et al. (författare)
  • Higher order moment processing of laser Doppler perfusion signals
  • 1997
  • Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668 .- 1560-2281. ; 2:4, s. 358-363
  • Tidskriftsartikel (refereegranskat)abstract
    • The laser Doppler technique is used to assess tissue perfusion. Traditionally an integrated, ω-weighted (first-order filter) power spectrum is used to estimate perfusion. In order to be able to obtain selective information about the flow in vessels with different blood cell velocities, higher order filters have been implemented, investigated, and evaluated. Theoretical considerations show that the output of the signal processor will depend on the flow speed, for a given concentration of blood cells, according to Sout∞νn where v is the average blood cell speed and n is the spectral filter order. An implementation of filters using zero-, first-, second-, and third-order spectral moments was utilized to experimentally verify the theory by using a laser Doppler perfusion imager. Two different flow models were utilized: A Plexiglas model was used to demonstrate the various signatures of the power spectrum for different flow speeds and filter orders, whereas a Delrin model was used to study the relationship between the flow velocity and the output of the signal processor for the different filters. The results show good agreement with theory and also good reproducibility. Recordings made on the skin of the wrist area demonstrated that the flow in small veins can be visualized by the use of higher spectral orders.
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  • Bergmasth, Mikael, 1967, et al. (författare)
  • The Role of Energy Efficiency in the Deregulated Swedish Electricity Market
  • 2000
  • Ingår i: ACEEE American Council for an Energy-Efficient Economy. Pacific Grove, Kalifornien, USA.
  • Tidskriftsartikel (refereegranskat)abstract
    • Four years have passed since January 1996 when retail competition was introduced in the Swedish electricity market. These years have been characterized by a rapid restructuring of the electricity supply industry through mergers and acquisitions, lower electricity prices, and a search for new marketing strategies in the competitive market. General trends and the results of two market surveys, undertaken in 1999, of energy efficiency services from electricity suppliers in Sweden are reported here. One survey targeted a sample of industrial and commercial customers, and one survey targeted all electricity suppliers. Energy services, in particular energy efficiency services, are offered by 83 per cent of the surveyed electricity suppliers. Customer relations and building customer loyalty is reported by 88 per cent of the suppliers as a motivation for offering energy services. Nearly half of the customers report a great confidence in the suppliers' ability and sincerity to deliver energy efficiency services. 22 per cent of the customers have contracted for energy efficiency services and those customers that have contracted for energy services have often contracted for several services. Less than 20 per cent of the customers think energy services is a way for suppliers to distract customers and remove focus from electricity price. In both surveys, roughly half of the respondents report that services are priced separately from electricity. The future role of government to facilitate and support the market for energy efficiency services is discussed based on market experiences so far.
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17.
  • Blanco, A., et al. (författare)
  • Performance of timing resistive plate chambers with relativistic neutrons from 300 to 1500 MeV
  • 2015
  • Ingår i: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • A prototype composed of four resistive plate chamber layers has been exposed to quasi-monoenergetic neutrons produced from a deuteron beam of varying energy (300 to 1500 AMeV) in experiment S406 at GSI, Darmstad, Germany. Each layer, with an active area of about 2000 × 500 mm2, is made of modules containing the active gaps, all in multigap construction. Each gap is defined by 0.3 mm nylon mono-filaments positioned between 2.85 mm thick float glass electrodes. The modules are operated in avalanche mode with a non-flammable gas mixture composed of 90% C2H2F4 and 10% SF6. The signals are readout by a pick-up electrode formed by 15 copper strips (per layer), spaced at a pitch of 30 mm, connected at both sides to timing front end electronics. Measurements of the time of flight jitter of neutrons, in the mentioned energy range, point to a contribution of the resistive plate chamber in the order of 150 ps, independent of the neutron energy.
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18.
