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Artykuły w czasopismach na temat "Janssen effect"
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Thorens, Louison, Knut Jørgen Måløy, Mickaël Bourgoin i Stéphane Santucci. "Taming the Janssen effect". EPJ Web of Conferences 249 (2021): 08004. http://dx.doi.org/10.1051/epjconf/202124908004.
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We investigate both experimentally and theoretically the apparent mass of a ferromagnetic granular assembly filling a cylindrical container and submitted to a magnetic field B, aligned vertically along the silo. We show that the mass of the ferromagnetic granular column depends strongly on the applied magnetic field. Notably, our measurements deviate strongly from the exponential saturation of the measured mass as a function of the true mass of the grain packing, as predicted by Janssen [H.A. Janssen, Vereins Eutscher Ingenieure Zeitschrift, 1045 (1895)]. In particular, the measured mass of tall columns decreases systematically as the amplitude of the magnetic field increases. We rationalize our experimental findings by considering the induced magnetic dipole-dipole interactions within the whole packing. We show the emergence of a global magnetic radial force along the walls of the silos, fully determined by the external magnetic field. The resulting tunable frictional interactions allows a full control of the effective mass of the ferromagnetic granular column.
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Maksuwan, Atirat. "Janssen’s Effect in Mechanical Behavior and Fracture of Granular Materials". Materials Science Forum 883 (styczeń 2017): 7–11. http://dx.doi.org/10.4028/www.scientific.net/msf.883.7.
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In 1985, H.A. Janssen studied the structure of the forces inside a silo filled with granular materials, so-called Janssen’s Effect Method (J.E.M). This method is a unique property of confined granular materials. The pressure at the bottom saturated with an increasing filling height due to internal friction with side walls. In this research, we focus on the study of granular cohesionless materials such as sands and gravels, these forces are explained by adsorption and capillary phenomenon. Our main result shows that positive water pressures generate a mechanical effect with tendencies of removing the components of the porous medium corresponding to the mechanical buoyancy force (FB) that increases with increasing θ from calculated by Janssen's effect method. The topic in this research is once importance in study physical processes of the problem in the Geology Physics (i.e. the factor causing landslide).
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Nurmohamed, M. T., I. Van der Horst-Bruinsma, A. W. Van Kuijk, S. Siebert, P. Bergmans, K. De Vlam, E. Gremese i in. "SAT0432 EFFECT OF SEX ON DISEASE CHARACTERISTICS AND DISEASE IMPACT IN PATIENTS WITH PSORIATIC ARTHRITIS (PsA): INSIGHTS FROM THE REAL-WORLD, OBSERVATIONAL MULTINATIONAL PsABio COHORT". Annals of the Rheumatic Diseases 79, Suppl 1 (czerwiec 2020): 1171.1–1173. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2771.
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Background:Female sex has been associated with more severe disease and poorer treatment outcomes in PsA. These observations are often based on small populations or national cohorts/registries.Objectives:To investigate the effects of sex on disease characteristics and disease impact in PsA, using data of 929 consecutive patients (pts) from PsABio.Methods:PsABio is a real-world, non-interventional European study in PsA pts treated with UST or TNFi based on their rheumatologist’s choice. Observed male and female baseline (BL) data were described and compared using 95% CI.Results:Women in PsABio (n=512 [55%]) were numerically older than men (mean [SD]: 50.5 [12.7] / 48.7 [12.3] years, respectively). Women were more obese (BMI >30), % (95% CI): F: 35 (30, 39), M: 24 (20, 29), men more overweight (BMI >25–30): F: 31 (27, 36), M:51 (46, 57). Age at diagnosis, delay from first symptom to diagnosis, and disease duration were similar for both sexes.Women entered PsABio more often on 3rd line treatment, whereas men started on 1st-line biologic treatment more often (F/M 1st line 47%/55%; 2nd line 34%/33%; 3rd line 20%/12%). Numerically, concomitant MTX was given more often to women vs men (32% vs 27%). At BL, 60% of women and 64% of men were on NSAIDs; 7.9% and 2.5% on antidepressant drugs. Women had significantly more comorbidities, with numerically more cardiovascular disease and anxiety/depression, and 3 times more IBD.Women had significantly higher 68 tender joint counts (TJC): 13.0 vs 10.4, while 66 swollen joint counts were not significantly different: 5.8 vs 5.5. Axial or combined axial-peripheral disease was similarly frequent, in 29% of women and 26% of men (Figs. 1, 2).Clinical Disease Activity index for PSoriatic Arthritis (cDAPSA) was higher in women (31.8 vs 27.3); pt-reported levels of pain, global disease activity (VAS scales) and higher TJC contributed to this. While enthesitis prevalence (based on Leeds Enthesitis Index) was comparable, men had significantly more frequent dactylitis, nail disease and worse skin psoriasis. At BL, 3.4% of women vs 7.1% of men, were in MDA.Regarding physical functioning (HAQ-DI), impact of disease (PSAID-12) and quality of life (EQ5D-3L health state), women with PsA starting a biologic (b)DMARD, expressed significantly greater negative impact and more limitations due to their disease (Fig. 2).Conclusion:In routine care, women with PsA starting a bDMARD presented with worse outcomes over a range of assessments compared with men (higher pt-reported pain and disease activity, TJC, and worse physical functioning and QoL), while men had worse dactylitis and psoriasis. Follow-up analysis will report whether the effects of biologic therapy are different in both sexes. The increased prevalence of associated features related to pain and impact on functioning and QoL may indicate the need for a more comprehensive treatment approach for women to avoid unnecessary and premature bDMARD stop or switch.Acknowledgments:This study was funded by Janssen.Disclosure of Interests:Michael T Nurmohamed Grant/research support from: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Consultant of: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Speakers bureau: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Arno WR van Kuijk Grant/research support from: Janssen, Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Consultant of: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – consultant, Speakers bureau: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – speakers bureau and honoraria, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Wim Noel Employee of: Janssen Pharmaceuticals NV, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Elke Theander Employee of: Janssen-Cilag Sweden AB, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB
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Saint-Michel, Brice, Marc Georgelin, Sylvain Deville i Alain Pocheau. "Wall friction and Janssen effect in the solidification of suspensions". Soft Matter 14, nr 46 (2018): 9498–510. http://dx.doi.org/10.1039/c8sm01572d.
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Helliwell, P., P. Rahman, A. Deodhar, A. Kollmeier, E. C. Hsia, B. Zhou, X. Lin, C. Han i P. J. Mease. "SAT0421 GUSELKUMAB DEMONSTRATED AN INDEPENDENT TREATMENT EFFECT ON FATIGUE AFTER ADJUSTMENT FOR CLINICAL RESPONSE (ACR20) IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM PHASE-3 TRIALS DISCOVER 1 & 2". Annals of the Rheumatic Diseases 79, Suppl 1 (czerwiec 2020): 1164.2–1164. http://dx.doi.org/10.1136/annrheumdis-2020-eular.401.
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Background:DISCOVER 1 and 2 are phase-3 trials of guselkumab (GUS, a monoclonal antibody that specifically binds the p19-subunit of IL-23) in patients with psoriatic arthritis (PsA). In both trials, treatment with GUS led to significantly more improvement than placebo (PBO) in the primary endpoint (ACR20) as well as in other measures of arthritis and psoriasis at week (W) 24.1,2Objectives:To evaluate the effect of GUS on fatigue in DISC 1 & 2 using the patient reported outcome (PRO) FACIT-Fatigue, which has demonstrated content validity and strong psychometric properties in clinical trials.3Methods:DISC 1 & 2 enrolled patients with active PsA, despite nonbiologic DMARDS and/or NSAIDS, who were mostly biologic naïve except for ~30% of patients in DISC 1 who had received 1-2 TNFi. Patients were randomized (1:1:1) in a blinded fashion to subcutaneous GUS 100 mg at W0 and W4 then every (q) 8W, to GUS 100 mg q4W, or to matching PBO. Concomitant treatment with select non-biologic DMARDS, oral corticosteroids, and NSAIDs was allowed. The FACIT-Fatigue is a 13-item PRO instrument assessing fatigue and its impact on daily activities and function over the past seven days, with a total score ranging from 0 to 52, higher score denoting less fatigue. A change of ≥4 points is identified as clinically meaningful.3Change from baseline in FACIT-Fatigue was analyzed using MMRM (Figure). Independence of treatment effect on FACIT-Fatigue from effect on ACR20 was assessed using Mediation Analysis4(Table) to estimate the natural direct effect (NDE) and natural indirect effect (NIE) mediated by ACR20 response.Results:At baseline in DISC 1 & 2, the mean FACIT-fatigue scores (SD) were 30.4 (10.4) and 29.7 (9.7), respectively, indicating moderate to severe fatigue. In both DISCOVER 1 & 2 trials, treatment with GUS led to improvements in FACIT-Fatigue scores compared with PBO as early as W8 (Figure). 54%-63% of GUS patients compared with 35%-46% of PBO patients achieved clinically meaningful improvement (≥4 points) in FACIT-Fatigue (P≤0.003). Mediation analysis revealed that the independent treatment effects on fatigue after adjustment for ACR20 response (Natural Direct Effect [NDE], Table) were 12-36% in the q8W GUS dosing group and 69% -70% in the q4W GUS group.Conclusion:In 2 phase-3 trials, treatment with GUS of patients with active PsA led to significant improvements compared to PBO in fatigue, including substantial effects on FACIT-Fatigue that were independent of the effects on ACR 20, especially for the q4W dosing group.References:[1]Deodhar et al. ACR 2019. Abstract #807. Arthr Rheumatol. 2019;71 S10: 1386[2]Mease et al. ACR 2019. Abstract # L13. Arthr Rheumatol. 2019;71 S10:5247[3]Cella et al. Journal of Patient-Reported Outcomes. 2019;3:30[4]Valeri et al. Psychologic Meth. 2013;18:137Table.Mediation Analysis of the Effect of ACR 20 Response on Change from Baseline in FACIT-Fatigue Score at Week 24EffectGUS 100 mg q8W vs. PBOEstimate (95% CI)GUS 100 mg q4W vs. PBOEstimate (95% CI)DISCOVER 1NDE0.36 (-1.7, 2.4)2.60 (0.6, 4.5)*NIE2.75 (1.4, 4.3)*1.20 (0.3, 2.3)*Total Effect3.12 (1.0, 5.2)*3.79 (1.9, 5.4)*Proportion Independent11.7%68.5%Proportion Mediated88.3%31.5%DISCOVER 2NDE1.44 (-0.1, 3.0)2.49 (1.0, 4.1)*NIE2.53 (1.6, 3.6)*1.09 (0.4, 1.9)*Total Effect3.97 (2.4, 5.5)*3.58 (2.1, 5.0)*Proportion Independent36.3%69.7%Proportion Mediated63.7%30.3%*P vs placebo<0.02NDE=Natural Direct Effect (effect on FACIT-F beyond effect on ACR20), NIE=Natural Indirect Effect (effect on FACIT-F mediated by ACR20)Mediation analysis4used linear and logistics regression models with Bootstrapping methodAcknowledgments:NoneDisclosure of Interests:Philip Helliwell: None declared, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xiwu Lin Employee of: Janssen Research & Development, LLC, Chenglong Han Employee of: Janssen Research & Development, LLC, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau
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Mease, P. J., X. Baraliakos, V. Chandran, E. Soriano, P. Nash, A. Deodhar, E. Rampakakis i in. "AB1108 EFFECT OF GUSELKUMAB ADMINISTERED EVERY 8 WEEKS IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS PERSISTS BETWEEN CONSECUTIVE DOSES AND IS DURABLE: POST HOC ANALYSIS OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY". Annals of the Rheumatic Diseases 82, Suppl 1 (30.05.2023): 1782–83. http://dx.doi.org/10.1136/annrheumdis-2023-eular.642.
