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BackgroundThis paper explores the impact of thermal radiation on boundary layer flow of dusty hyperbolic tangent fluid over a stretching sheet in the presence of magnetic field. The flow is generated by the action of two equal and opposite. A uniform magnetic field is imposed along the y-axis and the sheet being stretched with the velocity along the x-axis. The number density is assumed to be constant and volume fraction of dust particles is neglected. The fluid and dust particles motions are coupled only through drag and heat transfer between them.MethodsThe method of solution involves similarity transformation which reduces the partial differential equations into a non-linear ordinary differential equation. These non-linear ordinary differential equations have been solved by applying Runge-Kutta-Fehlberg forth-fifth order method (RKF45 Method) with help of shooting technique.ResultsThe velocity and temperature profile for each fluid and dust phase are aforethought to research the influence of assorted flow dominant parameters. The numerical values for skin friction coefficient and Nusselt number are maintained in Tables 3 and 4. The numerical results of a present investigation are compared with previous published results and located to be sensible agreement as shown in Tables 1 and 2.ConclusionIt is scrutinized that, the temperature profile and corresponding boundary layer thickness was depressed by uplifting the Prandtl number. Further, an increase in the thermal boundary layer thickness and decrease in momentum boundary layer thickness was observed for the increasing values of the magnetic parameter.

. The three-dimensional mixed convection boundary layer flow of a nanofluid induced by an exponentially stretching sheet is numerically investigated in the presence of thermal radiation, heat source/sink and first-order chemical reaction effects. The adopted nanofluid model incorporates the effects of Brownian motion and thermophoresis into the mathematical model. The first-order velocity slip boundary conditions are also taken into account. The governing boundary layer equations are transformed into a set of nonlinear ordinary differential equations by employing suitable similarity variables. The resultant equations are solved numerically using the Runge-Kutta-Fehlberg method. Obtained solutions are compared with previous results in a limiting sense from the literature, demonstrating an excellent agreement. To show the typical trend of the solutions, a parametric study is conducted. The axial velocity, transverse velocity, temperature and nanoparticle volume fraction profiles as well as the skin-friction coefficient, Nusselt and Sherwood numbers are demonstrated graphically as a representative set of numerical results and discussed comprehensively.

Purpose This paper aims to deal with the study of heat and mass transfer on double-diffusive three-dimensional hydromagnetic boundary layer flow of an electrically conducting Casson nanofluid over a stretching surface. The combined effects of nonlinear thermal radiation, magnetic field, buoyancy forces, thermophoresis and Brownian motion are taken into consideration with convective boundary conditions. Design/methodology/approach Similarity transformations are used to reduce the governing partial differential equations into a set of nonlinear ordinary differential equations. The reduced equations were numerically solved using Runge–Kutta–Fehlberg fourth-fifth-order method along with shooting technique. Findings The impact of several existing physical parameters such as Casson parameter, mixed convection parameter, regular buoyancy ratio parameter, radiation parameter, Brownian motion parameter, thermophoresis parameter, temperature ratio parameter on velocity, temperature, solutal and nanofluid concentration profiles are analyzed through graphs and tables in detail. It is found that the solutal component increases for Dufour Lewis number, whereas it decreases for nanofluid Lewis number. Moreover, velocity profiles decrease for Casson parameter, while the Nusselt number increases for Biot number, radiation and temperature ratio parameter. Originality/value This paper is a new work related to three-dimensional double-diffusive flow of Casson nanofluid with buoyancy and nonlinear thermal radiation effect.

