In order to combat corrosion issues, several studies on progressively replacing steel reinforcement elements with composite ones have been conducted in recent years. Hybrid steel–concrete thin slabs in which the steel acts as formwork are also candidates for update in the coming years. Achieving a reliable connection between fiber-reinforced polymer (FRP) and cast-in-place concrete is key to promoting this technology. This study analyzed different connection systems and proposes the novel approach of embedding a flexible fiber fabric as a superficially distributed connector between concrete and FRP. Eight specimens with four different connection strategies were tested using an experimental modal analysis and a quasi-static three-point bending test. The impact of the connection system on the vibrational response, flexural ultimate load, moment response, neutral axis position, shear and dissipated energy was obtained and compared. The results show that the use of an embedded mesh increases the frictional mechanism and produces the best performance in terms of load-bearing capacity and ductility. Traditional reinforced concrete (RC) structures exhibit aging problems related to the corrosion of the steel reinforcement, and there have been many recent studies into strengthening and retrofitting these structures using composite materials. Recently, the FRP–concrete concept was used in manufacturing hybrid slab , column There are two main typologies of FRP–concrete hybrid structures. In the first type, FRP is used as a tubular or box envelope for concrete, whereas in the second and more studied type, FRP is presented as a girder or a pultruded profile connected to a top concrete section to aid bending resistance. Regarding the first approach, several researchers have studied the bending resistance design of hybrid structures based on the box system. Yang et al.  performeFar more research can be found regarding the second hybrid FRP–concrete typology, which is based on connecting FRP pultruded profiles to upper concrete sections to generate hybrid beams. One of the pioneering works on hybrid composite single beams is by Hulatt et al. , in whicRegarding more specific tests on the connection between FRP profiles and concrete parts, Gonilha et al. 2014)  performe  performAs can be observed from the literature review, most of the developments in hybrid FRP–concrete structures have been oriented toward implementing beam-like solutions. There are few contributions to research on plane slab typology, in which FRP can even be used as formwork. On this topic, the work by Gai et al.  has to bIn addition, it can be seen that the connection systems between FRP and concrete always rely on epoxy-bonded solutions for previously cast concrete, or on mechanical punctual connectors for cast-in-place concrete. Accordingly, a novel connection system based on embedding a flexible fiber fabric bonded to FRP and mechanically interlocking it with concrete is proposed, tested and analyzed. This is an entirely new technology, to the best of our knowledge, with the closest research considering fiber fabrics together with FRP profiles being found in the work by Sutter et al. , who tesThe current work focuses on the description and mechanical characterization of the structural response of a novel hybrid slab system made with a thin CFRP sheet, which is also the formwork, and a concrete block that is connected through a flexible fiber fabric. An additional connection using particle-based frictional enhancement is also considered and compared. Among the mechanical characterization tasks, the experimental modal analysis is aimed at qualitatively relating the vibrational response with the particular studied typologies of FRP–concrete connection systems. In addition, three-point bending tests are presented to analyze the load-bearing capacity, strain distribution, evolution of the position of the neutral axis and the dissipated energy, among other parameters. The study presented herein analyses, for the first time, the effect of a flexible fabric mesh as a connector between CFRP sheet and concrete, for producing hybrid structures aimed to support bending efforts. The potential benefits of this study include (i) opening the possibility of replacing thin steel sheets with FRP sheets, avoiding the corrosion problems typical of aggressive environments; (ii) characterizing a connection technology based on distributing the load-transferring mechanism to be more compatible with FRP materials whose mechanical connection is always controversial; and (iii) providing the order of magnitude of the load-bearing capacity of thin slabs produced with this novel connection based on flexible fiber fabric. The materials and the manufacturing process can be seen in 3 of Portland cement with continuous 0 to 12 mm of limestone aggregates and plasticizer, and mixed with a water/cement ratio of 0.6 reaching a compressive strength below 25 MPa. This intended low compressive strength was designed to represent a poor cast-in-place material with the future aim of being combined with a natural composite with a lower performance than the CFRP sheets ) was used to connect the CFRP sheet with the concrete in the proposed novel approach. This mesh had a weight of 225 g/m 45 kN/m a. The fi 45 kN/m g and theSolid particles of different sizes were used to increase the friction interface between the CFRP sheet and the concrete c,d. The Eight hybrid slabs were manufactured with four different connection systems used to study the flexural performance of the slabs. In particular, the research was oriented to comparatively investigate the performance of: (i) mechanical connection provided by aggregates with different sizes bonded to the inner surface of CFRP modifying the roughness of the CFRP–concrete interface; (ii) the mechanical connection provided by a flexible fiber FRP mesh that was bonded to the CFRP sheet and that interlocked concrete into their gaps; and (iii) the orientation of the connection fiber mesh and its relationship with load transfer mechanisms. To provide comprehensive data according with these study aims, specimens were defined so to be able to compare the impact of including (G-S-SM) or not including (G-SM) small-size aggregate particles. It was also possible to study the impact of using (G-SM) or not using (G) the proposed novel connection based on flexible fiber fabric. Finally, it was also possible to analyze the impact of the fabric orientation by comparing specimens with straight mesh (G-S-SM) and inclined mesh (G-S-IM). Other parameters like the number of fabric layers, the material of the fabric, the shape of the thin FRP sheet or the type of adhesive used to bond aggregates and fabric with CFRP were not considered in this first study aimed to provide a global assessment of the novel use of a flexible fabric to connect FRP and concrete. All these parameters, among others, should be analyzed in future works. The labeling of the samples describes the connection system and the numbering of the specimens. Numbers at the end of the labeling (1 or 2) define the specimen repetition. Letters define the connection system: G- for bonded gravel particles; G-SM for the combination of bonded gravel particles and straight (0°) oriented glass fiber mesh; G-S-SM for the same as G-SM with the addition of sand particles to the gravel ones; and G-S-IM for the analogous case but with the mesh oriented at 45° with respect to the CFRP sheet nerves. The variety of specimens is defined in In order to study the different connection systems and to assess the novel proposal of using a flexible fiber fabric as a FRP–concrete connector, two types of tests were defined. First of all, experimental modal analysis was aimed to assess the performance of the studied connections in a non-destructive method with the final goal of providing a qualitative comparison. In addition, destructive bending tests were also conducted to provide quantitative data to compare the different studied connection systems. Direct results of these bending tests such as force–displacement curves, CFRP–concrete relative sliding and strain distribution are aimed to describe the mechanical response and the failure mechanism from a global point of view. In addition, some calculated variables are used to provide clear evidences of the failure mechanism , practical information of the equivalent shear transferring capability  or to assess the ductility of the studied connections . Experimental methods are described in detail in this section.From the hypothesis that the connection system affects the shear transmission between the concrete block and the CFRP sheet, it was expected that the vibrational information would also depend on this connection. Experimental modal analysis (EMA) tests were performed to estimate the vibrational modes, frequencies and damping ratios of the specimens with the different proposed connection systems. The main aim was to qualitatively detect the differences between the connection systems on the vibrational responses. This information could be used to pave the way for future research on the non-destructive assessment of the connection systems of thin hybrid CFRP–concrete slabs, although it is outside the scope of the current research.Specimens were placed as a simply supported beams with a free span of 1800 mm. Tests were conducted using impulse excitation based on ISO standard 7626-5 . An impaThree-point bending tests were performed on simply supported specimens to assess their performance with regard to bending and shear concomitance. The modal shapes and associated frequencies (ω) and damping ratios (ζ) were experimentally obtained via modal analysis for each specimen. Different mechanisms for load transfer are supposed to be developed depending on the analyzed specimen. First of all, aggregates (gravel and sand) bonded to the inner surface of the bottom plates of the CFRP sheets are providing a rigid mechanical interlocking with the concrete. This connection system allowed a full load transfer between concrete and CFRP sheet at the beginning of the test up to the failure of this particular connection. The fragile failure of this load transfer mechanism started at the central section (greatest bending moment) and extended to the extremes. Hence, there was little contribution of the aggregates to any partial connection mechanism. Additionally, it has to be noticed