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BackgroundThe efficacy of guselkumab (GUS), a fully human IL-23p19 subunit inhibitor, in patients (pts) with active psoriatic arthritis (PsA) has been previously shown across a variety of PsA domains and baseline (BL) pt characteristics[1-3]. Given the central role of the IL-23/Th17 pathway in PsA, it has been hypothesized that IL-23 inhibition with GUS may provide persistent and durable clinical responses between doses and over time when administered every 8 weeks (Q8W).ObjectivesTo assess at the pt level the persistence of effect of GUS Q8W between doses and its durability of effect over time.MethodsDISCOVER-2 was a phase 3, randomized, double-blind, placebo (PBO)-controlled study that enrolled pts with active PsA despite standard therapies. Pts were biologic-naïve, had tender and swollen joint counts (TJC/SJC) each ≥5, and C-reactive protein (CRP) ≥0.6 mg/dL. Pts were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO with crossover to GUS 100 mg Q4W at W24. In the current analysis, only pts treated with GUS Q8W (N=248) were included. Persistence of effect between consecutive dosing visits was described with the proportion of pts maintaining response (as defined below) in outcomes assessed during dosing visits (Disease Activity index for PsA [DAPSA], clinical DAPSA [cDAPSA]). Durability of effect was assessed with the Kaplan Meier estimator of the survival function where each pt contributed follow-up from the first time of achievement of clinical response within the 24-week period and the time of loss of response or last available assessment through W100. Definitions of clinical response included achievement of clear/almost clear skin (investigator’s global assessment [IGA] 0/1; among pts with BL IGA>1) or minimal clinically important improvements (MCII) in DAPSA (≥7.25), cDAPSA (≥5.7), skin visual analog scale (VAS; ≥15 mm), and PsA Disease Activity Score (PASDAS; ≥0.8).ResultsBetween consecutive (Q8W) dosing visits through W52, the proportion of pts maintaining response ranged from 93.3% (DAPSA MCII between W4 and W12) to 99.1% (DAPSA/cDAPSA MCII between W28 and W36), depending on the time interval. Among pts showing clinical response within the first 24 weeks, the estimated mean (SE) duration of maintenance was 58.6 (2.2) weeks for DAPSA MCII, 52.4 (2.0) weeks for cDAPSA MCII, 75.7 (1.6) weeks for.IGA 0/1, 71.7 (1.9) weeks for skin VAS MCII, and 76.7 (1.4) weeks for PASDAS MCII (Figure 1). As estimated probabilities of maintenance of effect at W100 were between 65% (IGA 0/1) and 90% (PASDAS MCII) for all outcomes assessed, median duration of effect could not be calculated.ConclusionTreatment with GUS Q8W was associated with long-lasting effects in both joint- and skin-related outcomes, as well as in multi-domain composite outcomes, in individuals with PsA. These results highlight that, in addition to continuous improvement in clinical response rates over time, GUS Q8W provides consistent and highly durable responses between consecutive doses.References[1]McInnes IB, et al.Arthritis Rheumatol. 2022;74:475.[2]Ritchlin CT, et al.RMD Open. 2022;8:e002195.[3]Ritchlin CT, et al.Arthritis Rheumatol. 2022;74 (suppl 9).Acknowledgements:NIL.Disclosure of InterestsPhilip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Xenofon Baraliakos Speakers bureau: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Vinod Chandran Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and Eli Lilly, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Peter Nash Speakers bureau: UCB, AbbVie, Pfizer, Eli Lilly, Novartis, GlaxoSmithKline, MSD, Samsung, Janssen, Gilead/Galapagos, Boehringer-Ingelheim, Sun, Consultant of: UCB, AbbVie, Pfizer, Eli Lilly, Novartis, GlaxoSmithKline, MSD, Samsung, Janssen, Gilead/Galapagos, Boehringer-Ingelheim, Sun, Grant/research support from: UCB, AbbVie, Pfizer, Eli Lilly, Novartis, GlaxoSmithKline, MSD, Samsung, Janssen, Gilead/Galapagos, Boehringer-Ingelheim, Sun, Atul Deodhar Speakers bureau: Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Inc., Natalie Shiff Shareholder of: AbbVie, Gilead, Iovance, Jazz Pharmaceuticals, Johnson & Johnson, Novavax, and Viatris, Employee of: Janssen Scientific Affairs, LLC, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies, Joseph F. Merola Consultant of: Amgen, Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Incyte, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma, Iain McInnes Shareholder of: Causeway Therapeutics, and Evelo Compugen, Consultant of: AstraZeneca, AbbVie, Bristol Myers Squibb, Amgen, Eli Lilly, Cabaletta, Compugen, GlaxoSmithKline, Gilead, Janssen, Novartis, Pfizer, Sanofi, Roche, and UCB, Grant/research support from: AstraZeneca, Bristol Myers Squibb, Amgen, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Roche, and UCB.
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Gossec, L., S. Siebert, P. Bergmans, K. De Vlam, E. Gremese, B. Joven-Ibáñez, T. Korotaeva i in. "SAT0398 PERSISTENCE OF USTEKINUMAB (UST) OR TNF INHIBITOR (TNFI) TREATMENT IN PSORIATIC ARTHRITIS (PsA): INSIGHTS FROM THE LARGE, PROSPECTIVE, MULTINATIONAL, REAL-WORLD PsABio COHORT". Annals of the Rheumatic Diseases 79, Suppl 1 (czerwiec 2020): 1149–50. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2127.
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Background:Several biologic DMARDs (bDMARDs) exist for PsA, TNFi and UST being the earliest on European markets. When bDMARDs are insufficiently effective, later-line bDMARDs typically have shorter persistence. Treatment persistence reflects a mix of effectiveness and adverse events (AEs), and persistence data are limited in PsA.Objectives:Comparative analysis of 1-year persistence of UST and TNFi within the prospective PsABio cohort.Methods:PsABio is an observational, multinational study of PsA patients (pts) treated with 1st to 3rd line UST or TNFi at their rheumatologist’s discretion.1Treatment persistence (up to 15 months of follow-up) was defined as time between start of first bDMARD treatment in PsABio, and either stop or switch to another bDMARD, or withdrawal.Persistence of UST and TNFi is shown by Kaplan-Meier curves and compared using Cox regression analysis, with propensity score (PS) to adjust for baseline imbalanced demographic and disease-related covariates (age, sex, bDMARD line, BMI, Clinical Disease Activity index for PSoriatic Arthritis [cDAPSA], 12-item PsA Impact of Disease [PsAID-12], Fibromyalgia Rapid Screening Tool [FiRST] score, co-treatments with MTX, NSAIDs, glucocorticoids, cardiovascular/metabolic comorbidities, dactylitis, enthesitis and body surface area [BSA]). Factors including concomitant MTX use and skin involvement: <3%, 3–10% and >10%, were added to the Cox model to investigate their impact on the PS-adjusted treatment effect.Results:Of 438 and 455 pts who started UST and TNF, respectively, 121 (28%) and 134 (29%) stopped or switched treatment before Month 15, with differences (as expected) according to treatment line (Fig. 1a, b). Reasons for stop/switch were related to safety/AEs in 12% (UST) and 28% (TNFi), and effectiveness (joints, nails or skin) in 77% (UST) and 69% (TNFi) of pts.The observed mean time on drug was 397 days for UST and 385 days for TNFi pts (1st line 410/397 days, 2nd 390/382 days, 3rd 381/338 days). Fig. 1b shows similar persistence for all drugs and treatment lines, except for lower persistence in TNFi 3rd line vs 1st/2nd. In PS-adjusted Cox analysis, no statistically significant difference between UST and TNFi persistence was seen; hazard ratio (HR; 95% CI) for stop/switch bDMARD (UST vs TNFi) was 0.82 (0.60, 1.13). In the model, bDMARD monotherapy (without MTX) and extensive skin involvement (BSA >10%), showed significantly better persistence for UST (HR 0.61 [0.42, 0.90] and 0.41 [0.19, 0.89] respectively; unadjusted Kaplan-Meier graphs shown in Fig. 1c, d). MTX co-therapy and low BSA did not affect the PS-adjusted treatment effect. Other factors added to the PS-adjusted Cox model did not show significant effects.Conclusion:In this real-world PsA cohort undergoing bDMARD treatment, persistence was generally comparable for UST and TNFi, but some clinical situations led to better drug persistence with UST compared to TNFi – particularly monotherapy, more extensive skin involvement, and in 3rd-line treatment. Our data emphasise the importance of skin involvement for pts with PsA.References:[1]Gossec L, et al.Ann Rheum Dis. 2018;77(suppl 2):Abstract AB0928Acknowledgments:This study was funded by Janssen.Disclosure of Interests:Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Consultant of: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – consultant, Speakers bureau: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – speakers bureau and honoraria, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Wim Noel Employee of: Janssen Pharmaceuticals NV, Michael T Nurmohamed Grant/research support from: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Consultant of: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Speakers bureau: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Elke Theander Employee of: Janssen-Cilag Sweden AB, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi
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Nash, P., I. McInnes, C. T. Ritchlin, W. C. Tsai, Y. Y. Leung, L. S. Tam, D. Furtner i in. "AB0525 GUSELKUMAB TREATMENT SHOWS RAPID ONSET OF EFFECT ON COMPONENTS OF AMERICAN COLLEGE OF RHEUMATOLOGY RESPONSE CRITERIA: RESULTS OF 2 RANDOMIZED PHASE 3 TRIALS". Annals of the Rheumatic Diseases 80, Suppl 1 (19.05.2021): 1290–91. http://dx.doi.org/10.1136/annrheumdis-2021-eular.434.
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Background:Guselkumab (GUS), an anti-interleukin-23p19-subunit monoclonal antibody, demonstrated efficacy vs placebo (PBO) in achieving American College of Rheumatology 20% improvement (ACR20) response in patients (pts) with active psoriatic arthritis (PsA) in two phase 3 trials, DISCOVER-1 & 2.1,2Objectives:To assess the differential treatment effects of GUS across individual components of ACR response in PsA pts participating in the DISCOVER-1 & 2 trials.Methods:In DISCOVER-1 & 2, 1120 pts were randomized & treated with GUS 100 mg every 4 weeks (Q4W; N=373); GUS 100 mg at Week (W)0 and W4, then Q8W (N=375); or matching PBO (N=372). Pts were evaluated by independent joint assessors at study visits. ACR20 response is defined as ≥20% improvement from baseline in both tender joint count (0-68 [TJC68]) and swollen joint count (0-66 [SJC66]) and ≥20% improvement from baseline in ≥3 of 5 assessments: Patient Assessment of Pain [Pt Pain], Patient Assessment of Global Disease Activity (arthritis) [PtGA], Physician Assessment of Global Disease Activity [PGA], Patient assessment of physical function as measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI), and C-reactive protein (CRP). For each ACR component, achievement of ≥20% improvement from baseline was assessed over time through W24 for the combined (Q4W+Q8W) GUS groups, and median time to onset of treatment effect was determined with Kaplan-Meier curves by randomized group.Results:Median time to response for all components except SJC66 occurred earlier with GUS than PBO. Time to onset of ACR20 treatment effect is shown in Figure 1. CRP data show 56% of GUS-treated pts had diminution of systemic inflammation by W4 (Table 1). Reduction in systemic inflammation was accompanied or rapidly followed by GUS-related improvement in both PtGA and PGA (median W4-8). Although SJC66/TJC68 data showed similar patterns, there was also a high PBO response (data not shown). Consistent with early reductions in systemic inflammation, 48-61% of GUS-treated pts had ≥20% improvement in TJC68/SJC66/PGA at W4 (Table 1), and 45-48% had ≥20% improvement in HAQ-DI, PtGA, and Pt Pain by W8. By W24, >80% of GUS-treated pts had ≥20% improvement in SJC66/TJC68/PGA, followed by 63-64% with this degree of improvement in PtGA, CRP, and Pt Pain, and 57% for HAQ-DI.Conclusion:GUS demonstrated ACR20 improvements with separation from PBO in ACR components as early as W4, which is consistent with reduced inflammation by GUS and prior serological studies.3 At early study time points, both pts and physicians were able to discern improvements in signs and symptoms of arthritis that rapidly followed reductions in systemic inflammation (CRP). The predominant drivers of ACR20 response rates at W24 in GUS pts were SJC66/TJC68/PGA.References:[1]Deodhar A et al. Lancet. 2020;395:1115-25[2]Mease P et al. Lancet. 2020;395:1126-36[3]Siebert S et al. EULAR 2020. Presentation OP0229Table 1.W4W8W12W16W20W24ACR20203950566061HAQ-DI score364552545657SJC66617484868788TJC68486575798081PGA506774788181PtGA354858596264Pt Pain324855586163CRP566062636464Figure 1Disclosure of Interests:Peter Nash Consultant of: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sandoz, Sun, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sandoz, Sun, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Janssen, Eli Lilly, Gilead, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and UCB, Wen-Chan Tsai Consultant of: AbbVie, Eli Lilly, Janssen, Pfizer, and Novartis, Ying Ying Leung Consultant of: Abbvie, Eli Lilly, Janssen, and Novartis, Lai-Shan Tam Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Lilly, Pfizer, and Sanofi, Grant/research support from: Amgen, Boehringer Ingelheim, Janssen, GSK, Novartis, and Pfizer, Daniel Furtner Employee of: Janssen, a division of Johnson & Johnson Pte. Ltd., May Shawi Employee of: Janssen Research and Development, LLC, Stephen Xu Employee of: Janssen Research and Development LLC, Shihong Sheng Employee of: Janssen Research and Development, LLC, Alexa Kollmeier Employee of: Janssen Research and Development, LLC, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB.
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Goupille, P., F. Behrens, L. C. Coates, J. Gratacos-Masmitja, P. J. Mease, D. D. Gladman, P. Nash i in. "POS1044 EFFECT OF SECUKINUMAB VERSUS ADALIMUMAB ON ACR CORE COMPONENTS AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM THE EXCEED STUDY". Annals of the Rheumatic Diseases 80, Suppl 1 (19.05.2021): 797–98. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1562.
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Background:EXCEED (NCT02745080) was the first fully blinded head-to-head trial to evaluate the efficacy and safety of secukinumab (SEC) versus (vs) adalimumab (ADA) monotherapy in patients with active psoriatic arthritis (PsA) with a primary endpoint of American College of Rheumatology (ACR) 20 at Week 52. Although SEC narrowly missed statistical significance for superiority vs ADA, numerically higher response for other musculoskeletal endpoints and composite indices were observed with SEC.1Objectives:To explore the effect of SEC and ADA on ACR core components, function and Health-related Quality of Life (HRQoL) outcomes.Methods:Patients were randomised 1:1 to receive SEC 300 mg (N=426) subcutaneous (s.c.) at baseline, Week 1-4, followed by every 4 weeks until Week 48 or ADA 40 mg (N=427) s.c. at baseline followed by same dosing every 2 weeks until Week 50. The primary, key secondary and some exploratory endpoints at Week 52 were previously reported.1 A supportive analysis for ACR50 response using logistic regression model and trimmed means model for Health Assessment Questionnaire-Disability Index (HAQ-DI) with gender and smoking status as factors was performed to adjust for imbalances in baseline characteristics. An exploratory analysis of ACR core components with SEC vs ADA at Week 52 was conducted using a mixed-effects repeated measures model that included tender and swollen joint counts, patient and physician global assessment, PsA pain (VAS) and erythrocyte sedimentation rate. HRQoL variables were also exploratory and assessed based on Short Form Health Survey Physical/Mental Component Summary (SF-36 PCS/MCS) scores and Dermatology Life Quality Index (DLQI).Results:The demographic and baseline disease characteristics were comparable across treatment groups, except for an imbalance in sex (females: 51.2% vs 46.4%) and smoking status (yes: 21.8% vs 17.8%) in SEC and ADA group, respectively. At Week 52, ACR50 responses were 49.0% and 44.8% (P=0.0929) and HAQ-DI mean change from baseline were −0.69 and −0.58 (P=0.0314) in SEC and ADA treatment groups, respectively after adjusting for gender and smoking status. No major difference across ACR core components was observed in both treatment groups at Week 52 (Table 1). At Week 52, SEC presented similar improvement in SF-36 PCS/MCS score and numerically higher improvement in DLQI compared to ADA (Figure 1).Conclusion:Secukinumab provided similar improvements in ACR core components and SF-36 based quality of life at Week 52 with adalimumab. Greater improvement in HAQ-DI response and DLQI was demonstrated with secukinumab compared to adalimumab.References:[1]McInnes IB, et al. Lancet. 2020; 395:1496–505.Table 1.ACR Core Components at Week 52VariablesSecukinumab 300 mg(N=426)Adalimumab 40 mg(N=427)P-valueBL, mean ± SELSM change from BL ± SEBL, mean ± SELSM change from BL ± SETender joint score(based on 78 joints)19.4 ± 13.86−14.27 ± 0.4420.6 ± 14.81−13.90 ± 0.450.5549Swollen joint score(based on 76 joints)9.7 ± 7.30−8.41 ± 0.1910.2 ± 7.86−8.06 ± 0.200.1962Patients global assessment64.0 ± 19.67−33.81 ± 1.1461.9 ± 20.75−31.61 ± 1.190.1825Physicians global assessment60.0 ± 17.12−46.24 ± 0.8061.4 ± 15.92−43.63 ± 0.840.0243Psoriatic arthritis pain (VAS)58.6 ± 23.49−30.21 ± 1.1857.9 ± 22.42−29.44 ± 1.230.6500Erythrocyte sedimentation rate (mm/h)23.8 ± 18.93−9.63 ± 0.6223.9 ± 17.99−9.28 ± 0.640.7029LS mean and nominal P-values are from a mixed-effects repeated measures model with treatment group, analysis visit as factors, weight and BL score as covariates, and by treatment and BL score as interaction terms, unstructured covariance structure. ACR, American College of Rheumatology; BL, baseline; LSM, least squares mean; N, total number of randomised patients; SE, standard error; VAS, visual analogue scaleFigure 1.HRQoL Analysis at Week 52Disclosure of Interests:Philippe Goupille Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Eli Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Eli Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Eli Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Frank Behrens Paid instructor for: Eli Lilly, Consultant of: Pfizer, AbbVie, Sanofi, Eli Lilly, Novartis, Genzyme, Boehringer Ingelheim, Janssen, MSD, Celgene, Roche and Chugai, Grant/research support from: Pfizer, Janssen, Chugai, Celgene and Roche, Laura C Coates Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Biogen, BMS, Celgene, Domain, Eli Lilly, Gilead, GSK, Janssen, Medac, Novartis, Pfizer, Serac and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Jordi Gratacos-Masmitja Speakers bureau: AbbVie, Amgen, BMS, Celgene, Janssen, Eli Lilly, Novartis and Pfizer, Consultant of: AbbVie, Amgen, BMS, Celgene, Janssen, Eli Lilly, Novartis and Pfizer, Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Eli Lilly, Novartis and Pfizer, Philip J Mease Speakers bureau: AbbVie, Amgen, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Galapagos, Celgene, Genentech, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Genentech, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB, Dafna D Gladman Consultant of: Amgen, AbbVie, BMS, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer and UCB, Grant/research support from: Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Peter Nash Speakers bureau: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, Celgene, UCB, Eli Lilly, MSD, Sanofi, Gilead, Consultant of: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, Celgene, UCB, Eli Lilly, MSD, Sanofi, Gilead, Grant/research support from: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, Celgene, UCB, Eli Lilly, MSD, Sanofi, Gilead, Arthur Kavanaugh Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, and UCB, Ruvie Martin Shareholder of: Novartis, Employee of: Novartis, Weibin Bao Shareholder of: Novartis, Employee of: Novartis, Corine Gaillez Shareholder of: Novartis and BMS, Employee of: Novartis, Iain McInnes Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, and UCB.
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Schett, G., W. Chen, S. Gao, S. D. Chakravarty, M. Shawi, F. Lavie, E. Theander, M. Neuhold, L. Coates i S. Siebert. "POS0308 EFFECT OF GUSELKUMAB ON SERUM BIOMARKERS IN PSORIATIC ARTHRITIS PATIENTS WITH INADEQUATE RESPONSE OR INTOLERANCE TO TUMOR NECROSIS FACTOR INHIBITORS: RESULTS FROM THE COSMOS STUDY". Annals of the Rheumatic Diseases 81, Suppl 1 (23.05.2022): 403.2–404. http://dx.doi.org/10.1136/annrheumdis-2022-eular.736.
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BackgroundGuselkumab (GUS), a selective IL-23 inhibitor, is efficacious in treating bio-naïve and TNFi-experienced active PsA patients (pts).1.2 In the COSMOS study of active PsA pts with lack of efficacy/intolerance, i.e., inadequate response (IR), to 1-2 TNFi, GUS demonstrated significantly greater response rates and mean improvements in PsA signs and symptoms vs. placebo (PBO) at Week (W) 24.3ObjectivesEvaluate baseline (BL) serum levels of pro-inflammatory biomarkers (CRP, serum amyloid A [SAA], TNFα, IFNɣ, IL-6, IL-10, IL-17F, IL-17A, IL-22) and their relationship to BL disease activity, GUS treatment (tx), and clinical response in COSMOS TNFi-IR pts.MethodsTNFi-IR pts ≥18 yrs with active PsA (≥3 swollen & ≥3 tender joint counts [SJC/TJC]) were randomized 2:1 to GUS 100 mg every 8 W (Q8W) through W44 or PBO with early escape (W16) or crossover (W24) to GUS Q8W. Samples for serum biomarker analyses, collected at W0, 4, 16, 24, and 48 from consenting pts, were compared with healthy controls (HC; independent of COSMOS). Associations between early biomarker changes and BL disease activity, GUS tx, and clinical response at W24 were assessed.ResultsAmong 285 COSMOS pts, 50/95 PBO and 100/190 GUS pts had available biomarker data. BL characteristics of the biomarker cohort were similar to the overall COSMOS population and well balanced across tx arms. At BL, levels of TNFα, IFNɣ, IL-6, IL-10, IL-17A, IL-17F, and IL-22 were significantly upregulated in TNFi-IR pts vs. HC (Table 1). IL-6, CRP, and SAA levels were associated with BL joint disease severity per Disease Activity Score (DAS) 28-CRP (but not with SJC [0-66]/TJC [0-68]). IL-17A and IL-17F levels were associated with BL PASI score. Through W24, significant decreases from BL in levels of CRP, SAA, IL-6, IL-17A, IL-17F, and IL-22 were seen in GUS-, but not PBO-tx pts. Reductions in IL-17A, IL-17F and IL-22 with GUS were significant by W4, decreased further by W16, and were sustained through W24 and W48. In GUS-tx pts, serum levels of IL-17F (from W16) and IL-22 (from W4) were not significantly different vs. HC. At W48, reductions in these same markers were seen in PBO-tx pts who crossed over to GUS at W16/24 (Figure 1; IL-17A, IL-17F, & IL-22 data shown). In these TNFi-IR pts, GUS-tx pts achieving ACR20 at W24 exhibited higher IL-22 and IFNɣ levels at BL than nonresponders (NR). All other biomarkers evaluated were not significantly associated with ACR20 response to GUS. In the subset of pts with IGA of psoriasis assessed, BL IL-6 and SAA levels were upregulated in W24 IGA 0/1 responders (R) vs. NR in the GUS arm. ACR20 and IGA 0/1 R at W24 exhibited an early greater reduction in IL-6 expression (at W4) than did respective NR in the GUS arm. No BL biomarkers were associated with ACR50 or PASI75 responses to GUS at W24.Table 1.Select Serum Biomarkers at BL in TNFi-IR pts vs. HC▫Biomarker, pg/mLHC N=24TNFi-IR N=150Fold differencep-valueCRP22.1 (1.5)22.8 (2.2)1.60.2895SAA21.7 (1.2)22.8 (2.4)2.10.0794IL-60.07 (1.1)0.98 (1.7)1.90.0314*IL-10-2.3 (1.1)-1.7 (1.0)1.50.0272*IL-17A-2.1 (1.3)-0.3 (1.5)3.3<0.0001*IL-17F0.05 (1.1)1.3 (1.5)2.40.0007*IL-221.9 (1.1)3.1 (1.3)2.40.0002*TNFα0.5 (0.75)1.4 (1.1)1.80.0002*IFNɣ2.4 (0.84)2.9 (1.3)1.50.0259*Data are mean (SD); *p<0.05 and |fold difference| >1.4; ▫adjusted for confounding factors age & sex.ConclusionGUS-tx TNFi-IR pts showed response-specific associations with BL biomarkers (IL-22, IFNɣ, IL-6, and SAA). GUS resulted in decreased levels of elevated CRP, SAA, IL-6, IL-17A, IL-17F, and IL-22, while no significant change was observed with PBO tx. Reductions in these biomarkers were evident as early as W4 and approximated levels seen in HC from W16 onward (W4 for IL-22), suggesting apparent normalization of effector cytokines associated with the IL-23/Th17 axis following GUS tx.References[1]Deodhar A et al. Lancet 2020;395:1115-25.[2]Mease PJ et al. Lancet 2020;395:1126-36.[3]Coates LC et al. doi:10.1136/annrheumdis-2021-220991.Disclosure of InterestsGeorg Schett Speakers bureau: Amgen, AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis and UCB, Warner Chen Shareholder of: Janssen, Employee of: Janssen, Sheng Gao Shareholder of: Janssen, Employee of: Janssen, Soumya D Chakravarty Shareholder of: Janssen, Employee of: Janssen, May Shawi Shareholder of: Janssen, Employee of: Janssen, Frederic Lavie Shareholder of: Janssen, Employee of: Janssen, Elke Theander Shareholder of: Janssen, Employee of: Janssen, Marlies Neuhold Shareholder of: Janssen, Employee of: Janssen, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Stefan Siebert Speakers bureau: AbbVie, Biogen, GSK, Janssen, Novartis, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Janssen, Novartis, UCB
Rozprawy doktorskie na temat "Janssen effect"
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Jansen, Michael [Verfasser]. "Silizium Nanoribbon Feld-Effekt Transistoren zur Kopplung an elektroaktive Zellen / Michael Jansen". Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2014. http://d-nb.info/1051508789/34.
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Jansen, Florian [Verfasser]. "Effects of non-thermal atmospheric pressure plasma on human fibroblasts / Florian Jansen". Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2021. http://d-nb.info/1231075120/34.
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Bertho, Yann. "Dynamique d'écoulements gaz-particules en conduite verticale". Palaiseau, Ecole polytechnique, 2003. https://pastel.archives-ouvertes.fr/tel-00171722.
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Schuster, Verena [Verfasser], i Andreas [Akademischer Betreuer] Jansen. "Investigating the Effects of Sex Hormones on the Female Brain – Necessary Prerequisites and a First Insight on the Influences on Gray Matter Volume / Verena Schuster ; Betreuer: Andreas Jansen". Marburg : Philipps-Universität Marburg, 2021. http://d-nb.info/1236692039/34.
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Janse, van Rensburg Belinda. "Distribution and quantification of Fusarium verticillioides in South African maize and its effect on grain quality and toxicity / Belinda Janse van Rensburg". Thesis, North-West University, 2006. http://hdl.handle.net/10394/8.
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Maize is the most important cereal crop produced in southern Africa. Worldwide,
Fusarium verticillioides and F. proliferatum are the most commonly reported fumonisin producing
fungi to infect maize. Both are important producers of fumonisins that are
associated with animal mycotoxicoses. F. verlicillioides-infected maize has also been
associated with human oesophageal cancer in South Africa, northern Italy and Iran,
Increased incidence of liver cancer has also been reported from certain endemic areas
of the People's Republic of China due to ingestion of F. verticillioides-infected maize.
The carcinogenic risk that fumonisins pose to humans was evaluated by the World
Health Organisation's - International Agency for Research on Cancer (WHO-IARC).
They were classified as Group 2B carcinogens, which means that they are probably
carcinogenic to humans. This potential threat highlights the necessity for screening
human and animal foodstuffs for fumonisins. A primary concern in evaluating potential
health risks associated with mycotoxin-contaminated foodstuffs is the reliability of
fumonisin detection methods, A number of detection methods have been developed,
but results are not consistent when compared. Substantial mycotoxin research has
been carried out but high variation in mycotoxin results and species identification
confounded statistical analysis of data. The aim of this study was to identify and
address sources of variation in the quantification of species identification and fumonisin
quantification. Chapter 1 provides a general overview of the importance of maize as
a primary crop for subsistence, resource-poor and commercial farmers and the
potential threat fumonisins pose to the safety of humans and animals. The objective
of chapter 2 was to determine whether fumonisin levels in milled maize samples
increase or decrease over time prior to testing for fumonisins, Grain samples from
Sannieshof, Ventersdorp and Lichtenburg was evaluated for fumonisin levels every two
months for a year. High variation in fumonisin levels quantified with the same samples
was observed over time, indicating sources of variation which needs to be studied.
Chapter 3 addressed sources of variation associated with sampling and improving
sampling procedures to reduce this variation. Maize kernel samples were selected from
five localities with high fumonisin levels. These samples were used for investigating the
following four sources of variation, namely 1) subsample size (increasing from 25 g to
1000 g, 2) establish variation of fumonisins within a single maize sample, 3) number of replications (5 to 25) using prescribed 25 g subsamples and modified 250 g subsamples
and 4) variation between laboratories and techniques for fumonisin detection. In
chapter 4 the incidence of F. verticillioides, F. subglutinans, F. proliferaturn and
fumonisins in maize from warmer production areas of South Africa was evaluated to
determine 1) the incidence and geographic spread of Fusarium pathogens from maize
grain silos in South Africa, 2) to study the relationship between isolation frequency,
fumonisin incidence and ergosterol concentration and 3) to establish the relationship
between fumonisin tevels and weather parameters. Chapter 5 aimed to 1) determine
Fusarium spp, variation in maize samples, 2) compare the accuracy of Fusarium spp.
identification on rose bengal-glycerine-urea (RbGU) as selective and identification
medium with split plates containing standard Carnation Leaf (CLA) & Potato Dextrose
Agars (PDA) as identification media and 3) detect and quantify potential bias among
enumerators (inter-enumerator reliability) in direct microscopic identifications of F.
verticillioides, F. proliferaturn and F. subglutinans. Reducing variation in quantification
of fumonisins and improving Fusarium spp. identification on maize kernels, would
increase confidence and accuracy in this technology. This will improve the value of
research on this topic. Improved accuracy in detection and quantification of fumonisins
will also contribute directly to the establishment of realistic and safe tolerance levels for
this toxin in basic and processed foodstuffs. This in turn is important in ensuring food
safety for humans and animals.Thesis (M. Environmental Science (Plant Protection))--North-West University, Potchefstroom Campus, 2007.
6
Courrech, du Pont Sylvain. "Avalanches granulaires en milieu fluide". Phd thesis, Université Paris Sud - Paris XI, 2003. http://tel.archives-ouvertes.fr/tel-00004216.
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Considérons une boite remplie de grains et inclinons la progressivement. Au-dessus d'un angle critique, un écoulement de surface se déclenche. Cette avalanche, d'amplitude et de durée finies, fait relaxer l'angle du tas de quelques degrés. Ce processus intervient fréquemment dans la nature, notamment sous la forme d'écoulements de débris qui se produisent aussi bien à la surface de la Terre que dans les fonds marins. Cependant, les écoulements denses de granulaires immergés dans un liquide ont été peu étudiés. Ainsi, le travail expérimental rapporté dans ce manuscrit s'attache à déterminer l'influence d'un fluide environnant, gaz ou liquide, sur l'amplitude et la dynamique des avalanches. Nous mettons en évidence trois régimes d'avalanches contrôlés par deux paramètres sans dimension : le rapport r entre la densité des grains et celle du fluide, et le nombre de Stokes St qui compare l'inertie d'un grain aux effets visqueux du fluide. Dans un gaz (grandes valeurs de r et de St), l'effet du fluide est négligeable. Dans les liquides (petites valeurs de r), l'amplitude des avalanches diminue tandis que leur durée augmente lorsque St diminue. Dans une deuxième partie, nous étudions l'effet d'un confinement du tas entre deux parois latérales sur sa stabilité. Maximale quand l'écart entre parois est minimum, la valeur des angles diminue sur une longueur caractéristique B lorsque l'écart entre parois augmente. Cet effet peut s'expliquer par la redirection d'une partie des contraintes internes au tas vers les parois, ce qui y induit des forces de frottement prévenant ou bloquant l'écoulement. Deux lois d'échelles dépendantes de la taille des grains sont mises en évidence pour la longueur B : l'effet des parois est géométrique pour les gros grains alors qu'un régime cohésif est observé pour les petits grains. Enfin, nous rapportons les résultats de premières expériences dans l'air où la vitesse des grains est mesurée et apparaÎt exponentiellement décroissante avec la profondeur.
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Krishnaraj, K. P. "Flow and structure of dense granular materials". Thesis, 2019. https://etd.iisc.ac.in/handle/2005/5060.
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Granular materials are frequently encountered in our daily lives and are widely processed forms
of matter in various industries. Despite decades of research, the mechanical behavior of
granular materials is not well understood. This thesis focuses on two problems in granular
materials, flow in a cylindrical Couette geometry, and emergence of the force network.
Recent experiments on granular materials sheared in a cylindrical Couette device revealed a
puzzling anomaly, wherein all components of the stress rise nearly exponentially with depth.
In this thesis, using particle dynamics simulations and imaging experiments, we show that the
stress anomaly arises from a remarkable vortex flow. For the entire range of fill heights
explored, we find a single toroidal vortex that spans the entire Couette cell, and whose sense is
opposite to the uppermost Taylor vortex in a fluid. In addition, we show that the vortex is
driven by a combination of shear-induced dilation, a phenomenon that has no analogue in fluids
and gravity flow. We also find that the secondary flow exhibits interesting features like dual
vortices in flow conditions where the inertia of grains is relevant. Dilation is a well-known
characteristic of a flowing granular medium, but not adequately represented in existing models.
This thesis makes a case for properly incorporating cross-streamline dilation in constitutive
models.
In the second part of this thesis, we focus on force transmission in amorphous materials. Force
transmission in amorphous materials like grains, suspensions, emulsions, and foams is
primarily characterised by a complex network of inter-particle contact forces called the force
network. Important transport and mechanical properties of these forms of matter have been
experimentally shown to be associated with the underlying force network. The origin and
features of the force network has remained elusive. By defining connectivity in particle
packings based on linearity of particle contacts, we show the existence of a criticality. The
paths with critical linearity are shown to be mechanically important and constitute the strong
force network observed in experiments. The origin of this criticality is shown to be a feature
that emerges out of geometric constraints inherent to particle packings. We explain how this
critical feature helps us understand particulate matter better, like the stress dip in granular piles
and Janssen effect in silos. With a simple path linearity dependent random walk model, we
provide insights about force transmission in amorphous materials.
8
Van, Vuuren Stefanus Hendrik Jansen. "Evaluating the effect of life cycle cost forecasting accuracy on mining project valuations / Stefanus Hendrik Jansen van Vuuren". Thesis, 2013. http://hdl.handle.net/10394/11727.
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The study was conducted to establish what effect life cycle cost forecasting accuracy has on project valuations with special reference to a global mining organisation’s coal business unit in South Africa. The research stemmed from the fact that the organisation identified through its own research in 2009 that its capital projects rarely met the originally budgeted life cycle cost forecasts estimated during the project development stages. These forecasts were generally found to be underestimated. Overrunning of cost budgets in project management terms results in project failure.
The study employed two main empirical research sections. The first section took a case study approach where past implemented project results were collated and analysed. The main aim was to determine how close to reality the original life cycle cost estimates were, and secondly how any variances to the originally budgeted costs impacted on the anticipated project value post implementation. Secondly, the study employed in-depth interviews with seven project specialists within the organisation that were also involved in the development stages of the investigated projects.
The study concluded that life cycle cost forecasts are very important project business case inputs and that the necessary time and effort should go into developing them so as to ensure that they are as comprehensive and accurate as possible. The sensitivity analysis that was conducted revealed that a coal mining project business case is the second most sensitive to variations in life cycle costs after variations in commodity price. The results indicated that a 20% increase in life cycle costs can destroy an equivalent project value of up to 100%. Accurate life cycle cost forecasting is therefore essential in order to estimate to a certain degree of accuracy the value of a project which in turn will be used to inform capital investment decision making.MBA, North-West University, Potchefstroom Campus, 2014
9
Jansen, Sabine [Verfasser]. "Laughlin's wave function, plasma analogies and the fractional quantum Hall effect on infinite cylinders / vorgelegt von Sabine Jansen". 2007. http://d-nb.info/985159480/34.
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Jansen, van Rensburg Francois Gysbert. "Effects of load shifting on water quality in a large potable water network / Francois Gysbert Jansen van Rensburg". Thesis, 2015. http://hdl.handle.net/10394/15301.
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Mathematical analyses indicated that significant possibilities exist for load shifting projects
on a Large Potable Water Utility (LPWU) in South Africa. A primary concern remained,
i.e. whether the load variation would have an effect on the water quality. Extensive
simulation and testing were initiated in order to prove that the load shift will not affect the
water quality.
In South Africa, the highest standard for drinking water is the Blue Drop award. The
LPWU has received this award multiple times and strives to maintain it. An investigation
was launched to determine if this load shifting project would have an effect on the quality
standards to which the utility holds (SANS 241 (2011)).
The LPWU has over 3000 km of pipelines to supply potable water to the industrial
heartland of the country as well as millions of domestic users. The LPWU network is the
longest pumping network in the world and is still expanding.
The investigation included a simulation of a pumping simulation package to determine
how the system would react to the changes. In this simulation, the load reduction in terms
of Mega litre per day (Ml/day) was established. Results were compared to the normal
operating parameters of the Water Treatment Works (WTW).
The mathematical analysis in this investigation concluded that an evening peak load shift
of 24.5 MW is achievable. This dissertation will emphasise the necessity of a detailed
investigation. The investigations and simulation will determine that the volume of water is
well within the operating parameters of the WTW. Studies were done on each area of the
plant. In-depth conversations with WTW personnel revealed that the reduction of the
volume of water in question will not have an effect on the water quality.
Further, it was established that it would be possible to use the sumps of the water
treatment works to achieve the desired load shift. By using the sumps of the WTW, a load
shift can be done without stopping any process in the WTW with the exception of
disinfection at the Booster Pump Stations (BPS), where the balancing reservoirs were
used as buffer capacity.
The investigation shifted to establish whether stagnant water and a change in dosage
would have an effect on the water quality in regard to the reduction and recovery load. As
expected, the water never became stagnant at any moment due to the fact that only a
small portion of the load was reduced.
The water quality and dosage report of the water utility was used and compared to normal
operations. The planned load shift had no effect on any aspects of the water quality. The
project is feasible and will reach the set targets without affecting the water quality.MIng (Mechanical Engineering), North-West University, Potchefstroom Campus, 2015
Książki na temat "Janssen effect"
1
Environment, Saskatchewan Ministry of. Jansen Project environmental impact statement: Response to technical comments. [Regina: Ministry of Environment], 2011.
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2
Kirkpatrick, Kate. French Sins, I. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780198811732.003.0002.
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Chapter 2 demonstrates that theology played a significant part in Sartre’s formation as a phenomenologist. It considers the ‘philosophical’ and ‘theological’ sources Sartre encountered, beginning with Augustine’s ontology of sin’s origins and effects, and then turning to the seventeenth-century French revival of Augustinianism in the works of Bérulle, Descartes, Jansen, Pascal, and Fénelon. These thinkers’ ontological conceptions of sin as le néant informed their accounts of the human person and the nature of freedom. This chapter demonstrates that Sartre was exposed to these Augustinianisms, laying groundwork for the claims to follow: that for Sartre, as for the theologians described here, the human exists in a tensive state between being and nothingness.
3
Palmer, Thomas. Two Case Studies. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198816652.003.0008.
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Chapter 7 continues the argument of chapter 6 into two central topics which constitute tests for the apparent movement among mid- and later seventeenth-century Anglicans away from an Augustinian theological framework. Jeremy Taylor has been charged with abandoning the traditional doctrine of original sin, and by consequence that of the atonement. Section II analyses his teaching, and shows that attempts to identify his doctrine with that of Socinian thinkers should be rejected. Section III analyses Herbert Thorndike’s discussion of Jansen’s teaching on liberty in the Augustinus. Thorndike adopted an understanding of human liberty which seems to resemble that of Molina, but his surprisingly sympathetic treatment of Jansen reflects his admiration for Augustine’s analysis of original sin and its effects, and his continued commitment to the understanding of conversion which it underwrites.
Części książek na temat "Janssen effect"
1
Nemèth, Balàzs. "Developing active citizenship through adult learning and education. Experiences from an INTALL Winter School Comparative Working Group". W International and Comparative Studies in Adult and Continuing Education, 67–78. Florence: Firenze University Press, 2020. http://dx.doi.org/10.36253/978-88-5518-155-6.05.
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Active citizenship became a research issue for adult learning and education in 1995 when the Council of Ministers decided to make 1996 the Year of Lifelong Learning. Moreover, the Lisbon programme, in the year 2000, reinforced the relevance of the issue and, along with employability, connected it to lifelong learning. That is why since 2001 comparative adult learning and education researchers have put a specific focus on analysing active citizenship and bridging it to adult learning. For this very reason, a distinguished Comparative Working Group was formed at the 2019 Winter School of the Erasmus+ Intall project—on the one hand, to collect different national/regional and local narratives and understandings of active citizenship and, on the other, to gather examples, good practices, formations of active citi-zens, or trajectories of how to learn for active citizenship as routes and processes of lifelong learning. The same Winter School comparative group tried to analyse the similarities and differences collected in an effort to relate them to existing theoretical frames offered by key authors on the topic, including Baert, Jansen, Jarvis, Johnston, Wildemeeersch, and others. This paper discusses the experiences of the comparative working group and formulates some special conclusions and comments for further actions of comparative studies in adult learning and education.
2
Bee, Grega Rúbia, Daniel Damazio Pinto, Ana Claudia Costa Alves da Silva, Tiago Oliveira i Jucicléia da Silva Arrigo. "Vaccines against COVID-19 available in Brazil". W DEVELOPMENT AND ITS APPLICATIONS IN SCIENTIFIC KNOWLEDGE. Seven Editora, 2023. http://dx.doi.org/10.56238/devopinterscie-222.
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SARS-CoV-2 is a virus that triggered a worldwide disaster after causing deaths in many countries and infecting millions of people causing the disease COVID-19. Several vaccines were developed in record time to contain the pandemic. This study aimed to identify, analyze and compare, through a literature review, the scientific publications on the different vaccines against COVID-19 administered in Brazil. For this, a qualitative literature review was carried out using recently published articles, obtained from the Pubmed, Scielo, Capes, and Lilacs platforms, as well as from the websites of the World Health Organization, Oswaldo Cruz Foundation, and other trustworthy health organizations, seeking relevant information, such as the different types of technologies used for the development of vaccines, composition, efficacy rates, expiration date, storage, doses, administration, adverse effects and contraindications of each manufacturer of vaccines against COVID-19. This study concluded that the four immunizers administered in Brazil: CoronaVac, AstraZeneca, Pfizer, and Janssen, showed reliability, efficacy, and few side effects. With the advance of vaccination, there was a decrease in severe cases and deaths caused by SARS-CoV-2.
3
Dinçer, Hasan, i Nazife Orhan. "Innovative Work Behaviors in Turkish Banking Sector". W Global Strategies in Banking and Finance, 293–303. IGI Global, 2014. http://dx.doi.org/10.4018/978-1-4666-4635-3.ch019.
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In relation to globalization and its worldwide effects, the requirement for a high level of emotional intelligence competency that both senior managers, junior administrative officers, and other employees should have has gained importance for a successful decision making process. In addition, the significance of innovative management strategies and also employees who are open to innovations has started to be more of an issue for companies since dynamic changes and developments in the field of technology owing to this fierce competition affect almost all sectors seriously. Taking all of these variables into consideration, this chapter aims to investigate the role and importance of innovative work behaviors in the Turkish Banking Sector by using the questionnaire technique as a data collection tool. Findings have been obtained from 332 staff through the survey on emotional intelligence competency by Wong and Law and the innovative work behavior survey by Janssen.
4
Taber, Douglass F. "Development of Flow Reactions". W Organic Synthesis. Oxford University Press, 2015. http://dx.doi.org/10.1093/oso/9780190200794.003.0015.
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For a review of a monograph by C. Wiles and P. Watts on applications of flow reactors in organic synthesis, see Org. Process. Res. Dev. 2011, 15, 947. For a review by Klavs S. Jensen of MIT of flow approaches, see Angew. Chem. Int. Ed. 2011, 50, 7502. Hans-René Bjørsvik of the University of Bergen described (Org. Process. Res. Dev. 2011, 15, 997) a multijet oscillating disc microreactor, and Andreas Schmid of the Technische Universität Dortmund (Adv. Synth. Catal. 2011, 353, 2511) and László Poppe of the Budapest University of Technology and Economics discussed (Adv. Synth. Catal. 2011, 353, 2481) continuous flow reactors for biotransformations. Gases are readily handled in a flow apparatus. S. Chandrasekhar of the Indian Institute of Chemical Technology, Hyderabad demonstrated (Tetrahedron Lett. 2011, 52, 3865) partial deuteration of 1 to 2, using D2O as the deuterium source. Peter H. Seeberger of the Max Planck Institute, Potsdam oxidized (Org. Lett. 2011, 13, 5008) 3 to 4 with singlet oxygen. Dong-Pyo Kim of Chungnam National University and Robert H. Grubbs of Caltech effected (Org. Lett. 2011, 13, 2398) ethenolysis of 5 to give 6 and 7. Takashi Takahashi of the Tokyo Institute of Technology showed (Chem. Commun. 2011, 47, 12661) that even phosgene could be handled in a flow system, using it to activate 8 for condensation with benzylamine to give 9. In the liquid phase, Stephen L. Buchwald of MIT prepared (Angew. Chem. Int. Ed. 2011, 50, 8900) 11 by the fluorination of 10. Jesús Alcázar of Janssen Pharmaceutical, Toledo, showed (Tetrahedron Lett. 2011, 52, 6058) that a nitrile 12 could be reduced in a flow system to the aldehyde 13. Mark York of CSIRO prepared (Tetrahedron Lett. 2011, 52, 6267) the furan 16 by condensation of 14 with 15. Floris P.J.T. Rutjes of Radboud University Nijmegen used (Org. Process Res. Dev. 2011, 15, 783) the careful controls of a flow reactor to optimize the exothermic combination of 17 with 18 to give 19. Professor Buchwald demonstrated (Angew. Chem. Int. Ed. 2011, 50, 10665) a flow protocol for the lithiation of 20 with in situ borylation and Pd-catalyzed coupling with 21 to give 22.
5
Hamerow, Helena. "Land and Power: Settlements in the Territorial Context". W Early Medieval Settlements. Oxford University Press, 2002. http://dx.doi.org/10.1093/oso/9780199246977.003.0008.
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As settlements became more clearly bounded and fixed in the landscape, so too did territories based on landed production, which became increasingly intensive and politically controlled (as we shall see in Chapter 5). These territories became formalized when leaders were able to exercise authority within them by protecting clients through juridical and/or military means, and by extracting surplus from, and controlling access to, landed resources. The identification of communities and individuals with a particular territory or region, whether this was defined by shared markets, dialect, military allegiances, or other commonalities, must also have grown in importance in this period, as ties of ethnicity and kinship began to give ground to bonds of clientship and rank. The formalization of territories was of course key to the formation of early kingdoms. What can archaeology tell us about the effects of territorialization and estate formation on rural communities? Certain regular features govern territorial formation in pre-industrial societies. In particular, universal ‘push–pull’ factors underlie the territorial structure and settlement pattern of agrarian communities. Briefly stated, every community needs to establish a territory in order to keep neighbouring communities at a distance and preserve its resources (‘push’ factors), but the necessity of maintaining certain social ties between communities, such as marriage, trade, and shared defence (‘pull’ factors), will act to minimize the distance between them (Heidinga 1987, 157). For example, the distribution of settlement in the Veluwe district of the central Netherlands shows that the northeast and the southwest regions were largely empty in the seventh century, even though their soils were suitable for farming and they were occupied both before and after this period. They lay outside the core area of the seventh-century resettlement of the Veluwe, however, and it appears that communities chose not to spread out thinly across the entire territory, but rather to remain relatively close to one another (Heidinga 1987, 162). In the Netherlands, Germany, and England, early territories could, under certain circumstances, be remarkably stable and survive to be detected in much later boundaries (e.g. Waterbolk 1982 and 1991a; Cunliffe 1973; Janssen 1976). In view of this stability and the behavioural ‘rules’ which appear to govern territorial formation, some archaeologists have attempted to reconstruct proto-historic territories. Several presuppositions underlie such reconstruction. The first is that the ‘push–pull’ factors already mentioned invariably operate between neighbouring communities.
6
Harding, Dennis. "Conclusion: A Sense of Place". W Iron Age Hillforts in Britain and Beyond. Oxford University Press, 2012. http://dx.doi.org/10.1093/oso/9780199695249.003.0015.
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It has often been supposed that the Anglo-Saxon poet lamenting the passing of an heroic society was referring to the ruins of Roman walls, for some reason decorated with serpentiform designs. But it seems more likely that the walls in question were those of an older order altogether, the grass-covered ramparts of a long-abandoned hillfort, winding serpent-like around the contours of a conspicuous local landmark like the Lambton Worm of Wearside folklore. However derelict, such sites must have retained a sense of place that heightened in collective memory the importance of people and events that were associated with them. Archaeology by convention characterizes ancient societies on the basis of the artefacts that they leave behind, whether structural and monumental, or portable and ephemeral. What survives will depend in significant measure upon the durability of material or construction, and upon a variety of taphonomic and environmental factors relating to the deposit or residual context. It will also self-evidently depend upon what communities chose to create and to leave behind, since artefacts are essentially proxy expressions of what they regarded as important, reflecting not just a basic utility but something of the identity and social values of the makers. As hillforts are the most substantial, monumental constructions of Late Bronze Age and Iron Age communities in north Alpine Europe, exceeding in scale even funerary monuments of those local groups that created lasting memorials to the dead, we may infer that they were the most potent expression of what mattered to the communities that built them. One of the recurrent frustrations of archaeology is that for periods or regions in which settlement remains are well represented, burial sites can prove elusive, and vice versa. What appears to be an exasperating demonstration of Murphy's Law nevertheless must have a significant explanation. In effect, some communities leave a mark predominantly in terms of settlement remains and others predominantly in funerary monuments. Diepeveen- Jansen (2007: 385) observed that in the Iron Age of the Marne-Moselle region, ‘the use of hillforts alternates with the employment of increasingly ostentatious burial practices’ (my emphasis), with the implication that this must reflect a meaningful shift in social expression.
Streszczenia konferencji na temat "Janssen effect"
1
De Clerck, F., R. Van de Wiele, B. Xhonneux, L. Van Gorp, Y. Somers, W. Loots, J. Beetens, J. Van Wauwe, E. Freyne i P. A. J. Janssen. "PLATELET TXA2 SYNTHETASE INHIBITION AND TXA2/PROSTAGLANDIN ENDOPEROXIDE RECEPTOR BLOCKADE COMBINED IN ONE MOLECULE (R 68070)". W XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643465.
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F 68070, an oxime-alkane carboxylic acid derivative (Janssen Pharmaceutica), is a potent inhibitor of thromboxane A2 (TXA2) synthetase activity (IC50 in vitro against thrombin-stimulated human platelets in plasma : R 68070 : 2.9 x 10-8 M; CGS 13080 : 6 x 10-8 M; OKY-1581 : 8.2 x 10-8 M; dazmegrel : 2.6 x 10-8 M; dazoxiben : 2.3 x 10-8 M).The compound specifically inhibits platelet TXA2 synthetase activity (14C-arachidonic acid metabolism by washed human platelets) without effect on the cyclo-oxygenase, lipoxygenase (platelets, RBL cells) or prostacyclin synthetase activities (rat aortic rings).The inhibitory effect of R 68070 against human platelet TXA2 synthetase activity increases upon prolongation of the contact time (ICsg at 0.5 min of contact : 5.2 x 10-7 M; at 5 min : 8.3 x 10-8 M; at 30 min : 2.5 x 10-8 M) and is reversed by washing of the platelets.In vivo, the compound has a comparatively strong inhibitory effect on platelet TXA2 synthetase activity after oral administration to rats (ED50 - 2 h : R 68070 0.013 mg/kg; CGS-13080 : 0.8 mg/kg; OKY-1581 : 0.61 mg/kg; dazmegrel : 1 mg/kg; dazoxiben : 4.1 mg/kg) and a protracted duration of action in rats and dogs (inhibition 8 h after 1.25 mg/kg orally > 80 %).In vitro, R 68070 inhibits the aggregation of human platelets in plasma stimulated with collagen (IC50 : 4 x 10-6 M), but also with U 46619 (IC50 : 3.8 x 10-6 M) without affecting the primary aggregation reaction elicited by ADP, 5-HT or adrenaline. The compound thus also produces platelet TXA2/prostaglandin endoperoxide receptor blockade.In rats and in dogs R 68070 (1.25 mg/kg I.V.) potently prevents thrombus formation in carotid and coronary arteries damaged by electrical stimulation.The combination of platelet TXA2 synthetase inhibition with TXA2/prostaglandin endoperoxide blockade in one molecule thus might offer an improved anti-thrombotic effectiveness.
2
Petrova, Petya G., C. Guedes Soares i Zhivelina I. Cherneva. "Influence of the Third Order Nonlinearity on the Distribution of Wave Height Maxima in an Offshore Basin". W ASME 2008 27th International Conference on Offshore Mechanics and Arctic Engineering. ASMEDC, 2008. http://dx.doi.org/10.1115/omae2008-58049.
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The effect of the coefficient of kurtosis, λ40, on the distribution of wave height maxima has been investigated. The data set used consists of water surface displacements in irregular deep water unidirectional wave fields generated in an offshore basin and defined by the JONSWAP spectrum. The full-scale records are of almost 3h17min duration. The measurements have been performed at ten equidistant gauges along the basin, which permits to follow the changes in wave statistics away from the wave-generator. Subsequently, the records have been split into series of different length, corresponding to N = 100, 200 and 300 waves, and the probability density functions and the exceedance probabilities of the maximum wave heights have been constructed conditional on λ40. They have been compared with the modified Edgeworth-Rayleigh model of Mori and Janssen [1] applied to the maximum wave heights. The theoretical expressions are formulated as a simple function of the coefficient of kurtosis and the number of waves in the sample. The coefficient of kurtosis, reflecting the third order nonlinearity, is found to increase with the distance from the wave-maker. The considered theoretical density curves describe only qualitatively the shift of the empirical mode towards higher values. The tendency of the peak of the distribution to diminish with increase of λ40 has been observed. However, the most probable wave height remains underestimated by the theory for all classes of λ40, regardless of the length of the time series. Finally, the probability that a certain normalized height level Hmax/Hs will be exceeded increases with the increase of λ40, as being theoretically predicted, although it is overestimated by the theory in the lower range of values of λ40 and underestimated over the higher range of values of λ40.
3
Zhao, David, i Mingxin Zhao. "On the Study of Packed Catalyst Bed Stresses for Outward Radial Flow Reactors". W ASME 2020 Pressure Vessels & Piping Conference. American Society of Mechanical Engineers, 2020. http://dx.doi.org/10.1115/pvp2020-21611.
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Abstract Pressure drop in a radial flow reactor occurs when process flow crosses the packed catalyst bed installed between the two concentric perforated screens during operation. This pressure drop generates the lateral bed stress against the reactor’s perforated screens to shift. The pressure drop will further grow as catalyst attrition increases in production. For an outward radial flow, the pressure drop may exert higher stresses to the outer screen as the packed bed is pushed toward it. An extreme case is when the entire catalyst bed could be pinned to the outer screen of the reactor by enough pressure drop. This could cause the internal components to be overly stressed on the excessive bed load, for which the components might not have been designed adequately. Predicting how radial pressure drop impacts the bed stress and shifts the load distribution is important in preventing mechanical failure during operation. In this study, an analytical model is derived based on Janssen’s theory, a classical semi-empirical granular solid material model, to examine a generic packed catalyst bed in an outward radical flow reactor. A modification to Janssen’s theory is introduced to include pressure drop in order to explore its effects on bed stress and load. The critical condition is derived.
4
Zheng, Xiang Yuan, i Torgeir Moan. "Freak Waves Within the Third Order Model". W ASME 2010 29th International Conference on Ocean, Offshore and Arctic Engineering. ASMEDC, 2010. http://dx.doi.org/10.1115/omae2010-20455.
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After the New Year Wave was recorded in January 1995, considerable works have been devoted to explore the definition, physical nature and occurrence probability of freak waves. Within the frame of classical wave theories, the linear and 2nd-order random wave models have been chosen most often in the numerical simulations to study the occurrence of freak waves. This paper employs the 3rd-order random wave theory in simulation to investigate the effects of higher-order wave interaction on the freak wave occurrence. The New Year Wave is used as the case study herein. Its crest is 18.5 m, a criterion applied to categorize the simulated wave trains. To efficiently simulate a wave train with complicated wave interactions, a 1D FFT method is suggested. It is pointed out that the high values of skewness and kurtosis excess of New Year Wave cannot be captured by the 2nd-order model. The 2nd-order model is more suitable for reproducing events of high crests. Extreme events need a higher-order wave model. This work extends the study by Prevosto and Bouffandeau (2002). With totally 75,000,000 waves simulated the occurrences of freak waves of crest > 18.5 m are compared among linear, 2nd- and 3rd-order wave models. The comparative study also includes the predictions by Forristall (2000), Prevesto (2000) and the one derived based on Mori and Janssen (2004). The simulation once again reveals the inadequacy of the 2nd-order model to generate freak waves. The occurrence probability of freak waves under the 3rd-order model is more than 6 times higher than that under the 2nd-order.
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Prigorkina, Veronika. "ORDER ICONICITY PRINCIPLE IN TEMPORAL INTERPRETATION OF RUSSIAN PERFECTIVE PARTICIPIAL AND CONVERBIAL CLAUSES". W Проблемы языка: взгляд молодых учёных. Институт языкознания РАН, 2023. http://dx.doi.org/10.37892/978-5-6049527-1-9-5.
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Pragmatic factors frequently affect the interpretation of grammatical constructions, and the category of relative tense is no exception. To arrange the events on the timescale with respect to each other interlocutors may resort to the implicit content of the phrase – implicatures. The current study observed the effect of a specific pragmatic phenomenon – Order Iconicity Principle (OIP) – on the interpretation of non-finite taxis constructions in Russian: perfective past participles (prichastija) and perfective converbs (deeprichastija). According to this principle, the perceptually and statistically preferred temporal interpretation of sequential events is the one which iconically corresponds to the predicates' order of mentioning. Based on a series of self-paced reading and interpretation acceptability judgements (IAJ) experiments, I suggest that OIP applicability scope can be extended from coordinated structures with perfective verbs [Paducheva 2017; Khrakovskij 2009] and dependent temporal clauses [Clark & Clark 1968; Sasanuma & Kamio 1976; Natsopoulos et al. 1991; Jansen 2008] to nonfinite constructions. In accordance with the hypotheses, for both Russian perfective participles and converbs there was a significant OIP effect, manifested in higher acceptability rates and shorter interpretation latencies for iconic temporal interpretation even when the interpretations were not contextually or lexically supported. Due to the difference in the syntactic and discourse properties of the constructions (scale of finiteness, syntactic function, preservation of the dynamic verb semantics and category of absolute tense; [Vjal'sova 2008]; [Krapivina 2009]; [Say 2020]), a significantly smaller OIP effect was noted for participles. Results of an additional pilot study including free-interpretation of these constructions even further suggest that highly debatable posteriority interpretation in Russian non-finite clauses [Rappaport 1984; Shigurov 1991; Weiss 1995; Akimova & Kozintseva 2001; Khrakovskij 2003; Birzer 2010] to be a specific realization of OIP implicature for Russian perfective converbs and of an absolute past reference for Russian perfective past participles.
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Morreira, Shannon. "Pandemic Pedagogy: Assessing the Online Implementation of a Decolonial Curriculum". W Seventh International Conference on Higher Education Advances. Valencia: Universitat Politècnica de València, 2021. http://dx.doi.org/10.4995/head21.2021.12861.
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The student protests in South Africa (2015–2017) triggered shifts in pedagogical practices, such that by 2020 many South African higher education institutions had begun to make some concrete moves towards more socially just pedagogies within teaching and learning (Quinn, 2019; Jansen, 2019). In March 2020, however, South Africa went into lockdown as a result of Covid-19, and all higher education teaching became remote and non-synchronous. This paper reports on the effects of the move to remote teaching on the implementation of a new decolonial ‘emplaced’ pedagogy at one South African university. The idea of emplacement draws on the careful incorporation of social space as a teaching tool within the social sciences, such that students can situate themselves as reflexive, embodied persons within concrete spaces and communities which carry particular social, economic and political histories. This paper draws on data from course evaluations and student assignments, as well as a description of course design, to argue that many of the benefits of careful emplacement in historical and contemporary context can happen even where students are never in the same physical spaces as one another or their lecturers. This relies, however, on students’ having access to both the necessary technology and to an environment conducive to learning.
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Zhao, Mingxin, i Pedro Vargas. "Prediction of Packed Catalyst Bed Stress and Load for Radial Flow Reactors". W ASME 2014 Pressure Vessels and Piping Conference. American Society of Mechanical Engineers, 2014. http://dx.doi.org/10.1115/pvp2014-28455.
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For the radial flow reactor with a packed catalyst bed, the pressure drop in radial direction will affect bed support stress and load condition significantly. Increased fines due to catalyst attrition during operation will increase the radial pressure drop. For an extreme case, the entire catalyst bed could be pushed inward and pinned to the reactor’s perforated center screen, potentially causing the internal components to be overly stressed by the excessive load. Understanding the impact of radial pressure drop to bed stress and load distribution is very important for reactor internals design and operation. In this study, a generic packed catalyst bed for a radial flow reactor is analytically modeled and examined for stress and load by a classical granular solid material model, i.e., Janssen’s theory, which is further modified to include the pressure drop effects for a radial flow reactor. Interactions between bed stress, load, and radial pressure drop are explored. The critical condition is derived.