Neoadjuvant chemoradiotherapy (CTRT) can effectively downstage esophageal squamous cell carcinoma (SCC) in patients with locally advanced disease and prolonged survival have been observed in patients with a pathological complete response (ypCR).This exploratory study aimed to identify immunological predictors of pCR after neoadjuvant CTRT within SCC microenvironment. The tumor regression after neoadjuvant therapy was measured according to the Mandard score system. Eighty‐eight consecutive patients with SCC of the thoracic esophagus who received neoadjuvant CTRT were included in this retrospective study. Inclusion criteria were neoadjuvant CTRT and the availability of representative histological samples taken at diagnosis. We investigated immunohistochemical expression of CD4, Tbet, FoxP3, CD8, CD80, PD‐L1, and PD‐1, in the pretreatment biopsies and correlated the immunohistochemical profiles to patients’ outcomes.P = 0.004, 73 (36‐147) vs 21 (7‐47), P = 0.0006 and 39 (23‐74) vs 5 (0‐13), P < 0.0001 respectively). The accuracy of expression of PD‐L1+, CD8+, and CD4+ lymphocyte rate in identifying responders was AUC = 0.76 (P = 0.001), AUC = 0.81 (P = 0.0001) and AUC = 0.75 (P = 0.0001), respectively. Within the ypCR group, all patients with high infiltration of CD4+ T cell recurred/relapsed while only the 38.9% of those with low CD4+ T cell infiltration did the same (P = 0.058).After neoadjuvant CTRT, 23 patients had pCR, while 65 ones had partial response, stable disease or progression. PD‐L1 expression and CD8+ and CD4+ lymphocyte rate were significantly higher in patients who had ypCR compared to those who had not (10 (0‐55) vs 0 (0‐0), PD‐L1 expression and CD8+ and CD4+ lymphocyte rate were predictive of ypCR after neoadjuvant CTRT for SCC of the thoracic esophagus with adequate accuracy. Furthermore, recurrence/relapse was associated with high level of CD4+ T cell infiltration. However, the small sample size prevented to draw definitive conclusions; further studies are necessary to evaluate the prognostic role of these markers. Mucosal expression of PDL1 and CD8+ and CD4+ lymphocyte rate is predictive of clinical complete response after neoadjuvant CT‐RT for SCC of the thoracic esophagus with adequate accuracy. Furthermore, recurrence/relapse after complete response is associated with high level of CD4+ T cell infiltration. Validation by immunohistochemistry staining suggested that combination with tumor‐infiltrated CD4+ and CD8+ T lymphocytes would yield higher performance of these predictors in distinguishing cases as high‐ or low‐risk of unfavorable prognosis.In the colorectal cancer, the immunologic landscape of the mucosa is associated with the pathological evidence of early metastatic invasion and with patients' survival,This exploratory study aimed to identify, by immunohistochemical profiling, immunological predictors of ypCR after neoadjuvant CTRT within the tumor microenvironment of the esophageal SCC samples obtained at diagnostic endoscopy. In addition, we sought possible predictors of cancer persistence/recurrence in presence of a clinical yCR.22.1This is a retrospective exploratory study to inform a validation study. The study was performed according to the REMARK guidelines.2.2When we revised the patients' records, we restaged all the TMN classification according to the seventh edition in order to have comparable data among the different periods. .2.3The definition of clinical complete response (ycCR) was: disappearance of the tumor lesion, ulceration, and absence of cancer cells in biopsy specimens upon endoscopic observation of the entire esophagus.2.42) on day 1 in association with 5‐fluorouracil from Day 1 to 5 (1000 mg/m2); this scheme was recycled two to three times accordingly to patients' response. Some of the patients received taxanes in association.Across the time frame considered for the study, different neoadjuvant chemotherapy regimens were adopted. The most common treatment administered consisted of platinum‐derived drugs  with a target field involving ±5 cm over the tumor extension, ±2 cm over pathologic lymph nodes, mediastinum and supraclavicular fossa. A total dose of 30.6 Gy was administered using anteroposterior‐posteroanterior fields in the initial phase. Subsequently, the radiation portal was extended in order to enclose primary tumor together with pathological lymph nodes including an additional margin of 2 cm employing an oV‐cord conformal oblique weld and reaching a final total dose of 45‐50.4 Gy. Patients not suitable for surgery underwent evaluation for further radiotherapy.2.5Surgery was planned from 4 to 6 weeks after the neoadjuvant treatment was completed.2.6Pretreatment endoscopy biopsy specimens from each patient were submitted to the Surgical Pathology Unit in an adequate volume of 10% formalin for 8 h and routinely processed according to a standardized local protocol.Sections (3‐4 μm) from formalin‐fixed and paraffin‐embedded human specimens were stained with hematoxylin and eosin and reevaluated according to WHO 2010 classification of the gastrointestinal tumors by a gastrointestinal pathologist (M.F.), who was unaware of clinical data.The end point of this study was the presence of ypCR. The tumor regression after neoadjuvant therapy was measured according to the Mandard score system.2.7Immunohistochemical staining was performed on formalin‐fixed, paraffin‐embedded tissue sections using a fully automated system . Briefly, tissue sections were deparaffinized in Bond Dewax Solution  at 72°C, rinsed in ethanol, and rehydrated in distilled water. Sections were pretreated using heat‐mediated antigen retrieval with sodium citrate buffer  for 30 minutes a 99°C. Specimens were then incubated respectively with PD‐1 , PD‐L1 , CD4 , CD8 , B7‐1/CD80 , FoxP3 , T‐bet/Tbx21  and detected using the Bond Polymer Refine Detection Kit  according to the manufacturer's protocols. The staining was visualized with 3,3′‐diaminobenzidine  and the slides were lightly counterstained with hematoxylin . Sections were then dehydrated, cleared, and mounted. Appropriate positive and negative control samples were run concurrently (data not shown).Slides were evaluated and jointly scored by two pathologists on a Leica DM4000B microscope (Leica Biosystems) and images were acquired by using the Leica Application Suite  software.PD‐L1 expression was assessed both in neoplastic epithelia and in infiltrating leukocytes. Three different parameters were considered: (a) PD‐L1 staining intensity in neoplastic cells categorizing cases in high (in presence of staining detected up to 5% of the neoplastic cells) and low (<5%) PD‐L1 expressionFor the other immunohistochemical markers, positive cells were counted in 5 HPF (40×).2.8Follow‐up visits were scheduled every 3 months in the first year after surgery, every 6 months during the next 2 years and every 12 months thereafter. An upper gastrointestinal endoscopy was performed regularly 1 year after surgery or earlier based on the clinical findings, with direct evaluation of the remaining esophagus, anastomosis, and of the esophageal replacement conduct. Functional results were assessed based on clinical and endoscopic findings.2.9Due to the retrospective design of the study and the relatively rarity of the primary end point occurrence, (ypCR) the sample size was not defined a priori and all the consecutive patients who met the inclusion criteria were included. Moreover, a posteriori power calculation was almost pleonastic since if a difference resulted statistically significant the sample size of the two groups was large enough to detect it. Only available data were analyzed, and no imputation was done for missing data. No multivariable models were created due to the small sample size.Median and interquartile range were used to describe continuous variables. The Mann‐Whitney test to compare continuous variables and the Fisher test was used to study categorical variables. The immunological markers of ypCR were tested in the subgroup of patients with the ROC curve analysis. Since there is no codified threshold value for T cell subpopulation infiltration in esophageal SCC, we dichotomized patients into low‐ or high‐positive cells  infiltration subgroups according to threshold values obtained from ROC curves analysis. The Kaplan‐Meier estimate was used to perform the survival analysis from the date of the initial diagnosis and the log‐rank test was used to compare the subgroup survival. Due to the small sample size, nonparametric combination test was used to compare immunosurveillance data in case of recurrence. All tests were two‐sided with a p‐value considered statistically significant when less than 0.05. The software used to perform statistical analysis was SAS 9.1  and R 3.5 .33.1All 938 patients referring for thoracic SCC to the Centre for Oesophageal Diseases located in Padua between 1 January 1992 and 31 December 2007 were retrospectively evaluated using a prospectively collected database. Among 349 patients who received CTRT, 18 were excluded due to clinical M1 stage and 35 due to unavailable restaging after neoadjuvant therapy (yTNM). Two hundred and four patients were referred for treatment of thoracic SCC to our center from other centers, thus the paraffin‐embedded blocks from endoscopic biopsy at diagnosis were not available in our Surgical Pathology archives. Ninety‐two patients had the endoscopy performed in our center at the diagnosis of SCC, thus the biopsy specimens were available for analysis. At histopathologic/immunological reexamination, four paraffin‐embedded blocks presented an inadequate amount of residual material to be further considered in the analysis. Patient selection is shown in Figure 3.2P = 0.03; Table Eighty‐eight patients who underwent neoadjuvant therapy for thoracic SCC from 1992 to 2007 were finally included in the analysis. . Moreover, in the ypCR group, CD4+ and CD8+ lymphocytes tumor infiltration was significantly higher than in yPPD group . On the contrary, CD80 expression was not different in ypCR and yPPD groups  . Similarly, CD4+ and CD8+ T cell infiltration showed an even better accuracy in predicting ypCR after neoadjuvant therapy    Figure A. Simila) Figure A. Finall) Figure B.3.4P = 0.008 and 0.0004, respectively). Similarly, patients with a low infiltration of the tumor with CD4+ T cells had a significantly worse overall survival compared with those with high CD4+ infiltration (P =0.05). High infiltration of the tumor CD4+ T cells was associated with lower clinical stage at diagnosis   Table . ROC cur4In our esophageal SCC series, a higher CD4+ T cells tumor infiltration was significantly associated to a better overall survival. Similarly, in several studies, CD8+ and CD4+ T cell and CD57+ NK cells infiltration was correlated with better overall survival.Since 2003, how the interplay between CD4+ and CD8+ T cells strongly correlates with esophageal SCC patients' prognosis has been shown,Moreover, in our series, a sub‐analysis taking in account only patients who had stage III‐IV, SCC and who underwent DDP+5FU CT scheme confirmed a higher level of CD8+ T lymphocytes infiltrating the tumor in yCR group compared to yPPD group. Tsuchikawa et al. observed that neoadjuvant chemotherapy utilizing 5‐fluorouracil and cisplatin in SCC was useful to induce CD4 and CD8 T lymphocytes infiltration within the tumor microenvironment and to maintain HLA class I expression levels in combination with its direct cytotoxic effects.Nowadays the clinical significance of PD‐L1 expression within the tumor remains a debated topic. In colorectal cancer, PD‐L1 expression cancer defines three subsets of tumor immune microenvironments that can influence the response to therapy and the prognosis.In the last two years, PD‐L1 expression in esophageal SCC was largely explored but its role in neoadjuvant therapy response is largely unknown. PD‐L1 expression can be increased following treatment with 5‐FU in gastrointestinal cancer cell lines, suggesting alternative mechanisms to classic immune‐mediated upregulation.Moreover, the inhibition of the PD‐1/PD‐L1 axis in a neoadjuvant setting has recently shown good results in lung cancer. In fact, neoadjuvant nivolumab (antibody against PD‐1) was associated with few side effects, did not delay surgery, and induced a major pathological response in 45% of resected tumors.Once the clinical CR is achieved, the main problem is how to predict the persistence of the response to CTRT. An accurate marker to persistence of yCR might be used to avoid unnecessary esophagectomy saving to patients' great risks, impaired quality of life and the costs of a major surgery procedure. In a recent multicenter series, among 593 patients who underwent neoadjuvant CTRT followed by esophagectomy, pCR was observed in 32% of patients but recurrence occurred in one third of these patients.4.1In fact, the relatively small sample size and the consequent low power of the analysis are the main limitations of this exploratory study. Moreover, no public database on esophageal SCC which includes clinical/pathological response and molecular is currently available. Thus, larger, and hopefully multicenter, studies are needed to clearly identify predictors of recurrence after yCR at neoadjuvant therapy and to validate our results. On the other hand, the lack of previous study that tries to correlate the immune tumor microenvironment and response to neoadjuvant therapy make this study the necessary step to lay the foundation for these future multicenter large studies.4.2In conclusion, in our series, PD‐L1 expression and CD8+, CD4+ and Tbet+ lymphocyte rate were predictive of clinical CR after neoadjuvant CTRT for SCC of the thoracic esophagus with adequate accuracy. These preliminary observations might be used to plan further study aimed to identify reliable predictors of response to CTRT in esophageal SCC.None to declare.According to the CRediT taxonomy, the author contributions are as follows: Conceptualization: Matteo Fassan, Massimo Rugge, Francesco Cavallin, Carlo Castoro, Marco Scarpa, Ignazio Castagliuolo; Data curation: Vincenza Guzzardo, Andromachi Kotsafti, Melania Scarpa, Rita Alfieri, Matteo Cagol, Vanna Chiarion‐Sileni, Luca Maria Saadeh; Formal analysis: Matteo Fassan, Francesco Cavallin, Marco Scarpa; Funding acquisition: Carlo Castoro, Marco Scarpa; Investigation: Matteo Fassan, Massimo Rugge, Francesco Cavallin, Carlo Castoro, Marco Scarpa, Ignazio Castagliuolo; Methodology: Massimo Rugge, Ignazio Castagliuolo; Project administration: Marco Scarpa, Carlo Castoro; Resources: Marco Scarpa, Carlo Castoro; Software: not applicable. Supervision: Marco scarpa, Ignazio Castagliuolo, Massimo Rugge, Matteo Fassan; Validation: Vincenza Guzzardo, Andromachi Kotsafti, Melania Scarpa, Rita Alfieri, Matteo Cagol, Vanna Chiarion‐Sileni, Luca Maria Saadeh; Visualization: Melania Scarpa, Andromachi Kotsafti, Luca Maria Saadeh; Writing original draft: Matteo Fassan, Francesco Cavallin, Marco Scarpa; Writing review and editing:, Vincenza Guzzardo, Andromachi Kotsafti, Melania Scarpa, Matteo Cagol, Vanna Chiarion‐Sileni, Luca Maria Saadeh, Rita Alfieri, Ignazio Castagliuolo, Massimo Rugge, Carlo Castoro. Click here for additional data file.


Recent advances in concrete recycling technology focus on novel fragmentation techniques to obtain aggregate fractions with low cement matrix content. This study assesses the aggregate liberation effectiveness of four different treatment processes including standard and innovative concrete fragmentation techniques. Lab-made concrete samples were subjected to either standard mechanical crushing technique (SMT) or electrodynamic fragmentation (EDF). For both fragmentation processes, the influence of a microwave weakening pre-treatment technique (MWT) was investigated. A detailed analysis of the particle size distribution was carried out on samples after fragmentation. The >5.6 mm fraction was more deeply characterized for aggregate selective liberation  and for cement matrix content (thermogravimetric measurements). Results highlight that EDF treatment is more effective than SMT treatment to selectively liberate aggregates and to decrease the cement matrix content of the >5.6 mm fraction. EDF fully liberates up to 37 wt.% of the >5.6 mm natural aggregates, while SMT only liberates 14–16 wt.%. MWT pre-treatment positively affects aggregate liberation and cement matrix removal only if used in combination with SMT; no significant effect in combination with EDF was recorded. These results of this study can provide insights to successfully implement innovative technology in concrete recycling plants. Continuous global population growth and ongoing economic development demand a thriving construction industry. This industry strongly depends on the production of concrete, the most widely used building material. Global production of concrete has increased up to 25 Gt per year . Yet, thFlanders (Belgium) has a long history in recycling and reuse of concrete and aggregates, especially since Flemish legislation banned landfilling of construction and demolition waste in 2009 . AlthougSeveral new concrete fragmentation techniques have recently been suggested to produce cleaner recycled aggregate fractions, including: i) microwave-assisted fragmentation (MWT) and ii) electrodynamic fragmentation (EDF). The technique of microwave-assisted fragmentation uses microwaves to internally heat concrete waste material. The moisture content of the different concrete constituents is strongly linked to the absorption of the applied microwave energy, because it directly affects the dielectric properties of the constituents . As a reFor recent years, microwave-assisted fragmentation and electrodynamic fragmentation have been assessed for their effectiveness of aggregate selective liberation ,16,17,18In this study, this concept was tested by assessing the combined effect of a microwave pre-treatment prior to electrodynamic fragmentation or standard mechanical treatment (impact crusher), on concrete fragmentation and aggregate liberation. The obtained fragmented material from the different treatments was evaluated based on the obtained particle size distribution. Additionally, the >5.6 mm fraction of the obtained material was characterised based on aggregate selective liberation (classification) and cement content.−3 cement, 249 kg m−3 water and 1940 kg m−3 aggregates (of which 1098 kg m−3 Rhine sand and 842 kg m−3 Moselle gravel), thereby also meeting the standard guideline of a water/cement ratio of 0.55. Additional water (38 kg m−3) was added to account for water absorption by aggregates. Afterwards, the prepared concrete was cured for one year , which operated at 180 kV and applied 30 pulses at a frequency of 5 Hz. The spacing between both electrodes corresponded to 40 mm. The estimated energy consumption of EDF was 30 kWh t−1. The SMT used a Hazemag impact crusher . The crusher operated with 1.1 kW power and with a rotation speed of 1600 rpm (~20 m s−1), resulting in an energy consumption around 0.5 kWh t−1. This mechanical treatment was included as a standard technique for concrete fragmentation.In order to fragment the concrete samples and assess aggregate selective liberation by several treatments, three different techniques were used: i) microwave treatment (MWT), ii) electrodynamic fragmentation (EDF) and iii) standard mechanical treatment (SMT). For MWT, a monomode microwave MEAM Mono-Explorer 6  was used. Without a pre-drying procedure, the samples were exposed to microwave radiation with a power of 3 kW and frequency of 2.45 GHz during a 60 s period (including the 5 s acceleration period). This MWT had an estimated non-optimised energy consumption of 450 kWh tThe different fragmentation treatments explored and evaluated in this study are presented in w0) in each sample was determined from the weight loss by a thermal treatment at 105 °C for 24 h. Consequently, the chemically bound water content (tw) of these samples was determined by the additional weight loss after a thermal treatment at 550 °C for 2 h, causing further dehydration and dehydroxylation of cement hydration products [w0 and tw values, the cement content (c) in each sample was estimated using the following formula:Samples obtained from the different fragmentation treatments were characterised based on size distribution, aggregate selective liberation (classification) and cement matrix content. First, the particle size distribution of the obtained fragmented samples was determined. Samples were screened at 0.25, 0.5, 1.0, 2.0, 4.0, 5.6, 8.0, 10.0, 16.0 mm . Gravimetric measurement of each fraction was used to obtain the particle size distribution curve. Secondly, a classification step was performed on the >5.6 mm fraction of each sample obtained after concrete fragmentation. This fraction was sorted by hand into three particle classes based on visual particle characteristics: fully liberated aggregates (FL), aggregates with adhering cement matrix (AC) and chunks of cement matrix (CM). The FL class had no visual signs of the presence of cement matrix on the aggregate and the AC class had pieces of cement matrix adhering to single aggregates. The CM class included  pieces of cement matrix, which could also contain several aggregates. The focus on the >5.6 mm fraction in this study was merely for the practical considerations related to the hand-sorting. Thirdly, the cement content of the obtained particle classes was measured using the thermogravimetric method. This method is based on the hydration reaction of cement with water during aging, assuming that (i) cement on average reacts with water for 24% of its weight  and (ii)products . The losTo determine the cement content of the particle classes, the FL, AC and CM particles were hand-sorted from the >5.6 mm fraction. The average cement content of each particle class was multiplied with the fraction of the corresponding class in each of the >5.6 mm samples, in order to obtain the total cement content of each >5.6 mm sample.The statistical significance of the differences in size fraction, aggregate selective liberation, aggregate recovery and cement content between the different fragmentation treatments was examined via a paired student t-test, thereby separating the treatments with or without MWT; the significance of a MWT pre-treatment was tested via a one-way ANOVA analysis. For both, the statistical program JMP Pro 11 (SAS) was used.The particle size distributions of the natural aggregate and of the samples obtained after fragmentation treatments are presented in The >5.6 mm fraction from each fragmentation treatment, also indicated in The relative amount of FL aggregates in the >5.6 mm fraction is determined to assess the aggregates liberation during the different treatments b. The amFrom the mass of the FL aggregates in the >5.6 mm fraction and the initial concrete aggregate content, the recovery of FL aggregates with the different treatments is calculated c. The hiUsing thermogravimetric analysis, the cement content of the particle classes present in the >5.6 mm fraction is determined . In geneThe cement content of the >5.6 mm fractions is determined by the relative content of the FL, AC and CM classes in the >5.6 mm fraction  