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Ductile fracture of metals is the net result of void nucleation, growth and coalescence mechanisms that operate at the microscale. Optimal scaling analysis provides the analytical form of the effective material law that models the ductile fracture phenomena at the macroscale. The upscaled model of ductile behavior assumes the form of a cohesive relation—surface traction versus displacement—of the power‐law type with well‐defined exponents. In the present work, we demonstrate how the effective cohesive law derived from optimal scaling can be conveniently inserted into macroscale calculations by recourse to cohesive elements. The plastic deformation outside the cohesive elements is of moderate size and can be modeled by means of conventional plasticity models. In particular, the mesh size is dictated by accuracy considerations at the macroscale structural level and is not in any way constrained by microscale features and mechanisms, which happen at the subgrid level and are accounted for by the effective cohesive law. We illustrate the multiscale paradigm by means of spall calculations. [ABSTRACT FROM AUTHOR]

Novel approaches are required to estimate the bycatch associated with artisanal fisheries. Foremost among these is the use of fisher knowledge (FK). An interview survey was conducted in ports along 2631 km of the Peruvian coast to assess the spatial patterns and bycatch rates of marine megafauna of the artisanal longline fishery and its relation with vessel characteristics and fishing operations. The survey allowed the assessment of 18% of the fleet, while only 1% of the Peruvian longline fleet has been monitored with on board observations in the past. The results indicate that big vessels (higher capacity, longline length and number of hooks) that travel long distances (average distance to coast: 123 nm) mainly catch turtles and show a small amount of seabird bycatches in north‐central Peru. Small vessels especially impact turtles in southern Peru and near the coast (63 nm on average). Contrary to previously published information, which indicates a low level of cetacean bycatch in this fishery, a group of fishers reported more than 1000 cetaceans were incidentally captured in 2009. Using FK allowed to integrate different sources of information and scale the implications of artisanal fisheries in terms of bycatch. FK could further be used to help managers deal with the uncertainties in the dynamics of these generally data‐ poor social‐ecological systems. [ABSTRACT FROM AUTHOR]

Introduction: Patients with haemophilia may have lower levels of bone mineral density (BMD) compared with the general population. Moreover, haemophilic patients have increased risk factors for low bone mineral density (LBMD) such as arthropathy and resulting immobility, increasing their risk for osteoporosis and fractures. Aim: To assess the prevalence of LBMD and associated risk factors among a group of Colombian haemophilic patients. Methods: In this case‐control study, 90 patients with haemophilia A and B, over the age of five, were recruited. Controls were healthy participants matched by age, gender, body mass index (BMI), socioeconomic status, and race. All participants underwent dual energy X‐ray absorptiometry (DXA) and the Global Physical Activity Questionnaire. Blood tests were collected to evaluate LBMD determinants in cases. Results: BMD was lower in cases than in the control group. BMD of femoral necks was 0.907 g/cm2 in cases vs. 1.020 g/cm2 in controls (P = .019), and BMD of hips 0.930 g/cm2 in cases vs. 1030 g/cm2 in controls (P = .019). The greater the severity of haemophilia, the lower BMD in spine, femoral neck, and hips. Elevated C‐protein levels were found in 44.1% of patients with LBMD and 14.8% with normal BMD (P = .003). The study found an adjusted prevalence ratio of 2.11, indicating that haemophilic patients are two times more likely to have LBMD (CI95% = 1.43‐3.11 P < .001). Conclusion: Results from the present study showed that haemophilia was associated with a higher frequency of LBMD. Severity of haemophilia, haemophilic arthropathy, and elevated C‐reactive protein levels was directly associated with LBMD. [ABSTRACT FROM AUTHOR]

We formulate extensions to data-riven computing for both distance-minimizing and entropy-maximizing schemes to incorporate time integration. Previous works focused on formulating both types of solvers in the presence of static equilibrium constraints. Here, formulations assign data points to a variable relevance depending on distance to the solution and on maximum-entropy weighting, with distance-minimizing schemes discussed as a special case. The resulting schemes consist of the minimization of a suitably defined free energy over phase space subject to compatibility and a time-discretized momentum conservation constraint. We present selected numerical tests that establish the convergence properties of both types of data-driven solvers and solutions. [ABSTRACT FROM AUTHOR]

Abstract: A new multiway/multivariate approach is proposed to study and model the spoilage of swordfish with time and temperature of storage through the profiles of putrescine, spermidine, histamine, tyramine, tryptamine, cadaverine, spermine, and 2‐phenylethylamine. The evolution of these biogenic amines in food is a complex process that cannot be characterized by a single parameter but by a modification of the amine profiles. An experimental strategy is designed to determine these profiles in such a way that data are structurally 3‐way. Modeling the joint evolution of the biogenic amines with a PARAFAC model which explains 97.8% of variability (CORCONDIA index equals 100%) leads to estimate the storage time, storage temperature, and biogenic amines profiles. A multiple regression (determination coefficient of 0.98) based on the loadings of the 2 factors of the time profile of the PARAFAC model enables the estimation of the storage time with an error of 0.5 days. [ABSTRACT FROM AUTHOR]

Abstract: Background: Most studies on functional gastrointestinal disorders (FGIDs) in children are based on data from the northern hemisphere. Scientific reports are arising in South American population, but little is still known about children from low socio‐economic status (SES), where Helicobacter pylori infection is endemic. Our objective was to evaluate the prevalence of FGIDs in school children from low SES and its relationship with H. pylori infection. Methods: Children from 3 public schools of low SES from Santiago de Chile were included. Students completed the Rome III Questionnaire and a survey about other symptoms. Also, the 13C urea breath test determined the presence of H. pylori infection. Results: Five hundred six children were included, where 48% were male, with a median age of 15.7 years (range 7.1–19.6). Forty‐two percent had some FGID, aerophagia and functional constipation being the most frequent. Females (adjusted OR 1.5, 95% CI [1.1, 2.2]), those children with parents within the lowest level of education (adjusted OR 1.6, 95% CI: 1.1–2.4), and family history of gastric cancer (adjusted OR 1.9, 95% CI: 1.2–3.1) were related to FGIDs. The prevalence of H. pylori infection was 55.9% (95% CI [50.7, 60.9]). In multivariable analysis, the presence of abdominal pain (OR 1.55, 95% CI [1.02, 2.36]), but not FGIDs, was related to H. pylori infection. Conclusions: FGIDs are common in low SES students. A low educational level of the household head, family history of gastric cancer. and being female are related to the development of FGIDs. In this study, no relationship between the presence of H. pylori and FGIDs was found. [ABSTRACT FROM AUTHOR]