  • Ekberg, Christian, 1967, et al. (författare)
  • Determining Stability Constants Using the AKUFVE Technique
  • 2019
  • Ingår i: Solvent Extraction and Ion Exchange. - : Informa UK Limited. - 0736-6299 .- 1532-2262. ; 37:3-4, s. 213-225
  • Tidskriftsartikel (refereegranskat)abstract
    • The AKUFVE techniques were developed by Rydberg and co-workers in the 1960s. The main aim was to be able to perform a series of liquid-liquid extraction data varying one or more parameters and at the same time achieve very pure phases. As such, this technique was later used for short-lived isotope studies in the SISAK system, but also as a standalone unit for a large number of thermodynamic studies of extraction systems both for fundamental understanding as well as more applied investigations. In this paper, the apparatus with modifications made over the decades is described. In addition, studies with stability constant determinations for the zirconium-water-acetylacetone system as well as lanthanide extraction using bromodecanoic acid are exemplified to demonstrate the potential use of the technique. The results shown clearly demonstrate the versatility and ability of the AKUFVE system.
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  • Ekberg, Christian, 1967, et al. (författare)
  • Introduction
  • 2019
  • Ingår i: Solvent Extraction and Ion Exchange. - : Informa UK Limited. - 0736-6299 .- 1532-2262. ; 37:3-4, s. 211-212
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Johansson, Oskar N., 1984, et al. (författare)
  • A quick and robust method for quantification of the hypersensitive response in plants
  • 2015
  • Ingår i: Peerj. - : PeerJ. - 2167-8359. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the most studied defense reactions of plants against microbial pathogens is the hypersensitive response (HR). The HR is a complex multicellular process that involves programmed cell death at the site of infection. A standard method to quantify plant defense and the HR is to measure the release of cellular electrolytes into water after infiltration with pathogenic bacteria. In this type of experiment, the bacteria are typically delivered into the plant tissue through syringe infiltration. Here we report the development of a vacuum infiltration protocol that allows multiple plant lines to be infiltrated simultaneously and assayed for defense responses. Vacuum infiltration did not induce more wounding response in Arabidopsis leaf tissue than syringe inoculation, whereas throughput and reproducibility were improved. The method was used to study HR-induced electrolyte loss after treatment with the bacterium Pseudomonas syringae pv. tomato DC3000 harboring the effector AvrRpm1, AvrRpt2 or AvrRps4. Specifically, the influence of bacterial titer on AvrRpm1-induced HR was investigated. Not only the amplitude, but also the timing of the maximum rate of the HR reaction was found to be dose-dependent. Finally, using vacuum infiltration, we were able quantify induction of phospholipase D activity after AvrRpm1 recognition in leaves labeled with (PO4)-P-33.
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  • Kilbo Edlund, Karl, et al. (författare)
  • Long-term ambient air pollution and coronary atherosclerosis : results from the Swedish SCAPIS study
  • 2024
  • Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Despite firm evidence for an association between long-term ambient air pollution exposure and cardiovascular morbidity and mortality, results from epidemiological studies on the association between air pollution exposure and atherosclerosis have not been consistent. We investigated associations between long-term low-level air pollution exposure and coronary atherosclerosis.Methods: We performed a cross-sectional analysis in the large Swedish CArdioPulmonary bioImaging Study (SCAPIS, n = 30 154), a random general population sample. Concentrations of total and locally emitted particulate matter <2.5 μm (PM2.5), <10 μm (PM10), and nitrogen oxides (NOx) at the residential address were modelled using high-resolution dispersion models. We estimated associations between air pollution exposures and segment involvement score (SIS), coronary artery calcification score (CACS), number of non-calcified plaques (NCP), and number of significant stenoses, using ordinal regression models extensively adjusted for potential confounders.Results: Median 10-year average PM2.5 exposure was 6.2 μg/m3 (range 3.5–13.4 μg/m3). 51 % of participants were women and 51 % were never-smokers. None of the assessed pollutants were associated with a higher SIS or CACS. Exposure to PM2.5 was associated with NCP (adjusted OR 1.34, 95 % CI 1.13, 1.58, per 2.05 μg/m3). Associations with significant stenoses were inconsistent.Conclusions: In this large, middle-aged general population sample with low exposure levels, air pollution was not associated with measures of total burden of coronary atherosclerosis. However, PM2.5 appeared to be associated with a higher prevalence of non-calcified plaques. The results suggest that increased risk of early-stage atherosclerosis or rupture, but not increased total atherosclerotic burden, may be a pathway for long-term air pollution effects on cardiovascular disease.
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23.
  • Kilbo Edlund, Karl, et al. (författare)
  • Long-term ambient air pollution and coronary atherosclerosis: Results from the Swedish SCAPIS study.
