Embedding this multi-element sensor in concrete enables the real-time and non-destructive monitoring of internal electrical resistivity, free Cl− (Clf) contents in the concrete pore solution at different depths, and steel corrosion parameters. Based on the monitoring data obtained by the multi-element sensor, the freezing-thawing (F-T) damage degree, the Clf diffusion coefficient, the quantitative relation between F-T damage degree and Clf diffusion coefficient, the initiation period of steel corrosion, and the critical content related to steel corrosion are determined. To conclude, the multi-element sensor provides key durability parameters for the establishment of the Clf diffusion model, the assessment of health condition, and the prediction of service life of concrete under the coexistence of the F-T cycle and Cl−.A design scheme of multi-element sensor which included electrical resistivity probes, multiple Cl Reinforld value . The sinresearch ,4. Howevl− works ,6,7. Speon depth ,9 in conon depth . The pre− induced steel corrosion. However, the reliability of monitoring steel corrosion parameters using embeddable Ag/AgCl reference electrode in concrete still needs to be confirmed in the condition of F-T cycle.On-demand maintenance of concrete structures ensures construction safety, prolongs the service life, and avoids further financial loss. For a scheduled and preventive maintenance program in concrete structure, the continuous and in-situ monitoring of parameters related to concrete durability is crucial ,12,13. R− content in concrete such as potentiometric measurement, electrical resistivity, impedance analysis, fiber optic sensor, laser breakdown spectroscopy, nuclear magnetic resonance, and X-ray diffraction analysis. However, most of them were limited to be used in the laboratory and unable to provide accurate information about the free Cl− (Clf) content in pore solution of concrete. Compared to other techniques, the potentiometric technique such as Ag/AgCl sensor is more appropriate conduct non-destructive and in-situ measurement of Clf concentration due to these advantages such as accuracy and simplicity [f concentration in simulated pore solution and mortar specimens. Elsener et al. [f concentration in synthetic concrete pore solution followed Nernst law. Furthermore, the Clf content determined by the Ag/AgCl sensor correlated well with that by pore solution expression. Angst et al. [f profiles and concluded that the Clf diffusion in mortar specimens followed the Fick’s law. Although a large amount of research has applied this type of potentiometric sensor to monitor the Clf content in mortar paste and concrete, determining the critical Cl− content of steel corrosion in concrete as an expression of Clf is scare. The critical Clf value related to the initiation of steel corrosion in concrete could be obtained by simultaneously monitoring the steel corrosion parameters and Clf content in the vicinity of steel in concrete using the embeddable reference electrode and Ag/AgCl sensor.Refs ,22 reviemplicity . As earlmplicity  and Climmplicity  reportedr et al.  found out et al.  suggestet et al.  have embFor concrete structures in the cold region, a freezing-thawing (F-T) cycle is usually the primary cause of the deterioration of concrete. Currently, widely used methods of characterizing the damage degree of concrete caused by F-T cycle are indirect techniques such as dynamic elastic modulus , mechanif content in concrete pore solution and F-T damage degree of concrete. This paper aims to provide a design method of multi-element sensor which includes electrical resistivity probes, multiple Cl− selective electrodes, a carbon steel electrode, an embedded solid reference electrode, and a counter electrode. Then, embedding the multi-element sensor in concrete to monitor the internal electrical resistivity and Clf contents at different depths of concrete and corrosion potential as well as corrosion rate of steel in concrete. As a result, parameters closely related to concrete durability, such as F-T damage degree, Clf diffusion coefficient, and threshold value of steel corrosion were determined. This provides an essential reference for the prediction of the residual service life of a concrete structure, especially in a coexisting environment of F-T cycle and Cl−.Currently, there lacks a multifunctional sensor to simultaneously detect corrosion condition of steel and Cl− selective electrodes, a carbon steel (working electrode), a solid Ag/AgCl reference electrode and a stainless-steel electrode (counter electrode). − selective electrodes with different lengths and a solid Ag/AgCl reference electrode containing saturated KCl gel electrolyte were inserted into corresponding holes  f content in concrete was monitored through the measurement of Cl− selective electrode potential because there existed a linear response between the logarithmic value of Clf content in pore solution and Cl− selective electrode potential. The potential of the Cl− selective electrode was directly recorded using the voltmeter with respect to the embedded reference electrode. Based on our previous research [− selective electrode potential and Clf content depended on the alkalinity of pore solution and therefore three rules were set in advance for calculating Clf content using electrode potential: (1) the response equation at pH of 13.5 was used once the pH of pore solution exceeded 13, (2) the equation at pH value of 12.5 was used when the pH value of pore solution was between 11 and 13, and (3) the equation at pH of 10 was used when the pH of pore solution was lower than 11.Clresearch , the res− selective electrode (distance <2 mm) was determined using the solid-liquid extraction method. Firstly, concrete power (excluding coarse aggregate) around Cl− selective electrode (distance <2 mm) was collected, ground, and then passed through a 0.16-mm sieve. Subsequently, 1 g of powder was soaked in 10 g of deionized water and the mixture was stood for 24 h after a powerful stirring. Then, the mixture was filtered, and the pH of filtrate was recorded by pH meter.The pH of concrete powder around ClI, approximately 0.5 mA) and potential difference (ΔV) between the other two electrodes (No. 3 and 4 in GF) [4 in GF) , as exprThe potential of carbon steel electrode was measured against the reference electrode using a voltmeter. In addition, the electrochemical impedance spectroscopy (EIS) measurement was performed by a three-electrode system in the frequency between 100 kHz and 0.1 Hz using a potentiostat .Ordinary Portland cement and grade II fly ash were used and their oxide compositions are listed in The 100 × 100 × 400 mm rectangular concrete specimens were casted. During the casting, the multielement sensor was placed in concrete and the diagram of concrete specimen containing sensor is indicated in After 28-day curing, concrete was subjected to the “rapid F/T testing method” introduced in the Chinese standard GB/T 50082–2009 . Firstly− selective electrode potential was measured vs. solid Ag/AgCl reference electrode and recorded in a total immersion period of 36 weeks. In addition, half-cell potential and electrochemical impedance spectroscopy of carbon steel were also operated during the immersion. 5 concrete specimens were used to obtain the average results.After exposure to 1, 25, 75, and 125 F-T cycles, five faces of concrete specimens were totally covered with epoxy resin and leaving one of side faces unsealed. Then concrete was soaked in 1 mol/L NaCl solution which was updated every two weeks. The ClThe electrical resistivity results indicate that the electrical resistivity of concrete at the end of the thawing stage decreases with F-T cycle. According to ref , the eleor” (FF) . The F-Tor” (FF)  and connor” (FF) : the morThe relative dynamic modulus of concrete has been widely used to characterize the F-T damage degree ,48 and r− selective electrode is converted to the potential versus SCE to directly calculate Clf content because in the authors’ previous research [− selective electrode versus SCE is applied to describe the quantitative relation between electrode potential and Clf content. − selective electrode potential at different immersion periods after F-T cycles. Electrode potential increases with the increasing depth and decreases with the immersion time and F-T cycle. This is dependent on the Clf content in concrete pore solution.The potential of Clresearch  the potef content at different depths of concrete after F-T cycle. The Clf content in concrete decreases with increasing depth from the exposed surface and increases with immersion time, this is attributed to the penetration of Clf from the external Cl− source solution to internal concrete. After same immersion period, Clf content in same distance from the exposed surface increases with the increasing F-T cycle, meaning that damage on concrete caused by F-T cycle accelerates the Clf diffusion in concrete. In addition, the distribution of Clf content in concrete follows Fick’s second law [f, f content , f content in concrete,f concentration acting as a function of Therefore, cond law ,50, as ef diffusion coefficient in concrete using Equation (5). The corresponding fitting results of Clf diffusion coefficient are summarized in f diffusion coefficient but the increasing degree on the diffusion coefficient depends on the concrete mixture. After exposure to small number of F-T cycles, concrete added with fly ash has significantly lower Clf diffusion coefficient than plain cement concrete and thereby fly ash improves the concrete resistance to Clf ingress because of the modification on concrete microstructure by fly ash [− [f diffusion coefficient than plain cement concrete and therefore air entraining agent weakens the concrete resistance to Clf penetration, which is possibly ascribed to the increase in the total porosity [f diffusion coefficient than both plain cement concrete and concrete added with fly ash, indicating F-T cycle has smaller effect on the resistance of concrete with air entraining agent to Cl− ingress but has profound effect on the resistance of concrete with fly ash to Cl− penetration. Concrete with joint addition of fly ash and air entraining agent keeps comparatively lower Clf diffusion coefficient after exposure to whether small or large amount of F-T cycles. Therefore, the simultaneous addition of fly ash and air entraining agent is an effective way of ensuring the considerable anti-chloride performance of concrete, whether in a light or severe F-T damage environment. fly ash ,52 and iy ash [− ; howeverporosity . After af diffusion coefficient, first of all, a definition of the change in Clf diffusion rate :t means the immersion period and m means the time-dependent reduction coefficient, f diffusion coefficient at immersion period (t), f diffusion coefficient at As shown in d. Refs. ,55 suggef diffusion coefficient while air entraining agent accelerates the decreasing rate of Clf diffusion coefficient. In addition, the F-T cycle reduces the time-dependent reduction coefficient and therefore the Clf diffusion coefficient in concrete suffering from F-T damage decreases more quickly compared with concrete suffered from no damage. The change in the time-dependent reduction coefficient :ve state , and ico2. The initiation of steel corrosion is also highlighted in  to refs ,62,63, sf content around steel and corrosion rate of steel. Thus, the critical content related to the initiation of steel corrosion in concrete could be determined. f content. The addition of fly ash decreases the critical content value, but air entraining agent slightly increases the critical content. Furthermore, the alkaline in concrete affects the corrosion initiation of steel [f content to the alkaline content of concrete (in term of Clf/OH−). The OH− concentration is directly calculated based on the pH value of concrete powder using the solid liquid extraction method [f/OH−) of steel in concrete with air entraining agent is slightly higher but the same value in concrete added with fly ash is four times higher than plain concrete. In addition, the critical content (expressed as Clf/OH−) of steel in concrete with joint addition of fly ash and air entraining agent is seven times as high as the plain concrete. From the viewpoint of Clf/OH−, concrete supplemented with fly ash and air entraining agent has the best anti-corrosion performance.The multi-element sensor enables the simultaneous monitoring of Clof steel  and the n method . From