We develop an optimal transportation mesh-free particle method for advection-diffusion in which the concentration or density of the diffusive species is approximated by Dirac measures. We resort to an incremental variational principle for purposes of time discretization of the diffusive step. This principle characterizes the evolution of the density as a competition between the Wasserstein distance between two consecutive densities and entropy. Exploiting the structure of the Euler-Lagrange equations, we approximate the density as a collection of Diracs. The interpolation of the incremental transport map is effected through mesh-free max-ent interpolation. Remarkably, the resulting update is geometrically exact with respect to advection and volume. We present three-dimensional examples of application that illustrate the scope and robustness of the method. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Limited data are available on direct-acting antivirals for treating hepatitis C virus ( HCV) infection in patients with severe renal impairment. The aim of this study was to evaluate the effectiveness and safety of ombitasvir/paritaprevir/ritonavir ( OBV/ PTV/r) ± dasabuvir ( DSV) ± ribavirin ( RBV) in patients with stage 4 or 5 chronic kidney disease ( CKD) and HCV genotype 1 or 4 infection in real clinical practice, and to investigate pharmacological interactions. This retrospective study included patients treated with OBV/ PTV/r+ DSV± RBV or OBV/ PTV/r+ RBV with CKD stage 4 ( eGFR: 15-29 mL/min/1.73m2) or 5 ( eGFR<15 mL/min/1.73m2 or requiring dialysis) and HCV infection by genotypes 1 and 4 between April 2015 and October 2015 in nine Spanish centres. Sustained virological response at 12 weeks ( SVR12) was assessed, and clinical and laboratory data, fibrosis stage, adverse events and pharmacological interactions were reported. Forty-six patients were included: 10 (21.7%) had CKD stage 4 and 36 (78.2%) CKD stage 5. Seventeen (36.9%) had cirrhosis. SVR12 rate in the intention-to-treat population was 95.7%. Twenty-one (45.6%) received RBV, which was discontinued in two (9.5%) patients. Anaemia (haemoglobin <10 g/dl) occurred in 12 patients (57.1%) with RBV vs 10 (40.0%) without RBV ( P=.246). Renal function remained stable during antiviral therapy. Nine patients (19.5%) experienced serious adverse events unrelated to antiviral therapy. Concomitant medication was discontinued or modified in 41.3% of patients. In conclusion, the effectiveness of OBV/ PTV/r± DSV± RBV in patients with CKD 4-5 was similar to that observed in those with normal renal function and was not associated with severe adverse events. [ABSTRACT FROM AUTHOR]

Under conditions that involve a high risk of competition for light among neighbouring plants, shade-intolerant species often display increased shoot elongation and greater susceptibility to pathogens and herbivores. The functional links between morphological and defence responses to crowding are not well understood. In Arabidopsis, the protein JAZ10 is thought to play a key role connecting the inactivation of the photoreceptor phytochrome B (phyB), which takes place under competition for light, with the repression of jasmonate-mediated plant defences. Here, we show that a null mutation of the JAZ10 gene in Arabidopsis did not affect plant growth nor did it suppress the shade-avoidance responses elicited by phyB inactivation. However, the jaz10 mutation restored many of the defence traits that are missing in the phyB mutant, including the ability to express robust responses to jasmonate and to accumulate indolic glucosinolates. Furthermore, the jaz10phyB double mutant showed a significantly increased resistance to the pathogenic fungus Botrytis cinerea compared with the phyB parental line. Our results demonstrate that, by inactivating JAZ10, it is possible to partially uncouple shade avoidance from defence suppression in Arabidopsis. These findings may provide clues to improve plant resistance to pathogens in crops that are planted at high density. [ABSTRACT FROM AUTHOR]

A computational method is presented for the assessment of rupture probabilities in soft collagenous tissues. This may in particular be important for the quantitative analysis of medical diseases such as atherosclerotic arteries or abdominal aortic aneurysms, where an unidentified rupture has in most cases fatal consequences. The method is based on the numerical minimization and maximization of probabilities of failure, which arise from random input quantities, for example, tissue properties. Instead of assuming probability distributions for these quantities, which are typically unknown especially for soft collagenous tissues, only restricted knowledge of these distributions is taken into account. Given this limited statistical input data, the minimized/maximized probabilities represent optimal bounds on the rupture probability, which enable a quantitative estimation of potential risks of performing or not performing medical treatment. Although easily extendable to all kinds of mechanical rupture criteria, the approach presented here incorporates stretch-based and damage-based criteria. These are evaluated based on numerical simulations of loaded tissues, where continuum mechanical material formulations are considered, which capture the supra-physiological behavior of soft collagenous tissues. Numerical examples are provided demonstrating the applicability of the method in an overstretched atherosclerotic artery. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A generic systems dynamics ( SD) model template for resilience is adapted to analyse flooding impacts on household assets and local government assets of Pasig City, Metro Manila. SD simulations are used to quantify the loss of system performance due to adverse impacts, and the recovery of the system due to response measures. The simulation results reflect the decreasing levels of resilience among low-income households, and the reliance of local government on budgeting cycles to replenish assets. The initial model needs to be expanded to include other determinants of resilience, but this exploratory study reflects the potential usefulness of SD simulations as a decision support tool for city policy makers. By quantifying changes in resilience measures over time, simulations can complement qualitative analyses and test policy and programme scenarios. [ABSTRACT FROM AUTHOR]