  • 2024
  • Ingår i: Atherosclerosis. - 1879-1484.
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite firm evidence for an association between long-term ambient air pollution exposure and cardiovascular morbidity and mortality, results from epidemiological studies on the association between air pollution exposure and atherosclerosis have not been consistent. We investigated associations between long-term low-level air pollution exposure and coronary atherosclerosis.We performed a cross-sectional analysis in the large Swedish CArdioPulmonary bioImaging Study (SCAPIS, n=30154), a random general population sample. Concentrations of total and locally emitted particulate matter <2.5μm (PM2.5), <10μm (PM10), and nitrogen oxides (NOx) at the residential address were modelled using high-resolution dispersion models. We estimated associations between air pollution exposures and segment involvement score (SIS), coronary artery calcification score (CACS), number of non-calcified plaques (NCP), and number of significant stenoses, using ordinal regression models extensively adjusted for potential confounders.Median 10-year average PM2.5 exposure was 6.2μg/m3 (range 3.5-13.4μg/m3). 51% of participants were women and 51% were never-smokers. None of the assessed pollutants were associated with a higher SIS or CACS. Exposure to PM2.5 was associated with NCP (adjusted OR 1.34, 95% CI 1.13, 1.58, per 2.05μg/m3). Associations with significant stenoses were inconsistent.In this large, middle-aged general population sample with low exposure levels, air pollution was not associated with measures of total burden of coronary atherosclerosis. However, PM2.5 appeared to be associated with a higher prevalence of non-calcified plaques. The results suggest that increased risk of early-stage atherosclerosis or rupture, but not increased total atherosclerotic burden, may be a pathway for long-term air pollution effects on cardiovascular disease.
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24.
  • Machado, J., et al. (författare)
  • Performance of timing Resistive Plate Chambers with protons from 200 to 800 MeV
  • 2015
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 10:1, s. C01043-
  • Tidskriftsartikel (refereegranskat)abstract
    • A prototype composed of four resistive plate chamber layers has been exposed to quasi-monoenergetic protons produced from a deuteron beam of varying energy (200 to 800 AMeV) in experiment S406 at GSI, Darmstadt, Germany. The aim of the experiment is to characterize the response of the prototype to protons in this energy range, which deposit from 1.75 to 6 times more energy than minimum ionizing particles. Each layer, with an active area of about 2000 × 500 mm 2 , is made of modules containing the active gaps, all in multigap construction. Each gap is defined by 0.3 mm nylon mono-filaments positioned between 2.85 mm thick float glass electrodes. The modules are operated in avalanche mode with a non-flammable gas mixture composed of 90% C 2 H 2 F 4 and 10% SF 6 . The signals are readout by a pick-up electrode formed by 15 copper strips (per layer), spaced at a pitch of 30 mm, connected at both sides to timing front end electronics. Results show an uniform efficiency close to 100% along with a timing resolution of around 60 ps on the entire 2000 × 500 mm 2 area.
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25.
  • Nacher, E., et al. (författare)
  • Proton response of CEPA4: A novel LaBr3(Ce)-LaCl3(Ce) phoswich array for high-energy gamma and proton spectroscopy
  • 2015
  • Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 769, s. 105-111
  • Tidskriftsartikel (refereegranskat)abstract
    • A new phoswich array, for the detection of high-energy protons and gamma rays from nuclear reactions, has been built. This new detector consists of four individual closely packed scintillator detectors, each of them made of 4 cm of LaBr3(Ce) and G cm of LaCl3(Ce) in phoswich configuration (optically coupled and with a common readout). In this paper we report on the results of a beam test performed at the Bronowice Cyclotron Centre (CCB) in Krakow, showing the response of this versatile instrument to high energy protons (70-230 MeV). Furthermore, for the first time we prove that we can reconstruct the original energy of fast protons (E > 200 MeV) which pass through the total length of the crystal while still retaining a good energy resolution.
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26.