combinedOverall, the data show that EDF, followed by a >5.6 mm size separation, is able to deliver a cleaner recycled aggregate fraction in comparison with the other tested treatments. Only in combination with SMT, MWT slightly increases the liberation and recovery of aggregates; no significant effect is shown for MWT as pre-treatment for EDF. Previous studies also confirmed the effectiveness of a MWT pre-treatment prior to SMT ,15,23. IFor the >5.6 mm fractions obtained from the different treatments, a link between the cement content of a recycled aggregate fraction and the relative abundance of the particle classes  in that fraction is expected. In this study, the total cement content of a >5.6 mm fraction clearly decreases with the increasing liberation of aggregates in that fraction. The FL particles have the lowest cement content, on average 2.7%. Remaining cement of these FL aggregates is likely related to minor amounts of cement matrix remaining in surface imperfections of the aggregates. The CM particles have the highest average cement content of the three particle classes (13.1%), which is comparable to the cement content of the initial concrete samples (14.2%). The results of the cement content of the material obtained from the different treatments are in line with the results from the aggregate liberation. The lowest cement content is obtained for EDF and only for SMT a MWT pre-treatment results in a significant decrease of the cement content. Here, it can be noted that lowering the cement content with aggregate liberation is only possible if the attached cement matrix not only is removed from the aggregate surface during treatment but also is excluded from the >5.6 mm fraction. In other words, not only the complete liberation of aggregates is a determining factor to decrease the cement matrix content in a certain fraction of fragmented concrete but also the impact of the different treatments on the fragmentation of the cement matrix phase plays a role.This study used lab-made concrete blocks with the strength class of C25/30. In comparison with many other concrete formulations, the compressive strength of these concrete samples is relatively low, which is related to the high water/cement ratio used for the concrete samples . It is eIt is implied that, although a significant effect was obtained for the MWT pre-treatment on the effectiveness of SMT, the EDF technique remains most promising for aggregate selective liberation from concrete: a recycled aggregate fraction with high aggregate selective liberation and low cement matrix content was obtained with EDF. However, so far the technology of EDF has not yet been applied in concrete fragmentation systems at large scale and current concrete fragmentation installations remain mainly based on mechanical fragmentation. Therefore, an additional microwave based pre-treatment to the existing fragmentation technology is likely a more feasible approach to increase aggregate liberation on short-term basis, even when the gains in aggregate liberation will be smaller.Next to the aggregate selective liberation of the different treatments, the energy consumption of these treatments is a major issue. Menard et al.  found thA high aggregate selective liberation during a concrete fragmentation treatment is of key importance to recover the aggregate fractions for high-quality applications. Therefore, research focusses on novel technology and treatments to increase aggregate selective liberation and thus aggregate quality. From this approach, this study assesses the significance of microwave weakening pre-treatment on the aggregate selective liberation from lab-made concrete samples. Results show that EDF treatments are more effective in aggregate selective liberation compared to SMT. Indeed, EDF resulted in a >5.6 mm recycled aggregate fraction with more FL aggregates and an overall lower cement content. The effect of a microwave pre-treatment was only significant in terms of aggregate liberation and lowering the cement content if followed by SMT, while MWT did not significantly influence EDF recycled aggregates. Future research can further elaborate on the effect of MWT pre-treatment for SMT or EDF treatment on concrete with varying strength properties and water/cement ratios, as this is likely to affect the relative effectiveness of the liberation treatments tested here. Also the liberation of aggregates smaller than 5.6 mm obtained via the studied treatments can be assessed.


N-phenylaminopropyl POSS (AM0281). The cure behavior and properties of these polymers were analyzed and compared using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA), Fourier transform far infrared (FTIR) measurements, and rheometric studies. The POSS-containing polymers showed higher chemical reactivity, better thermal stability and better mechanical performance in comparison to their unmodified counterparts. All the polymers showed water absorption below 1.5%. As revealed by FTIR measurements, the polymerization products contained triazine ring structures that were responsible for the superior thermal properties exhibited by these POSS-containing polymers.Phthalonitrile–polyhedral oligomeric silsesquioxane (POSS) copolymers were prepared by adding two different POSS cage mixtures: epoxycyclohexyl POSS (EP0408) and  Fiber-reinforced composites have been widely used over the past several decades in numerous structural applications  owing to their good mechanical performance and light weight. These materials have developed quickly due to their potential for future applications. Phthalonitrile polymers ,2,3,4,5,gT) temperatures and superior mechanical and oxidative or fire resistant properties) have been prepared in a large range of thermoplastic  and thermosetting  polymers [2-epoxy nanocomposites with enhanced thermal stability and UV resistance [N-phenylaminopropyl organic groups at the corners of the cage, respectively. Epoxycyclohexyl POSS (EP0408) and N-phenylaminopropyl POSS (AM0281) were chosen with the clear objective of studying the effect of POSS on the cure behavior, thermomechanical properties, and the reactive mechanism of phthalonitrile copolymers. The structures of the monomer and the two POSS reagents used herein are shown in The phthalonitrile monomer 4,4′-bisbiphenyl (BPh) was first synthetized by Keller ,2 and, spolymers ,28,29,30polymers  synthesipolymers . Pen presistance . DespiteAromatic amine was used with EP0408 and AM0281 to co-cure the phthalonitrile monomer such that the main structure of the phthalonitrile polymers is retained. N-phenylaminopropyl POSS  cage mixtures were obtained from Hybrid Plastics, Inc. .BPh  was synthesized at the Institute of Chemistry of the Chinese Academy of Sciences. 4,4′-bis(4-aminophenoxy)biphenyl  was purchased from Bailingwei Inc. . The two types of POSS denoted as epoxycyclohexyl POSS  and A mixture of BPh and BAPP  was melted at 260 °C. EP0408 and AM2081 were separately added at varying compositions  and the resulting mixtures were stirred for 10 min and cooled down to room temperature to prepare the prepolymers, respectively named the neat prepolymer, EP0408-X prepolymer, and AM2081-X prepolymer, where X indicates the POSS content in wt %. The prepolymers were pulverized before performing differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA) and rheological tests. Neat polymers and those containing EP0408 and AM2081 at 0.1, 0.5, 1, 5, and 10 wt % were cured at 260 (4 h), 300 (8 h), and 325 °C (8 h). Before the DMA experiments, phthalonitrile casting samples were cured in molds (50 × 10 × 2 mm) with an air-circulating oven at 260 (8 h), 300 (8 h), and 325 °C (8 h). The samples were subsequently post-cured under an inert atmosphere of nitrogen at 350 °C (4 h), 350 and 375 °C (4 h), 350 (8 h), and 375 °C (4 h). The rheological behavior of the neat prepolymers and the prepolymer–POSS blends was studied at 280 °C to obtain the complex viscosity–time plots. The neat prepolymers, polymers, and POSS polymers containing EP0408 and AM0281 were studied by Fourier transform far infrared (FTIR) analysis. β is the heating rate, pT is the peak temperature of each DSC curve at different heating rates, and R is the universal gas constant. Thus, the E value was obtained through the linear dependence of In(β/pT2) on 1/pT, at various heating rates.DSC experiments were conducted in a flowing nitrogen atmosphere on mixtures containing the monomer and either EP0408 or AM2081 . The experiments were conducted within a Perkin–Elmer Pyris-6 DSC calorimeter  at a heating rate of 10 °C/min. DSC curves at different heating rates  were measured. The activation energies were calculated using the following equation: G’) and damping factor (tanδ) of rectangular phthalonitrile polymer specimens (50 × 10 × 3 mm) were obtained by DMA on a DMS-6100 instrument  with a flowing nitrogen atmosphere and a temperature range of 30–400 °C . Thus, gT was estimated from the modulus–temperature plots obtained by the DMA. Dynamic viscosity measurements were performed on a TA Instruments AR-2000 rheometer . The water uptakes of the neat polymers and the phthalonitrile–POSS copolymers were monitored under ambient conditions. The FTIR studies were performed on a Nicolet Avatar 370 FT-IR spectrometer  with potassium bromide pellets containing a low amount of sample. Thermal analysis was performed on polymers with different contents of EP0408 and AM2081, using a TA Instruments SDTQ600 thermogravimetric analyzer . The TGA tests were carried out under flowing nitrogen (100 mL/min) at a scan rate of 10 °C/min. The dynamic storage modulus  were studied by DSC, and the results are shown in The TGA profiles of the EP0408- and AM0281-containing materials  are shown in Most of the AM0281-containing polymers, particularly the AM0281-1 polymer, showed excellent thermal stability compared to the other polymers. The weight retain percent at 900 °C is about 40% higher than that of the neat polymer (31%). However, the AM2081-10 polymer showed poorer thermal stability than the neat polymer. Since AM0281 bears a hindered amine with low reactivity, an excess of this POSS agent in the mixture caused the unreacted amine to decompose at high temperatures, thereby decreasing the stability of the polymer. DTG curves shown in As shown in From the TGA curves of each system, a gradual increase in the content of POSS has the thermal stability increasing at first, before decreasing. When a small amount of POSS agent was added to the system, the POSS ring will enter the network of triazine and make the cross-linked density higher as shown in DMA measurements were carried out to study the dynamic mechanical properties of the polymers as a function of different post-cured treatments. These preliminary studies were used to identify the curing conditions required to obtain polymers with optimum mechanical properties. Thus, the samples post-cured at 350 °C exhibited a sharp drop in the storage modulus and a peak in the tanδ curves as the temperature increased , 300 (8 h), and 325 °C (8 h) and subsequently post-cured under an inert atmosphere of nitrogen at 350 (8 h) and 375 °C (4 h) is shown in −1) and the formation of new peaks were studied to obtain information on the polymerization mechanism  than either the EP0408-0.5 (45% weight remaining) or AM0281-1 (40% remaining) polymers. Thus, polymers containing POSS showed superior thermal stabilities than the neat polymer.Conclusion 4: As revealed by FTIR, the polymerization products were triazine ring structures, which are believed to be responsible for the good thermal properties of the modified polymers.


