This study is aimed to investigate the effect of carbon nanotubes on the properties of lightweight aggregate concrete containing expanded glass and silica aerogel. Combinations of expanded glass (55%) and hydrophobic silica aerogel particles (45%) were used as lightweight aggregates. Carbon nanotubes were sonicated in the water with polycarboxylate superplasticizer by ultrasonication energy for 3 min. Study results show that incorporating multi-wall carbon nanotubes significantly influences the compressive strength and microstructural performance of aerogel based lightweight concrete. The addition of carbon nanotubes gained almost 41% improvement in compressive strength. SEM image of lightweight concrete shows a homogeneous dispersal of carbon nanotubes within the concrete structure. SEM image of the composite shows presence of C–S–H gel surrounding the carbon nanotubes, which confirms the cites of nanotubes for the higher growth of C–S–H gel. Besides, agglomeration of carbon nanotubes and the presence of ettringites was observed in the transition zone between the silica aerogel and cementitious materials. Additionally, flowability, water absorption, microscopy, X-ray powder diffraction, and semi-adiabatic calorimetry results were analyzed in this study. Carbon nanotubes can be categorized into single-wall carbon nanotube (SWCNT) and multiwall carbon nanotube (MWCNT). Inclusion of small doses of MWCNT can effectively improve the mechanical properties of cementitious composites improving early age and long-term durability2. The reinforcing efficiency of carbon nanotubes can be influenced by several parameters such as type of CNTs3, the concentration of CNT4, dispersion surfactants5, treatment of CNTs7, dispersion technique8, the interaction with cementitious materials and bond strength9, the water–cement ratio11 and geometry of CNTs13. Zou et al.8 and Collins et al.10 reported that ultrasonication energy and polycarboxylate-based superplasticizer could significantly influence the mechanical and microstructural properties of CNT incorporated cementitious composites by optimally dispersing the CNTs within a concrete structure10. Han et al.14 reported that polycarboxylate-based superplasticizer plays a double dispersion mechanism to disperse the cement and CNTs within the composite. Without proper dispersion technique, agglomeration of CNTs can be noticed in the concrete structure due to the strong van der Waals forces and can influence the mechanical and microstructural properties. The improvement in cementitious composites were found different for cement mortar, cement paste, and concrete. The highest improvement in compressive and flexural strength was observed 83.33%15 and 30%16 for cement paste; ~ 35%3 and 28.04%17 for mortar; 38.62% and 38.63% for concrete18, respectively.Nowadays, the use of carbon nanotubes in cementitious materials is getting attention for the improvement of physical and mechanical characteristics. Carbon nanotubes (CNTs) are an allotrope of carbon composed of coaxial hexagonal carbon rings, cylindrical in shape having around 132,000,000:1 length–diameter ratio. The nanoscale diameters and smooth surfaces of CNT’s could affect the early age hydration of cementitious materials19. Silica aerogel is a lightweight thermal insulating material having low density and high specific surface area, allowing its application in many areas20. Expanded glass aggregates is also a thermal conducting material with porous structure21. Lightweight aggregates are 25–35% lighter than the conventionally used aggregates19. However, the strength properties of lightweight aggregates are also much lower than the conventional aggregates; due to this fact, cement composites utilizing lightweight aggregates generally achieve lower mechanical properties and densities22. Mechanical properties of lightweight aggregate concrete also depend on the desired density of the composite; decreasing the density reduces the mechanical properties of composite23. Kurpińska and Ferenc25 investigated the importance of grading of lightweight aggregates. They reported that an optimal graduating of lightweight aggregates could reduce the porosity of lightweight aggregate concrete and improve mechanical performance. Major studies have been presented on the use of lightweight aggregate such as fly ash27, expanded glass aggregate28, silica aerogel21 in cement mortar. A study conducted by Yousefi et al.21 reported a decrease in compressive strength of cement mortar containing expanded glass aggregates, however inclusion of nano titanium dioxide as nanomaterials increased compressive strength by 39.02%.The strength development of cementitious composite also depends on the properties of aggregates and what kind of pozzolanic materials were used. With the increase in the consumption of natural aggregates, researchers are mainly focused on conserving the natural eco-system that leads to the use of lightweight aggregates such as expanded glass aggregates, silica aerogel30. In addition, hydrophobic silica aerogel has lower adhesive properties with water-rich cementitious materials. Several researchers observed the separation gaps between the aerogel and cementitious materials in the transition zone31. CNT is a well-known material for improving mechanical performance and cracks bridging mechanism32. The incorporation of CNT not only bridges the cracks and voids; it can also change the microstructure of hydration products33. Singh et al.34 identified new compounds due to the chemical bonds between the hydrates and carbon nanotubes. Liew et al.35, in their study, suggested that CNTs also provide sites for the growth of C–S–H, and CNT can coat the calcium silicate hydrate and provide a larger contact area between the hydration product and CNT. As a