PurposeThis paper aims to numerically investigate the two-dimensional unsteady laminar magnetohydrodynamic bioconvection flow and heat transfer of an electrically conducting non-Newtonian Casson thin film with uniform thickness over a horizontal elastic sheet emerging from a slit in the presence of viscous dissipation. The composite effects of variable heat, mass, nanoparticle volume fraction and gyrotactic micro-organism flux are considered as is hydrodynamic (wall) slip. The Buongiorno nanoscale model is deployed which features Brownian motion and thermophoresis effects. The model studies the manufacturing fluid dynamics of smart magnetic bio-nano-polymer coatings.Design/methodology/approachThe coupled non-linear partial differential boundary-layer equations governing the flow, heat and nano-particle and micro-organism mass transfer are reduced to a set of coupled non-dimensional equations using the appropriate transformations and then solved as an nonlinear boundary value problem with the semi-numerical Liao homotopy analysis method (HAM).Validation with a generalized differential quadrature (GDQ) numerical technique is included.FindingsAn increase in velocity slip results in a significant decrement in skin friction coefficient and Sherwood number, whereas it generates a substantial enhancement in Nusselt number and motile micro-organism number density. The computations reveal that the bioconvection Schmidt number decreases the micro-organism concentration and boundary-layer thickness which is attributable to a rise in viscous diffusion rate. Increasing bioconvection Péclet number substantially elevates the temperatures in the regime, thermal boundary layer thickness, nanoparticle concentration values and nano-particle species boundary layer thickness. The computations demonstrate the excellent versatility of HAM and GDQ in solving nonlinear multi-physical nano-bioconvection flows in thermal sciences and furthermore are relevant to application in the synthesis of smart biopolymers, microbial fuel cell coatings, etc.Research limitations/implicationsThe numerical study is valid for two-dimensional, unsteady, laminar Casson film flow with nanoparticles over an elastic sheet in presence of variable heat, mass and nanoparticle volume fraction flux. The film has uniform thickness and flow is transpiring from slit which is fixed at origin.Social implicationsThe study has significant applications in the manufacturing dynamics of nano-bio-polymers and the magnetic field control of materials processing systems. Furthermore, it is relevant to application in the synthesis of smart biopolymers, microbial fuel cell coatings, etc.Originality/valueThe originality of the study is to address the simultaneous effects of unsteady and variable surface fluxes on Casson nanofluid transport of gyrotactic bio-convection thin film over a stretching sheet in the presence of a transverse magnetic field. Validation of HAM with a GDQ numerical technique is included. The present numerical approaches (HAM and GDQ) offer excellent promise in simulating such multi-physical problems of interest in thermal thin film rheological fluid dynamics.

To assess the long-term effectiveness and safety of tocilizumab, abatacept, and tumor necrosis factor-α inhibitors (TNFi), in the Italian real-world setting of rheumatoid arthritis (RA). The records of adult RA patients from the Italian biologics’ registry Gruppo Italiano Studio Early Arthritis (GISEA) were analyzed. Demographic and clinical data were obtained at entry. The disease remission rate (28-joint disease activity score calculated using the erythrocyte sedimentation rate [DAS28-ESR] ≤ 2.6) and frequency of adverse events (AEs) were evaluated at 2 years. From 1999 to 2014, 7539 patients were treated with biologics (61.3% in first- and 22.6% in second-line), 68% of cases received TNFi, 9.1% tocilizumab, and 8.6% abatacept. Treatment groups showed a similar DAS28 at entry. As first-line, tocilizumab induced a significantly higher remission rate than abatacept or TNFi at 6 (51 vs 23.3 and 26.2%, respectively; p < 0.0001) and 24 months (52.3 vs 33.3 and 34.4%, respectively; p < 0.01). A similar pattern was observed in later lines. The most common AEs reported were infections, reactions to biologics (more frequent among TNFi-treated patients), increased transaminase (more frequent among TCZ-treated patients), and cardiovascular events. In clinical practice, TCZ induced a rapid and long-lasting remission and in a higher percentage of patients compared to abatacept and TNFi, with a good safety profile.

Purpose – The purpose of this paper is to numerically solve the problem of an unsteady squeezing three-dimensional flow and heat transfer of a nanofluid in rotating vertical channel of stretching left plane. The fluid is assumed to be Newtonian, incompressible and electrically conducting embedded with nanoparticles. Effect of internal heat generation/ absorption is also considered in energy equation. Four different types of nanoparticles are considered, namely, copper (Cu), alumina (Al2O3), silver (Ag) and titanium oxide (TiO2) with the base fluid as water. Maxwell-Garnetts and Brinkman models are, respectively, employed to calculate the effective thermal conductivity and viscosity of the nanofluid. Design/methodology/approach – Using suitable similarity transformations, the governing partial differential equations are transformed into set of ordinary differential equations. Resultant equations have been solved numerically using Runge-Kutta-Fehlberg fourth fifth order method for different values of the governing parameters. Effects of pertinent parameters on normal, axial and tangential components of velocity and temperature distributions are presented through graphs and discussed in detail. Further, effects of nanoparticle volume fraction, squeezing parameter, suction/injection parameter and heat source/sink parameter on skin friction and local Nusselt number profiles for different nanoparticles are presented in tables and analyzed. Findings – Squeezing effect enhances the temperature field and consequently reduces the heat transfer rate. Large values of mixed convection parameter showed a significant effect on velocity components. Also, in many heat transfer applications, nanofluids are potentially useful because of their novel properties. They exhibit high-thermal conductivity compared to the base fluids. Further, squeezing and rotation effects are desirable in control the heat transfer. Originality/value – Three-dimensional mixed convection flows over in rotating vertical channel filled with nanofluid are very rare in the literature. Mixed convection squeezing three-dimensional flow in a rotating channel filled with nanofluid is first time investigated.

BackgroundIn the age of targeted-synthetic disease-modifying antirheumatic drugs (tsDMARDs), filgotinib represents the last JAK inhibitor available in Europe for rheumatoid arthritis (RA). Filgotinib is characterized by predominantly inhibition of JAK1 and its efficacy and safety have been highlighted by phase 2/3 studies, but no real-life data in RA are currently available.ObjectivesThe aim of this study was to evaluate the effectiveness and safety profile of filgotinib in real-life setting in RA patients included in Italian GISEA (Group for the Study of Early Arthritis) registry.MethodsFor this study, data from RA patients treated with filgotinib recorded in Italian GISEA registry were analysed. Disease activity scores and patients reported outcomes (PROs) were compared at baseline and six months follow-up using paired t-tests. The retention rate was estimated by the Kaplan-Meier method, while a cox regression model was used to search for possible factors influencing drug survival.ResultsOne hundred and seventy-nine patients (female 89.4%, age 57.8±12 years, FR/ACPA+ 64.3%, current/former smoker 31.8%) included in GISEA registry started filgotinib for active RA. Most patients were taking filgotinib as second (23.5%) or further (43%) b/tsDMARDs line of treatment. Filgotinib was used in monotherapy in 66.5% of patients, while 52% were not on treatment with glucocorticoids (GCs) at baseline. All demographic and clinical data are reported in Table 1. A follow-up visit was available for 122 patients (mean time of first follow-up visit: 4±2 months). As shown in table 1, we observed a decrease of all disease activity scores and PROs. At first follow-up visit, 67.8% of patients were in remission/low disease activity according to CDAI and 65.4% according to SDAI. Kaplan-Meyer analysis highlighted that drug persistence was similar either in monotherapy or combination therapy (Figure 1a), and irrespective of GCs at baseline (Figure 1b). However, a better persistence was observed in RA patients on first line treatment with filgotinib (Figure 1c). Thirty-five patients stopped filgotinib during follow-up, 10 for lack of efficacy, 4 for loss of efficacy, 4 for adverse events, while for the remaining cases the cause of drug discontinuation was unknown. No major cardiovascular events were reported. Finally, univariate Cox-regression model showed that b/tsDMARD naïve patients had a lower risk of drug discontinuation (naïve vs other lines: HR 0.37, 95%CI 0.20-0.86).ConclusionIn Italian real-life setting, filgotinib confirms a good effectiveness and safety profile.Table 1.Demographic and disease characteristics at baseline and at first follow-up visit (T1) of RA patients treated with Filgotinib.Variablesbaseline (n. 179)T1 (n. 122)Agemean (SD), years57.8 (12.7)58 (12.6)Gendern. (%), femalen. (%), man160 (89.4)19 (10.6)110 (90.2)12 (9.8)BMIn. (%), underweightn. (%), heathy weightn. (%), overweightn. (%), obese4 (3.8)50 (48.1)21 (20.2)29 (27.9)4 (5.3)36 (47.4)15 (19.7)21 (27.6)Smokersn. (%), currently smokern. (%), former smokern. (%), never smoker13 (13.8)17 (18)64 (68.1)8 (13.5)12 (20.3)39 (66.1)IgG RF/ACPA +n. (%)74 (64.3)54 (71.1)VAS painmean (SD)63.1 (29.1)35 (30.7)***VAS PtGAmean (SD)60 (26.7)35 (29)***VAS PhGAmean (SD)44 (25.4)20.9 (23)***TJC28mean (SD)5.4 (5)2.7 (3.8)**SJC28mean (SD)3.3 (3.5)1.3 (2.2)***DAS28-ESRmean (SD)4.6 (1.3)3.3 (1.4)**CDAImean (SD)19.1 (11.3)9.6 (9.5)**SDAImean (SD)20.5 (12)10.3 (10)**HAQ-DImean (SD)1.3 (0.7)0.9 (0.7)***glucocorticoidn. (%)86 (48)47 (38.5)**Prednisone (equivalent), mg/diemean (SD)5.8 (3.7)3.4 (2.6)*csDMARD (in corso)n. (%)60 (33.5)31 (25.4)b/tsDMARD linen. (%), 1^ linen. (%), 2^ linen. (%), 3^ line or others60 (33.5)42 (23.5)77 (43)/Mean time of first follow-up visit: 4±2 months*p<0.05, **p<0.01, ***p<0.001Figure 1.Survival analysis in RA patients treated with Filgotinib.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Background:Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease marked by various clinical features that significantly impact the quality of life for affected patients. While upadacitinib (UPA) has shown promising results in improving the signs and symptoms of PsA in two RCTs, real-world evidence on its effectiveness remains limited.Objectives:This study aims at assessing the real-world effectiveness of UPA in a large multicenter cohort of PsA patients by investigating its impact on key disease activity scores on both axial and peripheral engagement of the disease.Methods:Data of patients meeting CASPAR criteria for peripheral PsA and/or ASAS criteria for axial PsA were collected from 28 Italian rheumatology centers. The study included bio-naïve patients with a history of failure or intolerance to at least one conventional synthetic DMARD, as well as patients who had experienced failure with at least one biologic DMARD (bDMARD). Disease activity scores, such as LEI, DAPSA, MDA, VLDA, and ASDAS-CRP, were assessed at baseline and at 12, 24, 36, and 52 weeks. Adverse events were recorded at each visit. Paired t-tests were employed to compare disease activity indices at baseline and various follow-up times, while McNemar’s test was used to assess differences in the proportions of patients achieving MDA and ASDAS inactive disease at different follow-up intervals. Treatment persistence was estimated using the Kaplan-Meier method.Results:A total of 253 PsA patients, consisting of 181 females (71.5%) and 72 males (28.5%), underwent UPA treatment. The average age was 55.8±10.9 years, with a mean disease duration of 111.2±102.5 months. Peripheral joint involvement was observed in 161 individuals (63.6%), with 49 (33.6%) presenting an oligoarticular and 97 (66.4%) a polyarticular pattern (Table 1). Axial involvement was diagnosed in 92 patients (36.4%). Notably, 89 individuals (94.5%) had previously experienced treatment failure with at least one biologic DMARD (Table 1). Global treatment persistence was 77%, with a mean follow-up duration of 21.82 months. There were no differences observed between the axial and peripheral disease subsets or among the first line and further lines of treatment (Figure 1). Compared to baseline, a significant decrease in DAPSA (mean reduction 11.68; p<0.001) and ASDAS-CRP (mean reduction 1.00; p<0.001) was observed already at 3-month follow-up and throughout the observation period up to 52 weeks (Figure 1). The mean LEI score dropped from 0.64 at baseline to 0.36 at 12 weeks and 0.46 at 52 weeks (p<0.001). Additionally, a noteworthy increase in the percentages of patients achieving MDA (31.1%) and ASDAS-inactive disease (40.7%) was recorded at 52 weeks compared to baseline (Figure 1). During the follow-up period, 51 patients discontinued UPA [lack of efficacy (10 cases), loss of efficacy (25 cases), adverse events (4 cases), and infectious events (3 cases)]. The reasons for the remaining discontinuations were not specified.Conclusion:This study, conducted on a large cohort of PsA patients in a real-life setting, confirms the substantial benefits of UPA on both peripheral and axial disease involvement in the long term. It highlights UPA rapid onset of action, evident as early as the 3-month follow-up.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Giuseppe Lopalco: None declared, Eleonora Celletti: None declared, Maria Morrone: None declared, Fabiola Atzeni: None declared, Eleonora Bruschi: None declared, Antonio Carletto: None declared, Alberto Cauli declares consultation fee and meeting expenses from Abbvie, Massimiliano Cazzato: None declared, Maria Sole Chimenti: None declared, Francesco Ciccia: None declared, Francesco Cipollone: None declared, Fabrizio Conti: None declared, Addolorata Corrado: None declared, Francesca Cozzini: None declared, Lorenzo Dagna: None declared, Rosario Foti: None declared, Stefano Gentileschi: None declared, ELISA GREMESE: None declared, Roberto Gorla: None declared, Giuliana Guggino: None declared, Alberto Lo Gullo: None declared, Michele Maria Luchetti: None declared, Carlomaurizio Montecucco: None declared, Roberta Ramonda: None declared, Angelo Semeraro: None declared, Fausto Salaffi: None declared, Carlo Salvarani: None declared, Carlo Selmi: None declared, Emanuela Praino: None declared, Roberto F. Caporali: None declared, Florenzo Iannone: None declared.

Background:Nowadays, numerous therapeutic options are available for patients with rheumatoid arthritis (RA), and the number of patients achieving remission has significantly increased. However, some patients have a disease defined by EULAR as “difficult-to-treat”1 (D2T), which today represents a new challenge for rheumatologists.Objectives:The primary objective was to evaluate the characteristics of the D2T-RA population recorded in the Italian GISEA registry undergoing treatment with b/tsDMARDs. The secondary objective was to assess the effectiveness and changes at 6 and 12 months in disease outcomes, stratifying the analysis by different mechanisms of action.Methods:For this study, data from RA patients treated with b/tsDMARDs recorded in the Italian GISEA registry from January 2017 to December 2023 were analyzed. Disease activity scores and patient-reported outcomes (PROs) were recorded at baseline, and at six- and twelve-month follow-up. D2T-RA patients were defined by meeting these three criteria: 1) failure of ≥ 2 b/tsDMARDs (with different mechanisms of action); 2) signs suggestive of active/progressive disease (at least moderate disease activity according to disease activity scores and/or glucocorticoid treatment ≥ 7.5 mg/day prednisone or equivalent); 3) patient VAS (Visual Analogue Scale) pain and/or PtGA (Patient Global Assessment) and/or PhGA (Physician Global Assessment) > 20. The retention rates were estimated using the Kaplan-Meier method and compared with log-rank test, while repeated measures ANOVA (Analysis of Variance) was used to assess changes in disease activity and PROs during follow-up.Results:The GISEA cohort included 5251 treatment lines with b/tsDMARDs. We were able to assess the D2T category for 3439 cases at the start of a new treatment. Overall, 1060 (30.8%) patients met all three criteria for D2T-RA, while 2379 (69.2%) patients were not categorized as D2T. Table 1 reports the demographic and clinical characteristics of D2T-RA patients. Patients with D2T-RA showed higher disease activity and PRO scores at baseline. Notably, JAK inhibitors (JAKis) were used more frequently in D2T-RA patients (48.8%) compared to non-D2T-RA patients (33.3%, p<0.05).Globally, the 5-year survival rate was significantly lower for D2T-RA patients compared to those with non-D2T-RA (47.5% vs 62.5%, p<0.001). No significant differences in persistence were observed among the classes of b/tsDMARDs used in D2T-RA (log-rank test: 6.76, p=0.15), with a 5-year survival rate of 38.7% for abatacept, 41.2% for TNFi, 48.1% for IL6r inhibitors, 62.3% for anti-CD20, and 49.6% for JAK inhibitors. Figure 1 shows changes from baseline in disease activity scores and VAS pain in D2T-RA according to b/tsDMARD class. DAS28-ESR was reduced in all b/tsDMARD classes, except for TNFi. CDAI was reduced in all b/tsDMARD classes without any differences among the classes. VAS pain was reduced in all classes. For VAS pain, we observed a significant difference between abatacept and JAK inhibitors, with JAK inhibitors showing greater reduction in VAS pain (p<0.05). Also filgotinib, the latest JAK inhibitor approved onto the market, exhibited a significant decrease on pain perception at both time points.Figure 1.Conclusion:Our study provides a snapshot of D2T-RA patients within the GISEA registry. All currently used b/tsDMARDs appear to be effective in this patient cohort. The higher efficacy of JAK inhibitors, particularly in managing pain symptoms in these patients, warrants further investigation.REFERENCES:[1] Nagy G, Roodenrijs NMT, Welsing PM, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31-35.Acknowledgements:We thank Ing. Massimiliano Dellisanti Fabiano Vilardi for his valuable contribution to database creation and management.Disclosure of Interests:None declared.

Background:Long-term observational data on the real-life use of JAK inhibitors (JAKis) for rheumatoid arthritis (RA) and their comparison with biological drugs are still very limited. Large population-based registries have been increasingly used to investigate the performance of targeted drugs in a real-life setting.Objectives:The aim of this study is to evaluate and compare the 3-year retention rate of JAKis, TNF inhibitors (TNFis) and biologic drugs with other mechanisms of action (OMAs) in the large cohort of RA patients included in the Italian national GISEA registry.Methods:Data of all RA patients treated with targeted synthetic or biologic drugs were prospectively collected in the Italian multicentric GISEA registry. The analysis was limited to patients who started a first- or second-line targeted drug in the period after the first JAKi was marketed in Italy (1st December 2017). The 3-year retention rate was calculated by the Kaplan-Meier method and compared between different drug classes by a log-rank test. A descriptive analysis of reasons for discontinuation was performed.Results:The study population included 1027 RA patients (79.8% females, mean age [±SD] 56.9 [±13.5] years, mean disease duration 9.8 [±9] years, mean baseline SDAI 17.5 [±11.9], ACPA positive 67.4%, RF positive 62.7%) who received JAKis (baricitinib or tofacitinib, n=297), TNFis (n=365), or OMAs (n=365) as first or second targeted drug. Main baseline characteristics of study population were overall well balanced between treatment groups. Retention rate was numerically but not statistically higher (p=0.18) in patients treated with JAKis compared with TNFis or OMAs (80.6, 78.9 and 76.4% at 1 year and 73, 56.8 and 63.8% at 3 years, respectively) (Figure 1). Drug survival was significantly higher in patients receiving concomitant methotrexate (MTX) compared with monotherapy only in TNFis (66.8 vs 47.1%, p=0.04) but not in JAKis (76.1 vs 70.1%, p=0.54) and OMAs (66.1 vs 61.9%, p=0.41) group. Therapy was discontinued in a total of 211 patients because of ineffectiveness (n=107), adverse events (n=88), or compliance/other reasons (n=16). The most frequent reason for treatment withdrawal was ineffectiveness in both JAKis (n=30 out of 56) and TNFis (n=45 out of 74) groups, whereas OMAs were discontinued more frequently because of adverse events (n=41 out of 81).Conclusion:Our data confirmed in a real-life setting a favorable 3-year retention rate of all available targeted mechanisms of action for RA therapy. As expected, concomitant MTX significantly impacted persistence on therapy of TNFis only. Discontinuations of JAKis for adverse events were infrequent overall, confirming the safety profile observed in randomized clinical trials.Figure 1.Three-year retention rate by treatment group[Figure omitted. See PDF]Disclosure of Interests:None declared