The mix design of ultra-high performance concrete (UHPC) is complicated by the presence of many “ingredients.” The fundamental packing density allows a simpler mix design with fewer ingredients to achieve optimum packing density and dense microstructure. The optimum particle grading increases the flowability of UHPC and eliminates entrapped air. This study presents a simplified particle grading design approach that positively influences the strength, autogenous shrinkage, and microstructure characteristics of UHPC. Carbon nanofibers (CNFs) of superior mechanical properties were added to enhance the strength of UHPC and to reduce its autogenous shrinkage. In addition, ground granulated blast-furnace slag (GGBS) was used as a cement replacement material to reduce the amount of cement in UHPC mixes. Test results showed that the presence of homogeneously dispersed CNF increased the compressive strength and compensated the autogenous shrinkage of UHPC. The findings indicated that an ideal particle distribution, which is close to the modified Andreasen and Andersen grading model, contributed to achieving high compressive strength and CNFs were capable of providing nano-bridges to compensate the shrinkage caused by GGBS. The recent developments in concrete engineering and technology have facilitated researchers around the world to synthesize ultra-high performance concrete (UHPC) with advanced engineering properties. UHPC is characterized by ultra-high strength and durability with or without fiber reinforcement and exhibits a 28-day compressive strength of more than 150 MPa . HoweverSeveral particle grading models have been discussed in literature ,10, and All UHPC designs are based on a low water/cement (w/c) ratio. Theoretically, a low w/c ratio results in high strength. However, UHPC shows an extremely high autogenous shrinkage, thereby leading to cracking at early ages. The early-age cracking due to restrained autogenous shrinkage affects and limits the progress of concrete construction . Low w/cNanomaterials such as nano-silica, nano-calcium carbonate, graphite nanoplatelets, carbon nanotubes (CNTs), and carbon nanofibers (CNFs) are used to enhance concrete properties due to their high surface area and fineness ,15,16. BShimoda et al.  reportedThe present study explores the simplified version of UHPC by optimizing the packing density in the matrix of concrete. GGBS was used as a pozzolanic supplementary cementitious material to increase the strength of concrete. After achieving the two best particle packing options, a new type of CNFs was incorporated to investigate the strength and shrinkage properties of the designated UHPCs under normal curing temperature. The microstructure of hardened UHPCs was also observed by means of a SEM.2. The grading (particle size distribution) curves of cement, GGBS, silica flour, and silica sand are shown in OPC (CEM I 52.5N), silica flour, silica sand, GGBS, superplasticizer (SP), and CNFs were used as the concrete constituent materials. A polycarboxylate-based SP with 35% solid content by weight was used as the water reducing and workability enhancing admixture. The chemical compositions of cement, GGBS, silica flour, and silica sand were determined using the X-ray Diffraction (XRD) technique . The results are summarized in The selected new type of CNFs with large diameter and length was produced using catalytic chemical vapor deposition technique. Due to a controlled chemical vapor deposition process, the resulting CNFs consisting of the nano-structural filaments in a herringbone structure have stronger and more stable characteristics . Such stAfter mixing, the flow table test was performed in accordance with ASTM C230  to evaluAfter conducting the flowability test, the fresh concretes were cast in 50 mm × 50 mm × 50 mm cube molds. The concrete cubes were demolded approximately 24 h after casting and then cured in water at approximately 23 °C. The cured cube specimens were tested at the ages of 1 day, 7 days, and 28 days to determine compressive strength in accordance with ASTM C109 . The resOver the years, many researchers studied the best packing of cement or binder (cement plus GGBS) and aggregates through optimum particle grading. In the present study, the cumulative mass of cement or binder and graded sand (silica flour plus silica sand) was calculated based on the modified Andreasen’s curve equation to achieve optimum packing. The combined grading curves of cement or binder and graded sand particles associated with optimum packing for different concrete mixes have been presented in q. The optimum design of a high content of fine materials is required in UHPC [q was fixed at 0.23 in the present study. In the UHPC mix design, the modified Andreasen and Andersen model (Equation (1)) plays the major role to optimize the composition of granular materials. In the study presented herein, all the concrete mixes were designed based on the modified Andreasen and Andersen model as follows:D is the particle size (μm), P(D) is the fraction of the total solids smaller than size D, Dmax is the maximum particle size (μm), Dmin is the minimum particle size (μm), and q is the distribution modulus.Different types of concrete can be designed using different values of the distribution modulus,  in UHPC ,30; the One-dimensional (1D) autogenous shrinkage was measured on the sealed specimens using a stainless steel apparatus by controlling the laboratory temperature at 23 °C and relative humidity at 20%. The specimen’s dimensions were 60 mm in height, 100 mm in width, and 1000 mm in length. External drying was prevented by sealing the specimens immediately after casting using two layers of polyethylene sheets. The free end of the specimen had a linear variable displacement transducer attached to measure the autogenous deformation continuously. The data were recorded every 10 min. The average strain values were reported. This test was performed in accordance with the recommendations given by Wei et al. .2 for all concrete mixes were obtained from 1-day old 40 mm × 40 mm × 160 mm prism specimens. For each concrete, the prism was cut to a thickness of 5 mm at the center section and oven-dried for 30 min. Then, the prepared 40 mm × 40 mm × 5 mm specimens were placed individually at a fixed object distance of 85 mm in front of the camera lens. The images were captured using a Nikon macro lens , Nikon 40 mm f/2.8 DX G.The entrapped air content of different concrete mixes was determined based on image analysis. For this test, 40 mm × 40 mm × 5 mm specimens were used. The cross-sections of 1600 mmThe cross-sections of all specimens were analyzed using image enhancing and analysis software, ImageJ. All images were set as 8-bit and analyzed using binary  analysis, which manually adjusts the threshold level to determine the optimum threshold range to differentiate the surface and depth. In this analysis, the white background represents the concrete surface, whereas the dark background represents the air voids on the surface . The sumThe microstructural/nanostructural characteristics of the hardened UHPC specimens were analyzed through the SEM technique, using the Quanta 200 SEM . For each case, three small-size specimens were prepared from the broken cube specimens, which were tested in compression at 28 days.The small specimens obtained from broken cubes were dried in an oven, subsequently ground and polished to ensure flattened surface, and then further dried in a desiccator for 24 h before analyzing by the SEM. The dried specimens were coated with gold and pasted with a carbon tape prior to capturing their images. The SEM images were produced using the prepared specimens and analyzed.Mix 1 to Mix 5 with different particle grading characteristics were prepared as the fundamental concrete mixes (without CNFs) to investigate the packing of each mix. The flowability or flow values of all fresh mixes, including Mix 1 to Mix 5, are shown in The entrapped air contents of different concrete mixes are shown in The microstructural analysis of different concrete mixes was performed through SEM. In the SEM images, the effects of GGBS and CNFs were particularly observed. Some selected SEM images are given in The compressive strength values of all concrete mixes at specific ages are shown in 2, sourced from GGBS as well as cement hydration) to produce secondary calcium silicate hydrates, which play a crucial role in the strength development at later ages. With 50% replacement of cement with GGBS, Mix 5 provided a relatively low early strength. However, its 28-day strength was close to that of Mix 4 as evident from The incorporation of CNFs did not produce any adverse effect on the compressive strength development in concrete. Mix 6 and Mix 7 had a higher early strength (1-day strength and 7-day strength) than their parent control mixes , as can be seen from The compression test results revealed that the compressive strength of the UHPC mixes is correlated with their flow  and entrThe age-dependent autogenous shrinkage results for different concrete mixes are shown in In the present study, Mix 2 and Mix 5 were prepared using GGBS as a 50% replacement of cement. The use of GGBS decreased the early-age autogenous shrinkage but increased the long-term shrinkage for Mix 2. In the case of Mix 5, both the early-age and long-term shrinkage were relatively low. This is probably because Mix 5 contained a lower amount of silica flour than Mix 2. The early-age shrinkage was also reduced because the pozzolanic reaction of GGBS is initially slower than the hydration of cement. When GGBS behaves similar to a filler , the increased GGBS content in total cementitious material also increases the effective w/c ratio due to a lower amount of cement. Accordingly, the early-age autogenous shrinkage is decreased. Also, for a lower amount of cement, the available water content for hydration becomes relatively high. This implies that self-desiccation as a result of the lack of water supply cannot develop over time ,14. TherThe incorporation of CNFs contributed to decreasing the autogenous shrinkage in UHPC. In Mix 6 and Mix 7, CNFs dispersed homogeneously in water beneficially provided sufficient water during hydration. CNFs at a good dispersion stage also impart uniform distribution of nanofibers in the matrix of concrete and, thus, bridge fine cracks and reduce autogenous shrinkage ,33. In tThe flow or flowability of concrete mix directly indicates its entrapped air content. A higher flowability contributes to reducing the entrapped air in concrete.The higher entrapped air content decreases the compressive strength as the air-voids act as a weak link in stress transfer.The ideal particle distribution, which is close to the modified Andreasen and Andersen grading greatly contributes to achieving high compressive strength.The fine particle grading increases the autogenous shrinkage in the matrix of concrete due to a greater specific surface area and more fine pores.CNFs provide nano-bridges in fine cracks to compensate the autogenous shrinkage caused by silica flour.CNFs improve the microstructure or nanostructure of the overall matrix in concrete through good dispersion and uniform distribution of the nanofibers.The present study demonstrated that optimum particle grading is desirable for dense microstructure and high compressive strength. As a 50% replacement of cement, GGBS addition mainly contributed to providing high strength at the later ages of concrete owing to the pozzolanic reaction. The use of CNFs contributed to decreasing the later-age autogenous shrinkage of UHPC. From this study, the following conclusions are drawn:


Sphingolipids (SL) modulate several cellular processes including cell death, proliferation and autophagy. The conversion of sphingomyelin (SM) to ceramide and the balance between ceramide and sphingosine-1-phosphate (S1P), also known as the SL rheostat, have been associated with oxidative stress and neurodegeneration. Research in the last decade has focused on the possibility of targeting the SL metabolism as a therapeutic option; and SL levels in biofluids, including serum, plasma, and cerebrospinal fluid (CSF), have been measured in several neurodegenerative diseases with the aim of finding a diagnostic or prognostic marker. Previous reviews focused on results from diseases such as Alzheimer’s Disease (AD), evaluated total SL or species levels in human biofluids, post-mortem tissues and/or animal models. However, a comprehensive review of SL alterations comparing results from several neurodegenerative diseases is lacking. The present work compiles data from circulating sphingolipidomic studies and attempts to elucidate a possible connection between certain SL species and neurodegeneration processes. Furthermore, the effects of ceramide species according to their acyl-chain length in cellular pathways such as apoptosis and proliferation are discussed in order to understand the impact of the level alteration in specific species. Finally, enzymatic regulations and the possible influence of insulin resistance in the level alteration of SL are evaluated. Cell membranes are composed of several hundreds of different lipid species, having lipids and proteins more or less restricted movements as a consequence of interactions between them and cytoskeletal molecules . SphingoIncreased oxidative stress is a central event in neuronal failure that induces the activation of the sphingomyelin (SM)-ceramide pathway, making SL key players in neurodegeneration. Moreover, the increase of ceramide formation from SM has been reported as specifically detrimental in neurons and oligodendrocytes compared to astrocytes and microglia, which contain higher levels of antioxidant defenses such as glutathione and manganese superoxide dismutase (MnSOD) . The impSL are characterized by the presence of a common sphingoid backbone structure. Humans have primarily sphingosine (d18:1), sphinganine or dihydrosphingosine (d18:0), and phytosphingosine or 4-hydroxysphinganine (t18:0) as sphingoid bases , and in de novo synthesis of SL starts in the endoplasmic reticulum (ER) with the condensation of mainly serine and palmitoyl-CoA by the rate-limiting membrane enzyme serine palmitoyltransferase (SPT) to form 3-ketodihydrosphingosine, which is then reduced to generate sphinganine. Ceramide synthases (CerS) catalyze the N-acetylation of sphinganine to form dihydroceramide which is converted to ceramide by the dihydroceramide desaturase. A second pathway termed “the salvage pathway” involves the degradation of complex SL such as gangliosides in the lysosome to generate ceramides and subsequently sphingosine by ceramidases. Sphingosine can also be N-acetylated by CerS in the ER to form ceramides again  encodes for a protein precursor that suffers differential protein modifications and trafficking, producing both the lysosomal SMase (L-SMase), and the secretory SMase (S-SMase) [A third synthesis pathway involves the hydrolysis of SM in cellular membranes to form ceramide and phosphorylcholine by sphingomyelinases (SMases). Several types of SMases have been described, with acid SMase and Mgcterized . The aciS-SMase) . The degS-SMase) . An incrS-SMase) , showingCeramide can be later galactosylated in the ER to produce galactosylceramide  or glucosylated in the cis-Golgi to produce glucosylceramide (GlcCer) . These cA review on sphingolipids faces the problem of species notation depending on the knowledge of the sphingoid base. The notation Cer C16:0 is sometimes used to include ceramides with different sphingoid bases and a fatty acyl chain of 16 carbon atoms and no double bonds. In other cases, Cer C16:0 is used exclusively for a ceramide with a sphingosine such as Cer d18:1/16:0, and dhCer C16:0 for a dihydroceramide with a sphinganine such as Cer d18:0/16:0. The method used for ceramide detection has been checked for each publication cited in this review, and when possible to clearly establish the sphingoid base, then a fatty acyl level notation  was used . If it wLipidomic studies in biofluids from patients with neurodegenerative diseases can be separated in studies with a case-control design, and longitudinal studies that focus on finding specific lipid species as predictors of a phenotypic characteristic or disease state see .Case-control studies have been carried out in several neurodegenerative diseases to find differences in SL species, mostly analyzing plasma samples, and in some studies measuring lipids in serum or CSF samples. In order to have a wider overview of possible changes in SL species in neurodegeneration, these studies are compared even though lipids were obtained from different fluids. From the two major classes of SL, some of the publications measured both ceramides and sphingomyelins, while others focused on one lipid class. Lipidomic or sphingolipidomic studies that reported measurement of several ceramide or SM species were included. Metabolomic studies that reported changes in one or two SL are mentioned when appropriate, but not necessarily considered for the main comparison analyses.Several of these studies reported level alterations on ceramide species with disease, allowing us to try a first comparison of neurodegenerative associated modifications. For this purpose, data were compiled from three studies in Alzheimer’s disease (AD) ,47,48, aWhile ceramides were consistently found increased in biofluids of patients, SM followed different patterns, although the majority of studies showed decreased levels in neurodegenerative diseases. Moreover, depending on the technique used to separate the molecules it is possible to identify the sphingoid base of each SM species, and therefore it is difficult to compare results from different studies at species level . Table 3In contrast with the results in other neurodegenerative diseases, ALS patients had elevated plasma levels of stearoyl SM (d18:1/18:0) compared to healthy controls in a metabolomics study of two independent cohorts of subjects . This SLSL other than ceramide and SM have been found to be altered in neurological diseases. For example, Zhang et al.  showed hThe Women’s Health and Aging Study II carried out in Baltimore is a population-based longitudinal study of older women followed up to nine years, and used by Mielke and coworkers ,61 to evA serum non-targeted metabolomics approach of samples from mild cognitive impairment (MCI) and age-matched AD subjects showed that sphinganine-1-phosphate (dihydro-S1P) can predict the conversion of MCI to probable AD . Both S1The changes in SL levels observed in plasma and CSF may be reflecting alterations in nervous tissues undergoing degeneration. In accordance with the results observed in plasma, AD patients presented elevated levels of ceramides, and in some cases GlcCer and GalCer, compared with control donors in white matter of temporal cortex and cerebellum , pre froIn the anterior cingulate cortex (ACC) of PD patients a shift from Cer d18:1 longer  to shorter  acyl chain composition was observed compared to control ACC . These sBrain SL are also abundant in the monounsaturated nervonic acid (24:1n-9) in comparison with other tissues, and the proportion of this LC fatty acid was reported to be lower in white matter and myelin samples of MS donors compared with controls , similarMost of the lipidomic studies presented in this review showed Cer d18:1/16:0 associated with disease or cognitive impairment. Lipid micelles containing Cer C16:0, and to a lesser extent Cer C24:0, were shown to induce oxidative stress and decrease neuronal maximal respiratory rate and the spare respiratory capacity in primary rat hippocampal neurons, while Cer C22:0 or no addition of ceramide had no effect . AccordiGrösch et al.  hypothesAs suggested before, regulation of SMases may cause the alteration of SL species observed in neurodegeneration. A recent study in a chronic psychosocial stress mice model, which is a risk factor for inflammatory disorders and major depressive disorder among others, showed that stressed mice presented an increase in hepatic and S-SMase activity and increased Cer d18:1/16:0 and decreased Cer d18:1/24:0 content in the liver . In patiCERS2 produces a shift in ceramide composition from C24 to C16 species conferring greater susceptibility to apoptosis induced by cisplatin, UV, or C6 ceramide [The shifts from VLC to LC ceramides in patients and mice models has been also suggested to be a consequence of a balance or compensation in CerS activities. A study using HeLa cells demonstrated that knockdown of ceramide . Similarceramide . Down-receramide . The autceramide .However, to what extent the fatty acyl chain of ceramides is responsible of certain cellular responses is still under discussion. CerS1-deficient mice presented decreased levels of Cer d18:1 with C18 acyl chain length and increased levels of species with other acyl chains, i.e., C16, C20, C22, and C24, compared to wild-type mice, and these changes were accompanied with neuronal apoptosis in the cerebellum . In oldeCERS6 mRNA expression and Cer C14:0, C16:0, C16:1, C18:0, C18:1, and C22:1 levels in adipose tissue compared to lean subjects, and a correlation between increasing CERS6 expression and insulin resistance [Ceramides have been associated with the development of insulin resistance . Obese hsistance . Accordisistance . Cer d18sistance ,93, withsistance , an imposistance , while Csistance . A recensistance .Insulin resistance has also been implicated in some of the neurodegenerative diseases reviewed here in which higher circulating ceramide levels were reported. The hippocampus has a high glucose demand and is an insulin-sensitive tissue, making it susceptible to insulin resistance during aging . AccordiThe main goal of this review was to have an outlook on SL alterations in biofluids of neurodegenerative diseases. A common finding in all the studies evaluated was an increase in ceramide species in different biofluids of patients compared to controls, with Cer d18:1/16:0 as the main species altered in a recurrent manner. These results evince that individual ceramide species may be considered general markers of neurodegeneration, rather than disease specific. However, it might be useful to make use of standardized methods for the measurement of SL in biofluids so as to enable the subsequent analysis of a common panel of SL species by innovative bioinformatics tools and to find disease-specific patterns. In this regard, two recent studies applied multivariate and bioinformatic analyses to differentiate between healthy individuals and patients according to several SL species. After applying unsupervised machine-learning to analyze serum concentrations of three lipid classes from MS patients and healthy controls, Lötsch et al.  found thCFH and ARMS2 genes may influence the association between Cer d18:1/16:0 and AMD, whereas genetic variants in genes involved in lipid transport and metabolism such as APOE, LIPC, and LPL may not [The results from sphingolipidomics in biofluids are also useful so as to understand mechanisms involved in the pathogenesis of diseases and their connection to other markers such as genetic and environmental factors. We found that genetic variants in  may not . Han et  may not  showed t may not . TherefoTechnical limitations for the comparison of SL levels in biofluids have arisen from the use of different platforms that are able to measure different panels of SL classes and species. Furthermore, the understanding and comparison of SM results were complicated by the non-identification of sphingoid bases. In order to translate findings to clinical approaches, such as disease specific SL patterns, common analytical methods need to be considered in the future.