GNSS localization in an urban environment remains a key issue that must be solved in order to enable innovative driver assistance systems or cooperative applications. This key issue exists not only in terms of accuracy but also in terms of integrity. Actually, one aims at reducing as much as possible the error mainly due to multipath on buildings and provide in the mean time a certain guarantee on the user position exactness. This article shows how a simple geometric modeling, named 'Urban Trench', of the city environment can improve significantly the positioning accuracy. Authors also propose an algorithm for computing an urban trench protection level, with a much higher reliability compared to conventional protection level whose open sky assumption is violated. Experimental results are given in the cities of Nantes, Paris, and Toulouse, France. Copyright © 2016 Institute of Navigation [ABSTRACT FROM AUTHOR]

Clinical and epidemiologic studies reveal an association between vitamin D deficiency and increased risk of cardiovascular disease. Because vascular smooth muscle cell (VSMC)-derived tissue factor (TF) is suggested to be critical for arterial thrombosis, we investigated whether the vitamin D molecules calcitriol and paricalcitol could reduce the expression of TF induced by the proinflammatory cytokine TNF-a in human aortic VSMCs. We found that, compared with controls, incubation with TNF-a increased TF expression and procoagulant activity in a NF-B-dependent manner, as deduced from the increased nuclear translocation of nuclear factor -light-chain-enhancer of activated B cells protein 65 (p65-NF-B) and direct interaction of NF-B to the TF promoter. This was accompanied by the up-regulation of TF signaling mediator protease-activated receptor 2 (PAR-2) expression and by the down-regulation of vitamin D receptor expression in a miR-346-dependent way. However, addition of calcitriol or paricalcitol blunted the TNF-a-induced TF expression and activity (2.01 ± 0.24 and 1.32 ± 0.14 vs. 3.02 ± 0.39 pmol/mg protein, P < 0.05), which was associated with down-regulation of NF-B signaling and PAR-2 expression, as well as with restored levels of vitamin D receptor and enhanced expression of TF pathway inhibitor. Our data suggest that inflammation promotes a prothrombotic state through the up-regulation of TF function in VSMCs and that the beneficial cardiovascular effects of vitamin D may be partially due to decreases in TF expression and its activity in VSMCs. [ABSTRACT FROM AUTHOR]

Background Vascular calcification ( VC) is highly prevalent in patients with chronic kidney disease ( CKD). Low magnesium levels are associated with VC, and recent in vitro studies confirm a protective role of magnesium, which is mediated by its entry into the VSMCs through the Transient Receptor Potential Melastatin 7 ( TRPM7) channel. The role of Angiotensin II (Ang II) on VC is still unclear. As Ang II is able to stimulate TRPM7 activity, we hypothesize that it might prevent VC. Thus, the aim of this study was to dissect the direct effect of Ang II on VC. Materials and methods We worked with a model of high phosphate ( HP)-induced calcification in human aortic smooth muscle cells, which resembles the CKD-related VC. Results Addition of Ang II to cells growing in HP decreased calcification, which was associated with the upregulation of the osteogenic factors BMP2, Runx2/Cbfa1, Osterix and ALP. A reduction of magnesium entry into the HP-calcifying cells was found. The treatment with Ang II avoided this reduction, which was reversed by the cotreatment with the TRPM7-inhibitor 2- APB. The protective effect of Ang II was related to AT1R-induced ERK1/2 MAPKinase activation. HP-induced calcification was also associated with the upregulation of the canonical Wnt/beta-catenin pathway, while its downregulation was related to attenuation of calcification by Ang II. Conclusion As hypothesized, Ang II prevented phosphate-induced calcification in VSMCs, which appears mediated by the increase of magnesium influx and by the activation of the ERK1/2 and the inhibition of the canonical Wnt/beta-catenin signalling pathways. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the improvement of tolerance development prediction in children aged 5 years or less than 5 years old who have allergy in egg through the ovalbumin-specific immunoglobulin E (IgE)/total IgE ratio.

The complexity of heat transport in silicon nanowires (SiNWs) and, specifically, its dependence on temperature and the nanowire diameter, is beyond continuum models of heat conduction and necessitate consideration of atomic-level heat-conduction models. In this work, we specifically aim to ascertain the ability of models based on non-equilibrium statistical mechanics to reproduce the observed anisotropy, temperature and size dependence of the thermal conductivity of SiNWs. In this approach, the atomic-level kinetic relations are regarded as empirical and subject to modeling. Within this framework, we find that a simple model, based on the introduction of a thin amorphous layer at the surface of the SiNWs, yields effective thermal conductivities that are in excellent agreement with the experimental data over a range of temperatures and diameters. (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

We develop an acceleration method for material-dominated calculations based on phase-space simplicial interpolation of the relevant material-response functions. This process of interpolation constitutes an approximation scheme by which an exact material-response function is replaced by a sequence of approximating response functions. The terms in the sequence are increasingly accurate, thus ensuring the convergence of the overall solution. The acceleration ratio depends on the dimensionality, the complexity of the deformation, the time-step size, and the fineness of the phase-space interpolation. We ascertain these trade-offs analytically and by recourse to selected numerical tests. The numerical examples with piecewise-quadratic interpolation in phase space confirm the analytical estimates. [ABSTRACT FROM AUTHOR]

Microcarriers have been proposed in tissue engineering, namely for bone, cartilage, skin, vascular, and central nervous system. Although polyester-based microcarriers have been already used for this purpose, their surface properties should be improved to provide better cell growth. The goal of this study was to prepare microbeads based on poly( d,l-lactide) acid, poly( l-lactide) acid, and to study cell behavior (adhesion, spreading, growth, and proliferation) in function of microbead topography and surface chemistry. To improve L-929 fibroblasts adhesion, microbead surface has been modified with three polycations: chitosan, poly(2-dimethylamino ethylmethacrylate) (PDMAEMA), or chitosan- g-oligolactide copolymer (chit- g-OLA). Although modification of the microbead surface with chitosan and PDMAEMA was performed through physical adsorption on the previously prepared microbeads, chit- g-OLA copolymer was introduced directly during microbead processing. This simple approach (1) bypass the use of an emulsifier (polyvinyl alcohol, PVA); (2) avoid surface 'contamination' with PVA molecules limiting a control of the surface characteristics. In vitro study of the growth of mouse fibroblasts on the microbeads showed that both surface topography and chemistry affected cell attachment, spreading, and proliferation. Cultivation of L-929 fibroblasts for 7 days resulted in the formation of a 3D cell-scaffold network. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 939-948, 2015. [ABSTRACT FROM AUTHOR]

Bovine leukocyte antigens ( BoLAs) are used extensively as markers for bovine disease and immunological traits. In this study, we estimated BoLA-DRB3 allele frequencies using 888 cattle from 10 groups, including seven cattle breeds and three crossbreeds: 99 Red Angus, 100 Black Angus, 81 Chilean Wagyu, 49 Hereford, 95 Hereford × Angus, 71 Hereford × Jersey, 20 Hereford × Overo Colorado, 113 Holstein, 136 Overo Colorado, and 124 Overo Negro cattle. Forty-six BoLA-DRB3 alleles were identified, and each group had between 12 and 29 different BoLA-DRB3 alleles. Overo Negro had the highest number of alleles (29); this breed is considered in Chile to be an 'Old type' European Holstein Friesian descendant. By contrast, we detected 21 alleles in Holstein cattle, which are considered to be a 'Present type' Holstein Friesian cattle. Chilean cattle groups and four Japanese breeds were compared by neighbor-joining trees and a principal component analysis ( PCA). The phylogenetic tree showed that Red Angus and Black Angus cattle were in the same clade, crossbreeds were closely related to their parent breeds, and Holstein cattle from Chile were closely related to Holstein cattle in Japan. Overall, the tree provided a thorough description of breed history. It also showed that the Overo Negro breed was closely related to the Holstein breed, consistent with historical data indicating that Overo Negro is an 'Old type' Holstein Friesian cattle. This allelic information will be important for investigating the relationship between major histocompatibility complex ( MHC) and disease. [ABSTRACT FROM AUTHOR]

SUMMARY The objective of the present work is to formulate a new class of discontinuous variational time integrators that allow the system to adopt two possibly different configurations at each sampling time t k, representing predictor and corrector configurations of the system. The resulting sequence of configuration pairs then represents a discontinuous-or non-classical-trajectory. Continuous or classical trajectories are recovered simply by enforcing a continuity constraint at all times. In particular, in systems subject to one-sided contact constraints simulated via discontinuous variational time integrators, the predictor configuration is not required to satisfy the one-sided constraints, whereas the corrector configuration is obtained by a closest-point projection (CPP) onto the admissible set. The resulting trajectories are generally discontinuous, or non-classical, but are expected to converge to classical or continuous solutions for decreasing time steps. We account for dissipation, including friction, by means of a discrete Lagrange-d'Alembert principle, and make extensive use of the spacetime formalism in order to ensure exact energy conservation in conservative systems, and the right rate of energy decay in dissipative systems. The structure, range and scope of the discontinuous variational time integrators, and their accuracy characteristics are illustrated by means of examples of application concerned with rigid multibody dynamics. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

SUMMARY Presented is a massively parallel implementation of the Optimal Transportation Meshfree (pOTM) method Li et al., 2010 for explicit solid dynamics. Its implementation is based on a two-level scheme using Message Passing Interface between compute servers and threaded parallelism on the multi-core processors within each server. Both layers dynamically subdivide the problem to provide excellent parallel scalability. pOTM is used on three problems and compared to experiments to demonstrate accuracy and performance. For both a Taylor-anvil and a hypervelocity impact problem, the pOTM implementation scales nearly perfectly to about 8000 cores. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Accurate predictors of natural tolerance development to cooked and uncooked egg are needed in egg-allergic patients. Objective To compare the diagnostic performance of different immunological tests in relation to egg allergy versus tolerance. Methods Children aged 5-18 years diagnosed with IgE-mediated egg allergy were prospectively recruited. All followed an egg-free diet. Prick test and specific IgE ( sIgE) to ovalbumin, ovomucoid and egg white, ovalbumin- sIgG4 and ovomucoid- sIgG4 were determined. By boiled and raw egg challenges, children were classified as cooked egg allergic (CEA, n = 50) or tolerant (CET, n = 35), and uncooked egg allergic (UEA, n = 64) or tolerant (UET, n = 21). Statistics. Comparative analysis ( CEA vs. CET and UEA vs. UET). Multivariate logistic regression. Partial receiver operating characteristic curve analysis of tests in relation to CEA and UEA. Negative decision points were defined as cut-offs with sensitivity 95%. Results Ovalbumin- sIgG4 resulted an independent protective factor for uncooked egg allergy. To identify patients with high probability of egg tolerance, ovalbumin- sIgE/ sIgG4 tended to perform better than sIgE and prick, specifically in children with ovalbumin- sIgE < 1.9 kU/L (for UEA) and ovomucoid- sIgE < 2.12 kU/L (for CEA). The most accurate cut-offs to recommend challenges were ovalbumin- sIgE/ sIgG4 below 2.49 for cooked egg and 1.45 for uncooked egg, which associated 89.5% and 80% probability of tolerance (negative likelihood ratios 0.08 and 0.06), respectively. These cut-offs identified correctly as tolerant an additional 23% and 14% of children with negative challenges to cooked and uncooked egg, respectively, in comparison with sIgE negative decision points. Additionally, prick test tended to perform better than sIgE alone in predicting cooked and uncooked egg tolerance for ovomucoid- sIgE < 0.92 kU/L and ovalbumin- sIgE < 1.37 kU/L, respectively. Conclusions Ovalbumin-specific IgG4 is an independent predictor of tolerance development to uncooked egg. Ovalbumin- sIgE/ sIgG4 ratio, followed by skin prick test (SPT), seems to perform better than sIgE in identifying egg-allergic children with high probability of tolerance to cooked and uncooked egg over follow-up. [ABSTRACT FROM AUTHOR]

SUMMARY The evolution of plastic deformations in metals, governed by incompressible flow rules, has been traditionally solved using the exponential mapping. However, the accurate calculation of the exponential mapping and its tangents may result in computationally demanding schemes in some cases, while common low-order approximations may lead to poor behavior of the constitutive update because of violation of the incompressibility condition. Here, we introduce the special-linear (SL) update for isochoric plasticity, a flow-rule integration scheme based on differential manifolds concepts. The proposed update exactly enforces the plastic incompressibility condition while being first-order accurate and consistent with the flow rule, thus bearing all the desirable properties of the now standard exponential mapping update. In contrast to the exponential-mapping update, we demonstrate that the SL update can drastically reduce the computing time, reaching one order of magnitude speed-ups in the calculation of the update tangents. We demonstrate the applicability of the update by way of simulation of single-crystal plasticity uniaxial loading tests. We anticipate that the SL update will open the way to efficient constitutive updates for the solution of complex multiscale material models, thus making it a very promising tool for large-scale simulations. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Oral immunotherapy ( OIT) is a promising treatment for food allergy but dose-related reactions are common. Objective To evaluate safety of egg- OIT. To identify predictors of dose-related reactions. Methods Fifty children aged 5-18 underwent egg- OIT after confirming IgE-mediated egg allergy by double-blind placebo-controlled challenge ( DBPCFC). All dose-related reactions over a median period of 18 months on- OIT (range: 12-28) were registered. Children were retrospectively divided into three subgroups: (1) children who stopped reacting to OIT-doses over time ( RR, Resolved Reactions); (2) children with ongoing dose-related reactions over the whole period on- OIT ( PR, Persistent Reactions); (3) children who discontinued OIT within induction phase due to frequent reactions not improved by protocol re-adaptation and medication ( ED, Early Discontinuation). Baseline clinical/immunological parameters associated with subgroups were investigated. Results Reactions occurred in 7.6% of doses. Adrenaline was required in 26% of children. The three subgroups corresponded to three different safety phenotypes: (1) twenty-four children (48%, RR) experienced infrequent and mainly mild reactions that resolved over time. None required adrenaline; (2) seventeen children (34%, PR) experienced more frequent and severe ongoing reactions over time; (3) nine children (18%, ED) discontinued OIT due to very frequent and mainly moderate reactions. Early discontinuation was associated with underlying asthma, higher specific IgE (sIgE) and lower threshold at DBPCFC. In contrast, lower sIgE and less severe reactions at DBPCFC were associated with subgroup RR. sIgE showed excellent performance in predicting belonging to subgroup RR. Levels below the optimal cut-off (ovomucoid-sIgE 8.85 kU/L) indicated 77% probability of belonging to subgroup RR, whereas levels above it indicated 95% probability of early discontinuation or ongoing reactions over time. Conclusions and Clinical Relevance Egg-OIT involves substantial risks. However, baseline parameters, particularly sIgE, may help identify children in whom the procedure is more likely to be safe. Egg-OIT safety needs improvement in children with more severe and persistent egg allergy. [ABSTRACT FROM AUTHOR]

SUMMARY We develop a mixed finite-element approximation scheme for Kirchhoff plate theory based on the reformulation of Kirchhoff plate theory of Ortiz and Morris [1]. In this reformulation the moment-equilibrium problem for the rotations is in direct analogy to the problem of incompressible two-dimensional elasticity. This analogy in turn opens the way for the application of diamond approximation schemes (Hauret et al. [2]) to Kirchhoff plate theory. We show that a special class of meshes derived from an arbitrary triangulation of the domain, the diamond meshes, results in the automatic satisfaction of the corresponding inf − sup condition for Kirchhoff plate theory. The attendant optimal convergence properties of the diamond approximation scheme are demonstrated by means of the several standard benchmark tests. We also provide a reinterpretation of the diamond approximation scheme for Kirchhoff plate theory within the framework of discrete mechanics. In this interpretation, the discrete moment-equilibrium problem is formally identical to the classical continuous problem, and the two differ only in the choice of differential structures. It also follows that the satisfaction of the inf − sup condition is a property of the cohomology of a certain discrete transverse differential complex. This close connection between the classical inf − sup condition and cohomology evinces the important role that the topology of the discretization plays in determining convergence in mixed problems. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The role of specific IgA ( sIgA) in oral immunotherapy ( OIT) and natural tolerance to foods is poorly understood. We aimed to study serum sIgA in induced and natural tolerance to egg. Children aged 5-16 years diagnosed with IgE-mediated egg allergy were recruited. After egg challenge, patients were classified as transient ( TEA) or persistent ( PEA) egg-allergic. PEA children were further divided into oral immunotherapy ( PEA- OIT) or egg avoidance ( PEA- EA). Allergy/tolerance was reassessed 9-12 months later (T1) in PEA- EA. Serum sIgA to ovalbumin and ovomucoid were determined at inclusion in all patients and repeated in PEA at T1. 21 TEA and 52 PEA children were recruited (28 PEA-OIT, 24 PEA-EA). Serum sIgA remained unchanged after OIT. TEA and PEA had similar serum sIgA. No specific trend on serum sIgA was observed in five PEA- EA who developed natural tolerance over follow-up. Thus, serum sIgA seems not to be associated with induced or natural egg tolerance. [ABSTRACT FROM AUTHOR]