th− content, in terms of different forms, related to steel corrosion in simulating concrete pore solution and cement-based materials obtained using various corrosion detection techniques. Specifically, there exists large scatter in the summarized critical Cl− contents of steel corrosion in cement-based materials due to the differences in experimental design such as composition of mixture, steel condition, inhomogeneity of mortar or concrete samples and corrosion detection methods. A recent research released by Isgor et al. [f content in concrete pore solution by which critical Clf content related to the occurrence of steel corrosion in concrete could be directly determined. To sum up, the multi-element sensor continuously monitors the durability parameters of reinforced concrete and thereby provides data support for the evaluation of service condition and prediction of residual life. On the other hand, the multi-element sensor has the potential to be regarded as a standardized testing instrument for the corrosion detection in laboratory and field studies.These literature ,65,66 rer et al.  highligh− selective electrodes, a carbon steel, an embedded reference electrode and a counter electrode. Embedding this sensor into concrete enables continuous and non-destructive monitoring of durability parameters of concrete, such as F-T damage degree, Cl− contents, and steel corrosion parameters. The F-T damage degree is evaluated using the variation of electrical resistivity of internal concrete: when the decreasing ratio of electrical resistivity is lower than 10%, concrete is in slight deterioration state. When the decreasing ratio of electrical resistivity is between 10% and 45%, concrete is in medium deterioration state. When the decreasing ratio of electrical resistivity is higher than 45%, concrete is in severe deterioration state. In addition, the apparent Clf diffusion coefficient and time-dependent reduction coefficient are determined by fitting the Clf contents at different depths in concrete using Fick’s second law. There exists an exponent relation between the change in Clf diffusion rate and the F-T damage degree and a linear relation between the change in the time-dependent reduction coefficient and the F-T damage degree. Moreover, the corrosion parameters of steel, such as potential and current density, are also directly measured using the multi-element sensor. The critical Clf content related to the onset of steel corrosion is obtained by combining the Clf content results and the determination of de-passivation period. Hence, the multi-element sensor provides key durability parameters for the establishment of a Cl− diffusion model, the health risk assessment, and the residual service life prediction of concrete under the F-T cycle and Cl− coexistence.This paper introduces a design scheme of multi-element sensor including electrical resistivity probes, multiple Cl− penetration. On the contrary, the addition of fly ash improves the concrete resistance to Cl− ingress but weakens the resistance to F-T damage. However, the joint addition of air entraining agent and fly ash ensures adequate resistance of concrete to both F-T deterioration and Cl− penetration, and thereby the simultaneous addition of air entraining agent and fly ash is an effective way of improving the durability of reinforced concrete structure located in coexisting F-T and Cl− environments.The addition of air entraining agent improves concrete resistance to F-T damage but weakens the resistance to Cl


An externally bonded fiber reinforced polymer (FRP) plate (or sheet) is now widely used in strengthening bending members due to its outstanding properties, such as a high strength to weight ratio, easy operating, corrosion and fatigue resistance. However, the concrete member strengthened by this technology may have a problem with the adhesion between FRP and concrete. This kind of debonding failure can be broadly classified into two modes: (a) plate end debonding at or near the plate end, and (b) intermediate crack-induced debonding (intermediate crack-induced (IC) debonding) near the loading point. The IC debonding, unlike the plate end debonding, still needs a large amount of investigation work, especially for the interface under fatigue load. In this paper, ten single shear pull-out tests were carried out under a static or fatigue load. Different load ranges and load levels were considered, and the debonding growth process was carefully recorded. The experimental results indicate that the load range is one of the main parameters, which determines the debonding growth rate. Moreover, the load level can also play an important role when loaded with the same load range. Finally, a new prediction model of the fatigue debonding growth rate was proposed, and has an excellent agreement with the experimental results. During these few decades, the carbon fiber reinforced polymer (CFRP) stood out from many strengthening materials for its numerous advantages, such as a high strength to weight ratio, corrosion and fatigue resistance ,2,3,4,5.Based on previous research, by using of externally bonded FRP plate, several premature debonding failures ,17,18,19Pmin (lower limit of fatigue load) influenced the fatigue life even the interfaces were loaded under the same load range. Bond joints loaded with Pmin = 0 had a greater fatigue life than those with Pmin ≠ 0. Finally, an S-N (stress level - fatigue life) curve was proposed. Dial et al. [da/dN (the length of debonding growth per cycle) suggested that da/dN can be determined by the fracture energy ratio, the fatigue load frequency and the debond length that has already developed. Carloni et al. [At present, a large amount of studies have been concentrating on the FRP–concrete interface under static load ,33, but l et al.  presentei et al.  applied i et al.  predictii et al.  tested F(1)To study the load capacity, the stress transfer length and failure mode of the FRP–concrete interface under a monotonic load;(2)To investigate the behavior and failure mode of the FRP–concrete interface under fatigue loads with different fatigue load ranges and load levels;(3)To define the rate of the debonding growth along the FRP–concrete interface under fatigue loads with different loading parameters;(4)To propose a prediction model, which can correctly describe this fatigue debonding growth rate.The main objectives of this study are:Ten single shear pull-out tests were conducted under monotonic or fatigue loadings. Specimens were made of concrete substrate bonded with unidirectional CFRP plate. The FRP concrete interface was loaded statically to failure to define the load capacity, in order to determine the following fatigue loadings. The fatigue tests consisted of groups with different load ranges and load levels. The upper limits of the fatigue load ranged from 60% to 80% of the ultimate load obtained from static tests and the lower limits varied as well. All fatigue loadings were at a frequency of 5 Hz. Experimental program is summarized in Smin = Pmin/Pu is the relative lower limit of fatigue load; Smax = Pmax/Pu is the relative upper limit of fatigue load; ΔS = (Smax − Smin )/2 and Smax + Smin )/2 are the relative load range and relative load level of the fatigue load; Pmin and Pmax are the lower and upper limit of applied fatigue load, respectively; Pu is the load capacity of the FRP–concrete interface obtained from static tests. From FT-1 to FT-5, the upper limits of the fatigue tests vary from 0.6 to 0.8 Pu, and the lower limits stay the same. FT-6 shares the same load range with FT-1, but higher load level. FT-7 and FT-4 also have the same load range but different load levels. FT-6 and FT-4 have the same upper limit of the fatigue load but FT-6 has higher lower limit.In 2 [The details of the tested specimen are shown in 2 .The surface preparation of concrete substrate consisted of two major steps, which were grinding and cleaning. First, the surface was grinded to certain depth by an abrasive dry grinder to expose most of the aggregates. This step was intended to remove the laitance on the top of concrete substrate, which would result in weak bonding between CFRP and concrete. Secondly, the grinded surface was cleaned by a brush and vacuum cleaner and wiped several times by alcohol pads to remove dust and particles. The photos of the surface preparation process and the comparison of the concrete surface before and after grinding were shown in The adhesive used in this work was provided by Nanjing Hitech Composites Co. Ltd.  and the type of the adhesive was Lica-131 A/B. The bond process was carried out after the concrete surface becoming totally dried. The mixture proportions by weight of the epoxy resin adhesive were epoxy resin: epoxy hardener = 2:1. The physical properties of the adhesive were listed in All the tests were performed under a typical single shear pull-out test configuration as shown in The CFRP plate was clamped by the upper hydraulic clip. When loaded, stress would gradually transfer from the CFRP plate to the concrete substrate through the FRP–concrete interface. The specimens (CFRP attached concrete blocks) were carefully placed before testing to ensure the upper clip, the CFRP plate and the gripping plate were along the same axis, so that the loaded system could be steady during static and fatigue tests. In addition, a 20 mm thick steel plate was inserted between the top of the concrete block and the steel rig, so that shear crack could develop in the concrete block.Longitudinal strain distribution of the CFRP plate was measured by densely installed strain gauges. Thirty-one strain gauges were mounted along the CFRP fiber direction, twenty-one of which were installed along the central axis and ten were transversely mounted to study the stain distribution along the plate width direction. The detail of strain gauges arrangement was shown in The relative slip between FRP and the concrete block was measured by the dial gauge. In this study, the relative slip was defined as the displacement between the aluminum plate  and a fixed base as shown in Three specimens MT-1, MT-2 and MT-3 were tested under monotonic loading up to failure. All the specimens were loaded at a constant rate equal to 0.005 mm/s (stroke rate of the upper clip of the servo-hydraulic testing machine) until the failure occurred. Relative slip between the concrete substrate and the CFRP plate was measured throughout each test. Pu, of the joints were listed in All the FRP–concrete joints expressed the same failure mode: debonding of the CFRP plate with a few millimeters thick of concrete attached on it, as shown in It is worthy to mention that, the ultimate load of the bond joint may not be reached at the first peak point, in another word, the applied load could still increase after a short decreasing portion of the load–slip curve. This is because the quality of the bond joint is inconsistent along the entire length of the joint. Furthermore, load capacity of the FRP–concrete interface mainly depends on the bond quality within the effective bond length ,13,16. SAs shown in The strain distribution curve at points before the peak load can be divided into two segments: the stress transfer segment with a high strain gradient and the low stress segment, which was almost parallel to the X-axle. Tensile stress on the CFRP plate gradually transfers to the concrete substrate through the interface. With the increasing load applied to the CFRP plate, the length of this portion extended and strain kept rising until the ultimate load was reached. At the peak point (Point D), the stress transfer length (210 mm) stayed constant and equaled the effective bond length referring to Chen and Teng strength model . After tSeven single shear pull-out tests were conducted under constant amplitude fatigue loading. These tests were designed to investigate the debonding propagation along the FRP–concrete interface under fatigue loading. In order to record relatively accurate debond length, attentive visual check during the test and strain profile analysis after the test were used and mutually proofread.Pmax) and a minimum load (Pmin), where Pmax and Pmin corresponded to certain percentages of the average ultimate load (Pu) obtained from the monotonic tests. In a typical fatigue test, the specimen was loaded to the mean value of the cyclic load range at a rate of 0.05 kN/s, then the cyclic load was performed at 5 Hz until a certain cyclic number was reached or failure occurred.Cyclic loading was performed