Preparation of deacetyl-, lyso-, and deacetyl-lyso-GM3 by selective alkaline hydrolysis of GM3 ganglioside

Abstract Three methods (using GM3 quantities ranging from a few milligrams to grams) have been developed to prepare, in high yield, the three derivatives of ganglioside GM3 [α-Neu5Ac-(2-3)-β-Gal-(1-4)-β-Glc-(1-1)-ceramide]: deacetyl-GM3 [α-Neu-(2-3)-β-Gal-(1-4)-β-Glc-(1-1)-ceramide], lyso-GM3 [α-Neu5Ac-(2-3)-β-Gal-(1-4)-β-Glc-(1-1)-sphingosine], and deacetyl-lyso-GM3 [α-Neu-(2-3)-β-Gal-(1-4)-β-Glc-(1-1)-sphingosine]. This is the first report of the preparation of lyso-GM3 by a one-pot reaction. We can now define the optimal conditions for the different preparations. Preparation of deacetyl-GM3: alkaline reagent, 2 M KOH in water; GM3 concentration, 33 mg/ml; reaction temperature, 90 °C; reaction time, 3.5 h; nitrogen atmosphere. Preparation of deacetyl-lyso-GM3: alkaline reagent, 8 M KOH in water; GM3 concentration, 10 mg/ml; reaction temperature, 90 °C; reaction time, 18 h; nitrogen atmosphere. Preparation of lyso-GM3: alkaline reagent, 1 M sodium tert-butoxide in methanol; GM3 concentration, 10 mg/ml; reaction temperature, 80 °C; reaction time, 18 h; anhydrous conditions. The percentage yield of deacetyl-GM3 was 70–75%, that of deacetyl-lyso-GM3 100%, and of lyso-GM3 36–40%. Deacetyl-GM3, deacetyl-lyso-GM3, and lyso-GM3 were purified by column chromatography, and chemical structures were confirmed by electron spray-mass spectrometry. —Valiente, O., L. Mauri, R. Casellato, L. E. Fernandez, and S. Sonnino. Preparation of deacetyl-, lyso-, and deacetyl-lyso-GM3 by selective alkaline hydrolysis of GM3 ganglioside

PACDIN statement of methods

This is an Accepted Manuscript of an article published by Taylor & Francis in Vehicle System Dynamics on 2014 available online: https://doi.org/10.1080/00423114.2014.963126[EN] PAntograph-Catenary Dynamic Interaction (PACDIN) is a code developed by the vehicle technology research centre (CITV) of the Universitat Politecnica de Valencia in collaboration with the railway company Talgo S.L. The model of the catenary is a finite element model using absolute nodal coordinates. It is based on a general formulation that can be applied for analysing a wide range of catenary configurations, including stitch wire, transitions or non-straight path tracks. The formulation is fully non-linear and includes large deformations, dropper slackening and contact interaction. The model is linearised when deformations are small, as in the case of the benchmark dynamic analysis. The results of the PACDIN code show a good agreement with the average results of other benchmark codes.The authors wish to thank Generatitat Valenciana for the financial support received in the framework of the PROMETEO 2012/023 Programme.Tur Valiente, M.; Baeza González, LM.; Fuenmayor Fernández, F.; Garcia, E. (2014). PACDIN statement of methods. Vehicle System Dynamics. 53(3):402-411. https://doi.org/10.1080/00423114.2014.963126S402411533Shabana, A. A. (1998). Nonlinear Dynamics, 16(3), 293-306. doi:10.1023/a:1008072517368BERZERI, M., & SHABANA, A. A. (2000). DEVELOPMENT OF SIMPLE MODELS FOR THE ELASTIC FORCES IN THE ABSOLUTE NODAL CO-ORDINATE FORMULATION. Journal of Sound and Vibration, 235(4), 539-565. doi:10.1006/jsvi.1999.2935Gerstmayr, J., & Shabana, A. A. (2006). Analysis of Thin Beams and Cables Using the Absolute Nodal Co-ordinate Formulation. Nonlinear Dynamics, 45(1-2), 109-130. doi:10.1007/s11071-006-1856-1Tur, M., García, E., Baeza, L., & Fuenmayor, F. J. (2014). A 3D absolute nodal coordinate finite element model to compute the initial configuration of a railway catenary. Engineering Structures, 71, 234-243. doi:10.1016/j.engstruct.2014.04.015Collina, A., & Bruni, S. (2002). Numerical Simulation of Pantograph-Overhead Equipment Interaction. Vehicle System Dynamics, 38(4), 261-291. doi:10.1076/vesd.38.4.261.828

Parametric model for the simulation of the railway catenary system static equilibrium problem

Dynamic simulations of pantograph catenary interaction are nowadays essential for improving the performance of railway locomotives, by achieving better current collection at higher speeds and lower wear of thecollecting parts.The first step in performing these simulations is to compute the static equilibrium of the overhead line.The initial dropper lengths play an important role in hanging the contact wire at an appropriate height. From a classical point of view, if one wants to obtain the static equilibrium configuration of the system for different combinations of dropper lengths, one static pro- blem must be solved for each combination of lengths, which involves a prohibitive computational cost. In this paper we propose a parametric model of the catenary, including the undeformed dropper lengths as extra-coordinates of the problem. This multidimensional problem is efficiently solved by means of the Proper Generalized Decomposition (PGD) technique, avoiding the curse of dimensionality issue. The capabilities and performance of the proposed method are shown by numerical examples.The authors would like to acknowledge the financial support of the FPU program offered by the Ministerio de Educacion, Cultura y Deporte under Grant number FPU13/04191. The funding from Universitat Politecnica de Valencia and Generalitat Valenciana (PROMETEO/2012/023) are also acknowledged.Gregori Verdú, S.; Tur Valiente, M.; Nadal, E.; Fuenmayor Fernández, FJ.; Chinesta, F. (2016). Parametric model for the simulation of the railway catenary system static equilibrium problem. Finite Elements in Analysis and Design. 115:21-32. https://doi.org/10.1016/j.finel.2016.02.007S213211

Maritime antarctic lakes as sentinels of climate change

Remote lakes, such as lakes from the Maritime Antarctica, can be used as sentinels of climate change, because they are mostly free of direct anthropogenic pressures, and they experience climate change as a main stressor capable of modifying the ecosystem structure and function. In this paper, the content of a lecture that has been presented at the First Conference of Lake Sustainability, which has been centred in our studies on lakes from Byers Peninsula (Maritime Antarctica), are summarized. These included physical, chemical and biological studies of these lakes and other freshwater ecosystems, which highlighted the relevance of biotic interactions for these ecosystems and its sensibility to temperature variations and to biological invasions, which is of rel- evance given the acute regional warming occurring during the last decades in the area, concomitant with the enhancement of dispersion of alien species linked to the increased presence of humans

Pitx2 Differentially Regulates the Distinct Phases of Myogenic Program and Delineates Satellite Cell Lineages During Muscle Development

The knowledge of the molecular mechanisms that regulate embryonic myogenesis from early myogenic progenitors to myoblasts, as well as the emergence of adult satellite stem cells (SCs) during development, are key concepts to understanding the genesis and regenerative abilities of the skeletal muscle. Several previous pieces of evidence have revealed that the transcription factor Pitx2 might be a player within the molecular pathways controlling somite-derived muscle progenitors’ fate and SC behavior. However, the role exerted by Pitx2 in the progression from myogenic progenitors to myoblasts including SC precursors remains unsolved. Here, we show that Pitx2 inactivation in uncommitted early myogenic precursors diminished cell proliferation and migration leading to muscle hypotrophy and a low number of SCs with decreased myogenic differentiation potential. However, the loss of Pitx2 in committed myogenic precursors gave rise to normal muscles with standard amounts of SCs exhibiting high levels of Pax7 expression. This SC population includes few MYF5+ SC-primed but increased amount of less proliferative miR-106b+cells, and display myogenic differentiation defects failing to undergo proper muscle regeneration. Overall our results demonstrate that Pitx2 is required in uncommitted myogenic progenitors but it is dispensable in committed precursors for proper myogenesis and reveal a role for this transcription factor in the generation of diverse SC subpopulations.BFU2015-67131 (Spanish Ministery of Economy and Competitiveness)PID2019- 107492GB-100 (Spanish Ministry of Science and Innovation

Efficient finite element methodology based on cartesian grids: application to structural shape optimization

This work presents an analysis methodology based on the use of the Finite Element Method (FEM) nowadays considered one of the main numerical tools for solving Boundary Value Problems (BVPs). The proposed methodology, so-called cg-FEM (Cartesian grid FEM), has been implemented for fast and accurate numerical analysis of 2D linear elasticity problems. The traditional FEM uses geometry-conforming meshes; however, in cg-FEM the analysis mesh is not conformal to the geometry. This allows for defining very efficient mesh generation techniques and using a robust integration procedure, to accurately integrate the domain's geometry. The hierarchical data structure used in cg-FEM together with the Cartesian meshes allow for trivial data sharing between similar entities. The cg-FEM methodology uses advanced recovery techniques to obtain an improved solution of the displacement and stress fields (for which a discretization error estimator in energy norm is available) that will be the output of the analysis. All this results in a substantial increase in accuracy and computational efficiency with respect to the standard FEM. cg-FEM has been applied in structural shape optimization showing robustness and computational efficiency in comparison with FEM solutions obtained with a commercial code, despite the fact that cg-FEM has been fully implemented in MATLAB.This work has been developed within the framework of research project DPI2010-20542 of the Ministerio de Economia y Competitividad (Spain). The financial support of the FPU program (AP2008-01086), the funding from Universitat Politecnica de Valencia, and Generalitat Valenciana (PROMETEO/2012/023) are also acknowledged. The authors also thank the support of the Framework Programme 7 Initial Training Network Funding under Grant no. 289361 "Integrating Numerical Simulation and Geometric Design Technology."Nadal, E.; Ródenas, J.; Albelda Vitoria, J.; Tur Valiente, M.; Tarancón Caro, JE.; Fuenmayor Fernández, FJ. (2013). Efficient finite element methodology based on cartesian grids: application to structural shape optimization. Abstract and Applied Analysis. 2013:1-19. https://doi.org/10.1155/2013/953786S1192013Moés, N., Dolbow, J., & Belytschko, T. (1999). A finite element method for crack growth without remeshing. International Journal for Numerical Methods in Engineering, 46(1), 131-150. doi:10.1002/(sici)1097-0207(19990910)46:13.0.co;2-jSukumar, N., & Prévost, J.-H. (2003). Modeling quasi-static crack growth with the extended finite element method Part I: Computer implementation. International Journal of Solids and Structures, 40(26), 7513-7537. doi:10.1016/j.ijsolstr.2003.08.002Strouboulis, T., Copps, K., & Babuška, I. (2001). The generalized finite element method. Computer Methods in Applied Mechanics and Engineering, 190(32-33), 4081-4193. doi:10.1016/s0045-7825(01)00188-8Strouboulis, T., Zhang, L., & Babuška, I. (2006). Assessment of the cost and accuracy of the generalized FEM. International Journal for Numerical Methods in Engineering, 69(2), 250-283. doi:10.1002/nme.1750Melenk, J. M., & Babuška, I. (1996). The partition of unity finite element method: Basic theory and applications. Computer Methods in Applied Mechanics and Engineering, 139(1-4), 289-314. doi:10.1016/s0045-7825(96)01087-0Stolarska, M., Chopp, D. L., Moës, N., & Belytschko, T. (2001). Modelling crack growth by level sets in the extended finite element method. International Journal for Numerical Methods in Engineering, 51(8), 943-960. doi:10.1002/nme.201Moumnassi, M., Belouettar, S., Béchet, É., Bordas, S. P. A., Quoirin, D., & Potier-Ferry, M. (2011). Finite element analysis on implicitly defined domains: An accurate representation based on arbitrary parametric surfaces. Computer Methods in Applied Mechanics and Engineering, 200(5-8), 774-796. doi:10.1016/j.cma.2010.10.002Legrain, G., Chevaugeon, N., & Dréau, K. (2012). High order X-FEM and levelsets for complex microstructures: Uncoupling geometry and approximation. Computer Methods in Applied Mechanics and Engineering, 241-244, 172-189. doi:10.1016/j.cma.2012.06.001Burman, E., & Hansbo, P. (2010). Fictitious domain finite element methods using cut elements: I. A stabilized Lagrange multiplier method. Computer Methods in Applied Mechanics and Engineering, 199(41-44), 2680-2686. doi:10.1016/j.cma.2010.05.011HEIKKOLA, E., KUZNETSOV, Y. A., & LIPNIKOV, K. N. (1999). FICTITIOUS DOMAIN METHODS FOR THE NUMERICAL SOLUTION OF THREE-DIMENSIONAL ACOUSTIC SCATTERING PROBLEMS. Journal of Computational Acoustics, 07(03), 161-183. doi:10.1142/s0218396x99000126Hetmaniuk, U., & Farhat, C. (2003). A finite element-based fictitious domain decomposition method for the fast solution of partially axisymmetric sound-hard acoustic scattering problems. Finite Elements in Analysis and Design, 39(8), 707-725. doi:10.1016/s0168-874x(03)00055-6Farhat, C., & Hetmaniuk, U. (2002). A fictitious domain decomposition method for the solution of partially axisymmetric acoustic scattering problems. Part I: Dirichlet boundary conditions. International Journal for Numerical Methods in Engineering, 54(9), 1309-1332. doi:10.1002/nme.461Ye, T., Mittal, R., Udaykumar, H. S., & Shyy, W. (1999). An Accurate Cartesian Grid Method for Viscous Incompressible Flows with Complex Immersed Boundaries. Journal of Computational Physics, 156(2), 209-240. doi:10.1006/jcph.1999.6356Jahangirian, A., & Shoraka, Y. (2008). Adaptive unstructured grid generation for engineering computation of aerodynamic flows. Mathematics and Computers in Simulation, 78(5-6), 627-644. doi:10.1016/j.matcom.2008.04.004Silva Santos, C. M., & Greaves, D. M. (2007). Using hierarchical Cartesian grids with multigrid acceleration. International Journal for Numerical Methods in Engineering, 69(8), 1755-1774. doi:10.1002/nme.1844Jang, G.-W., Kim, Y. Y., & Choi, K. K. (2004). Remesh-free shape optimization using the wavelet-Galerkin method. International Journal of Solids and Structures, 41(22-23), 6465-6483. doi:10.1016/j.ijsolstr.2004.05.010Mäkinen, R. A. E., Rossi, T., & Toivanen, J. (2000). A moving mesh fictitious domain approach for shape optimization problems. ESAIM: Mathematical Modelling and Numerical Analysis, 34(1), 31-45. doi:10.1051/m2an:2000129Victoria, M., Querin, O. M., & Martí, P. (2010). Topology design for multiple loading conditions of continuum structures using isolines and isosurfaces. Finite Elements in Analysis and Design, 46(3), 229-237. doi:10.1016/j.finel.2009.09.003Parussini, L., & Pediroda, V. (2009). Fictitious Domain approach with hp-finite element approximation for incompressible fluid flow. Journal of Computational Physics, 228(10), 3891-3910. doi:10.1016/j.jcp.2009.02.019Bishop, J. (2003). Rapid stress analysis of geometrically complex domains using implicit meshing. Computational Mechanics, 30(5-6), 460-478. doi:10.1007/s00466-003-0424-5Zhang, L., Gerstenberger, A., Wang, X., & Liu, W. K. (2004). Immersed finite element method. Computer Methods in Applied Mechanics and Engineering, 193(21-22), 2051-2067. doi:10.1016/j.cma.2003.12.044Roma, A. M., Peskin, C. S., & Berger, M. J. (1999). An Adaptive Version of the Immersed Boundary Method. Journal of Computational Physics, 153(2), 509-534. doi:10.1006/jcph.1999.6293García‐Ruíz, M. J., & Steven, G. P. (1999). Fixed grid finite elements in elasticity problems. Engineering Computations, 16(2), 145-164. doi:10.1108/02644409910257430Daneshmand, F., & Kazemzadeh-Parsi, M. J. (2009). Static and dynamic analysis of 2D and 3D elastic solids using the modified FGFEM. Finite Elements in Analysis and Design, 45(11), 755-765. doi:10.1016/j.finel.2009.06.003Bordas, S. P. A., Rabczuk, T., Hung, N.-X., Nguyen, V. P., Natarajan, S., Bog, T., … Hiep, N. V. (2010). Strain smoothing in FEM and XFEM. Computers & Structures, 88(23-24), 1419-1443. doi:10.1016/j.compstruc.2008.07.006Simpson, R. N., Bordas, S. P. A., Trevelyan, J., & Rabczuk, T. (2012). A two-dimensional Isogeometric Boundary Element Method for elastostatic analysis. Computer Methods in Applied Mechanics and Engineering, 209-212, 87-100. doi:10.1016/j.cma.2011.08.008Scott, M. A., Simpson, R. N., Evans, J. A., Lipton, S., Bordas, S. P. A., Hughes, T. J. R., & Sederberg, T. W. (2013). Isogeometric boundary element analysis using unstructured T-splines. Computer Methods in Applied Mechanics and Engineering, 254, 197-221. doi:10.1016/j.cma.2012.11.001Hughes, T. J. R., Cottrell, J. A., & Bazilevs, Y. (2005). Isogeometric analysis: CAD, finite elements, NURBS, exact geometry and mesh refinement. Computer Methods in Applied Mechanics and Engineering, 194(39-41), 4135-4195. doi:10.1016/j.cma.2004.10.008Zienkiewicz, O. C., & Zhu, J. Z. (1987). A simple error estimator and adaptive procedure for practical engineerng analysis. International Journal for Numerical Methods in Engineering, 24(2), 337-357. doi:10.1002/nme.1620240206Zienkiewicz, O. C., & Zhu, J. Z. (1992). The superconvergent patch recovery anda posteriori error estimates. Part 1: The recovery technique. International Journal for Numerical Methods in Engineering, 33(7), 1331-1364. doi:10.1002/nme.1620330702Wiberg, N.-E., Abdulwahab, F., & Ziukas, S. (1994). Enhanced superconvergent patch recovery incorporating equilibrium and boundary conditions. International Journal for Numerical Methods in Engineering, 37(20), 3417-3440. doi:10.1002/nme.1620372003Blacker, T., & Belytschko, T. (1994). Superconvergent patch recovery with equilibrium and conjoint interpolant enhancements. International Journal for Numerical Methods in Engineering, 37(3), 517-536. doi:10.1002/nme.1620370309Ramsay, A. C. A., & Maunder, E. A. W. (1996). Effective error sttimation from continous, boundary admissible estimated stress fields. Computers & Structures, 61(2), 331-343. doi:10.1016/0045-7949(96)00034-xRódenas, J. J., Tur, M., Fuenmayor, F. J., & Vercher, A. (2007). Improvement of the superconvergent patch recovery technique by the use of constraint equations: the SPR-C technique. International Journal for Numerical Methods in Engineering, 70(6), 705-727. doi:10.1002/nme.1903Díez, P., José Ródenas, J., & Zienkiewicz, O. C. (2007). Equilibrated patch recovery error estimates: simple and accurate upper bounds of the error. International Journal for Numerical Methods in Engineering, 69(10), 2075-2098. doi:10.1002/nme.1837Ródenas, J. J., González-Estrada, O. A., Díez, P., & Fuenmayor, F. J. (2010). Accurate recovery-based upper error bounds for the extended finite element framework. Computer Methods in Applied Mechanics and Engineering, 199(37-40), 2607-2621. doi:10.1016/j.cma.2010.04.010Ainsworth, M., & Oden, J. T. (2000). A Posteriori Error Estimation in Finite Element Analysis. doi:10.1002/9781118032824Xiao, Q. Z., & Karihaloo, B. L. (2006). Improving the accuracy of XFEM crack tip fields using higher order quadrature and statically admissible stress recovery. International Journal for Numerical Methods in Engineering, 66(9), 1378-1410. doi:10.1002/nme.1601Bordas, S., & Duflot, M. (2007). Derivative recovery and a posteriori error estimate for extended finite elements. Computer Methods in Applied Mechanics and Engineering, 196(35-36), 3381-3399. doi:10.1016/j.cma.2007.03.011Bordas, S., Duflot, M., & Le, P. (2007). A simple error estimator for extended finite elements. Communications in Numerical Methods in Engineering, 24(11), 961-971. doi:10.1002/cnm.1001Duflot, M., & Bordas, S. (2008). A posteriorierror estimation for extended finite elements by an extended global recovery. International Journal for Numerical Methods in Engineering, 76(8), 1123-1138. doi:10.1002/nme.2332Ródenas, J. J., González-Estrada, O. A., Tarancón, J. E., & Fuenmayor, F. J. (2008). A recovery-type error estimator for the extended finite element method based onsingular+smoothstress field splitting. International Journal for Numerical Methods in Engineering, 76(4), 545-571. doi:10.1002/nme.2313Abel, J. F., & Shephard, M. S. (1979). An algorithm for multipoint constraints in finite element analysis. 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Genetic variation of cork oak a tool for improving regeneration of cork oak woodlands

The European Academies' Science Advisory Council (2017) reports that the Mediterranean forest is already being affected by climate change (IPCC, 2014) and cork oak woodlands are particularly vulnerable to high-end climate scenarios that go above the Paris Agreement 2° C increase in temperature. Since longer, more frequent, and more intense drought periods are expected, stress caused by the expansion of arid and semi-arid climate will affect the species distribution. Consequently, not only established stands may be prone to tree mortality, but also the current reforestation effort may be jeopardized by low survival rates attributed to the use of unsuitable genetic material. It is expected that, through genetic adaptation and/or phenotypic plasticity, cork oak populations may have developed significant differences in fitness and the traits related to it. In this context, provenance and progeny trials are the best resource of material to assess the variability between and within populations from seed sources sampled in a wide range of locations (stands) covering the geographical distribution of the species. Profiting from the multi-locality provenance and progeny trials belonging to a Network, established in 1998, in the initiative frame of FAIR I CT 0202 for the evaluation of genetic resources of cork oak for appropriate use in breeding and gene conservation strategies”, where 35 cork oak populations covering all the natural distribution area are represented. The provenance trials that where set up in different countries are entering now the age of first debarking and this should allow to have first data about the influence of genetics on production by different site qualities. INCREDIBLE project should document this knowledgeFAIR I CT 0202info:eu-repo/semantics/publishedVersio

Quasiexperimental intervention study protocol to optimise the use of new antibiotics in Spain: the NEW_SAFE project

Introduction Ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam and ceftolozane-tazobactam are novel antibiotics used to treat infections caused by multidrug-resistant pathogens (MDR). Their use should be supervised and monitored as part of an antimicrobial stewardship programme (ASP). Appropriate use of the new antibiotics will be improved by including consensual indications for their use in local antibiotic guidelines, together with educational interventions providing advice to prescribers to ensure that the recommendations are clearly understood. Methods and analysis This study will be implemented in two phases. First, a preliminary historical cohort (2017-2019) of patients from 13 Andalusian hospitals treated with novel antibiotics will be analysed. Second, a quasiexperimental intervention study will be developed with an interrupted time-series analysis (2020-2021). The intervention will consist of an educational interview between prescribers and ASP leaders at each hospital to reinforce the proper use of novel antibiotics. The educational intervention will be based on a consensus guideline designed and disseminated by leaders after the retrospective cohort data have been analysed. The outcomes will be acceptance of the intervention and appropriateness of prescription. Incidence of infection and colonisation with MDR organisms as well as incidence ofClostridioides difficileinfection will also be analysed. Changes in prescription quality between periods and the safety profile of the antibiotics in terms of mortality rate and readmissions will also be measured. Ethics and dissemination Ethical approval will be obtained from the Andalusian Coordinating Institutional Review Board. The study is being conducted in compliance with the protocol and regulatory requirements consistent with International Council of Harmonisation E6 Good Clinical Practice and the ethical principles of the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and disseminated at national and international conferences

Quasiexperimental intervention study protocol to optimise the use of new antibiotics in Spain: the NEW_SAFE project

[Introduction] Ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam and ceftolozane-tazobactam are novel antibiotics used to treat infections caused by multidrug-resistant pathogens (MDR). Their use should be supervised and monitored as part of an antimicrobial stewardship programme (ASP). Appropriate use of the new antibiotics will be improved by including consensual indications for their use in local antibiotic guidelines, together with educational interventions providing advice to prescribers to ensure that the recommendations are clearly understood.[Methods and analysis] This study will be implemented in two phases. First, a preliminary historical cohort (2017–2019) of patients from 13 Andalusian hospitals treated with novel antibiotics will be analysed. Second, a quasiexperimental intervention study will be developed with an interrupted time-series analysis (2020–2021). The intervention will consist of an educational interview between prescribers and ASP leaders at each hospital to reinforce the proper use of novel antibiotics. The educational intervention will be based on a consensus guideline designed and disseminated by leaders after the retrospective cohort data have been analysed. The outcomes will be acceptance of the intervention and appropriateness of prescription. Incidence of infection and colonisation with MDR organisms as well as incidence of Clostridioides difficile infection will also be analysed. Changes in prescription quality between periods and the safety profile of the antibiotics in terms of mortality rate and readmissions will also be measured.[Ethics and dissemination] Ethical approval will be obtained from the Andalusian Coordinating Institutional Review Board. The study is being conducted in compliance with the protocol and regulatory requirements consistent with International Council of Harmonisation E6 Good Clinical Practice and the ethical principles of the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and disseminated at national and international conferences.[Trial registration number] NCT03941951; Pre-results.The study is funded by the Consejería de Salud, Junta de Andalucía, grant PI-0077-2018. The investigators also receive funds for research from the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001) through the Plan Nacional de I+D+ i 2013‐2016, cofinanced by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014‐2020