Background Strict avoidance is the only accepted management for cow's milk ( CM) allergy. CM oral immunotherapy ( CM- OIT) is under investigation. Objectives To evaluate long-term safety of CM- OIT. To identify clinical/immunological predictors of adverse events. Methods Prospective longitudinal epidemiological intervention study. CM-allergic children aged 5-18 underwent a Spanish-approved CM- OIT protocol without premedication. Clinical data, skin prick test ( SPT) and specific IgE ( sIgE) at baseline and 1 year after OIT were registered. All dose-related reactions, treatments needed and cofactors involved were recorded. Through survival analysis, we studied the cumulative probability of reactions resolution over time and clinical/immunological risk factors of reactions persistence. Results 81 children were recruited. Mean follow-up was 25 months. 95% of children suffered reactions, 91% of which affected a single organ. Reactions were heterogeneously distributed: (a) 60 children (75%) had occasional symptoms which ceased over time. 86% of them reached complete desensitization (200 mL). (b) 20 children (25%) suffered frequent (78% of total reactions), more severe and unpredictable reactions, which persisted during follow-up or led to withdrawal (6 cases). Reactions persistence was associated with a higher frequency and severity. Kaplan-Meier estimate revealed a cumulative probability of reactions resolution of 25% at 3 months (95% CI: 1.9-4.1) and 50% (95% CI: 6.1-9.9) at 8 months based on all patients. Cox proportional hazards multivariate regression model identified 3 variables (CM- sIgE ≥ 50 KU L−1, CM-SPT ≥ 9 mm and Sampson's severity grades 2, 3 and 4 at baseline food challenge) as independent risk factors of reactions persistence. The combination of 2 or 3 of these factors involved hazard ratios to develop persistent reactions of 2.26 (95% CI: 1.14-4.46; P = 0.019) and 6.06 (95% CI: 2.7-13.7; P < 0.001), respectively. Clinical implications CM- OIT was insufficiently safe in 25% of children. The above-mentioned clinical and immunological parameters would help clinicians to identify highly reactive patients before CM- OIT. In them, individualized schedules and premedication should be considered. [ABSTRACT FROM AUTHOR]

SUMMARY The present work is concerned with the verification and validation of a variant of the eigenfracture scheme of Schmidt et al. (2009) based on element erosion, which we refer to as eigenerosion. Eigenerosion is derived from the general eigenfracture scheme by restricting the eigendeformations in a binary sense: they can be either zero, in which case the local behavior is elastic, or they can be equal to the local displacement gradient, in which case the corresponding material neighborhood is failed or eroded. When combined with a finite-element approximation, this scheme gives rise to element erosion, i.e., the elements can be either intact, in which case their behavior is elastic, or be completly failed, or eroded, and have no load bearing capacity. We verify the eigenerosion scheme through comparisons with analytical solutions and through convergence studies for mode I fracture propagation, both in two and three dimensions and for structured and random meshes. Finally, by way of validation, we apply the eigenerosion scheme to the simulation of mixed modes I-III experiments in poly-methyl methacrylate plates. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and Purpose: This study establishes a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the time course and in vivo mechanisms of action of the antinociceptive effects of lumiracoxib, evaluated by the thermal hyperalgesia test in rats.Experimental Approach: Female Wistar fasted rats were injected s.c. with saline or carrageenan in the right hind paw, followed by either 0, 1, 3, 10 or 30 mg*kg(-1) of oral lumiracoxib at the time of carrageenan injection (experiment I), or 0, 10 or 30 mg*kg(-1) oral lumiracoxib at 4 h after carrageenan injection (experiment II). Antihyperalgesic responses were measured as latency time (LT) to a thermal stimulus. PK/PD modelling of the antinociceptive response was performed using the population approach with NONMEM VI.Results: A two-compartment model described the plasma disposition. A first-order model, including lag time and decreased relative bioavailability as a function of the dose, described the absorption process. The response model was: LT=LT(0)/(1 +MED). LT(0) is the baseline response, and MED represents the level of inflammatory mediators. The time course of MED was assumed to be equivalent to the predicted profile of COX-2 activity and was modelled according to an indirect response model with a time variant synthesis rate. Drug effects were described as a reversible inhibition of the COX-2 activity. The in vivo estimate of the dissociation equilibrium constant of the COX-2-lumiracoxib complex was 0.24 microg*mL(-1).Conclusions: The model developed appropriately described the time course of pharmacological responses to lumiracoxib, in terms of its mechanism of action and pharmacokinetics. [ABSTRACT FROM AUTHOR]

p21 is a cell-cycle inhibitor that is also known to suppress autoimmunity. Here, we provide evidence of a novel role for p21 as an inhibitor of macrophage activation. LPS stimulation of p21-deficient peritoneal macrophages induced increased activation compared with controls, with elevated production of proinflammatory mediators such as TNF-α and IL-1β. The enhanced activity of LPS-stimulated p21-deficient macrophages correlated with increased activity of the transcription factor NF-κB. LPS stimulation of p21-deficient macrophages led to increased IκBα kinase activity, and increased IκBα phosphorylation and degradation, resulting in elevated NF-κB activity. The effect of p21 in macrophage activation was independent of its cell-cycle inhibitory role. p21 mice showed greater sensitivity to LPS-induced septic shock than did WT mice, indicating that p21 contributes to maintenance of a balanced response to inflammatory stimuli and suggesting biological significance for the role of p21 in macrophage activation. Our findings project a role for p21 in the control of NF-κB-associated inflammation, and suggest that therapeutic modulation of p21 expression could be beneficial in inflammation-associated diseases. [ABSTRACT FROM AUTHOR]