that sand particles might not increase the mechanical interlocking as efficiently as particles of larger size such as gravels. According to the empirical evidences of the tests, the little size of sand particles (less than 4 mm) might determine a weaker sliding plane in the CFRP sheet–concrete interface compared to gravel aggregates. Regarding the load transfer mechanism of the fiber mesh, two cases have to be distinguished. Firstly, for straight mesh (G-SM and G-S-SM specimens), the grid geometry provided a flexible interlocking mechanism based on the shear deformation of the transversal fiber tows. The mesh was bonded to the CFRP sheet every 170 mm (top hat) and mechanically connected with concrete on every grid gap. The failure mechanism was based, in this case, in the shear progressive breaking of the transversal fiber tows, which started at the central section (between top hats) and progressed faster to the extreme edges (bonded). Full FRP mesh–concrete interaction and load transfer capability was observed up to this first breaking point. After shear breaking started, vertical deformation of bending specimens increased but load experienced a fall drop. Load was kept constant along the time while the breaking process moved from the mid span section towards the support edges. In the other, for inclined mesh (G-S-IM specimens), the grid geometry provided two concomitant resisting mechanisms: (i) shear resisting mechanism analogous to the case with straight mesh and (ii) axial resisting mechanism of the tows. Thus, fiber tows were subjected to shear and axial stresses at the same time. Due to the geometry, all tows were inclined and all of them contribute to the locking mechanism . As a result, all these tows of fiber were connected to a larger surface of concrete, in comparison with the straight orientation case, and more fiber quantity was involved in the failure mechanism. The observed failure was more progressive than the previous one, because of the concrete–mesh sliding process and the progressive tensile breaking of the mesh. These two mechanisms were allowed by the axial and shear response of the fiber. The corresponding global failure mode involved a larger FRP mesh–concrete connection area than the just the central section, resulting in higher load transfer capacity between these two phases and a higher load-bearing capacity. Complete interaction was only observed at the very beginning of the tests, whereas partial interaction mostly characterized these specimens’ performance (G-S-IM), even before the peak load.Pictures of the different specimens after failure are included in Plots representing the force–vertical displacement response for all the tested cases are shown in All measurements of CFRP–concrete sliding show precisely the same behavior: the relative CFRP–concrete sliding at the extreme edges of the slabs started at the maximum load. Thus, there is no doubt, according to the experimental results, that the failure of all the specimens was due to the loss of connection between the CFRP thin sheet and the concrete block. It is also noticeable that in all cases, except the G-1 specimen, there is an asymmetric response, so the sliding took place in only one of the halves of the specimens. This is the expected response because random imperfections tend to cause the failure to start on one side or the other one, but not on both of them simultaneously. Anomalous symmetric response of G-1 case may be one of the reasons for its greater load-bearing capacity in comparison with G-2 case.The plots gathering the strain–time results of all tested specimens are displayed in Initially, it should be noted that the vibrational response of mechanical systems is influenced by the supports. As all the tested specimens had the same support, the results obtained from the experimental modal analysis  can be uFirst, it is observed see  that theNon-destructive experimental modal analysis tests showed that there was a certain correlation between the dynamical response and the connection system. The inclusion of a connection mesh led to an increase in the natural frequency . The G sIn conclusion, including small-size particles for the roughness improvement of the CFRP–concrete contact surface (G-SM vs. G-S-SM) reduced the dynamic stiffness of the specimens and it was translated in a 12% lower frequency of vibration of the third bending mode. Thus, it is clear that small-size particles affect CFRP–concrete connection. In contrast, adding a straight mesh caused an increase of 20% of the vibration frequency (comparing G-SM and G cases), proving that the inclusion or not of this connection element may be comparatively assessed by experimental modal analysis. Finally, inclining the mesh has little effect (2.8% of the vibration frequency increase) supporting the idea that the orientation of the mesh has no effect in the lineal elastic response and only plays an important role at failure stage. It should be observed that the obtained results show clear trends, despite the significant variability. The differences between sample results are related to the uncertainty of hand manufacture and the complexity of the interaction in the interfaces for shear transmission. This could present a problem for practitioners that pretend to use it at work, and it means that quality control must be mandatory to produce homogeneous specimens. Therefore, the analysis of the impact of the different connection techniques between the CFRP sheets and concrete is mostly qualitative.Focusing on the overall comparison of the maximum load-bearing capacity, it can be observed that including the mesh connection  causes an average increase in the maximum load of approximately 60%. It can also be seen that placing sand, theoretically intended to increase the frictional response, provides the opposite result, reaching lower load-bearing capacities in comparison with the G-S-SM and G-SM specimens. This result is consistent with the observation from experimental modal analysis. Regarding the applied load, it is clear that incorporating a mesh  allowed the slabs to withstand a residual strength after reaching the maximum peak and the corresponding load drop see . Hence, Regarding the inclination of the mesh, it seems to have a positive effect on the load-bearing capacity of the proposed hybrid slabs (G-S-IM vs. G-S-SM). In addition, this case showed a better connection that translated to less bending cracks developing during tests and the failure mechanism that simultaneously mobilized almost all CFRP–concrete contact surfaces of one half of the slab. However, this case (G-S-IM) showed the second greatest load drop due to connection failure after no mesh (G) cases. Therefore, inclining the mesh helps to distribute the connection mechanism reaching higher loads, but also making the whole system more fragile, as the failure involves the full interface. Strain–time plots see  showed tSummarizing the effect of the key parameters on the direct results of the bending tests, it can be stated that including a flexible fabric connector (G-SM vs. G) increased the load-bearing capacity and brought residual strength. In contrast, including small-size particles in the CFRP–concrete contact (G-SM vs. G-S-SM) reduced the load-bearing capacity but allowed some post-peak strength because of higher frictional effect after contact failure. Finally, inclining the connection mesh (G-S_MS vs. G-S-IM) increased the load-bearing capacity and increased the residual strength but made the failure process more fragile. All these effects are related with the largest quantity of fibers simultaneously contributing (and simultaneously failing) to the connection strength of G-S-IM cases. The neutral axis is referenced from the bottom part of the cross-section. When the neutral axis position was over 35 mm, the CFRP sheet was subjected to tensile stresses, and the concrete below the axis was supposed to be cracked. Conversely, when the axis was below 35 mm, the CFRP sheet was partially compressed. This is shown in The corresponding positions of the neutral axis during the linear-elastic branch . This means that after the failure of the interface, a residual friction between the CFRP, the cracked concrete and the mesh still contributed a little, as was shown in Analyzing the effect of the studied parameters, it was observed that including the mesh (G vs. G-SM) allowed to stabilize the position of the neutral axis between 40 mm and 50 mm for a long period of the test up to the maximum load, whereas the cases without mesh showed a clear downward movement of the position of the neutral axis from the very beginning. Among the cases with meshes, no clear tendency is observed, so the response of the position of the neutral axis seems not to depend on the inclination of the mesh.2). This total compressive/tensile force was calculated from the strain distribution and the corresponding force equilibrium.The overall shape of the plots in The particular analysis of the study variables showed that including a flexible fabric connector (G vs. G-SM) increased the residual shear strength (from 30 kPa to 50 kPa). The same effect is observed when inclining the connection mesh (G-S-SM vs. G-S-IM) that doubled the residual shear strength. Finally, adding small-size particles to the CFRP–concrete interface (G-SM vs. G-S-SM) clearly reduced the shear strength (from 0.37 MPa to 0.11 MPa in average) although slightly increased the residual shear strength .After performing an experimental modal analysis and eight bending tests on CFRP sheet–concrete hybrid slabs with four different connection alternatives, including the novel approach of embedding a flexible fiber mesh, the following conclusions were reached:The structural bending response of this type of slab showed three stages. For small loads (approximately 2 kN in these tests), the specimens performed according Navier’s hypothesis with a linear elastic response of the cross-section. For higher loads, the concrete started to crack and the load–displacement response tended to be non-linear. The existence of interlocking elements  helped to keep the complex shear transmission mechanisms between materials. Finally, a peak load was reached, and a sudden failure occurred due to the loss of the connection between the concrete and CFRP sheet. The load dropped down and both materials were separated leaving a residual shear mechanism from