Receptor tyrosine kinases are essential for the development, growth, and progression of clear cell renal cell carcinoma (ccRCC). Targeted therapies using receptor tyrosine kinase inhibitors are widely used in ccRCC treatment. Myoferlin is a well-known protein that regulates various receptor tyrosine kinases. We aimed to identify myoferlin-associated receptor tyrosine kinases and their prognostic implications in ccRCC. After screening with proteomic analysis, we focused on c-Met and EPHA7 receptor tyrosine kinases. c-Met expression was associated with poor prognosis in ccRCC, and there was an indication that the c-Met pathway may be regulated by myoferlin. Although the expression of EPHA7 and myoferlin was not corelated, the expression of EPHA7 was also associated with unfavorable outcomes. These results suggest that c-Met and EPHA7 might be useful prognostic biomarkers, and the presumed myoferlin/c-Met pathway could be a novel therapeutic target in ccRCC.n = 410 and 506). Proteomic analysis suggested c-Met and EPHA7 as novel candidates for myoferlin-associated RTKs. We immunohistochemically validated the positive association between c-Met and myoferlin expression. High c-Met expression was independently associated with overall (hazard ratio (HR) = 1.153–2.919) and cancer-specific survival (HR = 1.150–3.389). The prognostic effect of high c-Met expression was also determined in an independent cohort . Although expression of EPHA7 and myoferlin was not correlated, EPHA7 expression was independently associated with progression-free (HR = 1.237–4.319) and cancer-specific survival (HR = 1.214–4.558). In addition, network-based prioritization showed co-functional enrichment of c-Met and myoferlin, suggesting a novel regulatory function of myoferlin in c-Met signaling. This study indicates that c-Met and EPHA7 might be useful prognostic biomarkers, and the presumed myoferlin/c-Met pathway could be a novel therapeutic target in ccRCC.Receptor tyrosine kinases (RTKs) are important targets for clear cell renal cell carcinoma (ccRCC) treatment. Myoferlin is a strong regulator of RTKs. To identify myoferlin-associated RTKs and their prognostic implications in ccRCC, we investigated the expression of RTKs and myoferlin using proteome-based evaluation and immunohistochemical staining in tissue microarray. Multivariate Cox analysis adjusted for TNM stage and WHO grade was performed ( Receptor tyrosine kinases (RTKs) are essential for the development, growth, and progression of clear cell renal cell carcinomas (ccRCCs) . Some RTMyoferlin is a well-known transmembrane protein that affects the expression, function, and stability of several RTKs, including VEGFR2, along with its ligand vascular endothelial growth factor-A (VEGFA) ,6, TEK , insulinIn this study, we aimed to identify myoferlin-associated RTKs and their prognostic implications in ccRCC. To this end, we comprehensively evaluated the correlation between RTKs and myoferlin in ccRCC by analyzing liquid chromatography with tandem mass spectrometry (LC–MS/MS) proteomic data taken from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) . The reshttps://www.genenames.org/; accessed on 30 October 2019) [Normalized LC–MS/MS proteome data of the RTK family and myoferlin were obtained from the CPTAC portal, which included 103 microscopically and molecularly confirmed ccRCCs . A comprer 2019) . The corWe included 410 patients with ccRCC who underwent partial or radical nephrectomy at Seoul National University Hospital between 2005 and 2008. An independent cohort of 506 patients with ccRCC 2009–2011) was also included to validate the prognostic effect of c-Met expression. Double 2 mm cores were obtained from formalin-fixed paraffin-embedded tissues for tissue microarray (TMA) construction. Samples that had been collected from patients that had received neoadjuvant treatment, presented with bilateral disease at the time of diagnosis, or had Von Hippel–Lindau syndrome were excluded from the study. The RTK ligands were selected based on the literature search . The fol was also2). According to the Korean Alcohol Guidelines for Moderate Drinking [Clinical data regarding lifestyle factors and International Metastatic RCC Database Consortium (IMDC) scores were collected from medical records. Body mass index (BMI) was calculated by dividing body weight (kg) by height squared , overall survival (OS), and cancer-specific survival (CSS) according to high or low IHC expression using Kaplan–Meier curves and log-rank tests. The optimal cutoff value of high RTK expression was determined based on the statistical significance in the survival analysis, resulting in scores of ≥6.5 for c-Met and ≥5.5 for EPHA7. PFS, defined as the interval between surgery and locoregional recurrence or distant metastasis, was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria . OS was We developed an interacting protein set for c-Met and myoferlin by reconstructing a combined network of proteins prioritized from STRING (ver. 11.5) , and Genp > 0.05). IHC expression scores were compared nonparametrically. Statistical analyses were performed using R software (ver. 3.6.3), with a two-tailed p-value < 0.05 being considered as significant.The χ2 test was performed for the clinicopathological variables. Pearson’s correlation coefficient was calculated for proteome abundance, with a prior normality assumption (Kolmogorov–Smirnov p = 0.0002), EPHA7 (p = 0.0007), and EGFR (p = 0.0149) were positively correlated with myoferlin expression, whereas HER2 (p = 0.0029) and TEK (p = 0.0498) were negatively correlated  , while mrrelated . We furtrrelated .2 = 0.0554, p = 0.0498)  , were ex2 (ranging between 22.7 and 26.4), 67 patients (18.6%) were current or ex-smokers, and 39 (10.8%) were heavy drinkers . Among the patients, 272 (66.3%) underwent radical nephrectomy, while the others (33.7%) underwent partial excision. There were 90 patients (22.0%) that were in TNM stage III or IV, and 217 (52.9%) that were in WHO grade 3 or 4. Lifestyle factors, including BMI, smoking status, and alcohol use, were available for 360 patients. The median BMI was 24.4 kg/mdrinkers . The medp < 0.0001) , high TNM stage , and high WHO grade  in clinicopathological data (p < 0.0001)  a. For su 0.0001) b, and lo 0.0001) c. Kaplancal data . High c- 0.0001) , and a pp = 0.0004), OS , and CSS  (p = 0.0105) and CSS  when adjusted for TNM stage (III/IV vs. I/II) and WHO grade (3/4 vs. 1/2)  = 2.516, 95% confidence interval (CI) = 1.514–4.183,  0.0001) . Multivavs. 1/2) . TNM stavs. 1/2) .n = 506). The male to female ratio was 2.8:1, and the median age was 56.5 years (ranging between 19 and 87). There were 93 patients (18.4%) that were in TNM stage III or IV, and 196 (38.7%) that were in WHO grade 3 or 4. The median follow-up period was 126 months. The expression of c-Met was classified similarly, as high in 49 (9.7%) and low in 457 (90.3%). Multivariate Cox regression analysis adjusted for TNM stage (III/IV vs. I/II) and WHO grade (3/4 vs. 1/2) showed that high c-Met expression was an independent, negative prognostic factor for OS   .p = 0.4215; p = 0.00015; p = 0.005; p < 0.0001; p = 0.0033) and CSS . When adjusted for TNM stage (III/IV vs. I/II) and WHO grade (3/4 vs. 1/2), low EPHA7 expression was selected as an independent, unfavorable prognostic factor for PFS  and CSS   .The aforementioned data, which showed a correlation between c-Met and myoferlin expression, were consistent with the functional relationship between myoferlin and various RTKs ,7,8,9,10p = 0.0061 and p < 0.0001, respectively; p = 0.6538; We next examined the expression of RTK ligands, including HGF a, EFNA5 Modulation of RTK pathways is important for ccRCC treatment, and myoferlin plays pivotal roles in the regulation of various RTKs . LC–MS/Mn = 100–200) and only used CSS as an endpoint [n = 410 and 506). In addition, the present cutoff score for high c-Met expression might be similar to what was used in a previous study that examined the use of c-Met inhibitor cabozantinib in ccRCC treatment, where patients with high c-Met expression (≥2+ staining in 50% of tumor cells) presented survival benefit from receiving cabozantinib therapy compared to the group taking sunitinib, but those without high c-Met expression did not [c-Met, a membrane-bound RTK that is constitutively activated by HIF-mediated transcriptional activation, stimulates ccRCC progression ,28,29,30endpoint ,32. We s did not . Thus, oThrough the reconstruction of a protein-interaction network, we also discovered a co-functional network connecting c-Met and myoferlin. This included CBL and CAV1, which have been shown to mediate myoferlin-induced regulation of RTKs ,9. Both In addition, the connection between c-Met and myoferlin establishes a potential alternative target for ccRCC treatment, which would counteract resistance to tyrosine kinase inhibitor therapies. Although anti-angiogenic strategies using VEGFR inhibitors, such as sorafenib and sunitinib, have shown considerable effects in ccRCC ,4, most We also demonstrated that EPHA7 expression is an independent prognostic factor for favorable PFS and CSS in ccRCC, which is a novel finding. Eph receptors are the largest RTK family that influences the behavior of cancers by regulating proliferation, migration, invasion, and angiogenesis ,39. We fAlthough the current study found that c-Met and myoferlin may have functional connections in ccRCC, the detailed regulatory action was not evaluated. Previous studies have revealed that myoferlin can control RTKs in various ways, including endocytosis, trafficking, recycling, and degradation . FurtherIn conclusion, c-Met and EPHA7 may be useful biomarkers for prognosis in ccRCC. Targeting the myoferlin-mediated regulation of the c-Met pathway could be a novel therapeutic strategy to enhance c-Met inhibitor treatment and decrease resistance in ccRCC.


During concrete construction in winter, the concrete performance is generally improved by adding a chemical admixture or providing protection using tents and hot-air blowers. However, long-term strength or safety accidents may occur due to the installation and removal of the tents. This study considered insulated gang forms to improve formwork methods. In this regard, the microstructure and micropore characteristics of concrete were investigated experimentally to examine the insulated gang form effect on the physical and mechanical properties of concrete. The micropore characteristics were investigated through scanning electron microscopy. The results confirm that applying insulated gangs improves workability and safety without adding chemical admixture. Moreover, the application of insulated gang forms reduces the use of tents and hot-air blowers. Therefore, insulated gangs provide excellent initial quality to the concrete. In modern high-rise building construction, reducing the period of frame construction is essential for ensuring project feasibility. Therefore, selecting an appropriate formwork method is crucial .Formwork construction represents a considerable proportion of the building construction cost as this step accounts for 30–40% of the structure construction cost and 10% of the overall construction cost ,3,4. In As a formwork method, gang forms have been mainly used for high-rise offices and apartments in various countries . For sucFormwork and concrete construction in winter have the problem of preventing early frost damage in the concrete and securing early strength . If earlThere are several countermeasures to prevent such early frost damage : (1) aftMethod (1) is the most typically used method; however, environmental problems, and problems such as the death of workers from suffocation, frequently occur due to the use of hot-air blowers and heaters. In Method (2), the cost of heating water and aggregate increases for ready-mixed concrete manufacturers. For (3), the cost increases owing to the increase in the amount of cement and change in cement type. For (4), protective insulation is used only for a part of the structure, and the labor cost and construction period increase when used for the entire structure. Finally, several studies have been conducted on method (5). As representative cases, Cullu and Arslan studied the physical and mechanical properties of concrete that used antifreeze in cold weather . Riza PoVarious types of chemical admixtures have been used to prevent early frost damage in fresh concrete in winter . HoweverHowever, some studies have pointed out that method (1) presents problems such as high fuel cost, increased installation cost, and environmental pollution ,17. ThusIn other studies, the effect of temperature on the composition of pore solution was investigated ,22,23,24The temperature change, due to the heat of hydration or external environment change, significantly affects the mechanical properties of concrete at an early age. Therefore, it is necessary to investigate and quantify the mechanical characteristics according to temperature and age . TherefoThe experimental design of this study is outlined in The insulated gang form is prepared as a 100% factory-made product, and there is no need for additional on-site fabrication process such as spraying or affixing insulation Therefore, it is easy to install, with small human resources loss, and exhibits a higher insulation effect than the existing protection methods in winter.For concrete, the typical concrete mix commonly used at construction sites in winter was used, without specifically adding admixture for facilitation of hydration reaction.As for the water/binder ratio, the general strength combination, which is commonly used in construction sites, was used, and the target slump and air volume were set at 180 mm and 4.5 ± 1.5%. As for experimental variables, after concrete pouring, the slump and air content were measures. For hardened concrete, the temperature history, compressive strength, microstructure (SEM), and micropores of the concrete were measured.The curing plan of this study considered an outside temperature in the range from 5 to −20 °C. The temperature inside the member was set to 5 °C or higher for three days after concrete pouring. Subsequently, the formwork was removed, and air curing was performed. The measured outside temperature ranged from −5 °C to 0 °C, which corresponded to the average temperature at the end of December (as in Asia–South Korea). For the conventional and insulted gang forms, a 3.0 mm-thick steel plate was used in addition to 50 mm × 30 mm × 2.3 mm rectangular pipes as vertical and horizontal members. A 30 mm-thick rigid urethane board was used as the insulation of the insulated gang form. For concrete, a ready-mixed concrete product, mainly used in general construction sites, was used. The experimental specimens were fabricated as a four-side closed box type with a wall thickness, width, and height of 200 m, 1800 mm, 600 mm, respectively, as shown in The specimens were fabricated as a four-sided closed box type to have conditions similar to those at the actual construction site. Moreover, a hot-air blower  was installed, and the internal space was heated so that the internal temperature could be maintained at 5 °C. Regarding the outside air condition for the specimens, curing was performed for three days by setting the temperature between 5 to −20 °C, which corresponds to cold weather conditions. Subsequently, the specimens were cured for 25 days at temperatures between −5 and 0 °C. This outside air condition was set based on the winter season in South Korea when insulated gang form is installed. The normal temperature condition (20 °C) was excluded from the experimental conditions as it did not meet the purpose of this study to prevent early freezing in winter.In the preparation of specimen for SEM analysis and pore diameter measurement, the central part of the specimen was crushed at each day of age, the crushed parts were passed through a 5mm sieve, and small pieces remaining on the 2.5 mm sieve were extracted. In the concrete specimen, the core was taken from the central part of the structure to avoid other effects such as bleeding and settlement of aggregates. Acetone was used to stop the hydration reaction immediately after crushing the concrete core. As a method for stopping the hydration reaction, the specimen was immersed in acetone immediately, and the free water in the specimen was replaced with acetone. Acetone immersion was conducted for about 24 h, and new acetone was replaced every 8 h. When this process was completed, it was dried at 100 °C for 1 day using a dryer.−3 to 0.0075006 × 10−3 N/m2 with the coated specimen, and care is taken during the process to minimize the evaporation of the volatile component in the adhesive or double-sided tape used. In addition, cement pastes in the initial stage of hydration or colloidal substances need to be handled carefully. In this experiment, samples of about 5 mm were taken from the specimen as shown in The resolution of the SEM  is determined by how small the working distance of the electron beam and whether the beam can be applied to the specimen with high brightness. For use of SEM, a conductive material is coated on the surface of the specimen. In addition, for the surface of the specimen, a free fracture surface is desirable for a concrete structure or a hydration structure, and the surface should be appropriately flat. The specimen fixed with an adhesive or double-sided tape on the observation stand, and gold and carbon are deposited on the surface with a sputtering device such as an ion coater. The SEM observation is conducted in a vacuum of 0.075006 × 10Concrete pore diameter distribution is affected by the materials used, mixing ratio, and curing method, but the total pore volume or pore diameter distribution of concrete varies depending on chemical degradation factors such as neutralization, sulfate corrosion, and acid rain or physical degradation factors such as frost damage. Due to such degradation, the durability of the concrete is reduced, but the measurements of pore diameter distribution are generally used for evaluation of various factors affecting the durability performance of the concrete rather than for quantitative diagnosis and evaluation of the concrete durability. That is, it is used as an indicator for evaluating various properties of concrete materials in many cases. As for the measuring tool in this experiment, pore distribution was measured using mercury intrusion with a porosimeter in The ideal temperature for concrete curing is 15 to 16 °C. The normal range of temperature for the concrete environment is between 5 and 32 °C . At tempIn the case of the insulated gang form, no significant increase was found in the heat of hydration due to the low outside temperature. However, the temperature history was higher than that of the conventional gang form. In addition, the temperature difference between the central and external surfaces was not large.The changes during the initial hydration reaction of cement are particularly pronounced within 28 days after hydration. In this process, calcium silicate hydrate (C-S-H) is the major products in addition to cement particles, and ettringite and monosulfate hydrates are also produced. In addition, relatively large calcium hydroxide crystals in the shape of a hexagonal plate can be seen at the early stage, which gradually decreases due to carbonation as well as the progress of hydration.At low temperatures, the hydration reaction starts very slowly, and ions dissolved before the precipitation of hydrates take longer time in diffusion and C-S-H hydrates with low density show more even distribution and small and irregular structure develop ,27,28. TThe interconnected needle shapes in However, when using the insulated gang form, the ettringite, C-S-H gel, and calcium hydroxide were generated at 3 days of age, indicating that its hydration reaction was better than that of the conventional gang form. At 7 days of age, the hydration products were denser than the conventional gang form.Mostly ettringite is the initial hydration product, which is bridging the binder grains, until the stiffening and setting occurs .The application of the insulated gang formed an accelerated hydration reaction owing to its excellent insulation performance; thus, it increased early compressive strength in addition to the temperature history and compressive strength characteristics shown in Irregular air voids in concrete cause reduced strength and concrete performance degradation. The fine pores in the hydration structure become even smaller as the hydration reaction proceeds, resulting in a denser microstructure.As for the conventional gang form, the hydration reaction was slow due to low concrete retention, which resulted in larger unhydrated cement particles in the early age and irregular cement structure. Therefore, for the conventional gang form, relatively large pores between 50 and 300 µm were observed at 7 days of age owing to the low curing temperature. At 28 days of age, the distribution of large pores decreased because of the hydration reaction. However, in the insulated gang form, a smaller number of large pores of 100 µm were observed at 7 days of age than in the conventional gang form. A similar tendency was confirmed in the 0.01–1 µm range. Hydration reaction was faster in the insulated gang form than in conventional gang form at low temperatures with no special hydration accelerator added.This is because, due to the development of hydration and pozzolanic reactions, precipitation of the primary and secondary hydration products occurred, filling the pores, and shifting the curve of pore size to a smaller size . PreventAt 28 days of age, more small pores in the 0.01–0.1 µm range were observed in the insulated gang form than in the conventional gang form, indicating superior micropores characteristics than when using the conventional gang form. In particular, pores smaller than 0.05 µm are known to be closely related to concrete strength because they are in the sizes of gel pores and capillary pores, as shown in The pore size distribution has a great impact on the durability of concrete. From the size distribution, large pores have a negative effect on the durability of the concrete. However, when pores are uniformly introduced as in the use of air-entraining (AE) agent, the concrete resistance to freezing and thawing improves.The results showed that the sample that used the insulated gang form exhibited a smaller cumulative pore volume than the samples that used the conventional gang form as the age increased.This experimental result shows the comparative analysis on the cement hydration results according to the insulation performance of the insulated gang form. The analysis according to the secondary cement-product, admixture, and aggregate type is not considered in this result. Further studies need to be conducted reflecting these details in the future.Immediately after concrete pouring, the conventional gang form exhibited a faster decrease in the heat of hydration than the insulated gang form, and the concrete surface temperature dropped below 0 °C at 28 h of age. These results are likely to have a great influence on the initial curing of concrete.The compressive strength of the conventional gang form did not exceed 5 MPa at 3 days of age. However, for the insulated gang form, the compressive strength at 3 days of age exceeded 5 MPa. This greatly contributes to the shortening of the construction period due to the rapid demolding time of the formwork.When the microstructure was analyzed according to the member type, a large amount of unhydrated cement was observed in the conventional gang form at 3 days of age because the hydration reaction was barely performed because of the low temperature. However, in the insulated gang form, ettringite, C-S-H gel, and calcium hydroxide, which are hydration products, were observed in large quantities at 3 days of age. These results indicate that the hydration reaction was further accelerated compared to the case when the conventional gang form was used.As age increased, large pores decreased and pores smaller than 1 µm increased. In addition, the distribution of relatively small pores increased in the insulated gang form compared to that in the conventional gang form. Overall, the insulated gang form exhibited a smaller cumulative pore volume than the conventional gang form as the age increased.The experiment in this study was performed under cold weather conditions with a minimum temperature of −20 °C. When the insulated gang form was applied under such conditions, the temperature history, compressive strength, microstructure, and micropore characteristics of concrete were analyzed. The main results are as follows:Summarizing the results of this study, the use of insulated gang form for the construction of apartment houses in cold winter will result in a denser concrete structure than that with the conventional gang form to ensure the concrete quality in winter.


Public misconceptions about antibiotic use persist despite the efforts of antibiotic awareness campaigns. These campaigns have often followed a top-down approach and have not sought input from the public. Communities need to see antibiotic campaign messages as relevant, accessible and important in order to have an influence on health-seeking behaviour and antibiotic use.To develop a series of evidenced-based infographics (EBIs) on antibiotic use for common infections in children and to evaluate their effectiveness at increasing parents' understanding of antibiotic use and antibiotic resistance.There were three phases to this research. In Phase 1 we set out to identify and summarize scientific evidence for the use of antibiotics for three common infections in children . Phase 2 focused on co-design of a series of prototype EBIs for each infection in focus groups with parents of young children and graphic designers, to test the face and content validity. Phase 3 tested the feasibility of EBIs in increasing parents' understanding about antibiotic use and the perceived relevance of antibiotic resistance in an online survey.n = 998). EBIs improved knowledge by more than a third across the board . Respondents confirmed that EBIs were novel and potentially useful, corroborating our focus group findings.We iteratively co-produced 10 prototype EBIs. Parents found the evidence displayed in the EBIs novel and relevant to their families. Parents did not favour EBIs that were too medically focused. The way the information was displayed influenced their understanding. Parents preferred one health message per EBI. We included eight EBIs in a national survey of parents (Co-designed EBIs have the potential to succinctly change parents' perceptions about antibiotics for acute respiratory tract infections in children. Further research should test EBIs in real-world settings to assess their reach as a potential public-facing intervention.


Antimicrobial resistance (AMR) is an urgent public health issue. The role of medical doctors in proper antibiotic use is crucial. The aim of this study was to evaluate the knowledge and practices of Polish doctors of antimicrobial prescribing and antibiotic resistance. The study group consisted of 504 medical doctors with an average age 32.8 ± 5.9 years, mostly women (65%). The paper questionnaire was developed on the basis of a survey tool developed by the European Centre for Disease Prevention and Control (ECDC) and Public Health England (PHE). According to our study, physicians were aware that: taking antibiotics has side effects, antibiotics cannot be used against viruses, unnecessary use of antibiotics leads to AMR and that healthy people can carry resistant bacteria (each item ≥98% correct responses). Only 47% of respondents knew that the use of antibiotics as growth stimulants in livestock is illegal in the EU. Of the respondents, 98.61% saw the connection between prescribing antibiotics and AMR. However, 65.28% of the respondents reported a lack of appropriate materials on AMR counseling. Nearly 92.5% of participants “never” or “rarely” gave out resources on prudent antibiotic use. Physicians in Poland underestimate the role of hand hygiene in stimulating antibiotic resistance (ABR) (74.4%), while demonstrating satisfying knowledge about antimicrobial use, the clinical application of antimicrobial guidelines and prevention of ABR. However, educational interventions are needed to help lead challenging communication with assertive patients. Appropriate patient resources would be helpful in reaching this goal. Antimicrobial resistance (AMR) is defined as the reduced or eliminated response of microbes to pharmacological treatment which can be intrinsic to species or obtained through complex mechanisms developed through evolutionary processes . UnjustiOn 18 November 2019, marking the European Antibiotic Awareness Day (EAAD) , the EurThe purpose of our study was to evaluate the knowledge and practice of doctors in Poland on antimicrobial prescribing and ABR and to complement the pan-European data released in 2019 by the ECDC and PHE.The study group comprised 504 medical doctors participating in specialization courses at the Center of Postgraduate Medical Education in Warsaw, Poland from November 2019 to March 2020, after the ECDC and PHE released their report.Purpose of the study is consistent with statutory objectives of the Centre of Postgraduate Medical Education (CMKP), which is a Polish public medical university supervised by the Ministry of Health, responsible for conducting, coordinating and controlling postgraduate education of physicians and other selected medical professionals throughout Poland ).The presented study is not considered a medical experiment, so according to Polish law, ethical approval is not required ). The survey used in this study was in line with the ethical standards of the institutional bioethical commission and the Declaration of Helsinki (1964). Although participation in the study was anonymous and voluntary, each surveyed participant expressed consent by filling in the survey.The research tool was a self-administered paper questionnaire prepared on the basis of a Polish translation of the validated tool used by the ECDC and PHE . ECDC anThe questionnaire included basic characteristics of the respondent , professional characteristics , multiple choice questions, questions testing antibiotic knowledge using a true or false answer, and statements assessing attitudes and behaviors towards antibiotics by using a 5-point Likert scale from strongly agree to strongly disagree.The questionnaire was piloted on a sample of 15 respondents working as medical professionals at the School of Public Health, Centre of Postgraduate Medical Education in Warsaw, Poland. As a result of the pilot study, some questions were modified.In Poland, each physician completing specialty training would attend a course in public health. Participation in this course is compulsory. Therefore, participants on the courses represented all medical specialties, from all regions and healthcare institutions all over Poland.Respondents’ knowledge was assessed in nine questions concerning antibiotic use and resistance.Value 1 was assigned to each correct answer, and value 0 to each incorrect answer. Knowledge score was constructed as a sum of scores from all the answers. In total, it was possible to obtain a minimum of zero points and a maximum of nine points. Thus, the antibiotic knowledge score had a positive direction; the higher the score, the better the knowledge of antibiotics.The statistical analyses were performed using STATISTICA 13.1 software . The mean (M) and standard deviation (SD) were estimated for numerical variables, as well as absolute numbers (n) and percentage (%) of the occurrence of items for categorical variables.t test was used to compare one variable in the Likert scale between two groups .Pearson’s chi-square test was used to investigate an association between two categorical variables. Variables in Likert scale or in other ordinal scale and numerical variables were correlated to each other using Spearman’s correlation coefficient. Student’s p < 0.05.The significance level was assumed to be The demographic and professional characteristics of the study group are presented in A total of 504 correctly completed questionnaires filled by medical doctors were included in the study. The participants were aged 25–59 years, 32.8 ± 5.9 years on average, mostly women (65%). The response rate was 81%. Analyzing in 10-year age groups, 30–39-year-old respondents predominated in the study group (58%), followed by 20–29-year-olds (30%), whereas older respondents constituted 11% of the study group. The majority of respondents lived in cities with over 500 thousand residents (54%). The questionnaire was delivered in paper form to physicians attending public health specialization courses at the CMKP.Respondents’ length of work as medical doctors was up to 39 years, with an average of 5.1 ± 5.8 years. Analyzing groups of work seniority, respondents who had been working 1–3 years predominated in the study (58%), followed by respondents who had been working 4–7 years (21%), while 17% of respondents had worked for at least 8 years as medical doctors.The main place of work for most respondents was a public hospital (42%), followed by a clinical hospital (40%). Participants represented all 77 medical specialties recognized in Poland. A total of 81% respondents had no specialization (ongoing), while 15% of respondents had already completed at least one specialization. The majority of respondents already completed or were during training in non-surgical specialization (80%), while 16% were in a surgical one.Furthermore, the majority of respondents correctly answered the following items: “Antibiotic-resistant bacteria can spread from person to person” (94.84%) and “Every person treated with antibiotics is at an increased risk of antibiotic-resistant infection” (89.88%), followed by “The phenomenon of drug resistance in the context of infectious diseases only occurs with bacteria ” (80.95%). An item which received least correct answers was “The use of antibiotics to stimulate growth in farm animals is legal in the EU” (47.02%).Based on nine items regarding antibiotic knowledge from The antibiotic knowledge scores did not correlate with gender, living or not in a large city, specialization status, type of specialization, working or not in a clinical hospital, nor with age and job seniority .The respondents least agreed with the following statements: “I have easy access to materials when I need to give advice on prudent antibiotic use and antibiotic resistance” and “Environmental factors such as wastewater contribute to antibiotic resistance in bacteria for humans”.p = 0.010).Female respondents perceived their role in helping control ABR as key significantly more often than men (4.9 ± 0.4 vs. 4.6 ± 0.6), (p = 0.027).Respondents working in clinical hospitals perceived their access to patient-targeted educational materials on prudent antibiotic use and ABR as less easy (3.5 ± 1.1) than those not working in clinics (3.9 ± 1.1), (p > 0.05) as well as with age and job seniority.The data on antibiotic subjective knowledge presented in p = 0.001 and 0.005, respectively).Too long duration of antibiotic treatments and too many broad-spectrum antibiotics were considered more important for the development of antibiotic resistance in the females’ opinion than in the opinion of men (p > 0.05) or with age and job seniority .The importance of factors responsible for antibiotic resistance did not correlate with specialization status, type of specialization, working in a clinical hospital or living in a large city , age (p = 0.308), job seniority (p = 0.463), specialization status (p = 0.542), type of specialization (p-0.402), working or not in a clinical hospital (p = 0.280), or living in a large city (p = 0.306).The frequency of prescribing or administering antibiotics to patients did not correlate with the respondents’ gender (p = 0.010). The prevalence of the three above-mentioned strategies for rational antibiotic prescribing did not correlate with age, job seniority, specialization status, type of specialization, working or not in a clinical hospital, or living in a large city (p > 0.05).Respondents used the following strategies for antibiotic prescription: the most common—patient education (73.02%), less common—delayed/back-up prescribing , (34.72%) and the least common—new patient consultation (11.90%). Male respondents marked new patient consultation more often ; with ongoing specialization rather than a completed one (67.91% vs. 56.96%), (p = 0.0.44) and in younger respondents (p = 0.010). The prevalence of other reasons why physicians were unable to provide resources to their patients did not correlate with gender, job seniority, type of specialization or working in a clinical hospital (p > 0.05).Only 4.56% of respondents were able to provide their patients with advice or resources as needed. The most common reasons were: the lack of available materials (indicated by 65.28% of respondents) and insufficient time (58.73%). Furthermore, 39.29% of respondents indicated that a patient was not interested in information, 17.86% that a patient did not need such information, 5.16% were not sure what advice to provide, 4.96% indicated difficulty in getting patients to understand the diagnosis, 3.77% indicated language barriers. Lack of materials available was significantly more prevalent among respondents living in large cities rather than villages or towns (69.94% vs. 56.29%), (p = 0.046). The respondents perceived their key role in helping control ABR as more important if they were without specialization (p = 0.040). Female respondents felt more confident in not prescribing antibiotics when not necessary (p = 0.006). The statements regarding some attitudes and behaviors on antibiotic use and antibiotic resistance presented in p > 0.05) or with age and job seniority .Respondents were more confident in making antibiotic prescribing decisions if they did not work in a clinical hospital  were presented by Italian and Jordanian researchers using the same questionnaire tool among prescribers ,18,19. IMost of our respondents declared that they know what antibiotic resistance is . Based on the ECDC/PHE data, 96% of respondents (HCW) know what ABR is, compared to 87% in the study completed in Jordan ,19. SimiRegarding factors promoting antimicrobial resistance, most relevant to our respondents were “too many antibiotic prescriptions” and “too low doses of antibiotics” with scores of 97.22% and 94.64% of respondents agreeing, respectively. According to a 2019 literature review by Chokshi et al., suboptimal hospital surveillance over antibiotics administered in clinics and the use of antimicrobials in animal farming are the biggest contributors to AMR in developed countries . ClinicaOur respondents agreed (90.28% of them) about the key role of physicians in controlling the spread of antimicrobial resistance. Doctors can contribute by encouraging the use of vaccines among patients, reinforcing infection-control procedures, managing antibiotic surveillance, engaging in research on novel therapy agents, promoting good practice of guideline-adherence when prescribing antimicrobials and finally, by educating future generations of health-care workers about AMR ,35,36. IBased on the results of our study, it occurred to us that much focus is needed regarding communication with the public on the inappropriateness of prescribing antibiotics when they are not necessary. Many of our respondents claimed that they do not feel confident in declining the demand for an antibiotic prescription even when it is not supported by clinical evidence. This is especially valid in treatment of acute upper respiratory tract infections (ICD-10 codes J00-J06), which in roughly 80% of cases are caused by viruses . ProblemIt stands out that doctors often feel challenged and unprepared to perform adamant yet amicable in-office communication about antibiotics. Miller et al. recommend focusing in patient–doctor conversations on the individual risks  rather than the societal charge of AMR when disproving unfounded pressure for antimicrobials . AccordiPhysicians in Poland occasionally have contacts with the pharmaceutical industry and cooperate with companies providing medicinal products . At the The study has a number of limitations. Firstly, the meaning of some questions could have been altered in translation to Polish. However, efforts were made to maintain the meaning and pilot-based adjustments were made to keep the Polish version of the questionnaire in line with the ECDC/PHE original. Another limitation is the usefulness of the original ECDC/PHE questionnaire when it is applied to survey exclusively physicians. However, keeping the original format allowed for easier and interesting comparison with the ECDC/PHE report as well as other studies based on the same model released in the meantime . It is worth noting that the ECDC/PHE survey was made online while in our study the participants filled paper forms. While it might pose a minor comparison bias, the outcomes of our research provide a valuable feed for didactic and policy agents in Poland which was our primary goal. Another limitation is the study group which only consisted of physicians undergoing specialty training accounted for 0.35% of over 150,000 physicians with active license in Poland (2019) . That isThe physicians in Poland who participated in this study demonstrated satisfactory knowledge about antimicrobial use, the clinical application of antimicrobial guidelines and the prevention of antibiotic resistance in their respective fields. However, educational interventions for prescribers are needed to help lead challenging communication with patients expecting antibiotics while maintaining unstrained relations. This could be strengthened by equipping doctors with approachable resources for patients on antibiotics and antimicrobial resistance. The One Health approach to the handling of antibiotics as well as hand hygiene in the context of antimicrobial resistance are areas of knowledge which should be highlighted more in continuous medical education for doctors in Poland.The outcomes of this study can be used to address medical education gaps in under- and postgraduate settings as well as to inform creators of information campaigns on AMR targeting prescribers in Poland. It would be optimal to carry out further studies among doctors of specialties which most often prescribe antibiotics in order to explore the topic in more depth.


Differences were observed in the compressive strength and in the modulus of elasticity as well as in the flexural and splitting tensile strength. The flexural tensile strength test was conducted on two different element shapes: square panel and beam samples. These mechanical properties could lead to recommendations for designers of façade elements made of HPFRC.High performance fiber-reinforced concrete (HPFRC) has been frequently investigated in recent years. Plenty of studies have focused on different materials and types of fibers in combination with the concrete matrix. Experimental tests show that fiber dosage improves the energy absorption capacity of concrete and enhances the robustness of concrete elements. Fiber reinforced concrete has also been illustrated to be a material for developing infrastructure sustainability in RC elements like façade plates, columns, beams, or walls. Due to increasing costs of the produced fiber reinforced concrete and to ensure the serviceability limit state of construction elements, there is a demand to analyze the necessary fiber dosage in the concrete composition. It is expected that the surface and length of used fiber in combination with their dosage influence the structure of fresh and hardened concrete. This work presents an investigation of the mechanical parameters of HPFRC with different polymer fiber dosage. Tests were carried out on a mixture with polypropylene and polyvinyl alcohol fiber with dosages of 15, 25, and 35 kg/m Since the development of concrete, RC constructions allow for more and more filigree and lightweight elements with the contemporary growth of structure loads . ReducedRecently, FRC has also been used for the production of pre-cast elements in which the fibers—in combination with ultra-high-performance concrete—enhance the durability of cracked concrete . As stud2 footprint. Without steel rebars, façade panels can be just a few centimeters thick [The possible benefits of using HPFRC are in sustainable resource management. A good example for the use of FRC are façade panels in building constructions, leading to a considerable reduction in the material volume . Therefors thick . For conrs thick .Vertical exterior elements of buildings exposed to environmental factors are investigated for structural performance under gravity and wind load. Concrete elements such as façade panels for certain boundary conditions are under flexural load. The wind pressure is distributed as area load, which causes tensile and compressive stresses in the cross-section of the building’s façade and results in deformation . TherefoTo understand the behavior of HPC and UHPC as well as concrete in general with fiber addition, scientific measurement methods in experimental research study have recently been published . TypicalThe aim of this work was to investigate the influence of fiber addition on the properties of high-performance concrete. As is known from other publications, the addition of fiber does not always have a positive effect on the mechanical properties. Other studies have also focused on other types of fibers in connection with HPFRC. Therefore, in this study, it was proposed to also consider the fiber type and shape variation of the concrete sample. Furthermore, this paper expands the database with an overview of the mechanical properties in HPFRC with polypropylene and polyvinyl alcohol fiber. It is suspected that the surface and length of used fiber influence the structure of fresh and hardened concrete. Optimization and a better quantity of fiber dosage will allow for a reduction and also a better use of the materials in the concrete mix design. Mechanical parameters of HPFRC enable the economical design of filigree, safe, and lightweight elements.In this study, only fine aggregates and particles were used to improve the homogeneity of high-performance concrete . In the In this study, the influence of two fiber types on the fresh concrete and the mechanical properties of hardened concrete is investigated: polypropylene fibers (PP) and polyvinyl alcohol fibers (PVA) see . The cha3 of the MasterFiber 401 (PVA). For comparison with the MasterFiber 235 SPA (PP), Mix ID 2 contained 35 kg/m3. To investigate the influence of the fiber dosage, Mix IDs 3, 4, and 5 contained 25 kg/m3, 15 kg/m3, and 0 kg/m3 of fibers, respectively. The mixtures were prepared by using a 55-L-capacity horizontal forcing type concrete mixer.For this experimental research, five different concrete mixtures with the same amount of cement, aggregates, and additives  were preThe appropriated HPFRC was produced with cement CEM I 42.5 R , quartz In this study, tests were carried out on fresh and hardened high-performance concrete with and without fibers. The compressive strength tests on the hardened concrete were performed on 150 mm cubes according to EN 12390-1 . Cylinde3) in accordance with EN 12467 [3) in accordance with EN 14651 [A test program based on the different fiber dosage was conducted . The fleEN 12467  and beamEN 14651 . For comEN 14651 ,40. For EN 14651   and ID 3 (25 kg/m3) showed similar bending tensile strengths. However, the dosage of fiber quantity for mixtures ID 2 and 3 differed. By comparing these two fiber dosages, an increase in the bending tensile strength of up to 200% was evident. Mixture ID 4 showed increases of up to 84%. The strain of mixture ID 4 measured with the clip gauge reached a plateau. Following this crack initiation, the measured strains increased with higher load capacity. For concrete without fibers (mixture ID 5), the stress–strain curve reached 3.14 MPa, then declined and reached zero.The same results as for the panels were achieved with beams according to EN 14651 . Figure s = 2.336). The correlation of the stress–strain curves showed that with a fiber addition between 15 kg/m3 and 35 kg/m3, the results of LOP were similar. A significant difference was found in the post crack behavior due to the addition of fibers to the mix. The samples with Mix ID 5 failed when the maximum flexural stresses were reached. This means that the CMOD with a value higher than 0.5 mm could not be determined.The test method for fiber reinforced concrete presented in EN 14651  enables ic fiber ,57. The 3 and 35 kg/m3, the maximum bending tensile strength varied between 6.30 MPa and 5.66 MPa for CMOD of 0.5 mm and 9.24 MPa–7.34 MPa for CMOD of 3.5 mm. For the fiber addition of 15 kg/m3, the residual post-cracking strength reached 3.06 MPa for CMOD of 0.5 mm and 4.94 MPa for CMOD of 3.5 mm.Based on experimental stress–strain curves, parameter 3. Although the PP fiber was longer than the PVA fiber, a similar maximum bending tensile strength was achieved with both types of material, regardless of the fiber length. In the study by Yoo [y by Yoo , the auty by Yoo .As tests of the fresh and hardened concrete show, HPFRC is strongly affected by the density of used fiber and the presence of the air voids. The bulk density, compressive strength, and modulus of elasticity decreased with fiber addition. This effect can be attributable to fiber dosage in the concrete mix. Liu et al.  analyzed3, which was not tested in the presented study. Therefore, the conclusion is that the correlation between compressive strength and modulus of elasticity depends on fiber dosage. For further studies, a lower fiber content should be tested.Another tendency showed in some cases of the normal strength concretes where the higher dosage increased compressive strength and modulus of elasticity. Kilmartin-Lynch et al.  tested a3 in comparison to the plain concrete. Rostami et al. [In the experiment, the fiber dosage improved the flexural properties of concrete. The flexural strength increased the maximal 31% for a fiber dosage of 25 kg/mi et al.  reportedi et al.  who repoNot only are the values of the flexural strength reflected in the studies on FRC, but the failure modes for specimens in flexural tests show similarities with other research. Abbas et al.  tested t3 in the concrete composition reduced the compressive strength from 83.2 MPa to 79.6 MPa. The higher fiber dosage showed a similar trend. Furthermore, it reduced compressive strength and the modulus of elasticity of the concrete.The percentage of air voids in the concrete corresponds to the compressive strength and the modulus of elasticity of the concrete. A significant difference was found in the compressive strength of the concrete due to the addition of fibers to the mix. The fiber addition of 15 kg/m3), 6.7 MPa (25 kg/m3), and 6.9 MPa (35 kg/m3).PP and PVA fibers have proven to be effective in increasing the splitting tensile strength of concrete, which allows better utilization of material capacities and has an impact on the production costs of FRC members. The comparison showed that the dosage of fibers increased from 4.0 MPa to 5.0 MPa  and MasterFiber 235 SPA (PP) in the post-crack phase. MasterFiber 235 SPA is intended to be used because of its higher ductility.The bridging effect, which improves the safety of the concrete components, was identified in the bending tensile test. The bending tensile strength of concrete with added fibers increased by up to 18% compared to materials without fibers. Some of the fibers reached their tensile strength and were no longer involved in the transfer of the load. The pull-out effect of the fiber changed the brittle fracture behavior of concrete into the ductility behavior of these materials.3. However, the addition of more than 25 kg/m3 of fibers to the concrete mix had less influence on the bending tensile strength of the concrete. This concrete mix had an overcritical fiber dosage and was characterized by tensile strain-hardening behavior. A comparison of the stress–deflection curves with the addition of 25 kg/m3 and 35 kg/m3 of fibers revealed that the cracking behavior of concrete for these two fiber contents did not differ significantly.In the present study, the highest PP fiber dosage examined in the concrete composition amounted to 35 kg/mFurther study of HPFRC comprises more mechanical experiments. New attempts will be focused on anchorage techniques for façade plates in building construction. A higher load capacity for the steel anchor system with a higher fiber dosage is expected.The objective of this work was to investigate how fiber dosage affects the mechanical parameters of high-performance fiber reinforced concrete. This study allows for the following conclusions to be drawn in the area of material properties:


Is hospital antibiotic exposure associated with multidrug-resistant organism (MDRO) colonization and room environment contamination in nursing homes?Clostridioides difficile infection and by exposure to high-risk World Health Organization Access, Watch, and Reserve antibiotic stewardship framework categories.In this secondary analysis of data from 642 patients enrolled in a prospective cohort study, recent antibiotic exposure was positively associated with both MDRO patient colonization and room environment contamination at nursing home study enrollment. The effect size of these associations increased when antibiotic exposure histories were stratified by risk for The findings suggest that high-risk hospital antibiotic prescribing is a potentially high-value antibiotic stewardship target to reduce MDRO burden in postacute care nursing homes. This secondary analysis of a cohort study characterizes antibiotic exposures across the nursing home patient’s health care continuum and investigates whether recent antibiotic exposure is associated with multidrug-resistant organism colonization and room environment contamination. Little is known about the contribution of hospital antibiotic prescribing to multidrug-resistant organism (MDRO) burden in nursing homes (NHs).To characterize antibiotic exposures across the NH patient’s health care continuum  and to investigate whether recent antibiotic exposure is associated with MDRO colonization and room environment contamination at NH study enrollment.This is a secondary analysis of a prospective cohort study (conducted from 2013-2016) that enrolled NH patients and followed them up for as long as 6 months. The study was conducted in 6 NHs in Michigan among NH patients who were enrolled within 14 days of admission. Clinical metadata abstraction, multi-anatomical site screening, and room environment surveillance for MDROs were conducted at each study visit. Data were analyzed between May 2019 and November 2021.Clostridioides difficile infection (C diffogenic agents), and 2019 World Health Organization Access, Watch, and Reserve (AWARE) antibiotic stewardship framework categories.Antibiotic data were abstracted from NH electronic medical records by trained research staff and characterized by class, route, indication, location of therapy initiation, risk for The primary outcomes were MDRO colonization and MDRO room environment contamination at NH study enrollment, measured using standard microbiology methods. Multivariable logistic regression was used to identify whether antibiotic exposure within 60 days was associated with MDRO burden at NH study enrollment. Additionally, antibiotic exposure data were characterized using descriptive statistics.A total of 642 patients were included . Of these, 422 (65.7%) received 1191 antibiotic exposures: 368 (57.3%) received 971 hospital-associated prescriptions, and 119 (18.5%) received 198 NH-associated prescriptions. Overall, 283 patients (44.1%) received at least 1 C diffogenic agent, and 322 (50.2%) received at least 1 high-risk WHO AWARE antibiotic (watch or reserve agent). More than half of NH patients (364 [56.7%]) and room environments (437 [68.1%]) had MDRO-positive results at enrollment. In multivariable analysis, recent antibiotic exposure was positively associated with baseline MDRO colonization  and MDRO environmental contamination . Exploratory stratification by C diffogenic agent exposure increased the effect size . Likewise, exploratory stratification by exposure to high-risk WHO AWARE antibiotics increased the effect size .The findings of this study suggest that high-risk, hospital-based antibiotics are a potentially high-value target to reduce MDROs in postacute care NHs. This study underscores the potential utility of integrated hospital and NH stewardship programming on regional MDRO epidemiology. Additionally, we evaluated the association of antibiotic exposure within 60 days of study enrollment with baseline NH MDRO colonization and NH room environment contamination, with a focus on high-risk antibiotic stewardship targets, as defined by heightened risk for CDI (C diffogenic agents)26 and by selection for antibiotic resistance, according to the World Health Organization’s (WHO) Access Watch and Reserve (AWARE) antibiotic stewardship framework.28Using data collected from a prospective, longitudinal cohort study of NH patients,16 The parent study conducted MDRO surveillance of patients and their room environment upon enrollment, at days 14 and 30, and monthly thereafter for as long as 6 months or until discharge.16 Patients were eligible if they  provided written informed consent and were enrolled within 14 days of NH admission.16 The parent study was approved by the University of Michigan’s institutional review board, and this secondary analysis was covered by the approval of the parent study. Here, we follow the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.Newly admitted NH patients were enrolled in a prospective, longitudinal cohort study in 6 Michigan NHs between 2013 and 2016.29 and the Physical Self-Maintenance Scale (PSMS) score.30 To understand a patient’s health care trajectory, we used the Minimum Data Set 3.0 at study enrollment and discharge to identify the patient’s locations before NH arrival, discharge destinations, and readmissions to the NH.31Patient characteristics were obtained at study enrollment. Demographic characteristics included the patient’s age, sex, and race. In the parent study, demographic data on patient race  and ethnicity (Hispanic or Latino [6 patients] and non-Hispanic or Latino [396 patients]) were collected by trained research personnel from patient-reported information. We analyzed race using a binary variable of White patients  and patients of other races (Asian and African American). Race and ethnicity data were required to be collected and reported by the funding source. Clinical characteristics included the presence of indwelling devices (feeding tube or urinary catheter), Charlson Comorbidity Index (CCI) score,Frontline study personnel (K.E.G. and B.J.L.) abstracted antibiotic exposure data from NH medical records on enrollment and each follow-up visit. Antibiotic-associated data of interest included the generic name, documented indication, and route of administration. For this study, antivirals, antifungals, topical antibiotics, and ocular antibiotics were excluded owing to low sample size. Additionally, antibiotic dose and duration were not used owing to missing data.33 NH prescriptions identified as a continuation of hospital therapy or associated with a hospital indication were also classified as hospital-associated prescriptions, unless identified as a novel new start. Therefore, antibiotics were classified as NH-associated prescriptions if they were initiated during the patient’s NH stay and were (1) for a new indication; (2) not a continuation of therapy for a prior diagnosis; and/or (3) not an oral transition from a previously intravenous antibiotic. Antibiotics prescribed in alternative locations  were classified as other.Antibiotic data were curated and characterized by an infectious disease physician with antibiotic stewardship expertise (P.K.P.) and an epidemiologist (K.J.G.) using a priori knowledge and prior literature. Antibiotics were classified as hospital-associated prescriptions if they were associated with indications diagnosed during the patient’s hospitalization  was defined as the concurrent prescription of 2 anti-anaerobic agents.38Antibiotics were further characterized using antibiotic stewardship metrics. We categorized antibiotics into their class and subclass. Antibiotics prescribed for skin and soft tissue infection (SSTIs) were subcategorized into complicated or uncomplicated SSTI.26 Patients without exposure to a high-risk C diffogenic agent but with exposure to other antibiotics were classified as having a low-risk antibiotic exposure history. Antibiotics were further classified by the WHO’s 2019 antibiotic classification framework Access, Watch, and Reserve (AWARE).27 Briefly, access antibiotics correspond to common front-line or second-line antibiotics; watch antibiotics indicate high-priority antibiotics with toxic effects or antibiotic resistance concerns; and reserve antibiotics are generally last-line treatments for MDRO infections.28 High-risk antibiotic classifications for study antibiotics are reported in eTable 1 in the Antibiotics were defined as high-risk, C diffogenic agents if they predispose patients to a markedly high-risk of CDI, as per literature. They include fluoroquinolones; third-, fourth-, and fifth-generation cephalosporins; penicillin combinations; lincosamides; and carbapenems.16 Patient wound, suprapubic catheter site, and enteral feeding tube insertion site specimens were collected when present and accessible. Surveillance of high-touch patient room environment sites was also performed at each visit.40 Specimen collection and isolation of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and resistant gram-negative bacilli (R-GNB) were performed using standard microbiology techniques described elsewhere.16 Gram-negative bacilli were classified as R-GNB isolates if they were resistant to 1 or more of the following antibiotics: ceftazidime (30 μg), ceftazidime/clavulanic acid (30 μg/10 μg), ciprofloxacin (5 μg), and imipenem (10 μg).16In the parent study, enrolled patients had their dominant hand, nares, oropharynx, groin, and perianal area cultured for MDRO colonization at each study visit.2 tests or Fisher exact tests (as appropriate) and 2-sample t tests to test for significant differences between subgroups.Descriptive statistics were used to report baseline patient characteristics. To align with our aims, the patient population was stratified by prestudy enrollment antibiotic exposure history. We used χ2 test. We focused analysis on our prespecified high-level antibiotic stewardship classifications to minimize the identification of spurious associations owing to small sample size .Next, we used descriptive statistics to characterize patient antibiotic exposures. For these analyses, we categorized patient antibiotic exposures as a dichotomous variable. Antibiotics were classified by time (preenrollment or during study participation) and location of therapy initiation . To assess whether there were significant differences between hospital- and NH-associated therapies, we compared the characteristics of hospital-associated prescriptions with NH-associated prescriptions using the χNext, to assess whether recent antibiotic exposure was associated with NH MDRO outcomes, we used multivariable logistic regression to investigate whether antibiotic exposure within 60 days of study enrollment was associated with patient colonization and room environment contamination on NH study enrollment. These analyses were performed for the presence of any MDRO and separately for each MDRO .16 All regression analyses were adjusted for clustering by facility. We used 2-tailed P < .05 as the threshold for statistical significance. Data were analyzed between May 2019 and November 2021 using SAS version 9.4 (SAS Institute).For each outcome, we used 2 logistic regression model iterations. The initial model used a dichotomous indicator variable for the patient’s antibiotic exposure history, while the second exploratory model iteration used 2 indicator variables: low-risk and high-risk antibiotic exposure history. For each model, the reference group consisted of patients without antibiotic exposure histories. The exploratory analyses were performed separately for our C diffogenic agent classification schema and our high-risk WHO AWARE exposure history classification schema. The WHO AWARE exposure categories were reclassified into a high-risk exposure framework to simplify interpretation and to account for a small sample size. Briefly, patients with exposure to only access agents were classified as having a low-risk exposure history, while patients with exposure to watch or reserve agents as their highest AWARE category exposure were classified as having a high-risk WHO AWARE exposure history. Each regression model was adjusted for age, sex, race (White vs other), PSMS score, CCI score, indwelling device presence on enrollment, hospital stay longer than 14 days, and NH days to enrollment. Variables were included into the model using a priori knowledge and prior literature.16 A total of 642 patients had nonmissing antibiotic exposure histories and were included in this analysis. The mean age was 74.7 years , 369 (57.5%) were women, and 402 (62.6%) were White individuals. At study enrollment, the median (IQR) CCI score was 2.0 (1.0-4.0), the median (IQR) PSMS score was 13.0 (11.0-17.0), and 66 patients (10.3%) had an indwelling device. Overall, 609 patients (94.9%) were admitted from an acute care hospital to the NH for postacute care. Of these, 60 (9.9%) had hospital stays longer than 14 days. The remaining patients were admitted for long-term care . After right-tail adjustment to 180 days, the median (IQR) NH duration of stay was 28.0 (18.0-50.0) days. The median (IQR) NH days to study enrollment was 6.0 days (3.0-7.0). Patient characteristics stratified by prestudy enrollment antibiotic exposure histories are reported in We enrolled 651 patients in the parent study.Of 642 patients, 422 (65.7%) received 1191 antibiotics, and 373 patients (58.0%) had an antibiotic exposure within 60 days of study enrollment. When stratifying preenrollment exposures by their location of therapy initiation, 355 (55.3%) received 818 hospital-associated prescriptions and 16 (2.5%) received 17 NH-associated prescriptions. In total, 368 patients (57.3%) received 971 hospital-associated prescriptions, and 119 patients (18.5%) received 198 NH-associated prescriptions across their health care continuum. Additionally, 13 patients (2.0%) received 22 antibiotics that were classified as other, either due to alternative prescribing locations (18 antibiotics) or missing data (4 antibiotics).Hospital-associated prescriptions and NH-associated prescriptions were categorized by class and stratified by their location of therapy initiation . Of the We further classified antibiotic exposures using antibiotic stewardship metrics: 38 of 201 SSTI treatments (18.9%) were classified as broad spectrum; 10 (5.0%) were treating complicated SSTIs. Overall, 163 patients (25.4%) received 243 anti-anaerobic antibiotics: there were 5 instances of inappropriate, double anti-anaerobic coverage. When classifying antibiotic exposures by risk for CDI, 283 patients (44.1%) patients received 525 (44.1%) C diffogenic agents. When classifying antibiotic exposures into WHO AWARE framework categories, 100 patients (15.6%) patients received only access antibiotic exposures, 296 (46.1%) received at least 1 watch antibiotic as their highest-risk exposure, and 26 (4.0%) received at least 1 reserve antibiotic. In total, 430 antibiotics (36.1%) were access agents, 733 (61.5%) were watch agents, and 28 (2.4%) were reserve agents. Collectively, 831 (69.8%) antibiotics were classified as a high-risk agent.P < .001). Broad-spectrum coverage for the treatment of SSTIs was often continued from acute care to NHs, as no significant difference was identified between hospital-associated prescriptions and NH-associated prescriptions . No significant difference in anti-anaerobic prescribing was identified between hospital-associated prescriptions and NH-associated prescriptions . High-risk, C diffogenic agents were more prevalent as hospital-associated prescriptions than NH-associated prescriptions . Furthermore, high-risk WHO AWARE antibiotics (watch and reserve agents) were more prevalent as hospital-associated prescriptions than NH-associated prescriptions .To align with our aims, we compared hospital-associated prescriptions with NH prescriptions using high-level antibiotic stewardship metrics. For antibiotics with known routes of administration, oral therapies were less prevalent as hospital-associated prescriptions than NH-associated prescriptions  had an antibiotic exposure within 60 days of NH study enrollment; 245 patients (38.2%) had a C diffogenic agent exposure and 279 (43.5%) had a high-risk, WHO AWARE antibiotic exposure (watch or reserve agent) before study enrollment.Overall, 364 patients (56.7%) were colonized with an MDRO on study enrollment: 104 (16.2%) with MRSA; 214 (33.3%) with VRE; and 205 (31.9%) with an R-GNB . In multP values are reported in eTable 2 in the A total of 437 patient room environments (68.1%) were contaminated on study enrollment: 177 (27.6%) with MRSA; 305 (47.5%) with VRE; and 190 (29.6%) with an R-GNB . In multThis study leveraged data collected from a prospective, longitudinal cohort study to characterize antibiotic exposures across the NH patient’s health care continuum . Our analysis highlighted that antibiotic exposure was common in our postacute care NH patient population. Of particular interest is the observation that most patients with antibiotic exposure were prescribed a high-risk antibiotic, as defined by heightened risk for CDI or the WHO’s AWARE antibiotic stewardship framework. In our population, hospital exposure to high-risk antibiotics was positively associated with baseline NH MDRO outcomes, largely owing to increased risk of VRE colonization and room environment contamination, on comparison with patients without antibiotic exposure histories. Collectively, our results suggest that patients receiving postacute care in NHs are a population with several high-value antibiotic stewardship targets.42 Given reduced antibiotic stewardship oversight, poor discharge documentation, and frequent empirical and broad-spectrum prescribing practices, antibiotic prescribing on discharge to NH is associated with adverse events, including rehospitalization and CDI.44 Alongside the large proportion of patients receiving a hospital-associated prescriptions, nearly one-fifth of enrolled patients received an NH-associated prescription for a new indication during their NH stay, predominantly for UTIs. Previous research demonstrated that NH antibiotic prescribing is often inappropriate, with some estimates surpassing 50%, particularly due to inappropriate urine culturing and treatment of asymptomatic bacteriuria.46 Furthermore, previous work has highlighted the need to study and design high-impact antibiotic stewardship interventions targeting postacute care NH patient populations.48Nearly two-thirds of enrolled NH patients had an antibiotic exposure during their health care continuum. In our study, nearly 60% percent of patients received an antibiotic before study enrollment: virtually all (96%) were associated with a prior hospitalization. Antibiotic prescribing at hospital discharge is common and often suboptimal.15 which can lead to increased susceptibility to CDI,49 sepsis,22 colonization, and intestinal dominance with VRE50 and patient shedding onto their proximal environment.21 Furthermore, our work complements research illustrating that specific antibiotics may predispose patients to a heightened risk for adverse events, such as patient colonization, shedding, and infection.23 Collectively, our observations uniquely link C difficile antibiotic stewardship and global antibiotic stewardship metrics with infection prevention efforts in NHs while supporting the emerging hypothesis that previous hospital exposures  have downstream consequences on regional NH MDRO burden.10Postacute care NH patients were often prescribed antibiotics, predisposing them to a heightened risk of CDI or selection for antibiotic resistance. We found that 44% of antibiotics could be classified as high-risk, C diffogenic agents, while 64% could be classified as high-risk antibiotics prone to selection for antibiotic resistance (per the WHO’s AWARE framework). Prestudy enrollment antibiotic exposure, markedly to either of our high-risk antibiotic categories, was positively associated with MDRO colonization and room environment contamination at NH study enrollment. Analysis of individual organisms demonstrated that the association between antibiotic exposure and our composite MDRO outcome was predominantly associated with the antibiotic exposure’s influence on VRE prevalence. These findings support previous research demonstrating that antibiotics have both short- and long-term effects on the intestinal microbiota,10 Emerging literature has identified that hospital-initiated NH antibiotic stewardship programming can improve NH antibiotic utilization and urine culturing practices.51 For example, a collaborative hospital-initiated, NH antibiotic stewardship intervention identified antibiotic stewardship targets and successfully demonstrated reduced fluoroquinolone (a high-risk C diffogenic agent and WHO watch antibiotic) days of therapy and CDI rates in participating NHs.51 Given the emerging interconnectedness between hospitals and NHs4 and the requirement for NH implementation of antibiotic stewardship programming,47 our research emphasizes the potential utility of applying the horizontal and vertical intervention paradigm52 to improve regional antibiotic utilization, reduce MDRO transmission, and minimize antibiotic-associated adverse events.These observations underscore the potential value of integrating hospital and NH antibiotic stewardship and infection prevention programming.54 Fifth, the determination of clinically relevant differences in hospital- and NH-antibiotic prescription practices requires further in-depth study. Sixth, facility variation in infection prevention and antibiotic stewardship efforts must be considered when evaluating the contribution of antibiotic exposures to MDRO epidemiology. Surveys conducted at our study facilities indicate both similarities and differences in infection prevention and cleaning practices.56 To account for facility-level variations, we adjusted for clustering by facility in our logistic regression models.This study has several limitations. First, antibiotic data were abstracted from the patient’s NH charts. We relied on the accuracy of NH documentation and hospital discharge reports from multiple medical records systems, 2 common sources of data inaccuracy, and thus, we can only make general assumptions about the antibiotic indications. Therefore, we used objective and common antibiotic stewardship metrics such as double anaerobic coverage. Second, the completeness of antibiotic duration data varied, including exposures from hospitalizations and NH stays. Thus, we defined antibiotic exposures by location of therapy initiation to minimize facility-associated biases in prescribing and antibiotic stewardship programming. Third, we did not assess the association between recent prestudy enrollment antibiotic exposures and longitudinal NH MDRO outcomes. Tailored cohort studies that comprehensively collect temporal antibiotic exposure data are needed to elucidate the association of antibiotic exposures with longitudinal MDRO outcomes, including patient shedding, new acquisition, and intrafacility transmission. Fourth, we did not perform room environmental surveillance before patient occupancy, and thus, we cannot directly measure patient shedding. The median (IQR) days from NH admission that patients were enrolled at was 6.0 , plenty of time for shedding to the room environment.In this study, we found that antibiotic use is common in our predominantly post-acute care NH patient population. Most antibiotics were classified as a high-risk exposure, as defined by heightened risk for CDI or according to the WHO’s AWARE antibiotic stewardship framework. Furthermore, we found that recent exposure to high-risk antibiotics was positively associated with MDRO colonization and room environment contamination at NH study enrollment. These findings highlight the potential importance of strengthening hospital and NH programming to improve antibiotic stewardship and reduce MDRO burden. Future research should elucidate the association of antibiotic exposures across a patient’s health care continuum with longitudinal NH MDRO outcomes. Furthermore, future studies should assess whether hospital-based antibiotic stewardship interventions, such as targeting high-risk antibiotics on discharge, produce beneficial downstream effects on regional MDRO epidemiology.


The predicted equation showed a strong relationship with the experimental compressive strength. Therefore, it can be used for the prediction of compressive strength of concrete with industrial waste as a replacement for fine aggregate.Schmidt rebound hammer test was employed in this study as a nondestructive test. This test method has been universally utilized due to its non-destructiveness for quick and easy assessment of material strength properties and quality of concrete of an existing structure. Industrial waste materials  were employed as replacement material for fine aggregates in this study. A normal strength concrete was designed to achieve 35 MPa at 28 days, with industrial waste materials replacing fine aggregate at different percentages , and then cured for 7, 28 and 180 days. The compressive strength values and rebound numbers for all the mixes obtained were correlated, and a regression equation was established between compressive strength and Schmidt rebound number. The correlation result showed an excellent relationship between rebound number and compressive strength of concrete produced in this study at all curing ages, with correlation coefficients of R Nondestructive testing has been widely used in the construction industry to test the properties (strength properties) of materials or structures, the differences in structural defects and characteristics, and the quality of materials and structures during and after construction and within the service life of the structure. This system of testing has been proven to be easy, quick and still gives a reliable result of the tested concrete structure or sample. Above all, it serves various testing purposes beyond being an effective testing tool for inspection and measuring of the strength and quality of hardened concrete or an existing concrete structure . ReboundNevertheless, it is important to understand that several factors should be in place when evaluating concrete structures using the Schmidt rebound hammer test. Factors such as the surface irregularity of sample, space between impact, surface hardness, age of the concrete sample, moisture of sample, presence of void and calibration of Schmidt rebound hammer ,13,20,21Evaluation of compressive strength and other strength properties of concrete using conventional direct tests such as compressive strength testing (using a compressive machine) is expensive, labor-intensive and time-consuming. On the other hand, reported studies have shown that the Schmidt rebound hammer test is reliable in the prediction of concrete strength when used in the correlation between Schmidt rebound hammer result and compressive strength of concrete. However, there are limited studies on concrete samples produced with some industrial waste materials  tested with the nondestructive test method. In this study, the Schmidt rebound hammer was used as a nondestructive test to measure and predict the strength of concrete samples with and without industrial waste material as a replacement for fine aggregate. However, some past studies employed different industrial waste as replacement material to improve the performance of concrete structures ,28,29. DThe use of industrial waste materials such as alum sludge, quarry dust and limestone dust will reduce the excessive consumption of natural river sand, which is being depleted with time. Most studies from the literature focused on existing reinforced structures ,19,23 anFrom the available literature, there is limited experimental study on the use of alum sludge and other industrial waste material as a replacement for fine aggregate to determine concrete strength using a nondestructive method of testing. Thus, this research provides an alternative choice for concrete testing using a nondestructive method (Schmidt rebound hammer test) to predict the compressive strength of concrete, with formulas derived from this study. This study contributes to the prediction of compressive strength of existing concrete with the empirical formula generated using the Schmidt rebound hammer test method. The use of Schmidt rebound hammer tests has been limited in the evaluation of concrete with alum sludge and other industrial waste materials as a replacement for fine aggregate. Thus, it is paramount to have a well-detailed experimental investigation on this industrial waste material using a nondestructive test method. In addition, this study provides further knowledge on the behavior of industrial waste materials introduced in concrete mix and the suitable proportion of these materials to produce concrete with better strength when compared to the control concrete sample. Invariably, the result from this study proves that the Schmidt rebound number can be used for the prediction of compressive strength even when new materials are introduced to the concrete mix. The cement used in this study is ordinary Portland cement that satisfied the specification for ordinary Portland cement according to ASTM C-150 . The finThe physical properties of all materials utilized for the production of concrete are presented in 2O3, K2O and MgO in both alum sludges in low concentrations. For limestone dust, the main element present is calcium oxide, with a concentration of 77.8%, and other elements are present in low concentrations, while quarry dust had silica as its main element with a concentration of 66.8%. It is seen that there are other elements present with very low concentration as shown in The chemical composition of all the materials as fine aggregate is presented in A normal concrete design of 35 MPa according to British Standard BS 8500, 2006 , was adoFirst, several factors were considered before performing the test. A calibration test was performed on the rebound hammer by testing it against the test anvil to have a dependable result, as the manufacturer of this test equipment has indicated. After the calibration was done, the surfaces of the testing concretes were smoothened to have a smoother surface to test on and avoid surface irregularity that could affect result accuracy. The samples were also allowed to dry so that the concrete sample would be free of moisture, which might affect the reading of the Schmidt rebound number. Then a light pressure was applied on the plunger, which released it from its lock position and thereby allowed it to extend to the test position which is a zero reading. After that, the plunger was pressed against the surface of the testing concrete specimen, keeping the rebound hammer perpendicular to the surface of the concrete. Then, a gradual increase in pressure was applied until the hammer impacted a hammer blow, and the plunger was locked to take the reading by pressing the bottom at the side of the equipment. This test was performed on three concrete cubes about 16 times (four times for each cube). One sample had about four blows of the rebound hammer until a consistent reading was achieved; thereafter, an average of the reading was taken see . Table 4The test was performed as specified in BS 1881, part 202 , for the30, while quarry dust in all replacement contents yields an increased strength with an increase in replacement content.The destructive method of compressive strength testing was used to determine the strength of concrete produced without industrial waste (control) and with industrial waste . The graph presented in The result for concrete produced with quarry dust showed an increase in compressive strength at all curing ages as replacement content increased; this behavior was different when compared with alum sludge. It was also observed that quarry dust had a better strength result than alum sludge. The result of the Schmidt rebound hammer test is presented in 30 and both concrete with alum sludge contents, it is seen that result for concrete with quarry dust was higher. This could also be attributed to their compressive strength performance (destructive test method). For limestone dust as a replacement for fine aggregate, it was found that the rebound number increased with an increase in limestone content. This behavior was found at all curing ages with limestone dust content. Among all industrial waste materials used in this study as replacements for fine aggregate, limestone dust had the best rebound hammer value. This behavior was similar to the performance of the concrete in compressive strength (destructive test method) based on the characterization of concrete quality as specified in BS:1881, part 202 [30 with rebound numbers above 30 and 40 is designated to be from a good layer to a very good hard layer. Quarry dust and limestone replacement for fine aggregate had a rebound number above 40 and was graded as very good hard layer concrete. The result of quarry dust as a replacement for fine aggregate presented in part 202 , for rebRn) and compressive strength (cf); these adopted empirical formulas from past studies are presented in Equations (1)–(4) [The relationship between compressive strength and rebound number for all ages is presented graphically in  (1)–(4) . The empEquations (1)–(4), adopted from Aliabdo and Elmoaty , appeare2 = 0.98, R2 = 0.99 and R2 = 0.98 respectively. Thus, the equation from the relationship graph result in Rn = rebound number and cf = compressive strength of concrete (MPa)The presented relationship graphs in ntR) when compared with experimental compressive strength (cf), having a similar strength value for all fine aggregate replacement contents. The derived theoretical compressive strength from Equation (4)  and Equation (5). This shows that the suggested empirical formula from this study (Equation (5)) can be used for the prediction and estimation of compressive strength from rebound number. The suggested equation from this study (Equation (5)) showed a very close relationship with the derived theoretical compressive strength ( Elmoaty ) was alscf). Thus, the suggested empirical formula from Equation (2) showed compressive strength that is somewhat similar to experimental compressive strength (cf). The result from Equation (2) showed a low prediction value at a higher rebound number and a low compressive strength at a low rebound number. The results from nt/fcR) from Rn increases, the ratio of theoretical compressive strength (nt/fcR) increases with an increase in concrete compressive strength (cf) for the predicted empirical formula used and all percentages of replacement of fine aggregate with different industrial waste materials . Similar behavior in correlation was observed in studies by Roknuzzaman et al. [Another equation suggested by Aliabdo and Elmoaty  from Equn et al.  and Alian et al. . The pre30) and experimental compressive strength (C30) have similar compressive strength values with 0.48 as the difference in compressive strength when compared. For AASR5, the difference between theoretical compressive strength and experimental compressive strength is 0.49. This indicates that the empirical formula derived from this study could be used for the prediction of compressive strength.Notwithstanding, it is seen that Aliabdo and Elmoaty  studied A graph of experimental compressive strength against the predicted theoretical compressive strength determined from the empirical formula from this study and the formula adopted from the past study is presented in Furthermore, the theoretical compressive strength from Equation (5) (predicted formula from this study) showed a strong relationship with the experimental compressive strength. Thus, it can be used for the prediction of compressive strength of industrial waste material  replacing fine aggregate for concrete production.All industrial waste materials employed in this study have proved to be good materials for the replacement of fine aggregate in concrete production up to long-term curing age (180 days). Among all the replacement materials, concrete produced with alum sludge waste from a drinking water treatment plant demonstrated impressive results in both destructive and nondestructive test methods. The Schmidt rebound number increases with an increase in industrial waste material and as percentage replacement content of concrete increases. The study also showed that the rebound number value progressively increases with an increase in curing age.The use of Schmidt rebound number for prediction and estimation of compressive strength yields values that are similar to the conventional concrete compressive strength values in this study. Hence, the Schmidt rebound number of the nondestructive test method is a reliable test method for the prediction of compressive strength of concrete.2 = 0.98, R2 = 0.99 and R2 = 0.98. Thus, it can be used for the prediction of the compressive strength of concrete.The proposed correlation showed an excellent relationship between rebound number and compressive strength of concrete produced in this study at all curing ages, with correlation coefficients of RThe effect of industrial waste material on Schmidt rebound number and the relationship between compressive strength and rebound number is studied in this research. The following conclusions are derived based on the result generated from the experimental work and analysis:Industrial waste materials employed in this study have shown some level of improvement in concrete strength and improvement in Schmidt rebound number when compared with the control concrete sample in this study. The experiment did not cover the behavior of concrete when alum sludge, quarry dust and limestone dust replace fine aggregate below 5% or above 15%. Therefore, further investigation on nondestructive test by Schmidt rebound hammer test when alum sludge is used at lower fine aggregate replacement content or replacement content above 15% should be done. Further experimental investigation should be conducted on Schmidt rebound hammer test utilizing alum sludge in different treatment temperatures , to replace cement in concrete production and to further understand the behavior and effect of the waste on concrete rebound number and predicted strength. Other common nondestructive test methods such as ultrasonic pulse velocity (UPV) should be applied using similar materials. Furthermore, a comparison of the Schmidt rebound hammer test method with other nondestructive methods could be studied in the future using industrial waste materials such as alum sludge, quarry dust and limestone dust.