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Sökning: WFRF:(Palazzo F)

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1.
  • Tabiri, S, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Bombarda, F., et al. (författare)
  • Runaway electron beam control
  • 2019
  • Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
  • Tidskriftsartikel (refereegranskat)
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  • Krasilnikov, A., et al. (författare)
  • Evidence of 9 Be + p nuclear reactions during 2ω CH and hydrogen minority ICRH in JET-ILW hydrogen and deuterium plasmas
  • 2018
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The intensity of 9Be + p nuclear fusion reactions was experimentally studied during second harmonic (2ω CH) ion-cyclotron resonance heating (ICRH) and further analyzed during fundamental hydrogen minority ICRH of JET-ILW hydrogen and deuterium plasmas. In relatively low-density plasmas with a high ICRH power, a population of fast H+ ions was created and measured by neutral particle analyzers. Primary and secondary nuclear reaction products, due to 9Be + p interaction, were observed with fast ion loss detectors, γ-ray spectrometers and neutron flux monitors and spectrometers. The possibility of using 9Be(p, d)2α and 9Be(p, α)6Li nuclear reactions to create a population of fast alpha particles and study their behaviour in non-active stage of ITER operation is discussed in the paper.
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  • 2018
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
  • Forskningsöversikt (refereegranskat)
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  • Overview of the JET results
  • 2015
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
  • Tidskriftsartikel (refereegranskat)
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  • 2018
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:9
  • Tidskriftsartikel (refereegranskat)
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29.
  • Abel, I, et al. (författare)
  • Overview of the JET results with the ITER-like wall
  • 2013
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
  • Tidskriftsartikel (refereegranskat)abstract
    • Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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  • Romanelli, F, et al. (författare)
  • Overview of the JET results
  • 2011
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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  • Aartsen, M. G., et al. (författare)
  • PINGU : a vision for neutrino and particle physics at the South Pole
  • 2017
  • Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 44:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The Precision IceCube Next Generation Upgrade (PINGU) is a proposed low-energy in-fill extension to the IceCube Neutrino Observatory. With detection technology modeled closely on the successful IceCube example, PINGU will provide a 6 Mton effective mass for neutrino detection with an energy threshold of a few GeV. With an unprecedented sample of over 60 000 atmospheric neutrinos per year in this energy range, PINGU will make highly competitive measurements of neutrino oscillation parameters in an energy range over an order of magnitude higher than long-baseline neutrino beam experiments. PINGU will measure the mixing parameters theta(23) and Delta m(32)(2), including the octant of theta(23) for a wide range of values, and determine the neutrino mass ordering at 3 sigma median significance within five years of operation. PINGU's high precision measurement of the rate of nu(T) appearance will provide essential tests of the unitarity of the 3 x 3 PMNS neutrino mixing matrix. PINGU will also improve the sensitivity of searches for low mass dark matter in the Sun, use neutrino tomography to directly probe the composition of the Earth's core, and improve IceCube's sensitivity to neutrinos from Galactic supernovae. Reoptimization of the PINGU design has permitted substantial reduction in both cost and logistical requirements while delivering performance nearly identical to configurations previously studied.
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34.
  • Aartsen, M. G., et al. (författare)
  • Measurement of Atmospheric Neutrino Oscillations with IceCube
  • 2013
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 111:8, s. 081801-
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first statistically significant detection of neutrino oscillations in the high-energy regime (> 20 GeV) from an analysis of IceCube Neutrino Observatory data collected in 2010 and 2011. This measurement is made possible by the low-energy threshold of the DeepCore detector (similar to 20 GeV) and benefits from the use of the IceCube detector as a veto against cosmic-ray-induced muon background. The oscillation signal was detected within a low-energy muon neutrino sample (20-100 GeV) extracted from data collected by DeepCore. A high-energy muon neutrino sample (100 GeV-10 TeV) was extracted from IceCube data to constrain systematic uncertainties. The disappearance of low-energy upward-going muon neutrinos was observed, and the nonoscillation hypothesis is rejected with more than 5 sigma significance. In a two-neutrino flavor formalism, our data are best described by the atmospheric neutrino oscillation parameters vertical bar Delta m(32)(2)vertical bar = (2.3(-0.5)(+0.6)) x 10(-3) eV(2) and sin(2) (2 theta(23)) > 0.93, and maximum mixing is favored.
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  • Bausch, Birke, et al. (författare)
  • Germline NF1 mutational spectra and loss-of-heterozygosity analyses in patients with pheochromocytoma and neurofibromatosis type 1.
  • 2007
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:7, s. 2784-92
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Neurofibromatosis type 1 (NF1) is a pheochromocytoma-associated syndrome. Because of the low prevalence of pheochromocytoma in NF1, we ascertained subjects by pheochromocytoma that also had NF1 in the hope of describing the germline NF1 mutational spectra of NF1-related pheochromocytoma.MATERIALS AND METHODS: An international registry for NF1-pheochromocytomas was established. Mutation scanning was performed using denaturing HPLC for intragenic variation and quantitative PCR for large deletions. Loss-of-heterozygosity analysis using markers in and around NF1 was performed.RESULTS: There were 37 eligible subjects (ages 14-70 yr). Of 21 patients with corresponding tumor available, 67% showed somatic loss of the nonmutated allele at the NF1 locus vs. 0 of 12 sporadic tumors (P = 0.0002). Overall, 86% of the 37 patients had exonic or splice site mutations, 14% large deletions or duplications; 79% of the mutations are novel. The cysteine-serine rich domain (CSR) was affected in 35% but the RAS GTPase activating protein domain (RGD) in only 13%. There did not appear to be an association between any clinical features, particularly pheochromocytoma presentation and severity, and NF1 mutation genotype.CONCLUSIONS: The germline NF1 mutational spectra comprise intragenic mutations and deletions in individuals with pheochromocytoma and NF1. NF1 mutations tended to cluster in the CSR over the RAS-GAP domain, suggesting that CSR plays a more prominent role in individuals with NF1-pheochromocytoma than in NF1 individuals without this tumor. Loss-of-heterozygosity of NF1 markers in NF1-related pheochromocytoma was significantly more frequent than in sporadic pheochromocytoma, providing further molecular evidence that pheochromocytoma is a true component of NF1.
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  • Angelico, R, et al. (författare)
  • Biocompatible lecithin organogels: Structure and phase equilibria
  • 2005
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 21:1, s. 140-148
  • Tidskriftsartikel (refereegranskat)abstract
    • The microstructure of organogels formed upon the addition of tiny amounts of water to a solution of lecithin in fatty acid esters (viz. isopropylpalmitate and ethyloleate) was investigated by means of molecular self-diffusion measurements. In both systems lecithin and water form disconnected cylindrical reverse micelles. The ternary phase map for the lecithin/water/isopropylpalmitate has been investigated in detail. The organogel exists in a narrow region close to the lecithin-oil binary axis; for higher water content equilibrium between lamellae and reverse micelles is found. Lamellar phase occupies the lecithin-rich region, close to the lecithin corner (with the exception of a small island of hexagonal phase) and coexists with neat water close to the water-lecithin axis. The remaining part of the phase map shows the three-phase coexistence of water, oil, and lamellar phase.
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  • Angelico, R, et al. (författare)
  • Phase behavior of the lecithin/water/isooctane and lecithin/water/decane systems
  • 2004
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 20:3, s. 619-631
  • Tidskriftsartikel (refereegranskat)abstract
    • The isothermal pseudo-ternary-phase diagram was determined at 25 degreesC for systems composed of lecithin, water, and, as oil, either isooctane or decane. This was accomplished by a combination of polarizing microscopy, small-angle X-ray scattering, and NMR techniques. The lecithin-rich region of the phase diagram is dominated by a lamellar liquid-crystalline phase (L-alpha). For lecithin contents less than 60% and low hydration (mole ratio water/lecithin = W-0 < 5.5), the system forms a viscous gel of branched cylindrical reverse micelles. With increase in the water content, the system phase separates into two phases, which is either gel in equilibrium with essentially pure isooctane (for lecithin < 25%) or a gel in equilibrium with L-alpha, (for lecithin > 25%). These two-phase regions are very thin with respect to water dilution. For 8 < W-0 < 54 very stable water-in-oil emulsions form. It is only after ripening for more than I year that the large region occupied by the emulsion reveals a complex pattern of stable phases. Moving along water dilution lines, one finds (i) the coexistence of gel, isooctane and L-alpha,(ii) equilibrium between reverse micelles and spherulites, and, finally, (iii) disconnected reverse micelles that fail to solubilize water for W-0 > 54. This results in a Winsor II phase equilibrium at low lecithin content, while for lecithin > 20% the neat water is in equilibrium with a reverse hexagonal phase and an isotropic liquid-crystalline phase. The use of the decane as oil does not change the main features of the phase behavior.
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43.
  • Barazeghi, Elham, et al. (författare)
  • 5-Hydroxymethylcytosine discriminates between parathyroid adenoma and carcinoma
  • 2016
  • Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7083 .- 1868-7075. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Primary hyperparathyroidism is characterized by enlarged parathyroid glands due to an adenoma (80-85 %) or multiglandular disease (similar to 15 %) causing hypersecretion of parathyroid hormone (PTH) and generally hypercalcemia. Parathyroid cancer is rare (<1-5 %). The epigenetic mark 5-hydroxymethylcytosine (5hmC) is reduced in various cancers, and this may involve reduced expression of the ten-eleven translocation 1 (TET1) enzyme. Here, we have performed novel experiments to determine the 5hmC level and TET1 protein expression in 43 parathyroid adenomas (PAs) and 17 parathyroid carcinomas (PCs) from patients who had local invasion or metastases and to address a potential growth regulatory role of TET1. Results: The global 5hmC level was determined by a semi-quantitative DNA immune-dot blot assay in a smaller number of tumors. The global 5hmC level was reduced in nine PCs and 15 PAs compared to four normal tissue samples (p < 0.05), and it was most severely reduced in the PCs. By immunohistochemistry, all 17 PCs stained negatively for 5hmC and TET1 showed negative or variably heterogeneous staining for the majority. All 43 PAs displayed positive 5hmC staining, and a similar aberrant staining pattern of 5hmC and TET1 was seen in about half of the PAs. Western blotting analysis of two PCs and nine PAs showed variable TET1 protein expression levels. A significantly higher tumor weight was associated to PAs displaying a more severe aberrant staining pattern of 5hmC and TET1. Overexpression of TET1 in a colony forming assay inhibited parathyroid tumor cell growth. Conclusions: 5hmC can discriminate between PAs and PCs. Whether 5hmC represents a novel marker for malignancy warrants further analysis in additional parathyroid tumor cohorts. The results support a growth regulatory role of TET1 in parathyroid tissue.
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  • Barazeghi, Elham, et al. (författare)
  • A role for TET2 in parathyroid carcinoma
  • 2017
  • Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 24:7, s. 329-338
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary hyperparathyroidism (pHPT) is rarely caused by parathyroid carcinoma (PC, <1-5% of pHPT cases). The TET proteins oxidize the epigenetic mark 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and inactivation by mutation or epigenetic deregulation of TET1 and TET2 play important roles in various cancers. Recently, we found that 5hmC was severely reduced in all of the analyzed PCs and with deranged expression of TET1 for the majority of PCs. Here, we have examined the expression of the TET2 protein in 15 5hmC-negative PCs from patients who had local invasion or metastases. Cell growth and cell migratory roles for TET2 as well as epigenetic deregulated expression were addressed. Immunohistochemistry revealed very low/undetectable expression of TET2 in all PCs and verified for two PCs that were available for western blotting analysis. Knockdown of TET2 in the parathyroid cell line sHPT-1 resulted in increased cell growth and increased cell migration. DNA sequencing of TET2 in PCs revealed two common variants and no obvious inactivating mutations. Quantitative bisulfite pyrosequencing analysis of the TET2 promoter CpG island revealed higher CpG methylation level in the PCs compared to that in normal tissues and treatment of a PC primary cell culture with the DNA methylation inhibitor 5-aza-2'-deoxycytidine caused increased expression of the methylated TET2 gene. Hence, the data suggest that deregulated expression of TET2 by DNA hypermethylation may contribute to the aberrantly low level of 5hmC in PCs and further that TET2 plays a cell growth and cell migratory regulatory role and may constitute a parathyroid tumor suppressor gene.
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  • Carroll, R. J., et al. (författare)
  • γ -ray spectroscopy of a four-quasiparticle isomer band in Re 174
  • 2020
  • Ingår i: Physical Review C. - 2469-9985. ; 101:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Excited states in Re174 have been populated in fusion-evaporation reactions at the Australian National University, and γ-ray spectroscopy has been used to determine the level structure and to deduce the underlying nucleon configurations. The half-life of the bandhead of the Kπ=8- band has been measured to be 2.7(4) ns. A band built on an isomeric state of spin-parity (14-) and a half-life of 53(5) ns has been observed here for the first time, and has been determined to have a four-quasiparticle structure. Contrasting reduced-hindrance values for its decay are discussed in terms of deformation and configuration changes, as indicated by configuration-constrained potential energy surface calculations.
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  • Iannaccone, M., et al. (författare)
  • Whole-transcriptome profiling of sheep fed with a high iodine-supplemented diet
  • 2020
  • Ingår i: Animal. - 1751-7311 .- 1751-732X. ; 14:4, s. 745-752
  • Tidskriftsartikel (refereegranskat)abstract
    • Iodine (I) is a micronutrient that mammals need for proper functionality of thyroid gland since it is the main component of thyroid hormones. Besides studies that have investigated the role of I in livestock nutrition, it is also important to know the transcriptomics changes in small ruminants following I supplementation. Therefore, the aim of this study was to investigate the effects of I on the whole blood transcriptome in sheep. Fifteen lactating cross-bred ewes (3 to 4-year-old, 55 to 65 kg BW) at their late lactation period were enrolled in this study. At the beginning, all the animals had a 2-week acclimation period where they were fed with a basal diet which includes an adequate level of I (2 mg I/animal per day) in the form of calcium iodate (CaI2O6). Then, the ewes were randomly divided into two groups and fed in individual troughs: the control group (n = 5) was maintained on basal diet and the experimental group (I, n = 10) was fed for 40 days with a diet containing a high I supplementation (equivalent to 30 mg I/animal per day), in the form of potassium iodide. Whole blood and milk were collected individually at the beginning (T0) and after the 40 days of supplementation (T40). Iodine quantification was assessed in serum and milk sample. Microarray gene expression analysis was performed on whole blood and, filtering data using a fold change >2 with an adjusted P < 0.05, we identified 250 differentially expressed genes (DEGs) in the I group (T40 v. T0). Looking for biological processes associated with our DEGs, we found significant association with cell growth regulation. Thus, our study unveils the role of I supplementation on gene expression in sheep improving the knowledge about micronutrients in animal nutrition.
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48.
  • Parodis, I., 1981-, et al. (författare)
  • De novo renal flares in SLE patients treated for active extra renal disease within five phase Ill clinical trials of belimumab : Implications for revisiting belimumab dose
  • 2023
  • Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 0300-9742 .- 1502-7732. ; 52:Suppl. 131, s. 46-46
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background including aims: Each lupus nephritis (LN) flare causes substantial nephron loss. Identification of reliable signals of impending flare is imperative. In light of observed cases of de novo LN during belimumab treatment, we evaluated predictors of de novo renal flare occurrence in patients with systemic lupus erythematosus (SLE) and no prior history of renal disease undergoing standard therapy with or without add-on belimumab within the frame of five phase III clinical trials.Methods: Data from five phase III clinical trials of belimumab in SLE i.e., BLISS-52 (NCT00424476; N=865); BLISS-76 (NCT00410384; N=819); BLISS-NEA (NCT01345253; N=677); BLISS-SC (NCT01484496; N=836); EMBRACE (NCT0163224; N=448) were utilised. De novo renal flares were defined as a change from renal British Isles Lupus Assessment Group (BILAG) E to A or B within a 52-week follow-up. Predictors of renal flare occurrence were investigated using Cox regression analysis.Results: Of 1844 eligible patients, 136 (7.4%) developed a de novo renal flare during a 52-week long follow-up. In multivariable analysis adjusting for potential confounders, Asian origin (HR: 1.97; 95% CI: 1.33–2.94; p=0.001), high mean prednisone dose from baseline until renal flare occurrence or throughout follow-up (HR: 1.03; 95% CI: 1.02–1.04; p<0.001), and positive levels of anti-dsDNA (HR: 1.32; 95% CI: 1.08–1.63; p=0.008) were associated with de novo renal flares. Low-dose intravenous (IV) belimumab (1 mg/kg) yielded a nearly 3-fold lower hazard of de novo renal flare occurrence (HR: 0.38; 95% CI: 0.20–0.73; p=0.004) and subcutaneous (SC) belimumab (200 mg weekly) yielded a lower, but less decreased, hazard (HR: 0.69; 95% CI: 0.54–0.88; p=0.003). However, the labelled dose of IV belimumab (10 mg/kg) did not provide protection (HR: 0.74; 95% CI: 0.50–1.09; p=0.127).Conclusions: Our findings corroborate the substantial vulnerability of Asian SLE populations to renal affliction. Add-on low-dose IV belimumab 1 mg/kg appeared most protective against renal flares in nephritis-naïve SLE patients, while the approved IV dose (10 mg/kg) yielded no clear protection.
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  • Parodis, Ioannis, 1981-, et al. (författare)
  • PREDICTORS OF DE NOVO RENAL FLARES IN SYSTEMIC LUPUS ERYTHEMATOSUS - TIME TO REVISIT BELIMUMAB DOSE FOR EXTRA-RENAL DISEASE? : RESULTS FROM FIVE PHASE III CLINICAL TRIALS OF BELIMUMAB
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 909-910
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Each lupus nephritis (LN) flare causes nephron loss that equals a decade or more of reduction in renal function lifespan, making prompt initiation of therapy imperative and prevention of flares even more desirable. Identification of readily available signals of imminent flare is therefore expected to improve prognosis.Objectives: In light of observed cases of de novo LN during belimumab treatment (1), we evaluated predictors of de novo renal flare occurrence in patients with systemic lupus erythematosus (SLE) and no prior history of renal disease undergoing standard therapy (ST) with or without add-on belimumab in clinical trial settings.Methods: Data from five clinical trials of belimumab in SLE (BLISS-52 NCT00424476; BLISS-76 NCT00410384; BLISS-NEA NCT01345253; BLISS-SC NCT01484496; EMBRACE NCT01632241) were utilised. The study population comprised 1932 patients with a baseline renal British Isles Lupus Assessment Group (BILAG) score E. De novo renal flares were defined as a change from renal BILAG E to A or B within a 52-week follow-up. Comparisons of baseline data were made using the Mann-Whitney U test, Pearson’s chi-squared (χ2) test or Fisher’s exact test as appropriate. Predictors of renal flare occurrence were investigated using univariable and multivariable Cox regression analysis. p values <0.05 were considered statistically significant.Results: De novo renal flares were documented in 146 (7.6%) patients. Among patients who developed at least one renal flare, greater proportions were Asians (30.8% versus 20.2%; p<0.003), had positive baseline anti-dsDNA levels (74.0% versus 61.3%; p=0.003), and had low baseline levels of C3 (51.4% versus 38.2%; p=0.002) and C4 (45.2% versus 35.8%; p=0.030) compared with patients who did not flare. In univariable Cox regression analysis, azathioprine use was protective against renal flares (HR: 0.70; 95% CI: 0.49–0.99; p=0.047), while anti-Sm positivity at baseline showed a trend towards an association with imminent renal flare (HR: 1.68; 95% CI: 0.99–2.85; p=0.057). In multivariable Cox regression analysis adjusting for age, sex, ethnicity, serum creatinine, and variables that differed significantly in univariable analysis, Asian ancestry (HR: 1.60; 95% CI: 1.03–2.49; p=0.036), high mean prednisone dose from baseline until renal flare occurrence or throughout the follow-up (HR: 1.03; 95% CI: 1.02–1.05; p<0.001), and baseline serum creatinine (HR: 1.02; 95% CI: 1.01–1.03; p=0.001) were associated with imminent de novo renal flare, while extra-renal clinical SLE Disease Activity Index 2000 (cSLEDAI) showed a negative association (HR: 0.92; 95% CI: 0.86–0.98; p=0.007). Notably, use of belimumab 1 mg/kg by intravenous (IV) infusion yielded a nearly 3 times decreased hazard of renal flare (HR: 0.37; 95% CI: 0.20–0.68; p=0.001), whereas IV belimumab 10 mg/kg and belimumab 200 mg administered subcutaneously (SC) displayed no clear protection.Conclusion: Asian patients appeared particularly susceptible to new-onset renal involvement, corroborating the substantial vulnerability of Asian SLE populations to renal affliction. Add-on low-dose IV belimumab on top of ST appeared protective against renal flares in SLE patients with no prior history of nephritis, while addition of the approved 10 mg/kg IV belimumab dose and SC belimumab yielded no clear protection. Discrepant results between low and high/approved belimumab doses warrant in-depth mechanistic exploration of underlying reasons e.g., potential effects of belimumab on B cell subsets that acquire regulatory properties.Reference: [1]Parodis I, Vital EM, et al. Rheumatology (Oxford). 2021;60(9):4348-54.
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