between a maximum load  propagation between the CFRP plate and concrete substrate up to a sudden explosive separation of the last bond joint, which was too short to carry the applied load. The results of all the tests were reported in fN > 1000 were plotted. The decreasing in the slope of load–slip response was noticeable with the number of cycles, indicating the reduction in the bond stiffness between CFRP plate and concrete. The bond stiffness was the overall behavior of the bond joint, reduction in which implied greater deformation of unconstrained CFRP plate generated, in other words, debonding has already formed in the joint.In The secant bond stiffness corresponding to normalized fatigue cycles was plotted in It is worth noticing that the bond stiffness mentioned above was the overall performance of the bond joint. The slip between the CFRP plate and concrete substrate at the aluminum plate level consisted of tensile deformation of the debonded CFRP plate and the remaining bond joint, hence the actual bond stiffness of the joint was higher than the stiffness calculated in the tests. However, the bond stiffness obtained by the slope of the load–slip curve was much easier to get and has more extensive practical usage.fN > 1000 under Pmax at different loading cycles were presented. The evolution of the strain profile with increasing cyclic number in the fatigue test was very similar with the one with increasing load in the static test. The strain distribution could also be divided into three segments: the fully debonded segment, the stress transfer segment and the low stress segment. The fully debonded segment, started from loaded end of CFRP plate, would not be found during the early stage of fatigue tests but then formed and extended after certain cycles.In Typically, at the first cycle, the strain on the FRP plate decreased very quickly. This is because the FRP–concrete interface was intact, the stress on the FRP plate can transfer into the concrete through the interface within a relatively short distance. The lengths of this stress transfer segments in fatigue tests were slightly shorter than the ones obtained from static tests. This difference could be mainly attributed to the much lower load applied in fatigue tests, therefore a full length of the effective bond region  cannot bThen with the increasing cycles, the strain on the FRP close to the load end would keep a higher level, which implied the debonding of the FRP plate. FT-4 as an example, the four curves show the strain profile on the FRP plate at the 1st, 1000th, 2000th and 5000th cycles, respectively. The first curve (black) expresses a sharp decreasing of the FRP strain, which implies no debonding occurred. The second curve (red) shows a short platform, which implies no stress transfer between FRP and concrete within this length. Combined with direct observation of the specimen, the length of this platform could be used to determine the debond length. As cycle numbers increased, the platform kept growing, which implies the growing of the debond length. However, the platform shows a downward trend at the 2000th (blue) and 5000th (pink) cycles. This is resulted from the friction between the debonded FRP plate and concrete, the friction would become more obvious as the length of debond increases.By using this method, the debond length of each specimen at each cycle could be determined. The debond length and the debonding growth rate will be discussed in the next section.From analyzing the strain profile in Pmax led to more rapid debonding growth at the first stage, after which, debonding growth apparently slowed down. Debonding growth rate da/dN was defined as the entire debond length (a) at the last check cycle over total fatigue cycles (N) before the last check [da/dN with the range of stress intensity ΔK (corresponding to stress range) at the tip of a crack. The basic expression of the Paris law was shown below:m and n are constants which can be obtained via experiments.As shown in st check . An incrst check , which rβ, was taken into account, which intended to involve the influence of the increasing debond length on the debond rate. The effect of fatigue loading frequency was also considered in the study. The final equation of debonding growth rate was given by:m1 and n1 were parameters obtained from the linear regression of the experimental results.Diab et al.  presentsCarloni et al.  providedm and n were parameters obtained via experiments.In order to reveal the relationship between the debonding growth rate and determinant parameters in fatigue tests of a certain FRP–concrete interface, a new prediction model was proposed in this paper. This new model was also based on Paris Law  and tookm and n equaling 1 × 109.3 and 11.3276, respectively. The equation fits very closely to the experimental results.Pu, and the upper limit were respectively the same as FT-4 and FT-5, which were 0.7 Pu and 0.8 Pu. As shown in It should be noted that, referring to previous research, the parameters probably are affected by the lower limit of fatigue loading . The dot(1)The failure modes of the FRP–concrete interface were the same whether under monotonic or fatigue load, both of which were debonding of CFRP plate with a thin layer of concrete attached on it;(2)The proposed prediction model relates the fatigue debonding growth rate in FRP–concrete interface to the parameters, which can be easily obtained before the fatigue tests, such as the relative load range and load level, and shows an excellent agreement with the experimental results;(3)The debond growth rate could be mainly affected by the fatigue load range and fatigue load level;(4)A greater fatigue load range and higher fatigue load level could lead to a more rapid debond growth rate and lower fatigue life of the bond joint;(5)Friction between the debonded FRP and the concrete substrate could play an important role in the fatigue behavior of the interface as debond propagating;(6)Further studies are needed to reveal the influence of FRP stiffness, load frequency, adhesive properties and other possible factors.In this paper, the main aim was to investigate the debond initiating and propagating process along the FRP–concrete interface under fatigue load. In order to analyze the debond length, the strain profile on the CFRP plate was recorded throughout the whole loading process at different check cycles. Moreover, visual observation was also adopted to define the actual debonding growth situation. Furthermore, a new prediction model of the debonding growth rate was proposed and had excellent agreement with the experimental results obtained from the fatigue tests in this work. Several conclusions can be obtained as follow:


The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. This is the third chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2The chapter features the pharmacokinetic and pharmacodynamics properties of the most frequently used antiinfective agents. In addition to the antimicrobial properties (pharmacodynamics) of a substance, the pharmacokinetic properties, i.e. the behavior in an organism, play a decisive role. Ultimately the question is whether the concentrations at the site of action are sufficient to inhibit the pathogens, kill them and possibly prevent the development of resistant pathogens. Adverse drug reactions and interactions should be minimized.For the purpose of predicting efficacy, one speaks of PK/PD (pharmacokinetics/pharmacodynamics) when pharmacokinetic parameters or, in the simplest case, plasma and tissue concentrations are associated with the antimicrobial properties in vitro or in vivo.Pharmacokinetic properties of drugs are determined by their physicochemical characteristics. The acid or base strength of a substance, its lipophilicity or hydrophilicity determine how the substance behaves under the physiological conditions of an organism. For example beta-lactam antibiotics and aminoglycosides are poor at penetrating membranes and therefore are located mainly in the extracellular space. An overview of pharmacokinetic parameters of individual substance groups is shown in Table 1 An important pharmacokinetic parameter that describes the distribution of the drug in the body is the volume of distribution. Lipophilic substances, which can easily pass through membranes, are passively taken up intracellularly. Their volume of distribution is therefore high; with fluoroquinolones and macrolides it can be a multiple of the body volume. Substances with large volumes of distribution have lower plasma and interstitial levels but high intracellular concentrations. Water-soluble substances, on the other hand, penetrate cell membranes with difficulty and therefore mainly remain in the plasma and interstitium. Most pathogens are located in the interstitium, so concentration in these cases is crucial.An important aspect of drug distribution is protein binding in serum. Depending on their physicochemical properties, antibiotics mainly bind to albumin. Concentration-dependent binding is reversible. There is a dynamic balance between the free and the bound portion. In general, only the free, non protein-bound portion of an antibiotic is responsible for its action. As demonstrated for some antibiotics, high protein binding need not adversely affect the efficacy of a substance as long as there are sufficiently high unbound concentrations at the site of action. Clinical studies that appear to demonstrate a negative influence of protein binding were often performed with low total doses , 2], , . De. De6]. Dmax) to the minimal inhibitory concentration (MIC) of the pathogen correlates with treatment success. For beta-lactam antibiotics, on the other hand, it is the percentage of the dosing interval in which the plasma concentration is above the pathogen MIC (t>MIC or %t>MIC). For fluoroquinolones and cyclic lipopeptides (daptomycin), the quotient of AUC (area under the curve) and MIC are considered predictive (the area under the 24-hour concentration time curve relative to the MIC: AUC24/MIC). This also applies to the group of glycopeptides. Previous findings on oxazolidinones  indicate that both concentration and duration of exposure are relevant. The validation of these models for humans has been shown for some antibiotic groups.The differences in the pharmacodynamic profile of the antibiotic groups are also explained by their different modes of action – concentration-dependent effect of fluoroquinolones, aminoglycosides, tetracyclines and glycylcyclines (tigecycline) and the time-dependent (non concentration-dependent) effect of beta-lactam antibiotics, lincosamides and macrolides Table 3 . In the Pseudomonas aeruginosa) including the avoidance of resistance development, concentration profiles may be more favorable in which the site concentrations remain well above the MIC  . . PseudomThe data on PK/PD correlations offer the possibility of adjusting the dosage individually using therapeutic drug monitoring (TDM), especially in high-risk populations  producers]) , 8], , .Clearance and volume of distribution determine the half-life of a substance. These parameters also co-determine the time the plasma concentration is above the MIC and for the total exposure (AUC) and play an important role in the calculation of the dosing interval.Decreased function of the drug-eliminating organs  results in reduced clearance of antibiotics and prolongs the half-life, which may be one reason for the increased rate of adverse effects. The relevance of impaired renal and hepatic function plays a lesser role for antibiotics with a wide therapeutic range  than for antibiotics with a narrow therapeutic range (such as aminoglycosides or vancomycin). Nevertheless, in intensive care patients it has been shown that increased plasma levels of beta-lactam antibiotics are associated with a poorer neurological outcome . In addiAntibiotics which are predominantly eliminated via the kidneys to varying degrees are also secreted by glomerular or tubular filtration (e.g. penicillins) or reabsorbed. If renal function is impaired, the dosage should be adjusted to the degree of renal impairment according to creatinine clearance. The following are crucial in determining the need for dose adjustment:the proportion of renal elimination of the drug in normal renal function,the toxicity of the substance, the degree of renal impairment; andthe increase of creatinine clearance beyond normal levels .In general the dosage specifications of the manufacturers should be