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61.
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62.
  • Gillen, Michael, et al. (författare)
  • Effect of a spacer on total systemic and lung bioavailability in healthy volunteers and in vitro performance of the Symbicort® (budesonide/formoterol) pressurized metered dose inhaler
  • 2018
  • Ingår i: Pulmonary Pharmacology and Therapeutics. - 1094-5539 .- 1522-9629. ; 52, s. 7-17
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Many patients with chronic obstructive pulmonary disease or asthma experience difficulties in coordinating inhalation with pressurized metered-dose inhaler (pMDI) actuation. The use of a spacer device can improve drug delivery in these patients. The aim of this study was to establish the relative bioavailability of single doses of Symbicort® (budesonide/formoterol) pMDI 160/4.5 μg/actuation (2 actuations) used with and without a spacer device. In addition, an in vitro study was conducted to characterize performance of the inhaler when used in conjunction with a spacer device. Methods: A Phase I, randomized, open-label, single-dose, single-center, crossover study in 50 healthy volunteers (NCT02934607) assessed the relative bioavailability of single-dose Symbicort® pMDI 160/4.5 μg/actuation (2 actuations) with and without a spacer (AeroChamber Plus® Flow-Vu®). Inhaled doses were administered without or with activated charcoal (taken orally) to estimate total systemic exposure and exposure through the lung, respectively. The in vitro study characterized the effect of the spacer with respect to delivered dose, fine particle dose, and dose during simulated breathing of budesonide and formoterol. Results: In terms of total systemic exposure, use of the spacer increased the relative bioavailability determined by AUC(0-last) and Cmax by 68% (spacer:no spacer treatment ratio, 167.9%; 90% CI, 144.1 to 195.6) and 99% (ratio, 198.7%; 90% CI, 164.4 to 240.2) for budesonide, and 77% (ratio, 176.6%; 90% CI, 145.1 to 215.0) and 124% (ratio, 223.6%; 90% CI, 189.9 to 263.3) for formoterol, respectively, compared with pMDI alone. Similarly, the lung exposure of budesonide and formoterol increased (AUC(0-last) and Cmax by 146% [ratio, 246.0%; 90% CI, 200.7 to 301.6] and 127% [ratio, 226.5%; 90% CI, 186.4 to 275.4] for budesonide, and 173% [ratio, 272.8%; 90% CI, 202.5 to 367.4] and 136% [ratio, 236.2%; 90% CI, 192.6 to 289.6] for formoterol, respectively) when the pMDI was administered through the spacer. When assessed by AUC(0-last) quartile without spacer, subjects in the lowest exposure quartile (indicating poor inhalation technique) with Symbicort® pMDI 160/4.5 μg/actuation (2 actuations) had markedly increased total systemic and lung exposure when the same dose was administered with the spacer. In contrast, for subjects in the highest exposure quartile with pMDI alone, total systemic and lung exposure of formoterol and budesonide was similar with and without the spacer. In the in vitro study, the fine particle dose (<5 μm) of both budesonide and formoterol from the spacer at delay time (i.e. pause period after actuation) = 0 s (instantaneous) after actuation was similar to the fine particle dose when not using the spacer. The delivered doses of budesonide and formoterol from the spacer were both lower compared with the doses administered without the spacer. There was also a decrease in delivered dose with increasing delay time. Conclusions: The clinical study demonstrated that in subjects with poor inhalation technique the use of the AeroChamber Plus® Flow-Vu® spacer increased the bioavailability of Symbicort® pMDI to a level observed in subjects with good inhalation technique without a spacer. The findings from the in vitro study support the fine particle dose characteristics of Symbicort® pMDI with the AeroChamber Plus® Flow-Vu® spacer.
63.
  • Granroth, Sari, et al. (författare)
  • Investigation of interface properties of Ni/Cu multilayers by high kinetic energy photoelectron spectroscopy
  • 2009
  • Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 80:9
  • Tidskriftsartikel (refereegranskat)abstract
    • High kinetic-energy photoelectron spectroscopy (HIKE) or hard x-ray   photoelectron spectroscopy has been used to investigate the alloying of   Ni/Cu (100) multilayers. Relative intensities of the corelevels and   their chemical shifts derived from binding energy changes are shown to   give precise information on physicochemical properties and quality of   the buried layers. Interface roughening, including kinetic properties   such as the rate of alloying, and temperature effects on the processes   can be analyzed quantitatively. Using HIKE, we have been able to   precisely follow the deterioration of the multilayer structure at the   atomic scale and observe the diffusion of the capping layer into the   multilayer structure which in turn is found to lead to a segregation in   the ternary system. This is of great importance for future research on   multilayered systems of this kind. Our experimental data are   supplemented by first-principles theoretical calculations of the   core-level shifts for a ternary alloy to allow for modeling of the   influence of capping materials on the chemical shifts.
64.