result, stronger bonds are created between them, which significantly helps to improve the mechanical properties of cementitious composites35.Similarly, hydrophobic silica aerogel is also a very lightweight and brittle material, and its incorporation in concrete results in a decrease in mechanical performanceIn this study, several lightweight concrete samples were prepared with different doses of CNTs. Expanded glass aggregates and hydrophobic silica aerogel were used as lightweight aggregates. Microscopy of the composite was deeply analyzed, especially surrounding the hydrophobic aerogel particles. The main aim was to improve the strength property of aerogel concrete by reducing the separation gaps between silica aerogel and cementitious materials. This is the first study that presents the use of CNTs to enhance the compressive strength property of lightweight concrete prepared with expanded glass aggregates and hydrophobic silica aerogel. The study also investigates fluidity, water absorption, and microstructural analysis.8, treatment of CNTs36, water-cement ratio37, the concentration of CNTs38, and types of fine fillers39. Mostly studied literature41 illustrates that the incorporation of CNTs reduced the flowability of cementitious composites. While there are several studies that indicate the increase in flowability of CNT incorporated cementitious composites42. Besides, the incorporation of silica aerogel also reduces the flowability of cementitious composites20. The results of the present study revealed that the flowability of CNT-LWAC was influenced by the quantity of CNT. The flowability of CNT-LWAC decreases with the escalating doses of CNTs. Almost a 17% reduction in flowability was measured for lightweight concrete specimen prepared with 0.6 wt% CNT. The flowability of CNT-LWAC specimens is shown in Fig. 32.The flowability of cementitious composites containing CNT depends on several parameters like ultrasonication energy20. The addition of CNTs to the cement paste having aerogel produced slightly higher heat as indicated in samples SA-3 and SA-4 and shortened setting time compared to sample SA-2. Besides, by increasing the concentration of CNTs, slightly high heat of the exothermic reaction was noticed.Figure 45. However, the incorporation of small doses of CNTs to the aerogel based lightweight concrete significantly increased the compressive strength. The increase in compressive strength can be attributed to the nucleating effects and improvement in the microstructure of CNT-LWAC. The C–S–H gel was identified surrounding the CNTs, moreover, hydration products and CNTs fill the micro crack/gaps of the lightweight concrete to provide additional support and increase compressive strength. Detailed discussion is given in section “Scanning electronic microscopy (SEM) of CNT-LWAC”. The literature studies confirm that the incorporation of nanoparticles improves the microstructure and provides a denser concrete structure32. The confidence intervals for compressive strength are presented in Fig. Figure 46, and Leonavičius et al.47 reported that at a lower concentration of CNTs, total pore volume was observed reducing attributed to filling of voids that lead to a reduction in water absorption. According to Leonavičius et al.47 and Kordkheili et al.48 high concentration of CNTs in concrete results in a more porous structure and reduces the mechanical performance of concrete48. In the present study, all nanocomposite concrete specimens showed a marginal decrease in water absorption rate by an increase in the concentration of CNTs. The reduction in water absorption can be attributed to the association of CNTs with the lightweight concrete that helped in decreasing the micropores and produced the denser concrete structure. Besides, a comparatively higher water absorption rate was observed than Leonavičius et al.47 and Kordkheili et al.48 due to the use of expanded glass aggregates in the study. Expanded glass aggregates are porous in structure that can absorb water up to 20–25%, attributed to an increase in water absorption.Figure 50 also indicate the brittleness of aerogel and a decrease in the mechanical performances with the incorporation of aerogel.The plain image of hydrophobic silica aerogel in Fig. 31 and Adhikary et al.20. While better adhesion was observed for expanded glass aggregates with cementitious materials, as indicated in Fig. Due to the hydrophobic nature of silica aerogel, it do not develop chemical bonds with the hydrophilic cement matrix. Figure 8, Vesmawala et al.5, and Collins et al.10 also reported that CNTs could be effectively dispersed within the concrete structure by ultrasonication energy and polycarboxylate superplasticizer, may be due to this fact high agglomeration of CNTs was not noticed. Unlikely in the present study, the needle-like structure of ettringite was observed along with the agglomeration of CNTs in the transition zone of aerogel, as shown in Fig. SEM image of CNT-LWAC, as shown in Fig. 45 suggested that due to the hydration process of cementitious materials, aerogel particles can slightly react with the pore solution and get partially dissolved in an alkaline environment to form C–S–H with a low Ca/Si ratio. de Fátima Júlio et al.51 and Hai-li et al.52 reported that aerogel particles could promote hydration due to high surface activity that leads to ASR, and Si–O–Si might form C–S–H. Incorporation of CNTs to the cement composite also provides sites for the formation of calcium silicate hydrate (C–S–H) by acting as a nucleating agent54. The honeycomb structure of C–S–H gel and its presence near to the CNTs can easily be observed in Figs. Zhu et al.2 at around 2θ = 22 and 23 °C for silica aerogel and expanded glass aggregates, respectively. In Fig. 55.Figures 56 standard, and 50 μm size (average particle size) zeolite powder was used as a pozzolanic additive. A total of 500 kg/m3 binding materials was used to prepare lightweight concrete samples, where 90% volume consists of cement and 10% consists of zeolite. The chemical composition of cement and zeolite are shown in Table 57 was followed for the combinations of four different sizes of expanded glass aggregates, and 1–2 mm size irregular shaped hydrophobic silica aerogel particles with bulk density 70 kg/m3 holding the approval No. Z-3.212-1948 from the DIBt—German Institute of Construction Technology were used as lightweight aggregates. The concrete specimens were prepared with 45% volume of total aggregates of silica aerogel having 70 kg/m3 bulk density while the rest of 55% of aggregate contains a combination of 1–2 mm, 0.5–1 mm, 0.25–0.50 mm, and 0.1–0.3 mm size expanded glass aggregates. The physical properties of expanded glass aggregates are shown in Table 2/g, and density was approximately 0.15 g/cm3. Resistivity was observed at 1412 μΩm. MWCNT was synthesized by the chemical vapor deposition (CVD) technique. Multiwall-carbon nanotubes (MWCNTs) were used as nanofibers to enhance the mechanical performance of the lightweight aggregate concrete. The properties of MWCNTs are shown in Table For the preparation of lightweight concrete specimens, ordinary Portland cement (OPC) of grade CEM I 42.4R was used as binding materials according to EN 197-1:2011The dispersion of carbon nanotubes in the cement matrix is more challenging than in the conventional concrete mixture. Due to the reliable van der Waals forces between carbon nanotubes, it is necessary to maintain the separation of aggregated carbon nanotube bundles to protect cement composites from defects. In this study, carbon nanotubes were sonicated separately in water by ultrasonication energy  with polycarboxylate based superplasticizer for 3 min. Ultrasonic treatment was carried out by Bandelin Electronic ultrasonic converter UW 3400 of 200 W power and 20 kHz frequency. After mixing lightweight concrete composition with 60% total water, sonicated carbon nanotubes liquid was added to the concrete mixture and manually mixed for another 5 min. After the final mixing process, the flowability test was carried out, and concrete samples were molded into 16 × 4 × 4 cm size prisms and kept at room temperature for 24 h for the hardening process. After the setting process, concrete samples were demolded and kept immersed in water until the 28th day of the hydration process in the climatic chamber, having more than 95% RH and 20 ± 1 °C temperature. The mixing composition of the lightweight concrete samples is shown in Table 58 standard requirements. For each type of concrete specimen, three times a flow table test was performed, and the mean value was taken as a result.The flowability of the CNT-LWAC was performed by flow table test satisfying EN 12350-5:200959 standard requirements. The mean value of three specimens was taken as a result of each type of concrete sample.Compressive strength of CNT-LWAC was measured on the 28th day of the curing process, satisfying BS EN 196-1:2016Water absorption kinetics observation of the lightweight aggregate concrete specimens reveals the increase in water absorption rate on the 28th day of hydration. LWAC specimens were oven-dried at 105 °C after the 28 days of hydration and immersed in water for 15 min, 1 h, 24 h, and 48 h to observe water absorption in the LWAC specimens.To perform a semi-adiabatic calorimetry test, several mortar samples were prepared with cement and aerogel containing different concentrations of CNTs. CNTs were sonicated in water for 3 min before mixing with the cement. Table Scanning electronic microscopy of CNT-LWAC was analyzed by a high-resolution electronic microscope FEI Quanta 200 FEG with Schottky field emission gun (FEG), an energy-dispersive X-ray spectrometer (EDS) with a silicon type drift droplet detector.The X-ray diffraction analysis of the composite specimens was performed with X-ray diffractometer DRON-6 with Bragg–Brentano geometry using Ni-filtered Cu Kα radiation and graphite monochromator, operating with the voltage of 30 kV and emission current of 20 mA. The step-scan was performed from the angular range 2°–70° (2θ), and each step of 2θ was 0.02°.The flowability of CNTLWAC was decreased by increasing the concentration of CNTs. At 0.6 wt% of CNT loading, an almost 17% reduction in flowability was measured for the lightweight concrete specimen.The utilization of CNTs significantly improved the compressive strength of the aerogel added lightweight concrete. Almost 41% improvement in the strength of lightweight concrete was observed at 0.6 wt% CNTs loading.The dispersion technique of CNTs by sonication with water and polycarboxylate based superplasticizer worked almost effectively to disperse the CNTs within the concrete structure. However, some agglomerations were identified in the transition zone of aerogel.CNTs were found to promote the growth of C–S–H, portlandite, and calcite. The study revealed the presence of more hydration products surrounding the CNTs.Separation gaps were identified in the transition zone between the hydrophobic silica aerogel and cementitious materials for the control specimen. The utilization of CNTs effectively helped to reduce the separation gaps by filling the voids and gaps. Moreover, the nucleating effects of CNTs were noticed; separations gaps and voids were not only filled by CNTs, but hydration products were also found in the gaps.Study results analyses the viability of using MWCNTs to improve the compressive strength of lightweight aggregate concrete prepared by silica aerogel and expanded glass aggregates. The following conclusions can be drawn based on the obtained results.


To review community-level consumption of antibiotics in rural Vietnam, according to the WHO Access, Watch, Reserve (AWaRe) classification of 2019, and identify factors associated with the choice of these antibiotics.In this cross-sectional study, data on antibiotic purchases were collected through a customer exit survey of 20 community antibiotic suppliers in Ba Vi District, Hanoi, between September 2017 and July 2018. Antibiotic consumption was estimated through the number of antibiotic encounters, the number of DDDs supplied and the number of treatment days (DOTs) with antibiotics, and analysed according to the AWaRe classification. The factors associated with watch-group antibiotic supply were identified through multivariable logistic regression analysis.P < 0.001), non-prescription antibiotic sale  and children .In total, there were 1342 antibiotic encounters, with access-group antibiotics supplied in 792 encounters (59.0%), watch-group antibiotics supplied in 527 encounters (39.3%) and not-recommended antibiotics supplied in 23 encounters (1.7%). No reserve-group antibiotics were supplied. In children, the consumption of watch-group antibiotics dominated in all three measures . Factors associated with a higher likelihood of watch-group antibiotic supply were: private pharmacy (OR, 4.23; 95% CI, 2.8–6.38; High consumption of watch-group antibiotics was observed, especially for use in children. The frequent supply of watch-group antibiotics at private pharmacies reconfirms the need for implementing pharmacy-targeted interventions in Vietnam. This reform also led to an increased number of private pharmacies and drug sellers, and unregulated access to antibiotics.,At the 21st meeting of the WHO Expert Committee on the Selection and Use of Essential Medicines in 2017 the WHO Model List of Essential Medicines (EML) and the Model List of Essential Medicines for Children (EMLc) were reviewed and updated.,This classification has been used in several antibiotic-use studies to review the current levels of the use of watch- and reserve-group antibiotics in different settings.Therefore, we conducted this study to assess community-level antibiotic consumption according to the WHO AWaRe groups and to identify the factors associated with the choice of watch- and reserve-group antibiotics in a rural area in Vietnam, an LMIC in Southeast Asia.This cross-sectional study was part of the ABACUS (AntiBiotic Access and Use) study.2 and has a population of 274 000 people within 31 communes. The healthcare system includes a district hospital with 300 beds, 3 public polyclinics and 31 commune health stations and village health workers, as well as private facilities and pharmacies.Our study used data collected through face-to-face customer exit surveys at 20 antibiotic suppliers, between September 2017 and July 2018, in Ba Vi District, located 60 km west of the centre of Hanoi, Vietnam. It covers 410 kmIn Ba Vi District, 20 of 502 antibiotic suppliers were selected for customer exit interviews. The selection was based on highest rank in number of daily antibiotic encounters. Four suppliers refused to participate in the survey at our first invitation and were replaced by four other suppliers. The final selected suppliers included 5 drug outlets in public health settings  and 15 private pharmacies. To limit biases caused by seasonal variations, the survey was performed four times over a 1 year period between September 2017 and July 2018. We selected 30 encounters per supplier from 20 suppliers to represent the study population, based on WHO and International Network for Rational Use of Drugs (WHO/INRUD) methodology.At the selected suppliers, each customer who left the pharmacy during one of the four 3 day data collection phases was approached and asked whether antibiotics had been supplied to them. In the case of an antibiotic encounter, the customer was asked to participate in the customer exit interview. To be included in the study, customers had to be willing to disclose whether antibiotics were supplied to them and consent to participate in an interview. Recruitment of participants was stopped when either the end of that survey round was reached or 30 customers with antibiotic encounters were recruited.JAC-AMR Online). Antibiotic purchases for children were defined according to the respondent’s report, with no pre-specified age range. All of the interviews were conducted by field workers of the FilaBavi Health Demographic and Surveillance Site, who had previous experience in data collection and were trained on the content of the questionnaire as well as interview skills. The REDCap data management platform (redcap.core.wits.ac.za) was used for data collection.Demographics of antibiotic purchasers, antibiotic supply  and self-reported health conditions for requesting antibiotics  were collected from antibiotic purchasers through face-to-face interviews using a structured questionnaire . For each antibiotic encounter, the number of DDDs was measured through the number of standard units supplied, the strength of antibiotic products and the DDD assigned for each drug by the WHO Collaborating Centre and the WHO International Working Group on Drug Statistics Methodology. In this study, we applied the DDD for both adults and children since the DDD database for children has not been created. For DOT measurement, the number of DOTs was defined according to the respondent’s report.The patterns of use were described according to the 2019 WHO AWaRe antibiotic classification, in which antibiotics were classified into four groups: access, watch, reserve and not recommended.,We performed multivariable logistic regression analysis to review the factors associated with the choice of watch- and reserve-group antibiotics because both of them are recommended by WHO as key targets of antibiotic stewardship programmes and monitoring.R version 3.5.1 was used for all data analyses.The study protocol was reviewed by the Oxford University Tropical Research Ethics Committee  and the National Vietnamese ethical committees [Vietnam Ministry of Health (MoH) Institutional Review Board (IRB) (6670/QD-BYT)] and the Ethical Committee of Hanoi Medical University (No. 195/HMU IRB).A total of 1404 antibiotic encounters were included in this study, of which 1342 antibiotic encounters were related to human use. Customers’ characteristics from these 1342 antibiotic encounters are presented in In addition to comparing antibiotic consumption by WHO AWaRE antibiotic groups, we performed an analysis of the consumption of different chemical classes of antibiotics (according to the 4th level WHO ATC classification) . The fivP < 0.001), antibiotic purchase for children , private pharmacies , dental symptoms  and urinary tract symptoms  were associated with a more frequent supply of watch-group antibiotics  and first-generation cephalosporins  were the most frequently purchased in a rural community in Vietnam, comprising nearly 60% of total antibiotic use by all three measures. This is similar to what was observed in a previous study, in which the three most commonly sold antibiotics in rural pharmacies in Vietnam were amoxicillin (27%), cefalexin (20%) and ampicillin (12%).Clostridioides difficile infection.,Streptococcus pneumoniae, especially in Asian countries.,S. pneumoniae collected from five major teaching hospitals, the rate of macrolide-resistant S. pneumoniae was over 90%.Around 40% of customers in our study population were treated with watch-group antibiotics, including oral second- and third-generation cephalosporins , macrolides  and fluoroquinolones (levofloxacin and ciprofloxacin). Because of higher resistance potential, the use of watch-group antibiotics is only recommended as first- or second-choice treatments for a limited number of indications.et al.,Another important finding of this study is the significantly higher proportion of use of watch-group antibiotics for children , confirmed to increase the likelihood of watch-group antibiotic supply in our multivariate analysis. This proportion is higher than observed in a study by Hsia ,,,,Although antibiotic supply without valid prescription is illegal in Vietnam, more than 90% of antibiotic dispensations in private pharmacies in rural areas were without prescription.,This study has several strengths. First, to our knowledge, this is among the first studies applying the 2019 WHO AWaRe classification in an analysis of antibiotic consumption in an LMIC. Compared with the 2017 classification, this updated version expanded the classification to cover non-essential antibiotics. Therefore, this minimizes the frequency of unclassified antibiotics in our study, which was commonly seen in previous studies.,This study is limited by the fact that it was conducted in only the 20 largest antibiotic suppliers in one rural district. Therefore, our results may not be representative of smaller suppliers, urban communities or other parts of Vietnam. In addition, the frequency of watch-group antibiotics dispensed by large suppliers may be higher because their customers may have more severe health issues than customers of small suppliers. Our small sample size (1342), compared with the expected sample size (2400), also affects the generalizability of this study (see In conclusion, although access-group antibiotics were the most commonly used antibiotics in community pharmacies in a rural area in Vietnam, the consumption level of watch-group antibiotics is remarkably high, especially among children. The factors significantly associated with a higher chance of supplying watch-group antibiotics were private pharmacy, non-prescription antibiotic supply and antibiotic sales for children. These findings elaborate earlier reports and confirm existing concerns regarding inappropriate antibiotic dispensing in rural Vietnam, which may be similar in other LMICs. There is an urgent need for pharmacy-targeted interventions to tackle this problem.dlaa048_Supplementary_DataClick here for additional data file.


During compaction of a concrete mix, when thin slabs are formed in a horizontal position, the components of this mix become segregated. Heavy components fall to the bottom, and light components (air and water) move to the top. This process may suggest that the upper layers of concrete elements formed in a horizontal position may have lower compressive strength than the remaining part of the element. This problem is recognized and documented in many publications, but there was a publication whose test results indicate a lack of variability in the compressive strength of concrete across the thickness of tested elements. The discrepancies appearing in the evaluation of concrete homogeneity was the reason for conducting destructive tests of the compressive strength of concrete across the thickness of horizontally concreted test elements that imitate thin slabs. The obtained results of the destructive compressive strength confirmed previous results regarding the heterogeneity of concrete. They clearly indicate that there is a differentiation of the compressive strength of concrete across the thickness of a thin element, which remained in a liquefied state for a certain time during its formation. The longer the duration of this state across the entire thickness of the formed element, the greater the differentiation of the compressive strength between the top and bottom layers. Thin horizontally formed concrete slabs include industrial floors, the thickness of which does not exceed 30 cm, with 20 cm often being sufficient. Monolithic ceiling slabs installed in buildings, especially residential ones, are thin and have a thickness of up to 20 cm. It is necessary to distinguish thin slabs from those that are relatively thick, e.g., ones with beams and binding joists, the thickness of which usually exceeds 30 cm. Thick elements and columns are formed in layers, whereas the execution of floors and monolithic ceiling slabs depends on the decision of the contractor. This is important due to the segregation of components in the concrete mix, which takes place during the vibration that causes its liquefaction. Heavy components fall to the bottom, and light components (air and water) move to the top. In elements formed in layers, the weakest top zone in the layer, which is already compacted, mixes with the strongest bottom zone of the subsequent layer. This causes the differentiation of the compressive strength of the concrete to be reduced to some extent, i.e., homogenization of the concrete. The described process appeared in the research presented in the publication . The resThe reasons presented above became the basis for the further analysis of the generally available literature regarding this topic, as well as for the undertaking of research that aims to explain the apparent contradiction. Compressive strength in horizontally formed concrete increases towards the bottom layer of the element . SimilarIn studies ,14,15,16The considered value of compressive strength and its variability across the structure’s height can be influenced by various factors, including the method of compaction, vibration time, consistency of the concrete mix, aggregate type, etc. Therefore, the testing of compressive strength on core samples for cores with various diameters was planned, and the sample elements for the tests were made with different compositions and by using different compaction technologies.In order to verify the variation of the compressive strength of concrete tested using the destructive method across the thickness of a horizontally formed sample element, a research project was undertaken in which the following was planned:I. The development of recipes of concrete mixes for concrete within three compressive strength ranges: 20 MPa, 40 MPa and 60 MPa. Cement CEM II/B-V 32,5R;Clean natural aggregate, grain size 0 ÷ 2 mm (river sand);Clean natural aggregate, grain size 0 ÷ 16 mm (gravel from the mine);Potable water taken from the municipal waterlines;Plasticizer FK-88.In order to make the concrete mixes for the three concretes with the assumed compressive strengths, the following was used:The compressive strength test was conducted according to standard  on standII. The execution of sample elements (thin slabs) with a thickness of 260 mm using three compaction methods: Compaction Method A—the vibrating of the concrete mix with a frequency of 50 Hz on a vibration table, the concrete mix being implemented in two layers, and the vibration taking 2 min for each layer with a time interval of 5 min; Compaction Method B—the vibrating of the concrete mix with a frequency of 50 Hz on the vibration table, the concrete mix being implemented in two layers, and the vibration taking 6 min for each layer with a time interval of 5 min; and Compaction Method C—the vibrating of the concrete mix with a frequency of 300 Hz for a period of 5 min using an immersion vibrator with ϕ 38 mm.III. The testing of the core samples with a height-to-diameter ratio equal to 1, which were cut from the core samples according to the concreting direction : The sam29.5 mm ;47 mm ;130 mm (center of the slab);213 mm ;230.5 mm .Since the sample elements from which the core samples were taken were 260 mm high, the compressive strength of the concrete was tested in the following layers measured from the bottom of the element :29.5 mm In the executed sample elements, the compressive strength was tested at five different levels, from which five core samples were taken for each diameter. A disadvantage of the chosen method was the fact that the extreme bottom and top layers, each 29.5 mm thick, were not tested, and these are the areas where the biggest dispersion of compressive strength might be expected.In order to determine the compressive strength of the core samples, steel disks with neoprene pads  accordinIn order to compare the compressive strength of the concrete at different levels, the values of the average compressive strength were calculated for five core samples (with a diameter of 59 mm and 94 mm) taken from each layer of the slab.The biggest differentiation of compressive strength across the thickness of the tested element made of 20 MPa concrete, which was determined for the core samples with a diameter of 94 mm, was registered in the case of using Compaction Method B on the vibration table:The greatest difference in the compressive strength of concrete between the extreme measurement planes is as high as 11.93 MPa. This means that the top part of the element is weaker than the bottom part of the element by 40.2%. The reduction of the dimensions of the core samples causes an increase in the distance between the measurement planes.The biggest differentiation of compressive strength across the thickness of the tested element made of 20 MPa concrete, which was determined for the core samples with a diameter of 59 mm, were registered in the case of using Compaction Method B on the vibration table:The above-mentioned results clearly indicate that the level of differentiation of compressive strength between the bottom and surface layers of the slab is affected by the method of compacting the concrete mix and also by the vibration time. Moreover, assuming that concrete at the height of the slab cross-section is homogenous is a distortion of reality.The consistency of the 40 MPa concrete mix was less fluid due to it being of class S1. Compaction Method A:Compaction Method B:Compaction Method C:Differentiation of compressive strength across the thickness of the tested element made of 40 MPa concrete, which was determined on the core samples with a diameter of 59 mm, is as follows:It is more difficult to transform less plastic concrete into a fluid state, and therefore the process of concrete component segregation is weaker. The reduction of the compressive strength of concrete in the top layer is then much lower and can amount to between 18.0% and 27.5%.The concrete with the highest compressive strength of 60 MPa also had S1 consistency but was less fluid. Compaction Method A:Compaction Method B:Compaction Method C:Differentiation of compressive strength across the thickness of the tested element made of 60 MPa concrete, which was determined on the core samples with a diameter of 59 mm is as follows:In the case of the concrete with a barely fluid consistency, the differentiation of compressive strength across the thickness of the sample elements was even lower and ranged from 16.7% to 27.4%.The figures presented above result from testing the compressive strength of concrete. The tests were conducted on core samples with different diameters, which were taken from thin slabs made of concrete that had different compressive strengths, differently compacted and formed of concrete mixes with different consistencies. The purpose of the completed research project was to verify previous test results  indicateThe authors’ tests were performed on core samples taken from nine sample elements, which were formed in a way similar to that of executing actual building elements. The concrete’s parameters , which change during the preparation and compaction of the concrete mix, were intentionally changed.The results obtained from the destructive compressive strength tests confirm previous results from ultrasonic tests. They clearly and unequivocally indicate that concretes with a high W/C ratio and significant plasticity show considerable differentiation of their compressive strength across the thickness of a thin sample element, during which formation remained in a liquefied state for a certain time. The longer this state lasts across the entire thickness of the formed element, the greater the differentiation of compressive strength that occurs between the top and bottom layers. The tests proved that the greatest weakening of the top layer was as much as 41.2%.The designer chooses the different safety formats   within tThe concretes made of a less fluid concrete mix did not achieve such a high differentiation of compressive strength across their thickness (the weakening of the top layer ranged from 18.0% to 27.5%). In the concretes with a very low W/C ratio  and dry consistency, the differentiation of compressive strength between the bottom and top layers only ranged from 16.7% to 27.4%. In order to reduce the differences in the compressive strength across the thickness of a slab, it is necessary to ensure an appropriate consistency and also a W/C ratio that will not liquefy the concrete mix. Thin structural elements made of concrete must be carefully formed by contractors who have experience in pouring and compacting concrete mixes.It is unfortunate that there are researchers (such as those mentioned at the beginning of the paper) who, on the basis of one experiment (one sample element), try to disqualify test results concerning the homogeneity of concrete. These results can be found in many sources and have been confirmed and verified many times using various methods.The systematic variability of concrete, unlike the random variability, should be evaluated using other parameters that refer to the differentiation of the compressive strength of concrete across the thickness of a slab or floor, e.g., the compressive strength gradient, as proposed in publication .The confirmed differentiation of the compressive strength across the thickness of thin concrete slabs should be taken into account when determining the compressive strength of concrete in a structure. Compressive strength should be determined on the basis of core samples taken from different layers of concrete slabs.


Heroin and methamphetamine are both popular illicit drugs in China. Previous clinical data showed that habitual users of either heroin or methamphetamine abuse the other drug for substitution in case of unavailability of their preferred drug. The present study aimed to observe whether heroin can substitute the methamphetamine reinforcement effect in rats, and vice versa. Rats were trained to self-administer heroin or methamphetamine (both 50 μg/kg/infusion) under an FR1 reinforcing schedule for 10 days. After having extracted the dose–effect curve of the two drugs, we administered methamphetamine at different doses (12.5–200 μg/kg/infusion) to replace heroin during the period of self-administration, and vice versa. The heroin dose–effect curve showed an inverted U-shaped trend, and the total intake dose of heroin significantly increased when the training dose increased from 50 to 100 or 200 μg/kg/infusion. Following replacement with methamphetamine, the total dose–effect curve shifted leftwards and upwards. By contrast, although the dose–effect curve of methamphetamine also showed an inverted U-shaped trend, the total dose of methamphetamine significantly decreased when the training dose decreased from 50 to 25 μg/kg/infusion; conversely, when the methamphetamine training dose increased, the total dose did not change significantly. The total