Tension stiffening is a characteristic behavior of reinforced concrete (RC) beams which is directly affected by the bond-slip property of steel bar and concrete interfaces. A beam strengthened with a near-surface mounted (NSM) technique would be even more affected by tension stiffening, as the NSM reinforcement also possess a bond-slip property. Yet assessing how much the tension stiffening of NSM contributes to the behavior of RC beams is difficult due to the fact that bond-slip effects cannot be directly incorporated into a strain-based moment-curvature analysis. As such, the tension stiffening is typically incorporated through various empirical formulations, which can require a great deal of testing and calibrations to be done. In this paper a relatively new method, which can be called the mechanics-based segmental approach, is used to directly simulate the tension stiffening effect of NSM reinforcements on RC beams, without the need for empirical formulations to indirectly simulate the tension stiffening. Analysis shows that the tension stiffening of NSM fiber reinforced polymer (FRP) contributes a significant portion to the stiffness and strength of the strengthened RC beam not only during serviceability, but at all load levels. In recent years, the focus of research on strengthening of reinforced concrete (RC) beams using fiber reinforced polymers (FRP) has changed slightly from externally bonded (EB) techniques ,2,3 to nTension stiffening has been known to cause increased flexural rigidity in cracked RC beams. While progress has been made on understanding the tension stiffening of NSM FRP, directly implementing the tension-stiffening effect in simulations had proven difficult. The moment-curvature approach, as a strain-based method, cannot directly incorporate the interface slips that are necessary to simulate tension stiffening. Due of this, empirically derived values or factors are usually introduced to indirectly simulate tension stiffening, such as effective flexural rigidities  and hingThe limitations imposed by empirically derived values prompted a new analysis approach to be introduced ,17,18,19In this paper, it will be shown how the segmental moment-rotation approach can be used to simulate the behavior of NSM FRP reinforcements. This is done by applying the partial interaction theory to create a numerical analysis that is used to simulate the tension stiffening load-slip relationship between FRP bars, epoxy adhesive and the adjacent concrete area. The moment-rotation approach is then validated against the experimental results by the authors and also against previous published results. The contribution of tension stiffening of NSM FRP reinforcements on the behavior of RC beams at all levels of load up to failure is also verified using a comparison study.M) is applied to the segment in A-A to B-B must be accommodated by a combination of both material strains within the segment and more importantly by the partial-interaction mechanisms.Consider a NSM FRP strengthened RC beam segment as shown in rb and Δrf as shown. In the compression zone, slip across a concrete-concrete sliding plane forms a wedge and accumulates along the sliding plane as shown. The method used to account for these partial-interaction mechanisms will be discussed in the following sections.For NSM FRP strengthened beams, in the tension region, slip between the steel and FRP reinforcement relative to the adjacent concrete will accumulate along the reinforcement, causing the slips ΔThe partial interaction theory has been used by several researchers to perform a numerical analysis using bond-slip properties ,17,18,19r as shown in Prior to cracking of the RC beam, both steel and carbon fiber reinforced polymer (CFRP) reinforcement are in full interaction with adjacent concrete, where due to a perfect bond, both the bars and adjacent concrete are uniformly extended as load is applied to the RC beam. Following the formation of the flexural crack, the steel and CFRP bars are in partial interaction as the bars slip relative to the concrete, resulting in the half crack opening ΔAr and modulus Er and the adjacent concrete of area Ac and modulus Ec. The prism is discretized into very short sections of length dx, and at the crack face (the first section) there is no force acting on the concrete as the concrete-concrete interfaces are not touching each other due to the flexural crack. Due to the load Pr, the reinforcement bars slips along the length of the prism as in x), which is the difference between the strain in the reinforcement and the concrete, is also known.To begin analyzing the effect of slip between the steel and CFRP bars with their adjacent concrete, consider the prism shown in Scr can be determined as it is known that cracks will form when the strain in the concrete reaches the tensile cracking strain εct as shown in Scr represents the minimum crack spacing, as a subsequent crack can form anywhere in the full interaction region to the right of the region Scr in Scr [Applying the boundary condition that full-interaction is achieved where the interfacial slip and the slip-strain reach zero at the same point, the primary crack spacing r in Scr .Ldef) as in Pr/Δr) relationship in this case can be determined following the same mechanism as for the infinitely long prism in Once primary cracks have formed along the prism as in The partial interaction analysis presented above is used to simulate the tension stiffening of steel and also FRP reinforcements between primary cracks. It should be noted that several assumptions were made with respect to NSM FRP strengthening. Firstly, slip is allowed between epoxy-CFRP interfaces, but perfect bonding is assumed between epoxy-concrete interfaces. Secondly, in order to apply the partial interaction theory, the CFRP bar must be located in the center of the prism, such that no moment is induced when the prism is loaded. Hence, it is assumed that the size of the prism for NSM-strengthened beams is as shown in Scr.The partial-interaction analysis is also able to capture the reduced crack spacing that occur due to the application of strengthening as seen in practice. As shown in Concrete softening can be captured using any empirically derived stress-strain relationship that takes into account the falling branch of concrete stress-strain. An example of this is the stress-strain model by Popovics . Howeveret al. [Ltest. The size of the concrete in a beam’s hinge section is taken as 2Ldef, as shown in a/Ec in the empirical stress-strain relationship for concrete, the strain of concrete that has been adjusted for size is: test is the corresponding strain for stress σa in the empirical stress-strain relationship and Ec is the elastic modulus of the concrete. The size-dependent strain should still have the same concrete strength (fc) while having a different shape compared to the empirical stress-strain relationship, as shown in The method proposed by Chen et al.  can be uM/θ) relationship of the beam will now be established. The rotation θ at the end of the hinge in rb and ΔNSM in The method for obtaining the moment-rotation  and the NSM reinforcement (PFRP) are no longer functions of the strain profile due to the partial interaction that occurs due to the bond with the adjacent concrete. Therefore, the Prb and PFRP, as shown in rb and ΔFRP, and using the load-slip relationship obtained using the numerical partial interaction analysis. Note that this requires two separate load-slip relationships, one for the steel reinforcement and the other for the FRP reinforcement. The depth of the neutral axis, dNA, is then adjusted until equilibrium of the forces is achieved. The moment is then calculated and the analysis is repeated until the required moment-rotation relationship is obtained. To change the rotation to curvature is simply a matter of dividing the rotation, θ by Ldef. Using the moment-curvature relationship, the load-deflection of the beam can be determined using the commonly used double integration method.Flexural cracking is considered to have occurred if the rotation causes the strain in the concrete layer around the steel reinforcement to reach the concrete cracking strain. After cracking, the loads developed in the steel bar . To complement this experimental programme, the data for other specimens were also taken from the published results of various researchers ,23,24. TAs/bd = 0.0085, where b is beam width and d is depth of beam) with two 12 mm diameter deformed bars as tensile reinforcement. Two 10 mm diameter deformed bars were used as hanger bars to hold the stirrups. Double-legged closed 8 mm diameter steel stirrups were used as shear reinforcement with a spacing of 90 mm centre-to-centre to ensure that a flexure failure would occur. Rectangular 2.3 m long RC beams with 125 mm × 250 mm cross-sectional dimensions were selected for the experimental study. The dimensions and material properties for the other researchers’ work can be found elsewhere ,23,24. T3 for NSM strengthening. These CFRP bars showed linear elastic response up to ultimate failure. To adhere the NSM bar to the concrete substrate, Sikadur® 30  was used as epoxy adhesive. The details of the concrete, steel and CFRP material properties are described in ® 30 properties [The concrete cube compressive strength, concrete cylinder compressive strength and flexural strength of the concrete were determined according to BS EN 12390-3:22009, ASTM C39 and BS EN 12390-5:22009 ,26,27 reoperties  at tempe® 30) was applied into the groove to fill around two-thirds of the groove depth. The CFRP bar was then gently inserted into the groove, and pressed lightly to ensure proper epoxy covering surrounding the bar. The groove’s outer surface was then levelled and left for one week to achieve proper epoxy strength. The beams were then tested under static loading using the four-point loading test. The setup of the four-point loading test is shown in Each of the strengthened beam specimens had a single groove (24 mm × 24 mm) made using a diamond-bladed concrete saw along the beam length to accommodate the CFRP bar. A hammer and hand chisel were used to remove the remaining concrete lugs from the groove and all the debris was then removed from the groove using airbrushing pressure. An epoxy adhesive (Sikadurversus mid-span deflection curves for the beams tested by the authors are shown in The load The second phase is from the first flexural cracking to yielding of the internal reinforcement of the beams, where a loss of stiffness can be observed. The strengthened beams were found to show higher stiffness compared to the control beam due to the CFRP bars in this phase. The third portion of the load-deflection behaviour is from yielding until failure. The strengthened beams show improved strength and stiffness compared to the control beam. While the control beam failed by concrete crushing after steel yielding, both the strengthened beams failed by concrete cover separation. A summary of the experimental test results is given in et al. [et al. [The experimental results from the authors, and also from previously published works, were simulated using the segmental moment-rotation approach. Several generic material models were used to obtain the simulated results. For the partial interaction analysis, the material models used are the local bond strength for FRP bar by Hassan and Rizkalla , local bet al. , bond stet al. , and bon [et al. . For con [et al. . As the Comparisons between simulated and experimental load-deflection are shown in To determine the contribution of the tension-stiffening effect of NSM FRP reinforcements to the behaviour of RC beams, a comparison is made in In this study, the segmental moment-rotation approach was used to predict the load-deflection behaviour of NSM FRP-strengthened beams. Through the application of partial interaction theory, the bond properties of the NSM FRP can be directly simulated, thereby allowing the tension-stiffening behaviour to be simulated for all level of loads of the strengthened RC beam. The model is generic, allowing it to cope with any type of bond and material properties for the NSM FRP reinforcement used. The results from the model have shown to be in good agreement with experimental results. It was also shown that the tension-stiffening behaviour of NSM FRP plays an important role in the behaviour of strengthened RC beams for all load levels.


However, tests for antibiotic susceptibilities, such as the disk-diffusion assay, evaluate only the concentration at which a bacterial strain stops growing, namely resistance level. High tolerance strains will not be detected using these tests. We present a simple modification of the standard disk-diffusion assay that allows the semi-quantitative evaluation of tolerance levels. This novel method, the “TDtest”, enabled the detection of tolerant and persistent bacteria by promoting the growth of the surviving bacteria in the inhibition zone, once the antibiotic has diffused away. Using the TDtest, we were able to detect different levels of antibiotic tolerance in clinical isolates of E. coli. The TDtest also identified antibiotics that effectively eliminate tolerant bacteria. The additional information on drug susceptibility provided by the TDtest should enable tailoring better treatment regimens for pathogenic bacteria.Antibiotic tolerance - the ability for prolonged survival under bactericidal treatments - is a potentially clinically significant phenomenon that is commonly overlooked in the clinical microbiology laboratory. Recent  A few daily exposures for 3 hours were sufficient to evolve this high level of tolerance to the antibiotic, and led to treatment failureduration of the transient antibiotic exposure rather than to its precise chemical nature and evaded antibiotic killing by remaining dormant for the duration of the treatment, without becoming resistant. Since the regime of antibiotic exposure in vitro is similar to a typical treatment in patients, detecting tolerance in the clinic may be crucial for identifying mechanisms related to survival and for devising effective treatment regimens. Moreover, studies showed that tolerance, leading to treatment failure, can rapidly evolve for other classes of antibioticsTolerant and persistent bacteria can survive antibiotic treatments without having acquired a resistance phenotype1234The goal of this study was to provide a simple detection assay to evaluate tolerance or persistence levels in clinical isolates. Our assay is based on the Kirby–Bauer disk diffusion antibiotic susceptibility testingWe propose the Tolerance Disk Test (TDtest), a modification of the standard Kirby–Bauer disk diffusion assay that enables, in addition to determining resistance, to identify tolerance to an antibiotic by evaluating survival.vapBC toxin-antitoxin module did not reveal any reduction of the inhibition zone  and distance (r) from the source (center of disk), assuming isotropic diffusion in a two-dimensional plate. D is the diffusion coefficient, A is the initial antibiotic amount in the disk and h is the height of the agar in the plate.Where A, after overnight incubation, the antibiotic concentration in the inhibition zone can drop below the MIC   . Strain 5 μg/ml) ,B shows 5 μg/ml) ,D shows 5 μg/ml) . Moreove5 μg/ml) –H, cells5 μg/ml) –K. Becau cloacae .The TDtest was evaluated also for bacteria grown on other media typically used in the clinical microbiology, namely Mueller-Hinton agar and Mueller-Hinton blood agar .E. coli tolerant strain tbl3a, obtained by evolution under intermittent exposure to ampicillinUsing the TDtest, we were able to screen for antibiotics more effective against tolerant bacteria. We compared the effect of different antibiotics on the same We verified this finding by measuring survival in liquid culture after exposure to the two antibiotics. An overnight culture was diluted and exposed either to ampicillin (100 μg/ml) or kanamycin (100 μg/ml). In accordance to the results of the TDtests, the survival fraction under ampicillin was three orders of magnitude higher than under kanamycin . Thus, aLate-growing bacteria, leading to tolerance or persistence, may survive an antibiotic treatment and might lead to treatment failureSlower killing rate of tolerant bacteria may not always be relevant to treatment outcome; preventing bacterial growth is often sufficient because the immune system will be able to clear the infection. For example: for patients with large bacterial burdens, such as nosocomial pneumonia, it is imperative to kill ≥2 log10 CFU/g early after treatment initiation, to allow the granulocytes to contribute optimally to bacterial clearancein vitro.A limitation of the TDtest is its sensitivity to the growth conditions, as tolerance and persistence phenotypes are often triggered by external conditions, such as tolerance that requires passage through to stationary phase conditionsIn addition to its potential benefit for the clinical setting, the TDtest may enable screens for compounds or combinations that are potent against tolerant and persistent bacteria and speed up drug development. Finally, the simplicity and low cost of the TDtest technique may be used in third world country to characterize strains and classify them according to the rapidity of their killing under several antibiotics.Growth medium was LB Lennox (LBL) and all other chemicals, unless stated otherwise, were purchased from Sigma Chemical Co. Ampicillin stock solution 100 mg/ml in Double Distilled Water (DDW) was kept as single use aliquots at −20 °C. Ertapenem (MERCK) stock solution (20 mg/ml in DDW) was kept at −20 °C. Kanamycin stock solution (30 mg/ml in DDW) was kept at −20 °C.Antibiotic content in disks: ampicillin 10 μg (Bio-rad) and kanamycin 7.5 μg (Bio-rad), ertapenem 0.25 μg, cefazolin 7.5 μg (OXOID), ciprofloxacin 0.1 μg, imipenem 2.5 μg (OXOID).Glucose (D-glucose) was purchased from JT Baker.Mueller-Hinton (MH) plates and MH + 5% sheep blood (MH-BD) agar plates were purchased from Novamed.The TDtest consists of two steps:Step I: similar to reference disk diffusion assay6–107 bacteria at stationary phase were plated on LBL nutrient agar plate.Circa 10The amount of antibiotics in the disks was adjusted to reach a concentration below the MIC in the inhibition zone after a day of incubation (at 37 °C). Many commercial disks contain amounts that are too high for the concentration to fall below the MIC within the inhibition zone after a day. When this was the case, custom disks for the TDtest were prepared (see below).If the MIC is not known, preparing several disks that contain different amounts of antibiotics and performing the TDtest in parallel for those disks is recommended See . We founStep II: The antibiotic disk was replaced with a glucose (2 mg) disk after 18 hours and the plate was incubated for an additional overnight.Adding the glucose solution directly on the antibiotic disk, instead of replacing it.Using other nutrients instead of glucose.Alternatives for this step:Filter paper  were cut in circles of 6 mm diameter, sterilized by autoclave and impregnated with either 5 μl of a 40% sterile glucose solution for glucose disks, or 4–10 μl of antibiotic solution, according to final required amount for antibiotic disks, and left to dry at room temperature. Alternatively, commercial disks were cut in half or quarter to reduce the amount. Note that the exact amount of antibiotics is not important as long as it is high enough to create a large inhibition zone, and low enough to allow the concentration to fall below the MIC after 18 hours. The amount of antibiotic in each disk shown in the figures, is mentioned in the legend.Imaging of plates was done using an automated multiple scanner system (ScanLag), as described in ref. To measure the diffusion coefficient we used a one-well rectangular plate (12*7.5 cm), filled with agar 1.5%, to a height of 0.4 cm (similar to the plates used for the TDtest assays). We added a drop of a fluorescent agent  at a single point in the middle of the plate, and measured the temporal and spatial dynamics of fluorescence over time at 37 °C, for 672 points in the plate, using multiplate reader Infinite M200 (Tecan). The diffusion coefficient estimate was extracted by fitting the data to the 2D diffusion equation  See Sup.Overnight cultures were diluted 1:100 in fresh medium containing antibiotic and incubated at 37 °C with shaking at 270 rpm, for designated time. Bacterial survival was determined by the most probable number-counting method (MPN)Time-lapse microscopy was performed as in ref. 4 bacteria/well. The plate was incubated overnight at 37 °C. The Minimal Inhibitory Concentration (MIC) is the highest concentration supporting visible growth.Each column in a 96 wells plate was filled with fresh LBL supplemented with ascending amount of ampicillin and inoculated with approx. 10How to cite this article: Gefen, O. et al. TDtest: easy detection of bacterial tolerance and persistence in clinical isolates by a modified disk-diffusion assay. Sci. Rep.7, 41284; doi: 10.1038/srep41284 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


P < 0.00001) and higher T stage . In addition, patients with c-Met-high HNSCC showed significantly worse disease-free survival  and overall survival  than those with c-Met-low tumor. In conclusion, this meta-analysis demonstrates that high c-Met expression is significantly associated with worse pathological features and prognosis, indicating c-Met overexpression is an adverse prognostic marker for patients with HNSCC.High c-Met expression has been observed in head and neck squamous cell carcinoma (HNSCC). However, its clinicopathological impact remains controversial. We performed this meta-analysis to evaluate the pathologic and prognostic impacts of c-Met overexpression in patients with HNSCC. A systematic computerized search of the electronic databases was carried out. From 16 studies, 1,948 patients with HNSCC were included in the meta-analysis. Compared with HNSCCs showing low c-Met expression, tumors with high c-Met expression were significantly associated with higher rate of lymph node metastasis (odds ratio = 3.26, 95% CI: 2.27–4.69,  Head and neck cancers (HNCs) are classified as epithelial neoplasms of the oral cavity (including tongue and tonsils), nasal cavity, paranasal sinuses, pharynx, and larynx. HNCs have been increasing worldwide, comprising one of the most common groups of cancer –3. DespiWith understanding of molecular mechanisms of carcinogenesis, treatment of recurrent or metastatic HNSCC has changed over the last decade. Cetuximab, a monoclonal antibody to the epidermal growth factor receptor (EGFR), was the first to receive FDA approval with survival advantage when combined with radiation or platinum-based chemotherapy , 6. In 2MET located on chromosome 7 [MET, c-Met may be activated by protein overexpression or paracrine/autocrine signaling of HGF [c-Met, the tyrosine kinase receptor for HGF, is encoded by the proto-oncogene mosome 7 . The dysmosome 7 , 13. In g of HGF –16. The g of HGF , lung cag of HGF , gastricg of HGF , colorecg of HGF , cervicag of HGF , renal cg of HGF , and pang of HGF .The expression of c-Met has also been detected in HNSCC –45. ManyFigure In 13 studies , 44, 45,There was a marked heterogeneity in the criteria used to dichotomize c-Met expression status (low or high) among studies. The IHC criteria were briefly summarized in the P < 0.00001) .From nine studies , 35–39, ) Figure . The fixT stage. There was a positive correlation between c-Met overexpression and higher T classification (T3 and T4)  .From eleven studies –42, 44, ) Figure . The fixP = 0.03) .From 9 studies , 44, 45,) Figure . The ranP = 0.0007) .From 12 studies , 42–45, ) Figure , compareVisual inspection of the funnel plots for LN metastasis, T stage, DFS and OS showed symmetry, indicating there were no substantial publication biases Figure .In this meta-analysis, we investigated the pathologic and prognostic impact of high c-Met expression in patients with HNSCC. The results show that c-Met overexpression significantly correlated with poor pathological features and prognosis. To our knowledge, this is the first meta-analysis to evaluate the clinicopathological impacts of high c-Met expression in patients with HNSCC.MET activation has been proven to play a critical role in the pathogenesis and progression of many tumor types [MET activation include mutations, amplification, and overexpression of both c-Met and HGF protein [MET amplification has been detected in up to 13% of tumors and MET mutations are less common in HNSCCs [MET amplification has been proposed as an independent prognostic factor for DFS and OS in locoregionally advanced HNSCC [MET amplification and increased MET gene copy number have been detected at a low frequency in HNSCC tumors, they are associated with the overexpression of c-Met protein [et al. evaluated c-Met expression in 211 patients with oral cavity SCC and failed to find any prognostic impact in regard to tumor size or stage, LN metastasis, and OS [or types –16. Mech protein , 16. METn HNSCCs , 47. METed HNSCC . While M protein , 45. c-M protein , 36. Man protein , T class protein , 41, 44, protein , 37–39,  protein , 32, 35, protein  or OS [2 protein , 42. How protein , 45. ForP < 0.00001) and higher T-stage . In addition, patients with c-Met-high HNSCC showed significantly worse DFS  and OS  than those with c-Met-low tumor. Our findings indicate that high c-Met expression represent a significant adverse prognostic marker in patients with HNSCC.In the current meta-analysis, we included studies comparing the major pathological features (LN metastasis and T classification) and survival outcomes (DFS and OS) according to the c-Met expression status. All the studies used IHC to test c-Met expression. Compared with HNSCCs showing low c-Met expression, tumors with high expression showed significantly higher rate of LN metastasis  and EGFR are biomarkers that have been extensively studied in HNSCCs. Some studies have suggested that aberrant c-Met/HGF signaling is associated with HPV status , 44. Qiave tumor . Howeverve tumor , 40, 45.ve tumor . In the sitivity . HoweverP = 0.06) and OS  [Recently, c-Met activation has been proposed as a potential mode of resistance to anti-EGFR therapy in HNSCC –57. The  = 0.07) . These f = 0.07) , 55. Thein situ hybridization, and real-time quantitative PCR are currently used to test c-Met expression, but there are no standardized criteria for overexpression. The discrepancies in the clinicopathological impacts of c-Met among studies might be attributable to the different methods and criteria for high c-Met expression. Therefore, the definition of reliable criteria for c-Met status is essential to verify the prognostic role of c-Met expression and investigate the efficacy of c-Met inhibitors.The major challenge for clinical development of c-Met inhibitors is that there is no consensus of the reliable criteria for c-Met overexpression. A variety of methods, such as IHC, Western blot, fluorescence Our study has several inherent limitations. First, the included studies had various primary sites in the head and neck. Second, because of the limited number of studies, we could not perform subgroup analyses according to the primary sites and HPV status. Third, most studies were retrospectively carried out. Fourth, although almost all patients had SCC of the head and neck, some studies included patients with undifferenciated carcinoma; however, because they occupied only a very small portion of patients, inclusion of these patients does not seem to affect the results. Fifth, while most studies had patients with a locoregionally advanced disease, one was conducted in recurrent or metastatic setting . BecauseIn conclusion, this meta-analysis demonstrates that c-Met overexpression is significantly associated with poor pathological features and prognosis. These findings indicate that high c-Met expression is a potential adverse prognostic marker for patients with HNSCC. However, larger studies using standardized methods and criteria are still needed to verify the prognostic role of c-Met expression in HNSCC with various primary sites.This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . We carrEligible studies were required to meet the following inclusion criteria: (i) patients had a pathological diagnosis of head and neck squamous cell carcinoma; (ii) articles had criteria for high c-Met expression; (iii) pathological features (LN metastasis or T classification) and/or survival outcomes (DFS or OS) were stratified according to c-Met expression status; (iv) sufficient data were provided to estimate OR or HR with 95% CI; (v) articles were published in English.The data were collected independently by two investigators (BJK and HSK). If these two authors did not agree, the other investigator (JHK) was consulted to resolve the discrepancies.The following data were extracted from all eligible studies: the first author's name, publication year, country, number of patients, tumor sites, T classification, LN metastasis, primary treatment, methods to test c-Met expression, cut-off values adopted to dichotomize c-Met expression status, and HR with 95% CI for DFS or OS and OR with 95% CI for pathological features.Q statistic and the I2 inconsistency test. The fixed-effects model (Mantel–Haenszel method) was selected for pooling homogeneous outcomes when P≥ 0.1 and 2 ≤I 50%, whereas the random-effects model (DerSimonian–Laird method) was applied when there was a significant heterogeneity (P < 0.1 and 2I > 50%). The RevMan software (version 5.2) was used to combine data and report outcomes. All P-values were two-sided and P < 0.05 was considered statistically significant. Publication bias was assessed graphically by the funnel plot method [Statistical values were obtained directly from the original articles. If OR or HR with 95% CI were not provided, the Engauge Digitizer (version 9.1) was used to estimate the needed data from the results and Kaplan-Meier curves. The strength of the association between c-Met overexpression and pathologic features (LN metastasis or T stage) was shown as ORs with their 95% CIs. The effect size of DFS and OS was pooled through HR with its 95% CI. The heterogeneity across studies was tested by the t method .


Immunoglobulin G4-related disease is increasingly recognized as a systemic autoimmune disorder characterized by immunoglobulin G4-positive lymphocyte infiltration. Organ biopsy and histopathology are the most important diagnostic methods; however, the significance of a cytological examination in immunoglobulin G4-related disease cases is still unclear.18F-fluorodeoxyglucose imaging revealed inflammatory foci in his pericardium. A surgical pericardiectomy was performed and the resultant specimen showed significant immunoglobulin G4-positive plasma cell infiltration and marked fibrous thickening of his pericardium; therefore, a diagnosis of constrictive pericarditis due to immunoglobulin G4-related disease was made. Oral administration of 0.6-mg/kg/day prednisolone resolved his heart failure and he was discharged on foot 1 week later.A 73-year-old Asian man who was a former tobacco smoker presented with progressive exertional dyspnea, systemic edema, and pericardial effusion. A cytological examination of his pericardial effusion detected three or four plasma cells per high-power field by Giemsa staining. Moreover, immunoglobulin G4-positive plasma cells were detected by immunostaining. Cardiac catheterization after pericardiocentesis revealed that both ventricular pressure traces showed an early diastolic dip and plateau. Positron-emission tomography with Our experience with this case indicates that cytological examination of pericardial effusion was useful in the diagnosis of immunoglobulin G4-related disease. Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic inflammatory disease characterized by IgG4-positive lymphocyte infiltration that causes fibrosclerotic change in various tissues and organs , 2. AlthA 73-year-old Asian man, a former tobacco smoker with hypertension and diabetes, presented to the emergency department in our hospital with a 2-month history of progressive exertional dyspnea. He was diagnosed with congestive heart failure due to arterial fibrillation and tricuspid regurgitation; he had been hospitalized five times over the previous 5 years and had been treated with bisoprolol and furosemide. Pericardial friction rub or knock, or pericardial effusion was not detected in any previous hospitalizations. He had a family history of congestive heart failure, lung cancer, and gallbladder cancer. He was prescribed 2.5 mg bisoprolol, 40 mg furosemide, 60 mg azosemide, and 80 mg valsartan before the current illness. An initial physical examination on the first day of hospitalization revealed the following: blood pressure, 101/56 mmHg; pulse rate, 108 beats/minute; respiratory rate, 20 breaths/minute; body temperature, 37.0 °C; and oxygen saturation 95% while he was breathing room air. Jugular venous distension, Kussmaul’s sign, and leg edema were observed. A neurological examination did not reveal any abnormal objective findings. Chest radiography revealed bilateral pleural effusion with an increased cardiothoracic ratio of 84.4% Fig. . Laborat18F-fluorodeoxyglucose (18F-FDG) in his pericardium as well as in his gastric wall and in his hilar lymph nodes  demonstrated pericardial effusion with a pericardial cavity that was 24-mm thick. Pericardiocentesis revealed 900 mL of exudative effusion, Giemsa staining revealed three or four plasma cells per high-power field in the pericardial effusion Fig. , and IgGdes Fig. . Serial ium Fig. .Fig. 2ThA thoracoscopic pericardiectomy was performed and a histopathological analysis demonstrated lymphoplasmacytic inflammation with scattered plasma cells among a fibrous stroma in specimens of the pericardium in hematoxylin and eosin-stained sections Fig. . Elastic18F-FDG-PET scanning to judge the extent of inflammatory foci [18F-FDG-PET scanning showed abnormal uptake in atypical organs such as his pericardium, his gastric wall, and in his hilar lymph nodes, but not in his pancreas, his lacrimal and salivary glands, or kidneys that were reported as common sites of IgG4-RD [18F-FDG-PET findings.IgG4-RD may affect multiple organs in 60 to 90% of patients with IgG4-RD, including cardiovascular organs –5; it reory foci –10. The  IgG4-RD . Finallyet al. [18F-FDG-PET revealed hypermetabolic lesions in 97.1% patients with IgG4-RD [67gallium scintigraphy [18F-FDG-PET scanning should be chosen to make a definitive histopathological diagnosis after identifying the presence of IgG4-RD by a cytological evaluation.Only a few studies have reported cytological examinations in patients with IgG4-RD. Kabara et al.  demonstret al. . They diet al. . On the  IgG4-RD  and was tigraphy . Our casWe report the rare case of a patient with IgG4-RD who presented with CP that was identified by a cytological examination in pericardial effusion and diagnosed by a histopathological analysis of the pericardium.


The potential growth-promoting effects of antibiotics are not well understood among undernourished children in environments with high pathogen exposure. We aimed to assess whether early antibiotic exposure duration and class were associated with growth to 2 years of age across 8 low-resource sites in the MAL-ED birth cohort study.z scores to 2 years. We assessed the impact of class-specific exposures and duration, and compared these results to effects of antibiotic exposures after 6 months of age.We followed 1954 children twice per week from birth to 2 years to record maternally reported antibiotic exposures and measure anthropometry monthly. We estimated the associations between antibiotic exposure before 6 months of age and weight-for-age and length-for-age (LAZ) Antibiotic use before 6 months of age was associated with increased weight from 6 months to 2 years, whereas associations with length were less consistent across sites and antibiotic classes. Compared to unexposed children, 2 or more courses of metronidazole, macrolides, and cephalosporins were associated with adjusted increases in weight-for-age of 0.24 : 0.04, 0.43), 0.23 , and 0.19  from 6 months to 2 years, respectively.Antibiotic use in low-resource settings was most associated with the ponderal growth of children who had multiple exposures to antibiotics with broad spectrum and anaerobic activity in early infancy. Opportunities for rational and targeted antibiotic therapy in low resource settings may also promote short-term weight gain in children, although longer-term physical growth and metabolic impacts are unknown. What Is KnownAntibiotics are growth-promoting in livestock, and early life exposure to antibiotics has been recently associated with obesity in several high-income countries.The effect of antibiotic use may be different among children in highly contaminated environments in low-income settings in which undernutrition is more common than obesity.What Is NewAntibiotic-associated growth promotion can also occur among children in low-resource settings who are often undernourished.Antibiotic use in the first 6 months of life was associated with increased weight, especially among children with 2 or more exposures to macrolides, metronidazole, and cephalosporins.After decades of antibiotic use to promote growth of livestock in the agricultural industry, researchers have begun to explore the potential role of antibiotic use in promoting growth in humans as well . EvidencIn low-income settings, obesity among young children is less common, and poor growth and undernutrition is often a more pressing public health concern. In these settings, antibiotics are recommended by the WHO as part of the treatment for severe acute malnutrition , despiteTo appropriately account for these factors, we leveraged the high-resolution illness and treatment data from The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED), a birth cohort study performed at 8 sites in South America, sub-Saharan Africa, and south Asia. Antibiotic use was highly prevalent in almost all sites . We aimez scores were calculated using the 2006 WHO child growth standards  and as a categorical variable by number of class-specific courses received, using the models above and additionally adjusting for other antibiotic class exposures to isolate class-specific effects. We also explored effect measure modification by malnutrition (stunted and underweight) at 6 months and pathogen burden from 0 to 5 months (presence of detected ) by inclz scores at the beginning of the age period.To assess the period during which the effects of early antibiotic use (before 6 months of age) were manifested, we estimated these effects on anthropometry at different age periods, from 0 to 5, 6 to 11, 12 to 17, and 17 to 24 months, adjusting for the child's anthropometric To compare early life exposures with later exposures, we used linear regression to estimate the effects of exposures from 6 to 24 months on cross-sectional WAZ and LAZ at 2 years. A child's measurement closest to 24 months, between 23 and 25 months was considered their anthropometry at 2 years. Adjustment variables included the same baseline characteristics as above, including enrollment WAZ, enrollment LAZ (for length models only), illness burden as characterized above over the whole 2 years of follow-up, and antibiotic use in the first 6 months of life. Using these models with cross-sectional outcomes of WAZ and LAZ at 2 years, we demonstrated that the early life effects were insensitive to further statistical adjustment for illnesses and antibiotic use after 6 months of age.Across 8 sites in the MAL-ED cohort, 1954 children were followed until at least 6 months of age and had at least 1 subsequent anthropometric measurement. The majority of these children  remained under surveillance and had anthropometric measurements at 2 years. Baseline characteristics, early antibiotic exposure, and growth outcomes differed across sites Table . Mean enA 7-day increase in duration of antibiotic exposure in the first 6 months of life was associated with an adjusted 0.03  higher WAZ from 6 months to 2 years of age compared to unexposed children. There was no difference between boys and girls, and this association was largely consistent across sites, except in Brazil and South Africa, where antibiotic use was least common and the estimates are least precise Fig. A. The laThe associations of duration of antibiotic exposure with LAZ were more varied across sites Fig. B. There In the assessment of class-specific exposure, macrolide and metronidazole use on at least 1 day during the first 6 months were associated with an adjusted 0.14  and 0.17  increase in WAZ, respectively. Cephalosporins, fluoroquinolones, and penicillins were associated with smaller and nonsignificant increases in WAZ. Associations with LAZ were generally smaller and not statistically significant for any antibiotic class  greater WAZ compared to children receiving 3 courses or less . These children had further gains of 0.08  and 0.04  in WAZ compared to children receiving 3 courses or less from 6 to 11 and 12 to 17 months, respectively. Adjusting for their WAZ at 18 months, there was no further difference in WAZ from 18 to 24 months associated with early antibiotic use . Children who did not, however, receive early antibiotics did not catch-up during this period such that the majority of the overall WAZ difference was maintained to 24 months. More than 3 courses of antibiotics was associated with a similar increase in LAZ by 6 months , but there were no associations in periods after 6 months  or overall as shown above.In contrast to the antibiotic effects in early infancy, duration of antibiotic exposure after 6 months of age were not associated with cross-sectional WAZ or LAZ at 2 years , adjusting for exposure before 6 months and illnesses across the first 2 years of life. Among the antibiotic classes, only fluoroquinolones were associated with increases in size at 2 years of age. Two or more courses of fluoroquinolones after 6 months of age were associated with an adjusted increase of 0.21  in WAZ at 2 years . The associations with other antibiotic classes were near the null and/or did not show a dose-response trend.We demonstrate that the growth-promoting phenomenon of early life antibiotic exposure among healthy children is not unique to high-resource settings and can also occur in populations with low average weights and lengths. Antibiotic exposure was associated with increases in weight in the MAL-ED cohort, and this effect was limited to early exposures in the first 6 months of life, which is consistent with previous studies ,9,13,14.A larger impact of macrolides compared to other antibiotics on BMI was similarly documented in a retrospective US study . Broad-sOur results provide support for the hypothesized mechanism through the gut microbiota. The influence of antibiotics on the diversity and composition of the gut microbiota can persist long after treatment is completed ,31, espeBecause the effect of early life antibiotics did not, however, affect growth rates after 18 months of age, the impact of an altered microbiota may be short lived. This evidence that the microbiota is not necessarily permanently “reprogrammed” to cause increased growth rates long after exposure is supported by a recent large study in the United States that found that early antibiotic use was not associated with higher rates of weight gain after the exposure period . Their rStill, because the unexposed children in the MAL-ED cohort did not complete catch-up growth, such that the weight difference associated with antibiotic exposure was still present at 24 months, these exposures may have sustained impact on a child's attained size. Short-term growth and attained size have been negatively associated with hospitalization and mortality , and posCampylobacter and enteroaggregative E coli in the first 6 months of life  relied on caregiver recall of antibiotic exposures at a minimum of 4 years after exposure and caregiver report of anthropometry . A previThis analysis was limited by the inability to assess long-term growth outcomes 5 to 10 years after exposure. This may explain why there was no observable effect of antibiotic exposure after 6 months of age, which may only become apparent later in childhood ,12,14. TAn association between antibiotics and weight gain in high-income settings is often discussed as a negative side effect of treatment since obesity is a growing public health problem and particularly pernicious among children. The cost-benefit analysis may, however, be different in low-resource settings where children may benefit from improvements in growth and are commonly infected with enteropathogens even in the absence of diarrhea . On the


The purpose of the present paper is to establish some new retarded weakly singular integral inequalities of Gronwall-Bellman type for discontinuous functions, which generalize some known weakly singular and impulsive integral inequalities. The inequalities given here can be used in the analysis of the qualitative properties of certain classes of singular differential equations and singular impulsive equations. ThenLetbe a continuous, differentiable and increasing function onwiththenwhereis the well-known beta-function andSuppose that the positive constantsβ, γ, ξ, andsatisfy conditions: ifandifandthenandare valid forLetbe a continuous, differentiable and increasing function onwithIfsatisfies the following inequality:Thenwheret and using ,,\documenmentclasspt{minimaequality  we get tequality . The proLetandthenIf }δ≤1, by , 18]  Ifandwe havewhere(2) If mentclass2pt{minimmentclass2pt{minim=\frac{1+\gamma}{(4γ)/γ to  and 16)\documentLetis a nonnegative piecewise continuous function with discontinuous of the first kind in the pointsand letbe a continuous, differentiable and increasing function onwithLetp, β, γbe positive constants, Ifsatisfies the inequality ds]p, , and usiimations  for \docConsequently, by using a similar procedure for imations  for \docentclass1pt{minimaLetis a nonnegative piecewise continuous function with discontinuous of the first kind in the pointsand letbe a continuous, differentiable and increasing function onwithLetp, q, m, n, ξ, β, γbe positive constants withIfsatisfies the inequality   If\docuIfandwe havewhereare the same as in Theorem andare the same in (1) of Theorem (2) mentclass2pt{minimWhen [t0,t1),  can be r). Since  and 40)\documentThen, when [t1,t2),  can be rds. From and 40)  \documenConsider the following Volterra type retarded weakly singular integral equations: Pečarić  discusseLetandbe continuous functions onand letbe continuous, differentiable and increasing functions onwithLetp, q, β, γ, δbe positive constants withAssumesatisfies equation (equation .Ifandwe havewhere(1) Ifandwe havewhere(2) From , we have1+δ)) to  and 52)53\documet and x on Consider the following impulsive differential system:Then the impulsive differential system  and 55)55) are eondition , from (5We see that  is the pIn this paper, we generalized the weakly singular integral inequality. The first inequality was a generally weak singular type, the second inequality was a like-weakly singular type with discontinuous functions, the third inequality was a type of weakly singular integral inequality with impulsive. We used analytical methods, reducing the inequality with the known results in the lemma, and the estimations of the upper bound of the unknown functions were given. The results were applied to the weakly singular integral equation and the impulsive differential system.


This paper firstly introduces the importance of temperature control in concrete measurement, then a passive radio frequency identification (RFID) sensor tag embedded for concrete temperature monitoring is presented. In order to reduce the influences of concrete electromagnetic parameters during the drying process, a T-type antenna is proposed to measure the concrete temperature at the required depth. The proposed RFID sensor tag is based on the EPC generation-2 ultra-high frequency (UHF) communication protocol and operates in passive mode. The temperature sensor can convert the sensor signals to corresponding digital signals without an external reference clock due to the adoption of phase-locked loop (PLL)-based architecture. Laboratory experimentation and on-site testing demonstrate that our sensor tag embedded in concrete can provide reliable communication performance in passive mode. The maximum communicating distance between reader and tag is 7 m at the operating frequency of 915 MHz and the tested results show high consistency with the results tested by a thermocouple. Temperature control for concrete plays a dominant role during its curing and maturation period . The hydThe traditional measuring techniques, such as thermocouple temperature measurement (TTM) ,9,10 andVarious types of RFID temperature sensors have been already reported. The simplest type of RFID temperature sensors is the chipless type ,20, whicOur previous work proves the feasibilities of applying RFID sensors for concrete monitoring , howeverIn order to avoid concrete cracking during the concrete cooling process, there are three basic principles that should be considered, including maximum temperature control, the rate of temperature change control, and abnormal temperature control . FirstlyT represents the concrete temperature, τ is the time variable, c is the specific heat capacity, and Q represents the power density of the internal heat source per volume. Considering the temperature field as a steady field, we can obtain the following equation:θ is the adiabatic temperature rise function of concrete, wρ, wc, and wq represent the density, specific heat capacity, and water flow of the pipe, respectively, cρ, cc, and cV represent the density, specific heat capacity, and volume of concrete, respectively, and w-inT and w-outT represent the water inflow and discharge of the pipe, respectively. According to the target temperature, we can obtain the theoretical water flow in Equation (3):Considering the internal heat source, a basic equation of three-dimensional heat conduction can be obtained according to the Fourier Law :(1)∂T∂τ=Therefore, a basic flow of temperature control, proposed in η0 is the intrinsic impedance of air and η1 represents the intrinsic impedance of concrete. Then the propagation loss can be expressed in dB as:d represents the depth of propagation and α is the attenuation coefficient.As we all know, concrete is a high-loss material for electromagnetic wave transmitting and, hence, its impact on RFID communication performances should be taken seriously into account. The overall loss of electromagnetic waves penetrating concrete can be divided into two parts: transmission loss and propagation loss . The traη1 and α are both highly influenced by humidity conditions of concrete, the transmission loss, propagation loss, as well as overall loss of electromagnetic waves penetrating concrete should be investigated at various concrete humidity conditions. Since From ,24,25, ttP can be derived from the equation below [rP represents the effective radiation power of a RFID reader, aG represents the gain of tag antenna, tη is the power conversion efficiency of RF-to-DC of the tag, λ is the wavelength of the electromagnetic wave, and d is the communication distance between reader and tag. According Equation 6, the communication distance d can be described as following:The operating power of a RFID tag on below :(6)Pt=PrE is limited by the RFID communication standards (4 W is the maximum transmitted power) and aG is approximately decided by the allowable antenna area (1.64 for the λ/2 dipole antenna). The communication distance is the most important parameter for designing the RFID tag and guarantees the stability and the reliability of the RFID system. According to Equation (7), in order to achieve higher d, lower tP and higher rη are critical for the UHF RFID tag design.Generally, rε = 4.4, thickness h = 2 mm). These transmission lines are designed to transmit the energy collected by the antenna to the inner part of the tag in concrete. The microstrips are insulated from both sides to prevent any degradation of the communication performance. In order to transmit all of the power received by the antenna to the sensor chip, the length of the transmission line must be a multiple of λ/2 in the medium. In this design, the length of the transmission line is 14.2 cm.This work aims to design a RFID sensor tag to perform temperature measurement at the required depth in concrete; therefore, the design of tag antenna should take concrete’s influence on communication into consideration. From the discussion above, the overall loss of 915 MHz at the depth of 0.2 m is about 10 dB, resulting in the UHF RFID tag being hardly read from the external RFID reader. Hence, we proposed a T-type antenna design in Generally, the power dissipation of a passive RFID tag is not over 25 µW, the power of the sensor integrated in the RFID tag is always limited to under 5 µW. Hence, the power of the sensor is the key for the integration between the RFID tag and the sensor . Furthertf. The DCO is used to generates a digital-controlled frequency df, which is controlled by the PD’s output ob. PD detects the phase difference between the TCO and DCO and then generates a corresponding digital signal ob. PD combines with TCO and DCO to form a PLL loop. The counter, utilizing tf as the reference clock, is responsible for converting ob into a corresponding digital code sensB. When the entire loop is stabilized, sensB represents the digital value of the temperature information.The architecture of the proposed temperature sensor is shown in oscf can be expressed as:dt is the delay time of the loop, lI is the current flowing through the inverter, lC is the equivalent load capacitor of the loop, and mV is the swing range of the output voltage which mostly equals the supply voltage DDV. According to Equation (8), each inverter of the TCO adopts a proportional to absolute temperature (PTAT) current source tI, resulting in the frequency of TCO tf being a PTAT frequency. Different from the TCO, the current source of DCO tI is set equal to the quiescent part of tI, the resulting df equals the quiescent part of tf when the capacitor mC is connected to the DCO loop. The mC connects or not to the DCO loop depending on the output ob from the PD. The value of mC is designed to make df slightly larger than tf when mC connects to the DCO loop.The schematic of the proposed temperature sensor is shown in rη of the rectifier. When the input power is smaller (or larger) than the optimal point of the rη curve, an extra bias-voltage can be added positively (or negatively) to promote the effective gate-source voltage of the switches. In addition, the extra bias-voltage equals zero when the input power comes at the optimal point, which means the bias-voltage is dynamic. From the above rules, N11-22 and PMOS transistors MP11-22, the gate-source voltage of which are boosted by the bias-voltage NV,21 and PV,21, respectively. The large resistor SR is adopted to block the AC component of NV,21 and PV,21. In order to avoid the large silicon area in the CMOS process, a PMOS transistor which operates in the cut-off region could replace SR.Inspired by Kamalinejad , a gate-2.The sensor tag was firstly tested and calibrated in the laboratory, as shown in The performances of the proposed antenna is shown in mC. Compared with [In order to test the temperature performances, the proposed sensor tag is put into the climate chamber together with an antenna of the RFID tester. The measured digital outputs of the tag at different input powers  are shown in red with ,24,25, tTo verify the RFID communication of the proposed sensor tag, the testing parameters are chosen as follows: the operating frequency is 915 MHz, the distances between the two antennas and the sensor tag are both 0.5 m, the transmitting power is 1 W. The overall communication flow is shown in 3 and this block is composed of 50% ordinary Portland concrete and 50% sand. The SHT75 humidity sensor and the proposed RFID temperature sensor tag are all buried in the concrete, then a handheld RFID reader is placed on the surface of concrete to measure the maximum communication distance between the reader and the antenna of the sensor tag under different humidity conditions. If the successful reading ratio is more than 80%, the communication distance can be considered an effective communication distance. The measurement results are shown in The exploited RFID temperature sensor tag is buried in concrete for temperature monitoring, so the transmission loss of the sensor tag under different humidity conditions significantly influences its performance. Thus, the transmission loss under different humidity conditions is experimentally measured. A Sensirion SHT75 humidity sensor is employed to measure the concrete humidity. As is shown in The temperature performances of the concrete during the maturation process were tested by the proposed RFID sensor. The tests were repeated when the RFID sensor was immersed at depths of 15, 10, and 5 cm, respectively. Three additional thermocouples were, respectively, placed in the same location as the references. Two hours after casting, the specimen used for testing was heated by an oven to the temperature of 50 °C for three hours, then the oven was turned off for the analysis of the cooling process of the concrete. During the heating and cooling process, the temperature was measured by both the thermocouples and the proposed RFID temperature sensor tag. The temperature measured results without intelligent control are shown in The monitoring software interface for concrete temperature is shown in The proposed non-destructive concrete temperature monitoring system can track the temperature inside the large volume concrete in real-time, compared with traditional methods, it reduces the cost and avoids a complex layout. Temperature monitoring plays a dominant role in concrete measurement. In this work a wireless temperature sensor tag based on the EPC generation-2 UHF communication protocol is proposed to monitor the temperature inside concrete online. Considering the high losses of electromagnetic waves in concrete, a T-type antenna is proposed to ensure the sensor tag can work inside the concrete. The temperature sensor employs a PLL-based architecture and can transfer the sensor values to a digital output in the frequency domain without a reference clock. The measured results show the proposed sensor tag achieves high temperature linearity. The communication flow of the proposed sensor tag was tested in the laboratory, the maximum operating distance and the temperature measurement were tested on a construction site. The measured temperature results by the RFID sensor and thermocouple are almost consistent. The whole experiment demonstrates that the proposed sensor tag can provide reliable performance in wireless concrete temperature measurement.


P = 0.001) and pT stage . In addition, patients with c-Met-high RCC showed significantly worse overall survival than those with c-Met-low tumor . In conclusion, this meta-analysis demonstrates that high c-Met expression correlate with significantly worse pathological features and overall survival, indicating c-Met overexpression is a potential adverse prognostic marker for patients with RCC.c-Met overexpression has been observed in renal cell carcinoma (RCC). However, its clinicopathological impacts remain uncertain. We performed this meta-analysis to evaluate the pathologic and prognostic impacts of high c-Met expression in patients with RCC. A systematic computerized search of the electronic databases PubMed and Embase was performed. From 12 studies, 1,724 patients with RCC were included in the meta-analysis. Compared with RCCs showing low c-Met expression, tumors with high c-Met expression showed significantly higher nuclear grade (odds ratio = 2.45 [95% CI: 1.43–4.19],  Renal cell carcinoma (RCC) is the most common malignant renal neoplasm, accounting for approximately 85% of kidney cancers , 2. MostWith understanding of molecular mechanisms of carcinogenesis, treatment of RCC has dramatically changed. The molecular targeted agents such as sorafenib, sunitinib, axitinib, pazopanib, or temsirolimus are currently recommended with improved outcomes for patients with metastatic RCC –10. HoweMET located on chromosome 7. The HGF-c-Met signaling pathway regulates multiple cellular functions, including differentiation, proliferation, and angiogenesis .In RCC, many studies have suggested that c-Met expression is associated with significantly inferior clinicopathological features, such as tumor grade , 36, 38,= 0.015) . Recentlat al. had also performed the similar meta-analysis regarding clinicopatholigical impacts of c-Met expression in RCC [P = 0.001) and pT stage . In addition, patients with c-Met-high RCC showed significantly worse OS than those with c-Met-low tumor . Our findings indicate that high c-Met expression represent a potential adverse prognostic marker for patients with RCC. In the subgroup analyses, however, the OS failed to show statistically significant difference between patients with c-Met-high tumor and those with c-Met-low tumor in both pRCC  and ccRCC . Because the limited number of studies was included in the subgroup analyses, further studies are needed to evaluate the prognostic role of c-Met expression in the subtypes of RCC.In the current meta-analysis, we included studies comparing the major pathological features (nuclear grade and pT stage) and cancer-specific survival outcome according to the c-Met expression status. Chen n in RCC . They inn in RCC , 25 and n in RCC , 27. ComP = 0·00026) and progression-free survival . Based on these results, the U. S. FDA approved cabozantinib for patients with advanced RCC who have received prior anti-angiogenic therapy. In a phase II study with RCC, interestingly, therapeutic response of foretinib  was closely associated with the germline MET mutations [Several meta-analyses in other cancers have also demonstrated that high c-Met expression is an adverse prognostic marker for survival –23. Thusutations . In addiutations , 47. TheMET amplification/upregulation has been proposed as a mechanism of resistance to anti-angiogenic therapy [et al. retrospectively analyzed c-Met expression in 137 patients with metastatic RCC treated with sunitinib and found that high c-Met expression was associated with poor survival [Recently,  therapy , 47. Ant therapy . c-Met a therapy . Peltolasurvival . c-Met usurvival .in situ hybridization, reverse transcription-polymerase chain reaction (RT-PCR), and molecular invasion probe are currently used to assess c-Met status, but there are no standardized criteria for overexpression. There are also differences in the IHC criteria for high c-Met expression. The discrepancies in the clinicopathological impacts of c-Met among studies might be due to the different methods and criteria for high c-Met expression. Therefore, the definition of reliable criteria for c-Met status is essential to verify the prognostic role of c-Met expression and develop c-Met inhibitors in solid tumors.The major limitation for clinical application of c-Met inhibitors is that there is no consensus of the reliable criteria for high c-Met expression. A variety of methods, such as IHC, Western blot, fluorescence Our study has several inherent limitations. First, the meta-analysis included a small number of studies. Second, all the studies were retrospectively performed. Third, as we mentioned above, the studies used different IHC methods  for assessing c-Met expression. In addition IHC criteria to stratify c-Met status were also various among studies. Fourth, because of limited information in most studies, we could not consider the impact of systemic therapies that would have inevitably affected the OS. Finally articles published only in English were included, which might bias the results.In conclusion, our results show that c-Met overexpression is significantly associated with poor pathological features and prognosis. These findings indicate that high c-Met expression is a potential adverse prognostic marker for patients with RCC. However, larger studies using standardized methods and criteria are still needed to verify the prognostic roles of c-Met expression in various subtypes of RCC.We performed this meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . A systeEligible studies should meet the following inclusion criteria: (i) patients had a pathological diagnosis of RCC; (ii) pathological features (nuclear grade and/or pT stage) or OS were analyzed according to c-Met expression status; (iii) ORs with 95% CIs for pathological features or HR with 95% CI for OS were provided or could be estimated from the data provided; (iv) articles were published in English.Articles with no criteria for c-Met expression status were excluded. We also excluded articles with very low cutoff value (IHC staining in < 10% of tumor cells) for high c-Met expression.The required data were collected independently by two investigators (BJK and JHK). If these two authors did not agree, the other investigator (HSK) was consulted to resolve the discrepancies.The following data were recorded from all eligible studies: the first author’s name, publication year, country, histology, nuclear grade, pT stage, methods to test c-Met expression, antibody and detection kit for IHC, number of patients, treatment, cutoff values adopted to dichotomize c-Met expression as ‘high’ or ‘low’, and HR with 95% CI for OS and OR with 95% CI for pathological features.Q statistic and the I2 inconsistency test. The fixed-effects model (Mantel–Haenszel method) was selected for pooling homogeneous outcomes when P ≥ 0.1 and I2≤ 50%, whereas the random-effects model (DerSimonian–Laird method) was applied for pooling heterogeneous outcomes when P <  0.1 and I2 > 50%. The RevMan (version 5.2) was used to combine data and report outcomes. All reported P-values were two-sided and P < 0.05 was considered statistically significant. Publication bias was assessed graphically by the funnel plot method [Statistical values were obtained directly from the original articles. When OR or HR with 95% CI were not provided, the Engauge Digitizer (version 9.1) was used to estimate the needed data from the results and Kaplan-Meier curves. The strength of the association between c-Met overexpression and nuclear grade or pT stage was shown as ORs with their 95% CIs. The effect size of OS was pooled through HR with its 95% CI. The heterogeneity across studies was tested by the t method .


In particular, LiFePO4/Li cells based on the HPE deliver good rate capability and long-term cycling performance with an initial discharge capacity of 152.1 mAh g−1 and a capacity retention ratio of 88% after 150 cycles with a current density of 0.5 C at 80°C, demonstrating great potential application in high-performance LIBs at elevated temperatures.A new class of freestanding cross-linked hybrid polymer electrolytes (HPEs) with POSS as the cross-linker was prepared by a one-step free radical polymerization reaction. Octavinyl octasilsesquioxane (OV-POSS) with eight functional corner groups was used to provide cross-linking sites for the connection of polymer segments and the required mechanical strength to separate the cathode and anode. The unique cross-linked structure offers additional free volume for the motion of EO chains and provides fast and continuously interconnected ion-conducting channels along the nanoparticles/polymer matrix interface. The HPE exhibits the highest ionic conductivity of 1.39 × 10 LiTFSI was stored in a desiccator and dried under vacuum condition at 120°C for 12 h before used. Tetrahydrofuran (THF), 2,2-azobisisobutyronitrile (AIBN), ethyl acetate and petroleum ether, purchased from Sinopharm Chemical Reagent Co., Ltd., were used as received.Poly(ethylene glycol) methyl ether methacrylate , SMA  and AIBN  were dissolved in 8 mL of ethyl acetate to obtain solution A. Various amounts of OV-POSS  were dissolved in 8 mL of THF to form solution B. Solutions A and B were mixed in a 50 mL three-neck flask equipped with a condenser and the mixture was heated to 70°C in an oil bath under constant stirring and NPEGMEM/SMA-g-POSS copolymers and LiTFSI with a desired [EO]/[Li] molar ratio were dissolved in THF and then poured into the Teflon mold with groove. The mixed solution was transferred to the fume hood and stood for 12 h at room temperature. The HPEs were obtained after the mixture was dried in vacuum oven at 100°C for 12 h. And then the HPEs with cross-linked branching structure with POSS as the cross-linker were obtained, as shown in Scheme 1, and stored in glove box for further used. The thickness of polymer electrolyte membrane is around 200 μm.1H NMR analysis  was used to characterize the structure of HCPs. Gel permeation chromatography (GPC) test (Waters 515–2410 instrument) was used to measure the molecular weight of HCP. Thermogravimetric analysis (TG)  was performed to assess the thermal stability. Field emission scanning electron microscopy (FE-SEM) analysis (Nova Nano SEM230) was carried out to investigate the microstructure of electrolytes.−1. The symmetric Li/HPE/Li cells were fabricated to evaluate the interfacial stability between the electrolyte and lithium electrode. LiFePO4/HPE/Li coin cells were also assembled to investigate the electrochemical performance of HPEs in LIBs. Energy-type LiFePO4 was purchased from a reliable commercial source. The mixture of LiFePO4 (80 wt%), carbon black (10 wt%), and PVDF (10 wt%) was dispersed in N-methyl-2pyrrolidone (NMP) to form a slurry. Subsequently, the resultant slurry was coated onto aluminum foil, and then dried under vacuum at 110°C for 12 h to remove the residual NMP. The diameter of LiFePO4 cathode, electrolyte membrane and Li metal electrode in the coin cell is 12, 18, and 16 mm, respectively. The galvanostatic charge/discharge tests were carried out in a battery testing system  between 2.5 and 3.7 V at different rates.Symmetric stainless steel/HPE/stainless steel cells were assembled to measure the ionic conductivity of HPEs using a PARSTAT 4000 system (Ametek Advanced Measurement Technology INC.) over the frequency range of 0.1 Hz−100 kHz from 25 to 80°C with a perturbation voltage of 10 mV. Linear sweep voltammetry (LSV) was taken on stainless steel/HPE/Li cells to estimate the electrochemical stability of HPEs at a scan rate of 5 mV s1H NMR spectrum of the copolymers with the POSS molar ratio of 5% (HCP-5) is shown in Figure 2-CH2-O (EO) units in PEGMEM segments :Ii+j represents the integral area of the resonance peaks at 5.88–6.07 ppm from the unreacted vinyl protons of POSS, Ia represents the integral area of the resonance peaks at 1.92 ppm from the reacted vinyl protons of POSS, Ie represents the integral area of the resonance peak of protons from CH2 units in SMA segments at 1.23 ppm and Ig represents the integral area of the resonance peak from the protons of CH2-CH2-O (EO) units in PEGMEM segments at 3.41–4.32 ppm. The calculated values of various POSS mole contents are summarized in Table where Mw) of are in the range of 13.2–14.8 × 10−3 g mol−1 and values of polydispersity index (PDI) are ranging from 1.23 to 1.30, suggesting that the distribution of molecular weights for these HCPs was quite narrow.Gel permeation chromatography (GPC) was used to measure the molecular weight of HCPs and the results are summarized in Table Figure + can be observed at 25, 80, and 120°C, respectively, suggesting that the electrolyte is less stable at high temperatures. Even so, such electrolyte still exhibits a high stable electrochemical window (>5.0 V vs. Li/Li+) at high temperatures, demonstrating great potential in high-potential LIB applications.Thermal and electrochemical stabilities are two important parameters used to estimate the safety of the electrolyte. As shown in the inset of Figure Symmetric stainless steel/HPE/stainless steel cells were assembled to measure the ionic conductivity of HPEs using a PARSTAT 4000 system. The ionic conductivity was obtained by the following equation (Equation 2):where L and S were the thickness and area of the HPEs respectively, and R was the bulk resistance of the HPEs obtained from the Nyquist plot. The ionic conductivities of HPEs with various POSS contents  at different LiTFSI concentrations were investigated, as shown in Figure −5 S cm−1 at 25°C and 1.39 × 10−3 S cm−1 at 80°C, much higher than that of the PEGMEM/SMA polymer electrolyte  equation (Equation 3):T is the testing temperature; Ea is the activation energy; k is Boltzmann constant (8.314 × 10−3 kJ mol−1 K−1) and stands for is the equilibrium glass-transition temperature  and conductivity (3.94 × 10−5 S cm−1 at 25°C and 1.39 × 10−3 S cm−1 at 80°C) are observed for the HPE containing 5 wt.% POSS, indicating that the introduction of POSS could facilitate the transmission of charge carriers by increasing free volume for the motion of EO chains. However, the ionic conductivity decreases with the further increase of POSS, since the bulky POSS segments act as a barrier to restrain the migration of charge carriers. The value of Ea in Table −1, which is in agreement with the value for solid polymer electrolyte  and T0 (213 K) also could be observed for the HPE containing 5 % POSS. Figure Table Tm), melting enthalpy (ΔHm) and degree of crystallinity (Xc) obtained from DSC are summarized in Table + transport, resulting in higher ionic transmission efficiency, as schematically illustrated in Figure The improvement in ionic conductivity for the HPE with 5% POSS content can be attributed to the reduced crystallinity of the EO groups. Figure −2 for a Li/Li symmetric cell was carried out to investigate the interfacial stability at 25 and 80°C. As shown in Figure −2 is ~0.698 and 0.046 V at 25 and 80°C, respectively. When the current density increases to 0.2 mA cm−2, polarization voltage presents ~1.288 and 0.144 V at 25 and 80°C, respectively. No obvious fluctuations could be observed during the whole cycling process, demonstrating that such HPE exhibits stable interfacial compatibility with lithium metal electrode and shows great potential for application in high performance LIBs.Interfacial stability between polymer electrolyte and electrode materials is the key factor to affect the performance of lithium ion batteries. Polarization testing with a constant current density of 0.1 mA cm4/Li coin cells using HPEs with 5 wt.% POSS content were assembled for evaluating the battery performance. Figure 4/Li coin cell under various C-rates with a charge current density of 0.1 C at 80°C. Discharge capacities of 154 mAh g−1 were achieved at 0.1 C and ~140 mAh g−1 could be observed at 0.2, 0.5, 1, and 2 C, and the flat potential plateaus could also be observed up to 2 C rate. Even at higher discharg rates of 5 and 10 C, the discharge capacities of 99 and 61 mAh g−1 could still be obtained, respectively. Figure 4/Li battery assembled using HPEs with 5 wt.% POSS content with a current density of 0.5 C at 80°C. Note that the cell delivers an initial discharge capacity of 152.1 mAh g−1 with a capacity retention ratio of 88% after 150 cycles and the coulombic efficiency of ~99% could be observed in the charge/discharge process, which is higher than other PEO-based solid polymer electrolyte (Table LiFePOte Table . The res4/Li cells assembled using HPEs with 5 wt.% POSS content delivers not only good rate capability but also enhanced long-term cycling performance at 80°C, displaying great potential application in high-performance LIBs at elevated temperatures.A new class of freestanding cross-linked HPEs with POSS as the cross-linker was prepared by a one-step free radical polymerization reaction. PEGMEM/SMA-g-POSS HPEs exhibit unique cross-linked structure and provide low energy, fast and continuously interconnected ion-conducting channels along the nanoparticles/polymer matrix interface. Compared to PEGMEM/SMA polymer electrolyte, such cross-linked HPEs exhibit enhanced thermal and electrochemical stabilities, improved ionic conductivity and interfacial compatibility. Moreover, LiFePOJZ and CM carried out the experimental work and the data collection and interpretation. XL participated in the design and coordination of experimental work, and acquisition of data. YL and HW participated in the study design, data collection, analysis of data and preparation of the manuscript. YW, SH, and WW carried out the study design, the analysis and interpretation of data and drafted the manuscript. All authors read and approved the final manuscript.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. The reviewer, BQ, and handling Editor declared their shared affiliation.


Detailed research is carried out to ascertain the inhibitory effect of waste glass powder (WGP) on alkali-silica reaction (ASR) expansion induced by waste glass aggregate in this paper. The alkali reactivity of waste glass aggregate is examined by two methods in accordance with the China Test Code SL352-2006. The potential of WGP to control the ASR expansion is determined in terms of mean diameter, specific surface area, content of WGP and curing temperature. Two mathematical models are developed to estimate the inhibitory efficiency of WGP. These studies show that there is ASR risk with an ASR expansion rate over 0.2% when the sand contains more than 30% glass aggregate. However, WGP can effectively control the ASR expansion and inhibit the expansion rate induced by the glass aggregate to be under 0.1%. The two mathematical models have good simulation results, which can be used to evaluate the inhibitory effect of WGP on ASR risk. Since the 1980s, the use of waste glass (WG) in concrete has been investigated in USA and Europe. With regard to concrete production, WG can be used as fine aggregate to replace sand after being crushed or as a supplementary cementitious material to replace cement after being ground. In the former case, glass exhibits double effects on properties of concrete, both positive and negative. If the replacement ratio is greater than 20%–30%, the mechanical properties will decrease as the replacement ratio increases  and duraWG contains a significant amount of alkali and silicon dioxide (reactive silica). It may lead to alkali-silica reaction (ASR) risk and concrete cracking, which is the main reason accounting for the early stagnation of research on the use of WG in concrete. Lots of research ,2,3,6 inIn this paper, ASR expansion and its mechanism of mortar containing WG as fine aggregate are investigated. The inhibitory effect of WGP as a replacement of cement on ASR is studied and verified by macro and micro tests. In addition, the results refer to used green glass, which is a soda-lime glass. Even slight changes in the compositions  could possibly lead to somewhat different results. The micro properties are also tested by scanning electron microscopy (SEM), which can be used to explain the ASR mechanism in depth.Raw materials used in this paper include cement, glass, water and standard sand. The cement is 42.5 Portland cement, whose chemical compositions are listed in i.e., 15%.Soda-lime glass is employed in this work due to its popularity all over the world. WG aggregate is prepared by collected green glass after being cleaned, dried, crushed, and taken for a screening test according to GB/T14684-2001 Sand for construction . The mas2, 14.10% Na2O and 10.52% CaO, and it is a typical soda-lime glass . WGP may have pozzolanic activity even cementing property due to high lime and silicon content. Meanwhile, it may also raise ASR risk of concrete due to the high alkali and silicon content.WGP refers to the glass particles with a maximum particle size below 300 μm in this work. WGP is prepared by grinding the WG fine aggregate in ball mill. Furthermore, WGP is divided into seven finenesses, named GA, GB, GC, GD, GE, GF and GG by controlling the grinding time. Its chemical compositions are also presented in i.e., 300–500 μm and 200–400 μm, respectively. The size distribution of GC is similar to that of GD. The particle size distribution of GE, GF and GG are similar to that of cement. No cement particle is larger than 100 μm, while the three WGPs contain small amounts of particles with a size higher than 100 μm. Furthermore, the specific surface area of the three WGPs is greater than that of cement because specific surface area depends on both particle size and particle shape of WGP. WGP contains more slender angular particles due to its fragile features, which leads to a higher specific surface area. Compared with cement, GF and GG have more particles below 20 μm and fewer particles with the size over 30 μm.3 (3). The particle morphology of WGP is shown in The density of WGP is about 2.5 g/cm3 , which ii.e., the amorphous silica.As can be seen from 3. The mix proportions are shown in In order to study the ASR activity and expansion development induced by WG aggregate, the mortar bar method  and theAfter ASR test, small clean specimens are taken out from the central of the mortars by a hammer and soaked in anhydrous ethanol to avoid carbonization before SEM observation, less than two weeks. The samples are dried for 2–3 h at 60 °C in a vacuum drying oven and placed in a vacuum coating machine for dehumidifying and gilding treatment.i.e., 0%, 10%, 30%, 50%, 70%, 90% and 100%, labeled as WG0, WG10, WG30, WG50, WG70, WG90 and WG100.The ASR risk of glass aggregate used to replace standard sand is tested by controlling the replacement ratio, According to 2 and promotes more ASR gel. When the replacement ratio is higher than 90%, the increasing amount of SiO2 in the pore solution results in more OH− absorption, which leads to insufficient OH− to participate in ASR locally so that the amount of ASR gel decreases. WG aggregate has five size grades and contains partial WGP, which has inhibitory effect on ASR expansion because of its pozzolanic activity. Thus the expansion of samples containing more glass aggregate is a little lower. While some researchers found that ASR expansion shows increasing trend as glass aggregate replacement ratio increases [The expansion of 14 days reaches the maximum when WG content is 90%, which is the worst point for the ASR of concrete , but notncreases . This isncreases ,14,15 haThe mortar bar method is also used and compared with the accelerated mortar bar method. The main difference is the curing temperature. In order to test the ASR activity rapidly, the period of the accelerated mortar bar method is 14 days, and the curing temperature is 80 °C. The temperature of the mortar bar method is 38 °C, which is closer to the actual engineering application ,16. FiguAs temperature can greatly improve the ASR, ASR expansion of the mortar bar method is much lower than that of the accelerated mortar bar method. When the replacement ratio of glass aggregate is greater than 30%, the expansion is larger than 0.05% at 90 days; when the replacement ratio increases to 50% or more, the expansion improves rapidly and reaches the most harmful level at 90% replacement ratio at 60, 90 and 180 days, which verifies the results observed by the accelerated mortar bar method.In order to analyze the inhibitory effect of WGP on ASR risk induced by WG aggregate, WGP is used to replace cement. The mix proportions are shown in 2 in solution is consumed, which leads to the reduction of ASR expansion. Meanwhile, calcium silicate hydrates (C–S–H) produced by WGP’s pozzolanic reaction combines with a part of alkali [As shown in f alkali ,18, whicf alkali , which mThe growth of ASR expansion rate is leveling off after mixing WGP, and the time-expansion curve converged gradually, especially for the samples containing 30% WGP. The pozzolanic activity of WGP is more obvious at later age, so it is more effective for reducing ASR.The prevailing research shows that ASR expansion will decrease with the reduction of glass particle size when WGP is used as a cement substitute at the same replacement ratio. Recycled soda-lime glass aggregate shows the highest expansion in the size range of 1.18–2.36 mm when maintaining the same composition and mineralogy . If the 2 from the particle surface will be dissolved into the solution and react with Ca(OH)2 to form C–S–H gel until the local depletion. Thereafter, SiO2 react with alkali to generate ASR gel. However, as for fine WGP particles, WGP only conducts pozzolanic reaction and can be completely dissolved. Furthermore, WGP contains higher level of Ca2+, which is released for pozzolanic reaction and involved in the hydrated products [2 to form ASR gel. And ASR gel swelling caused by WGP, which belongs to the uniform expansion, will not cause local destruction of concrete. The finer WGP has higher pozzolanic activity. The active aggregate is wrapped by WGP particles whose dissolution causes pozzolanic reaction to form C–S–H gel. Then, these small particles of C–S–H gel react with SiO2 of glass again to generate C–S–H gel with low Ca/Si ratio. ASR expansion rate can also be controlled in the safe level when the WGP content is 10%, 20% and 30% with its average particle size less than 8.2, 16.95 and 144.08 μm, respectively.WGP with different particle size used to evaluate its inhibitory effect is shown in products . So therAt the same time, it can be drawn from 2/kg, respectively, according to the interpolation calculation.In practice, the actual temperature of concrete is different, so it is necessary to consider the effect of curing temperature on the ASR expansion. The ASR expansion under normal (40 °C) and high temperature condition (80 °C) is compared in As high temperature can improve ASR, the development of ASR expansion under 40 °C is slower than that under 80 °C, and the expansion at 14 days is maintained at safe levels (<0.1%). The chemical reaction rate increases as well as ASR become more obvious along with the increase of curing temperature; meanwhile, higher temperature results in more alkali releasing to the pore solution and increasing ASR risk . NeverthAs shown in i.e., average particle size and content of WGP) controlling the inhibitory effect on ASR expansion. According to above analysis, there are two comprehensive factors :Yis the reducing rate of ASR expansion rate compared with the sample without WGP at 14 days, and Y = 1 − (ASR expansion of the sample with WGP/ASR expansion of the sample without WGP); A, B and C are Parameters; P is the WGP content; and D is the average particle size of WGP.As can be seen from the above data characteristics, the reasonable law should be studied to provide a reference for the use of WGP. ASR expansion inhibitory rate Using the software of Excel, parameters determined by fitting the data using linear regression, as calculated by Equation (2):As the fitting case is plotted , the inhY is the reducing rate of ASR expansion rate compared with the sample without WGP at 14 days, Y = 1 − (ASR expansion of the sample with WGP/ASR expansion of the sample without WGP); a, b and c are Parameters; P is the WGP content; and S is the specific surface area of WGP.From the data characteristics above, there is a high correlation among the specific surface area and content of WGP, and inhibitory rate of ASR expansion, as Equation (3):Based on the linear regression fitting, the parameter can be obtained as Equation (4):2/kg, respectively.As shown in 2 again to generate C–S–H with low Ca/Si ratio. ASR is a slow process that is later than the pozzolanic reaction, it generates C–S–H wrapping of the aggregate to improve the cementing property between the aggregate and the surroundings, and prevents ASR to some degree.2 of WGP and Ca(OH)2 of the initial cement hydration [2 continues reacting with the C–S–H gel with high Ca/Si ratio to form C–S–H gel with low Ca/Si ratio. Besides, 2 to generate C–S–H gel and avoid ASR.The Ca/Si ratio of C–S–H gel in the mortar with WGP is low and is close to 1 d. C–S–H ydration ,29. Addi(1)WG aggregate has high alkali reactivity. The ASR expansion increases with the increase of the replacement ratio of glass aggregate, and reaches the maximum values at 90% replacement ratio.(2)WGP can greatly reduce the ASR expansion induced by glass aggregate. The ASR expansion decreases with the increase of the content and fineness of WGP. When WGP size is less than 209.2 μm, it will add no ASR expansion and, meanwhile, it has a certain inhibitory effect on ASR expansion.(3)2/kg, respectively, or with low average particle size according to the calculation.The specific surface area of WGP and the ASR expansion have an anti-correlation, which leads the pozzolanic reaction more intense and faster and higher inhibitory effect on ASR expansion. The ASR expansion can be controlled in a safe range when WGP content is 10%, 20% and 30% with its specific surface area greater than 1137.40, 604.37 and 71.34 m(4)Higher temperature can promote both the pozzolanic reaction and ASR, and the inhibitory rate increases under high temperature for low WGP content (<20%), but decreases for high WGP content (30%).(5)Microstructural study confirms the macro testing. There will be ASR reaction ring around the large glass aggregate particle and the microcrack in the mortar without WGP, but C–S–H gel with low Ca/Si ratio and no ASR will appear in the mortar with WGP.


Over the last several decades, antibacterial drug use has become widespread with their misuse being an ever-increasing phenomenon. Consequently, antibacterial drugs have become less effective or even ineffective, resulting in a global health security emergency. The prevalence of multidrug-resistant organisms (MDROs) varies widely among regions and countries. The primary aim of antibiotic stewardship programs is to supervise the three most influential factors contributing to the development and transmission of MDROs, namely: (1) appropriate antibiotic prescribing; (2) early detection and prevention of cross-colonization of MDROs; and (3) elimination of reservoirs. In the future, it is expected that a number of countries will experience a rise in MDROs. These infections will be associated with a high consumption of healthcare resources manifested by a prolonged hospital stay and high mortality. As a counteractive strategy, minimization of broad-spectrum antibiotic use and prompt antibiotic administration will aid in reduction of antibiotic resistance. Innovative management approaches include development and implementation of rapid diagnostic tests that will help in both shortening the duration of therapy and allowing early targeted therapy. The institution of more accessible therapeutic drug monitoring will help to optimize drug administration and support a patient-specific approach. Areas where further research is required are investigation into the heterogeneity of critically ill patients and the need for new antibacterial drug development. International health organizations, including the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), have used terms such as “crisis,” “catastrophic consequences” and “nightmare scenario” to highlight the rapid emergence and spread of antibiotic resistance –4. The WS aureus (20.5 %) was the most frequent organism isolated, despite the overall predominance of Gram-negative organisms as a group: 62.2 %  .Tab.Tab66].T90 of tedizolid was 0.5 μg/mL for MRSA, which was fourfold lower than that of linezolid [MRSA is a major MDRO in ICU’s around the globe. It is frequently treated with vancomycin, linezolid, daptomycin, ceftaroline or tigecycline. Linezolid was found to be superior for the treatment of HAP in the ZEPHyR trial  in termsinezolid .Enterococci are Gram-positive facultative anaerobes that live as commensals in the gastrointestinal tract, but they are not as virulent as S. aureus or S. pneumoniae. Donskey et al. [Enterococci spp. are likely to function as a reservoir of drug resistance determinants and can serve as the springboard for the spread of these genes to other Gram-positive pathogens [y et al.  conductey et al. . Limitinathogens . It is iathogens . New ageathogens .Enterobacteriaceae spp. using monotherapy is often inadequate, and challenging cases may require the use of highly toxic agents. Aminoglycosides, polymyxins, tigecycline, fosfomycin and occasionally fluoroquinolones form the backbone of treatment. Recently, the US Food and Drug Administration (FDA) issued a warning regarding the risk of increased mortality in patients treated with tigecycline, observed in the clinical trials [P. aeruginosa, including various MDR types [Pseudomonas ssp. is the use of intra-tracheal antibiotics (ITA), consisting mainly of aminoglycosides and polymyxins, with encouraging results seen to date. In mechanically ventilated patients, the use of ITA for prevention or treatment of VAP has shown less toxicity as compared to systemic formulations [Acinetobacter spp. similar to P. aeruginosa have ample ways to develop and horizontally transfer resistance. Of greatest significance is the production of beta-lactamases and aminoglycoside-modifying enzymes [Acinetobacter spp. However, a recent paper has highlighted the risk of nephrotoxicity when colistin and vancomycin are used in combination with no benefit to clinical outcome [Treatment of carbapenem-resistant l trials . An obsel trials  found itl trials . Emerginl trials . Ceftazil trials . A newlyDR types . Anotherulations . A recenulations . Acineto enzymes . Combina outcome .K. pneumoniae had an enhanced efficacy over either agent alone both in vitro and in vivo in animal models. Giamarellou et al. [K. pneumoniae.More recently, studies have been conducted revealing the benefits of treatment with “new” combination therapies for XDR or PDR organisms. In terms of PDR Gram-negative infections, Bulik et al.  found thu et al.  found thAs the vast majority of the antibiotic treatment is short term, many companies struggle to generate profit from the sales of anti-infective agents. The majority of products being approved are second-, third- or fourth-generation antibiotics, meaning they are follow-up compounds, without a novel mechanism of action. In addition to this, many novel antibiotics have struggled to reach the market due to difficulties in demonstrating efficacy or unacceptable side effects. Furthermore, for licensing purposes, new antibacterials must demonstrate non-inferiority against already marketed drugs. Finally, healthcare authorities are frequently reluctant to pay the high costs associated with clinical trials, hindering the development of novel antimicrobial agents.P. aeruginosa) could induce an antibody response in healthy volunteers [As a result of the declining effectiveness of existing antibiotics and the steady decrease in new antibiotic development, alternative approaches to antibiotic therapy are appearing including immunotherapy and the use of bacteriophages. Immunotherapy initiated at the outset of an antibiotic course has the potential to result in beneficial effects; however, use is frequently limited by a narrow spectrum of action against specific target antigens. Another attractive approach to address the critical need for new antibiotics is the engineering of various components of the immune response such as monoclonal antibodies. For instance, a randomized, placebo-controlled phase I study found that IC43   or β-lacStaphylococcus aureus and the spread of multiresistant strains of pathogens in patients without classic risk factors in the ICU are key areas to delineate in future studies. Guidelines and recommendations will need to incorporate the ecology of the hospital setting and the severity of patient illness to provide a personalized patient approach to antimicrobial treatment in the future.In summary, a steady resistance increase particularly to Gram-negatives, rising minimum inhibitory concentration in methicillin-resistant