  • Granroth, Sari, et al. (författare)
  • Understanding interface properties from high kinetic energy photoelectron spectroscopy and first principles theory
  • 2011
  • Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - 0368-2048 .- 1873-2526. ; 183:1-3, s. 80-93
  • Forskningsöversikt (övrigt vetenskapligt)abstract
    • Advances in instrumentation regarding 3rd generation synchrotron light sources and electron spectrometers has enabled the field of high kinetic energy photoelectron spectroscopy (HIKE) (also often denoted hard X-ray photoelectron spectroscopy (HX-PES or HAXPES)). Over the last years, the amount of investigations that relies on the HIKE method has increased dramatically and can arguably be said to have given a rebirth of the interest in photoelectron spectroscopy in many areas. It is in particular the much increased mean free path at higher kinetic energies in combination with the elemental selectivity of the core level spectroscopies in general that has lead to this fact, as it makes it possible to investigate the electronic structure of materials with a substantially reduced surface sensitivity. In this review we demonstrate how HIKE can be used to investigate the interface properties in multilayer systems. Relative intensities of the core level photoelectron peaks and their chemical shifts derived from binding energy changes are found to give precise information on physico-chemical properties and quality of the buried layers. Interface roughening, including kinetic properties such as the rate of alloying, and temperature effects on the processes can be analyzed quantitatively. We will also provide an outline of the theoretical framework that is used to support the interpretation of data. We provide examples from our own investigations of multilayer systems which comprises both systems of more model character and a multilayer system very close to real applications in devices that are considered to be viable alternative to the present read head technology. The experimental data presented in this review is exclusively recorded at the BESSY-II synchrotron at the Helmholtz-Zentrum Berlin fur-Materialien und Energie. This HIKE facility is placed at the bending magnet beamline KMC-1, which makes it different from several other facilities which relies on undulators as the source. We will therefore also briefly describe some of the salient design features of this facility.
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65.
  • Grayson, Samuel, et al. (författare)
  • Blood flow dynamics in reconstructed auricles
  • 2013
  • Ingår i: Journal of Plastic Surgery and Hand Surgery. - Taylor & Francis. - 2000-656X. ; 47:4, s. 313-316
  • Tidskriftsartikel (refereegranskat)abstract
    • Ear reconstruction with autologous rib cartilage is performed in stages. Restitution of blood flow between the separate stages is crucial to obtain a good result. Laser Doppler perfusion imaging (LDPI) and local temperature were measured in reconstructed and normal ears in response to indirect heating. Ten persons who had had a unilateral ear reconstruction were included in the study. At a minimum, 157 days had passed since the last operation. LDPI showed no difference in blood flow between the reconstructed ear and the normal ear, neither before nor after indirect heating. The upper part of the normal ear was slightly cooler than the corresponding part in the reconstructed ear. Indirect heating caused an increase of LDPI-values and temperatures in the upper, middle, and lower part of the ear both in the reconstructed ear and the normal one. Skin blood flow recovers after 3-stage ear reconstruction and shows normal dynamic response upon indirect heating.
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66.
  • Grossi, Mario, et al. (författare)
  • Pyk2 inhibition promotes contractile differentiation in arterial smooth muscle
  • 2017
  • Ingår i: Journal of Cellular Physiology. - John Wiley & Sons. - 0021-9541. ; 232:11, s. 3088-3102
  • Tidskriftsartikel (refereegranskat)abstract
    • Modulation from contractile to synthetic phenotype of vascular smooth muscle cells is a central process in disorders involving compromised integrity of the vascular wall. Phenotype modulation has been shown to include transition from voltage-dependent toward voltage-independent regulation of the intracellular calcium level, and inhibition of non-voltage dependent calcium influx contributes to maintenance of the contractile phenotype. One possible mediator of calcium-dependent signaling is the FAK-family non-receptor protein kinase Pyk2, which is activated by a number of stimuli in a calcium-dependent manner. We used the Pyk2 inhibitor PF-4594755 and Pyk2 siRNA to investigate the role of Pyk2 in phenotype modulation in rat carotid artery smooth muscle cells and in cultured intact arteries. Pyk2 inhibition promoted the expression of smooth muscle markers at the mRNA and protein levels under stimulation by FBS or PDGF-BB and counteracted phenotype shift in cultured intact carotid arteries and balloon injury ex vivo. During long-term (24–96 hr) treatment with PF-4594755, smooth muscle markers increased before cell proliferation was inhibited, correlating with decreased KLF4 expression and differing from effects of MEK inhibition. The Pyk2 inhibitor reduced Orai1 and preserved SERCA2a expression in carotid artery segments in organ culture, and eliminated the inhibitory effect of PDGF stimulation on L-type calcium channel and large-conductance calcium-activated potassium channel expression in carotid cells. Basal intracellular calcium level, calcium wave activity, and store-operated calcium influx were reduced after Pyk2 inhibition of growth-stimulated cells. Pyk2 inhibition may provide an interesting approach for preserving vascular smooth muscle differentiation under pathophysiological conditions.
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67.
