Objective
To conduct a long‐term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV).
Methods
Fifty‐nine ...patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non‐RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non‐RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months.
Results
Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% P < 0.0001), as well as at 3 months (92.9% versus 13.8% P < 0.0001), 6 months (71.4% versus 3.5% P < 0.0001), and 24 months (60.7% versus 3.5% P < 0.0001). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2; P < 0.001) up to month 24 (4.4 ± 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated.
Conclusion
RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.
Progression of inflammatory osteolytic diseases, including rheumatoid arthritis and periodontitis, is characterized by increased production of proinflammatory mediators and matrix-degrading enzymes ...by macrophages and increased osteoclastic activity. Phenotypic changes in macrophages are central to the healing process in virtually all tissues. Using a murine model of periodontitis, we assessed the timing of macrophage phenotypic changes and the impact of proresolving activation during inflammatory osteolysis and healing. Proinflammatory macrophage activation and TNF-α overproduction within 3 wk after induction of periodontitis was associated with progressing bone loss. Proresolving activation within 1 wk of stimulus removal and markers of resolving macrophages (IL-10, TGF-β, and CD206) correlated strongly with bone levels. In vivo macrophage depletion with clodronate liposomes prevented bone resorption but impaired regeneration. Induction of resolving macrophages with rosiglitazone, a PPAR-γ agonist, led to reduced bone resorption during inflammatory stimulation and increased bone formation during healing. In vitro assessment of primary bone marrow–derived macrophages activated with either IFN-γ and LPS (proinflammatory activation) or IL-4 (proresolving activation) showed that IL-4-activated cells have enhanced resolving functions (production of anti-inflammatory cytokines; migration and phagocytosis of aged neutrophils) and exert direct anabolic actions on bone cells. Cystatin C secreted by resolving but not inflammatory macrophages explained, in part, the macrophage actions on osteoblasts and osteoclasts. This study supports the concept that therapeutic induction of proresolving functions in macrophages can recouple bone resorption and formation in inflammatory osteolytic diseases.
The well-known Crab Nebula is at the center of the SN1054 supernova remnant. It consists of a rotationally powered pulsar interacting with a surrounding nebula through a relativistic particle wind. ...The emissions originating from the pulsar and nebula have been considered to be essentially stable. Here, we report the detection of strong gamma-ray (100 mega-electron volts to 10 giga-electron volts) flares observed by the AGILE satellite in September 2010 and October 2007. In both cases, the total gamma-ray flux increased by a factor of three compared with the non-flaring flux. The flare luminosity and short time scale favor an origin near the pulsar, and we discuss Chandra Observatory x-ray and Hubble Space Telescope optical follow-up observations of the nebula. Our observations challenge standard models of nebular emission and require power-law acceleration by shock-driven plasma wave turbulence within an approximately 1-day time scale.
► A prestressed unbounded reinforcement (PUR) system was developed. ► The performance of cracked beams strengthened by the PUR system was examined. ► A theoretical method was developed to estimate ...the crack arrest prestressing level.
Bonded fiber reinforced polymers (FRPs) reinforcement systems have traditionally been found to be an efficient method for improving the lifespan of fatigued metallic structures and have attracted much research attention. Nevertheless, the performance of a bonded FRP reinforcement system under fatigue loading is basically dependent on the FRP-to-metal bond behavior. In this paper, a prestressed unbonded reinforcement (PUR) system was developed. The proposed PUR system can be used as an alternative to bonded FRP reinforcement, particularly when there is concern about the effects of high ambient temperatures, moisture, water and fatigue loading on the FRP-to-metal bond behavior. The performance of cracked beams strengthened by the PUR system was compared with that of cracked beams strengthened by the prestressed bonded reinforcement (PBR) system. A theoretical method was developed to estimate the level of prestressing sufficient to arrest fatigue crack growth (FCG). Furthermore, the method was used to examine different passive, semi-active and active crack modes with a loaded, strengthened beam. The mechanism by which a prestressed FRP plate forms a compressive stress field at the vicinity of the crack tip was also examined. Finite element (FE) modeling was conducted and the results were compared with experimental results.
We propose a probabilistic model to determine landslide hazard at the basin scale. The model predicts where landslides will occur, how frequently they will occur, and how large they will be. We test ...the model in the Staffora River basin, in the northern Apennines, Italy. For the study area, we prepare a multi-temporal inventory map through the interpretation of multiple sets of aerial photographs taken between 1955 and 1999. We partition the basin into 2243 geo-morpho-hydrological units, and obtain the probability of spatial occurrence of landslides by discriminant analysis of thematic variables, including morphological, lithological, structural and land use. For each mapping unit, we obtain the landslide recurrence by dividing the total number of landslide events inventoried in the unit by the time span of the investigated period. Assuming that landslide recurrence will remain the same in the future, and adopting a Poisson probability model, we determine the exceedance probability of having one or more landslides in each mapping unit, for different periods. We obtain the probability of landslide size by analysing the frequency–area statistics of landslides, obtained from the multi-temporal inventory map. Assuming independence, we obtain a quantitative estimate of landslide hazard for each mapping unit as the joint probability of landslide size, of landslide temporal occurrence and of landslide spatial occurrence.
The antiphospholipid triangle GALLI, M.
Journal of thrombosis and haemostasis,
February 2010, Letnik:
8, Številka:
2
Journal Article
Recenzirano
Odprti dostop
See also Pengo V, Ruffatti A, Legnani C, Gresele P, Barcellona D, Erba N, Testa S, Marongiu F, Bison E, Denas G, Banzato A, Padayattil Jose S, Iliceto S. Clinical course of high‐risk patients ...diagnosed with antiphospholipid syndrome. This issue, pp 237–42.
One of the conclusions of the subcommittee meeting on Lupus Anticoagulant/Phospholipid dependent antibodies, held in Geneva on 2007, was the need to update the guidelines on Lupus Anticoagulant (LA) ...detection. Particular emphasis was given to several aspects discussed in this official communication. A new paragraph is dedicated to the patient selection, and aims to minimize inappropriate requests for LA testing. Modalities for blood collection and processing are fully delineated and the choice of tests is limited to dRVVT and a sensitive aPTT. Calculation of cut‐off values for each diagnostic step are clearly stated. A final paragraph reports the interpretation of the results in general and in particular situations.
We report on an elementary quantum network of two atomic ions separated by 230 m. The ions are trapped in different buildings and connected with 520(2) m of optical fiber. At each network node, the ...electronic state of an ion is entangled with the polarization state of a single cavity photon; subsequent to interference of the photons at a beam splitter, photon detection heralds entanglement between the two ions. Fidelities of up to (88.0+2.2-4.7)% are achieved with respect to a maximally entangled Bell state, with a success probability of 4×10^{-5}. We analyze the routes to improve these metrics, paving the way for long-distance networks of entangled quantum processors.
Paraffin waxes are widely recognized as emerging marine pollutants, even their classification by the recent monitoring programs and the knowledge of their occurrence, and sources of contamination in ...marine ecosystems are poorly defined and reported. Wax presence and distribution have been evaluated in different environmental compartments in the Pelagos Sanctuary (Mediterranean Sea) floating on the sea surface and stranded on beaches, focussing on their characterization, accumulation areas and pollution inputs. More than 2500 yellow paraffin residues were detected and analysed in the study area showing a prevailing dimension smaller than 5 mm. The Genoa Canyon and the waters facing Gorgona Island resulted in the more polluted areas representing two distinct hotspots of wax accumulation potentially related to the high density of tanker vessels sailing to and from the harbour of Genova and Livorno. Higher concentrations of beached particles were found along the Tuscan coast (11 items/100 m) and on Pianosa Island (110 items/m2). This study gives valuable insights into paraffin wax pollution in the Pelagos Sanctuary, emphasizing the need for harmonized monitoring and detection methods to elucidate the potential impacts on marine organisms. Moreover, mitigating actions are crucial to prevent and curb the waxes pollution of marine ecosystems.
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•Urgently needs to standardise wax classification and assess its ecological implications.•Paraffin waxes have been detected floating on the sea surface and stranded on beaches.•ATR-FTIR used for chemical identification reveals the PE composition of waxes.•Paraffin wax distribution seems to be related to tanker navigation routes in the North-Western Mediterranean Sea.•Management strategies are essential to address and reduce the impacts of waxes.
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