followed. If these are not available, the dosing regimen for renal insufficiency should be adjusted by calculating the individual elimination fraction (Q) according to Dettli , 12]..12].Helpful links for dose adjustment in renal insufficiency: http://www.infektio.de/antiinfektiva/dosierung-bei-niereninsuffizienz/http://www.dosing.de/Critically ill intensive care patients have a special status in terms of substance-specific pharmacokinetics. Recommended dosages and sensitivities  are based on the assumption that the pharmacokinetics of the drug are equivalent to those of a “standard patient”. In fact, however, the distribution and elimination capacity of drugs in the critically ill is very variable and difficult to predict. The renal function of patients with severe infections alone shows great inter- and intra-individual variability, so that the drug clearance and thus the optimal dosage of predominantly renally excreted anti-infective drugs can vary by a factor of 10 . This prUnlike creatinine clearance in renal insufficiency, clinical scores in hepatic insufficiency  are not good predictors of drug metabolization and elimination.Liver diseases have a different, unpredictable influence on the individual cytochrome P450 isoenzymes. Existing tests allow only a rough assessment of the function of the individual isoenzymes. The reduction in hepatic clearance and the associated need for dose adjustment may be relevant to antibiotics that are almost exclusively metabolized by liver enzymes, predominantly those with high lipophilicity and low polarity that can be poorly eliminated via the kidney . When dosing with other tetracyclines, clavulanic acid, flucloxacillin, macrolides or streptogramins, higher grade hepatic insufficiency with reduced metabolization performance must also be considered. For antibiotics with a high presystemic elimination rate (e.g. ciprofloxacin), hepatic impairment may significantly increase the bioavailability after oral administration and thus the plasma concentration.For all stages of renal and hepatic insufficiency, the loading dose , which depends on the volume of distribution, should be identical to that for a healthy kidney or liver. Otherwise, initially reduced doses of antibiotics may take several days to reach an effective level. Since the success of antibiotic treatment mainly depends on the initial selection and an adequate dosage, this would jeopardize treatment success.The dosage of antibiotics in overweight patients is a particular pharmacotherapeutic problem. The kinetics of many antibiotics are sometimes unpredictable due to unusual distributional processes in these patients. There is no clear relationship between the lipophilicity of the substances and their distribution in obese patients. Altered volume of distribution, clearance and problems in assessing kidney function using creatinine clearance are just some of the reasons that often cause overweight patients to be inadequately treated with standard doses of antibiotics. Subtherapeutic concentrations may then lead to clinical treatment failure and development of resistance, while supratherapeutic/excessively high concentrations usually lead to undesirable side effects (with the exception of aminoglycosides). Since an increased volume of distribution and increased clearance is generally to be expected in these patients, a weight-adapted dose adjustment is necessary. Which weight  should be used as the basis for the dose calculation is dependent both on the antibiotic itself (e.g. in tigecycline with a distribution volume of 7 to 10 l/kg ) as wellHydrophilic antibiotics   are lessFor special patient populations  Therapeutic Drug Monitoring (TDM) is recommended , 8], ,  but onlyMany antibiotics are characterized by significant inter- and intra-individual differences in pharmacokinetic properties, especially in elimination behavior and volume of distribution. This is especially true in intensive care patients with severe sepsis, septic shock and consecutive multiple organ failure and profound changes in distribution spaces (e.g. capillary leak and infusion treatments) , 8]. As. As8]. APrerequisites or indications for conducting TDM above all are:Therapeutic and toxic effects are in a concentration related cause and effect relationship.The substance has a narrow therapeutic range and exceeding the concentration range by even relatively degree can lead to toxic effects.The pharmacokinetics of the drug are subject to significant intra- and inter-individual variability, especially in intensive care patients with severe sepsis and septic shock.max, Cmin, AUC) are known.Pharmacokinetic target parameters  , 6], , , 13]. I. I13]. Imax/MIC>10) are aimed for , , , 29], , , 31], , , 33], , , 35], , . Taking imed for , 38]. T. Tmax/MIimed for . In the treatment of endocarditis and neutropenic patients, single dose administration is sufficient in most cases. For severe endocarditis , single dose administration is not recommended and multiple administration recommended, for example in combination with a synergistic antibiotic attacking the cell wall .In treatment with the glycopeptide antibiotics vancomycin and teicoplanin the aims are permanent concentrations above the MIC of the relevant pathogens in accordance with their pharmacodynamic parameters. As mandated by TDM, trough levels are monitored . For theFor the treatment of bone or prosthetic infections, teicoplanin trough levels of 20–25 mg/l are recommended . When teBeta-lactam antibiotics are effective if the MIC of the pathogens is exceeded as permanently as possible during the growth phase of the cell wall. Initially, the bactericidal activity increases with increasing concentrations of the antibiotic up to 4 to 5 times the MIC but higher levels will not improve the therapeutic outcome. This pharmacokinetic-pharmacodynamic relationship is described as a time-dependent (non-concentration-dependent) bactericide. For beta-lactam antibiotics, the concentration of unbound antibiotic should exceed the MIC of the pathogen at the site of infection for at least 40–60% of that time , with apThe pharmacokinetic properties of beta-lactam-antibiotics do not show great variability one from another. Beta-lactam antibiotics are rapidly distributed in the extracellular space after parenteral administration. At steady state, similar concentrations are reached after intermittent administration and bolus administration followed by continuous infusion , 60], , , 62], , , 64]..64].2, congestive heart failure, edema, haemofiltration , dialysis patients  and pregnant women . T. T10]. Tnt women . In contnt women , 65], , , , , , ..2, congeRecommendations for prolonged administration (over 3–4 hours) or continuous administration of beta-lactam antibiotics are based on theoretical considerations supported by experimental studies or simulations. Clinical examinations show advantages for prolonged or continuous administration with longer-lasting serum levels above the MIC even at lower daily doses , 79], , , 81], , , 83], , , 85], , ,87], , 7, 88], , 90], , , 92], , , 94], , , 96] wi wi96] wiBeta-lactam antibiotics have limited stability after preparation. It is not only the degree of degradation that is crucial but also the type of decomposition products that have allergenic potential. This fact is insufficiently considered in numerous studies on the stability of the substances. According to these studies, solutions of beta-lactam antibiotics are considered to be stable over a period of time if their degradation level is below 10%. The extent of the degradation depends on the solvent, the effects of light, the concentration of the antibiotic, the type of application aids as well as their production and temperature. In the case of close-fitting pump application in outpatient parenteral antibiotic therapy (OPAT), significant stability losses must be taken into account due to increased ambient heat.The use of the recommended solvents is of great practical importance to ensure optimum solubility and stability. Almost without exception, all penicillins (dry substances) must be dissolved in aqua ad injectabilia in order to accelerate the dissolution behavior and to ensure particle freedom. Further dilution is then usually possible in conventional infusion solutions. Many beta-lactam antibiotics show a number of incompatibility reactions with other medicines when administered in the same infusion system. The manufacturer’s information on compatibility must be observed.The most common adverse drug reactions of penicillins are allergies and pseudoallergic reactions. The cause of these reactions is the presence of an unstable beta-lactam structure or specific side chains. Penicillins in solution vary in stability depending on their side chains and the pH. The degradation products of penicillins act as haptens and can form covalent bonds with the body’s own proteins. They form a hapten-protein complex that can induce an allergy-producing immune response. The degradation products of penicillins have a significant potential for allergic reactions. Further information on safety can be found in chapter 4 .The nature and extent of the degradation of the beta-lactam antibiotics are substance-dependent. Acylaminopenicillins, isoxazolylpenicillins, cephalosporins and aztreonam are generally more stable than benzylpenicillin because of their structure. Ring-opening, however, is also possible with cephalosporins by nucleophilic or (more rarely) electrophilic attack, as the example of ceftazidime and other cephalosporins shows . The cheLike beta-lactam antibiotics in patients with severe infections, linezolid has a high variability in serum concentrations, with insufficient blood levels under standard dosage regimens. Current data indicate that a continuous application can also make a useful contribution to achieving PK/PD goals , 113]..113].Due to pharmacokinetic/pharmacodynamic considerations, prolonged or continuous infusion of beta-lactam antibiotics is superior to intermittent administration with respect to the therapeutic goal of exceeding the MIC of the pathogens as continually as possible. There is some clinical data on the significant superiority of this treatment regimen.Continuous and intermittent infusions of a beta-lactam antibiotic show a comparable side effect profile.Prolonged/continuous administration is recommended in patients whose pharmacokinetic parameters  are significantly different from normal population data . Continuous application is only recommended under TDM. Prolonged administration of a beta-lactam antibiotic is safe even without TDM. Prolonged/continuous administration of the antibiotic should always be preceded by a bolus dose. For substances with a high volume of distribution (for example tigecycline), a higher dose should be given initially.Possible economic advantages result from continuous administration, since similar serum concentrations in steady state compared to intermittent administration can be achieved with lower daily doses in patients who are not seriously ill.Some beta-lactam antibiotics are not suitable for continuous administration due to their low stability at room temperature. In these cases, only a prolonged infusion period (3–4 hours) is possible.The manufacturer’s recommendations regarding the type of solvents and the concentrations of the antibiotic solutions must be strictly adhered to. Deviations can result in considerably limited stability.Continuous administration of beta-lactam antibiotics requires separate access or lumen, as there are numerous incompatibility reactions with other medicinal products.Bioavailability data of the antibiotics for sequential therapy can be found in Table 5 An important cause of unwanted side effects may be interactions with other drugs. In particular, the inhibition of hepatic monooxygenases, the cytochrome P450 enzymes, usually cause a higher risk of side effects, for example through some macrolides and fluoroquinolones as well as azole antifungals.Also, induction-enhanced expression of enzymes of the cytochrome P450 enzyme system is possible, for example through rifampicin, barbiturates and carbamazepine. The consequence is a reduced plasma level with reduced effectiveness of the particular drug concerned.More important examples of interactions of antibiotics with other drugs are presented in Table 6 nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.This is the third chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2The authors declare that they have no competing interests.