the friction of the rough surfaces. Thus, the structural response of this novel connection system between thin FRP sheets and concrete is qualitatively described. Gravel particles bonded to the CFRP sheet surface provided a superficial connection with concrete. The performance of this connection was fragile and presented the lowest values of load-bearing capacity. This connection system as a stand-alone is not recommended for practical applications.The novel inclusion of a flexible glass-fiber mesh directly bonded onto the CFRP, as a connector between the composite sheet and the concrete, allowed an increase in the load-bearing capacity of the slabs, produced residual strength after connection failure and increased the stiffness of the vibrational response of the slab specimens. A qualitative relationship between the vibrational response obtained from the experimental modal analysis and the load-bearing capacity was observed, although further research is required to confirm this fact and to progress its quantification.The inclusion of sand particles bonded to the inner bottom surface of the CFRP had the unexpected effect of reducing the load-bearing capacity and the cohesion between the concrete and the CFRP sheet, although the post-peak residual strength was slightly increased. The inclination of the mesh clearly contributed to uniformly distributing the shear forces in the interface of the materials. This is likely to be because more fibers were oriented in a direction closer to the shear effort to be resisted, compared to the case of a straight position. Therefore, the inclined mesh seems to be the best choice of the two orientations of this novel connection strategy.All CFRP sheet–concrete hybrid slabs failed when the neutral axis moved into the CFRP area (under 35 mm) causing the top part of the CFRP and the connection of the glass fiber mesh, when existing, to be compressed and to definitively separate from the concrete. Even thin CFRP can suffer buckling, as was observed.The amount of cumulative energy corresponds with a qualitative estimation of the capacity of the slabs to dissipate energy and resist damage. The inclined mesh solution was confirmed to be the most competitive one. In conclusion, the main design lines of thin hybrid FRP–concrete slabs based on flexible fiber fabric connectors are provided as results of this study. Two of them have to be highlighted: using aggregates larger than 5 mm to provide roughness to the inner FRP surface and positioning the fiber fabric in an inclined orientation to distribute the load-transfer mechanism after reaching maximum load along a greater area. Finally, this study opens the door to a wide research field on the characterization of the structural response of these type of structures (or other ones based on the novel proposed flexible distributed connectors), including the study of different materials, geometries or adhesives. These results also put the basis for the development of analytical and numerical models of these systems.


Monitoring of antibiotic prescription and consumption behavior is crucial. The Access, Watch, and Reserve (AWaRe) classification of antibiotics has been recently introduced in order to measure and improve patterns of antibiotic use. In this study, retrospective data about systemic antibiotic consumption (expressed in defined daily dose per 1000 inhabitants per day (DID)) in pediatric outpatients in a region in northern Spain  from 2005 to 2018 were analyzed and compared with antibiotic consumption in general population in Spain. The pattern of use was analyzed by the percentage of the current AWaRe categories, the Access-to-Watch index, and the amoxicillin index. Data were calculated annually and compared into two periods. Mean antibiotic consumption in pediatric outpatients was 14.0 DID (CI 95% 13.38–14.62). It remained stable throughout the study and was lower than consumption in general population in Spain, particularly from 2016. Changes in the consumption of the main active principles have led to an improvement in the three metrics of the pattern of use. It is important to have a thorough knowledge of the methodology applied in studies about antibiotic consumption. There is a lack of an optimal standardized metric for the pediatric population. Reducing unnecessary and inappropriate use of antibiotics is a public health priority. Continuous monitoring of antibiotic prescription and consumption behavior is essential to control increasing antibiotic resistance worldwide .The World Health Organization (WHO) launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015, which collects data on antibiotic consumption of 65 countries .The ECDC collects antibiotic consumption information according to the Defined Daily Dose (DDD) methodology developed by the WHO Collaborating Centre for Drug Statistics Methodology. In January 2019, this organism changed the DDDs for several antibiotics . MoreoveAntibiotics are among the most commonly prescribed drugs in pediatrics ,7. NeverThis study aims to describe antibiotic consumption and to analyze the pattern of antibiotic use in pediatric outpatients in a region in northern Spain, pointing out difficulties when analyzing data of antibiotic consumption, particularly in children.Retrospective and descriptive study about consumption of antibacterials for systemic use  in pediatric outpatients (up to 14 years old) from 2005 to 2018 in Principado de Asturias, a region in northern Spain, with 101,767 children protected by the National Health System in 2018. Data were collected from the billing data of the containers dispensed in the pharmacy offices run by the National Health System.Information about antibiotic consumption was expressed as DDD per 1000 inhabitants per day (DID) according to the latest and the previous available ATC/DDD index ,10. DIDsTo analyze the pattern of use, antibiotics were classified into the four current AWaRe categories: Access, Watch, Reserve, and Not Recommended. Antibiotics that could not be assigned to the AWaRe categories were left unclassified categories . Three mt-test. Statistical analyses were performed using IBM SPSS Statistics software  version 23.0. The statistical significance level was defined as a two-tailed p-value < 0.05.Antibiotic consumption and the pattern of use were calculated annually and compared into two periods (2005–2011 and 2012–2018). From the middle of 2018, an antibiotic stewardship program was implemented in our region, following the guidelines of the National Plan of Antimicrobial Resistance (PRAN) . This prMean antibiotic consumption in pediatric outpatients in Asturias, a region in northern Spain, between 2005 and 2018 was 14.0 DID (CI 95% 13.38–14.62), showing no statistically significant changes between periods. The most consumed therapeutic groups were J01C , J01F , and J01D . The consumption of ten active principles represented 97.6% of the global use, and the consumption of amoxicillin and amoxicillin-clavulanate accounted for 72.8%. Consumption of amoxicillin, phenoxymethylpenicillin, azithromycin, and doxycycline significantly increased, whereas consumption of cefuroxime, cefixime, and clarithromycin decreased throughout the study .The consumption of Access antibiotics was greater than 70% every year  . HistoriSecond, there has been a noticeable increase of antibiotic consumption rates in Spain since 2016. Spain changed the source to report community consumption data from 2016 onwards from reimbursement data to National Health System to sales data, which resulted in a substantial technical increase of antibiotic consumption compared with previous years. The major limitation of reimbursement data is that antibiotics dispensed without a prescription and non-reimbursed prescribed antibiotics are not included. Spanish data are currently more reliable and comparable with those of other countries, as just a quarter of countries reporting information to ESAC-Net still provide reimbursement data . Rates oThird, prescriptions in children are commonly based on patient weight. Measuring antibiotic consumption by DDD can be found questionable in children, as it quantifies the volume of antibiotic administered but does not take into account body weight. Over 25 different measures can be found to describe antibiotic use in pediatric population, referring to the proportion of exposed patients and quantity and duration of antibiotic therapy . The curIn relation to the pattern of antibiotic use, the majority of non-Access antibiotic consumption in our study was from Watch Antibiotics, with Reserve and Not Recommended antibiotic consumption accounting for less than 0.15%. We observed an improvement in the pattern of antibiotic use in our population in the three mentioned metrics. Azithromycin was the main Watch antibiotic whose consumption increased over time in our study and the active principle with the highest increase in the study region . Recent The main current and global problem is the increasing consumption of both Access and Watch antibiotics, with the consumption of Watch antibiotics rising much faster than Access antibiotics, especially in low- and middle-income countries. This challenges the achievement of the AWaRe target for Access antibiotics to account for 60% of the global consumption by 2023 in these countries ,22,23. TOur study presents several limitations, mostly derived from the analysis and comparison of antibiotic consumption given the already-mentioned particularities of the different populations and measures and changes on the methodology. We did not include data about the hospital sector, below 1.5% of global consumption in our population , since tAntibiotic consumption in pediatric outpatients between 2005 and 2018 in the study region, placed in northern Spain, remained stable and was lower than consumption in the general Spanish population. The pattern of antibiotic use improved throughout the study, but some points, such as increasing the amoxicillin index or controlling consumption of some Watch antibiotics, such as azithromycin, need to be improved. There is still a lack of an optimal standardized metric for the pediatric population. The reader must take into account the different methods of measurements and major changes on the data collection methodology used by the main international consumption surveillance systems when interpreting and comparing data about antibiotic consumption.


Inappropriate antibiotic prescribing upon hospital discharge poses an increased risk of excess costs, adverse drug reactions, readmission, and resistance. Despite high rates of antibiotic prescription errors upon discharge, there is no widely accepted antimicrobial stewardship initiative to prevent such errors. This study evaluated the impact of hospital-based clinical pharmacist discharge prescription review on the appropriateness of antibiotic prescriptions. Clostridioides difficile infections, acute skin and skin structure infections (ABSSSI), or Gram-negative bacteremia between January 2019 and July 2020. The two cohorts that were studied were patients on Hospitalist services versus patients on Medicine services, in which only the Medicine services had rounding pharmacists who perform discharge prescription reviews. Outcomes included demographics, appropriateness of therapy, 30-day readmission rates, and error types in discharge prescriptions. Appropriateness of therapy was validated by evidence-based guidelines and three Infectious Diseases-trained pharmacists.This was a retrospective assessment of patients with discharge antibiotic prescriptions for treatment of pneumonia, urinary tract infections, Our study included 300 patients, 150 per cohort. Baseline characteristics were similar between groups, with the exception of increased age (p=0.025) and fewer cases of ABSSSI (p=0.001) in the Hospitalist cohort. A statistically significant higher rate of inappropriateness was seen in the Hospitalist group versus Medicine (pharmacist) group, [69/150 ]. The difference in appropriateness was mainly driven by pneumonia and UTI prescriptions. Thirty day readmission rates were 17% (26/150) for the Hospitalist cohort versus 11% (16/150) in the Medicine (pharmacist) cohort (p=0.134). The most common prescription error was the duration of therapy.Appropriateness of antibiotic discharge prescriptions significantly improved in the setting of pharmacist discharge prescription review. This initiative highlights the important role of clinical pharmacists in the setting of outpatient antimicrobial stewardship.All Authors: No reported disclosures


Based on the characterization of the bond between Fiber-Reinforced Polymer (FRP) bars and concrete, the structural behavior of cracked Glass-FRP (GFRP)-Reinforced Concrete (RC) tensile elements is studied in this paper. Simulations in which different bond-slip laws between both materials (FRP reinforcement and concrete) were used to analyze the effect of GFRP bar bond performance on the load transfer process and how it affects the load-mean strain curve, the distribution of reinforcement strain, the distribution of slip between reinforcement and concrete, and the tension stiffening effect. Additionally, a parametric study on the effect of materials  on the load-mean strain curve and the tension stiffening effect was also performed. Results from a previous experimental program, in combination with additional results obtained from Finite Element Analysis (FEA), were used to demonstrate the accuracy of the model to correctly predict the global (load-mean strain curve) and local (distribution of strains between cracks) structural behavior of the GFRP RC tensile elements. The use of Fiber-Reinforced Polymer (FRP) materials as an alternative to traditional steel reinforcement for Reinforced Concrete (RC) structures has been promoted in the last decades, especially in corrosive environments or when the effects of electromagnetic fields may be present. However, different FRP products are available in the market, whose properties may have a significant effect on the structural performance of the RC element. In particular, the relatively low modulus of elasticity when compared with steel, especially for Glass Fiber-Reinforced Polymers (GFRP), leads to larger crack widths, and serviceability requirements often govern the design of FRP RC elements .Suitable modelling of the deformational cracking and post-cracking behavior of RC elements needs to correctly account for the tension stiffening effect. Due to the interaction between reinforcement and concrete, the intact tensioned concrete between adjacent cracks is able to sustain certain level of tensile stresses, thus contributing to the stiffness of the RC element ,3,4. TheSeveral approaches exist to account for the tension stiffening effect as, for instance, the use of an effective cross-sectional area for tensile elements based on the combination of the uncracked and cracked cross-sectional area  or the aIn this paper, a comparative study about the effect of different GFRP bar types (with different bond performance) on the structural behavior of GFRP RC tensile elements is presented. To this end, a numerical model for cracked elements based on bond stress-slip behavior between materials was used, in which any experimental bond-slip law can be assumed. Previous to the study, the numerical model was validated through the comparison of numerical predictions with experimental results and FEA predictions. The study of the effect of type of GFRP bar  was thereafter followed by a parametric study on the effect of concrete grade and reinforcement ratio on the load-mean strain curve and tension stiffening effect.L, subjected to uniaxial tensile force P , ρ is the reinforcement ratio , rp is the perimeter of the embedded reinforcement, and τ(x) and s(x) are two unknown functions, which are related through the bond-slip law.For the development of the numerical model, the following assumptions were considered: (1) the elastic behavior of the reinforcing bar and concrete under serviceability conditions and (2) strains, stresses, and displacements were examined along the longitudinal direction of the composite element, and these values were assumed not to vary with the radial coordinate. Along with these assumptions, strain compatibility and equilibrium of forces at any section were also imposed, which led to the well-known differential Equation (1), where In the solution process, the definition of a bond-slip law is fundamental because it will describe the interaction between the reinforcing bar and the concrete. The capability of the numerical non-linear model to use any bond-slip law allows for its application to any type of reinforcement and, therefore, to consider the singularities of the interaction when material different to steel is used.The finite difference method was applied to solve the problem. It should be mentioned that, within the numerical procedure, cracks were assumed to appear at the halfway section between two existing cracks. Therefore, after first cracking, two new blocks with shorter length were considered, and load was increased until new cracking was attained. More details can be found in . As a reWith the aim at confirming that the numerical model was suitable for the proposed study on the structural behavior of GFRP RC tensile elements, the model was validated for this section. To this end, a comparison of predictions with experimental results and results from FEA are presented.ρ = 0.51%, 0.71%, 1.00%, and 1.69%). The ties were casted with concrete, having a target compressive strength of 50 MPa, and were 1200 mm length. The test matrix , which were thereafter modelled by using surface-to-surface contacts and connector elements, respectively. More details on the proposed methodology can be found in .Experimental results (hereinafter referred to as Exp) and numerical predictions of the FEA analysis (hereinafter referred to as FEA) were used to demonstrate the accuracy of the more simplified numerical non-linear model (hereinafter referred to as FDM) and assumptions to correctly predict the structural behavior of the GFRP RC tensile elements. Predictions of the structural behavior were checked at two levels: (1) the local level, through the comparison of the distribution of the reinforcement strain along the length of the RC tensile element at different load levels, and (2) the global level, through the comparison of the load- mean strain curves.Experimental bond-slip laws used for both the FDM model and the FEA analysis were obtained in an experimental program on pull-out tests . Bond-slThe validation through comparison of the reinforcement strain distribution obtained from the bond-slip law was only feasible in the case of the RC tensile element with three perimeter notches, where cracks were forced to appear at specific sections  in Therefore, the non-linear model (FDM) was demonstrated to be an effective tool for the analysis of the cracking process of RC tensile elements, both at the local and global levels, allowing us to include the effect of bond-slip constitutive laws. Additionally, the simpler FDM model had a reduced computational cost when compared to FEA. Besides, the tension stiffening effect (the ability of tensioned concrete between cracks to sustain a certain level of stresses) can be derived from the load-mean strain curve. This way, the FDM non-linear model was used for the next sections for studying the possible effect of the variables involved in the deformational behavior of the FRP RC tensile elements.Different types of GFRP bars exist in the market. They may differ in their mechanical properties (tensile strength and modulus of elasticity) and on the surface configuration used to provide the bond interaction with the surrounding concrete. In fact, different bond mechanisms are activated depending on the surface configuration of the reinforcing bar and on the confinement provided by concrete.As a result of the lack of standardization of the surface characteristics, several studies have been conducted in which bond behavior between GFRP bars and concrete was analyzed and different bond-slip law were reported ,12,13,14ρ = 1.69%.In this