Background and Purpose: Acemetacin is a non-steroidal anti-inflammatory drug which is rapidly bioconverted to indomethacin, but produces significantly less gastric damage than indomethacin. This study was performed to investigate several possible mechanisms that could account for the gastrointestinal tolerability of acemetacin.Experimental Approach: The gastric and intestinal damaging effects of acemetacin and indomethacin were examined in the rat. Effects of the drugs on blood levels of leukotriene B(4) and thromboxane B(2), on leukocyte-endothelial adherence in post-capillary mesenteric venules, and on gastric expression of tumour necrosis factor-alpha (TNF-alpha) were determined. The two drugs were also compared for gastric toxicity in rats pretreated with inhibitors of COX-2 and NOS.Key Results: Acemetacin induced significantly less gastric and intestinal damage than indomethacin, despite markedly suppressing COX activity. Indomethacin, but not acemetacin, significantly increased leukocyte adherence within mesenteric venules, and gastric expression of TNF-alpha. Pretreatment with L-nitro-arginine methyl ester or lumiracoxib increased the severity of indomethacin-induced gastric damage, but this was not the case with acemetacin.Conclusions and Implications: The increased gastric and intestinal tolerability of acemetacin may be related to the lack of induction of leukocyte-endothelial adherence. This may be attributable to the reduced ability of acemetacin to elevate leukotriene-B(4) synthesis and TNF-alpha expression, compared to indomethacin, despite the fact that acemetacin is rapidly bioconverted to indomethacin after its absorption. [ABSTRACT FROM AUTHOR]

Little is known about how diabetes affects the health status of Hispanic people living in colonias located along the USA/Mexico border. The purpose of this report is to describe the demographic factors, prevalence of diabetes, and the health status of the residents living in a colonia on the border between El Paso, Texas, USA, and Juarez, Mexico, and to report the residents' adherence to the Behavioral Risk Factor Surveillance System (BRFSS) protocols for the management of type 2 diabetes. This study included 188 participants. The instruments used included a demographic questionnaire, the Short Acculturation Scale for Hispanics, 'Cutting Down, Annoyance by Criticism, Guilty Feelings, and Eye-openers', BRFSS, and the Short Form-36 (v2). The prevalence of diabetes was 15.4% and 41.3% of the residents had a Body Mass Index score > 30. The rate of hypertension, elevated cholesterol, and depression for those reporting diabetes was significant. The SF-36 v2 physical score for the diabetic residents was 42.9 and it was 52.4 for the non-diabetic residents. The average resident of the colonia who reports diabetes has many health disadvantages when compared to those in other parts of Texas and the USA generally. [ABSTRACT FROM AUTHOR]

In an attempt to delineate the area of origin and migratory expansion of the highly successful invasive weedy species Hypochaeris radicata, we analysed amplified fragment length polymorphisms from samples taken from 44 populations. Population sampling focused on the central and western Mediterranean area, but also included sites from Northern Spain, Western and Central Europe, Southeast Asia and South America. The six primer combinations applied to 213 individuals generated a total of 517 fragments of which 513 (99.2%) were polymorphic. The neighbour-joining tree presented five clusters and these divisions were supported by the results of Bayesian analyses: plants in the Moroccan, Betic Sierras (Southern Spain), and central Mediterranean clusters are all heterocarpic. The north and central Spanish, southwestern Sierra Morena, and Central European, Asian and South American cluster contain both heterocarpic (southwestern Sierra Morena) and homocarpic populations (all other populations). The Doñana cluster includes two homocarpic populations. Analyses of fragment parameters indicate that the oldest populations of H. radicata are located in Morocco and that the species expanded from this area in the Late Quaternary via at least three migratory routes, the earliest of which seems to have been to the southwestern Iberian Peninsula, with subsequent colonizations to the central Mediterranean area and the Betic Sierras. Homocarpic populations originated in the southwestern Iberian Peninsula and subsequently spread across north and central Spain, Central Europe and worldwide, where they became a highly successful weed. [ABSTRACT FROM AUTHOR]

The fluorimetric determination of tetracycline is usually carried out in the presence of some metals that, through the formation of a complex with this antibiotic, enhance its fluorescence emission, giving more sensitive determination methods. It is well established that magnesium is one of these metals. However, it is possible that higher signals do not mean a real improvement in the quality of the analytical method. In this work, the univariate and multivariate fluorescence determination of tetracycline is performed in the presence and absence of Mg2+, comparing the quality of the analyses through some performance characteristics that, according to Commission Decision 2002/657/EC define the functional qualities of analytical methods. The methods with the best performance characteristics were multivariate determinations carried out in the absence of Mg2+, both when emission or excitation spectra were taken, the decision limits (CC α) being 13.1 and 20.1 µg/L and the detection capabilities (CC β) 25.3 and 38.5 µg/L, respectively. This study points out through a case study that higher analytical signals do not necessarily mean better performance characteristics of a method of analysis. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim To develop a scale to assess the severity of hepatic encephalopathy using simple dichotomic items. Methods A list of 48 items was created by selecting items that are simple to recognize and categorize; it was applied to thirty-six cirrhotic in-patients with episodic encephalopathy, in addition to the adapted-West-Haven Criteria and the Glasgow Coma Score. The list underwent an item reduction process and principal component analysis; the metric characteristics were evaluated. Results Multiple neurological abnormalities were observed and a Clinical Hepatic Encephalopathy Staging Scale of nine items was constructed. The principal component analysis of the Clinical Hepatic Encephalopathy Staging Scale obtained two factors that explained 77% of the variance. The Clinical Hepatic Encephalopathy Staging Scale exhibited adequate internal consistency and reproducibility. The scores of the Clinical Hepatic Encephalopathy Staging Scale correlated to those of adapted-West-Haven Criteria and the Glasgow Coma Score. Conclusions This study confirms that the evaluation of multiple neurological manifestations is not necessary to classify hepatic encephalopathy adequately, which can be simply undertaken by an assessment of the patient’s orientation, alertness, ability to respond to commands and to talk. A list of nine items is proposed as a linear scale from normality (Clinical Hepatic Encephalopathy Staging Scale = 0) to deep coma (Clinical Hepatic Encephalopathy Staging Scale = 9). [ABSTRACT FROM AUTHOR]

To detect potential Pleistocene refugia and colonization routes along the Atlantic coast, we analysed amplified fragment length polymorphisms (AFLPs) in 140 individuals from 14 populations of Hypochaeris salzmanniana (Asteraceae), an annual species endemic to the southwestern European and northwestern African coastal areas. Samples covered the total distributional range of the species, with eight populations in southwestern Spain and six populations in northwestern Morocco. Using nine primer combinations, we obtained 546 fragments in H. salzmanniana and its sister species H. arachnoidea of which 487 (89.2%) were polymorphic. The neighbour-joining tree shows that the populations south of the Loukos river in Morocco are clearly differentiated, having more polymorphic, private, and rare fragments, and higher genetic diversity, than all the other populations. The southernmost populations in Morocco, south of the river Sebou, form a large panmictic population. They are probably the oldest populations that have been relatively unaffected by stochastic processes resulting from Pleistocene glaciations. Northward migration of populations during this period may have resulted in loss of genetic diversity in specific regions, perhaps due to bottlenecks caused by rise in sea level during interglacial periods, and, in some cases, by changes in the breeding system. [ABSTRACT FROM AUTHOR]

Objective Several studies have suggested that the analysis of heart rate variability (HRV) during gestation provides indications of the development or maturation of fetal cardiovascular regulatory mechanisms. In this study, we evaluate the existence of short-range fractal-like correlations in fetal RR fluctuations data from the second half of human gestation. Methods Fifty-six short-term abdominal ECG recordings were obtained from low-middle-risk pregnant women. Gestational age varied from estimated 21 weeks to term. For comparison, RR-interval data of 51 healthy adults were also analysed. Results Principal findings along the gestational period explored were the existence of fractal RR dynamics in prenatal fetal data as revealed by the short-range scaling exponent α1. No significant differences of α1( p = 0.4770) were found between fetal (median 1.2879) and adult data (median 1.3214), either between the fetal cases before or after 24 weeks ( p = 0.6116) despite observing more variation at early stages. However, fetal RR data did involve lower magnitude in comparison with adults as we found significant differences in pNN20 and SDNN values. Conclusion The fetal short-range fractal behaviour of RR data could then be linked to the functional development of the parasympathetic activity, which appears to become manifested before 21 weeks of gestation. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim: To identify the effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) in single administration on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects. Methods: A randomized, single-blind, cross-over, clinical trial was carried out in 14 young, healthy, non-obese, volunteers. A basal metabolic profile, which included glucose level, insulin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinine, and uric acid, was measured. Subjects received a single administration of 300 kcal, gauged with water at 350 ml, of each of the following (at least 3 days apart): glucose 75 g, polymeric supplement (Ensure high calcium) 315 ml or Glucerna SR 323 ml. At the beginning of each administration and 30, 60, 90 and 120 min later, glucose and insulin concentrations were measured. Areas under the curve of glucose and insulin were calculated. First-phase and total insulin secretions and insulin sensitivity were also estimated. Results: Glucose level at 120 min was significantly lower after receiving Ensure high calcium or Glucerna SR. Administration of Glucerna SR resulted in a significant reduction in the areas under the curve of glucose and insulin, as well as in total insulin secretion with a tendency to be lower in their first phase. Insulin sensitivity was increased. Conclusions: A single administration of Glucerna SR to healthy subjects decreased the postprandial glucose and insulin states, as well as the insulin secretion; insulin sensitivity increased. [ABSTRACT FROM AUTHOR]

An industrial Cu-based low-temperature water-gas shift (LTWGS) reactor, subject to deactivation by irreversible chlorine adsorption, has been modeled and optimized. Both the chlorine adsorption kinetics and deactivation kinetics were assumed first order to chlorine partial pressure, and the rate constants were considered independent of temperature. The Efficient Production (EP) method has been used to compute the reactor production until the outlet CO conversion decays below a permissible minimum level. Two alternative strategies for the inlet temperature have been used to maximize the EP: constant and time-variable. Compared to the EP obtained for the optimum constant inlet temperatures, EP resulting from the use of the optimum time-variable inlet temperature sequence were higher, affording important energy savings. Furthermore, a sensitivity study with respect to most influential operational variables, such as inlet total flow rate, steam-to-gas ratio, pressure, and concentrations of chlorine, hydrogen, carbon monoxide, and inert content, was carried out. [ABSTRACT FROM AUTHOR]

Cholesterol- and sphingolipid-rich membrane microdomains (lipid rafts) are widely recognized as portals for pathogenic micro-organisms. A growing body of evidence demonstrates mobilization of host plasma cell membrane lipid rafts towards the site of contact with several pathogens as well as a strict dependence on cholesterol for appropriate internalization. The fate of lipid rafts once the pathogen has been internalized and the nature of the pathogen components that interact with them is however less understood. To address both these issues, infection of the J774 murine cell line withMycobacterium aviumwas used as a model. After demonstrating thatM. aviuminduces lipid raft mobilization and thatM. aviuminfects J774 by a cholesterol-dependent mechanism, it is shown here that mycobacterial phagosomes harbour lipid rafts, which are, at least in part, of plasma cell membrane origin. On the other hand, by using latex microbeads coated with any of the three fractions ofM. avium-derived lipids of different polarity, we provide evidence that high-polarity, in contrast to low-polarity and intermediate-polarity, mycobacterial lipids or uncoated latex beads have a strong capacity to induce lipid raft mobilization. These results suggest that high-polarity mycobacterial lipid(s) interact with host cell cholesterol-enriched microdomains which may in turn influence the course of infection. [ABSTRACT FROM AUTHOR]