P = 0.08). Our network meta-analysis showed that both neoadjuvant CRT and neoadjuvant CT were effective in improving the survival of patients with ESCC. Individual clinical decisions need further study in the future.The optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is still a debatable point; however, randomized trials for strategies including neoadjuvant or adjuvant chemotherapy (CT), radiotherapy, or chemoradiotherapy (CRT) are not always available. This network meta-analysis aimed to identify an effective approach through indirect comparisons. An extensive literature search comparing multimodality treatment and surgery was performed, and a network meta-analysis was conducted with the frequentist method. Twenty-three trials including a total of 3636 ESCC patients were included. Neoadjuvant CRT and neoadjuvant CT, which were recommended by most guidelines for esophageal cancer, were associated with an overall survival advantage compared with surgery alone . A statistically significant survival benefit from neoadjuvant CRT compared with neoadjuvant CT could not be demonstrated in our study (HR = 0.61, 95% CI 0.32–1.17,  Esophageal squamous cell carcinoma (ESCC) is the most frequent histological subtype3. The 5-year survival rate of patients with ESCC is still low4.Esophageal carcinoma has the eighth highest incidence and is the sixth leading cause of carcinoma-related deaths worldwide5, including chemotherapy (CT), radiotherapy (RT), or synchronous chemoradiotherapy (CRT) performed before or after surgery7. Multimodality treatments show overall survival (OS) differences in a large number of trials conducted in the past, even though some conclusions were controversial; for example, preoperative CT followed by surgery was demonstrated to improve survival in one trial8, while another trial had different results9. Presently, there is a paucity of evidence directly comparing neoadjuvant or adjuvant therapies, and the optimal choice among them remains unclear.Surgery is still a potentially curative treatment; however, neoadjuvant or adjuvant therapies have been proven to improve survival10. Although NMAs on multimodality treatments of ESCC have been conducted12, the evidence is still not enough, and new evidence has been presented in the last 2–3 years.When there is a lack of randomized controlled trials (RCTs) directly comparing different treatments, network meta-analysis (NMA) can be used to combine the available evidence and compare the treatments indirectly, under the conditions that heterogeneity and inconsistency are fulfilledOur study aimed to perform a NMA comparing OS for neoadjuvant and adjuvant CT, CRT, and RT in patients with resectable ESCC.The protocol of this NMA was registered in the PROSPERO database (identification code: 212733).13 and Cochrane guidelines14. A combination of “[o]esophageal cancer (or neoplasms)” and the following different terms were used: “squamous cell”, “chemotherapy”, “chemoradiotherapy”, “radiotherapy”, “chemoradiation”, “neoadjuvant”, “adjuvant”, “preoperative”, “postoperative”, and “surgery (or esophagectomy)”. We also used the terms searching for systematic reviews and meta-analyses. References of the articles were also searched for potentially available studies. Abstracts or posters of international meetings such as American Society of Clinical Oncology (ASCO) meetings, European Society for Medical Oncology (ESMO) congresses or Chinese Society of Clinical Oncology (CSCO) meetings were also screened using the abovementioned keywords.A systematic search was carried out for available literature published up to July 2018. The searches were limited to articles describing RCTs published in English. RCTs were searched in the EMBASE, MEDLINE, and Cochrane Library databases from 1990. A systematic review of RCTs was conducted following the PRISMA for Network Meta-Analyses (PRISMA-NMA)Only full-text articles were included. We focused on treatments for ESCC, and RCTs published in English were included regardless of histology if the following criteria were met: sufficient data of the ESCC subgroup could be obtained or the majority of the patients had ESCC. Patients were confirmed to undergo radical/curative intent resection without distal metastasis. The latest published studies were chosen if there were data published repeatedly.The studies were excluded in the following situations: non-RCT design, including patients never undergoing surgery, insufficient data for the ESCC subgroup or less than 80% of patients had ESCC.17. The HR, 95% CI and standard error of lnHR were carefully extracted from the survival curve.Three authors independently reviewed the full text of the enrolled studies. The study endpoint was OS, and the outcome measure was the hazard ratio (HR) with 95% confidence interval (CI). However, HRs and CIs were not available at most times, and they could be estimated using a previously introduced method18. The quality can be downgraded due to publication bias, indirectness, inconsistency or imprecision.All enrolled articles underwent quality assessment, and the quality of evidence can be graded to 4 levels: high, moderate, low, and very low19. Enrolled RCTs were classified into 3 categories: high risk, low risk, or unclear risk. Yongqiang Wang and Lei Shan extracted the data, and Wenhao Zhang verified the data independently.All articles were assessed for risk of bias using the Cochrane risk of bias tool for RCTs20. If a direct comparison was based on 2 or more studies, the study heterogeneity was quantified using the I-squared statistic, and it was considered low, moderate, or high for I-squared values of < 25%, 25% to 50%, and > 50%, respectively21. A network of evidence can be constructed in the absence of direct comparisons between treatments22. The methods for indirect treatment comparisons are categorized as Bayesian or frequentist23. The frequentist method was used in our study, and it was also known as the adjusted indirect treatment comparison (AITC) method, which has been described previously24. A random effects NMA was carried out with a frequentist setting25. More information about the research synthesis methods could be obtained from the article28. The use of Stata in dealing with more complicated networks is introduced in the article29, including the evidence for publication bias . The adjusted indirect method we also used was introduced by Branko Miladinovic et al.30. A heterogeneity parameter (tausquared) was assumed across all comparisons. Each summary effect is presented along with 95% CI and predictive interval. The predictive interval was calculated using the between-study variance tau-squared, providing information on the magnitude of heterogeneity. Contribution matrix is generated during the direct and indirect analysis using Stata 12.029.OS was used as the study endpoint. Standard pairwise meta-analysis was performed for direct comparisons using the inverse variance DerSimonian-Laird random effects model31; for example, if the information of surgery versus neoadjuvant chemoradiation and surgery versus neoadjuvant chemotherapy is available, then the information of the neoadjuvant chemoradiation versus neoadjuvant chemotherapy comparison can be obtained for the NMA. Usually, the treatment of surgery alone is assumed to be the common treatment as the transitivity assumption and is regarded reasonably consistent among all studies. Participants could be principlely randomized to any of the treatments in the network. Lack of transitivity can present as inconsistency between direct and indirect estimates (loop inconsistency) or between estimates deriving from different study designs (design inconsistency). The inconsistency between direct and indirect estimates or between estimates from different study designs can be studied using the design-by-treatment interaction model32.Transitivity is one of the key assumptions of NMAStatistical tests were 2-sided. The statistical analysis and graph drawing were performed with Stata 12.0 .55 (published from 1990 to 2018) were intended to be included in the NMA, and 23 RCTs were enrolled after an article from the 2018 CSCO Meeting55 was excluded because of limited stage and therapy (only N1 patients were enrolled and there was only one article for adjuvant radiotherapy) , which indicated that adjuvant CT did not provide a further benefit compared with surgery. There were no significant differences between neoadjuvant CRT and neoadjuvant CT, neoadjuvant CRT and neoadjuvant RT, neoadjuvant CRT and adjuvant CRT, neoadjuvant CRT and adjuvant CT, neoadjuvant CT and neoadjuvant RT, neoadjuvant CT and adjuvant CRT, neoadjuvant CT and adjuvant CT, neoadjuvant RT and adjuvant CRT, neoadjuvant RT and adjuvant CT, and adjuvant CRT and adjuvant CRT.The network of eligible comparisons for NMA is shown in Fig. The common treatment (surgery) was reasonably consistent across trials, and no evidence of violation of the transitivity assumption was observed. The participants could be randomized to any treatments being compared in the network due to the equal distribution of the modifiers across studies.There was no severe risk of bias in the eligible RCTs  rate was higher in these patients. A high-quality study by Bosset et al.40 reported that recurrence-free survival was significantly improved in patients with squamous cell carcinoma with no benefit of OS. The patient characteristics, including histological type and stage, and CRT protocols varied greatly in the meta-analysis performed in North America and Europe, and radical surgery was regarded as a vital factor for long-term survival. Guidelines for the diagnosis and treatment of carcinoma of the esophagus in Japan59 recommended neoadjuvant chemotherapy with cisplatin + 5-fluorouracil (5-FU) in patients with resectable stage II or III thoracic esophageal carcinoma according to JCOG920443 and JCOG99078. Postoperative irradiation was only suggested for use when there was local residual tumor or local recurrence. However, few cases presented pCR60, and few meta-analyses demonstrated its survival benefit over surgery alone61. The role of neoadjuvant RT remains unsatisfactory, and its impact can be affected by several elements, such as the volume of irradiation, daily fractions, total dose, and interaction with other treatments. It has been reported that daily fractionation > 40 Gy with radiation could increase the late toxicity risk62, and as a result, it may be harmful to long-term survival. The value of neoadjuvant RT remains controversial, and no recommendation has been made in the clinical guidelines until now.As poor outcomes are presented with surgery alone, combined therapies are required. Neoadjuvant therapy has been compared with postoperative therapy or surgery alone for resectable ESCC for curative intent. Stage I patients have not yet been evaluated. The expected advantages of neoadjuvant therapy are as follows. 1. The patients’ response to chemotherapy or radiotherapy can be evaluated through neoadjuvant therapy, and downstaging is expected to make the surgical procedure easier and improve the radical resection rate. 2. Neoadjuvant therapy is expected to kill the micrometastasis, which may be potentially useful to prolong the long-term survival of patients. 3. Patients more easily complete the treatment plan before surgery, and chemotherapeutic drugs can reach the target before the local blood supply is destroyed. Most studies have focused on neoadjuvant CRT and neoadjuvant CT. The recent National Comprehensive Cancer Network (NCCN) guidelines suggest preoperative chemoradiation for patients with stage cT1b-T4a and N0 or N + , and its multidisciplinary recommendation is that combined modality therapy is effective for patients with localized esophageal cancer. Three articles are cited64.The value of postoperative adjuvant therapy for stage I patients has not yet been studied. The expected advantages of postoperative adjuvant therapy are to address the residual tumor, lymph node metastasis, and possible micrometastasis. However, disadvantages also existed, as no visible target could be used to evaluate the effect of postoperative adjuvant therapy and lower compliance compared with that of neoadjuvant therapy. More evidence suggests better survival benefits for neoadjuvant therapy than for adjuvant therapyP = 0.008). This may be due to four mechanisms: 1. radiation damage can be enhanced by cell repair inhibition; 2. radioresistant-phase tumor cells can be cleared and radiosensitive-phase cells can be accumulated; 3. hypoxic cells can be cleared; and 4. the repopulation of tumor cells can be inhibited65. Theoretically, chemotherapy can control micrometastatic tumor cells, and radiotherapy can control regional tumors; therefore, the effect of spatial cooperation was presented. Sometimes it can lead to downstaging with a higher radical resection rate, which may improve OS66. Nonetheless, it could not be denied that neoadjuvant CRT was also associated with a higher risk of postoperative mortality than neoadjuvant CT or surgery alone67. As mentioned before, treatment outcomes differ according to the individual cases, the administration of the drug, the dosage of the radiation and so on. Additional high-quality randomized trials with larger sample sizes are needed.Our analysis showed that neoadjuvant CRT may have the best OS benefit and seems to significantly improve OS compared with surgery alone ; however, a statistically significant survival benefit of neoadjuvant CRT compared with neoadjuvant CT could not be demonstrated in our study . The result was similar to that of Sjoquist et al.’s study63. Neoadjuvant CT was reported to have a survival benefit over surgery, but they were not able to demonstrate a statistically significant survival benefit for neoadjuvant CRT against neoadjuvant CT after enrolling patients with both squamous cell carcinoma and adenocarcinoma . It is always difficult to conduct a direct comparison of neoadjuvant CRT against neoadjuvant CT because of the limited sample size, and our NMA seemed to provide some of the latest evidence for the multiple-disciplinary treatment for patients with ESCC.In our study, we also suggest that neoadjuvant CT had a survival benefit over surgery alone , and there was no subgroup analysisIn summary, regional variability exists in the use of multimodality therapy in patients with ESCC, neoadjuvant CRT is preferred in Europe and the United States, neoadjuvant CT is recommended in Asian countries, and there is no clear recommendation in China due to the controversy. Our NMA suggests that neoadjuvant CRT or neoadjuvant CT may prolong survival in patients with ESCC. Individualized molecular markers may provide some information for clinical decisions in the future.Supplementary Legends.Supplementary Table 1.Supplementary Table 2.Supplementary Table 3.


Escherichia coli is one of the most important foodborne pathogens causing disease even at low cellular numbers. Thus, the early and accurate detection of this pathogen is important. However, due to the formation of viable but non-culturable (VBNC) status, the golden standard culturing methodology fails to identify O157 E. coli once it enters VBNC status. Crossing priming amplification (CPA) is a novel, simple, easy-to-operate detection technology that amplifies DNA with high speed, efficiency, and specificity under isothermal conditions. The objective of this study was to firstly develop and apply a CPA assay with propidium monoazide (PMA) for the rapid detection of the foodborne E. coli O157:H7 in VBNC state. Five primers  were specially designed for recognizing three targets, which were rfbE, stx1, and stx2, and evaluated for its effectiveness in detecting VBNC cell of E. coli O157:H7 with detection limits of pure VBNC culture at 103, 105, and 105 colony-forming units (CFUs)/ml for rfbE, stx1, and stx2, respectively, whereas those of food samples (frozen pastry and steamed bread) were 103, 105, and 105 CFUs/ml. The application of the PMA-CPA assay was successfully used on detecting E. coli O157:H7 in VBNC state from food samples. In conclusion, this is the first development of PMA-CPA assay on the detection of VBNC cell, which was found to be useful and a powerful tool for the rapid detection of E. coli O157:H7 in VBNC state. Undoubtedly, the PMA-CPA method can be of high value to the food industry owing to its various advantages such as speed, specificity, sensitivity, and cost-effectiveness.O157  To induce the entry of VBNC state, the culture was diluted to the final density of 108 CFU/ml with saline (pure culture system) and food homogenate  (food system) and stored at −20°C.Induction of VBNC cells and the establishment of PMA-CPA assays were performed on E. coli O157. The induction culture was serial diluted with 0.9% sodium chloride and inoculated on trypticase soy agar at 37°C for 24 h. When the number of colonies was <1 CFU/ml for 3 days, it was considered that the survived cells might have entered into the non-culturable state  at a distance of 15 cm for 15 min to complete the combination of DNA and PMA 2SO4, 10-mM KCl, 8.0-mM MgSO4, 0.1% Tween 20, 0.7-M betaine (Sigma), 1.4-mM dNTP (each), 8-U Bst DNA polymerase , a 1.0-μM primer of 2a/1s, a 0.5-μM (each) primer of 2a and 3a, 0.6-μM (each) primer of 4s and 5a, 1-μl mixture chromogenic agent , and 1-μl template DNA, and the volume was made up to 26 μl with nuclease-free water. The mixed chromogenic agent consists of 0.13-mM calcein and 15.6-mM MnCl2.4H2O.The CPA reaction was performed as mentioned before , using tThe mixed reaction solution was incubated at 65°C for 60 min and heated at 80°C for 2 min to terminate it. PMA-CPA amplified products were visualized under visible light or the appearance of the laddering pattern on 1.5% agarose gel electrophoresis. However, instead of the laddering pattern, apparent bright strip might present, which can also be regarded as positive results. This experiment was performed in triplicate to ensure reproducibility.E. coli O157 in normal viable and VBNC state was analyzed using the LIVE/DEAD® BacLight Bacterial Viability Kit. Under a fluorescence microscope, the VBNC cells showed green, whereas dead cells exhibited red  encoded by stx1 and stx2 can result in gastrointestinal symptoms, such as diarrhea and hemorrhagic colitis, and may also progress to a hemolytic uremic syndrome, a severe sequela of this infection (E. coli O157:H7 in VBNC cell, as well as its virulence factors. The detection limits of PMA-CPA assay showed consistency with that of CPA assay, no matter in pure bacterial culture or food samples, which had been performed previously (E. coli O157:H7 in VBNC state from food samples.athogens . There infection . Consideeviously . To the rfbE, stx1, and stx2 genes for the effective detection of E. coli O157:H7 VBNC cell. Therefore, being simple, rapid, sensitive, and specific, PMA-CPA assay can be a useful and powerful method in the field and also an alternative diagnostic tool for the detection of E. coli O157:H7 in VBNC cell and its related virulence factors in testing as part of an outbreak investigation.In conclusion, the designed CPA primers targeted the All datasets presented in this study are included in the article/supplementary material.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Mycobacterial culture remains the gold standard for the diagnosis of tuberculosis. However, an appropriate digestion and decontamination method (DDM) is essential for the effective recovery of tubercle bacilli in culture. Therefore, the current study was designed to compare the performance of papain-cetylpyridinium chloride [papain-CPC] and pepsin-cetylpyridinium chloride [pepsin-CPC] DDMs against N-acetyl L-Cysteine-sodium hydroxide (NALC-NaOH) DDM for recovery of mycobacteria from clinically suspected pulmonary tuberculosis cases. To evaluate papain-CPC, pepsin-CPC and NALC-NaOH DDMs, sputum samples (N = 1381) were cultured on Löwenstein-Jensen medium and the results were compared. The papain-CPC DDM showed sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 93.27%, 71.7%, and 100%, respectively as compared to NALC-NaOH DDM. Similarly, pepsin-CPC DDM demonstrated sensitivity, specificity, positive predictive value and negative predictive value of 98.94%, 94.7%, 76.11%, and 99.81%, respectively. In summary, both papain-CPC and pepsin-CPC DDMs are highly sensitive and specific techniques for recovery of mycobacteria as compared to NALC-NaOH DDM. However, when the overall performances of all DDMs compared, papain-CPC DDM isolated increased number of mycobacterial isolates with comparatively higher numbers of colonies on LJ media than both pepsin-CPC and NALC-NaOH DDMs, indicating its potential to replace the NALC-NaOH DDM for recovery of mycobacteria from sputum samples. Mycobacterium tuberculosis (MTB) in culture. In the past years, various DDMs have been established to isolate MTB from clinical specimens  and 4 g of papain  in 100 ml of distilled water] was added to a 14 ml BD Falcon tube containing 2–3 ml of sputum aliquot. The contents were mixed by vortexing (1 min), and were incubated at 37°C for 30 min. After incubation, the volume was brought to 14 ml with the addition of distilled water. Then, this mixture was thoroughly mixed by inversions and vortexing (1 min) and centrifuged at 3000 x