section, the effect of the bond performance of the GFRP bar on the structural response of GFRP RC tensile elements was analyzed. To this end, the FDM model was used to simulate three GFRP RC tensile elements, which differed in the type of GFRP reinforcing bar assumed. The modelled GFRP-reinforced tensile elements were 1200 mm length and had a 110 mm × 110 mm concrete section with one centered GFRP bar having a nominal diameter of 16 mm, thus giving a reinforcement ratio equal to ctmf, of 2.2 MPa and a modulus of elasticity, cmE, of 30 GPa were assumed, which corresponded to an experimental mean compressive strength, cmf, equal to 28 MPa, according to Eurocode 2 [rE equals 40.8 GPa, 60 GPa, and 46 GPa for G1, G2, and G3, respectively).Three different GFRP bars with different surface characteristics were considered: (1) GFRP bar with a helical wrapping surface and some sand coating, referred to as G1; (2) GFRP bar with a grooved surface, referred to as G2; and (3) GFRP bar with a sand-coated surface, referred to as G3 see a. Experirocode 2 . FinallyThe predicted load-mean strain curves along with the corresponding bare bar curves are presented in To further analyze the effect of the type of bar on the force transfer process, the reinforcement strain profile along half of the GFRP RC tensile element length is presented in maxs, before and after each crack formation are presented in As an additional check of the effect of the bond performance of the GFRP bar on the force transmission process, slips obtained with the numerical simulations were also analyzed. As an example, the evolution of slips along the length of the element reinforced with bar G1 before and after the second crack formation is shown in It should be mentioned that slips occurring during the crack formation stage did not exceed the slip corresponding to the bond strength . This is an indication of descending branches of the bond-slip law not being attained under service conditions.nρ value, the lower the tension stiffening effect. The Reinforcement ratio (ρ) was constant in the presented predictions. However, this was not the case for n, as the three GFRP bars considered had different modulus of elasticity . This explains the lowest and larger amounts of tension stiffening for G2 and G1, respectively.As mentioned in previous paragraphs, the tension stiffening effect was deduced from the load-mean strain curve. The tension stiffening effect derived from curves in cmf, equal to 54 MPa was assumed, which corresponded to a mean concrete tensile strength, ctmf, of 3.8 MPa and a modulus of elasticity, cmE, of 36.5 GPa, according to Eurocode 2 [In this section, the FDM model was used to analyze the possible effect of concrete strength on tension stiffening. The analysis was performed through the comparison of six numerical predictions, three of which corresponded to predictions of the previous section (with concrete C1). The three new predictions corresponded to the same geometrical characteristics but assuming a higher concrete grade . For the numerical simulations, an experimental mean compressive strength, Numerical predictions on load-mean strain curves for simulations with low concrete grade (C1) are shown in nρ value due to a larger modulus of elasticity for concrete C2 when compared to concrete C1. It can be also stated that bond performance of the reinforcing bars had no significant effect on the tension stiffening effect.The tension stiffening effect derived from load-mean strain curves presented in To better compare the effect of concrete strength on tension stiffening, and with the aim at removing any possible effect of GFRP bar surface configuration and modulus of elasticity, numerical predictions for the three different reinforcing bars are separately presented in In this section, the non-linear FDM model was used to analyze the effect of the reinforcement ratio on the tension stiffening effect. Experimental bond-slip laws, presented in ρ2 = 0.71%. Dimensions for the concrete section corresponding to ρ2 were 170 mm × 170 mm. Besides, mechanical properties for concrete were assumed to be equal to those of Predictions used for the analysis in ρ =1.69% are presented in Predictions on load-mean strain curves corresponding to specimens with a reinforcement ratio equal to 0.71% are presented in ρ = 0.71% was derived and is presented in ρ = 1.69% presented in Based on the load-mean strain curves presented in Finally, numerical predictions were analyzed to determine the effect of the reinforcement ratio on the tension stiffening effect. With the aim at having representative plots, separate subfigures are presented in Bond-slip curve of a GFRP reinforcing bar has an effect on the force transfer process taking place in the cracked RC elements  and, as a consequence, on the loads causing cracking in the crack formation stage.The lower bond strength and the initial stiffness in the bond-slip law (characteristic of bar G1) corresponded to a larger transfer length, required to fully recover the composite action between reinforcement and concrete, and a larger prediction of slips. The stiffer bond-slip law of bar G3 derived from a more efficient force transfer process (with shorter transfer length and slips).Under service conditions, the slips occurring along the RC tensile element were comparable to slips registered in the ascending branch of the bond-slip law, irrespective of the reinforcing bar.No significant effect of GFRP bar bond performance on tension stiffening effect was visible in the simulations with high concrete grade (C2), and differences appearing in the simulations with low concrete grade (C1) were attributed to changes in the modular ratio.Tension stiffening effect is proportional to concrete grade (irrespective of the GFRP embedded bar surface configuration and reinforcement ratio) and inversely proportional to reinforcement ratio (irrespective of the GFRP embedded bar surface configuration and concrete strength).The numerical model was validated at a local level  and a global level (RC tensile element load-mean strain curve), and good accuracy in its predictions was demonstrated.The effect of the bond performance between different types of GFRP reinforcement  and concrete on the deformational behavior of cracked GFRP RC tensile elements was studied in this paper. Numerical predictions of a bond-based model were used to analyze the bond transfer process and its effect on load-mean strain curve, reinforcement strain distribution, slip distribution, and tension stiffening effect. The goodness of the model to properly predict the local and global structural behavior was checked through comparison of numerical predictions with experimental results and predictions obtained with FEA. Additionally, a parametric study on the effect of concrete grade and reinforcement ratio on tension stiffening effect was performed. The following conclusions were drawn:


Several clinical studies have reported a double dissociation between abstract and concrete concepts, suggesting that they are processed by at least partly different networks in the brain. However, neuroimaging data seem not in line with neuropsychological reports. Using the ALE method, we run a meta-analysis on 32 brain-activation imaging studies that considered only nouns and verbs. Five clusters were associated with concrete words, four clusters with abstract words. When only nouns were selected three left activation clusters were found to be associated with concrete stimuli and only one with abstract nouns (left IFG). These results confirm that concrete and abstract words processing involves at least partially segregated brain areas, the IFG being relevant for abstract nouns and verbs while more posterior temporoparietal-occipital regions seem to be crucial for processing concrete words, in contrast with the neuropsychological literature that suggests a temporal anterior involvement for concrete words. We investigated the possible reasons that produce different outcomes in neuroimaging and clinical studies. This effect is known as “concreteness effect”, and it increases in aphasic patients. This is especially evident in non-fluent aphasia, for example in patients with agrammatism2, where it has been found in spontaneous speech3, reading4, writing5, repetition6, naming7, and comprehension8. Several theories12 have been proposed to explain this advantage of concrete words but they share a common feature, namely a quantitative distinction between concrete and abstract concepts, with concrete items more strongly represented than abstract ones, either because they benefit from a verbal and visuo-perceptual representation10 or thanks to a larger contextual support12 or a larger number of semantic features11. For instance, the Dual Coding Theory10 postulates that concrete concepts are supported by both perceptual and verbal representations while abstract words are based exclusively on linguistic information. From the Dual Coding Theory perspective, the advantage of concrete compared to abstract concepts is attributed to the additional contribution of the sensory-motor systems triggered by imagery-based richer representations, presumably involving both hemispheres (not only the left hemisphere) and to a greater number of units activated in the semantic system for concrete words10. The hub-and-spokes model assumes that words are processed in a neural network containing one or more amodal hubs, sensorimotor modality-specific regions, and connections between them  were the main hub, but, later on, other potential high-order and low-order hubs have been introduced 16. From the Dual Hub Theory18 perspective the ATL processes taxonomic knowledge  while the temporo-parietal areas, including the posterior middle temporal gyrus (pMTG), are involved in thematic knowledge .An advantage for concrete words as compared to abstract words has been demonstrated in a series of psycholinguistic studies. Neurologically unimpaired participants perform better on concrete than abstract words in free recall, cued recall, paired-associate learning and recognition; their reaction times in visual lexical decision are shorter with concrete than abstract words29, and group studies34, who consistently show better performance on abstract as compared to concrete words.However, these theories cannot explain the reversal of concreteness effect that has been documented in a number of brain-damaged patients, both single cases20. An alternative explanation by Crutch and Warrington35, points to a fundamental difference in the architecture of concrete and abstract word representations: the primary organization of concrete concepts is categorical, whereas abstract concepts are predominantly represented by association to other items. In this framework, a reversed concreteness effect might result from selective damage to categorical information .To account for the reversed concreteness effect, it has been proposed that abstract and concrete concepts are distinguished by the manner in which they are acquired, and by the relative weight of sensory-perceptual features in their representation29 and semantic dementia both in single cases25, and group studies34, that typically affect anterior temporal regions. These results have been confirmed in patients after left temporal pole resection33 and during direct electrical stimulation in awake surgery36. All these data seem to suggest a role of the left prefrontal cortex and the anterior temporal lobe, in processing abstract and concrete concepts, respectively. Notably, with the exception of Yi et al.’s34 and Bonner et al.’s30 studies, the reversal of concreteness effect has been found for nouns but not for verbs.The selective impairment of concrete and abstract concepts suggests different anatomical correlates. In aphasic patients, an increase of the concreteness effect has been associated to vascular damage in the territory of the left middle cerebral artery, involving the prefrontal cortex. Cases of reversed concreteness effect, in contrast, are associated to herpes simplex encephalitis37, based on 19 fMRI and PET studies, also showed an activation of the middle temporal gyrus (MTG), and, crucially, concrete concepts compared to abstract ones seem to activate the left posterior cingulate, precuneus, fusiform gyrus, parahippocampal cortex, therefore, posterior regions. However, Wang et al.37 took into consideration not only nouns and verbs, but also sentences and fixed expressions, such as idioms. Thus, we hypothesized that this incongruence between clinical and neuroimaging studies could partly depend on the use of very different type of stimuli.Neuroimaging data, however, do not totally match clinical evidence. Indeed, while the role of the left inferior frontal gyrus (IFG) for abstract words is confirmed, a previous meta-analysis39. Accordingly, we did not include studies using complex stimuli as sentences, or short stories since these publications might tap on different cognitive processes including for example attention and working memory.The present systematic review and meta-analysis aimed at addressing which regions are consistently activated across experiments that require participants to process abstract and concrete words, trying to adopt more stringent criteria considering type of stimuli and modality of presentation . The rationale of these sub-analyses is based on the fMRI literature suggesting that stimulus type, presentation modality, but also tasks could impact on the pattern of activation40 in two aspects:We exclusively selected papers that used only words stimuli and presented specific contrasts (concrete > abstract and abstract > concrete stimuli).43 (ALE) as compared to the multilevel kernel density analysis (MKDA)44 applied by Wang et al.37. MKDA and ALE produce similar results, both using the location (xyz-coordinates) of local maxima reported by the individual studies, but MKDA uses a spherical kernel whose radius is determined by the analyst45 while ALE applies a Gaussian kernel whose FWHM is empirically determined. Moreover, our analyses are conducted on the last version of the GingerAle software, which managed to rectify some of the previous limitations of this instrument, e.g., the frequently used FDR correction is no longer supported43 and proposes new best-practice ALE recommendations like the cluster-level family-wise error (FWE) corrected threshold of p < 0.0546.We used a different method, choosing the more popular Activation Likelihood EstimationConsequently, our study differs from previous meta-analysesFinally, this is also an update of the previous reviews, including publications from the last 10 years.47.The present systematic review was conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelineshttps://www.ncbi.nlm.nih.gov/pubmed), PsycARTICLES , PsycINFO (via EBSCOHost) and Web of Science (https://webofknowledge.com/). The search terms used were: (1) “semantic decision”, “semantic judgment”; “abstract words”, “concrete words “, “abstract concepts”, “concrete concepts”, “lexical decision” AND (2) “imaging”, “MRI”, “PET”. Additional sources such as reference lists of included studies and relevant systematic reviews were also checked.Our meta-analysis is based on 32 neuroimaging studies exploring the neural basis of concrete and abstract words processing, using either PET or fMRI on adult participants, published between January 1996 and February 2021. Studies were selected using four electronic databases: MEDLINE ,Whole-brain voxel-based data analyses,More than 5 participants in each study,Sample population of healthy, adult participants,Reported concrete > abstract or abstract > concrete contrast,Word stimuli,Published in English,Inclusion criteria:Region-of-interest analyses,Multiple single-case analyses,Sample population of minors,Sample population of neurological, brain-damaged, cognitively impaired or psychiatric patients,Only concrete > baseline or abstract > baseline contrasts,Articles from the gray literature ,Presentations from international meetings with no specific data provided, perspective and opinion publications, case reports, series of cases, previous reviews or meta-analyses,Studies not published in, or translated into English,Phrases or sentences stimuli,Studies without adequate information  to analyze the concrete vs. abstract contrasts and no reply from the authors after asking for the missing data.Exclusion criteria:We used a general and broad initial search. We looked for publications that reported word stimuli and concrete > abstract or abstract > concrete MRI and PET contrasts. In a second time, we distinguished the included papers taking into consideration the type of knowledge, type of task, type of stimuli, and type of investigation method. These classifications led to exploratory sub-analyses, with the purpose of controlling as much as possible confounding factors. As previously specified, we looked for publications that reported concrete > abstract words or abstract > concrete words contrast, without analyzing the exact strategies that the authors applied to divide word stimuli into the two categories. Often, the abstractness/concreteness constructs are operationalized in the papers based on two rating methods: (1) asking participants to classify a word as concrete taking into consideration the degree to which it refers to a tangible entity in the world ; (2) or by evaluating its imageability, i.e., the ease with which the word elicits a mental image. Generally speaking, words referring to something that exists in reality, and one can have an immediate experience of it through the senses are considered concrete ; while words whose meaning cannot be experienced directly but can be defined by other words, internal sensory experience, and linguistic information, are classified as abstract .49; or reported only words > baseline contrasts50. The more conservative concrete > abstract and abstract > concrete contrast (as opposed to concrete > baseline or abstract > baseline contrasts) was chosen in order to avoid a variety of baselines that could range from resting state, fixation cross51 to pseudowords52 and number or letters53 and could affect the interpretation of the results, since subtractions from different baselines create different activation patterns. We acknowledge that this type of contrast does not reveal which brain regions equally support the processing of both concrete and abstract words. The question that this meta-analysis can answer is which are the most replicated data in the literature (in terms of brain activation and words representation) when contrasting abstract and concrete words. Moreover, since concrete and abstract words can dissociate, we aimed at assessing in which anatomical correlates they differ, and not the common ones.After removing duplicates, research papers which did not satisfy the above criteria were excluded. For example, several studies focused on sentences or phrases55.If the same data were reported in different publications, we chose the most recent one and with the highest number of participantsUncertainties regarding some inclusions were solved by the authors through discussion.The PRISMA flow of information diagram was used to track the search process as presented in Fig. 56 were transformed into the MNI  stereotaxic space57 using the tal2icbm transforms implemented in the GingerALE software58.From the selected papers, only the stereotactic coordinates representing the concrete > abstract or abstract > concrete contrasts were extracted. Following this procedure, we obtained 295 foci from a total sample of 535 participants. The stereotaxic coordinates reported in terms of the Talairach and Tournoux atlasFor all the stereotaxic coordinates we extracted the relevant information about the statistical comparisons that generated them. More explicitly, we reported the MNI coordinates , the name of the first author, the journal and the year of publication of the paper, the technique (PET or fMRI) and the stereotactic space used, the age of participants, the type of task, the nature of the contrast from which the peak was extracted, the statistical thresholds, the stimulus type (nouns or verbs) and the presentation modality .43 implemented into GingerALE software Version 3.0.258 . The ALE algorithm aims to identify areas with a convergence of reported coordinates across experiments that are higher than expected from a random spatial association. The logic behind this approach implies a spatial probability distribution modeled for each activation peak included in the dataset of interest. Reported foci are treated as centers of 3D Gaussian probability distributions capturing the spatial uncertainty associated with each focus58. The between-subject variance is weighted by the number of participants per study, since larger sample sizes should provide more reliable approximations of the “true” activation effect. The voxel-by-voxel union of these distributions is used as an activation likelihood map, subsequently tested for statistical significance against randomly generated sets of foci. ALE was proven to be a reliable way of blending evidence from multiple studies43 and was used successfully in different fields e.g.,59.Once obtained the set of MNI coordinates, the meta-analyses were carried out using the revised ALE algorithmAnatomical filtering—we applied a first filtering of the coordinates using the most conservative  mask available in the GingerALE software and 17 foci from the total of 295 fell out of the mask.43;ALE maps (quantify the degree of overlap in peak activation across experiments) were calculated using the modified ALE algorithm and the random-effects modelp < 0.001 (uncorrected). In order to increase test sensitivity to false positives significance was corrected with a cluster-level family-wise error threshold of p < 0.0546 as used by other meta-analytic studies60.Thresholding procedure—for each ALE calculation described below significance was tested using 1000 permutations with a cluster forming threshold of More specifically we used the following procedure:Unfortunately, ALE cannot deal with multiple independent variables designs, and in this paper we intended to consider the role of different variables like (1) stimulus type , (2) modality of presentation , and (3) task specificity . The ALE strategy we choose in this case was to consider separate sets of foci for each variable and run one meta-analysis for each of these sets when the number of papers was large enough. To this purpose, the overall dataset was divided a-posteriori into several subsets, which automatically implied running meta-analyses on a low number of foci (lowering the power). An important limitation of this approach is that we are not able to statistically assess the interaction between variables like stimuli type and task.word processing independently of the stimulus type and taskconcrete words > abstract words included 149 stereotactic activation loci from 22 studies, 353 participants (8 foci out of mask)79;abstract words > concrete words included 146 stereotactic activation loci from 25 studies, 415 participants (9 foci out of mask)88;An analysis included the activation peaks associated with noun processing only  for a specific analysis on this type of stimuli83)concrete nouns > abstract nouns included 107 stereotactic activation loci from 15 studies (5 foci out of mask), 251 participants;abstract nouns > concrete nouns included 99 stereotactic activation loci from 18 studies (8 foci out of mask), 324 participants;An analysis with peaks associated with visually presented stimuliconcrete words > abstract words visual stimuli only included 121 stereotactic activation loci from 18 studies, 301 participantsabstract words > concrete words visual stimuli only included 135 stereotactic activation loci from 22 studies, 374 participantsAn analysis included the activation peaks associated with word processing independently of the stimulus type , but taking into consideration only The analyses were based on the following contrasts:89.(4)lexical (words or non-words classification task), or semantic decision tasks , excluding all the studies based on: memory tasks (2 studies), perceptual decision task (1 study), mental image generation (3 studies), passive reading (2 studies).concrete > abstract word  included 114 stereotactic activation loci from 16 studies, 273 participantsabstract > concrete word  included 116 stereotactic activation loci from 17 studies, 289 participantsAn analysis on peaks associated with Since only 5 studies included auditory stimuli we could not perform a specific analysis for this categoryWe explored a-posteriori the role of the (1) stimulus type (nouns), (2) modality of presentation , and (3) task specificity  in order to control as much as possible for each of these variables, i.e., to increase the results accuracy.It might be argued against the inclusion of PET and fMRI studies in the same meta-analysis due to the substantial methodological differences between the two techniques in terms of experimental design, processing, spatial localization and cluster accuracy. Because the number of studies investigating concrete vs. abstract words is small, we decided to include data from both techniques in order to increase power in the analyses. Nevertheless, in https://www.nitrc.org/projects/mricron).For anatomical labeling and figures, we capitalized on the Automatic Anatomical Labeling (AAL) template available in the MRIcron visualization Software  to meta-analytically remodel available neuroimaging data.The GingerALE procedure run over the concrete words > abstract words set of coordinates identified a total of 5 clusters, with 1–4 individual peaks each, from 4 to 11 different studies Fig. . RegionsA similar activation pattern, except for the right hemisphere involvement, was observed when only studies reporting exclusively noun stimuli were taken into consideration (concrete nouns > abstract nouns). We observed three left activation clusters Fig. , Table 3The ALE procedure run over the concrete words > abstract words, visual stimuli only set of coordinates, identified a total of 5 clusters, with 1–6 individual peaks each, from 4 to 8 different studies  were analyzed, the results indicated a single cluster with two peaks, from 9 studies, in the left inferior frontal gyrus Fig. , Table 7We identified three clusters associated with abstract words processing in a healthy population when only studies reporting abstract visual stimuli were included Fig. , from 4 When only foci from lexical and semantic tasks were analyzed, the results indicated 2 clusters , in the left inferior frontal gyrus, superior and middle temporal gyrus  verbs only, (2) other types of tasks present in the included publications like mental image generation, memory tasks, or perceptual decision task only; (3) auditory stimuli only.In Table In 38. This question becomes even more difficult when we try to separate abstract and concrete nouns, and abstract and concrete verbs . Both, Wang et al.37 and Binder et al.40 combined different types of stimuli, e.g., words, sentences, fixed expressions such as idioms, and short stories without further focusing on the stimulus type. Furthermore, since Binder et al.’s40 objective was to investigate the semantic processing in general and not concrete and abstract distinction , the activation peaks meta-analyzed were obtained from different contrasts: concrete and abstract stimuli > baseline, concrete > abstract and abstract > concrete stimuli. This choice is comprehensible given their objective but the results could be biased by the type of contrast applied; indeed, discrepancies in the patterns of cortical activation across studies may be attributable, at least in part, to differences in baseline tasks, and hence, reflect the limits of the subtractive logic.As we pointed out in the introduction, neuropsychological studies suggest a role of the lateral prefrontal cortex in processing abstract words and of the left anterior temporal lobe in processing concrete ones. These data are not confirmed by neuroimaging studies. We run a meta-analysis using more stringent criteria to assess whether imaging data can support not only this segregation but also in which components the two networks differ. There are many variables that could influence our findings concerning the neural correlates, like the type of task, type of stimuli, stimuli presentation modality. We tried to control for all these factors in order to obtain accurate results. Since the number of studies was limited, we could not analyze data according to type of task , but at least we excluded those studies without a semantic or lexical decision task. The task performed during fMRI scan is particularly relevant because the activation observed during passively hearing/reading words might be very different from the one observed during semantic judgments for concrete vs. abstract . Regarding the stimulus type, there is an ongoing debate concerning nouns vs. verbs in general90, in order to have a separate dataset with this type of methods. Unfortunately, we found a very small number of publications preventing a further meta-analytic procedure92.Thirty-two imaging studies were included, which evaluated the activation patterns in response to concrete and abstract concepts. All the data included in the ALEanalysis are based on general linear model, GLM. We also looked for studies that used the more modern multivariate pattern analysis, i.e., a set of methods that analyze neural responses as patterns of activity40, confirmed that concrete and abstract words processing relies, at least in part, on different brain regions. Based on the currently available data we could not investigate the existence of overlapping networks between concrete and abstract words. The ALE procedure was completely data-driven, without a prior theoretical basis, and the results are constrained only by the nature of our data , and by our inclusion/exclusion criteria.The results of this meta-analysis, consistent with those of previous ones40 found significant overlapping for concrete stimuli in the angular gyrus bilaterally, left mid-fusiform gyrus, left posterior cingulate, and left dorsomedial prefrontal cortex (DMPFC). With the exception of DMPFC that might be related to the stimuli complexity and/or different baselines, all the other regions are confirmed by our data. At variance with Wang et al.’s meta-analysis37 we found a bilateral involvement of the posterior cingulate cortex (PCC), angular and precuneus gyri. Although involved in many semantic-based tasks, the function of the PCC in semantic cognition is still debated. The following hypothesis are proposed: (1) this region could act as a supramodal convergence zone40, (2) PCC activation could reflect the greater engagement of an imagery-based perceptual system for concrete stimuli, or (3) PCC might be an interface between semantic knowledge and episodic memory91. The precuneus also seems associated with visuospatial imagery, a hypothesis supported by experiments conducted on episodic memory retrieval and linguistic tasks which required the processing of high imagery words or mental image generation83. The same regions were found when only nouns were considered (concrete nouns > abstract nouns contrast) with the difference that the right hemisphere activation disappeared. The two right hemisphere clusters might be specifically correlated with action verbs but this result could also be a consequence of the lack of power due to the limited number of studies (15 studies in the nouns dataset vs. 22 in the noun-and-verb database).As previously mentioned, experiments testing for greater activation for concrete than abstract words (concrete words > abstract words) converge in the temporo-parieto-occipital regions; namely, the left middle temporal gyrus, left fusiform, left parahippocampal and lingual gyri, bilateral angular gyrus and precuneus, bilateral posterior cingulate, left superior occipital gyrus and left culmen in the cerebellum. The neuroimaging evidence indicates that concrete concept processing is at least partly associated to the perceptual system, and also rely on mental imagery . Binder et al.37 and Binder et al.40; higher activation for abstract compared to concrete words conditions (abstract words > concrete words) is more frequently reported in a left lateralized network, encompassing the inferior frontal gyrus , a very small portion of the precentral gyrus, the superior and middle temporal gyri, and inferior parietal. They are also in line with the results observed in brain-damaged patients.The results on abstract words replicated those reported by Wang and colleagues93. Step 1 constitutes controlled access to stored representations when bottom-up input is not sufficient. Step 2 operates at post-retrieval and is thought to bias competition among representations that have been activated during Step 1. According to Badre and Wagner94, both steps recruit VLPFC, though different parts of it, with BA 45 involved in Step 2. In other words, IFG activation could reflect a higher level of semantic control processes  since abstract stimuli might require semantic selection, irrelevant cues inhibition, effortful integration, top-down control and working-memory related processes95, in agreement with the context availability theory96. In line with this hypothesis, this region showed greater activation for abstract words when a judgment task was performed following irrelevant cues and reduced activation when semantic decisions were made with contextual help, supporting the idea that this area responds more strongly to abstract words because their meanings are inherently more variable and require more control during linguistic processing as compared to the concrete ones97. An alternative explanation is offered by Della Rosa98 using a lexical decision task; they found that the left IFG was particularly active during presentation of words characterized by low imageability and low context availability. The authors’ interpretation was that this area could be a functional convergence zone between imageability and context availability, differentiating abstract from concrete concepts.It has been suggested that the ventrolateral prefrontal cortex (VLPFC) implements semantic control in two stepsIn neuroimaging studies, besides the IFG, additional clusters were found in the left superior and middle temporal lobe. However, when only nouns were considered (and not verbs), these clusters lost significance, supporting the idea that the cerebral networks deputed to noun and verb processing might be slightly different.33.On the other side, results on concrete words do not support neuropsychological data. Indeed, apart from several single case reports, a study comparing the behavioral variant of frontotemporal dementia (FTD), in which there is a predominant prefrontal atrophy, to the semantic variant, with anterior temporal atrophy showed that while the former group had an increase of the concreteness effect, the reversal was found in the semantic variant group. Similarly, patients with left Anterior Temporal Lobe (ATL) resection show the same pattern of reversal concreteness effect36, for example, using direct electrical stimulation (DES) for brain mapping during awake surgery found no behavioral differences between BA 44 and BA 38 stimulation while patients performed a lexical decision task, but they registered a dissociation between abstract and concrete words during a concreteness judgment task; in particular, abstracts words were impaired during stimulation of BA 44 and concrete words during BA 38 stimulation.One possibility of this inconsistent results is the type of task; the neuroimaging studies used pleasantness judgments, memory tasks, lexical decision, etc. while, in general, patients are examined by means of naming and comprehension tasks and, occasionally, also semantic judgments. Orena et al.74] were presented while in other studies, only four words were repeated for more than 140 trials78. Moreover, selected stimuli greatly varied among studies encompassing emotions, mind states, living and nonliving things, of different frequency of use, age of acquisition and imageability. In addition, many studies used interchangeably “concreteness” and “imageability” , which are in fact two distinct properties that can differently affect naming and recall101.Neuroimaging studies are often hard to compare, and many variables could influence the reported results as the duration of the stimuli presentation, stimuli number, stimulus types. For example, in the same type of experiment a large number of stimuli [e.g., 164 nounsWe also controlled for presentation modality. When only visually presented words were included in the analysis no relevant differences were observed between auditory and visual stimuli combined, and only visually presented words  concrete nouns > abstract nouns, only 15 independent experiments, and (2) lexical and semantical task—concrete words > abstract words, 16 studies. This indicates that, in these two cases, we cannot properly control the influence of individual experiments and that we might have failed to detect small effects. Another limitation is related to the sample size of the included experiments that ranged from 6 to 28 participants. We acknowledge the need to consider only well-designed and controlled studies but taking into account the limited number of papers we were forced to include data from studies with uncorrected p values , we observed activation patterns in areas considered neural crossroads of the semantic network like the posterior cingulate region, the anterior temporal lobe, and the left inferior frontal gyrus103 , but these data cannot be interpreted in the frame of this theoretical model.Considering the main question, we can confirm that concrete and abstract words involve at least partially segregated brain areas, the IFG being relevant for abstract nouns and verbs; in contrast, we could not find evidence of the ATL involvement for concrete items. Our data indicate a more posterior activation for concrete words in regions that are often correlated with mental imagery processes. This meta-analysis seems to support the hypothesis that abstract and concrete words have partly separate neural correlates but the specific features that differentiate between these two classes of stimuli are still open to discussion. The cortical regions that are commonly activated in imaging studies investigating concrete and abstract words seem more congruent with the Dual Coding TheoryThe lack of converging evidence from clinical neuropsychological and neuroimaging data might be explained by several variables like task and stimuli type, differences in terms of age and brain plasticity between the two populations (young vs. elderly people), etc. These discrepancies deserve further investigation, for example by means of balanced groups of healthy and clinical participants, combining different techniques in the same experiment as TMS-EEG, or TMS and fMRI.Supplementary Information.