The bond calibration method (BCM) was designed as a calibration procedure to determine the effective Young’s modulus (E) of a compact aggregate of discrete bonded particles. By systematically varying the Young’s modulus of each particle–particle link (EB), the BCM adjusts the E of the aggregate, disregarding additional macroscopic parameters such as the Poisson’s ratio (ν) and the ultimate compressive strength (UCS). In this study, an extension of the BCM is presented in which E, ν, and UCS are the target properties in the micro-characterization of the material. This new approach relies on parametric analysis of the influence of the bond microproperties on the macroscopic mechanical indices of the aggregate obtained from discrete element simulations of uniaxial compression tests (UCTs). The proposed methodology includes three main steps: (i) determination of the influence of particle–particle bond shear modulus (GB) on ν; (ii) calibration of the particle–particle bond Young’s modulus (EB) based on UCT simulations; (iii) setting an appropriate value for the friction angle (ϕB), and performing discrete element method simulations to establish the influence of the cohesion microparameter (cB) on UCS. The reliability of the BCM was tested through DEM simulations of UCTs of Dokoohak limestone specimens with different particle radius distributions (5≤RmaxRmin≤10). The mean relative errors between the target macroproperties and the DEM simulations with microproperties obtained from BCM were 9.74%, 5.17%, 1.55%, for ν (0.25), E (26GPa), and UCS (52MPa) respectively.

Key Points Question What barriers and enablers to pediatric early warning systems (PEWS) implementation in resource-limited hospitals are reported by health care professionals? Findings In this qualitative study including 5 resource-limited pediatric oncology centers in 4 countries in Latin America, many barriers to PEWS implementation were identified, including inadequate resources and staff resistance to change. Most barriers were successfully converted to enablers during implementation through strategies such as early stakeholder engagement, adapting PEWS to the local context, and changing the hospital setting to support use of PEWS. Meaning The findings of this study suggest that barriers to implementation of evidence-based interventions in resource-limited settings are not immutable and can be converted to enablers through targeted implementation strategies.

Mirochnick, E.; Graetz, D. E.; Ferrara, G.; Puerto Torres, M.; Gillipelli, S. R.; Elish, P.; Muniz Talavera, H.; Gonzalez Ruiz, A.; Armenta, M.; Barra, C.; Diaz, R.; Hernandez, C.; Juarez, S.; de Jesus Loeza, J.; Mendez, A.; Montalvo, E.; Penafiel, E.; Pineda, E.; Agulnik, A. Author Information

Agulnik, A.; Graetz, D. E.; Ferrara, G.; Puerto Torres, M.; Gillipelli, S. R.; Elish, P.; Muniz Talavera, H.; Gonzalez Ruiz, A.; Armenta, M.; Barra, C.; Diaz, R.; Hernandez, C.; Juarez, S.; Loeza, J.; Mendez, A.; Montalvo, E.; Penafiel, E.; Pineda, E.; Mckay, V. Author Information

This paper presents data on the levels of pH, soluble salts and corrosion potential, of concrete from buildings that are up to 30 years old, in order to investigate its condition and preservation. The results suggest evident effects of the carbonation phenomenon, obtaining pH values in the order of 9 units. In addition, the presence of salts such as chlorides and soluble sulfates does not correlate with this reduction in pH or with the levels of corrosion potential that fall into the range of low probability of corrosion mostly, mostly obeying the affectation to environmental CO2.

Tumor associated myeloid cells are major promoters of progression and metastasis. Monocytic and granulocytic myeloid-derived suppressor cells (M-MDSC and G-MDSC) together with tumor associated macrophages (TAM) are among the main contributors to tumor-induced immunosuppression. The influence of the tumor microenvironment on their differentiation is well-accepted but the specific molecular changes leading towards MDSC subsets and TAM are not well-characterized. Here, we describe the main differences between MDSC subsets and TAMs, focused on differential pathways by high-throughput proteomics. We used an ex vivo differentiation system for MDSCs and TAM by modelling the tumor microenvironment from C57BL/6J mouse bone marrow cells in conditioning medium (1). We also differentiated resting macrophages (M0) as controls using standard techniques. Flow cytometry and microscopy confirmed their phenotype by assessing their morphology and presence of characteristic lineage markers. Three global experiment of mass spectrometry-based quantitative (shotgun) proteomics were performed. Construction of functional interactomes from up- or down-regulated proteins was conducted with the Ingenuity Pathway Analysis (IPA) Tool from Quiagen. Targeted proteins were evaluated using western blot. Bibliography: 1) Liechtenstein T, Perez-Janices N, Gato M, et al. Oncotarget. 2014;5(17):7843-7857. We observed morphological differences in ex vivo differentiated myeloid populations. High-throughput proteomics uncovered protein expression patterns characteristic of populations modelling tumor-infiltrating subsets, result of the tumor microenvironment pressure. MAPK1 was identified as upstream regulator using IPA tool. We identified upregulation of STAT3 phosphorylation in all tumor-associated subsets. Both TAM and MDSC have strongly upregulated phosphorylation on S727. Moreover, strong increase in STAT3 Y705 phosphorylation was observed in TAM versus both monocytic and granulocytic MDSC. In the present study, we identified differences in proteomic signatures between myeloid cells modelling M-MDSCs, G-MDSC and TAMs related to lineage, and cancer-driven polarization.

Total knee arthroplasty is one of the most frequently performed orthopaedic surgeries. However, up to 20% of patients develop persistent postoperative pain. Persistent postoperative pain may be an extension of acute postoperative pain, but can also occur after more than 3 months without symptoms. Risk factors associated with persistent postoperative pain after arthroplasty have now been characterised within the patient's perioperative context (preoperative, intraoperative and postoperative), and can be grouped under genetic, demographic, clinical, surgical, analgesic, inflammatory and psychological factors. Identification and prevention of persistent postoperative pain through a multimodal and biopsychosocial approach is essential in the context of perioperative medicine, and has been shown to prevent or ameliorate postoperative pain.

Cancer stem cells (CSCs) represent a small proportion of tumor cells characterized by their high self-renewal and proliferative potential, and they have been proposed as one of the main explanations for the transience of the effect of antineoplastic agents. However, whether they arise from pre-existing populations after selection or are the result of metabolic adaptation of differentiated cells is still under debate. By individually silencing AKT isoforms in pancreatic adenocarcinoma we have observed the acquisition of stem-cell characteristics, with sharp differences between each isoform. We have individually silenced AKT isoforms using short hairpin RNAs (shRNAs) delivered by lentivirus. When cells adapted to the modification, high-throughput quantitative proteomics analyses were performed to evaluate the differentially altered molecular routes. We have evaluated accepted CSCs features as mitochondrial mass and metabolism, CD44 and EpCAM expression, ALDH activity, NANOG expression, spheroid growth and autophagy. We have generated constitutively active and dominant negative c-MYC pancreatic adenocarcinoma cell lines. The adaptation induced deep proteomic changes that affected cells differently depending on the AKT isoform silenced. c-MYC was the main transcription factor associated to potential regulation of the proteomes induced by the silencing of AKT isoforms. c-MYC expression was downregulated in shAKT1 expressing cell line. Mitochondrial mass was increased in the 3 isoforms, although only shAKT1 had greater mitochondrial respiration. Higher basal autophagy was observed in shAKT1 and shAKT3 compared with shAKT2 and control, as well as spheroid formation, regarding both number and size. An increase in NANOG was apparent in shAKT1. CD44 and EpCAM co-expression was increased only in shAKT1, while it was abrogated in c-MYC T58A expressing cell line. The silencing of each AKT isoform induce distinct degrees of CSC dedifferentiation in pancreatic adenocarcinoma. c-MYC is a main regulator of this process.

This work proposes a highly novel centrifugally spun lanthanide doped nonwoven fibrous mat as a non-contact optical pressure sensor with a wide linear dynamic range and good pressure sensitivity. The sensor properties are based on the spectral shift, broadening and intensity enhancement of Ce(3+ )ion in Ce doped PVDF fiber upto significantly high pressure. Two different systems: Ce(NO3)(3)center dot H2O and (NH4)(4)Ce(SO4)(4)center dot 2H(2)O doped PVDF flexible fibers (CeN-PF and CeS-PF) were produced using the Forcespinning (R) technique. Both CeN-PF and CeS-PF fibers displayed violet-blue emission under UV irradiation due to a 5d-4f transition of Ce3+ ions. Our emission results show that both CeN-PF and CeS-PF spectral characteristics are influenced by high pressures, inducing significant spectral ref shift in 5d-4f. The pressure-induced monotonous changes in bandwidth and emission intensity enhancement along with red shift suggesting the potential application of these fibers for pressure sensing applications. The CeN-PF fiber exhibits a high-pressure sensitivity (d lambda/dP approximate to 0.28 nm/GPa) under a comprehensive linear dynamic range (0-64 GPa) with no pressure-induced luminescence quenching. The changes in CeS-PF is less pronounced with a lower pressure sensitivity of 0.10 nm/GPa compared to CeN-PF due to large crystal field splitting energy of nitrate ion compared to sulphate ion. This work presents a highly efficient, cost effective, scalable lanthanide doped flexible fibrous based system with negligible high pressure quenching and a wider linear dynamic range for optical pressure sensing applications. (C) 2019 Elsevier B.V. All rights reserved.

To assess the value of applying reflective MCDA to the generation of drug Therapeutic Positioning Reports (TPR) in Spain. TRP are evaluation reports performed by the AEMPS to support P&R in Spain. AEMPS healthcare professionals involved in the generation of TPR participated in two MCDA sessions using the EVIDEM (v 4.0) framework. TPR currently considers the assessment of “comparative effectiveness”, “safety”, “criteria of use” and “follow-up” for the drug under assessment. In each session, the EVIDEM criteria were presented and weighted using a direct rating scale (1: low relative importance; 5: high relative importance). An example of the assessment of a biological drug in psoriasis was used to rate the evidence matrix and numbers were used to establish a reflective discussion among participants. A total of 15 AEMPS representativesparticipated in the session. Using a direct rating scale, the criteria considered most important (≥4.0 points) were: “comparative effectiveness” (4.5), “disease severity” (4.5), “comparative safety / tolerability” (4.3), “type of therapeutic benefit” (4.1), “unmet needs” (4.1) and “quality of evidence” (4.0). The criteria considered less important (≤3.0) were “comparative cost consequences – non-medical costs (2.9), “size of affected population” (2.9) and “expert consensus/clinical practice guidelines” (2.8). The scores assigned to each criterium regarding the comparative drug assessment were discussed to understand the value contribution of each criteria to the overall drug value. The relative importance assigned by participants to the priority criteria used in TPR (comparative effectiveness and safety) was highly consistent. Additional criteria not included explicitly in TPR, such as, “disease severity”, “quality of evidence” and “unmet needs” were also classified as very relevant. In general, reflective MCDA was considered as a positive methodology which could add transparent reasoning behind evaluators’ discussions during TPR generation.