g for 20 min . The supernatant was carefully decanted and the remaining sediment was re-suspended in 200 μl of distilled water. This re-suspended pellet (0.2 ml) was inoculated on two slants of LJ media (one media with glycerol and the other with sodium pyruvate) followed by incubation at 37°C  for 8 weeks aerobically with manual monitoring of once per week for the growth of MTB.For pepsin-CPC DDM, 2–3 ml of sputum aliquot was mixed with equal quantity (2–3 ml) of 4% pepsin-CPC working solution [the stock solution of pepsin and CPC were prepared by dissolving 4 g of pepsin  and 4 g of CPC  in 100 ml of distilled water] and vortexed (1 min). Then, pepsin-CPC method was performed as described in the papain-CPC DDM.5'-CCT GCG AGC GTA GGC GTC GG 3' and T5-5' CTC GTC CAG CGC CGC TTC GG 3'  and the expected band size was 123 bps . In the current study, all the MTB isolates , were further confirmed by IS6110 PCR assay. However, this assay couldn’t amplify DNA of five MTB isolates that were identified by conventional methods. This may be probably due to the absence of IS6110 elements in these MTB strains or may also be due to the presence of some PCR inhibitors present. The current study used sputum specimens that were collected at microscopy-designated center of RNTCP (for routine microscopic examination) to presumptively diagnose PTB. However, final diagnosis of PTB was based on direct sputum smear, culture, chest X-ray examination, histopathological evidences and clinical characteristics or as recommended by trained physician. Patients with smear positive cases (and other investigations suggestive of TB) usually started with treatment as per the RNTCP guidelines [The current study evaluated the performance of NALC-NaOH DDM (reference method) with newly proposed papain-CPC and pepsin-CPC DDMs for the recovery of mycobacteria from sputum specimens that collected from clinically suspected PTB patients. The digested and decontaminated specimens were inoculated on two slants of LJ media; one LJ media with sodium pyruvate  between all the DDMs studied  after treatment with NALC-NaOH DDM. This higher recovery rate of MTB in culture (as compared to direct LED FM) is likely due to the increased sensitivity of culture that detects 10–100 bacilli/ml of specimen. Further, NALC-NaOH DDM possesses few limitations such as; technically intricate, instability of NALC solution, and relatively expensive (5g cost ~ 500 INR). In the present study, a diminished colony count was also noted when samples were digested and decontaminated using NALC-NaOH DDM as compared to papain-CPC and pepsin-CPC DDMs. This reduction in number of colonies may be due to death of bacilli in the sputum samples because of the toxicity induced by NaOH during the treatment procedure. In this study, around 20% of the positive cultures were isolated on 8 studied . However4 colony-forming units per ml [In the papain-CPC and pepsin CPC DDMs, both papain and pepsin functions as mucolytic agent and CPC as decontaminating agent. In our earlier study, it was found that overnight incubation of sputum with 1% CPC could effectively decontaminate the specimens . Howevers per ml . The oths per ml . Howevers per ml . Althougs per ml , 28. NevIn summary, both papain-CPC and pepsin-CPC DDM could effectively isolate reasonably higher number of mycobacterial isolates particularly in sputum specimens with smear-negative cases as compared to NALC-NaOH DDM. However, when the overall performances of both papain-CPC and pepsin-CPC DDMs compared, papain-CPC DDM could isolate increased number of mycobacterial isolates with comparatively higher number of colonies on LJ media as compared to both pepsin-CPC DDM and NALC-NaOH DDM, indicating the potential of papain-CPC DDM to replace the currently available NALC-NaOH DDM for the recovery of mycobacteria from sputum samples.


Digital Image Correlation (DIC) provides measurements without disturbing the specimen, which is a major advantage over contact methods. Additionally, DIC techniques provide full-field maps of response quantities like strains and displacements, unlike traditional methods that are limited to a local investigation. In this work, an experimental application of DIC is presented to investigate a problem of relevant interest in the civil engineering field, namely the interface behavior between externally bonded fabric reinforced cementitious mortar (FRCM) sheets and concrete substrate. This represents a widespread strengthening technique of existing reinforced concrete structures, but its effectiveness is strongly related to the bond behavior between composite fabric and underlying concrete. To investigate this phenomenon, a set of notched concrete beams are realized, reinforced with FRCM sheets on the bottom face, subsequently cured in different environmental conditions (humidity and temperature) and finally tested up to failure under three-point bending. Mechanical tests are carried out vis-à-vis DIC measurements using two distinct cameras simultaneously, one focused on the concrete front face and another focused on the FRCM-concrete interface. This experimental setup makes it possible to interpret the mechanical behavior and failure mode of the specimens not only from a traditional macroscopic viewpoint but also under a local perspective concerning the evolution of the strain distribution at the FRCM-concrete interface obtained by DIC in the pre- and postcracking phase. Digital Image Correlation (DIC) is a noncontact measurement technique that is increasingly used in several engineering fields. DIC techniques provide full-field maps of response quantities like strains and displacements, which represent a more complete set of information than local measurements obtainable by traditional approaches. On the one hand, there are required (preliminary) operations of DIC such as the need to apply a stochastic pattern (sprayed pattern) to the surface of the material, which might not always be possible. On the other hand, there are many advantages of DIC, such as the relatively simple experimental setup, the adjustable spatial and temporal resolutions, the possibility of examining specimens with different dimensions and involved materials, and the adaptability to different loading rates ranging from quasistatic to dynamic . What isSome of the most interesting applications of DIC include the investigation of the mechanical behavior of concrete structures. Indeed, concrete is a heterogeneous material characterized by a complex fracture behavior, which is difficult to be analyzed with conventional contact measurement approaches like local strain gauges. Moreover, analyzing the failure process of concrete structures is challenging because cracks exhibit micrometric dimensions, are broadly diffused on the material, and rapidly evolve in the internal microstructure. In this regard, DIC proves to be a reliable full-field measurement approach, as demonstrated by the good results reported in previous studies. Choi et al.  were amoOf particular relevance to this research work, DIC can be usefully employed to investigate the interface behavior between externally bonded composite systems and concrete substrate, which represents a widespread strengthening technique for retrofitting existing concrete structures. The oldest and most popular strategy consists of externally bonding fiber-reinforced polymer (FRP)  sheets oAs a more recent alternative, fabric reinforced cementitious mortar (FRCM) sheets represent the natural evolution of FRP systems in which an inorganic (cement-based) matrix is used in place of an epoxy matrix ,19. The In the literature, FRCM-concrete bond behavior was generally investigated by single-lap shear tests wherein the load is directly applied to the strengthening system. Instead, in this paper the bond behavior is analyzed by an alternative notched beam test setup in accordance with ASTM D7958/D7958M standards . In the Experimental three-point bending tests on concrete notched beams with externally bonded PBO-FRCM sheets are conducted for specimens subject to different environmental conditions (humidity and temperature), in order to assess whether these factors influence the bond behavior .Mechanical tests are performed vis-à-vis DIC measurements using two distinct cameras simultaneously, one focused on the concrete front face and another focused on the FRCM-concrete interface. This experimental setup makes it possible to interpret the mechanical behavior and failure mode of the specimens not only from a traditional macroscopic viewpoint but also under a local perspective concerning the evolution of the strain distribution at the FRCM-concrete interface obtained by DIC.Along such research line, in this paper an experimental application of DIC for the investigation of PBO FRCM-concrete interface bond behavior is documented. The novel contributions of this experimental work in comparison to other studies are summarized as follows:Prismatic concrete beams are prepared using an ordinary Portland cement. The characterization of the concrete properties is made in terms of compressive strength and flexural strength, evaluated on standard specimens at 28 days in accordance with UNI EN 12390-3:2009 and UNI EN 12390-5: 2002 standards, respectively. The mean compressive strength of six standard cubes of 150 mm side is 47 MPa, with a coefficient of variation (CoV) of 9%; the mean flexural strength of six prismatic specimens is 6 MPa, with a CoV of 1.92%. The FRCM is made of PBO mesh embedded in a cement-based mortar. The PBO bidirectional woven has an unbalanced configuration in the two directions, with fiber density higher in the main direction compared to the lateral direction, as shown in Prismatic concrete beams with nominal dimensions 150 × 150 × 500 mm are casted in preformed formworks, demolded after 24 h, and wrapped with a wet cloth to prevent water evaporation during the next 28 days, as shown in DIC is a nondestructive and noncontact optical measurement technique widely used to investigate the distribution of strains and displacements of different structures . This meM + 1) × (2M + 1) pixels, where M is a positive integer number and other than 0. The subset size is critical to DIC accuracy, so it should be properly selected according to the actual random intensity distributions of the speckle patterns [P, centered in a reference facet, moves to the new position P’0 within the deformed facet. This displacement and the consequent strain are estimated using a cross-correlation (CC) or sum-squared difference (SSD) correlation algorithm, which identifies the similarity between the reference and the deformed facet. From a mathematical