Background: The consumption of antibiotics is one of the metrics used to evaluate the impact of antimicrobial stewardship programs (ASP). The aim of this study was to determine the prevalence of antibiotic consumption in Brazilian intensive care units (ICUs) and estimate the deviation of the prescribed daily dose (PDD) from the defined daily dose (DDD).Methods: This is a multicenter, observational, point-prevalence study carried out in adult ICUs of 8 Brazilian hospitals from August 2019, to February 2020. We collected data on the patient’s demographic and clinical characteristics, antibiotic therapy, classification and site of infections. The DU90 (antibiotic accounting for 90% of the volume utilized) was calculated, and the antibiotics were classified by the Anatomical Therapeutic Chemical (ATC) Index and the World Health Organization (WHO) Access, Watch, Reserve (AWaRe) groups. For the most prevalent antibiotics, the deviation of PDD from DDD was determined.Results: Three hundred thirty-two patients from 35 ICUs were analyzed. The prevalence of antibiotic use was 52.4%. The patients in use of antibiotics were predominantly over 60 years of age (81.6%) with pulmonary infections (45.8%). A predominance of empirical regimens was observed (62.6%) among antibiotic therapies. The highest frequencies of prescriptions observed were for piperacillin + tazobactam (16.1%), meropenem (13.3%), amoxicillin + clavulanate (7.2%), azithromycin (7.2%), and teicoplanin (6.1%). The watch (64.2%) and reserve (9.6%) categories of the AWaRe classification accounted for 73.8% of all antibiotics, and they were prescribed alone or in combinations. High variability of doses was observed for the most prescribed antibiotics, and large deviations of PDD from the DDD were observed for meropenem, teicoplanin, and tigecycline.Conclusions: The high prevalence of antibiotic prescription was related to a predominance of empirical regimens and antibiotics belonging to the WHO Watch classification. High variability of doses and large deviations of PDD from DDD for meropenem, teicoplanin, and tigecycline was observed, suggesting that DDD may be insufficient to monitor the consumption of these antibiotics in the ICU population. The variability of doses found for the most prescribed antibiotics suggests the need for monitoring and intervention targets for antibiotic stewardship teams. The consumption of antibiotics is an essential metric to estimate the impact of antimicrobial stewardship programs (ASP) on the rational use of antibiotics and the control of drug resistance. In critical care settings, ASP is especially challenged by frequent antibiotic use due to health care-associated infection, high prevalence of multiresistant bacteria, and systematic empirical therapy.The defined daily dose (DDD) is a metric widely used to estimate and follow the consumption of drugs. However, it may not be ideal for evaluating antibiotics in intensive care units (ICUs) since the average daily dose for adults may not correspond to the mean daily dose prescribed (prescribed daily dose—PDD) to critical care patients. If the doses used are higher than the DDD  or lower , the estimation of the number of days of therapy may not be accurate, making monitoring unreliable . AlternaRecently, the WHO advocated the point prevalence methodology in low- and middle-income countries (LMICs) to estimate the prevalence of antibiotic use in hospitals . In addi® , Rio de Janeiro, Brazil. Data were collected in a single day from August 5th, 2019, to February 20th, 2020. All adult inpatients in the selected ICUs hospitalized at or before 08:00 a.m. were considered eligible. We restricted the inclusion to ICUs registered in the Brazilian Research in Intensive Care Network  database® . The BRI® program to obtain primary and secondary diagnoses , origin, type of admission, Simplified Acute Physiology Score  to prevent an initial infection, the recurrence or reactivation of an infection, or the prevention of infection by the elimination of a colonizing organism . EmpiricWe only analyzed antibiotics prescribed for systemic use. The exceptions were tobramycin for inhalation and vancomycin by oral/enteral inhalation, which were also included. One therapy with antibiotic(s) was considered a prescription of one or more antibiotics directed to one site of infection and/or to one bacterial agent. If the patient was receiving treatment for more than one site of infection and/or for a polybacterial infection and/or for another type of use , each one was considered a different therapy.The antibiotics were classified using the Anatomical Therapeutic Chemical (ATC) Classification System 2021 and WHO AWaRe Classification Database of Antibiotics 2021 for evaluation and monitoring. In the ATC classification system, the active substances are classified in a hierarchy with five different levels. The system has fourteen main anatomical/pharmacological groups or 1st levels. Each ATC main group is divided into 2nd levels, which could be either pharmacological or therapeutic groups. The 3rd and 4th levels are chemical, pharmacological, or therapeutic subgroups, and the 5th level is the chemical substance. The 2nd, 3rd, and 4th levels are often used to identify pharmacological subgroups that are considered more appropriate than therapeutic or chemical subgroups .The AWaRe Classification is intended to be used as a tool for countries to better support antibiotic monitoring and stewardship activities. Antibiotics are classified into three groups: Access, Watch, and Reserve. The Access group includes antibiotics that have activity against a wide range of commonly encountered susceptible pathogens while also showing lower resistance potential than antibiotics in the other groups. The Watch group includes antibiotic classes with higher resistance potential and/or antibiotics at relatively high risk of selection for bacterial resistance. These medicines should be prioritized as critical targets of stewardship programs and monitoring. Last, the Reserve group includes antibiotics and antibiotic classes that should be reserved for the treatment of confirmed or suspected infections due to multidrug-resistant organisms. These medicines could be protected and prioritized as key targets of national and international stewardship programs involving monitoring and utilization reporting to preserve their effectiveness . In the t test was performed for the variable absolute deviation of PDD from DDD, using a test value equal to zero. A significance level of 5% was considered significant.Data analysis was performed using SPSS software. Absolute and relative frequencies and interquartile ranges (IQRs) of demographic and clinical characteristics of the studied individuals were described. The calculation of the total prevalence of the use of antibiotics and of the DU90 (antibiotics accounting for 90% of the volume utilized) was performed. For the most frequent antibiotics, the mean, median, minimum and maximum descriptive statistics of the PDD are presented. The absolute deviation of PDD from DDD was calculated using the formula DDD-PDD. The relative deviation was calculated using the formula [(DDD - PDD)/DDD)]*100. The one-sample This study was conducted by the principles set out in the Declaration of Helsinki and the national and international ethical guidelines. The protocol was approved by the IDOR Institutional Review Board (register CAAE 03963418.8.0000.5249). The need for informed consent was waived. The principles of Good Clinical Practice (GCP) and other applicable regulations were used to guide procedures and considerations. Questionnaire collection was done with the RedCap system on tablets, and all data management was centralized in accordance with GCP and LGPD (Brazilian data protection law). Data integration and analysis were carried out on a secure server prepared for this purpose and conducted according to the analytical plan by the research team. The program was conducted with the clinical staff and those involved in the study ensured that participant’s privacy and confidentiality was maintained. Participants are not identified in any published reports of this study. All records kept confidential to the extent provided by international and local law. All evaluation forms, reports, study protocol, documentation, data and all other information generated will be held in strict confidence.We analyzed the prescriptions of 332 adult patients from 35 ICUs of the 8 hospitals included in the study. Of these, 174 (52.4%) had a prescription for one or more antibiotics on the day of inclusion. The demographic and clinical characteristics of the 174 patients in antibiotic use(s) are summarized in Pseudomonas aeruginosa (25.5%), which was identified mostly in respiratory (50%) and urinary infections (17%). Other frequent pathogens were Staphylococcus aureus (12.8%) and Klebsiella sp. (10.6%). Multidrug-resistant strains were also observed, such as Pseudomonas aeruginosa and Klebsiella sp ESBL-positive or carbapenem-resistant and methicillin-resistant Staphylococcus aureus , followed by definitive (23.4%) and prophylactic (7.5%). The number of infections was 171, and 52.6% were health care-associated infections. Of the 168 sites of infections observed in this study, the majority were pulmonary (45.8%) and intra-abdominal (15.4%) . Table 3The total number of prescribed antibiotics was 279. p value <0.05 were observed for the antibiotics meropenem (−55.0%), teicoplanin (−79.4%) and tigecycline (−62.5%). The negative values of the deviations indicate that the mean PDDs were higher than their respective DDDs. It is also noteworthy that there is a high variability of prescribed doses for most of the antibiotics analyzed in The analysis of the deviation of the PDD from the DDD was performed for the most frequently prescribed antibiotics . Larger Point prevalence studies are being widely used to determine exposure to antimicrobials . The usevs. 12.8%; hemodialysis 17.8 vs. 2.8%. The high prevalence of antibiotic prescription found in this study (52.4%) is probably related to the severity of disease in the ICU population and the frequency of sepsis as a diagnosis. This prevalence is similar to those found for other ICUs in the world, even though in this case, the comparison is difficult because the studies are mainly performed for antimicrobials (not only antibiotics), and comprehensive clinical data of the patients have not been published. In the Brazilian Point Prevalence Study performed in 2017 at 18 hospitals, the authors found a prevalence of 60.3% for antimicrobial use in adult ICUs (Disease in this study’s population seemed more severe than that described in the Brazilian ORCHESTRA study, which evaluated 59,693 patients from 78 national ICUs in 2013 . The medult ICUs . In the ult ICUs . In the ult ICUs .Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella sp. These bacteria are prevalent in the ICUs of Brazil, including resistant strains (Pseudomonas aeruginosa and Klebsiella sp. are considered critical by the World Health Organization and were identified in this work. Staphylococcus aureus, methicillin-resistant, and Enterococcus sp vancomycin-resistant are considered of high priority in this list and were also identified in this work. A finding that stands out is that we did not observe any infection caused by Acinetobacter baumannii in our study. This bacterium is prevalent in Brazilian ICUs (The predominance of empirical treatments observed here is probably related to disease severity, the predominance of pulmonary infections, the high prevalence of sepsis, and the advanced age of patients. The high selective pressure favoring resistant bacteria and the local epidemiology might also be considered. Regarding the definitive therapies, we identified a predominance of the pathogens  strains . In 2017 strains . Carbapeian ICUs .Previous studies on the consumption of antibiotics were conducted using various metrics, miscellaneous methodologies, and patient profiles. In addition, it should be noted that the current study was conducted before the COVID-19 pandemic was declared. Nevertheless, we consider that the results obtained for the most prescribed antibiotics present similarities to those obtained by recent studies performed in Brazilian ICUs . In all On the other hand, studies from other LMICs observed that third-generation cephalosporins were the most consumed antibiotics . ConsideDDD is a universally accepted metric for drug utilization research . Thus, tIn a systematic review followed by a RAND-modified Delphi consensus conducted by This work presents limitations that are intrinsic to its methodology. As a point prevalence study, incidence could not be reported, and long-term treatments may be overrepresented. Additionally, patients were not followed-up in time. Data from different hospitals were collected on different days, and we cannot exclude the possibility of seasonal differences.In conclusion, this study reinforced the high prevalence of antibiotic use in a population of critically ill adults and provided additional evidence that the DDD metric presents limitations for monitoring antibiotic use in ICUs. More studies are necessary to determine the adequate metrics or combination of metrics. More accurate metrics may improve antimicrobial stewardship, benchmarking and future pooling of data in systematic reviews.


Upper respiratory tract infection (URTI) is a self-limiting viral infection and should not be treated with antibiotics. The aim was to evaluate antibiotic prescriptions for children with uncomplicated URTI in a large nationwide private clinic network between 2014 and 2020. Special focus was given to macrolide prescriptions and costs. The data were obtained from the electronic health records (EHR) of the largest private healthcare company in Finland . The collected variables included diagnoses, age, visit year, speciality of the doctor, and prescribed antibiotics. The number of uncomplicated URTIs in < 18-year-old children was 156,187 (53.0% in boys). The prescription rate of antibiotics decreased from 18.0% in 2014 to 8.8% in 2020, and that of macrolides from 6.1 to 1.7%. The costs decreased accordingly. Paediatricians prescribed antibiotics less often than general practitioners or ear, nose, and throat specialists.Conclusion: Antibiotic prescriptions for uncomplicated URTIs, especially macrolides, decreased substantially during the 7-year surveillance period; however, 8.8% of children still received unnecessary antibiotics. To further reduce unwarranted antibiotic prescriptions, active interventions are needed that can be performed by applying the available EHR system.The online version contains supplementary material available at 10.1007/s00431-022-04512-w. Upper respiratory tract infection (URTI) is the most common infection in children, with an average of six to eight URTI episodes a year at preschool age . URTIs lEar and sinus infections and pneumonia are bacterial complications of URTI in children. Approximately 70% of children suffer from acute otitis media before the age of 2 years . The annThe task force set up by the European Paediatric Association concluded that the over-consumption of antibiotics in children with spontaneously recovering respiratory tract infections is one of the most important healthcare problems in children in Europe . Less coThe aim of the present study was to evaluate antibiotic prescriptions for children with uncomplicated URTIs in a nationwide private outpatient clinic network in Finland. Special focus was paid to macrolide prescriptions. An additional aim was to estimate the cost of prescribed antibiotics, as well as variations in antibiotic prescriptions based on age, time, and the speciality of the doctor.The study was conducted using data from the electronic health records (EHR) of Terveystalo, the largest private healthcare company in Finland, with about 250,000 paediatric visits annually around the country. Terveystalo has more than 300 clinics in each of the 20 hospital districts in mainland Finland.th codes J00, J06, J06.80, J06.89, J06.9). The children were classified into four age groups: < 2 years, 2–4.9 years, 5–11.9 years, and 12–17.9 years. Patients with a concomitant bacterial diagnosis were excluded  is a tool utilised by Terveystalo for handling EHR data. The data for this analysis were collected and combined from records containing the required personal information, visit information, diagnoses, and medications as registered in DynamicHealth by the practitioner. Patients’ birth date information was derived from the EHR and used in calculating patients’ age upon visit from 2014 to 2020. The doctors were classified into paediatricians; general practitioners (GP); ear, nose, and throat specialists (ENT); and others. The patient data was actively managed in adherence with the European Union’s General Data Protection Regulation (GDPR) and the data security legislation of Finland.Antibiotic prescriptions were identified from the EHR, with the antibiotic-related cost estimated by the 2021 price of each product in euros. The data included the name of the prescribed medicine, but detailed information on the dosage and size of the prescribed packets was missing. In Finland, the Pharmaceutical Pricing Board determines the national reference prices for medicinal products, such as antibiotics, that are reimbursable under the Health Insurance Act. Thus, these prices are the same in every pharmacy across the country; therefore, these reference prices were used for cost estimation in this study. The costs were estimated with the lowest price  and the highest price (largest size of packet) for each antibiotic. In this way, variations in the costs could be found and were comparable between the study years. The annual costs and costs per patient were estimated with the presumption that every prescribed antibiotic was purchased.All URTI visits of all cases during the study period were included in the analyses. Therefore, power analyses or formal sample size calculations were not performed. IBM SPSS Statistics for Windows, version 26 , was used in the data analysis. The age and gender of the child, speciality of the doctor, and visit year were included as co-variates in the multivariate logistic regression, and the results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The statistical analyses focused on percentages, considering that respiratory infections were reduced by lockdown measures throughout 2020 , 12. TheThis study was a quality assessment and development project. All data were coded, and patients were not contacted. According to Finnish law, approval from the Ethics Committee was not required, and informed consent was not needed from the subjects and/or their legal guardians. This study was carried out in accordance with national regulations and was approved by the chief medical officer of Terveystalo.The total number of doctoral visits in < 18-year-old children was 1,629,187 (52.6% in boys) during the period of 2014–2020  and later visit year (OR 0.88) were associated with lower ORs for receiving antibiotics in a multivariate logistic regression adjusted by the age and gender of the child, visit year, and speciality of the doctor. Compared to paediatricians, the respective ORs were 1.64 for GPs and 1.71 for ENT specialists Table .In 2014–2017, the estimated annual total costs related to antibiotics followed a trend of the number of URTI visits. Meanwhile, in 2018 and 2019, URTI visits increased, but the annual total costs decreased remarkably, and in 2020, both the visits and costs decreased. The annual total costs varied between €62,327 in 2017 and €19,885 in 2020, when the highest antibiotic prices were used for estimation. The mean antibiotic-related cost per patient decreased consistently from €3.2 (in 2014) to €1.5 (in 2020) when the highest prices were used  took place in macrolide prescriptions. This decrease was similar in all age groups and in all doctoral speciality groups. Third, paediatricians prescribed antibiotics less often than GPs and other specialists, a finding in agreement with other recent studies .The main strength of the present study was that the analysed data came from outpatient clinics covering different areas across the country and consisted of almost 159,200 children younger than 18 years with uncomplicated URTI diagnoses. The information was electronically entered and obtained for this study from the centralised and uniformly coded EHR. Our study has some limitations. The data are retrospective and come from the private sector and thus may not fully represent the whole Finnish child population. Moreover, we lacked data on the lengths of the antibiotic treatments as well as on definite medicine purchases. It is also possible (though unlikely) that not all diagnosis codes were recorded during the URTI visit, and some children were treated  without the code for a condition warranting antibiotic therapy being recorded.The COVID-19 pandemic started at the end of 2019 and was ongoing during the last year of our study. Due to social distancing restrictions and hygiene recommendations, the circulation of all respiratory viruses was lower during than before the pandemic , 12. In A recent questionnaire study on parental antibiotic use for URTIs in their children included 3,188 families across three provinces in China . 46.0% oIn a French register study, the authors analysed 221,768 paediatric visits for different respiratory infections in a national sample, including 680 GPs and 70 community paediatricians . The desA register study from Canada collected data from the national Electronic Medical Records Primary Care database . The stuThe construction and dissemination of treatment guidelines have no doubt played a role in the change in clinical practices. Antibiotic stewardship programmes and other interventions have increased the awareness of doctors and parents about the indications, advantages, and disadvantages of antibiotics, the spread of antibiotic resistance in the population, and the need for activities to enhance antibiotic stewardship –22. ThisThe decreasing trend of antibiotic prescriptions in children with URTI was constant during our study period. The current antibiotic consumption level, < 9% in 2020, has been reached by means of recommendations and information disseminated to doctors as well as by the increased general awareness regarding antibiotics among parents. The evidence-based Current Care Guidelines in Finland have a long history. For years, they have been published online and are easily accessible by doctors and laypeople free of charge. All guidelines emphasise that respiratory tract infections of viral origin should not be treated with antibiotics and that macrolides are not first-line alternatives for any respiratory infection, except for pertussis in infants.Mycoplasma CAP as monotherapy because Streptococcus pneumoniae is common in mixed infections and is not sufficiently susceptible to macrolides in Finland, like in many other countries [The first Finnish Current Care Guidelines for lower respiratory tract infections in children, including CAP, pertussis, laryngitis, wheezing bronchitis, bronchiolitis, cough, otitis media, and sinusitis, were published in 2014. Macrolides are not recommended even for ountries , 24. Theountries . The Finountries .In addition to the readily available national guidelines in the healthcare company, where the present study was done, an active intervention was carried out during 2017–2020 aiming to stop prescribing cough medicines for children , 28. TheA study from the Netherlands evaluated the cost-effectiveness of GP- and parent-directed intervention aiming to reduce antibiotic prescriptions for respiratory tract infections in children. The intervention was effective, as 25% compared to 50% of the controls received an antibiotic over the study period. The mean cost per patient associated with a respiratory tract infection was higher in the intervention group (€217.95) compared to usual care (€207.68) from a societal perspective. However, the mean healthcare costs per patient, including the intervention costs, were lower  . In a JaAntibiotic prescriptions decreased constantly during the 7-year surveillance period of this study. Despite this, 8.8% of the children still received unnecessary antibiotics due to uncomplicated URTI cases. The most notable reduction in antibiotic use was for macrolides; this was seen in all age and speciality groups. To further reduce unwarranted antibiotic prescriptions, active interventions are needed, and such interventions should be, in the case of URTI, especially targeted to general practitioners and ear, nose, and throat doctors.Supplementary file1 (DOCX 105 KB)Below is the link to the electronic supplementary material.


As the construction industry is striding towards the industrialization of green buildings, a precast concrete frame beam-column joint with high-strength reinforcement was proposed. Simulate reversed cyclic loading was carried out on two precast connections and one cast-in-place connection to examine the seismic behavior of the proposed new precast connection. The main test variables between the two precast connections were the strength of the reinforcement at the bottom of the beam. The failure shape, hysteresis curve, skeleton curve, strength, deformation ability, stiffness degradation, and energy dissipation were monitored and compared with the cast-in-place connection. The findings of this paper showed that the precast joints had good strength reserve, and the seismic performance in the later stage of loading even exceeds the cast-in-place joints. It was also found that the plastic hinge zone of the beam could be moved away from the column surface via reinforcement method. Additionally, based on the experiment, a detailed nonlinear finite element analysis (FEA) method was developed to reproduce the test response of specific types of bending moment-resistant precast concrete beam-column connections under a reversed loading test, which provided a theoretical reference for further research of the connections. The application of concrete has a long history, and the research on concrete structures has never ceased, especially regarding concrete beams, columns, walls and slabs . HoweverA large number of scholars have proposed post-cast monolithic prefabricated concrete frame joint systems with reinforced anchorage or lap connection. Im et al.  proposedTo solve the problem that steel bars were prone to collision in the panel zone, some scholars had proposed a series of measures to enhance the connection performance. Gou et al.  proposedThis paper presents an assembled concrete frame beam-column joint with high-strength reinforcement. The small-diameter high-strength bars are used to replace ordinary steel bars at the bottom of the prefabricated beam. When assembling the prefabricated components, the small-diameter steel bars can move freely within the range of the keyway to avoid collision between the tensile bars of beams and columns. Additionally, to avoid the premature failure of the concrete in the keyway of the prefabricated beam with high strength reinforcement under loading, the core beam is set in the keyway. Besides, in the context of global initiatives for energy conservation and emission reduction, it has become a general trend to promote the future use of high-strength materials in the construction industry. The application of high-strength materials can improve the service life of a structure, reduce the weight of a structure, reduce the dense configuration of steel bars, facilitate construction, ensure project quality, and promote energy conservation and environmental protection.The connection design was improved based on the reference by Yu et al. . ThroughThe specimens were tested, including a full-scale cast-in-place specimen and two full-scale precast specimens. The cast-in-place specimen was labeled as XJ, as shown in All specimens were processed and manufactured in a precast component factory. The XJ connection was poured in a flat-laying manner. First, the steel cage was bound. Then, the formwork was supported, and, finally, the concrete was poured. After the pour was completed, it would be cured under natural conditions. The production process of precast connections is as follows: The first step was to make the precast components as shown in Three cubes were made for each batch of concrete, and then they were cured under the same conditions as the full-scale specimens. Three samples were taken for each kind of steel bar for direct tensile tests. The mechanical properties of concrete and rebars are shown in In this test, a 1500 kN hydraulic servo control system (MTS) was used to apply a horizontal load on the top of the column. The axial load of the column was applied to the steel strand through a through-hole jack. The axial pressure ratio was controlled to 0.27, corresponding to the axial load carrying capacity. The loading device is shown in For quasi-static loading tests, Chinese code recommends the use of a load-deformation dual-control loading system  . HoweverThere were no cracks that appeared during preloading with a drift ratio of 0.034% and 0.069%. The specimen was loaded with a 0.2% drift ratio for the first stage, and several cracks at the bottom of the beam appeared at approximately 5 cm, 10 cm, 35 cm, and 62 cm from the beam-column joint surface. When loading at a drift ratio of 0.35%, a crack with a width of 0.06 mm at the top of the beam appeared at approximately 55 cm from the beam-column joint surface. When loaded at a 0.5% drift ratio, there were many vertical bending cracks at the top of the beam, and the cracks in the upper and lower beams penetrated each other. When loaded to a 0.75% drift ratio, visible cracks appeared at the beam-column junction with a width of 0.6 mm. As the loading drift ratio increased, the width, length, and number of cracks increased. The distribution of the cracks gradually expanded toward the loading end, and the number of diagonal cracks increased. When loaded at a drift ratio of 4.25%, the concrete at the lower end of the beam experienced substantial spalling. It was observed that the lower longitudinal rebar was bent when it was compressed. At a distance of 10 cm from the beam-column interface, a wide main crack formed in the middle of the beam, and the load dropped significantly, lower than 80% of the peak load, and the loading was complete. The final failure pattern of specimen XJ is shown in First, we carried a single load of 0.034%, 0.069%, and 0.10% drift ratio on YZ1. When the 0.069% drift ratio was loaded, a crack with a width of 0.02 mm appeared in the lower part of the beam at a distance of 11 cm from the beam-column interface. When loaded to a drift ratio of 0.10%, bending cracks that developed from the bottom to top appeared at the bottom of the beam at 6 cm, 38 cm, and 60 cm from the beam-column interface, respectively. After loading to the drift ratio three times per stage, the cracks gradually developed until the specimens were damaged. When loading at a 4.25% drift ratio, the concrete at the beam end was continuously crushed, and the lower concrete continuously fell. It could be observed that while the lower longitudinal reinforcement bends when compressed, the concrete inside the core beam was also crushed, and the above-mentioned diagonal cracks continued to widen, forming a major diagonal crack. When the 4.25% drift ratio was repeatedly loaded for the second time, the load value was significantly reduced, the specimen was damaged, and the loading was stopped.The specimen YZ2 failure pattern was almost similar to the YZ1 specimen. When loaded to a drift ratio of 3.5%, a large amount of concrete under the beam spalled off. The steel strand was exposed, the strand came loose when pressed, and the stiffeners fractured. When the third loading was carried out at a drift ratio of 3.5%, the load dropped to 80% of the peak value, and the testing was ceased.Through the low-cycle repeated loads test process of three joints, it was found that all specimens had experienced the elastic stage, crack propagation stage, and failure stage. During the loading process, the cracking load of the cast-in-situ joint was higher than that of precast joints, because the precast joints had the new and old concrete interface, cracks appeared at this place during the loading process, and they would soon penetrate up and down. In general, the expected beam end bending failure occurred at the three joints, and only a few small cross-oblique cracks appeared in the joint core area.(1)It can be seen that the XJ specimen exhibits better linear elasticity in the initial loading stage. The hysteresis loop is close to a straight line, and the energy absorption is minimal. With the increase in the loading displacement, the cracks gradually expand, the residual deformation increases, and the signs of fusiform hysteresis loops gradually appear. When the load corresponds to a lateral displacement of 43.5 mm, the curve shows a clear yield platform segment corresponding to the specimen yielded. The curve has begun to pinch, showing a bow-shaped hysteresis loop, mainly due to cracks in the lower part of the beam end and small amounts of concrete being crushed and falling. The curves of the three cycles of each stage have a high degree of coincidence when the load corresponds to a lateral displacement of 58 mm. This indicates that the component has a strong recovery ability and has little effect on the performance of the component in repeating loading. When the load corresponds to a lateral displacement of 79.8 mm, due to the spalling of the precast beam concrete, the restoration performance of the members is significantly reduced. At the level of 123.3 mm, the pinch effect of the curve is more obvious, showing a certain inverse S-shape, and the lower longitudinal bars show obvious buckling and slipping. The load reaches 80% of the peak load after a load cycle, and the specimen is damaged. In general, the hysteresis curve is full, corresponding to good energy absorption.(2)It can be seen in the YZ1 specimen that the hysteresis loop changes similar to that of the XJ specimen. However, the hysteresis capability of the YZ1 at the level of 101.5 mm is still strong. Compared with the XJ specimen, the yield load and ultimate load are similar, and the hysteresis curves are identical. However, the pinch phenomenon of the YZ1 specimen was better than that of the XJ specimen at 123.3 mm. The hysteresis and ultimate load-carrying capacity of the YZ1 specimen were stronger than those of the XJ specimen.(3)The YZ2 specimen uses steel strands as longitudinal bars. The fullness of the hysteresis curve is not as good as that of the XJ specimen. The hysteresis loop begins to shrink into an inverse S shape at the 21.8 mm level. From the 43.5 mm level, the recovery performance of the YZ2 specimen begins to decline. It is damaged at the level of 101.5 mm, indicating that YZ2 has insufficient bearing capacity under large displacements. In general, compared with the XJ, the YZ series has a weaker energy absorption capacity and seismic performance.The hysteresis curve shows the deformation process of the component, which can be used to fully understand the characteristics of stiffness, strength, deformation, energy absorption, and damage to the component of a structure. The hysteresis curves of the three specimens are shown in Stiffness degradation reflects the cumulative damage of the component under repeated loading, and it is one of the important indicators to analyze the dynamic structural characteristics. The stiffness calculation formula is as follows, and the stiffness regression curve is shown in It can be found in The equivalent area method has a relatively clear physical meaning and is widely accepted to determine the yield point . In thisThe yield strength and peak strength are summarized in The displacement ductility ratio μ is defined as the ratio of the ultimate displacement to the yield displacement of the joint; the displacement ductility ratio μ in the tensile and push directions are calculated, respectively.The displacement ductility ratio is summarized in The equivalent viscous damping coefficient is an important indicator for measuring the energy absorption capacity of structures for earthquake resistance . The calIt can be seen in Concrete was modeled by the C3D8R element , and concrete was modeled by concrete constitutive provided by the code for the design of concrete structures  . The speUniaxial tensile constitutive of concrete.Uniaxial compression constitutive of concrete.The strength of concrete used in this paper is C40, and the tensile-compression stress-strain curve is shown in s was the initial stiffness; shK was the hardening stiffness; srK was the unloading stiffness.The constitutive model of rebars was shown in m − ε0)/εy, the literature  stipulates that the unloading stiffness varies according to the size of β; that is, the unloading stiffness is calculated according to the following formula.Set β = α={The ultimate displacement and ductility coefficient of the YZ1 was higher than those of the cast-in-place node, which indicated that the ductility of the YZ1 was not lower than that of the XJ and ensures that the YZ1 had better ductility under the action of seismic.(2)YZ2 shows insufficient ductility and energy consumption. When the component is damaged, the deformation of the ordinary additional steel bar is small, so the seismic performance is not as good as that of the cast-in-place component.(3)Using the steel hysteresis model proposed in this article, the mechanical performance of precast concrete beam-column joints can be simulated more accurately, which provides a theoretical reference for the further improvement and design of joints.(4)The strength of the beam-column joint could be enhanced by adding additional steel bars, dampers, and pre-embedded section steel at the beam-column joints to promote the plastic hinges moving outward to the beam ends, and this could help to avoid the collapse of the entire structure due to the development of the plastic hinge in the panel zone.This study has improved the connection based on previous research. Also, the seismic performance of the connections was studied, and the following conclusions were obtained through the research.


Klebsiella quasipneumoniae is an opportunistic pathogen causing antibiotic-resistant infections of the gastrointestinal tract in many clinical cases. Orally delivered bioactive Klebsiella-specific antimicrobial proteins, klebicins, could be a promising method to eradicate Klebsiella species infecting the gut.K. quasipneumoniae strain DSM28212. Four study groups were used  to test the antimicrobial efficacy of orally delivered klebicin KvarIa: vehicle-only group , and other three groups with bacteria, antibiotic therapy and 100 µg of uncoated Kvarla, 100 µg coated KvarIa, 1000 µg coated-KvarIa. Because of the general sensitivity of bacteriocins to gastroduodenal proteases, Kvarla doses were coated with Eudragit®, a GMP-certified formulation agent that releases the protein at certain pH. The coating treatment was selected based on measurements of mouse GI tract pH. The quantity of Klebsiella haemolysin gene (khe) in faecal samples of the study animals was used to quantify the presence of Klebsiella.Mouse infection model was established based on infection of antibiotic-treated BALB/C mice with K. quasipneumoniae was achieved only in the antibiotic-treated mice groups. Significant changes in khe marker quantification were found after the use of Eudragit® S100 formulated klebicin KvarIa, at both doses, with a significant reduction of K. quasipneumoniae colonization compared to the vehicle-only control group.GI colonization of K. quasipneumoniae can be achieved if natural gut microbiota is suppressed by prior antibiotic treatment. The study demonstrates that GI infection caused by K. quasipneumoniae can be significantly reduced using Eudragit®-protected klebicin KvarIa.Mouse GI tract colonization with  Klebsiella is a gram-negative and facultative anaerobic bacterium of the Enterobacteriaceae family that colonizes various environmental niches including normal flora of the human mouth or intestines  Colicins encapsulated into hydrogel particles were shown to be released from the protective coat at pH above 5 and reduce colonizing E. coli numbers in the gut and in feces, although complete eradication of the pathogen was not achieved [In this study recombinant bacteriocins KvarIa ability to eliminate the intestinal tract infection was judged using achieved . ConsequK. quasipneumoniae can be achieved but it requires the eradication of gut resident microbiota with an antibiotic. We also evaluated the antimicrobial activity of the orally delivered Eudragit S100-formulated klebicin in the mouse intestinal tract and show that thus formulated bacteriocins could be employed as oral antimicrobials for efficient control of antibiotic-resistant Klebsiella.This study demonstrated that successful colonization of the mouse intestinal tract by


There is an interesting potential for the use of GFRP-pultruded profiles in hybrid GFRP-concrete structural elements, either for new constructions or for the rehabilitation of existing structures. This paper provides experimental and numerical investigations on the flexural performance of reinforced concrete (RC) specimens composite with encased pultruded GFRP I-sections. Five simply supported composite beams were tested in this experimental program to investigate the static flexural behavior of encased GFRP beams with high-strength concrete. Besides, the effect of using shear studs to improve the composite interaction between the GFRP beam and concrete as well as the effect of web stiffeners of GFRP were explored. Encasing the GFRP beam with concrete enhanced the peak load by 58.3%. Using shear connectors, web stiffeners, and both improved the peak loads by 100.6%, 97.3%, and 130.8%, respectively. The GFRP beams improved ductility by 21.6% relative to the reference one without the GFRP beam. Moreover, the shear connectors, web stiffeners, and both improved ductility by 185.5%, 119.8%, and 128.4%, respectively, relative to the encased reference beam. Furthermore, a non-linear Finite Element (FE) model was developed and validated by the experimental results to conduct a parametric study to investigate the effect of the concrete compressive strength and tensile strength of the GFRP beam. The developed FE model provided good agreement with the experimental results regarding deformations and damaged patterns.  Fiber Reinforced Polymer (FRP) materials are taking place in several applications in civil construction such as bridges and buildings, which are new or degraded structures . There aBased on the literature, understanding the behavior of the GFRP-section with RC was the main objective of many researchers ,14,15,16Previous numerical investigations were conducted on the behavior of encased GFRP beams under the effect of static and impact loading ,18,19,20Previous studies were reported on the behavior of normal- and high-strength concrete reinforced with GFRP rebars ,22,23. ACurrently, research on encased GFRP beams with high-strength concrete is very limited. This manuscript adds valuable test data for encased pultruded GFRP I-beam with high-strength concrete under static loading. From this source and the latest studies in this field, this paper provides experimental and numerical investigations on the flexural performance of RC specimens composite with encased pultruded GFRP I-sections. Five simply supported composite beams were tested. Besides, the effect of using shear studs to improve the composite interaction between the GFRP beam and concrete as well as the effect of web stiffeners were explored. In addition, a non-linear FE model was developed and validated with the experimental results to conduct a parametric study to investigate the effect of the concrete compressive strength and tensile strength of the GFRP beam.Five simply supported composite beams were tested to investigate the static flexural behavior of encased GFRP pultruded I-beams with high-strength concrete. The test matrix for the conducted experimental program is listed in G), 100 mm flange width (bf), and flange and web thickness of 10 mm (t), as shown in All beams were simply supported with overall and effective lengths of 3000 mm and 2750 mm, respectively. Rectangular cross-sections with 200 mm in width and 300 mm in height were adopted. The details of the tested beams are shown in The concrete mix proportion of the used high-strength concrete is listed in Tension tests were carried out on steel rebars of 16 and 10 mm diameters. Three specimens for each diameter were tested in the Consulting Engineering Bureau, College of Engineering, the University of Baghdad according to ASTM A615/A615M-18 . The obtThe GFRP I-beams used in this study were made by an international manufacturer of FRP products . They were made of isophthalic polyester resins reinforced with E-glass fibers. The mechanical and geometric properties of the pultruded GFRP I-section are listed in ε1 to ε6) were used to measure the strains in the steel rebars, concrete, and GFRP I-section at the mid-spans, as illustrated in The specimens were tested as simply supported beams under the effect of a concentrated load at the mid-spans. A hydraulic jack, with 490 kN capacity, was used to apply the load. The applied load and corresponding deflection were recorded using a load cell and linear variable differential transforms (LVDT), respectively, as shown in The load versus mid-span deflection curves for the tested beams are shown in The initial crack load for each specimen is listed in The strain records are illustrated in Eμ) was calculated based on Equation (1) depending on the load-deflection relationships for the tested beams.TE is the total energy calculated from the area under the load-deflection curve, EE is the stored elastic energy calculated from the load-deflection relationships as shown in S) was obtained from the following equation:There are many definitions for ductility and ductility index of conventional RC structures with only steel rebars. The ratio of deflection at ultimate load to the deflection at yield load can define the ductility of these members. The FRP materials have a linear stress-strain relationship until failure, and the energy released for FRP beams is linear, which is different from that for steel reinforcement. Therefore, the ductility in this study is based on the energy theory . The ducThe total energy, elastic energy, and ductility of the tested specimens are illustrated in Finite Element (FE) models were developed, using the general-purpose FE code Abaqus , to simuDifferent element types were used to model the different components of the encased beams . Continuum eight-node solid element with reduced integration (C3D8R) was used to simulate the nonlinear behavior of concrete, shear connectors, and steel plates. The interface between the bearing plates and concrete was modeled as a surface-to-surface interaction. The pultruded GFRP beam and web stiffeners were modeled by using the four-node doubly curve shell element with reduced integration (S4R). The longitudinal and transverse reinforcements were modeled using the 2-node linear 3D truss element (T3D2). Several nonlinear analyses with different element sizes were performed to select the best mesh size to obtain accurate results at a reasonable solving time. The FE mesh showing the different components of the encased beams is illustrated in The experimental boundary conditions were adopted in the FE analysis as simply supported beams. The first support was constrained in the Y- and Z-directions, representing the hinge support. At the same time, the second support was constrained only in the Y-direction, which expressed the roller support. The whole model was constrained in the X-direction. The full bond technique was assumed to simulate the connection between the concrete and steel rebars. However, the bond between the GFRP beam surface and the surrounded concrete was simulated using surface-to-surface contact pairs. The contact property was represented by the tangential behavior with a penalty friction formulation. The tangential shear stress was adopted from the push-out test as 0.422 MPa  and the ψ was 36°, the value of the plastic flow potential eccentricity (e) was 0.1, and the ratio of the initial equibiaxial compressive yield stress to initial uniaxial compressive yield stress (σbo/σco) was 1.16. Moreover, the coefficient (Kc) was 2/3 and the viscosity parameter was 0.001. The elastic properties of concrete were specified according to the ACI 363R-92 [The compressive behavior of concrete was defined using the concrete damaged–plasticity (CDP) model . In this 363R-92  and ACI  363R-92  guidelin 363R-92 ,35. Figuf as listed in The steel reinforcement was simulated as an elastic–perfectly plastic material. The modulus of elasticity and yielding stress were used to define the stress-strain curve. The degradation in the GFRP I-beam was modeled according to Hashin’s criteria . AccordiThe conventional load-deformation curves for the tested specimens were used to validate the FE results, as shown in The FE crack patterns for concrete were represented in Abaqus by defining the post-cracking damage properties for the CDP model by visualizing the tensile damage at the integration point DAMAGET. The influences of the compressive strength of concrete and tensile strength of the GFRP beam on the flexural behavior of encased GFRP I-beam were investigated using the verified FE model.The influence of various concrete compressive strengths of 45 MPa, 53.8 MPa, and 65 MPa on the flexural performance of encased beams under static load was studied. The different compressive strengths were implemented in Abaqus through the stress-strain curves as well as the CDP model. The peak loads of the analyzed specimens are shown in To study the effect of tensile strength of GFRP I-beam on the flexural behavior of the encased beams, two tensile strengths of 258 MPa and 416.6 MPa  were invThis paper provides experimental and numerical investigations on the flexural performance of RC specimens composite with encased pultruded GFRP I-sections. Five simply supported composite beams were tested in this experimental program to investigate the static flexural behavior of encased GFRP pultruded I-beams with high-strength concrete. Besides, the effect of using shear studs to improve the composite interaction between the GFRP beam and concrete as well as the effect of web stiffeners of GFRP were explored. Moreover, a non-linear FE model was developed and validated by the experimental results to conduct a parametric study to investigate the effect of the concrete compressive strength and tensile strength of the GFRP beam. The following conclusions can be drawn based on the experimental and FE results.Encasing the GFRP beam with concrete enhanced the peak load by 58.3%. Using shear connectors, web stiffeners, and both improved the peak loads by 100.6%, 97.3%, and 130.8%, respectively, relative to the classical reinforced concrete. The shear connectors and web stiffeners increased the beams’ rigidity. In addition, the GFRP beams improved the ductility by 21.6% relative to the reference one. Moreover, the shear connectors, web stiffeners, and both improved the ductility by 185.5%, 119.8%, and 128.4%, respectively, relative to the reference beam.The strains of the pultruded GFRP beams increased almost linearly until failure. The GFRP beams contributed to providing more strength to the encased beams. The contribution of the GFRP beams increased by adding the studs and web stiffeners because the bottom flanges of these beams exhibited additional strains due to increasing the composite interaction with concrete.The peak loads increased with increasing the compressive strength of concrete. For the reference beam without a GFRP beam, the peak load increased by 3.76% and 11.92% for the compressive strength of 53.8 MPa and 65 MPa, respectively. However, the most enhancements in the peak loads were for the encased beam, which were 24.78% and 32.32% for the compressive strengths of 53.8 MPa 65 MPa, respectively, with respect to the compressive strength of 45 MPa.The peak loads and the corresponding mid-span deflections increased as the tensile strength of GFRP increased. The increase in the peak loads ranged between 6% and 18% when the tensile strength was 347.5 MPa, while the improvements ranged between 14% and 27% for the tensile strength of 416 MPa.


At present, a large number of studies have demonstrated that c-Met generally exerts a crucial function of promoting tumor cells proliferation and differentiation in digestive system tumors. c-Met also mediates tumor progression and drug resistance by signaling interactions with other oncogenic molecules and then activating downstream pathways. Therefore, c-Met is a promising target for the treatment of digestive system tumors. Many anti-tumor therapies targeting c-Met  have been developed in treating digestive system tumors. Some drugs have been successfully applied to clinic, but most of them are defective due to their efficacy and complications. In order to promote the clinical application of targeting c-Met drugs in digestive system tumors, it is necessary to further explore the mechanism of c-Met action in digestive system tumors and optimize the anti-tumor treatment of targeting c-Met drugs. Through reading a large number of literatures, the author systematically reviewed the biological functions and molecular mechanisms of c-Met associated with tumor and summarized the current status of targeting c-Met in the treatment of digestive system tumors so as to provide new ideas for the treatment of digestive system tumors. Digestive system tumors (DSTs) mainly include gastric cancer(GC), hepatocellular carcinoma (HCC), pancreatic cancer(PC) and colorectal cancer(CRC), which are general cancers in worldwide . AlthougMET gene is involved not only in the proliferation, differentiation and invasion of various human tumor cells, but also in the resistance of anti-tumor drugs . It is oResearches have demonstrated that c-Met normally mediates downstream signals by combining with its corresponding ligand, hepatocyte growth factor (HGF), to promote the proliferation and differentiation of tumor cells. It was also found that c-Met can also activate downstream pathways through signaling interaction with some carcinogenic molecules in the absence of ligands , 27. Thec-Met is a glycosylated membrane protein consisting of transmembrane β chains (145 kDa) and extracellular α chains (50 kDa). HGF, as a ligand of c-Met, is composed of a 103 kDa soluble heterodimer, which consists of α-chain and β-chain linked together by disulfide bonds . Bindingin vitro and in vivo. According to the above findings, simultaneous targeting of these two targets may be promising in the treatment of tumors. A number of clinical studies have also verified the antitumor activity of targeted EGFR and c-Met combination therapy  receptor is a member of the tyrosine kinase receptor family. The homologous similarity between the extracellular domain and kinase domain and c-Met domain was 25% and 63%, respectively. The activation of RON can lead to the activation of MAPK, PI3K and other signaling pathways. RON ligand is hepatocyte growth factor-like protein (HGFLP) . Accordic-Met is essential for several events including angiogenesis, myoblast migration, bone remodeling, and nerve germination during the processes of embryogenesis . In vertHGF is defined as a secretory factor responsible for enhancing cell motility, invasion and causing cell dispersal . HGF in The association of c-Met activity with tumor growth, invasion, and poor prognosis has been demonstrated . C-Met aIn the past few years, a number of c-Met inhibitors have been developed for therapeutic studies in tumors and have shown significant antitumor activity in preclinical studies of DSTs –73. SomeIn 2020, hepatocellular carcinoma (HCC) was the sixth most common cancer and the third leading cause of cancer deaths in worldwide, with approximately 906,000 new cases and 830,000 deaths . ConventTivantinib, a selective small molecule inhibitor of c-Met, has shown significant antitumor activity in phase I clinical trials for the treatment of HCC. However, hematologic toxicity of tivantinib, mainly with neutropenia, was observed in phase II clinical trials . Santoroin vitro and inhibit HCC metastasis in vivo. MinKe He et al.  is a highly lethal disease with a 5-year survival rate of only 10% . The disin vitro also showed that c-Met inhibitor XL184 could significantly suppress the formation of tumor globules, suggesting that cells with high expression c-Met increased the tumorigenic potential of mice. In NOD SCID mice, the use of c-Met inhibitors slowed tumor growth in pancreatic tumors. In addition, other studies have found that c-Met inhibitors PHA665752 and AMG102 can not only block the HGF/c-Met axis by reducing the phosphorylation level of c-Met, but also weaken the epithelial mesenchymal transformation and chemotherapy resistance , causing more than 1 million new cases and an estimated 769,000 deaths in 2020, ranking respectively fifth and fourth globally in morbidity and mortality, remains an important cancer worldwide . Clinicain vitro and in vivo. Paul R. Gavine et al. , which is associated with irinotecan resistance. Since then, KRC-408, KRC-00715 and Simm530 have been identified as selective inhibitors of c-Met, all of which have been shown in preclinical studies to inhibit the growth of GC cells  is the third most common malignancy in the world and a familiar cause of cancer-related death. It is estimated that there were more than 1.9 million new CRC cases and 935,000 deaths of CRC in the United States in 2020, accounting for about one in 10 cancer cases and deaths . In receCrizotinib, Capmatinib and Tivantinib are also used as selective inhibitors of c-Met in the treatment of CRC. Feng Du et al.  found thin vitro; what’s more, the growth of xenograft tumors was inhibited in vivo  is a demethylated analogue of Cantharidin and has strong anti-tumor activity , 129. StIn recent years, c-Met monoclonal antibody has also been widely used in the treatment of DSTs. The studies mainly include the use of monoclonal antibodies alone, antibodies combination with other drugs and antibody-drug coupling in anti-DSTs  in order to evaluate the efficacy and safety of c-Met CAR-T cells and c-Met/PD-L1 CAR -T cells in the treatment of solid tumors.in vivo studies demonstrate antitumor activity by intratumoral injection of c-Met CAR-T cells. On the one hand, local injection in the tumor is not suitable for the later clinical application. On the other hand, it is not conducive to the killing of peripheral circulation and metastatic tumor cells. Therefore, c-Met-CAR-T cells need gene editing to enhance their proliferative activity and persistence.Nakajima et al.  found thIn vitro and in vivo studies showed that c-Met/PD-L1 CAR-T cells exhibited better antitumor activity against c-Met and PD-L1 positive HCC cells than c-Met CAR T cells or PD-L1 CAR-T cells. These studies also suggest that bi-specific c-Met/PDL1 CAR-T cells are feasible in current T cell engineering techniques. In addition, BING LIU1 et al.  and Baiyin City 2019 Science and technology plan project .Thanks to all the authors who participated in the design and data analysis of this paper, as well as the Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine for providing convenience.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Concrete is a composite material that is commonly used in the construction industry. It will certainly be exposed to fires of varying intensities when used in buildings and industries. The major goal of this article was to look into the influence of mineral additions such as foundry sand and marble dust on the residual characteristics of concrete. To examine the behavior of residual characteristics of concrete after fire exposure, marble dust was substituted for cement and fine sand was substituted for foundry sand in varying amounts ranging from 0% to 20%. It aided in the better disposal of waste material so that it might be used as an addition. The purpose of the experiment was to see how increased temperatures affected residual properties of concrete, including flexural strength, compressive strength, tensile strength, static as well as dynamic elastic modulus, water absorption, mass loss, and ultrasonic pulse velocity. At temperatures of 200 °C, 400 °C, 600 °C, 800 °C, and 1000 °C, the typical fire exposure behavior of concrete was investigated. The effects of two cooling techniques, annealing and quenching, on the residual properties of concrete after exposure to high temperatures were investigated in this study. Replacement of up to 10% of the cement with marble dust and fine sand with foundry sand when concrete is exposed to temperatures up to 400 °C does not influence the behavior of concrete. At temperatures above 400 °C, however, the breakdown of concrete, which includes marble dust and foundry sand, causes a rapid deterioration in the residual properties of concrete, primarily for replacement of more than 10%. The inhabitants of a structure must adhere to certain fire safety standards stated in the building regulations. Several kinds of research on concrete’s behavior under fire have been carried out. The results show that when concrete is subjected to fire at high temperatures, the various properties of concrete reduce or are affected negatively. Some of such properties of concrete include tensile strength, elastic modulus, compressive strength, and many others ,2,3,4. TAs per many incidences of fire in India, the temperature during the fire was observed up to 800 °C [Yuksel et al.  examinedAnother study was carried out by Poon et al.  incorporSiddique and Kaur  researchA study carried out by Kore Sudarshan D. and Vyas  examinedThe main scope of this study is fire safety to protect people’s lives and property from fire accidents. A fire outbreak has become the third major risk to business continuity and operations, as recorded by the India Risk Survey (Indian Risk Survey report) 2018 . In the The main objectives of this study are to investigate the behavior of residual concrete properties such as tensile strength, flexural strength, compressive strength, ultrasonic pulse velocity, static as well as dynamic elastic modulus, and mass loss when exposed to higher temperatures (between 200 °C and 1000 °C). Following the ISO-834 fire curve standards , the conFor the present study, Jaypee Cement’s Ordinary Portland Cement of grade 43 was used. The specific gravity of 3.15 is in line with IS 8112:2013  for this2 with a specific gravity of 2.6. In addition to it, the fine aggregates have been partially replaced with foundry sand with a specific gravity of 2.6 and water absorption of 0.68%. The particle size distribution curve for fine aggregate, foundry sand, coarse aggregate, and marble dust is shown in For the present investigation, cement has partially been replaced with marble dust. The composition of marble dust has been illustrated in For the present investigation the concrete mix was made according to IS 10262:2009  using maThe specimen with the specified ratio of Concrete mix with marble dust and foundry sand was developed. To determine the 28th-day compressive strength of prepared samples in accordance with BIS: 516-1999  150 mm ×The concrete samples were heated in a furnace at a steel plant in Chandigarh as shown in Two methods were employed to cool down the specimens: quenching and annealing. The process of annealing was carried out by holding the testing specimens in the furnace for 24 h even after turning off the furnace when the target temperature was reached. In quenching, the specimen was heated in the furnace until the target temperature was reached and was then put into a water bath. A special trolley was used to lift out the heated specimens from the furnace which also helped in immersing the specimens in the water bath for cooling.A total of 54 specimens were examined  including three specimens at ambient temperature (29 °C) and other specimens tested after high-temperature exposure ranging from 200–1000 °C. The concrete specimens were heated in a furnace used in the steel industry. The heating rate of specimens increased with time and varied from 5 °C/m to 6 °C/m. Some studies have previously investigated a similar heating rate (4.5 °C/m to 8 °C/m) ,39. The 2/m as per BIS: 516-1999 [The 28th-day compressive strength of samples was evaluated by testing cubes with dimensions 150 mm × 150 mm × 150 mm using a compressive testing machine at a loading rate of 13.7 N/mm516-1999 . At the 2/mm. Three specimens were examined at room temperature, while the remaining fifteen were tested after being exposed to high temperatures.Beam specimens with dimensions of 100 mm × 100 mm × 500 mm were cast to determine the flexural strength as per BIS: 516-1999 . The spe2/m to determine the 28th-day tensile strength as per BIS: 516-1999 [Tests were conducted on 150 mm × 300 mm cylinders using a compression testing machine with a loading rate of 13.7 N/mm516-1999 . At the 2/s. The applied load as well as the associated stresses were measured. The elasticity modulus was then determined using the following equation:The elastic modulus was evaluated using an ASTM C469  cylinderHere, The measured Ultrasonic Pulse Velocity was used to compute the dynamic elastic modulus of hardened concrete subjected to elevated temperatures (UPV) as per IS 13311 (Part 1): 1992 . The dynE = dynamic modulus of elasticity (MPa), V = ultrasonic pulse velocity (m/s), ρ = density (kg/m3) and μ = dynamic Poisson’s ratio (0.2 to 0.35).Here 2 on the concrete surface. The depth of penetration of the water was reported after 3 days of testing of specimens by compression testing machine.A water retention test was performed on concrete specimens including foundry sand and marble dust that had been subjected to fire at varying temperatures as per sub-clause 2.1 of DIN 1045:1988 . For thiMass loss of the concrete specimen was obtained through cube samples with dimensions 150 mm × 150 mm × 150 mm after exposure to elevated temperature. The loss in mass of each cube specimen was determined by weight measurement of the cube specimen after exposure to an elevated temperature ranging from 200 °C to 1000 °C.The ultrasonic pulse velocity of the specimens was recorded once they were exposed to high temperatures of 200 °C, 400 °C, 600 °C, 800 °C, and 1000 °C. Cube specimens were subjected to an ultrasonic pulse velocity test in accordance with IS 13311 (Part 2): 1992  even befThe strength of a control mix and concrete containing marble dust and foundry sand in compression when exposed to higher temperatures in the range 200–1000 °C in the case of annealing is shown in (i)The compressive strength of concrete samples tested at ambient temperature (29 °C) increased by 10.7% when 10% of the cement was replaced by marble dust and fine sand was replaced by foundry sand, and decreased by 11% when 20% of the cement was replaced by marble dust and fine sand was replaced by foundry sand, and at elevated temperatures increased by 21.5% in the case of annealing and 16.3% in the case of quenching under up to 400 °C elevated temperature on 10% replacement of cement by marble dust and fine sand replaced by foundry sand, and then decreased 54.8% and 52.5% as the temperature increased from 600 °C to 1000 °C in cases of annealing and quenching. This is related to the creation of tiny fractures in both normal and marble dust and foundry sand concrete owing to the breakdown of C-S-H gel along with the voids and empty water capillaries(ii)The flexural strength of concrete samples tested at elevated temperatures increased by 12.7% with a 5% replacement of marble dust and foundry sand in the case of annealing and 15.6% with a 10% replacement of marble dust and foundry sand in the case of quenching up to 400 °C, and then decreased by 40% and 51.7% with an increase in temperature ranging from 600 °C to 1000 °C elevated temperature in case of annealing and quenching. The rapid drop in flexural strength is attributed to the development of widening fractures around 1000 °C. However, the connection between aggregate and cement pastes is weakened by shrinkage produced by the evaporation of free water and chemically bound water from the cement paste.(iii)The tensile strength of concrete samples tested at elevated temperatures increased by 31.1% in the case of annealing and 16.9% in the case of quenching under up to 400 °C elevated temperature on 10% replacement of cement by marble dust and fine sand replaced by foundry sand, and then decreased by 52.5% and 53.3% in cases of annealing and quenching as the temperature increased from 600 °C to 1000 °C.(iv)The percentage reduction in static modulus was increased with elevated temperature; at 1000 °C the reduction was higher for concrete containing marble dust and foundry sand (77.4% for 5% and 86.9% for 20% replacement) than the control mix (72.7%). Similarly, for dynamic modulus the percentage reduction was increased with elevated temperature, at 1000 °C was higher for concrete containing marble dust and foundry sand (76% for 5% and 94.1% for 20% replacement) than for the control mix (81.5%). The larger decrease can be ascribed to the decomposition of marble dust and foundry sand, which causes cracks and voids in the cement paste matrix, causing the concrete structure to weaken.(v)Water absorption was measured at 13.3% by weight up to 400 °C for 10% replacement, suggesting that pores did not expand significantly as the temperature rose. However, at higher temperatures (1000 °C), it increased by approximately three times, indicating fast degradation in all mixtures.(vi)The mass loss of concrete containing marble dust and foundry sand was similar to the control mix when subjected to a temperature up to 400 °C. In both situations, this is due to water loss from the matrix owing to evaporation. Because of the development of voids in concrete, a higher mass loss of 40.7% was observed for marble dust and foundry sand concrete samples exposed at 600 °C and beyond.(vii)Although all concrete mixes have UPV values of more than 3.2 km/s, as specified by IS 13311 (Part 1): 1992, up to 600 °C, temperature increases porosity in concrete mixes, resulting in lower UPV values.Based on the test results for both concrete mixes (with and without replacement), the following conclusions may be drawn:According to the results of the experiments presented in this study, substituting up to 10% of marble dust and foundry sand had no effect on the residual properties of concrete when subjected to temperatures up to 400 °C. However, at temperatures above 400 °C, the degradation of concrete was observed, resulting in a rapid reduction in the residual properties of concrete, mainly for replacement of more than 10% of the mixture.


Receiver operating characteristic (ROC) curve was used to determine the optimal cut‐off value for GAR. Survival curve and cox regression analysis were applied to assess the prognostic power of GAR. The prognostic accuracy of GAR was compared with other variables by ROC curve. The optimal cut‐off value for GAR was 1.3655. Preoperative high GAR was closely related to tumour number, lymph node invasion and GGT. The survival curve of derivation and validation cohorts showed that patients in the high GAR group had significantly shorter overall survival (OS) and disease‐free survival (DFS) than patients in the low GAR group. Multivariate analysis in the derivation cohort confirmed that GAR was an independent prognostic factor for survival outcomes. Moreover, the ROC curve revealed that GAR had better predictive accuracy than other variables. High GAR predicted poor OS and DFS in ICC patients after hepatectomy. GAR may be a novel, simple and effective prognostic marker for ICC patients.Inflammation has been reported to play an important role in tumour progression and prognosis. In this study, we evaluated the prognostic significance of γ‐glutamyl transpeptidase (GGT) to albumin ratio (GAR) in patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy. We retrospectively analysed 650 ICC patients underwent hepatectomy at three Chinese medical centres between January 2009 and September 2017. Patients were classified into derivation cohort ( In addition, we further compared the predictive power of GAR with other variables.2This study complied with the ethical guidelines of the Declaration of Helsinki.2.1p < 0.05 was considered statistically significant.The optimal cut‐off value of GAR was determined by receiver operating characteristic (ROC) curve. We divided the derivation and validation cohorts into high and low GAR groups based on the optimal cut‐off value. The independent sample T‐test or the KruskaI Wallis test was used to analyse continuous variables. Fisher's exact test or the chi‐square test was used to explore categorical variable. The Kaplan–Meier curve was applied to describe survival data. Cox regression model was used for univariate and multivariate analysis to explore the valuable prognostic factors. The predictive ability of GAR was evaluated by the area under ROC curve. SPSS Software  and GraphPad Prism  were used for data analysis. 33.1p = 0.002), tumour number (p = 0.032), node invasion (p < 0.001), perineural invasion (p = 0.021), GGT (p < 0.001) and OS were observed significantly different in the two groups. No differences were found in other indexes, such as Age, Gender, HBsAg, hepatolithiasis, differentiation, capsular invasion, MVI, cirrhosis, TNM stage and ALB. The clinicopathological information of patients in the validation cohort was shown in Table A total of 509 patients  from West China Hospital were included in the derivation cohort. 141 patients  from the Third Affiliated Hospital of Sun Yat‐sen University and Chongqing University Cancer Hospital were included in validation cohort (Table 3.2p = 0.038), tumour size (p = 0.039), tumour number (<0.001), MVI (p = 0.001), node invasion, (p < 0.001), perineural invasion, (p = 0.005), 8th TNM stage (p = 0.035), ALB (p = 0.009) and GAR (<0.001) were risk factors for adverse OS. However, multivariate analysis showed that tumour number , MVI , node invasion :1.515–2.617, p < 0.001) and GAR  were independent risk factors for poor OS. Similarly, tumour size (p < 0.001), tumour number (p < 0.001), MVI (p < 0.001), node invasion (p < 0.001), 8th TNM stage (p = 0.005) and GAR (p < 0.001) were closely related to poor DFS in univariate analysis. Multivariate analysis suggested that tumour number , MVI  and GAR  were independent risk factors for poor DFS. Detailed results were presented in Table In the derivation cohort, univariate analysis showed that hepatolithiasis  due to insufficient data.In summary, our study suggested that high GAR predicted poor OS and DFS in ICC patients after hepatectomy. GAR may help to stratify ICC patients to identify high‐risk patients for individualized treatment. As an easily detectable blood inflammatory marker, GAR provided additional prognostic information for ICC patients and could be considered as a biomarker in the clinical management of ICC. More high‐quality randomized controlled studies were needed to test our findings and further examine the clinical value of GAR in ICC.The authors have declared no conflict of interest.Hui Li:Data curation ; Formal analysis ; Methodology ; Writing – original draft . Rongqiang Liu: Data curation ; Formal analysis ; Methodology ; Writing – original draft . Jiawang Li: Data curation ; Formal analysis ; Methodology ; Writing – original draft . Jiaxin Jiaxin Li: Investigation ; Supervision ; Validation . Hong Wu: Investigation ; Supervision ; Validation . Genshu Wang: Investigation ; Supervision ; Validation . Dewei Li: Funding acquisition ; Writing – review & editing . Zhenhua Li: Data curation ; Writing – review & editing .Table S1‐S3Click here for additional data file.


In the present paper, the effects of thermal insulation cover curing on the rise in temperature of concrete, and further on the mechanical properties of the concrete are measured experimentally. In the experiments, polyurethane foam boards of 100 mm thickness were used for thermal insulation, and three concrete strength grades of C30, C50 and C80, were used as concrete samples. Conventional standard curing, and two heat curing methods with a constant temperature of 40 °C and 60 °C were used for comparison. The pore structure of the cement paste subject to the different curing procedures, including insulation cover curing, heat curing and standard curing, was experimentally measured using mercury intrusion porosimetry. The test results show that rate of increase in compressive strength compared with standard curing is 22–34%, 16–26%, and 23–67%, respectively, for C30, C50, C80 concrete after being subject to 1 to 3 days thermal insulation cover curing in the initial period after concrete casting. As expected, initial heat curing of concrete will result in a reduction in the long-term strength of the concrete. At 28 days, the strength reduction rate compared with standard curing due to the insulation cover curing is 3.1–5.9%, 0.6–3.0%, 0–3.2%, respectively, for C30, C50, C80 concrete. By contrast, the compressive strength reduction compared with standard curing at 28 days is 8.6–10.5%, 8.6–9.1%, 4.7–5.6%, respectively, for C30, C50, C80 concrete after being subject to a constant heat curing of 40 °C and 60 °C in the initial period after concrete casting. Measurement of the pore structure of the paste subject to different curing procedures initially after casting shows that rising curing temperature leads to coarser pores, especially an increase in capillary pore fraction. Among the four curing methods used in the present study, the effect of insulation cover curing and low temperature (40 °C) heat curing on the capillary pore content is small, while the effect of high temperature (60 °C) heat curing is significant. As a widely used construction material, the production of concrete members or structures is normally divided into cast-in-place and cast-in-plant. In concrete production, curing of concrete is normally necessary to attain the required performance of the concrete, whether the concrete is produced on site or in the plant. In particular, for concrete member cast-in-plant, the purpose of curing of concrete includes speeding up the stripping of forms, increasing strength of the elements and shortening the stay-age in plant . To reacIn concrete, the reaction between Portland cement and water is an exothermic process. If adiabatic conditions between the test sample and environment are satisfied, the temperature inside the concrete sample should gradually increase with hydration age, and finally go into a steady state with a nearly constant temperature. In all other cases, the hydration heat will be lost gradually and the temperature inside the concrete should tend to the temperature of the environment. The amount of cement hydration heat generated in the concrete element depends on the cement amount and/or the concrete volume, water to cement ratio, cement hydration degree and its development with age, and addition of cementitious materials used in the concrete. The temperature rise inside the concrete is dependent on the heat generation and insulation condition of the boundary between concrete and the environment . For exaIn the present paper, cement hydration heat is used as a curing heat resource in concrete production by putting a heat insulation cover on the surface of concrete specimens. The effect of the insulation cover curing initially after concrete casting on the temperature rise of the concrete, and further on compressive strength of the concrete were experimentally studied. Comparative curing methods, including standard curing according to the Chinese standard GB/T 50081-2019  and tradTo investigate the effect of concrete strength or water to binder ratio on temperature rise under insulation conditions, three concrete mixtures with water to binder ratio (W/B) of 0.62, 0.43 and 0.30 to form three kinds of concretes with compressive strength at 28 days around 30 MPa, 50 MPa and 80 MPa, which are labeled as C30, C50 and C80, respectively, were used in the experiments. All mixtures were made with the same Portland cement. For C30 and C50 concrete, 20% fly ash of the total binder weight was used. For C80 concrete, 10% silica fume of the total binder weight was used. Oxide compositions of the cement, fly ash and silica fume, as well as the mineral compounds of the cement, are listed in Natural sand and crushed limestone with a maximum particle size of 5 mm and 20 mm, respectively, were used as normal fine and coarse aggregates. The concrete mixture proportions used in the present work are listed in 3 cube specimens was used to cast concrete. The processes of the present heat insulation curing are presented in In the tests, the mold used to store concrete specimens was made of polyurethane board with thickness of 100 mm. Thermal conductivity of the polyurethane board is 0.030175 W/(m K). A plastic mold that can cast three 100 mmTo make a comparative study with conventional heat curing of concrete, some concrete specimens were made and cured according to the following schedule. After casting, vibrating and finishing, the mold was stored in a room for 1 day. Then the specimen was moved into a heater to raise the temperature to 40 °C and 60 °C, respectively, for heat curing of 1, 2, 3 and 6 days. After that, specimens were demolded and moved into the standard curing room for another certain number of days until the total age is 28 days before compressive strength testing. In the present study, specimens subject to 40 °C and 60 °C heat curing are labeled as LH and HH, respectively, for convenience of analyzing. In addition, specimens under standard curing   were alsTo investigate the effect of curing temperature in the initial period after concrete casting on pore structure of the cement paste, cement paste of each concrete (without sand and stone) was prepared and cured as well as the concrete used. The pore structures of the cement paste were measured by mercury intrusion porosimetry (MIP). The test pressure range was 0.0036–413.370 MPa, and the minimum pore diameter was 3.2 nm. At specific age of the curing, some particles with a diameter of 10–15 mm were obtained from the paste sample of the concrete. The samples were placed in absolute ethanol for 24 h and then in an oven at 40 °C to a constant weight to stop hydration.Now, it should be interesting to look at the effect of the temperature rise of concrete under insulation condition on the compressive strength of the concrete. From For C50 concrete b, a simiFor C80 concrete b, comparFrom the test results showed in Mercury intrusion porosimetry is a widely used technique to evaluate the pore structures of cementitious materials, including pore size distribution and pore volume fraction. From Under insulation curing, see From the pore distribution result of the paste subject to a constant temperature of 40 °C (LH) in the initial few days after casting c, first,As the curing temperature rises to 60 °C (HH), see A similar observation was presented as well in a previous studies; for example, Bahafid  found anFor pastes of C50 concrete  and C80 From the pore composition data listed in A quite similar variation trend in the pore composition of the paste of C50 concrete at 28 days under the four curing procedures, see By comparing the results displayed in (1)The temperature of concrete is obviously increased after putting a thermal insulation cover on the surface of the concrete after casting. The temperature rise can not only be observed in high strength concrete (C80), but also in low strength concrete (C30). As 100 mm thick polyurethane foam boards are used and the concrete is cast at room temperature of about 25 °C, t the temperature rise is 10.5 °C, 15.2 °C and 20.3 °C, respectively, for C30, C50 and C80 concrete. The higher the concrete strength, the higher the temperature rise.(2)For C30 concrete, compared with standard curing, the rate of increase in compressive strength due to insulation cover curing is 34%, 22% and 24% at 1, 2 and 3 days, respectively. As expected, initial heat curing of concrete will result in a reduction in long-term strength of the concrete. At 28 days, the strength reduction rate due to the insulation cover curing compared with standard curing is 4.2%, 5.9% and 3.1%, respectively, for insulation curing of 1, 2 and 3 days at the beginning after casting. With respect to the concrete subject to heat curing with a constant temperature of 40 °C and 60 °C initially at the beginning 3 days after casting, the strength reduction rate at 28 days is 8.9% and 10.5%, respectively.(3)For C50 concrete, compared with standard curing, the rate of increase in compressive strength due to insulation cover curing is 24%, 26% and 16%, respectively, after insulation curing of 1, 2, 3 days. At 28 days, the strength reduction rate due to the insulation cover curing compared with standard curing is 0.6%, 3.0% and 2.2%, respectively, for insulation curing of 1, 2 and 3 days at the beginning after casting. With respect to the concrete subject to heat curing with a constant temperature of 40 °C and 60 °C initially at the beginning 3 days after casting, the strength reduction rate at 28 days is 8.6% and 9.1%, respectively.(4)For C80 concrete, compared with standard curing, the rate of increase in compressive strength due to insulation cover curing is 67%, 33% and 23%, respectively, after insulation curing of 1, 2, 3 days. At 28 days, the strength reduction rate due to the insulation cover curing compared with standard curing is −0.8% (increasing), 2.5% and 3.2%, respectively, for insulation curing of 1, 2 and 3 days at the beginning after casting. With respect to the concrete subject to heat curing with a constant temperature of 40 °C and 60 °C initially at the beginning 3 days after casting, the strength reduction rate at 28 days is 4.7% and 5.6%, respectively.(5)Compared with the standard curing, insulation cover curing (within 1–3 days) may also lead to coarsening of the pore structure of the cement paste, which is displayed as an increase in capillary pore fraction. Among the four curing methods used in the present study, the effect of insulation cover curing and low temperature (40 °C) heat curing on the capillary pore content is small compared with that of standard curing, while the effect of high temperature (60 °C) heat curing is significant. This is observed not only inn the measurement of the paste of C30 concrete, but also in that of C50 and C80 concrete.In the present paper, an experimental study of the effects of thermal insulation cover on the temperature rise of concrete, and further on the development of mechanical properties of the concrete is performed. One hundred millimeter thick polyurethane foam boards were used for thermal insulation, and three concrete strength grades of C30, C50 and C80, were used as concrete samples. Conventional standard curing, and two heat curing methods with a constant temperature of 40 °C and 60 °C were used for comparison. Pore structures of the cement paste subject to the different curing procedures, including insulation cover curing, heat curing and standard curing, were experimentally measured using mercury intrusion porosimetry. The conclusions obtained in the present study are summarized as following: