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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.

AIMS: To identify risk as well as protective factors related to compliance with the gluten-free diet in a cohort of teenagers with celiac disease (CD). PATIENTS AND METHODS: Two hundred four patients with CD (European Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria) older than or equal to 13 years and residents of Campania (southern Italy) were enrolled in the study. Patients underwent clinical examination and blood sampling, and were interviewed about school performance, social relationships, family integration, smoking habit, and compliance with a gluten-free diet. Anti-tissue transglutaminase antibodies were assayed with an enzyme-linked immunosorbent assay. RESULTS: One hundred fifty of 204 (73.5%) reported no dietary transgressions, and 54 of 204 (26.5%) reported occasional or frequent transgressions. During the previous month 29 of 54 (53.7%) poor compliers ate from 0.001 to 1 g of gluten per day, 14 (25.9%) from 1 to 5 g, and 11 (20.4%) more than 5 g. The daily intake of gluten was significantly related to anti-tissue transglutaminase antibodies (chi2 = 38.872, P = 0.000). Height was below the third percentile in 19 of 204 (9.3%), and weight was above the 97th percentile in 20 of 204 (9.8%). Diet compliance did not seem to influence the weight and height. One hundred eleven of 150 good compliers (74%) and 31 of 54 (57.4%) poor compliers were asymptomatic. Most patients reported good family relationships (88.7%), social relationships (91.2%), and school integration (88.2%). Alternatively, 54% of patients reported some limitation in their social life. Compliance was good in patients who reported excellent school integration (83%) and social relationships (81%). CONCLUSION: Optimal school integration significantly contributes to the likelihood of good compliance. A better understanding within the school environment about CD-related issues could improve motivation to adhere to a gluten-free diet.

Background: Several studies have shown an elevated prevalence of coeliac disease (CD) in sibs of coeliac patients (risk 8-12%). Aim and method: This study seeks to evaluate the risk that sibs of children with CD will also develop CD. This cohort of 188 Italian families was composed of probands with CD, at least one sib, and both parents. CD status was determined and HLA-DQ genotyping performed for all family members. The study also used a data set of Italian triads (127 probands and both their parents) also genotyped for HLA-DQ. Results: The overall risk that a sib of a CD patient will develop the disease is estimated at 10% in this sample. The risk estimate ranges from 0,1 to 29% when HLA-DQ information of the proband, parents and sib is considered. We found a negligible risk (lower than 1%) for 40% of the sibs of probands, a risk greater than 1% but less than 10% for 30%, and finally a high or very high risk (above 25%) in one third of families. Conclusion: These results make it possible to provide more accurate information to parents with child with CD about the real risk for another child. An antenatal estimate of the order of risk of CD is now possible. Specific follow-up can thus be offered for babies at high risk.

In this work we reported on the preparation by melt blending and on the characterization of a series of eco-composites containing wool (WFs) or hemp (HFs) fibres and polypropylene (PP) or biodegradable polyesters as matrices. In particular, different amounts of WFs were added, and several pre-treatments or chemical modification were also developed. The use of adhesion promoters, such as maleinized PP, was investigated for PP-based composites.

In this work, composite materials based on wool fibers, raw or chemically modified, and thermoplastic matrices, either polyolefins or biodegradable polyesters, were prepared and thoroughly characterized in terms of morphology, thermal properties and mechanical performances.

Compositi a base di polipropilene e fibre di lana sono stati preparati e caratterizzati attraverso prove di calorimetria a scansione differenziale, termo gravimetria e trazione uniassiale per valutare la dipendenza delle proprietà dei compositi dal contenuto di lana e dalle condizioni di preparazione dei materiali. L'influenza sulle proprietà dei materiali della presenza di compatibilizzante polimero/lana e di una modifica superficiale della lana è stata analizzata.

In the present work polypropylene (PP)-based composites containing wool fibers, grinded, washed and desiccated, were prepared by melt blending in an internal batch mixer. The effect of wool fibers content on the composite mechanical properties was determined. Wool fibers have a hydrophilic character due to the presence of about 70% of hydrophilic amino acids in the amino acidic sequence of keratin. For this reason, in order to increase their compatibility with a hydrophobic matrix, small amounts of PP grafted with maleic anhydride (PP-g-MA) were added to the composites. Adhesion, thermal and mechanical properties of the composites were evaluated as a function of both the grafting degree of the compabilizer and the fiber length.

PP-based composites were prepared by adding increasing amounts of keratin fibres obtained from wool. PPs grafted with different amounts of maleic anhydride were used as compatibilizer. Morphology, thermal and mechanical properties of the composites were investigated.

Introduction Chikungunya virus (CHIKV) is a mosquitoborne alphavirus indigenous to African countries, the Indian Subcontinent, and Southeast Asia, where it causes endemic and epidemic chikungunya (CHIK) fever [1]. Chikungunya infection is transmitted by biting mosquitoes belonging to the genus Aedes. Since the identification of the virus in the 1950s [2] in Africa, transmission to humans has been usually associated with bites of A. aegypti mosquitoes. In recent outbreaks occurring in the South-eastern islands of the Indian Ocean, transmission has also been associated with A. albopictus, also known as the “tiger mosquito.” This species is indigenous to Southeast Asia, the Western Pacific, and the Indian Ocean, but has recently spread to Africa, the Middle East, Europe, and the Americas. [3]. Although tropical forests are considered to be their original habitat, A. aegypti and A. albopictus have developed the capacity to exploit artificial environments [4]. Besides the natural habitat consisting of tree holes filled with water and other small natural pools, they are capable of breeding in any artificial habitat with small reservoirs of stagnant water, such as vases, buckets, tires and other containers found around houses in urban and periurban areas.

Living coccolithophore distributions from the Gulf of Manfredonia (Southern Adriatic Sea) were investigated and comparedwith the coccolith assemblages in the underlying surface sediments. In total, 55 samples from 13 stations in four transects collected at the end of October 2000 were analyzed to determine spatial and vertical distribution of individual taxa in the coastal environment. At all stations, the maximum coccosphere densities were between 10m and 30m of water depth (maximum values were ~4x104 coccospheres per litre of seawater). Coccolithophore absolute abundances show a vertical stratification and spatial variation, as well as variable species diversity, increasing from the coast to the open sea and decreasing with depth. Different coccolithophore communities are recorded in the shallow and deep photic zone. Emiliania huxleyi, Syracosphaera spp., Rhabdosphaera spp., Coronosphaera spp., Umbellosphaera tenuis and holococcolithophores are present mainly in the surface waters, above the thermocline between 25-30m depth. In the deeper water samples, there is a significant increase in coccospheres of Florisphaera profunda. The coccolithophore cell density variability is compared with in situ measurements of environmental parameters (temperature, salinity, nitrates and phosphates). Cell densities of all dominant taxa are most highly correlated with temperature variability. The low correlations of cell densities with nitrates and phosphates may be caused by insufficient sampling resolution, nutrient levels close to detection limits, or both. The comparison of the living assemblage with surface sediment records shows significant differences in the presence and abundance of some species. The recognised fossil record in the surface sediments ismainly represented by Cretaceous-Pleistocene reworked species, showing stronger dynamic processes at the bottom, such as terrigenous input and resuspension, than phytoplankton growth. Most marked correspondence between living and fossil assemblages has been found in the deeper and open sea sediments.

This paper presents a benchmark exercise for the seismic assessment of unreinforced masonry (URM) buildings as a follow-up of a blind prediction test organized in the context of the European Conference of Earthquake Engineering Series. The blind prediction exercise was aimed at better defining the open issues in current procedures for modeling and performing seismic analysis of URM buildings, by highlighting the uncertainty that can influence the results. This work presents an overview of the approaches used by different research teams and the scope of predictions. The benchmark structure was a three-story building with traditional European architecture from which two Cases were considered: A) stone masonry walls and flexible horizontal diaphragms and B) brick masonry walls and rigid horizontal diaphragms. A wide range of approaches was used by the participating teams concerning modeling strategies, methods of analysis and criteria for the attainment of limit states, which are here addressed as potential sources for the dispersion of predictions. The results were compared in terms of capacity curves, predicted failure mechanisms compatible with the fulfillment of limit states of near collapse and damage limitation, and related minimum values of peak ground acceleration (PGA). The results show an overall good agreement for damage patterns and collapse mechanisms in both benchmark structures, presenting some differences in the type of failure mode and its extent. However, the scatter of predicted capacity curves and critical PGAs is very high, especially for the Case with brick masonry and rigid diaphragms, indicating that clearer procedures in the building codes are required for professionals., This work was partly financed by FCT/MCTES through national funds (PIDDAC) under the R&D Unit Institute for Sustainability and Innovation in Structural Engineering (ISISE), under reference UIDB/04029/2020.

The localization of the rubber vulcanization reaction close to the silica filler surface was investigated in isoprene rubber composites (IR NCs): the main goal was to highlight the role of curing agents’ dispersion and filler surface features on the spatial propagation of the rubber cross-links and the resulting mechanical behavior of the material. The study was realized by tailoring the morphology of the curing activator, i.e. by vulcanizing IR NCs with Zn@SiO2 double function filler, composed of Zn(II) single sites anchored on SiO2 filler, in comparison to silica filled IR NCs vulcanized with microcrystalline ZnO. The microscopic cross-links distribution was measured by Transmission Electron Microscopy for network visualization (NVTEM) and Time Domain Nuclear Magnetic Resonance (TD-NMR). Besides the NCs mechanical behavior was characterized both at small strain and at fracture. In the presence of Zn@SiO2, higher cross-link density in proximity to SiO2 particles was evidenced, which gradually spreads from the filler surface to the bulk, induced by localization of the Zn(II) centers. IR NCs with Zn@SiO2 resulted stiffer (+45%) and with a lower fracture toughness (less than one third), compared to m-ZnO based NCs, which shows a quite homogeneous structure of the rubber cross-links network. The results highlighted the correlation between the composites structural features and their macroscopic behavior, paving the way to modulating the mechanical properties of elastomeric materials by tuning the nature of the curing agents.

The crosslink density and distribution inside the polymer matrix affect the mechanical properties of rubber nanocomposites (NCs). Since the catalytic activity of zinc has a central role in the formation of crosslinks, this study focuses on the effect that the structure of the catalytic sites and their localization inside the polymer matrix have on the mechanical behavior of rubber materials. To do this, a new highly efficient activator, Zn@SiO2 based on zinc single sites anchored onto the silica surface, is used as double function filler, acting as both activator and reinforcing filler. The mechanical properties of rubber NCs prepared with Zn@SiO2 are compared to NCs conventionally cured with ZnO particles. The results suggest that localizing the catalytic sites at different distance from the filler particles dispersed in the rubber matrix is a promising tool to control the crosslinking density and distribution, which means tuning the mechanical properties of rubber NCs.

BACKGROUND & AIMS: The extensive infiltration of CD8(+) T cells in the intestinal mucosa of celiac disease (CD) patients is a hallmark of the disease. We identified a gliadin peptide (pA2) that is selectively recognized by CD8(+) T cells infiltrating intestinal mucosa of HLA-A2(+) CD patients. Herein, we investigated the phenotype, the tissue localization, and the effector mechanism of cells responsive to pA2 by using the organ culture of CD intestinal mucosa. The target of pA2-mediated cytotoxicity was also investigated by using the intestinal epithelial cell lines Caco2 and HT29, A2(+) and A2(-), respectively, as target cells. METHODS: Jejunal biopsy specimens from CD patients were cultured in vitro with pA2, and cellular activation was evaluated by immunohistochemistry and cytofluorimetric analysis. Cytotoxicity of pA2-specific, intestinal CD8(+) T cells was assayed by granzyme-B and interferon-gamma release and by apoptosis of target cells. RESULTS: pA2 challenge of A2(+) CD mucosa increased the percentage of CD8(+)CD25(+) and of CD80(+) cells in the lamina propria, the former mainly localized beneath the epithelium, as well as the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling-positive cells (TUNEL(+)) in the epithelium. Intraepithelial CD3(+) cells and enterocyte expression of Fas were also increased. CD8(+)CD25(+) and CD8(+)FASL(+) T cells were significantly increased in cell preparations from biopsy specimens cultured with pA2. CD8(+) T-cell lines released both granzyme-B and interferon-gamma following recognition of pA2 when presented by Caco2 and not by HT29. CONCLUSIONS: These data indicate that gliadins contain peptides able to activate, through a TCR/HLA class I interaction, CD8-mediated response in intestinal CD mucosa and to induce the enterocyte apoptosis.

This study demonstrated that there were basic differences in facial morphology between patients with cleft lip and palate and subjects with non clefting. The findings are obtained on cephalometric analysis of skull's teleradiograph L-L. These differences are for all pratical purposes confined to the maxillary complex. The mandible appear, instead, normal unless in the position in every respect in the not cleft lip and palate subjects.