This paper provides an experimental investigation on the cracking process and residual mechanical properties of concrete after exposure to elevated temperatures. A total of 36 standard concrete prism specimens were tested after exposure to high temperatures of up to 600 °C. The failure modes, cracking process, residual mechanical properties, deformation characteristics and the strain distribution on the surface during the loading procedure were presented. The influences of exposure temperature and water–cement ratio (w/c) were interpreted. The digital image correlation (DIC) method was applied to quantitatively and visually characterize the development of cracking and relative displacement on the concrete surface. The findings suggest that the residual compressive strength and elastic modulus of the concrete decreases gradually with the increasing temperature, especially in the specimens with lower w/c ratio. The DIC technique provides an effective means to measure very precise and detailed information, including the crack opening and distribution of strain on the concrete surface. Concrete is one of the most widely used building materials, but it is vulnerable to explosive spalling at elevated temperatures caused by fire, explosion or furnaces nearby ,4,5,6,7.In the past decades, researchers have focused on the mechanical properties of concrete after exposure to elevated temperatures, such as compressive strength, splitting tensile strength and elastic modulus. Results have indicated that the degree of deterioration depends on the peak temperature, exposure time, cooling system and concrete composition ,9,14,15.The research discussed above mostly focused on macro properties using traditional instruments, such as strain gauge, extensometer and displacement sensor. However, there are few studies on micro-damage research reflecting the damage process and the full field strain distribution in concrete. Recognizing the drawback of traditional measurement tools, optical measurement methods have gradually gained the attention of researchers. Holographic interference, electronic speckle interference, moiré interference and digital image correlation (DIC) are several commonly used optical measurement methods. Compared with other optical measurement methods, DIC technology has the advantages of simple optical path and insensitive to vibration. DIC technology is widely used in many fields because of its characteristics such as full-field test, simple operation and low requirement for experimental environment ,21,22,23In this paper, an experimental investigation on the cracking process and residual mechanical properties of concrete after exposure to elevated temperatures was carried out, and a combination of the DIC technique and mechanical test were proven as a viable approach for the health monitoring of concrete. According to the design codes  ), after The guiding ideal of this experiment was to evaluate the behavior of concrete with exposure to elevated temperatures. For this purpose, 36 specimens were designed to investigate the influence of the w/c and the peak temperature on the mechanical properties and cracking process of concrete. The specimens’ variables were the w/c ratio  and the exposure temperature . The specimens were named according to their w/c ratio and exposure temperature. For instance, C-1-200 corresponds to the mixture produced with a 0.5 w/c ratio and exposed to 200 °C. The details of specimens are shown in The specimens were prepared by using common ordinary Portland cement with 28 days strength of 42.5 MPa, local river sand with a fineness modulus of 2.4 and coarse aggregates with a size range of 5–10 mm approximately. The mix design for the concrete to be tested was determined using steps outlined in Specification for mix proportion design of ordinary concrete (JGJ55-2011)  and was An electrical furnace, 80 cm × 80 cm in cross section and 110 cm in height, was used to simulate the fire situation, as shown in The axial compression tests on heated and unheated specimens were performed using a hydraulic press machine with a maximum ability of 5000 kN and controlled by the actuator displacement at a rate of 0.2 mm/min according to Standard for test method of mechanical properties on ordinary concrete (GB/T 50081-2002) . A YHD dDIC was originally developed by Peters and Ranson  from theP, a square reference subset centered on point The basic principle of the DIC technique is to search for a maximum correlation between small regions  of the specimen in the undeformed and deformed states, as illustrated in ed image .g is the gray value of the center point In order to assess the similarity degree between the undeformed subset and the deformed subset, a cross-correlation (CC) criterion or sum-squared difference (SSD) correlation criterion was adopted. The matching process was conducted through searching the peak position of distribution of the correlation coefficient. When the extremum of the correlation coefficient was detected, the position of deformed subset was determined. The most popular correlation criteria include the zero-normalized cross-correlation (ZNCC) and zero-normalized sum of squared differences (ZNSSD). These two criterion were highly recommended for practical use, and were theoretically unaffected by changes in illumination, as they were invariant to a linear transformation in gray intensity ,35. The It was reasonable to assume that the shape of the reference square subset was changed in the deformed image. However, based on the assumption of the deformation continuity of a deformable entity, a set of adjacent points in the reference subset were still regarded as the adjacent points in the target subset. As shown in 2. DIC analysis considers the subset and step size set as 51 and 9 pixels, respectively. In this test, as 2)—which is the pivotal element in cement paste—decomposed and caused a dry shrinkage of the cement paste. This discoloration can be explained by the presence of iron compounds, which dehydrate or oxidize in this temperature range.By observing the concrete surface, damage to the concrete after exposure to elevated temperatures can be roughly detected. The assessment of fire damage concrete usually begins with visual observation of color changes, cracking and spalling on the concrete surface. The spalling of concrete generally occurs when it is exposed to elevated temperatures or mixed by lower w/c ratios. When the temperature is below 300 °C or the w/c ratio is higher than 0.32, the spalling of concrete rarely occurs . When suIn order to study the effect of high temperature on the weight loss of concrete, the specimens were weighed before being placed in the furnace and after cooling to ambient temperature. The electronic scale with an accuracy of 0.1 g was used to weigh the specimens. 2) [2) . From thFailure modes of three different w/c ratio specimens after the compressive loading are shown in In the case of the C-1 group, when the mechanical load reached about 70% of the peak value, cracks on the reference specimen began to appear near the top left corner. With the load increase, the cracks continued to grow, and some new, fine cracks appeared. They then developed towards the specimens’ end, producing a slant crack map. At the descending stage, several small pieces of concrete peeled off. At temperatures of about 200 °C and 400 °C, the effect of elevated temperature on the sequence of failure progression was not significant, except that the bearing capacity decreased slowly. When exposed to a temperature of 600 °C, more fine cracks appeared on the concrete surface, and concrete spalled off at an early period. The same situation can be observed in the C-2 and C-3 groups, as shown in In the case of specimen exposure to the same temperature, the damage of the lower w/c ratio specimens were more serious. At a temperature of about 600 °C, the failure modes of the C-3-600 specimen had a significant difference compared with the C-1-600 and C-2-600 specimens, as shown in the rightmost three photographs in The compressive stress–strain curves for different specimens are shown in In 2)—which is one of the most important compounds in cement paste—decomposed, partially resulting in the shrinkage of cement paste. Cement paste is an important link between coarse aggregate, which is the strength-giving compound of concrete. As a result of the shrinkage of cement paste, many cracks were formed between coarse aggregates inside the concrete, resulting in a 50 to 70% reduction in the compressive strength of concrete. Most of the changes that concrete experiences at this temperature level are considered irreversible. It should be noted that the shrinkage of cement paste and the expansion of aggregate plays an important role in the reduction of the compressive strength of concrete after exposure to elevated temperatures.In 2) further increased the pore pressure. These factors led to a greater loss of compressive strength in specimens with smaller w/c ratios.cT/Ec) with and increasing temperature were similar in the three different w/c ratio specimens. When the temperature reached 600 °C, the relative elastic moduli were about 20% of the original unheated specimens. The effect of the w/c ratio on the elastic modulus of concrete was obvious after heating to 200 °C. The different w/c ratios resulted in different free water content, causing various void pressures at the concrete interiors under elevated temperatures, which caused many fine cracks. When the temperature reached 400 °C or above, the effect of the w/c on the elastic modulus was not obvious. In this temperature range, the decrease in the elastic modulus was mainly due to the deterioration of the microstructure and chemical changes, which can be used to explain the above phenomenon.Concrete with different w/c ratios present similar colors and cracking when exposed to the same temperature. The deterioration of concrete performance occurs after exposure to 400 °C or above. After heating to the same temperature, the specimens with low w/c ratio were easy to crack, especially beyond 400 °C. As for the specimens with the same w/c ratio, with a temperature increase, concrete cracked at the early loading stage.The residual compressive strength at 200 °C still retained about 85% of the original unheated value, however, the values at 400 and 600 °C reduced to 75% and 45% on average, respectively. The degeneration of compressive strength mainly occurred between 400 °C and 600 °C. The decrease of compressive strength in this temperature range accounted for more than 50% of the total decrease. The effect of the w/c ratio on compressive strength was most obvious at 600 °C. The effect of elevated temperature on the elastic modulus of concrete was more obvious than that on the compressive strength. After heating to 600 °C, the decreased value of elastic modulus was about 80% of the control specimen.In this research, the average error between the result of DIC technology and YHD displacement meter was about 14%. However, from The axial compression tests on ordinary concrete were carried on using a servo-hydraulic testing machine. The crack development process based on DIC technology was monitored. The following conclusions can be drawn from the experimental results of this research:


Immunoglobulin G4‐related disease (IgG4‐RD), which affects many organ systems, has been recognized as a distinct clinical entity in human medicine for just over a decade but has not been previously identified in dogs. In humans, IgG4‐RD is characterized by diffuse IgG4‐positive lymphoplasmacytic infiltrates that commonly lead to increased serum concentrations of IgG4 and IgE, peripheral eosinophilia, tumorous swellings that often include the parotid salivary glands, obliterative phlebitis, and extensive fibrosis. Herein we describe the diagnosis, clinical progression, and successful treatment of IgG4‐RD in an 8‐year‐old female spayed Husky mixed breed dog. Immunoglobulin G4‐related disease should be considered as a differential diagnosis for dogs with vague clinical signs, lymphoplasmacytic swellings, restricted polyclonal gammopathy, eosinophilia or some combination of these findings. AGEagarose gel electrophoresisCZEcapillary zone electrophoresisIFimmunofixationIMGTImmunogenetics Information SystemMCHmajor histocompatibilityMUM1multiple myeloma 1/interferon regulatory factor 4 proteinSPESerum Protein ElectrophoresisPARRPCR for antigen receptor rearrangementRIreference interval1An 8 year old female spayed Husky mixed breed dog initially was presented to the primary care veterinarian for evaluation of lethargy, mild hyporexia, intermittent soft feces, vomiting, and coughing. Physical examination at that time disclosed a mildly thin body condition and low‐grade periodontal disease, but no other clinically relevant abnormalities. Thoracic auscultation was normal, the abdomen was soft and nonpainful, and no orthopedic or neurological abnormalities were noted.3 cells/μL  and mild basophilia of 0.68 3 cells/μL . The total leukocyte count was 16.9 3 cells/μL, . Moderate hematuria  and proteinuria  were identified on a voided urine sample .Serum biochemical analysis (Beckman Coulter AU 680) performed at Marshfield Laboratories  identified hyperproteinemia of 10.4 g/dL  characterized by hyperglobulinemia of 8.0 g/dL . Serum albumin concentration was slightly decreased at 2.4 g/dL. Additionally, a mild increase in serum AST activity  and mild decrease in serum GGT activity  were present. Serum electrolyte concentrations were normal except for mild hyponatremia . Complete blood count  was normal except for moderate eosinophilia of 6.08 2‐gamma globulin region, a second smaller amplitude peak in the cathodal end of the gamma globulin region and a broad beta‐gamma peak that induced beta‐gamma bridging  and basophilia . A right humeral bone marrow aspirate was performed to assess for possible plasmacytosis. Bone marrow cytology findings included a myeloid‐to‐erythroid ratio of approximately 2:1 with approximately two‐thirds of the myeloid lineage being eosinophils or eosinophilic hematopoietic precursors. In addition, well‐differentiated plasma cells, found both individually and within small aggregates, accounted for approximately 4% of the total nucleated cell population.The patient was referred for further evaluation and treatment of possible multiple myeloma. Physical examination again was unremarkable, and no peripheral lymphadenopathy was identified. The dog was normotensive (Doppler blood pressure 110 mmHg) and no lytic lesions were identified on survey spinal radiographs . A CBC disclosed persistence of eosinophilia  also was performed. The patterns of the AGE and IF were consistent with polyclonal gammopathy and marked IgG4 hypergammaglobulinemia.To further characterize the gammopathy, serum protein electrophoresis and immunofixation (IF) were performed at Colorado State University  due to persistent eosinophilia . Serum biochemistry  identified persistent hyperproteinemia  due to hyperglobulinemia . Mild hypoalbuminemia  and moderately increased AST activity  also were present. Urinalysis disclosed persistent proteinuria  with a specific gravity of 1.010 . A urine protein : creatinine ratio was 1.097 . Abdominal ultrasound examination at this time also identified moderate splenomegaly with heterogenous echotexture and mildly enlarged left medial iliac lymph node (0.77 cm). Fine‐needle aspirate samples of the spleen were of low cellularity, but cytology indicated eosinophilic hematopoiesis with rare plasma cells. Fine‐needle aspirate and cytology of the mandibular lymph nodes disclosed plasmacytosis with eosinophilic inflammation and extramedullary hematopoiesis.Two weeks later, the patient was noted to have developed bilateral chemosis and conjunctival hyperemia, firm swollen parotid salivary glands, and enlarged mandibular lymph nodes. A repeat CBC  disclosed mild leukocytosis . The prednisone dosage again was decreased to 0.5 mg/kg PO q24h and after 1 month at this dosage, the patient's clinical signs had not recurred and serum protein concentrations remained normal . Moderate splenomegaly however persisted but the parenchymal echotexture had returned to normal. The prednisone was discontinued and after 1 month, the patient remained clinically normal and serum protein concentrations remained within the reference range . Both AGE and IF results returned to a normal electrophoretic pattern with notably less prominent labeling for IgG4  in a dog, which ultimately could not be confirmed.c gamma receptors and are considered similar for the purposes of this work.Because of the use of different evolving and mutually overlapping nomenclature systems, the literature and nomenclature on canine IgG subclasses can be confusing.Immunoglobulin G4‐related disease was first described as a distinct entity in the human medical literature as a sclerosing (autoimmune) pancreatitis associated with IgG4 lymphoplasmacytic (IgG4‐producing plasma cells) infiltration and fibrosis of the pancreas.Tumoral swellings in the parotid salivary gland developed weeks after documentation of a monoclonal gammopathy in our case and may represent a reactive process secondary to the underlying IgG4 disorder. The observed mass‐like lesions were not histologically evaluated, but cytologic evaluation of the lymph nodes, spleen and bone marrow indicated a cellular response consistent with the expected IgG4‐RD cellular findings. The number of IgG4‐positive plasma cells and presence of fibrosis and obliterative phlebitis could not be evaluated by cytology in our case. Histologic evaluation ideally would have been performed to eliminate neoplasia, evaluate for fibrosis and phlebitis, and aid in the diagnosis of IgG4‐RD.Eosinophilia and increases in serum IgE concentration both have been suggested as markers of IgG4‐RD in humans.The initial serum protein electrophoresis identified a high‐concentration and restricted protein band in the beta‐gamma globulin region, which mimicked a monoclonal gammopathy. Immunoglobulin G4 typically is found in very low concentrations in health and may not be readily apparent on routine SPE of the dog.The extended immunofixation panel used in our case identified the large beta‐gamma peak as IgG4 and identified a polyclonal IgG response comprised of other IgG subclasses. Although IF does not allow direct quantification, correlation with the electrophoretogram can inform a semiquantitative assessment of protein abundance. In our case, it suggests a substantial component of IgG4, which resolved with treatment. A markedly increased IgG4 fraction is thought to be common in humans with IgG4‐RD, but is variable and may be present in only 51% of cases.Human patients with IgG4‐RD typically are highly responsive to glucocorticoids, if treatment is initiated before the onset of substantial fibrosis.The clinical findings and response to treatment in our case support a diagnosis of IgG4‐RD. The mass‐like lesions, plasmacytosis, and marked hyperglobulinemia with restricted polyclonal gammopathy, which could be interpreted as a monoclonal gammopathy all raised concern for an immunoglobulin‐secreting neoplasm. Previous cases of IgG4‐RD in dogs may have been misclassified as a neoplastic process, as has been documented in human medicine. Clinical awareness of this disease entity in the dog as a differential diagnosis is important when evaluating patients with possible monoclonal gammopathy, plasmacytosis, and eosinophilia.Authors declare no conflict of interest.Authors declare no off‐label use of antimicrobials.Authors declare no IACUC or other approval was needed.Authors declare human ethics approval was not needed for this study.Appendix S1. Supporting Information.Click here for additional data file.


Under cold environments, the freezing and thawing cycles of water in concrete reduce the lifetime and durability of concrete structures. For enhanced freezing and thawing resistance, entrained air voids are generally required, but malfunctioning of air entrainment is sometimes reported in the field. To evaluate the quality of air entrainment, this study proposes a nondestructive method that is a preceding evaluation before damage to the concrete. A nonlinear resonance vibration method is adopted in samples having an identical air void content. The durable concrete sample with resistance to freezing and thawing cycles shows higher nonlinearity in its resonance. Thus, the quality of air entrainment and, furthermore, the potential freezing and thawing resistance can possibly be evaluated by measuring the nonlinearity parameter of the concrete, which is preliminary study to attempt the preceding evaluation of freezing and thawing resistance using nondestructive method. The freezing of concrete causes the volume expansion of the water trapped in the capillary pores. Powers’ hypothesis indicates that ice formation in pores ranging from 0.01 to 10 μm is associated with hydraulic pressure from the constraints of space . The preAir entrainment is required to provide concrete with freezing and thawing resistance. Air contents of 4.5% for normal concrete or 3.5% for high-strength concrete (over 35 MPa) are generally asked for in the field . NeverthNondestructive assessment using an acoustic method was reported and the evaluation of void and crack due to freezing and thawing cycle was performed by X-ray computed tomography . NonlineThe above applications of nonlinear ultrasound evaluate the progression of damage related to the strength and durability of concrete, but the prediction or preceding evaluation of a sample’s performance has not been attempted. This study attempts to evaluate the resistance of freezing and thawing damage of concrete before occurrence of damage in sound concrete, and the verification of the proposed method was performed for the first time. Nonlinear resonance vibration is herein adopted to assess the potential freezing and thawing resistance and the quality of air entrainment in concrete. Finely distributed air voids, which contribute to better freezing and thawing resistance, are one of the contact-type defects affecting the characteristics of the nonlinear ultrasound. As a preliminary study on preceding evaluation using a nondestructive method, the sensitivity and efficiency of the proposed method are discussed based on experimental results from four concrete samples.ε = dε/dt is the strain rate, Δε is the strain amplitude change over the previous period, sign(ε) = +1 if ε > 0 or −1 if ε < 0, and β and δ are the quadratic and cubic orders of nonlinearity, respectively. The hysteretic nonlinearity parameter, expressed by α, has been previously used to evaluate amplitude-dependent resonance frequency shifts [f0 is the linear resonant frequency and f is the biased resonance from a higher amplitude of the impact strain (ε). The background theory assumes that the resonant frequency is proportional to the amplitude of strain.Increasing the free-fall height of the steel bead gave a higher amplitude of the impact resonance. The resonant frequency of the disk specimen increased with a higher amplitude of the impact. y shifts ,28,29. Tw/b) of samples A, B, C, and D were 0.34, 0.41, 0.50, and 0.60, respectively. The compressive strength of each sample was between 29 MPa and 63 MPa after 28 days. The binders for samples A and B consisted of Type I Portland cement having 3.15 specific gravity, supplementary cementitious materials such as fly ash and ground granulated blast-furnace slag (GGBFS), and calcium sulfoaluminate-type expander (Expander in C and D used only the cement. A and B. The HRWRA used was a polycarboxylate-based admixture with a solid content of 30% by mass (ADVA 128). Accordingly, samples A and B incorporated 3.5% entrained air, which is the amount required for high-strength concrete in field specifications. The amount of air voids in the fresh mix of all samples was measured three times following the ASTM C 231 pressure method [C and D were mixed without air entrainment, and they were considered the control samples. Represented values of air content in A and B, the mix proportions were selectively determined based on several pretests.e method . SamplesEach sample group having different mix proportions was mixed for 20 min and fabricated cylindrical samples were cured under water at 21 °C for 28 days. After curing, samples were moved to water at 4 °C in freezing and thawing equipment as saturated conditions. The freezing and thawing resistance of the samples was tested in accordance with ASTM C 666 . ProceduB was not acceptable, as shown in DF) was calculated as DF = N·NP/300, where NP is the relative dynamic modulus of elasticity at N cycles [A contained good-quality entrained air for the freezing and thawing resistance.Damage to the concrete occurred during the accelerated freezing and thawing cycles. N cycles . In summf0) was approximately 12 to 14 kHz, where the amplitude of the reference impact was approximately 200 m/s2 in acceleration. 2, which was the maximum damage range employed in previous studies to evaluate the progression of damage [2, regardless of air entrainment—while a fire-damaged sample in a previous study [2 acceleration is not sensitive to the entrained air voids. Such a small amplitude is not sufficient to activate the contact-type defects or voids in concrete. This means that the previously proposed range for damage evaluation of concrete samples using measurement of nonlinearity parameter is a meaningless and uninfluential range to preceding evaluation of the undamaged concrete sample which is zero cycle  and group B  were tested, and the measured resonant frequencies of A1 and B1 with respect to the applied acceleration were recorded as shown in 2 and 6 km/s2 in A and B, and they were also consistent on the other samples. To implement the initial evaluation of the undamaged concrete, the amplitude of the impact was increased up to 6 km/sA and B including groups C and D as the control sample. The relative shifts based on the linear curve fitting to the total measurements were 0.09% and 0.04% for sample groups A and B, respectively, at 4 km/s2 acceleration. The nonlinearity parameters calculated using Equation (2) were 0.242 × 10−6 and 0.092 × 10−6 for samples A and B, respectively, where Δε is proportional to the peak amplitude of the acceleration and then compensated in the calculation. The relative shift of sample B was still in the trend of the sound state; this can be seen from the fact that extrapolating the linear curve in C and D, having no entrained air, were also in the trend of the sound state. This result shows sensitivity of the nonlinear resonance vibration method on entrained air in undamaged concrete. The nonlinearity parameter of sample A was 2.6-times larger than the result of sample B and its difference was 163%. This result indicates that Sample A has inherent potential contact-type defects that correspond to the entrained void when compared to Sample B. The measurement of air content in concrete has been accepted to evaluate the freezing and thawing resistance [A and B) had the similar amount of air content at the fresh state, the other factor (i.e. inadequate size of the air voids) in Sample B caused the hardships to be detected by the nonlinear resonance vibration method, and they also provided deficient freezing and thawing resistance.sistance , and thesistance ,39. Acco2 acceleration) because they are contact-type defects sensitively responding to the nonlinear ultrasound. Even though experimental result hardly provides a qualitative evaluation, as preliminary study, the proposed method can allow us to evaluate the quality of air entrainment, resulting in a preceding evaluation of the freezing and thawing resistance of concrete.This study proposed a nondestructive method to evaluate the quality of air entrainment in concrete. Finely distributed air voids are important for securing freezing and thawing resistance in concrete. An example mix is reported which indicates that air voids that are inadequate in size are not beneficial, despite having an acceptable air content. The nonlinearity parameter of the example mix, measured via impact resonance vibration, is in the range of sound concrete having no contact-type defects. Non-air-entrained concrete also shows the same range for the nonlinearity parameter. In contrast, good-quality entrained air voids increase the nonlinearity parameter at a high amplitude (up to 6 km/s


Despite evidence supporting the effectiveness of best practices of infection prevention and management, many surgeons worldwide fail to implement them. Evidence-based practices tend to be underused in routine practice. Surgeons with knowledge in surgical infections should provide feedback to prescribers and integrate best practices among surgeons and implement changes within their team. Identifying a local opinion leader to serve as a champion within the surgical department may be important. The “surgeon champion” can integrate best clinical practices of infection prevention and management, drive behavior change in their colleagues, and interact with both infection control teams in promoting antimicrobial stewardship. In 2017, a global declaration for appropriate use of antimicrobials across the surgical pathway was shared by over 230 experts from 83 different countries [In that declaration, efforts to prevent healthcare-associated infections (HAIs) were not specifically highlighted . HAIs inSurgical site infections (SSIs) are a major clinical problem in terms of morbidity, mortality, length of hospital stay, and overall direct and indirect costs globally , 4. HoweThe World Health Organization (WHO) , the CenPreoperative antibiotic prophylaxis (PAP) is a cornerstone of SSIs prevention. The use of PAP contributes considerably to the total amount of antibiotics used in hospitals worldwide. PAP has been shown to be an effective measure for the prevention of SSIs, but its use should be limited to specific, well-accepted indications to avoid cost, toxicity, and antimicrobial resistance, and should never substitute for the good medical practice of infection prevention and control. Guidelines stress the importance of cessation of antibiotic prophylaxis immediately after surgery and refrain from the extension of prophylaxis outside the operating theater . High raAntibiotic therapy is an additional key component of daily surgical practice. Antibiotics are life-saving when treating bacterial infections but are often used inappropriately, specifically when not indicated. Antibiotic therapy plays an integral role in the management of surgical infections, especially in critically ill patients who require immediate empiric antibiotic therapy. Poor antibiotic coverage and inappropriate regimens are the variables most strongly associated with unfavorable outcomes , 11. TheClostridium difficile infections) [Surgeons prescribing antibiotics have two opposing responsibilities. They have to (1) offer optimal therapy for the individual patient under their care and (2) restrain from overprescribing antibiotics to preserve their efficacy and minimize the rate of emergence of antimicrobial resistance, while also preventing collateral damage from antibiotics (such as ections) .Because most surgeons have already established their attitudes and behaviors with regard to antibiotic usage, it is difficult to change their deeply established views and practice patterns. A range of factors such as diagnostic uncertainty, fear of clinical failure, time pressure, or organizational issues can influence prescribing decisions. However, due to cognitive dissonance (recognizing that an action is necessary but not implementing it), it is very challenging to change the prescribing behavior .Surgeons should be aware of their role and responsibility for maintaining the effectiveness of current and future antibiotics. Although most of them are aware of the problem of antimicrobial resistance (AMR), many still underestimate this problem in their own hospital and in their patients. Inappropriate use of antibiotics, as well as poor prevention and control of infections such as hand hygiene, is contributing to the development of AMR. Surgeons are at the forefront in managing patients with infections and should take a proactive role in ensuring both effective antibiotic therapy and the avoidance of inappropriate and unnecessary antibiotic exposure .Successful and cost-effective strategies to reduce AMR should involve a multi-faceted approach aimed at optimizing antibiotic use, strengthening surveillance and infection prevention and control, and improving clinician education regarding the appropriate use of antibiotics.Clostridium difficile infections in hospitalized patients [A growing body of evidence demonstrates that hospital-based programs dedicated to improving antibiotic use can both optimize the treatment of infections and reduce the adverse events associated with antibiotic use . “Antibipatients . Every hASPs should be linked to infection control and prevention programs in order to improve antibiotic prescribing practices and to prevent infections.Dedicated efforts, such as the establishment of locally adopted multi-disciplinary, evidence-based protocols and guidelines; unit specific antibiotic sensitivity data; and compliance monitoring, are required to maximize the performance.p < 0.05). The pathogen detection rate increased from 16.7 up to 41.8% after intervention. The intensity of antibiotic consumption reduced from 74.9 defined daily doses (DDDs) per 100 bed-days to 34.2 DDDs per 100 bed-days after the interventions.To investigate the effects of the antibiotic stewardship program on prevention and control of SSIs during clean surgery, Liu et al.  comparedp < 0.01). The overall SSI rates before and after intervention were 5.4% (95% CI 4.3–6.5) and 4.6% (95% CI 3.6–5.4), respectively.Van Kasteren et al.  in a proRaising awareness is a crucial factor in changing behaviors. Efforts to improve educational programs are thus required, and this should preferably be complemented by active interventions such as prospective audits and feedback to clinicians to stimulate further changes. It would be advisable to introduce specific courses and training about antibiotics in the core curriculum of medical students, with emphasis on the rational prescription of antibiotics that emphasizes more the behavior of medical students towards antibiotics use rather than the advance of knowledge alone .The best means of improving ASPs worldwide should involve collaboration among various specialties within a healthcare institution including prescribing clinicians. ASPs have many contributors, steps, and actions specifically related to the prevention and management of infection. The multidisciplinary approach reinforces the concept that all professionals bring with them their particular expertise and are responsible for their respective contributions. In this context, the direct involvement of surgeons can be highly effective.Surgeons with adequate knowledge in surgical infection who are involved in an ASPs may provide feedback and integrate the best practices of infection prevention and treatment among surgeons.Very few studies have focused on the relationship between ASPs and surgeons. In 2011, Dortch et al.  reportedIn 2015, Çakmakçi  suggesteA retrospective study published in 2016 showed  that theIdentifying a local opinion leader to serve as a champion may be important because the “surgeon champion” may integrate best clinical practices and drive their colleagues into changing behaviors while maintaining a tight collaboration with antimicrobial stewardship and infection control teams. The “champion” should possess a wide knowledge of surgical microbiology, as well as considerable expertise in the antibiotic management of surgical infections. Furthermore, the “champion” should increase the awareness of surgical infections in young staff surgeons and surgical residents.We think that the concept of the “surgeon champion” can be a crucial way to improve the infection prevention and antibiotic prescribing practices across the surgical practice pathway.Surgeons must be aware that appropriate antibiotic utilization is an integral part of any stewardship program and necessary to maximize clinical cure and minimize the emergence of antimicrobial resistance.Antimicrobial restriction is not more effective than the persuasive strategy in achieving the goal of controlling antimicrobial use in the long term . MoreoveSurgeons with good knowledge of surgical infections involved in ASPs may audit antibiotic prescriptions, provide feedback to the prescribers, and integrate the best practice of infection prevention and management among surgeons. We think that the concept of the “surgeon champion” is a crucial way to improve infection prevention and antibiotic prescribing practices across the surgical practice pathway.