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1.
  • Farnebo, Jacob, et al. (författare)
  • Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma
  • 2014
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14, s. 408-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression-free patient survival. Methods: Thirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n = 18), sorafenib (n = 19) or pazopanib (n = 2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression-free survival. Results: Thirty-five patients with at least one metabolically active metastatic lesion prior to treatment underwent additional FDG-PET examinations after 14 (n = 32) and/or 28 days (n = 30) of treatment. Changes in either SULpeak or total lesion glycolysis were correlated to both progression-free and overall survival (for TLG2.5 responders, HR = 0.38 (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders, HR = 0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders, HR = 0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In contrast SUVmax response did not predict progression-free or overall survival (HR = 0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively). Conclusions: Assessment of early changes in SULpeak and total lesion glycolysis undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly predict progression-free and overall survival in patients with mRCC.
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2.
  • Aartsen, M. G., et al. (författare)
  • The IceCube Neutrino Observatory : instrumentation and online systems
  • 2017
  • Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.
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3.
  • Abbasi, R., et al. (författare)
  • Calibration and characterization of the IceCube photomultiplier tube
  • 2010
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 618:1-3, s. 139-152
  • Tidskriftsartikel (refereegranskat)abstract
    • Over 5000 PMTs are being deployed at the South Pole to compose the IceCube neutrino observatory. Many are placed deep in the ice to detect Cherenkov light emitted by the products of high-energy neutrino interactions, and others are frozen into tanks on the surface to detect particles from atmospheric cosmic ray showers. IceCube is using the 10-in. diameter R7081-02 made by Hamamatsu Photonics. This paper describes the laboratory characterization and calibration of these PMTs before deployment. PMTs were illuminated with pulses ranging from single photons to saturation level. Parameterizations are given for the single photoelectron charge spectrum and the saturation behavior. Time resolution, late pulses and afterpulses are characterized. Because the PMTs are relatively large, the cathode sensitivity uniformity was measured. The absolute photon detection efficiency was calibrated using Rayleigh-scattered photons from a nitrogen laser. Measured characteristics are discussed in the context of their relevance to IceCube event reconstruction and simulation efforts. (C) 2010 Elsevier B.V. All rights reserved.
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4.
  • Abbasi, R., et al. (författare)
  • The IceCube data acquisition system : Signal capture, digitization, and timestamping
  • 2009
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 601:3, s. 294-316
  • Tidskriftsartikel (refereegranskat)abstract
    • IceCube is a km-scale neutrino observatory under construction at the South Pole with sensors both in the deep ice (InIce) and on the surface (IceTop). The sensors, called Digital Optical Modules (DOMs). detect, digitize and timestamp the signals from optical Cherenkov-radiation photons. The DOM Main Board (MB) data acquisition subsystem is connected to the central DAQ in the IceCube Laboratory (ICL) by a single twisted copper wire-pair and transmits packetized data on demand. Time calibration is maintained throughout the array by regular transmission to the DOMs of precisely timed analog signals, synchronized to a central GPS-disciplined clock. The design goals and consequent features, functional capabilities, and initial performance of the DOM MB, and the operation of a combined array of DOMs as a system, are described here. Experience with the first InIce strings and the IceTop stations indicates that the system design and performance goals have been achieved. (c) 2009 Elsevier B.V. All rights reserved.
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  • Gustafson, Per, et al. (författare)
  • Tuberculosis in Bissau: incidence and risk factors in an urban community in sub-Saharan Africa
  • 2004
  • Ingår i: International Journal of Epidemiology. - Oxford : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 33:1, s. 163-172
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Despite the long history of tuberculosis (TB) research, population-based studies from developing countries are rare. Methods In a prospective community study in Bissau, the capital of Guinea-Bissau, we assessed the impact of demographic, socioeconomic and cultural risk factors on active TB. A surveillance system in four districts of the capital identified 247 adult (greater than or equal to15 years) cases of intrathoracic TB between May 1996 and June 1998. Risk factors were evaluated comparing cases with the 25 189 adults living in the area in May 1997. Results The incidence of intrathoracic TB in the adult population was 471 per 100 000 person-years. Significant risk factors in a multivariate analysis were increasing age (P < 0.0001), male sex (odds ratio [OR] = 2.58, 95% CI: 1.85, 3.60), ethnic group other than the largest group (Pepel) (OR = 1.64, 95% CI: 1.20, 2.22), adult crowding (OR = 1.68, 95% CI: 1.18, 2.39 for >2 adults in household), and poor quality of housing (OR = 1.66, 95% CI: 1.24, 2.22). Household type was important; adults living alone or with adults of their own sex only, had a higher risk of developing TB than households with husband and wife present, the adjusted OR being 1.76 (95% CI: 1.11, 2.78) for male households and 3.80 (95% CI: 1.69, 8.56) for female households. In a multivariate analysis excluding household type, child crowding was a protective factor, the OR being 0.68 (95% CI: 0.51, 0.90) for households with >2 children per household. Conclusions Bissau has a very high incidence of intrathoracic TB. Human immunodeficiency virus (HIV), increasing age, male sex, ethnicity, adult crowding, family structure, and poor housing conditions were independent risk factors for TB. Apart from HIV prevention, TB control programmes need to emphasize risk factors such as socioeconomic inequality, ethnic differences, crowding, and gender.
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7.
  • Jalilehvand, F., et al. (författare)
  • New class of oligonuclear platinum-thallium compounds with a direct metal-metal bond. 5. Structure determination of heterodimetallic cyano complexes in aqueous solution by EXAFS and vibrational spectroscopy
  • 2001
  • Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 40:16, s. 3889-3899
  • Tidskriftsartikel (refereegranskat)abstract
    • The structures of three closely related heterodimetallic cyano complexes, [(NC)(5)Pt-Tl(CN)(n)](n-) (n = 1-3), formed in reactions between [Pt-II(CN)(4)](2-) and Tl-III cyano complexes, have been studied in aqueous solution. Multinuclear NMR data ((TI)-T-205, Pt-195, and C-13) were used for identification and quantitative analysis. X-ray absorption spectra were recorded at the Pt and TlLIII edges. The EXAFS data show, after developing a model describing the extensive multiple scattering within the linearly coordinated cyano ligands, short Pt-Tl bond distances in the [(NC)(5)Pt-Tl(CN)(n)](n-) complexes: 2.60(1), 2.62(1), and 2.64(1) Angstrom for n = 1-3, respectively. Thus, the Pt-Tl bond distance increases with increasing number of cyano ligands on the thallium atom. In all three complexes the thallium atom and five cyano ligands, with a mean Pt-C distance of 2.00-2.01 Angstrom, octahedrally coordinate the platinum atom. In the hydrated [(NC)(5)Pt-Tl(CN)(H2O)(4)](-) species the thallium atom coordinates one cyano ligand, probably as a linear Pt-TI-CN entity with a Tl-C bond distance of 2.13(1) Angstrom, and possibly four loosely bound water molecules with a mean Tl-O bond distance of about 2.51 Angstrom. In the [(NC)(5)Pt-Tl(CN)(2)](2-) species, the thallium atom probably coordinates the cyano ligands trigonally with two TI-C bond distances at 2.20(2) Angstrom, and in [(NC)(5)Pt-Tl(CN)(3)]Tl3- coordinates tetrahedrally with three TI-C distances at 2.22(2) Angstrom. EXAFS data were reevaluated for previously studied mononuclear thallium(III)-cyano complexes in aqueous solution, [Tl(CN)(2)(H2O)(4)](+), [Tl(CN)(3)(H2O)], and [Tl(CN)(4)](-), and also for the solid K[TI(CN)(4)] compound. A comparison shows that the TI-C bond distances are longer in the dinuclear complexes [(NC)(5)Pt-TI(CN)(n)](n-) (it = 1-3) for the same coordination number. Relative oxidation states of the metal atoms were estimated from their Pt-195 and (TI)-T-205 chemical shifts, confirming that the I(NC)5Pt-TI(CN),]n- complexes can be considered as metastable intermediates in a two-electron-transfer redox reaction from platinum(II) to thallium(III). Vibrational spectra were recorded and force constants from normal-coordinate analyses are used for discussing the delocalized bonding in these species.
