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The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown.We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore1 [range, 0 to 3] on any of the four Mayo scale components).The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo.Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).

Among all the approaches commonly used to study masonry structures, micro- modelling is the most accurate. Masonry can be seen as a composite material made of bricks and mortar joints. Their different mechanical properties, their geometry and their arrangement inside the micro-structure, lead to very complex behaviours that are often difficult to represent using equivalent homogenous constitutive models commonly available in commercial and research FEM solvers. Micro-modelling can capture the complex non-linear behaviours of masonry by explicitly modelling the micro-structure inside the computational model. Micro- modelling leads to models with a large number of finite elements, thus increasing prohibitively the computational time. This is also due to the problem of solving complex nonlinear solutions involving damage and strain localization, leading to very small time-steps required to achieve convergence. Another issue with micro-modelling is the increased complexity in generating the finite element mesh with all the details of the micro-structure. This work presents some advanced tools that can decrease the high computational time required by micro- modelling. A 2-parameter tension-compression plastic-damage constitutive model is presented as an extension of an existing model previously formulated by some of the authors [1,2,3]. The model is implemented in the open-source FEM code OpenSEES [12] with the IMPL-EX method [5], a mixed implicit-explicit integration method that renders the response of this constitutive model step-wise linear, thus removing the convergence issues typically encountered when dealing with softening responses. This research also presents a tool implemented in the STKO (Scientific ToolKit for OpenSees) pre- and post-processor [4] able to automatically convert a homogeneous CAD geometry of a building into a micro-model.

INTRODUCTION The production of rubber composites in tire industries involves a compounding phase and a curing process. To get highly performant materials, a homogeneous distribution of chemicals, reinforcing fillers and curing agents in rubber is required. Among them, ZnO is the most efficient worldwide employed curing activator, even though its poor dispersion in rubber matrix generally implies a high demand of ZnO. However, as ZnO undergoes leaching during tire life-cycle, the reduction of ZnO amount is becoming an urgent issue. In this context, the present work aims at improving the dispersion of ZnO in rubber nanocomposites, simultaneously reducing the employed ZnO amount. The impact of a different distribution was studied by comparing the vulcanization efficiencies and the mechanical properties of cured rubber nanocomposites prepared by using either a novel double function filler, ZnO/SiO2, constituted by ZnO nanoparticles (NPs) anchored to silica or the conventional micro-crystalline ZnO (m-ZnO). MATERIAL AND METHODS ZnO/SiO2 was prepared through a sol-gel procedure; ZnO NPs (3-5 nm) were anchored on silica particles, as demonstrated by the morphological and structural characterization. ZnO/SiO2 and m-ZnO were used to prepare two polyisoprene (IR) nanocomposites with a brabender. The compounds were calendered at 50°C and vulcanized in a compression molding press. A dynamic-mechanical analysis was performed at room temperature in tensile loading conditions: a 0.1% of amplitude dynamic strain was superimposed to a static deformation, at a frequency of 10 Hz. Uniaxial tensile tests were also performed at constant nominal strain rate and at room temperature, up to failure. RESULTS AND DISCUSSION ZnO/SiO2 showed higher curing efficiency in sulfur cross-linking of IR composites compared to m-ZnO and the cured materials presented dynamic-mechanical properties suitable for tire production at lower Zn amount. Besides, different mechanical behaviors were registered for the two rubber nanocomposites using a different distribution of ZnO. The higher curing efficiency of ZnO/SiO2 was explained by a more homogeneous distribution of zinc in rubber and higher accessibility of the Zn2+ ions during the process. The immobilization of ZnO NPs was responsible of a different reaction mechanism, which accounts for the higher cross-linking density and different mechanical properties of the cured material.