  • Nilsson, Erik, 1939-, et al. (författare)
  • Cholecystectomy : costs and health-related quality of life: a comparison of two techniques
  • 2004
  • Ingår i: International Journal for Quality in Health Care. - : Oxford University Press (OUP). - 1353-4505 .- 1464-3677. ; 16:6, s. 473-482
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Outcomes of previous health economic evaluations comparing minilaparotomy cholecystectomy and laparoscopic cholecystectomy have been inconsistent.Objective. To compare costs for minilaparotomy cholecystectomy and laparoscopic cholecystectomy and to study changes in quality of life induced by these operations.Design. Single-blind, randomized controlled trial, run from 1 March 1997 to 30 April 1999.Setting. One university hospital and four non-university hospitals in Sweden.Main measures. Cost and perceived health estimation according to the global quality of life instrument EuroQol-5D.Results. Of 1719 cholecystectomy patients at five centres, 724 entered the trial and were treated with minilaparotomy cholecystectomy or laparoscopic cholecystectomy, 362 in each group. Total health care costs were less for minilaparotomy cholecystectomy than for laparoscopic cholecystectomy (median values US$2428 for minilaparotomy cholecystectomy versus US$2613 or US$3006 for laparoscopic cholecystectomy with 100 operations per year and reusable trocars or 50 operations per year and disposable trocars, respectively). There was no significant difference in total costs (including costs due to loss of production) between minilaparotomy cholecystectomy and laparoscopic cholecystectomy with 100 operations per year and reusable trocars in laparoscopic cholecystectomy (US$3731 versus US$3649, respectively). However, in calculations assuming 50 operations per year and disposable trocars in laparoscopic cholecystectomy, this technique was more expensive than minilaparotomy cholecystectomy (US$4042 versus US$3731). Health-related quality of life was slightly but significantly lower for the minilaparotomy cholecystectomy group 1 week after surgery. One month and 1 year postoperatively no difference between the randomized groups was found.Conclusion. Total costs did not differ between minilaparotomy cholecystectomy and laparoscopic cholecystectomy with high-volume surgery and disposable trocars, whereas laparoscopic cholecystectomy was more expensive with fewer operations and disposable trocars. The gain in health-related quality of life with laparoscopic cholecystectomy compared with minilaparotomy cholecystectomy was small and of limited duration.
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29.
  • Ros, Axel, et al. (författare)
  • Non-randomised patients in a cholecystectomy trial : characteristics, procedures, and outcomes
  • 2006
  • Ingår i: BMC Surgery. - : Springer Science and Business Media LLC. - 1471-2482. ; 6:17
  • Tidskriftsartikel (refereegranskat)abstract
    •   BackgroundLaparoscopic cholecystectomy is now considered the first option for gallbladder surgery. However, 20% to 30% of cholecystectomies are completed as open operations often on elderly and fragile patients. The external validity of randomised trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy has not been studied. The aim of this study is to analyse characteristics, procedures, and outcomes for all patients who underwent cholecystectomy without being included in such a trial.MethodsCharacteristics (age, sex, co-morbidity, and ASA-score), operation time, hospital stay, and mortality were compared for patients who underwent cholecystectomy outside and within a randomised controlled trial comparing mini-laparotomy and laparoscopic cholecystectomy.ResultsDuring the inclusion period 1719 patients underwent cholecystectomy. 726 patients were randomised and 724 of them completed the trial; 993 patients underwent cholecystectomy outside the trial. The non-randomised patients were older – and had more complications from gallstone disease, higher co-morbidity, and higher ASA – score when compared with trial patients. They were also more likely to undergo acute surgery and they had a longer postoperative hospital stay, with a median 3 versus 2 days (p < 0.001 for all comparisons). Standardised mortality ratio within 90 days of operation was 3.42 (mean) (95% CI 2.17 to 5.13) for non-randomised patients and 1.61 (mean) (95%CI 0.02 to 3.46) for trial patients. For non-randomised patients, operation time did not differ significantly between mini-laparotomy and open cholecystectomy in multivariate analysis. However, the operation for laparoscopic cholecystectomy lasted 20 minutes longer than open cholecystectomy. Hospital stay was significantly shorter for both mini-laparotomy and laparoscopic cholecystectomy compared to open cholecystectomy.ConclusionNon-randomised patients were older and more sick than trial patients. The assignment of healthier patients to trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy limits the external validity of conclusions reached in such trials.
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31.
  • Sukonina, Valentina, et al. (författare)
  • FOXK1 and FOXK2 regulate aerobic glycolysis.