  • Gustafsson, Nils, et al. (författare)
  • Elite and non-elite agenda-setting on Twitter: the case of #almedalen 2018
  • 2019
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • In this paper, we study activity on Twitter in relation to the Swedish political festival Almedalsveckan, a week-long event where political parties, interest organizations, corporations and other actors for decades have gathered on the island of Gotland to discuss politics and public affairs. In 2018, a total of 4311 events (speeches, seminars, debates etc.) were arranged by 1929 separate actors and attended by an estimated number of 45 000 unique visitors (Almedalsveckan, 2018). The intensive news reporting and public debates surrounding it have been shown to have a crucial effect on the political agenda-setting, pivotal during an election year, as in 2018 (Wendt, 2012; Östberg, 2013). The event has spawned counterparts in the other Nordic countries: Folkemødet (Denmark). Arendalsuka (Norway), Suomiareena (Finland) and Fundur Fólksins (Iceland). The Nordic political festivals are events that take place at a physical site at a certain point in time, but they are also mediated through a plethora of media channels and platforms. Twitter and social media in general have been posited as important channels in so-called inter-media agenda-setting (Vliegenhart and Walgrave, 2008), a process in which news coverage in one platform/ channel influences the agenda in another channel/platform. Some argue that power over the agenda is displaced from traditional mass media (telling its audience what issues they should consider), to social media users who tell their networks (including the traditional mass media) what issues they consider important (Delwiche 2005). Such statements might be somewhat exaggerated, but it is relatively well-established that in a hybrid media setting social media and traditional media interact in intricate ways, providing more opportunities for “non-elite interventions” (Chadwick, 2017). Almedalsveckan is an event dominated by established elite actors, but with opportunities for non-elite actors to make intrusions in the agenda-setting process. The agenda-setting attempts in relation to Almedalsveckan on Twitter thus becomes interesting both in relation to agenda-setting in other channels, and as a study object in its own right. In order to study these issues, we collected all tweets (N=104 173) containing the hashtag #almedalen during 1-8 July, 2018 (ie during the event). Preliminary results indicate that whereas communication tend to revolve around elite actors, reflecting the dominating presence of establishment organizations in Almedalen, the most active users and user networks represent non-elite actors. Of special interest is the discussions on Twitter, dominated by non-elite actors, indicating a large attention given to the presence of right-wing extremists and Nazis at the event. The results form the basis for a discussion on the interaction between elite and non-elite actors in agenda-setting in a hybrid media system.
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68.
  • Haberska, Karolina, et al. (författare)
  • Activity of lactoperoxidase when adsorbed on protein layers
  • 2008
  • Ingår i: Talanta. - Elsevier. - 1873-3573. ; 76:5, s. 1159-1164
  • Tidskriftsartikel (refereegranskat)abstract
    • Lactoperoxidase (LPO) is an enzyme, which is used as an antimicrobial agent in a number of applications, e.g., food technology. In the majority of applications LPO is added to a homogeneous product phase or immobilised on product surface. In the latter case, however, the measurements of LPO activity are seldom reported. In this paperwe have assessed LPO enzymatic activity on bare and protein modified gold surfaces by means of electrochemistry. It was found that LPO rapidly adsorbs to bare gold surfaces resulting in an amount of LPO adsorbed of 2.9mg/m2. A lower amount of adsorbed LPO is obtained if the gold surface is exposed to bovine serum albumin, bovine or human mucin prior to LPO adsorption. The enzymatic activity of the adsorbed enzyme is in general preserved at the experimental conditions and varies only moderately when comparing bare gold and gold surface pretreated with the selected proteins. The measurement of LPO specific activity, however, indicate that it is about 1.5 times higher if LPO is adsorbed on gold surfaces containing a small amount of preadsorbed mucin in comparison to the LPO directly adsorbed on bare gold.
69.
70.
  • Hadimeri, Henrik, et al. (författare)
  • A fixed protocol for outpatient clinic routines in the care of patients with severe renal failure
  • 2013
  • Ingår i: Renal failure. - Informa Healthcare. - 0886-022X. ; 35:6, s. 845-854
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:The primary aim of this study was to assess whether a fixed protocol, using a specially trained team, for intermediate follow-up to fulfillment of guideline targets is non-inferior to conventional follow-up in the care of uraemic patients. A secondary aim was to investigate possible impact on patient outcome.METHODS:The cohort comprised 424 patients from seven centers. Inclusion criteria were either serum creatinine exceeding 200 µmol/l or calculated clearance below 30 ml/min, representing CKD 4 or 5a. Six centers followed a standardized protocol (group 1). One center provided controls (group 2). The study design was prospective and interventional. The variables measured were blood hemoglobin, bicarbonate, calcium, phosphate, intact parathyroid hormone, albumin, renal function variables, blood pressure and RAAS blockade. The number of patients achieving the set goals was analyzed as a time trend to determine if the intervention resulted in an improvement.RESULTS:At baseline, group 1 had significantly lower GFR and higher serum creatinine, calcium, phosphate, calcium × phosphate product and bicarbonate, lower mean arterial pressure (MAP), systolic blood pressures and less use of RAAS. During the intervention, group 1 improved in the direction of guidelines for blood hemoglobin, albumin, bicarbonate and MAP. Outcome of secondary endpoints gave a risk of death of 30% in both groups, while the risk of renal replacement therapy was higher in group 1.CONCLUSIONS:However, the time to renal replacement therapy was significantly shorter in the intervention group, indicating that other variables than guideline achievements are important for the patient.
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