point of view, this involves searching for the peak of the distribution of the correlation coefficients. Specifically, the location of the target subset is identified, once the maximum or the minimum correlation coefficient has been found, depending on the used correlation criterion. Instead, the strain field can be obtained by numerical differentiation.The fundamentals of the DIC measurement process  are illupatterns . As the The registration and computation algorithms aim to ensure the best correlation between the interrogated facets. However, to achieve this goal, it is necessary to pursue a balanced compromise between spatial resolution, pattern speckle quality and computation time . In factThree-point bending tests are performed according to ASTM D7958/D7958M standards , using afour specimens are cured in air at laboratory environmental conditions for 31 days (temperature 23 °C ± 2 °C and relative humidity 65–75%);four specimens are placed in a curing tank for 31 days, with their bottom face  immersed in water (relative humidity 100%) at a controlled temperature of 30 °C;four specimens are placed in a curing tank for 31 days, with their bottom face  immersed in water (relative humidity 100%) at a controlled temperature of 50 °C.The tests comprise different environmental conditioning of the specimens. After the application of the externally bonded PBO-FRCM sheet, three curing conditions are considered see :four speThe goal of this investigation is to ascertain the influence of the environmental factors in the FRCM-concrete interface bond behavior. Apart from the laboratory conditions, two serviceability conditions are considered. The first conditioning temperature (30 °C) can be meant as a service temperature that is frequently experienced in summer seasons, while the second conditioning temperature (50 °C) can represent an ultimate limit state condition that is hardly exceeded in ordinary conditions.The use of correct lens and of high-resolution images plays a crucial role in the correct evaluation of the response and is essential for obtaining reliable results. For this reason, an appropriate DIC test setup has been conceived in this experimental campaign to ensure the highest resolution and a correct measurement ,67.Two reflex cameras, models Nikon D3100 and Nikon D300s, are used in this work, called camera 1 and camera 2 in The synchronization of the acquisition is carried out by connecting a trigger port of the mechanical test equipment with a remote control for the two cameras. The rate of acquisition is set as one photo every 6 s, until the specimen failure. Depending on the lens models used in the two cameras, it is necessary to adopt different focal values, as listed in The set of digital images was elaborated using the DIC software GOM Correlate 2020 .The results of the three-point bending tests on the notched concrete beams with externally bonded PBO-FRCM sheets are illustrated here in terms of load-deflection curves. The graphs in All the recorded curves show an initial elastic branch, in which the behavior of both concrete and FRCM composite system is linear. A clear peak is observed at a deflection equal to approximately 0.5 mm for all the specimens. Thereafter, a decrease of load occurs according to a typical trend of a concrete beam structure. The second part of all curves exhibits a local maximum and a slow nonlinear reduction of the measured load. This curve can be interpreted from a mechanical point of view, by also critically considering alternative single-lap shear tests available in the literature for the same material . The peaFor all the beams, the complete failure is related to the PBO mesh debonding from the mortar matrix. As shown in Considering the reasonably good agreement between the four repetitions of beams for each curing class, only some representative results among the tested specimens are selected and discussed concerning DIC test results. As said above, the two cameras allow the examination of two distinct regions of interest of the beams, namely concrete front face above the notch (camera 2) and FRCM-concrete interface (camera 1). In The DIC-processed images of the longitudinal strains refer to different stages of the loading application, which are identified by a set of characteristic points A-F in the relevant load-deflection curve (the point S represents a “starting point” close to the origin). The branch S-A denotes a linear elastic behavior of both concrete and FRCM. This is corroborated by the corresponding DIC strain distributions shown for the two regions of interest. Specifically, point A highlights the incipient cracking of concrete, while point B denotes the incipient cracking of mortar, with the concrete above the notch already partially cracked. By further increasing the load from point A to point B leads to the attainment of the tensile strength above the notch and, consequently, the neutral axis depth moves from the area close to the notch tip up to the loading point. This leads to the formation of a main crack above the notch, with a resulting tortuous pattern up to the top compressed fiber of the concrete beam (point B) and complete reduction of concrete contribution to the element strength, with the crack width gradually increasing (point C). The whole process is visible in terms of strain distribution between point A and point C obtained by camera 2 . ConcurrIn the initial beam behavior, the beam contribution and the FRCM contribution are mutually interacting. Once the concrete cracking and mortar cracking occur, the FRCM contribution prevails. In the interfacial bond behavior, the concrete is completely cracked, as shown in the DIC images. The load level C corresponds to the attainment of the mortar cracking. Once the critical deflection of point C (around 0.5 mm) is exceeded, a clear softening branch is observed from point C to point D, which is related to the residual tensile stress of concrete observed in the range of narrow crack widths ,70. ThisIt is worth noting that the characterization of the bond behavior at the FRCM-concrete interface is assisted by the DIC images, which allow a clearer interpretation of the mechanical behavior of the notched concrete beam, especially in the precracking phase. More specifically, the DIC-processed images explain the interaction of the two parallel resisting contributions in the specimens and the stress transfer mechanism with the increase of the vertical deflection of the beam. By inspection of the images related to the camera 1, it can be seen that the DIC strain maps are very useful to anticipate the incipient crack initiation of both concrete and mortar matrix under service conditions and the subsequent initiation and development of PBO mesh sliding from mortar matrix. To clarify this aspect and to investigate the effect of the different curing conditions of the samples, some DIC images aimed at capturing the occurrence of incipient crack and crack development are reported in Finally, In conclusion, as demonstrated by these outcomes, the DIC technique can be used to assess the bond behavior at the FRCM-concrete interface or to determine the status of the interfacial properties after an exceptional event , which could be useful to plan local repair interventions and, in general, for structural health monitoring purposes. After a first initial stage in which an almost zero displacement is observed, once the concrete beam has started its cracking then the notch opening grows linearly with the deflection. It is interesting to observe that the opening of the notch proceeds with an almost linear trend. Consequently, it is not significantly affected by the cracking of the mortar matrix and by the progressive debonding of PBO.Any slippage of the concrete beam with respect to the FRCM would highlight a limited adhesion capacity of the mortar matrix to the concrete substrate. This paper has presented an experimental campaign focused on the characterization of the interfacial bond behavior between externally bonded PBO-FRCM sheets and concrete substrate, assisted by DIC. The FRCM-concrete interface bond behavior is investigated via DIC technique by using two cameras simultaneously, one focused on the concrete area above the notch and another focused on the FRCM-concrete interface. Three-point bending test on notched concrete beams in accordance with ASTM D7958/D7958M standards are carried out. Prior to testing, the specimens were subjected to different environmental conditions (humidity and temperature), in order to assess whether, and to what extent, these factors influence the bond behavior.Twelve specimens have been analyzed, and the qualitative trends of the load-deflection curves are quite similar and are marginally affected by the curing conditions. This demonstrates that the performance of the FRCM system is not negatively affected by temperature increase, at least for the relatively short duration of the thermal treatment and temperature range involved in this experimental campaign .After the attainment of cracking in concrete (above the notch) and in FRCM mortar (at the interface), the subsequent branches of the load-deflection curve are related to the stress transfer mechanism at the FRCM-concrete interface and resemble the typical stress-global slip curve observed in alternative single-lap shear tests available in the literature for the same material. For all the beams, the failure mode is ascribed to the PBO mesh debonding from the mortar matrix.DIC images of the longitudinal strains have facilitated the interpretation of the mechanical behavior of the specimens and have better explained the interaction of the two parallel resisting systems (concrete and FRCM composite), something that is impossible to capture by the observation of the mere load-deflection curves. These images have revealed that the temperature condition applied to the bottom part of the specimen has slightly altered the stress transfer mechanism with the increase of the vertical deflection of the beam in the precracking phase and has generated a premature cracking of concrete above the notch.By inspection of the DIC images it is clearly seen that the curing conditions affect the mechanical behavior of the specimen in the precracking phase only. On the contrary, after cracking of mortar takes place, the elongation of the PBO mesh increases until subsequent debonding from the mortar matrix, and this phenomenon is almost comparable in the two curing conditions, which is also confirmed by the qualitative agreement of the load-deflection curves observed for the two classes of specimens.The main results of this research work are summarized as follows: