Using point-prevalence methodology and the World Health Organization (WHO) Access, Watch, and Reserve Classification, we measured antibiotic use in 5 hospitals in Okinawa, Japan, on October 1, 2020. Overall, 29% of patients were prescribed an antibiotic on the survey date and the 3 most used antibiotics in the “Watch” category were cefazolin, ampicillin-sulbactam, and ampicillin. Although the prevalence of antibiotic stewardship programs (ASPs) has increased in Japan, published data on the uptake of ASPs in the country are limited. To better inform nationwide efforts on antibiotic use, we sought to understand inpatient antibiotic use in the prefecture of Okinawa, Japan, where there has been little published in the realm of antimicrobial stewardship. Point-prevalence studies of antibiotic use have been used internationally to provide regional data on antibiotic use. The World Health Organization (WHO) Access, Watch and Reserve (AWaRe) Classification is a tool developed in 2019 that can compare antibiotic use from different geographic regions. The AWaRe criteria were intended to improve international antibiotic monitoring and use, with an emphasis on potential for antimicrobial resistance. “Access” antibiotics are common frontline antibiotics, “Watch” antibiotics are high-priority antibiotics with toxicity or resistance concerns, and “Reserve” antibiotics are last-line treatments for multidrug-resistant infections. We hypothesized that Access and Watch antibiotics would comprise most antibiotics used in this group of hospitals.Recently, a nationwide push in Japan has spurred action against antimicrobial resistance, including establishment of a national action plan.We evaluated the proportion of total eligible hospitalized patients who received antibiotics on the assessment date. We also categorized antibiotics according to indication, drug class, and AWaRe classification.A point-prevalence study was conducted in 5 hospitals in Okinawa, Japan, on October 1, 2020. These hospitals are community hospitals, with bed sizes ranging from 308 to 559 beds. Each hospital has 1 physician antimicrobial stewardship champion, and 3 of these hospitals have an ID-trained physician as the antimicrobial stewardship champion. All 5 hospitals also had a pharmacist and microbiologist on the antimicrobial stewardship team. All antimicrobial stewardship physician champions had supported, dedicated effort from their hospital to conduct antimicrobial stewardship. All inpatients who were hospitalized on October 1, 2020, the day of data collection, were included. A site physician champion at each site conducted chart reviews of all inpatients receiving intravenous antibiotics. A pilot point-prevalence study was conducted by the lead Japanese author (N.S.) at a single hospital to help optimize the data collection sheet and process. Type of antibiotic, reason for use, duration, and microbiologic data were collected. Information on whether the antibiotic was being used empirically or directed at a specific pathogen was also collected.Descriptive statistics were used to estimate the point prevalence of antibiotic use and to derive the distributions of AWaRe classifications and drug class. All statistical analyses were conducted using Stata MP version 14.1 software .Across the 5 hospitals, 1,728 unique patients were included. On the assessment date, 504 (29%) received at least 1 antibiotic. In total, 559 antibiotics were used for these 504 patients. Of those patients prescribed an antibiotic, 451 (89.5%) received 1 antibiotic, 51 (10.1%) received 2 antibiotics, and 2 (0.4%) received 3 antibiotics. Overall, 123 antibiotics (22.0%) prescribed across 114 patients were for prophylaxis and 436 antibiotics (78.0%) prescribed across 390 patients were for treatment. Of the 390 patients who received antibiotics, 385 (98.7%) had a documented infection source. The most common treatment indications for antibiotic use were pneumonia , urinary tract infection , and intra-abdominal infection .Overall, 241 (43.1%) of all 559 antibiotics were categorized as Access drugs, 304 (54.4%) were Watch drugs, and 12 (2.1%) were Reserve drugs. Only 2 (0.4%) of the antibiotics prescribed were in the “Not Recommended” category  and ampicillin-sulbactam  were the most used antibiotics in the Access category. Cefmetazole  and ceftriaxone  were the most used antibiotics in the Watch category. The antibiotics most used in the Reserve category were aztreonam  and daptomycin .The classification of directed versus empiric therapy was available for 488 (87.3%) of the antibiotics prescribed. When comparing directed therapy to empiric therapy, categorizations in the AWaRe categories were similar to overall findings. Among agents used for directed therapy, 60 (38.2%) were in the Access category, 89 (56.7%) were in the Watch category, and 8 (5.1%) were in the Reserve category. In the empiric therapy category, 134 (40.2%) were in the Access category, 193 (58%) were in the Watch category, and 4 (1.2%) were in the Reserve category. Although national and regional information is scarce regarding the composition of stewardship programs, study hospitals all had physician stewardship champions, often infectious diseases-trained, with supported effort for stewardship activity. In addition, several programs had pharmacy and microbiology support. These characteristics might not be common in Japan and are very uncommon internationally.In conclusion, 29% of inpatients in these 5 Okinawan hospitals were prescribed an antibiotic on the survey date. Regional data on antibiotic use varies, but this number is lower than has been reported in many international studies; however, it is similar to previous published work from Japan. Due to multifaceted issues involving industrial complexities and supply chain fragility, the shortage took 10–11 months to resolve. Drug shortages can critically affect a prescriber’s choice of antibiotic and have been shown to influence appropriateness of antibiotic use in Japan and supply of other antibiotics.In the Access category, the 3 most used antibiotics were cefazolin, ampicillin-sulbactam and ampicillin. In the Watch category, the 3 most used antibiotics were all cephalosporins . In the Reserve category, the most used antibiotic was aztreonam. Japanese Respiratory Society Guidelines for management of pneumonia recommend ampicillin-sulbactam and ceftriaxone and cefotaxime for nonsevere healthcare-associated pneumonia treatment and ampicillin-sulbactam and ceftriaxone as first-line therapy for admitted ward patients for nonsevere community-acquired pneumonia. Given that the most common indication for antibiotics in our study was pneumonia, concordance with national guidelines provides some insight into antibiotic use in this study. Moreover, 22% of all antibiotics used were also for prophylaxis, and this could explain some of the cefazolin use, the most used Access antibiotic in our study. A previous national shortage of cefazolin in Japan in 2019 led to a significant increase in third-generation cephalosporins, especially ceftriaxone.The strengths of this work are that a multicenter point-prevalence survey of antibiotic use has not been done in this region of Japan and could inform future work in antibiotic stewardship. This study also had several limitations. Point-prevalence surveys are restricted to a single point in time, so variation of trends in antimicrobial use or seasonality may not be adequately represented. In addition, appropriateness of antimicrobial agents was not assessed. Given that we studied only 5 hospitals, generalizability to other institutions is limited. Additionally, patient-level data were not collected. Focusing on antimicrobial stewardship strategies  that consider risk of antimicrobial resistance could be effective and beneficial. The impacts of such strategies could be assessed using repeated point-prevalence studies and the WHO AWaRe classification. Further work to understand how antibiotics are selected at Japanese hospitals would support the idea that using the AWaRe framework when considering institutional or national antimicrobial stewardship guidelines could affect the choice of antibiotic.The most used antibiotics in this study fall under the WHO AWaRe Watch classification. Antibiotics in this classification may be more likely to cause resistance compared to Access antibiotics. Recent international work has shown that there is significant variability in how different countries use antibiotics when compared to using the AWaRe classificiation.


The civil research community has been attracted to self-healing bacterial-based concrete as a potential solution in the economy 4.0 era. This concept provides more sustainable material with a longer lifetime due to the reduction of crack appearance and the need for anthropogenic impact. Regardless of the achievements in this field, the gap in the understanding of the importance of the bacterial role in self-healing concrete remains. Therefore, understanding the bacterial life cycle in the self-healing effect of cement-based materials and selecting the most important relationship between bacterial contribution, self-healing effect, and material characteristics through the process of microbiologically  induced carbonate precipitation is just the initial phase for potential applications in real environmental conditions. The concept of this study offers the possibility to recognize the importance of the bacterial life cycle in terms of application in extreme conditions of cement-based materials and maintaining bacterial roles during the self-healing effect. The concept of “smart concrete” is based on innovations such as translucent, 3D printed, or lightweight concrete, but also self-healing or self-repairing concrete . As the material ,6,7,8,9.material . The impThe understanding of the relationship between bacterial contribution and the self-healing effect of cement-based materials is presented for the first time from different aspects, including the cruciality of the bacterial activity in the self-healing effect in bacteria-based concrete , mandato3 crystal is inevitable [3 precipitation can occur in environments rich in calcium ions (Ca2+), during a metabolic activity that provides carbonate ions (CO32−) and enables system supersaturation. Some ubiquitous bacteria with BICP potential have the ability to biocalcify in a wide range of environmental conditions. This phenomenon has been used as a sustainable engineered alternative to conventional techniques in consolidation of soil, sand, stone, and cement, in the improvement of soil characteristics, and in remediation of pollutants in soil, water, and wastewater [3 formation, the SH effect of concrete can be accelerated or bio-stimulated using bacteria whose presence and activity may affect crack repairing.The SH effect of bacteria-based concrete can be explained as an effect of autogenously repairing the capacity of material and bio-stimulation of this process by bacterial cells, without any external analysis or anthropogenic intervention . Namely,evitable . This prstewater ,11,12. C3 formation. BICP is consequently a result of metabolic activity, CaCO3 nucleation, and crystal formation around individual bacterial cells. Besides bacterial contribution to changes in ion concentration and pH value, active bacterial cells have the potential to be efficient nucleation centres during CaCO3 formation and repairing cracks. A high concentration of bacterial cells in cracks will also contribute to a higher degree of nucleation and rate of repairing [The essential step that enables the SH effect of bacteria-based concrete is the bacterial production of carbonate ions which are transferred from cell to environment. This step also immediately provides an increase in system alkalinity . Howeverepairing . Theoretepairing . As showepairing . In theiepairing  reported2+ and CO32+ ions in the bacteria microenvironment, with the formation and maturation of CaCO3 crystalline on an electronegative cell surface. This would confirm the previously stated fact that bacterial cells are attributed to the BICP effect as nucleation centres. In summary, bacteria refer to inevitable changes in the system, increasing the reactivity of the resulting metabolite to Ca2+ ions, as well as accumulation of all other ions on a cell surface [The result of the SH effect in bacteria-based concrete is a chemical reaction between Ca surface .Complete characterization ;Methods for reproduction and application of the bacterium, which are in accordance with biosafety laws ;Defining stability, activity, packaging, and storage of a biological agent in compliance with legal regulations;Comprehensive assessment of unpredictable environmental  risks for release of  bacterium into the environment .Due to the fact that BICP is widely used in various engineering techniques, the selected bacterial culture, in addition to meeting preconditions of an efficient BICP process, must be safe for use in all environments. Vidaković et al.  emphasiz3 precipitation is a lateral effect of metabolic activities such as ureolysis, denitrification, ammonification, sulphate reduction, methane oxidation, i.e., in all effective metabolic reactions in which extracellular release of carbonate ions occurs and causes pH changes [2, especially in marine sediments [CaCO changes . Figure ediments .2S and releasing bicarbonate and carbonate ions. Among anaerobic processes, denitrification, which involves nitrate reduction to nitrogen, is the most efficient metabolic activity for BICP. Adopting nitrates, denitrifying bacteria increase the pH value due to the utilization of hydrogen ions and creation of carbonates, which results in supersaturation [Furthermore, abiotic dissolution of gypsum will provide an environment rich in sulphates and calcium ions, with sulphate-reducing anaerobic bacteria efficiently generating Hturation . The by-turation . Additio3 precipitation since they produce ammonium and carbonate ions quickly, alkalizing a medium and enabling rapid precipitation in concrete [3 precipitation effectiveness, and morphology and phases of crystals, can be a basis for selection of bacterium as an effective agent in BICP [In view of simpler application in engineering processes, aerobic metabolic processes, such as amino acid ammonification and ureolysis, are far more desirable. They not only represent a simpler process, but also give a far greater chance to study. Ammonification involves amino acids decomposition into carbonate and bicarbonate ions. Subsequent ammonia hydrolysis accumulates hydroxyl ions which cause system supersaturation . Ureolysconcrete ,24. When in BICP .Bacillus [Sporosarcina [B. lentus, B. subtilis, B. megaterium, and B. thuringiensis stand out, as well as S. pasteurii, S. globispora, S. ginsengisoli, and S. koreensis. In addition, strains of Lysinibacillus genus have often been isolated [Bacillus species stand out, but Pseudomonas, Salinivibrio, Halomonas [Paenibacillus [Acinetobacter, and Pseudomonas isolates [Bacillus strains from sedimentary sludge. closely related to aquatic systems is isolation from sand, where the presence of representatives of Bacillus, Paenibacillus, and Sporosarcina have been confirmed [A review of the scientific literature shows that interest in isolating natural strains of bacteria with BICP potential in the SH effect of cement-based materials has expanded in the last ten years. On the other hand, an identical scheme of isolation and selection has rarely been followed. Random isolation schemes vary from the ultimate goal of selection, and differ both in the initial steps of sample processing, and further manipulation and application. Isolation sites for bacteria with BICP potential are closely related to ecosystems in which a special contribution of these bacteria is expected. Namely, the largest number of bacterial strains with BICP potential was isolated from alkaline and calcifying soils. It is noticeable that isolates belong to the genera Bacillus ,27,28 anosarcina ,27,29. Aisolated ,31,32. Aalomonas , Paenibabacillus , Acinetoisolates  have alsisolates  isolatedonfirmed ,38.Bacillus species are predominantly present in samples of cement, mortar, limestone, and concrete, but are also isolates from surfaces of historical monuments, historical limestone, cement substrate, and painted mural layers. For application in cement-based materials, reference strains are often found, which is either a working microorganism or a relevant strain for comparing the obtained results ;Level of SH effect ;Characteristics of concrete .Further, it is noticeable that scientific groups related to the creation of bacteria-based concrete have used different bacterium, but also different initial concentrations of cells, often without optimization of this parameter during primary laboratory testing. Although the crack-repairing effect has been established in all selected research articles, it is difficult to compare results among authors due to different experimental setups and used methodologies. Different experimental setups are a consequence of the absence of universal standard methods with good practical settings for the evaluation of SH bacteria-based concrete performances. Bacterial contribution to the SH effect of a concrete matrix is based only on a comparison of differences between control and bacteria-treated samples, while the monitoring of bacteria role, activity, or viability was not defined in almost all mentioned papers. It can be summarized that many investigations related to bacteria-based concrete lack microbiological and biotechnological points of view. As a multidisciplinary approach in the field of a new generation of concrete is required, this can be an appropriate critical point for further optimization of bacteria-based SH concrete. Consequently, reducing the large costs of SH concrete implementation can be strongly associated with optimization of the number of bacterial cells, the amount of essential nutrients, determination of bacterial behavior and contribution to the SH effect, etc.3 nucleation centres. The connection between the physical contribution of cells and the SH effect can be based on:Cell geometric compatibility  and motility;Cell−surface electronegativity and hydrophobicity ;Cell membrane permeability (in a function of extracellular carbonate production rate);Biofilm production (possibility and rate of adhesion on inorganic surfaces) ;2 and between 0.3 and 1.64 µm3, respectively [3 precipitation.The cell size can be a crucial parameter for bacterial activity in view of variable concrete porosity during dry/wet cycles in material . Figure ectively . ConsideEach cell can additionally contribute to the SH effect through physical predisposition. In particular, this role of bacterial cells in the SH effect is strongly associated with the potential of active cells to be CaCO3 nucleation because of its cell electronegativity and hydrophobicity. These characteristics of the cell surface originate from the considerable number of chemical bonds present on cell walls [3 crystals [3 crystal accumulation around electronegative cells , resulting in cell adhesion and biofilm formation during bacterial activity. Hoffman et al. [There are two assumptions about what happens in this situation: spore formation (unfavorable conditions are achieved) or cell death (complete stopping of viability). Neither of these two has been proven, but both can be a reason for the absence of a long-term SH effect when the initial number of cells in concrete is low. Therefore, it is important to initially provide a high number of active cells in a concrete matrix . For exan et al.  have sug3 deposits, and it is necessary to degrade EPS to begin the SH effect [H effect .The bacteria-based SH effect is often influenced by variable environmental conditions in cement-based materials. After choosing a metabolic pathway that will mediate the process in terms of efficient extracellular production of carbonate ions, as well as investigation of all potential impacts of bacteria during the SH effect, the potential for bacterial survival in adverse environmental conditions is also very important .3 precipitation can be a pH decrease [3 precipitation, with rapid and abrupt changes towards a highly alkaline matrix at the very beginning of the SH effect. This would mean that alkalotolerant or alkalophilic bacteria are more preferred in the SH effect. Alkalophilic bacteria have optimum growth at pH values around 10, showing satisfactory BICP potential in the SH effect [Concrete represents an alkaline environment, but is very changeable during its lifetime. Namely, the pH value of ordinary Portland cement concrete varies between 12.5 and 13. Such a high value can be decreased over time by different deterioration mechanisms such as chloride ingress, carbonation, acid attack, or the carbonation process. These formations can reduce the pH value of concrete to values less than 9 . The metdecrease . Gat et decrease  proved tH effect ,95.Bacillus strains [Concrete represents a matrix rich in calcium, but not all calcium is available for the SH effect in materials. Namely, a very low concentration of calcium ions is present in extracted pore solution compared with calcium ions in the alkali−silica reaction in concrete. One of the inevitable phenomena in cement-based materials is calcium leaching, which represents a degradation mechanism through a progressive dissolution of hydrates and migration of calcium sources, especially to pores . Calcium strains . By fixi strains . Althoug strains . However strains . In the  strains . However strains , suggest+, Mg2+, K+, Cl−, Br− does not affect bacterial activity, whereas the presence of Mn2+ may cause a decrease in bacterial activity and increase the sporulation effect. Bacterial activity can be improved, but is not completely dependent on the presence of Li+, Zn+, and Ba+ ions [2 has a well-known killing effect on bacteria cells, and its presence in a material can have a biocide effect on numerous bacteria [Although 80% of the composition of concrete is normally aggregate and has a large mineral composition that is unreactive, some of the components in (non)hydrated concrete can have a stimulative or inhibitive effect on bacterial activity. The influence of different ions in concrete during the SH effect can be two-fold. Namely, the chemical composition of concrete is variable and depends on the raw materials, but usually consists of calcium silicates, aluminates, and ferrites, in combination with calcium, silicon, aluminium, magnesium, manganese, titanium, sodium, potassium, sulphur, and iron, in forms which react with water . From a Ba+ ions . In addibacteria . On the bacteria . In summ3 precipitation and the self-healing effect [3 precipitation in a short period. If the main nutrient accumulates in the system of nutrients are not available for bacteria, the metabolic activity can be inhibited, but also if there is a deficiency of calcium ions, supersaturation will be absent [Concrete represents an extremely harsh environment for bacteria due to its low nutrient availability . Therefog effect . For exag effect  proved te absent . Most ofe absent , and thue absent , perillae absent , and wase absent , etc.Bacillus genera [Some additional influences of the cement-based material environment on bacterial activity and the SH effect can be summarized through the presence of chlorides and sulfates, but also the carbonation process in the concrete matrix. Cracks in marine environments appear in concrete due to penetration of chloride and sulfate ions. The chloride concentration in the cracks is similar to that on the outer concrete surface exposed to the chloride environment. The repercussion of this process can be the promoted corrosion of rebars and the destructive process of the infrastructure unit . Therefos genera ,115. Thes genera , but thes genera . Some evs genera , indicatPermeability (due to the water availability);Porosity (due to space limitation);Crack size ;Aging rate.Concrete is a specific, multicomponent and polydisperse matrix that is obtained by homogenizing a mixture of aggregates, cement, water, and additives. The characteristics of concrete are generally a function of an extremely large number of different influencing factors, such as characteristics of the applied components, qualitative ratios of the components in the mass of concrete, many technological factors, etc. . HoweverThese characteristics can be explained through the concept of limiting factors for bacterial activity in some media. Namely, when a bacterium is under stable conditions, the essential factor existing in quantities closest to a critical minimum needed for that bacterium will tend to be a limiting factor for growth and activity . This coConcrete contains numerous pores of broadly varying sizes, from several nanometres to several millimetres. Variations in space are a consequence of the intrinsic heterogeneity of pore sizes in concrete . As a me3 amount. The same number of bacteria in a narrower crack could be sufficient for the full SH effect. This is the critical point where the optimization of the number of bacterial cells and CaCO3 productivity are necessary. As shown in Cracking in concrete is very usual and affects the lifetime of a structure, but also enables a higher influence of environmental actions. Cracks provide an additional source of water and waterborne ions, which can have an essential role in the SH effect through the activation of bacterial cells in cracks. Besides water, cracks can be filled with different fluid phases, for example, air, salt, acid solution, etc. . Crack sThe aging of concrete is an inevitable process and usually begins to appear in individual elements of the structures, leading to nonuniform behavior and cracks appearing . In viewThe use of self-healing bacteria-based concrete certainly represents an innovative and cutting-edge issue for the sustainable cement-based materials industry. Considering that many research designs of this concrete have disregarded the microbiological view of the SH effect of bacteria-based concrete, a major recommendation is that one of the laboratory steps include an assessment of the microbiological aspect. The first step is essential and has to include a selection of best-performing bacteria for the SH of cement-based materials. The selection of bacteria will depend on the available source isolates from nature, purchases from a national collection of microorganisms, genetic modification, etc. An ideal bacterium for the SH effect of cement-based materials has an efficient metabolic activity that leads to the production of carbonate, tolerance to the alkalinity of concrete matrix, high survival, and rapid activation of cells in concrete, but also has a physical predisposition for the effective SH effect. Bacterial contribution in the crack filling, decreasing the possibility for the formation of wider cracks, and reducing the permeability and porosity, leads to an increase in stability and a longer lifetime of the concrete. Therefore, the optimization of using bacteria in concrete is necessary for reducing additional costs and creating more economic materials.Perhaps the biggest potential problem during the creation of SH concrete is obtaining homogeneous treatment and monitoring processes in real conditions. Successful implementation requires upgrading the system established at the laboratory level. Unlike laboratory conditions where most parameters can be controlled, it is necessary to monitor multiple variables in in situ treatment, both during the application of SH concrete and after/during the cracking process. These variables have to include the monitoring of microbiological activity. The possibility of the complete stop of the self-healing effect over time can be expected due to the loss of a bacterial role in crack repairing. The reason for this is the dependence of bacterial activity on a large number of environmental factors . A design in which it is possible to monitor and influence microbiological activity in a large system is a difficult task, not only because of geological accessibility, but also because of the heterogeneous distribution within the system, as well as the lack of standardized monitoring methods.


Background: The European Centre for Disease Prevention and Control describes the community pharmacist as the gatekeeper to the quality of antibiotic use. The pharmacist has the responsibility to guard safe and effective antibiotic use; however, little is known about how this is implemented in practice. Aims: To assess the feasibility of a method to audit the quality of antibiotic dispensing in community pharmacy practice and to explore antibiotic dispensing practices in Greece, Lithuania, Poland, and Spain. Methods: The Audit Project Odense methodology to audit antibiotic dispensing practice was adapted for use in community pharmacy practice. Community pharmacists registered antibiotic dispensing on a specifically developed registration chart and were asked to provide feedback on the registration method. Results: Altogether, twenty pharmacists were recruited in four countries. They registered a total of 409 dispenses of oral antibiotics. Generally, pharmacists were positive about the feasibility of implementing the registration chart in practice. The frequency of checking for allergies, contraindications and interactions differed largely between the four countries. Pharmacists provided little advice to patients. The pharmacists rarely contacted prescribers. Conclusion: This tool seems to make it possible to get a useful picture of antibiotic dispensing patterns in community pharmacies. Dispensing practice does not seem to correspond with EU guidelines according to these preliminary results. Community pharmacists are in a unique position to positively impact antibiotic use and reduce antimicrobial resistance ,2. The ECurrently, little is known about dispensing practices for antibiotics in community pharmacies and to what extent pharmacists fulfil the role as gatekeeper to antibiotic use in daily practice. In their systematic review on documenting dispensing practices , CerqueiTo assess the feasibility of registering antibiotic dispensing using the registration chart in the community pharmacy setting;To collect feedback from community pharmacists on the implementation of the APO method;To describe antibiotic dispensing practices in four European countries.One way to document healthcare practice is through self-registry by healthcare professionals. In general practice for example, the Audit Project Odense (APO) methodology was developed for quality improvement  and is un = 19) returned the questionnaire. The participation of pharmacy staff differed between the pharmacies. In 10 pharmacies, both pharmacists and pharmacist technicians participated in the pilot study. In four pharmacies, only one staff member participated; this could either be a pharmacist or a pharmacist technician. In three pharmacies, more than one staff member participated, although not the entire staff. In the remaining two pharmacies, only pharmacists participated. All pharmacies reported that registration of patients took less than one minute per dispensed antibiotic or between one and two minutes, except for one pharmacy that needed two to three minutes per registration. In all countries, pharmacy staff managed to register all patients with a prescription for an oral antibiotic or only missed a couple of dispenses during the study period. Reasons for not registering included high workload or forgetting. Most of the pharmacists found the registration chart, instruction form, and list of antibiotics clear and easy to use.In total, 20 pharmacies were recruited to participate in the pilot study, five in each of the four countries. One pharmacy in Greece dropped out of the study due to intense workload. All participants . The most frequently dispensed antibiotics were amoxicillin and amoxicillin/clavulanic acid, followed by macrolides or clindamycin and cephalosporines, although frequencies differed per country. In total, 77% of the dispenses were registered by pharmacists, 22% by other pharmacy staff, in 2% this was not reported. Nearly half of the dispensed antibiotics were prescribed for acute respiratory tract infections. The indication for the prescribed antibiotic was unknown to the pharmacy staff for 11% of the total number of dispenses. There was contact between the pharmacist and the prescriber for 14 (3%) of the dispenses, which led to changes to the prescription in nine (2%) cases. In Poland, there was no contact with prescribers at all, and in 12% of the dispenses this information was not reported .The frequency of checking for drug-drug interactions, contraindications, and allergies during the dispensing process differed largely between the countries. In total, in 49% of the dispenses none of the three safety checks were performed. However, in 70% of the cases in Lithuania none of the checks were performed, whereas in Greece no checks were performed in 18% of the cases. When looking at the individual safety checks, checking for contraindications was performed the least often (21%) and checking for allergies most often (36%). Only in Spain and Greece were there dispenses for which all three safety checks were performed, in 24% and 22% of registrations, respectively .Overall, in 66% of the dispenses, the pharmacy staff discussed treatment duration with patients. Other general advice that is deemed appropriate to give during dispensing of all antibiotics was given less frequently: information about side effects (21%), informing about risk of AMR (18%), seeking medical help if symptoms worsen (19%), and bringing back leftovers (4%). In 13% of the dispenses, the pharmacist did not provide the patient with any advice .Treatment duration was unknown for 7% of the dispensed antibiotics. In 70% of the dispenses, the pharmacy staff deemed the prescription appropriate for the specific situation on a clinical basis , in 3% the pharmacy staff did not agree, and in 26% the staff reported to not have sufficient information to make this judgement. This information was missing in 1%. In 31 cases, pharmacists judged a prescription as appropriate despite not knowing the indication and/or treatment duration, which was considered as inappropriate agreement . Four anMost feedback was about the domain of advice on the registration chart and instruction form. For example, for “discuss treatment duration” one Spanish pharmacist commented: ‘does this mean to explain and reinforce the importance of not stopping treatment until finishing it, or only explain the duration of treatment?’. Moreover, pharmacists reported they found some advice unnecessary to give while missing other information, although this feedback differed per pharmacy, within and between the countries. Several other topics were suggested to be added to the registration chart, including veterinarian use, probiotics, prophylaxis, injectable antibiotics, metronidazole, treatment preparation, and storage.Similarly, suggestions were provided for changes to other domains of the registration chart. Pharmacists in Greece described that it was difficult and uncommon to contact prescribers. In Lithuania, pharmacists reported that most of the time it was almost impossible to contact prescribers for clarification or changes to the prescription. Interestingly, the registrations during the pilot study show that in Greece there was contact with the prescriber in 5.5% of the cases and in Lithuania in 8.2% of the cases, whereas in Poland this was 0%. Additionally, some Lithuanian pharmacists mentioned that safety checks for contraindications and interactions were not performed in their pharmacies and patients were usually not informed about side effects from drug use. This aligns with the registered dispenses, as contraindications were only checked in 1.0% of cases, interactions, and allergies in 9.7% and 15.5%, respectively, and information about side effects was provided in 2.9% of the dispenses. Polish pharmacists reported that it was often not possible to give an assessment of the treatment as they did not know the indication for prescriptions and do not have access to patients’ medical history. Despite this, Polish pharmacists only reported an unknown location of infection in 10.8% of the dispenses. Finally, in Spain, the difference between pharmacists and other pharmacy staff was reported by multiple pharmacies. As only pharmacists are allowed to evaluate interactions and contraindications for new patients, it was suggested to exclude technicians from the study. Indeed, the registrations show a difference between pharmacists and non-pharmacists in Spain, as they checked for interactions in 44.0% and 10.5% of the dispenses, respectively, and comparably for contraindications (46.6% vs. 0%) and allergies (62.1% vs. 7.0%).Based on the written feedback that was provided by the participating pharmacy staff and the results obtained during registering the dispensing practice, several changes have been made to the registration chart . FirstlyAntibiotic dispensing in community pharmacies is complex and varying practices within countries and across borders exist. This study shows that a simple tool to measure the antibiotic dispensing process can be implemented in community pharmacy practice. When it comes to antibiotic dispensing in community pharmacies, practice does not seem to match EU guidelines. On the one hand, this could mean that proper guidelines should be based on a real-life setting involving practicing pharmacists in establishing such guidelines. On the other hand, registration of dispensing practices using the APO methodology reveals many possibilities for improvement, although the emphasis of such improvements should be dependent on contextual factors within and between countries.This is the first testing of the APO methodology in community pharmacy practice. The APO methodology has been proven to be effective in general practice over several decades ,8,10. DuThe complexity of the dispensing process makes it difficult to measure all topics related to it on a registration chart that can be completed within a few minutes. Within that framework, we attempted to include the most relevant parts of the antibiotic dispensing process but had to eliminate or simplify many topics from the registration chart. Several topics have been discussed and considered but not included in the final registration chart. These include registration of multiple other antibiotics and antibiotic classes, symptom assessment of patients without an antibiotic prescription, the patients’ perspective on the dispensing process, patient’s adherence to antibiotic therapy, the use of point-of-care tests, the use of “wait-and-see” prescriptions, and more specific details on safety checks and a wider range of possible appropriate advice. Through this method we developed a registration chart that takes little time to complete. Nevertheless, completing the chart during dispensing will take up additional time of pharmacists, which may mean that implementation might not be possible in all pharmacies for all antibiotic dispenses.Although it was estimated that the use of antibiotics without a prescription comprised about 7% of total antibiotic use in the EU , over-thThere is only limited literature available on documenting dispensing practice, even more so for antibiotics specifically. Cerqueira Santos et al.  reviewedThe ECDC has described a large role for the community pharmacist towards improving the quality of antibiotic use and therewith reducing antimicrobial resistance . NonetheThis pilot study is part of the Health Alliance for Prudent Prescription and Yield of Antibiotics in a Patient-centered Perspective (HAPPY PATIENT) project. This project aims to further implement the EU AMR guidelines on the prudent use of antimicrobials in humans . The proData collection was attempted in 25 community pharmacies, five pharmacies in five different countries with differences in scale and patterns of antibiotic use , and sprThe layout of the registration chart, with multiple variables categorized within overarching domains, was kept consistent with the original audit chart developed for GP practice as earlier published ,10. The The registration chart has been discussed during several meetings with expert groups: the developers of the original GP registration chart, local partners in the target countries, practicing community pharmacists and the complete HAPPY PATIENT project group. The list of antibiotics and antibiotic classes included in the registration chart was composed in collaboration with the local and clinical partners, for consistency throughout the project. The registration chart comprised nine domains with a total of 46 variables related to antibiotic dispensing, and two patient variables—age and sex ; it focu® SPSS® and Stata™ files by partners at the Research Unit for General Practice, Institute of Public Health of the University of Southern Denmark.The registration chart and an instruction document  were disTo assess the feasibility of implementing the registration chart in practice and to acquire feedback on the registration chart, the pharmacy’s staff was requested to complete a questionnaire following the pilot study . This quAll answers to the questionnaire were translated to English by the partners in the target countries. Due to the small number of participating pharmacies, the received feedback was discussed by the core research group in full. Any unclarities were solved, and suggestions towards increasing the ease of use of the documents or reducing the time needed to complete them were considered if these were relevant in all target countries. Similarly, the content of the registration chart was adjusted based on this questionnaire. To this extent, any topic suggested to include or remove was discussed within the core research group and compared to WHO and ECDC reports and SmPC texts. Topics mentioned by multiple pharmacists were given a higher priority. Any topic was only included if deemed relevant in all four countries and consistent with EU AMR guidelines. Additionally, the data collected with the registration chart was used to further improve its contents.The data collected with the registration chart were also used to illustrate community pharmacy practice regarding antibiotic dispensing using Stata/MP 16. Data were analyzed descriptively for pharmacies per country and for the countries together. Crosstabs of different combinations of domains were created to analyze combinations of dispensed antibiotics and provided advice. Appropriateness of advice was determined by comparing the collected data to SmPC information for the specific antibiotics. Safety checks of contraindications, interactions, and allergies were deemed to have to be performed for all dispensed antibiotics, as described as the role of the pharmacists in the EU AMR guidelines .The registration chart based on the APO methodology appears to be a feasible way to obtain detailed data on the antibiotic dispensing practices in community pharmacies. Pharmacists from different countries have been able to implement the registration chart in their daily practice. Although the complex process of antibiotic dispensing cannot be documented entirely within a few minutes, this tool does make it possible to obtain useful information about antibiotic dispensing. Nevertheless, the effectiveness of this tool is not solely based on its design; it will substantially depend on the implementation of interventions that result from using the tool in practice. This pilot study indicates the presence of considerable inconsistencies between the EU guidelines on dispensing and the everyday practices in the pharmacies.


The coupled effect of the chloride attack environment and train load seriously affects the safety and durability of urban rail transit viaducts and dramatically reduces their service life. In this research, a corrosion-fatigue life prediction model of the prestressed concrete (PC) beam under the coupled effect of the chloride attack environment and train load was developed. This proposed model was illustrated by a 30 m-span PC U-shaped beam in an urban rail transit viaduct. The competitive relationship between concrete fatigue cracking time, non-prestressed reinforcement corrosion initiation time, and concrete corrosion-induced cracking time was discussed. The effects of train frequency, the chloride attack environment grade, and the environmental temperature and relative humidity were investigated on corrosion-fatigue life. Results indicate that train frequency, the chloride attack environment grade, and the environmental temperature can reduce the corrosion-fatigue life of a U-shaped beam by up to 30.0%, 50.7%, and 21.5%, respectively. A coupled chloride attack environment and train frequency can reduce the corrosion-fatigue life by up to 61.2%. Distinct from the environmental temperature, the change of relative humidity has little effect on the corrosion-fatigue life of the U-shaped beam. With the increasing traffic volume on urban roads, traffic congestion is a common phenomenon in the urban city, and the situation is rapidly deteriorating . Urban rReinforcement corrosion is widespread in reinforced concrete (RC) structures . The deg5 cycles of loading with the fatigue load upper and lower limit values of 240 kN and 25 kN, respectively. Cui et al. [Currently, some studies have been carried out on the life prediction of RC structures under the coupled effect of corrosive environment and fatigue loading. Cui et al.  developei et al.  establisBased on the operation characteristics of urban rail transit, this study presents a corrosion-fatigue life prediction model of the PC beam for urban rail transit. A 30 m-span PC U-shaped beam on the urban rail transit viaduct in a coastal city was analyzed to illustrate the proposed model. The metro train load model was created to calculate the load impact as the train passes through the beam. The rain flow counting approach was used to calculate the stress range and corresponding cycles of non-prestressed reinforcement in the U-shaped beam. The fatigue damage and corrosion-fatigue life of a U-shaped beam were evaluated under the coupled chloride attack environment and train load. The effects of train frequency, the chloride attack environment grade, and the environmental temperature and relative humidity on fatigue damage and corrosion-fatigue life were discussed. The findings hope to provide insights for the corrosion-fatigue life prediction of PC structures.C is the concentration of chloride ion in the environment (kg/m3); Dcl is the diffusion coefficient of chloride ion (m2/years); x is the distance from the concrete surface (mm); and t is the exposure time (years).Chloride ions ingress into concrete is a complex process involving several transport mechanisms. The diffusion process is considered the dominant mechanism of chloride ion ingress into concrete. Fick’s second law can be used to explain the diffusion process :(1)∂C∂t=C  = Cs and C  = C0, Equation (2) can be obtained as the analytic solution to Equation (1), as follows [C is the concentration of chloride ions in concrete at x depth from the concrete surface at exposure time t (kg/m3); Cs is the chloride ion concentration around concrete (kg/m3); and C0 is the initial concentration of chloride ion in concrete (kg/m3); erf(∙) is the error function.When the initial boundary conditions are  follows :(2)C = Ccr, and x = c, the corrosion initiation time tini can be calculated as:c is the concrete cover thickness (mm); and Ccr is the critical chloride ion concentration of reinforcement corrosion (kg/m3).The corrosion initiation time of tensile reinforcement is affected by many factors, including the initial chloride ion concentration in concrete, chloride ion diffusion rate, concrete cover thickness, and critical chloride ion concentration. When Dcl can be calculated as [T is the environmental temperature (°C); and w/c is the water-cement ratio, which can be estimated as [fcu is the cubic compressive strength of concrete (MPa).In addition to the water-cement ratio, the chloride ion diffusion coefficient also depends on the environmental temperature. When the chloride ion diffusion coefficient remains constant over time, lated as :(4)Dcl=(mated as :(5)w/c=2iini (mm/year) of reinforcement before the concrete cover cracking can be calculated as:i is the reinforcement corrosion current density (μA/cm2), which can be computed using the following formulas:Cs1 is the concentration of chloride ion around the reinforcement (kg/m3); mcl is the local environmental coefficient ; kρ is the coefficient related to the water-cement ratio; Ccl is the average concentration of chloride ion in concrete cover (kg/m3); RH is the relative humidity (%); and tcr,c is the concrete corrosion-induced cracking time (years).Pitting corrosion occurs in the local position along the length direction of reinforcement in a chloride attack environment. As a result, many corrosion pits are formed on the surface of the reinforcement. Chinese standard GB/T 51355-2019  suggestsfficient ; p is thd is the initial reinforcement diameter (mm).With the increase in corrosion degree, corrosion products accumulate on the interface between reinforcement and concrete, causing corrosion-induced cracking of concrete cover. At this time, the reinforcement corrosion depth can be estimated as:β1 is the correction coefficient for considering the migration of corrosion products around the corrosion pit on the cracking time of concrete cover; β2 is the correction coefficient for considering multiple corrosion pits distribution on the cracking time of concrete cover.The concrete cover cracking increases the paths of chloride ion entry into the concrete , resultift is the concrete tensile strength (MPa); and Ncr is the number of fatigue loading cycles during which fatigue cracking develops in concrete.The concrete cover also cracks when the PC beams are subjected to the train load for a long time. The fatigue cracking time of concrete cover can be calculated by the stress response of concrete at the bottom of the beam, the S-N curve of concrete cracking, and Miner’s rule. The S-N curve of concrete fatigue cracking given in the literature  can be enicr, is the number of concrete tensile stress cycles under the different maximum tensile stresses nicr, is the total number of tensile stress cycles in concrete.The equivalent maximum tensile stress for variable-amplitude fatigue load can be determined using Miner’s rule. Therefore, the equivalent maximum tensile stress can be calculated as:Dcr of tensile concrete induced by a single fatigue load can be computed as:The fatigue damage f for n years, the cumulative fatigue damage Dcr,t of concrete can be calculated as:When operating at the annual working frequency Dcr,t reaches 1, the concrete occurs to crack and the corresponding concrete fatigue cracking time tcr,f (years) can be obtained.When tcr (years) can be taken as the smaller value between the corrosion-induced cracking time tcr,c (years) and the fatigue cracking time tcr,f. Thus, the concrete cracking time tcr can be calculated as:Concrete fatigue cracking occurs when the maximum tensile stress of the fatigue load on the concrete is greater than the tensile strength of the concrete. The concrete cracking time acr,f (mm) can be computed as:When the concrete crack occurs due to fatigue load, the reinforcement corrosion depth acr (mm) can be taken as the smaller value between the corrosion depth acr,c (mm) of corrosion-induced concrete cracking and the corrosion depth acr,f of fatigue cracking. Thus, the corrosion depth acr can be expressed as:When concrete cracking occurs (corrosion-induced concrete cracking or corrosion-induced concrete cracking), the corrosion depth icr (mm/year) of reinforcement after concrete cracking (fatigue cracking or corrosion-induced cracking) can be calculated as [Fatigue cracking of concrete also accelerates reinforcement corrosion. It is assumed that the corrosion rate of reinforcement after fatigue cracking and corrosion-induced cracking is equal. The corrosion rate lated as :(19)icr=t, the corrosion depth of reinforcement a(t) can be expressed as:Then, when the beam operates to the time N is the number of stress cycles at reinforcement fatigue fracture within the reinforcement stress range Δσ; and C and m are the material coefficient for the reinforcement.The evaluation method based on the S-N curve of reinforcement is convenient and widely used for fatigue life prediction. The fatigue failure mode of the beam is mainly the fatigue failure of reinforcement ,39. The iσ and its corresponding number of cycles in. The damage caused by the variable amplitude stress cycles of reinforcement can be calculated by Miner’s rule, which can be determined as:Db is the cumulative fatigue damage of the reinforcement, Db ≥ 1 indicates the fracture of the reinforcement; in is the number of reinforcement stress cycles at the stress range ∆iσ; and iN is the number of stress cycles when fatigue failure occurs in the reinforcement under the stress range ∆iσ.The reinforcement in the beam will produce variable amplitude stress cycles under the train load . The raiσe (MPa) with the same damage can also be obtained, and the corresponding number of cycles is ∑in, the fatigue failure number N0 under the action of this equivalent stress range can be obtained according to Equation (21):According to Miner’s rule, an equivalent stress range Δσe is:The reinforcement fatigue damage caused by the action of stress range ΔDb = D0, the equivalent stress range Δσe is expressed as:According to C to indicate its attenuation with time. The time-varying effect of parameter m is not addressed in the prediction of corrosion-fatigue life since the attenuation effect of m with time is relatively modest. Therefore, the S-N curve in Equation (21) can be rewritten as:The fatigue performance of beams in a chloride attack environment differs from that in a corrosion-free environment. The corroded reinforcement will no longer be suitable for the S-N curve in Equation (21). A coefficient is required for the material constant C(t) can be expressed as [C0 is the material constant of uncorroded reinforcement; and ϕ(t) is the attenuation coefficient, which is obtained by fitting the test results of corroded reinforcement in the literature [w(t) is the reinforcement cross-sectional loss ratio, which can be expressed by the ratio of the reinforcement corrosion pit area Apit(t) to the initial reinforcement area Aini, and the initial reinforcement area Aini = πd2/4.The time-variant material constant essed as :(27)C(t)terature ,47,48,49σ0 is the uncorroded reinforcement stress range (MPa).The reduction in the cross-sectional area increases the stress range of reinforcement, which can be expressed as :(29)Δσ of reinforcement can be represented as:in is the total number of stress range cycles.The equivalent stress range ΔDs(t) due to the single train load can be computed as:The reinforcement fatigue damage n years with an annual passing frequency of f, the cumulative fatigue damage Dc(t) of the beam can be expressed as:The cumulative fatigue damage of steel bars will increase steadily with the extension of service time without taking maintenance measures. When the train operates for Dc(t) ≥ 1, fatigue failure will occur.When (1)Input the structural, train, material, and environmental parameters and calculate the stress range of non-prestressed reinforcement and concrete.(2)Determine the chloride ion transport process using Equations (1) and (2).(3)Compute the corrosion initiation time and corrosion rate of reinforcement before the concrete cracking and corrosion-induced cracking time of concrete using Equations (3)–(11).(4)Calculate the fatigue damage of concrete and concrete cracking time produced by fatigue loading using Equations (12)–(15).(5)Compute the corrosion rate and corrosion depth following concrete cracking and the concrete cracking time using Equations (16)–(20).(6)Calculate the cross-sectional area loss of reinforcement using Equation (30).(7)Obtain the equivalent stress range of uncorroded reinforcement using Equations (21)–(25).(8)Determine the fatigue resistance reduction behavior using Equations (26)–(29).(9)Calculate the reinforcement cumulative fatigue damage using Equations (31)–(33).(10)Dc(t) reaches 1.Output the corrosion-fatigue life by determining if The above prediction model is applied to a 30 m-span PC U-shaped beam in the urban rail transit viaduct. The flow chart of the calculation process is listed in To validate the proposed model, the model is used to predict the fatigue life of corroded RC beams in the literature ,52. The A 30 m-span PC U-shaped beam in an urban rail transit viaduct was evaluated to illustrate the corrosion-fatigue life prediction model of PC structures under the coupled chloride attack environment and train load. The analyzed U-shaped beam with a span of 30 m, depth of 1.8 m, and width of 5.17 m is the most widely used in the whole urban rail transit viaduct. The strength grade of concrete used for the U-shaped beam is C55, and the concrete cover thickness is 35 mm. The non-prestressed reinforcement is HRB400  with a diameter of 12 mm. Chemical compositions of the non-prestressed reinforcement are listed in C and m are taken as 1.4213 × 1010 and 1.7637, respectively.The urban rail transit viaduct is located on the coast. As a result, the chloride attack environment grade of the U-shaped beam is grade A , and theThe axle load and wheelbase of metro trains are the main factors affecting the safety performance of bridges. The urban rail transit viaduct operates the B-type metro vehicle, which is a six-carriage train, and the axle weight of the train is 14 t. It is necessary to consider the dynamic amplification effect of the moving train load when computing the midspan load response of the U-shaped beam, which can be considered by multiplying the train load by the dynamic coefficient. For the urban rail transit single line, the dynamic coefficient of the U-shaped beam is 1.4 . It is aUnder the chloride attack environment of grades A to D, the corrosion initiation time of non-prestressed reinforcement in the PC U-shaped beam is 31.7 years, 8.1 years, 5.7 years, and 4.8 years, respectively, and the corrosion-induced cracking time under the corresponding corrosive environment is 41.9 years, 15.8 years, 11.5 years, and 8.6 years, respectively. The fatigue cracking time of the U-shaped beam under four train frequencies of 109/day, 217/day, 433/day, and 721/day are 26.3 years, 13.2 years, 6.6 years, and 3.9 years, respectively.When the train frequency is 109/day, fatigue cracking of the U-shaped beam develops before the non-prestressed reinforcement corrosion in the A-grade chloride attack environment. Fatigue cracking occurs after corrosion-induced concrete cover cracking in the chloride attack environment of grades B to D. Under the train frequency of 217/day, fatigue cracking of the U-shaped beam occurs before the corrosion of non-prestressed reinforcement in the A-grade chloride attack environment, and fatigue cracking occurs between the non-prestressed reinforcement corrosion and the corrosion-induced concrete cover cracking in the B-grade chloride attack environment. For the chloride attack environment grades of C to D, fatigue cracking occurs following the corrosion-induced concrete cover cracking. Under the train frequency of 433/day, fatigue cracking of the U-shaped beam in the A-grade and B-grade chloride attack environment occurs before the corrosion of non-prestressed reinforcement. The fatigue cracking occurs between the corrosion of non-prestressed reinforcement and the corrosion-induced concrete cover cracking with the C-grade and D-grade chloride attack environment. For the train frequency of 721/day, the fatigue cracking of the U-shaped beam occurs before the corrosion of non-prestressed reinforcement.The corrosion-fatigue life of the U-shaped beam is impacted by the chloride attack environment grade and train frequency. The corrosion rate of steel bars is affected by the degree of chloride attack in the environment, and the train frequency influences the fatigue damage accumulation rate of concrete and non-prestressed tensile steel bars in the PC beam. To investigate the effects of the chloride attack environment grade and train frequency on corrosion-fatigue life, the cumulative fatigue damage and corrosion-fatigue life of a 30 m-span PC U-shaped beam were evaluated under different chloride attack environments and train frequencies. Under each calculation condition, the environmental temperature and relative humidity are the same as with the design service condition.To study the influence of train frequency on the corrosion-fatigue life of the PC beam, It can be seen from The environmental temperature and relative humidity of the service environment will affect the corrosion-fatigue life of the PC beam. This research investigates the effects of environmental temperature and relative humidity on the corrosion-fatigue life of a 30 m-span PC U-shaped beam. As a consequence, the corrosion-fatigue life of the U-shaped beam at various environmental temperatures (5–25 °C) and relative humidity (55–85%) was predicted. Under each calculation condition, the chloride attack environment and train frequency are the same as the design service condition.As can be seen from (1)The corrosion-fatigue performance of the 30 m-span PC U-shaped beam is well under the design service condition. After 100 years of operation, the cumulative fatigue damage value is only 0.181, and the final corrosion-fatigue life of the U-shaped beam is 164.8 years. During the operation of the U-shaped beam, it is necessary to strengthen maintenance and repair to avoid concrete cracking.(2)Increasing the chloride attack environment grade and train frequency decreases the corrosion-fatigue life of the U-shaped beam substantially. The chloride attack environment grade and train frequency, when compared to the design service condition, can decrease the corrosion-fatigue life of the U-shaped beam by up to 50.7% and 30.0%, respectively. The corrosion-fatigue life is shortened by up to 61.2% when the chloride attack environment grade and train frequency increase simultaneously.(3)The corrosion-fatigue life of the U-shaped beam decreases significantly with the increase in environmental temperature. However, relative humidity has an insignificant effect. The environmental temperature and relative humidity can reduce the corrosion-fatigue life by up to 21.5% and 0.36%, respectively, compared with the design service condition. The increased environmental temperature and relative humidity simultaneously can cause the corrosion-fatigue life to decrease by up to 21.9%.This study developed a corrosion-fatigue life prediction model of PC beam under the coupled chloride attack environment and train load. A 30 m-span PC U-shaped beam in an urban rail transit viaduct was used to illustrate the suggested model. The impacts of train frequency, chloride attack environment grade, and environmental temperature and relative humidity on the corrosion-fatigue life of the U-shaped beam were analyzed. The findings are summarized as follows:


Sarcopenia is receiving attention in oncology as a predictor of increased chemotherapy toxicities. Research into body composition change during neoadjuvant chemotherapy for breast cancer is both urgently needed and generally lacking. This study assessed sarcopenia prevalence before and after neoadjuvant chemotherapy using CT imaging, evaluated body composition changes during neoadjuvant chemotherapy, and determined predictors of sarcopenia status after neoadjuvant chemotherapy for breast cancer.In this retrospective, descriptive study, we used data collected from 2017 to 2020 to measure body composition parameters on cross-sectional CT slices for 317 Korean women with breast cancer patients before and at completion of neoadjuvant chemotherapy. Changes in skeletal muscle index, visceral fat index, subcutaneous fat index, and sarcopenia were assessed and correlated, and multivariate logistic regression was conducted to identify predictive factors associated with sarcopenia status at completion of neoadjuvant chemotherapy.2/m2 (t (316) = 2.15, p <.5). Lower skeletal muscle index at baseline was associated with greater loss of muscle mass during neoadjuvant chemotherapy . Multivariate logistic regression showed that baseline sarcopenia status was the only significant predictor of sarcopenia status after neoadjuvant chemotherapy (p <.001). Specifically, the log odds of sarcopenia after neoadjuvant chemotherapy were 3.357 higher in the baseline sarcopenia group than in the group without baseline sarcopenia .Of the 80 breast cancer patients (25.2%) who had sarcopenia before beginning neoadjuvant chemotherapy, 64 (80.0%) retained their sarcopenia status after chemotherapy. Weight, body mass index, body surface area, and visceral fat index showed significant increases after neoadjuvant chemotherapy; notably, only skeletal muscle index significantly decreased, showing a reduction of 0.44 cmSarcopenia during neoadjuvant chemotherapy can be obscured by an increasing proportion of fat in body composition if clinical assessment focuses on only body mass index or body surface area rather than muscle mass. For breast cancer patients who have sarcopenia when they begin neoadjuvant chemotherapy, the risk of muscle mass loss during treatment is alarmingly high. To reduce masking of muscle mass loss during treatment, comprehensive evaluation of body composition, beyond body surface area assessment, is clearly needed. Breast cancer, with an estimated 2.1 million cases diagnosed globally in 2018  producedSarcopenia, or decreased muscle mass, has been receiving attention in oncology as a predictor of increased chemotherapy toxicities and as a sensitive early marker of treatment effectiveness –9. The pDetermination of sarcopenia status involves assessment of alterations in body composition. Changes in body composition have been reported to occur in breast cancer patients during chemotherapy and endocrine therapy . In addiAlthough urgently needed, research in the area of body composition change during neoadjuvant chemotherapy for breast cancer is generally lacking. Descriptive analyses of body composition during other forms of cancer treatment  have been performed, for various cancer types –20, but We used a retrospective, descriptive, observational study design to determine body composition change and sarcopenia prevalence among breast cancer patients who had visited the breast cancer clinic at Severance Hospital in Seoul, Korea, from January 2017 to November 2020. Eligible participants were Korean women 20 years or older who had received a diagnosis of breast cancer at the hospital, completed neoadjuvant chemotherapy, and received at least two abdominal CT scans, before and after neoadjuvant chemotherapy, that provided images of the third lumbar spine vertebra (L3). We excluded patients with stage IV breast cancer and patients with CT images that were insufficient or inappropriate for analysis of body composition. Our sample size of 317 cases was sufficient to meet the study objectives. Initially, the target sample size was determined using G*Power 3.1 software. To accommodate regression analysis and pseudo R2 (0.39), a required sample size of 265 was calculated based on an odds ratio of 1.3. a power of 0.8.Approval for this study was obtained from the Severance Hospital Institutional Review Board (#4-2021-0452) at Yonsei University Health Systems, Seoul, Korea. The Severance Hospital Data Review Board also approved the study data set with respect to protection of patients’ data and assessment of data-protection risks and tools.in situ findings.The Big Data Team in the Yonsei University Health System provided comprehensive information from the selected sample’ medical records, including sociodemographic data and clinical data such as cancer- and treatment-related information. We used this information to assess age, clinical stage, TN stage, Ki-67, breast cancer subtype, chemotherapy regimen, duration of neoadjuvant chemotherapy, and BMI and BSA . For Ki-67, we used a cutoff value based on the expressed cell ratio (<14% and ≥14%). For breast cancer subtype, we evaluated both hormone receptor and human epidermal growth factor receptor 2 (HER2); to explore HER2 gene amplification, we also assessed silver stain hybridization 2). The Hounsfield unit values used for measurement ranged from −29 to 150 for muscle, −190 to −30 for subcutaneous fat, and −150 to −50 for visceral fat. 2/m2) was calculated as skeletal muscle area (in cm2) divided by height squared (in m2); both subcutaneous fat area and visceral fat area were also divided by height squared to determine the associated indexes. With respect to the sarcopenia cutoff value, we applied the value introduced by Prado et al. (SMI <38.5 cm2/m2) as an SMI cutoff for women . Using the analysis program provided in the software, we analyzed the CT slices at L3 as a standardized landmark. We calculated the total cross-sectional areas of skeletal muscle, subcutaneous fat, and visceral fat  before and after neoadjuvant chemotherapy. We calculated Pearson correlation coefficients to evaluate associations among body composition parameters. Finally, we applied multivariate logistic regression to determine predictors of sarcopenia at completion of neoadjuvant chemotherapy. All p values were two-tailed, and p values <.05 were considered significant.Data analysis was performed using Stata/IC 16 statistical software . We conducted descriptive analyses to characterize the study sample and to assess their body composition before (at baseline) and at completion of neoadjuvant chemotherapy. In addition, we used a paired n = 132, 41.6%), followed by obese  and overweight .n = 214, 67.5%), followed by the docetaxel, carboplatin, trastuzumab, and pertuzumab regimen . The mean duration of chemotherapy was 142 days, with durations ranging from 49 to 196 days. Stage II cancer was the most common in the sample .Among the combinations of chemotherapy drugs used, the combination of anthracyclines and taxanes was the most common (t (316) = −3.84, p = .001). Similarly, BMI and BSA (both based on weight in relation to their height) showed significant increases after neoadjuvant chemotherapy, by an average of 0.24 kg/m2 for BMI and 0.01 m2 for BSA.2/m2 (from 29.97 to 31.28 cm2/m2). There was no significant difference in subcutaneous fat index (SFI) before and after chemotherapy. SMI showed the only significantly decrease during neoadjuvant chemotherapy, by 0.44 cm2/m2 (from 42.37 to 41.93 cm2/m2).Among the body composition changes during neoadjuvant chemotherapy, visceral fat index (VFI) significantly increased by 1.31 cmn = 93, 29.34%). Of the 80 patients who had sarcopenia before their chemotherapy, 64 (80%) retained their sarcopenia status after chemotherapy.r = −.24, p <.001). Baseline SFI and VFI showed a similar direction of association with the mean differences in body composition parameters; lower VFI at baseline was associated with a greater loss of subcutaneous fat and visceral fat mass during neoadjuvant chemotherapy . All mean differences in body composition parameters—including muscle, subcutaneous fat, and visceral fat mass—after neoadjuvant chemotherapy were positively related to one another. All significant relationships between body composition parameters were observed both at baseline and at completion of neoadjuvant chemotherapy.2[9] = 140.67, p = .0000, pseudo R2 = 0.3908). Baseline sarcopenia status was the only significant predictor of sarcopenia status after neoadjuvant chemotherapy. Specifically, the sarcopenia after neoadjuvant chemotherapy increased for the group with baseline sarcopenia, with 3.357 times increasing log odds . Other variables showed no significant association with sarcopenia risk after neoadjuvant chemotherapy. Finally, no interactions of baseline sarcopenia status with other variables were observed to predict sarcopenia status after neoadjuvant chemotherapy.As shown in We conducted this study to improve understanding of the current status of sarcopenia in breast cancer patients by evaluating body composition changes during neoadjuvant chemotherapy, using CT imaging to assess sarcopenia prevalence before and after neoadjuvant chemotherapy, and determining predictors of sarcopenia status after neoadjuvant chemotherapy in this population. To our knowledge, this is the first study to use CT imaging to comprehensively quantify body composition changes during neoadjuvant chemotherapy in Korean breast cancer patients. Determination of sarcopenia status is often complicated or obscured by obesity; sarcopenia is difficult to recognize visually without medical imaging. Therefore, this study used abdominal CT scans, which are routinely performed during treatment and are among the most accurate measures of body composition parameters, to accurately quantify body composition changes.Our study generated meaningful findings regarding sarcopenia status and body composition changes among patients with breast cancer undergoing neoadjuvant chemotherapy. Notably, BMI and BSA increased significantly during neoadjuvant chemotherapy. This finding is clinically significant because BSA is typically used in clinical oncology settings to calculate chemotherapy doses. Additionally, an unchanged BSA during chemotherapy can mask more specific changes to body composition, such as alterations in the proportions of fat and muscle. For example, the detailed body composition results in our study showed that although visceral fat mass significantly increased during neoadjuvant chemotherapy, SMI significantly decreased. While the observed weight gain indicates that most body composition–related variables increased or were maintained, that gain can also mask significant decreases in the actual amount of skeletal muscle mass. These findings suggest that weight maintenance and muscle mass maintenance during chemotherapy are not proportional, and thus that muscle mass loss could be easily overlooked in clinical settings.n = 64) maintained their sarcopenia status after completing chemotherapy. Additionally, 12.2% of those who did not have sarcopenia at baseline (n = 29) were newly diagnosed with the condition after neoadjuvant chemotherapy. A similar result was reported by a systematic review and meta-analysis involving 11 studies of patients receiving neoadjuvant therapy for esophageal cancer, which found that 15.4% of participants showed new incidence of sarcopenia after neoadjuvant chemotherapy  during neoadjuvant chemotherapy. Furthermore, the retrospective data available to us were limited to muscle mass measurements, as muscle strength and physical performance data had not been collected. Consequently, we focused our evaluation on secondary sarcopenia, for which muscle mass data would suffice. Based on the available evidence on various factors related to sarcopenia, future studies should comprehensively investigate potential mediators, their associations with sarcopenia, and their underlying mechanisms, with the goal of minimizing muscle mass loss during cancer treatment. Finally, as sarcopenia is more prevalent in the general population of Korea than is the case in the United States and Europe, our study sample may have been subject to selection bias.Comprehensive body composition analysis can improve our understanding of subtle yet meaningful changes in muscle and fat mass among breast cancer patients undergoing neoadjuvant chemotherapy. To reduce masking of muscle mass loss during cancer treatment in clinical settings, active interpretation of body composition beyond BSA and BMI assessment is clearly needed. This is particularly true for patients who have sarcopenia when they begin neoadjuvant chemotherapy, as their risk of muscle mass loss during treatment is alarmingly high. Assessment of body composition and sarcopenia status beginning at breast cancer diagnosis and extending throughout the neoadjuvant chemotherapy period should become a cornerstone for successful completion of planned cancer treatment.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study was reviewed and approved by the Severance Hospital Institutional Review Board in the Yonsei University Health Systems, Seoul, Korea (#4-2021-0452). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements. Written informed consent was not obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.MJ, SK, SP, and JG, study concept and design. MJ and SK, data acquisition and data quality control. MJ and CP, data analysis and interpretation, manuscript preparation. MJ, SK, SP, CP, JG, and AD, contributed to the article, reviewed the manuscript, and approved the submitted version. All authors contributed to the article and approved the submitted version.This work was supported by a National Research Foundation of Korea (NRF) grant, which was funded by the government of the Republic of Korea through the Ministry of Science and ICT (NRF No. 2021R1C1C2004628).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.


The usage of glass fiber reinforced polymer (GFRP) composite cross-arms in transmission towers is relatively new compared to wood timber cross-arms. In this case, many research works conducted experiments on composite cross-arms, either in coupon or full-scale size. However, none performed finite element (FE) analyses on full-scale composite cross-arms under actual working load and broken wire conditions. Thus, this work evaluates the performance of glass fiber reinforced polymer (GFRP) composite cross-arm tubes in 275 kV transmission towers using FE analysis. In this study, the performance analysis was run mimicking actual normal and broken wire conditions with five and three times more than working loads (WL). The full-scale assembly load test experiment outcomes were used to validate the FE analysis. Furthermore, the mechanical properties values of the GFRP composite were incorporated in simulation analysis based on the previous experimental work on coupons samples of GFRP tubes. Additionally, parametric studies were performed to determine the ultimate applied load and factor of safety for both normal and broken wire loading conditions. This research discovered that the GFRP composite cross-arm could withstand the applied load of five times and three times working load (WL) for normal and broken wire conditions, respectively. In addition, the factor of safety of tubes was 1.08 and 1.1 for normal and broken wire conditions, respectively, which can be considered safe to use. Hence, the composite cross-arms can sustain load two times more than the design requirement, which is two times the working load for normal conditions. In future studies, it is recommended to analyze the fatigue properties of the composite due to wind loading, which may induce failure in long-term service. Transmission towers are electrical pylons that function to support overhead power lines. The transmission tower designs were categorized into two types, namely, monopole steel tubes and latticed steel towers. The transmission tower lines usually supply electrical power from the power generator to sub-stations before going to consumers . The powNeobalanocarpus hemii) is used due to its excellent strength and arc quenching during the strike of lightning. However, the wooden cross-arms started to experience failure after giving the service for more than 20 years [Generally, the materials used for cross-arms in transmission towers are wood, steel and Glass Fiber Reinforced Polymers (GFRP) ,10. Hist20 years . The fai20 years ,13,14, m20 years ,16,17,1820 years ,20. Addi20 years ,22,23. W20 years ,25,26,2720 years ,29,30, c20 years ,32,33,3420 years ,36,37, m20 years ,39, avia20 years ,41,42 an20 years ,44,45. D20 years .Recently, several kinds of research were carried out involving the various modes of studies in order to attain technical data on the influence of material configurations on the cross-arm’s integrity. In this case, Asyraf et al.  developeEven though many studies were implemented experimentally, it can be found that there is a lack in the analysis of computer simulation for GFRP cross-arms. Most of the literature revealed that the existing design of the GFRP cross-arm is still impended due to failure that occurred on the GFRP cross-arm after six months of installation ,54,55. FThis research article is expected to demonstrate the parametric studies conducted on the GFRP composite cross-arm in a 275 kV transmission tower using numerical modelling to measure its ultimate load and factor of safety. At the end of the study, the research outputs from this analysis are intended to set a baseline for mechanical profiling of full-scale GFRP composite cross-arms. Thus, the outcomes of this study are projected to provide a practical perspective to researchers and engineers for understanding the mechanical performance of GFRP composite cross-arms.3), Poisson ratio (0.28) and Young’s modulus in the x-axis , y-axis  and z-axis (3100 MPa), and they were added to the structural analysis. The inputs were updated in the setting of the computational simulation correlating the fundamental of the laminated composite laminate modelling. The overall process is displayed in In this study, the structural analysis was commenced using the modelling process of the finite element (FE) simulation, replicating the real conditions of the experiment. The initial inputs such as mechanical properties of GFRP composite cross-arm were installed in the FE simulation after finalizing the size and dimension GFRP composite cross-arm model. These inputs of the GFRP composite are density  was used as a sub-component system to analyze the layer of the GFRP cross-arm. SOLID46 elements were suitable to mesh the GFRP cross-arm model . The matNumerical analysis was performed to attain the deformation shape and values of the GFRP structure in vertical loading, as shown in In this section, a parametric study was conducted using numerical modelling involving two cases: a normal condition and a broken wire condition. The condition, when all the wires are intact at the GFRP cross-arm, is called a normal condition, while the condition when the simulation conductor or earth wire is discovered broken is called the broken wire condition. The variable parameters of these parametric studies are load and deformation. Other than that, the failure of the GFRP cross-arm was also calculated by the minimum Factor of Safety (FOS) :(1)ComprNon-linear analysis was carried out to obtain the maximum working load (WL), deformation and minimum safety factor. The working load shown in 2, while the maximum stress ply for the first layer of the tie member is 275.28 N/mm2.As discussed in this section, the deformation, stress ply, compressive strength and safety factors of the GFRP cross-arm were implemented for normal conditions, as shown in Results of parametric study for GFRP composite cross-arm in broken wire condition are shown in 2, while the maximum stress ply for the first layer of the tie member is 274.35 N/mm2. In conjunction with this issue, the Factor of Safety (FOS) is 3.22, higher than 1, which is considered safe. Referring to In this section, the factor of safety on both conditions, normal condition and broken wire condition, was studied. The summarized safety factor for the GFRP composite cross-arm is presented in In conjunction with these findings, it can be deduced that the maximum loading for normal and broken wire conditions was only withstood up to five and three times higher than WL. This finding proved that the composite cross-arm can withstand any fiber tensile and compressive damages below these values. Higher values than this result in compressive fiber damage, with the highest displacement taking place in the localized around the area of the pinned arms. Subsequently, it would cause composite damage initiation, which leads to structural failure. This study is aligned with the findings led by Daud et al. .Failure criteria is a parameter that evaluates various failure modes when more than one stress is applied. For Hashin criteria, it is a parametric analysis that indicates the failure indication comprised of fiber and matrix failures with both tension and compression. Failure of the cross-arm was measured using the Hashin theory analyzed in ANSYS software. Five layers (laminas) of continuous fiber rovings were interspaced with four layers (laminas) of the stitched glass fiber mat. The strength ratio was evaluated to check which lamina (layer) would fail first when the load was applied. The lamina of composite were considered to fail if the value was equal or more than 1.0, as calculated in Equations (2)–(5). Fiber tension and compression are calculated in Equations (2) and (3). Fiber matrix tension and compression are calculated in Equations (4) and (5).σ = Stress in planetX = Longitudinal tensile strengthcX = Longitudinal compressive strengthtY = Tensile strength in transverse directioncY = Compression strength in transverse directionS12 = Longitudinal shear strengthS23 = Transverse shear strengthThe results of the strength ratio for the GFRP composite cross-arm for Hashin theory are shown in Based on The effect of load magnitudes and conditions on structural properties of GFRP composite cross-arm assembly was evaluated in this FE study. The analytic forecasting analysis displayed that the stress state developed based on the variation of load magnitude and loading conditions of the structure and remarkably affected the strength. The simulated work was validated with the experiment from the FE analysis. The difference between experimental and numerical deformation shows a difference of 0.02 cm (0.23%), which falls below 5%. The allowable percentage difference between experimental and numerical analysis must fall below 5% to be considered acceptable. Two different loading conditions, such as normal and broken wire conditions, are simulated with six load levels. In this case, the six load levels were set based on between one to six times working loads (WL) for both conditions, in which the maximum load capacity of the cross-arm was 5 and three times WL for normal and broken wire conditions, respectively. The simulated results showed that the GRFP cross-arm’s minimum safety factor was 1.08 and 1.1 for normal and broken wire conditions, respectively. These results showed that the GFRP composite cross-arm’s current design is susceptible to resisting the heavy loading from power cables and insulators in both normal and broken wire conditions with good safety values. Additionally, the composite cross-arm can withstand up to five times WL before its lamina fails with −45° orientation. Therefore, it can be concluded that the current cross-arm can sustain load two times as compared to the design requirement, which is two times the working load for normal conditions.Future studies recommend evaluating the influence of joint connections on the creep properties of the GFRP cross-arm in a 275 kV transmission tower. Moreover, it is suggested that the current composite cross-arm may be subjected to dynamic loading due to the wind effect over the long-term period. The dynamic loads from the wind would cause the structure to be fatigued and later fail at a certain point in time. The study on the fatigue resistance and strength of GFRP composite cross-arms extends into another dimension of analysis. Thus, this study would broaden the information and perspective in full-scale cross-arm research for both engineers and researchers.