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  • Linderholm, Mats, et al. (författare)
  • Local host response in the lower respiratory tract in nephropathia epidemica
  • 1993
  • Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 25:5, s. 639-646
  • Tidskriftsartikel (refereegranskat)abstract
    • Various lines of evidence suggest a respiratory route of transmission of nephropathia epidemica (NE). To study the response of the respiratory tract in NE, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed in 5 patients in the acute phase of the disease. Compared to a reference group of 15 healthy individuals, BAL fluid of NE patients contained significantly higher total numbers of cells (p < 0.05) and significantly higher numbers of lysozyme-positive macrophages (p < 0.01), CD8+ T cells (p < 0.01), and natural killer (NK) cells (p < 0.01). There was no significant difference in numbers of CD4+ T cells, B cells, or neutrophils. When blood samples of 16 patients were examined at various intervals after onset of NE, a significant decrease in the number of NK cells (p < 0.01) was found in the acute phase of the disease. The findings are compatible with the presence of a local host response in the lower respiratory tract to NE virus infection.
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  • Loring, John S, et al. (författare)
  • Rethinking Arsenate Coordination at the Surface of Goethite
  • 2009
  • Ingår i: Chemistry: A European Journal. - Weinheim : Wiley. - 1521-3765 .- 0947-6539. ; 15:20, s. 5063-5072
  • Tidskriftsartikel (refereegranskat)abstract
    • A fundamental precept of geochemistry is that arsenate coordinates at mineral surfaces in a predominately bridging-bidentate fashion. We show that this is incorrect for the model system, arsenate adsorbed at the surface of goethite (alpha-FeOOH), using a combination of XRD, EXAFS, and IR spectroscopic results. We report the crystal structure of pentaamminecobalt(III) arsenate, which consists of monodentate-coordinated metal-arsenato complexes that have Co-As distances of only 3.25 angstrom. This result implies that metal-arsenic distances are not diagnostic for the coordination mode of arsenate. We show that the K-edge EXAFS spectra of pentaamminecobalt(ill) arsenate and arsenate-goethite surface complexes are strikingly similar, which suggests that arsenate could be coordinated at the goethite surface in a monodentate fashion. Refinements of the k(3)-weighted EXAFS spectra of arsenate adsorbed on goethite results in values of CNAs-Fe between 0.8-1.1 (+/- 0.7), and there is no evidence that the coordination mode of arsenate changes as a function of pH or arsenate surface coverage. We report IR spectra from the first simultaneous IR and potentiometric titration of arsenate adsorbed on deuterated goethite (alpha-FeOOD) in D2O, and we show for the first time the As-O stretching bands of arsenate-goethite surface complexes. We deduce that arsenate-goethite surface complexes are un-, singly, or doubly protonated, depending on pH, from a principal component analysis of the As-O stretching region and an interpretation of the Type-B OH stretching region. In summary, our cumulative results show that arsenate coordinates at the water-goethite interface in a predominately monodentate fashion. Furthermore, we find no evidence for bridging-bidentate coordination, which is a finding that impacts oxoanion bioavailability and challenges theories of mineral dissolution and surface complexation.
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  • Macheridis, Stella, et al. (författare)
  • Preliminary strontium isotope (87Sr/86Sr) baselines for the Bjäre Peninsula and Halland in southern Sweden
  • 2024
  • Ingår i: Frontiers in Environmental Archaeology. - 2813-432X. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • During the last decade, the application of strontium isotope analysis (87Sr/86Sr) has increased rapidly. The understanding of the strontium isoscape and the construction of a strontium isotope baseline in southern Scandinavia are biased toward Denmark and southwestern to eastern Scania. We report the results of new baseline samples in Halland and the Bjäre Peninsula, adding to the rich strontium isotope library that exists for southern Scandinavia. We add nuance to the previous divisions of Scania, in which the Bjäre Peninsula is not well represented. The results show that the Bjäre Peninsula is characterized by relatively low 87Sr/86Sr values gathered in the preliminary baseline 0.7100 ± 0.0024 (2s, n = 8), similar to that of southwest Scania and Zealand in Denmark. There is a greater variation and higher values among the Halland samples. Together with previously published faunal samples, a preliminary 87Sr/86Sr baseline for Halland is 0.7122 ± 0.0055 (2s, n = 24). We apply these baseline results to archaeological cases, both human and animal, from recent excavations in the Bjäre Peninsula. The results imply that there was a certain degree ofmobility and interaction across the landscape in this region of southern Scandinavia in prehistory.
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14.
  • Muszynska, Carolina, et al. (författare)
  • Predictors of incidental gallbladder cancer in patients undergoing cholecystectomy for benign gallbladder disease : Results from a population-based gallstone surgery registry
  • 2017
  • Ingår i: Surgery. - : Elsevier BV. - 0039-6060 .- 1532-7361. ; 162:2, s. 256-263
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Gallbladder cancer is a rare neoplasm with a poor prognosis. Early diagnosis and correct treatment strategy is important. The aim of this study was to identify predictors for incidental gallbladder cancer. Methods: Data from cholecystectomies registered in the nationwide Swedish Register for Gallstone Surgery between 2007 and 2014 were analyzed for incidental gallbladder cancer. Exclusion criteria were patients with a gallbladder not sent for histopathology, preoperative suspicion of polyps/gallbladder cancer, and indication for operation for other reasons than gallstone disease. Predictive factors for incidental gallbladder cancer were identified using multivariable logistic regression. Results: A total of 86,154 procedures were registered in the Swedish Register for Gallstone Surgery. Of these, 36,355 patients were included in the analysis, and 215 of the included patients had incidental gallbladder cancer (0.59%). Mean age was 70 ± 11 years for index cases and 54 ± 16 years for the control group, and 80% of cases and 60% of controls were female. Predictors for incidental gallbladder cancer were older age (odds ratio = 1.08; P < .001), female sex (odds ratio = 3.58; P < .001), previous cholecystitis (odds ratio = 1.37; P = .045), and the combination of acute cholecystitis without jaundice (odds ratio = 1.39; P = .041) and jaundice without acute cholecystitis (odds ratio = 2.02; P = .009). A preoperative risk model including these factors gave an area under receiver operating characteristic curve of 0.82. By adding macroscopic evaluation of the gallbladder by the surgeon, the area under receiver operating characteristic curve increased to 0.87. Intraoperatively suspected gallbladder cancer was confirmed as cancer in 31% of the cases. Conclusion: Incidental gallbladder cancer is more likely to be diagnosed in older patients, women, and after previous cholecystitis. Jaundice and acute cholecystitis were also shown to be important risk factors. Intraoperative inspection of the gallbladder improved the risk model.
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  • Rahman, Hafizur, et al. (författare)
  • The effect of increased pulp yield using additives in the softwood kraft cook on the physical properties of low-grammage handsheets
  • 2017
  • Ingår i: Nordic Pulp & Paper Research Journal. - : AB SVENSK PAPPERSTIDNING. - 0283-2631 .- 2000-0669. ; 32:3, s. 317-323
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of increasing the pulp yield by the addition of sodium borohydride (NaBH4) or polysulfide (PS) in softwood kraft cooking, i.e. enhancing the retention of glucomannan, on the physical properties of low-grammage handsheets was studied. In addition to the yield improvement, an increase in tensile index was observed, especially at lower degrees of beating. These higher yield pulps showed an increase in pore volume, indicating an increased degree of swelling of the fibres. Presumably, the increased flexibility of the fibres affects the bonding strength and leads to the higher tensile index observed.
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  • Saldaño, H. P., et al. (författare)
  • SuperCAM CO(3-2) APEX survey at a 6 pc resolution in the Small Magellanic Clouds
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 687
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The Small Magellanic Cloud (SMC) is an ideal laboratory for studying the properties of star-forming regions thanks to its low metallicity, which has an impact on the molecular gas abundance. However, a small number of molecular gas surveys of the entire galaxy have been carried out in the last few years, limiting the measurements of interstellar medium (ISM) properties in a homogeneous manner. Aims. We present the CO(3-2) APEX survey at a 6 pc resolution of the bar of the SMC, observed with the SuperCAM receiver attached to the APEX telescope. This high-resolution survey has allowed us to study certain properties of the ISM and to identify CO clouds in the innermost parts of the H2 envelopes. Methods. We adopted the CO analysis in the SMC bar comparing the CO(3-2) survey with that of the CO(2-1) of a similar resolution. We studied the CO(3-2)-To-CO(2-1) ratio (R32), which is very sensitive to the environment properties (e.g., star-forming regions). We analyzed the correlation of this ratio with observational quantities that trace the star formation such as the local CO emission, the Spitzer color [70/160], and the total IR surface brightness measured from the Spitzer and Herschel bands. For the identification of the CO(3-2) clouds, we used the CPROPS algorithm, which allowed us to measure the physical properties of the clouds. We analyzed the scaling relationships of such physical properties. Results. We obtained R32 = 0.65 ± 0.02 for the SW bar and a slightly higher ratio, R32 = 0.7 ± 0.1, for N66 in the SMC. We found that R32 varies from region to region, depending on the star formation activity. In regions dominated by HII and photo-dissociated regions (e.g., N22, N66) R32 tends to be higher than the median values. Meanwhile, lower values were found toward quiescent clouds. We also found that R32 is correlated with the IR color [70/160] and the total IR surface brightness. This finding indicates that R32 increases with environmental properties, such as the dust temperature, total gas density, and radiation field. We identified 225 molecular clouds with sizes of R > 1.5 pc and signal-To-noise ratios (S/N) of >3, of which only 17 are well resolved CO(3-2) clouds with S/N 5. These 17 clouds follow consistent scaling relationships to the inner Milky Way clouds but with some departures. For instance, CO(3-2) tends to be less turbulent and less luminous than the inner Milky Way clouds of similar sizes. Finally, we estimated a median virial-based CO(3-2)-To-H2 conversion factor of 12.6-7+10 M-(K km s-1 pc2)-1 for the total sample.
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  • Sandstrom, K., et al. (författare)
  • Inhibition of the CD28-CD80 co-stimulation signal by a CD28-binding affibody ligand developed by combinatorial protein engineering
  • 2003
  • Ingår i: Protein Engineering. - : Oxford University Press (OUP). - 0269-2139 .- 1460-213X. ; 16:9, s. 691-697
  • Tidskriftsartikel (refereegranskat)abstract
    • CD28 is one of the key molecules for co-stimulatory signalling in T cells. Here, novel ligands (affibodies) showing selective binding to human CD28 (hCD28) have been selected by phage display technology from a protein library constructed through combinatorial mutagenesis of a 58-residue three-helix bundle domain derived from staphylococcal protein A. Analysis of selected affibodies showed a marked sequence homology and biosensor analyses showed that all investigated affibodies bound to hCD28 with micromolar affinities (K-D). No cross-reactivity towards the related protein human CTLA-4 could be observed. This lack of cross-reactivity to hCTLA-4 suggests that the recognition site on hCD28 for the affibodies resides outside the conserved MYPPPYY motif. The apparent binding affinity for hCD28 could be improved through fusion to an Fc fragment fusion partner, resulting in a divalent presentation of the affibody ligand. For the majority of selected anti-CD28 affibodies, in co-culture experiments involving Jurkat T-cells and CHO cell lines transfected to express human CD80 (hCD80) or LFA-3 (hLFA-3) on the cell surface, respectively, pre-incubation of Jurkat cells with affibodies resulted in inhibition of IL-2 production when they were co-cultured with CHO (hCD80(+)) cells, but not with CHO (hLFA-3(+)) cells. For one affibody variant denoted Z(CD28:5) a clear concentration-dependent inhibition was seen, indicating that this affibody binds hCD28 and specifically interferes in the interaction between hCD28 and hCD80.
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  • Sandstrom, Per, et al. (författare)
  • Highly selective iNOS inhibition and sphincter of Oddi motility in the Australian possum
  • 2004
  • Ingår i: Acta Physiologica Scandinavica. - 0001-6772 .- 1365-201X. ; 181:3, s. 321-331
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim:  Inducible nitric oxide synthase (iNOS) plays a major role in acute pancreatitis. Selective inhibitors of iNOS are being developed as therapeutic agents. Sphincter of Oddi (SO) dysfunction may cause pancreatitis and nitric oxide is necessary for SO relaxation. A new highly selective iNOS inhibitor, AR-C102222AA (AR-C), is evaluated together with the established iNOS inhibitor, l-N6-(1-iminoethyl)lysine (l-NIL), and the selective neuronal nitric oxide synthase (nNOS) blocker S-methyl-l-thiocitrulline (SMTC).Methods:  In anaesthetized Australian Brush-tailed possums, the effect of topical, i.v. or i.a. administration of these drugs was evaluated on spontaneous SO motility, blood pressure (BP) and pancreatic vascular perfusion. SO motility was recorded by manometry and pancreatic vascular perfusion by laser Doppler fluxmetry. Also, the effect of SMTC and AR-C on electrical field stimulation (EFS)-induced non-cholinergic non-adrenergic (NANC) SO relaxation in vitro was evaluated.Results:  Infusion of AR-C (0.1–30 μmol kg−1) increased SO contraction frequency (P = 0.026) only at the two highest doses. l-NIL infusion (0.15 to 14.7 μmol kg−1) also increased SO contraction frequency at 8.8 μmol kg−1 (P < 0.05) and reduced SO contraction amplitude at the two highest doses (P < 0.05). SMTC injections (0.5 nmol–2.4 μmol) produced a dose-dependent increase in SO contraction frequency (P = 0.009), but no effect was seen on the other parameters. In vitro SMTC (40–400 μm) inhibited EFS-induced NANC relaxation in a dose-dependent manner (P < 0.0005). In contrast AR-C (10–500 μm) had no effect on EFS-induced NANC relaxation (P > 0.05).Conclusions:  At low doses, AR-C does not effect SO motility or EFS-induced NO mediated relaxation. However, high doses of AR-C and L-NIL in vivo influenced SO motility by inhibiting nNOS activity and these effects need be considered in relation to therapeutic doses of this agent.
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  • Sandstrom, Ulf G., et al. (författare)
  • Ecological diversity of birds in relation to the structure of urban green space
  • 2006
  • Ingår i: Landscape and Urban Planning. - : Elsevier BV. - 0169-2046 .- 1872-6062. ; 77:1-2, s. 39-53
  • Tidskriftsartikel (refereegranskat)abstract
    • A functional network of green space is important for the maintenance of the ecological dimension of a sustainable urban landscape. We used avian ecological diversity as a proxy for evaluating the functionality of different types of urban green space. The urban landscape of the municipality of Orebro in Sweden was stratified into four strata (City centre, Residential, Greenway and Periphery). Bird species found in these strata were classified into four ecological groups with decreasing degree of specialisation (woodpeckers, hole-nesters, forest birds and urban birds). Overall there was lower bird species richness in the City centre and Residential areas compared to the Greenway and Periphery. Woodpeckers, hole-nesters and forest birds showed an increasing trend in the number of species as well as individuals from the City centre to the Periphery while urban birds showed the opposite trend. The amount and quality of green space as well as natural vegetation increased from the City centre to the Periphery. Species richness of woodpeckers, forest birds and hole-nesters were positively correlated with tree density while urban birds showed an inverse correlation. There was no dead wood in City centre, Residential and Greenway in contrast to the Periphery, which held some dying trees, stumps and old windthrows. Our findings emphasise the importance of urban green space with natural structures to maintain high ecological diversity. Finally, we discuss how conflicts between habitat for biodiversity maintenance and other functions of green space could be handled by zoning. (c) 2005 Elsevier B.V. All rights reserved.
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  • Sjöberg, Elin, et al. (författare)
  • A minority-group of renal cell cancer patients with high infiltration of CD20+B-cells is associated with poor prognosis
  • 2018
  • Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 119:7, s. 840-846
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The role of B-lymphocytes in solid tumours is unclear. Tumour biology studies have implied both anti- and pro-tumoural effects and prognostic studies have mainly linked B-cells to increased survival. This study aimed to analyse the clinical relevance of B-lymphocytes in renal cell cancer (RCC), where information on the prognostic impact is lacking.METHODS: Following immunohistochemistry (IHC) stainings with a CD20 antibody, density of CD20+ B-cells was quantified in an RCC discovery-and validation cohort. Associations of B-cell infiltration, determined by CD20 expression or a B-cell gene-signature, and survival was also analysed in 14 publicly available gene expression datasets of cancer, including the kidney clear cell carcinoma (KIRC) dataset.RESULTS: IHC analyses of the discovery cohort identified a previously unrecognised subgroup of RCC patients with high infiltration of CD20+ B-cells. The B-cell-high subgroup displayed significantly shorter survival according to uni- and multi-variable analyses. The association between poor prognosis and high density of CD20+ B-cells was confirmed in the validation cohort. Analyses of the KIRC gene expression dataset using the B-cell signature confirmed findings from IHC analyses. Analyses of other gene expression datasets, representing 13 different tumour types, indicated that the poor survival-association of B-cells occurred selectively in RCC.CONCLUSION: This exploratory study identifies a previously unrecognised poor-prognosis subset of RCC with high density of CD20-defined B-cells.
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25.
  • Slingerland, Marije, et al. (författare)
  • A phase I, open-label, multicenter study to evaluate the pharmacokinetics and safety of oral panobinostat in patients with advanced solid tumors and various degrees of hepatic function
  • 2014
  • Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 74:5, s. 1089-1098
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate the pharmacokinetics and safety of oral panobinostat in patients with advanced solid tumors and varying degrees of hepatic function. Patients with advanced solid malignancies, acceptable bone marrow and renal function, and normal or impaired hepatic function, per NCI-ODWG criteria, were eligible. Initially patients received a single oral dose of 30 mg panobinostat for a 1-week pharmacokinetic study (core phase). Subsequently, patients received thrice-weekly panobinostat for as long as beneficial (extension phase safety assessment). Core phase serial blood samples for panobinostat and metabolite BJB432 assay were collected pre-dose and up to 96 h post-dose. Twenty-five patients were enrolled, median age 58 years (range 45-76). Fifteen patients had hepatic dysfunction (8 mild, 6 moderate, and 1 severe). Reductions in panobinostat plasma clearance were 30 and 51 %, with concomitant 43 and 105 % increase in exposure, for patients with mild and moderate hepatic dysfunction, respectively. Median peak plasma concentrations were 1.4-(mild) and 1.8-(moderate) fold higher than the normal group. Hepatic impairment did not alter panobinostat absorption with Tmax unchanged at 2 h. Geometric mean ratios of BJB432 to panobinostat plasma AUC(0-a) were similar in patients with normal, mild, or moderate hepatic impairment. Safety data were consistent with known safety profile of panobinostat in patients with advanced cancers and normal liver function. Despite increased plasma exposure, patients with mild or moderate hepatic dysfunction could be safely treated with the same starting dose of panobinostat as patients with normal hepatic function, with careful monitoring and dose adjustments as required.
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26.
  • Stattin, Pär, et al. (författare)
  • Real World Outcomes in Patients With Metastatic, Castration-Resistant Prostate Cancer Treated With Radium-223 in Routine Clinical Practice in Sweden
  • 2023
  • Ingår i: Clinical Genitourinary Cancer. - : Elsevier. - 1558-7673 .- 1938-0682. ; 21:1, s. 107.e1-107.e9
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: Estimate the effect of Radium-223 (Ra-223) on the incidence of bone fractures, prostate cancer death, and all-cause death compared with other standard treatments for metastatic, castration-resistant prostate cancer (mCRPC).METHODS: Using a cohort design, we estimated the effect of Ra-223 on the risk of bone fractures, all-cause and prostate cancer-specific mortality across different lines of treatment for mCRPC using Prostate Cancer data Base Sweden (2013-2018). The comparator group comprised other standard treatments for mCRPC. We used 36-month risk differences and hazard ratios (HRs) as effect estimates.RESULTS: The number of eligible individuals was 635, 453, 262, and 84 for the first-, second-, third-, and fourth-line cohorts, respectively. When compared Ra-223 to other standard treatments, the difference in the 36-month risk of fracture was 6% (95% confidence interval [CI], -7% to 18%) in the first-line cohort (n = 635) and 8% (95% CI, -7% to 18%) in the second-line cohort (n = 453). The number of fractures in the third-/fourth-line cohorts was too small for an adjusted comparison. The difference in 36-month mortality was higher in the first-line cohort 13% (95% CI, -3% to 31%), but lower in the second- and third-/fourth-line cohorts-8% (95% CI, -23% to 7%) and -14% (95% CI, -21% to 16%) respectively. Most deaths were due to prostate cancer.CONCLUSION: Results suggest that the difference in the risk of fractures is small, if any. A difference in the risk of mortality may be present in first-line treatment, but a decreased risk of mortality was observed in second and later lines of treatment. The results on mortality need to be considered in the context of potential unmeasured or residual confounding.
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27.
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28.
  • Wedin, Madelene, et al. (författare)
  • Validation of the Lymphoedema Quality of Life Questionnaire (LYMQOL) in Swedish cancer patients
  • 2020
  • Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 59:3, s. 365-371
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this study was to validate a translated Swedish version of the lymphoedema-specific quality of life questionnaire (LYMQOL) in a cohort of Swedish cancer patients with secondary lymphoedema of the limbs after cancer treatment.Material and methods: We recruited 102 patients with lymphoedema of the arms or legs after cancer treatment who were visiting lymphoedema therapists at the departments of oncology at the university hospitals in Linköping and Umeå. The LYMQOL questionnaires were translated forward and backward from English to Swedish. Content and face validity were evaluated. The construct validity was assessed by comparing the LYMQOL with the Short Form Health Survey (SF-36) and the perceived degree of lymphoedema of the limbs, respectively. Reliability was determined through test-retest. The internal consistency was assessed by determining Cronbach’s alpha and by factor analysis.Results: The content and face validity assessments showed that LYMQOL was an easy, clear and not too long questionnaire to use for patients with lymphoedema. Construct validity was high in both versions when compared with the SF-36. The association between the degrees of perceived lymphoedema and the LYMQOL was only significant in the domains Function and Body Image in the arm version, whereas all domains in the leg version were significant. The reliability was good for the arm version (intra-class-correlation coefficients 0.53–0.87) and very good for the leg version (intra-class-correlation coefficients 0.78–0.90). The internal consistency was acceptable to excellent, with Cronbach’s alpha values between 0.79–0.93 (arm-version) and 0.87–0.94 (leg-version). The factor analysis confirmed the usefulness of the four domains in the LYMQOL versions.Conclusions: This study confirmed the validity of the Swedish version of LYMQOL and demonstrated that LYMQOL may be a simple and useful tool for use in clinical practice and scientific contexts for evaluating QoL in patients with lymphoedema of the limbs.
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