  • 2019
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 566, s. 279-283
  • Tidskriftsartikel (refereegranskat)abstract
    • Adaptation to the environment and extraction of energy are essential for survival. Some species have found niches and specialized in using a particular source of energy, whereas others-including humans and several other mammals-have developed a high degree of flexibility1. A lot is known about the general metabolic fates of different substrates but we still lack a detailed mechanistic understanding of how cells adapt in their use of basic nutrients2. Here we show that the closely related fasting/starvation-induced forkhead transcription factors FOXK1 and FOXK2 induce aerobic glycolysis by upregulating the enzymatic machinery required for this (for example, hexokinase-2, phosphofructokinase, pyruvate kinase, and lactate dehydrogenase), while at the same time suppressing further oxidation of pyruvate in the mitochondria by increasing the activity of pyruvate dehydrogenase kinases 1 and 4. Together with suppression of the catalytic subunit of pyruvate dehydrogenase phosphatase 1 this leads to increased phosphorylation of the E1α regulatory subunit of the pyruvate dehydrogenase complex, which in turn inhibits further oxidation of pyruvate in the mitochondria-instead, pyruvate is reduced to lactate. Suppression of FOXK1 and FOXK2 induce the opposite phenotype. Both in vitro and in vivo experiments, including studies of primary human cells, show how FOXK1 and/or FOXK2 are likely to act as important regulators that reprogram cellular metabolism to induce aerobic glycolysis.
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32.
  • Synnergren, Jane, 1967, et al. (författare)
  • Cardiomyogenic gene expression profiling of differentiating human embryonic stem cells.
  • 2008
  • Ingår i: Journal of biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 134:1-2, s. 162-70
  • Tidskriftsartikel (refereegranskat)abstract
    • Human embryonic stem cells (hESCs) can differentiate into a variety of specialized cell types. Thus, they provide a model system for embryonic development to investigate the molecular processes of cell differentiation and lineage commitment. The development of the cardiac lineage is easily detected in mixed cultures by the appearance of spontaneously contracting areas of cells. We performed gene expression profiling of undifferentiated and differentiating hESCs and monitored 468 genes expressed during cardiac development and/or in cardiac tissue. Their transcription during early differentiation of hESCs through embryoid bodies (EBs) was investigated and compared with spontaneously differentiating hESCs maintained on feeders in culture without passaging (high-density (HD) protocol). We observed a larger variation in the gene expression between cells from a single cell line that were differentiated using two different protocols than in cells from different cell lines that were cultured according to the same protocol. Notably, the EB protocol resulted in more reproducible transcription profiles than the HD protocol. The results presented here provide new information about gene regulation during early differentiation of hESCs with emphasis on the cardiomyogenic program. In addition, we also identified regulatory elements that could prove critical for the development of the cardiomyocyte lineage.
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33.
  • Synnergren, Jane, 1967, et al. (författare)
  • Differentiating human embryonic stem cells express a unique housekeeping gene signature.
  • 2007
  • Ingår i: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 25:2, s. 473-80
  • Tidskriftsartikel (refereegranskat)abstract
    • Housekeeping genes (HKGs) are involved in basic functions needed for the sustenance of the cell and are assumed to be constitutively expressed at a constant level. Based on these features, HKGs are frequently used for normalization of gene expression data. In the present study, we used the CodeLink Gene Expression Bioarray system to interrogate changes in gene expression occurring during differentiation of human ESCs (hESCs). Notably, in the three hESC lines used for the study, we observed that the RNA levels of 56 frequently used HKGs varied to a degree that rendered them inappropriate as reference genes. Therefore, we defined a novel set of HKGs specifically for hESCs. Here we present a comprehensive list of 292 genes that are stably expressed (coefficient of variation <20%) in differentiating hESCs. These genes were further grouped into high-, medium-, and low-expressed genes. The expression patterns of these novel HKGs show very little overlap with results obtained from somatic cells and tissues. We further explored the stability of this novel set of HKGs in independent, publicly available gene expression data from hESCs and observed substantial similarities with our results. Gene expression was confirmed by real-time quantitative polymerase chain reaction analysis. Taken together, these results suggest that differentiating hESCs have a unique HKG signature and underscore the necessity to validate the expression profiles of putative HKGs. In addition, this novel set of HKGs can preferentially be used as controls in gene expression analyses of differentiating hESCs.
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