dose–effect curve shifted rightwards after heroin was substituted with methamphetamine. Although heroin and methamphetamine had their own independent reward effects, low doses of methamphetamine can replace the heroin reward effect, while high doses of heroin can replace the methamphetamine reward effect. These results demonstrated that heroin and methamphetamine can substitute each other in terms of reinforcement effects in rats. Drug abuse remains a significant public health concern in China and worldwide. The 2016 Annual National Drug Report of China counted about 2.95 million drug abusers registered in China; moreover, real drug users were estimated to be more than 14 million . PreviouHeroin is a µ-opioid receptor agonist that mimics the effects of endogenous opioids, resulting in euphoria, analgesia, and sedation . On the The present study investigates whether heroin and MA can substitute each other in terms of reinforcement effect in rats. First, we observed whether MA could replace heroin reinforcement effects in heroin intravenous self-administered rats. Second, we evaluated whether heroin could substitute MA reinforcement effects in MA self-administered rats.ad libitum. To simulate the rodents’ natural state, all experiments were conducted during the dark phase of the light–dark cycle (lights on from 7:30 am to 6:30 pm). We performed the experiments following the Guide for the Care and Use of Laboratory Animals by the National Institutes of Health (8th edition).Male Sprague–Dawley rats initially weighing 260 to 300 g were individually housed in a temperature-controlled and ventilated colony room, with food and water available We used heroin (diacetylmorphine HCl) and D-methamphetamine — obtained from the National Institute of Forensic Science  — dissolved in sterile 0.9% physiological saline.The rats were anesthetized with sodium pentobarbital  and implanted with chronically indwelling jugular catheters as previously described , 14. TheThe rats were trained to self-administer heroin or MA in operant chambers following an FR1 schedule for 4 h/d during 10 consecutive days. Every session started with a blue light inside the “active” nose-poke hole. The rat received a single infusion following a nose-poke inside the “active” hole based on an FR1 schedule. Each infusion was paired with 5 s of illumination at room light, as well as with the noise from the infusion pump, as a discrete conditioned stimulus (CS). Further, we set a timeout period of 20 s during which the response produced no programmed consequences but was still recorded. Illumination of the blue light in the “active” nose-poke signaled the end of the timeout period. Nose-poking in the “inactive” hole produced no programmed consequences.Heroin self-administration: All rats (n=19) were trained to self-administer heroin for 10 days  based on an FR1 reinforcement schedule.Dose–effect response in heroin self-administration: On the 11th day, the rats were randomly divided into three groups (n = 6–7/group). Each group self-administered heroin for 4 h with doses of either 5, 12.5, or 25 μg/kg/infusion instead of the original dose of heroin (50 μg/kg/infusion). On the 12th day, all rats recovered with the original dose of heroin. On the 13th day, the rats were randomly divided into two groups (n = 9–10/group) and each group was given either 100 or 200 μg/kg of heroin for 4 h.MA substituted for heroin reinforcement: Following another recovery day, on the 15th day, the rats were randomly divided into two groups (n = 9–10/group) with the order mixed and counterbalanced. Each group self-administered MA doses of either 12.5 or 50 µg/kg/infusion for 4 h. Then, MA doses of 25 or 100 μg/kg/infusion were given for 4 h on alternate days, using the original heroin dose for recovery on interval days. Then in one groups (n=9) MA dose of 200 μg/kg/infusion were given for 4 h on alternate days.MA self-administration: All rats (n=16) were trained to self-administer MA for 10 days  as described above.Dose–effect response in MA self-administration: On the 11th day, the rats were randomly divided into two groups (n=8/group). Each group self-administered MA doses of either 25 or 100 μg/kg/infusion instead of the original dose of MA (50 μg/kg/infusion) for 4 h. On the 12th day, all rats recovered with the original dose of MA (50 μg/kg/infusion). On the 13th day, the rats were randomly divided into two groups (n = 7–8/group) and each group was given either 50 or 200 μg/kg of heroin for 4 h. One rat was abandoned due to an unexpected physical condition.Heroin substituted for MA reinforcement: After 1 day for recovery, the rats were randomly divided into two groups (n = 5–6/group) with the order mixed and counterbalanced. Each group used a dose of either 12.5, 25 μg/kg/infusion heroin to replace the original dose of MA (50 μg/kg/infusion) for 4 h; then, the heroin doses changed to either 50 or 200 μg/kg/infusion on alternate days, using the original heroin dose (50 μg/kg/infusion) on recovery interval days.via One-way ANOVAs with Bonferroni post hoc testing when appropriate. And the t test was used to compare between the two groups. A P-value< 0.05 was considered statistically significant.Data are expressed as mean ± SEM. All statistic tests were performed using SPSS . The mean amount of “active” and “inactive” pokes, infusions, and total dose during self-administration were analyzed 5, 41 = 7.6, P<0.01), infusions , and total dose of heroin intake . The post hoc comparisons indicated that at the number active pokes and infusions at the dose of 25 μg/kg/infusion was significantly increased compared to other doses. The dose–effect curve of heroin showed an inverted U-shaped trend, whose peak likely being 25 μg/kg/infusion. Nevertheless, the active pokes and the infusions of high dose of heroin changed not so significantly . Besides, the total dose of heroin intake showed a linear trend, being higher at high doses   and infusions . However, post hoc comparisons indicated that MA significantly increased the active pokes and the infusions only at low doses .When the rats were allowed to self-administer several MA doses instead of heroin, they exhibited significant changes in terms of active pokes , infusions , and total intake dose of MA  at different training doses. Post hoc comparisons showed that active pokes and infusions decreased significantly at high MA doses (100 or 200 μg/kg/infusion) compared to 50 μg/kg/infusion doses (P<0.01). The dose–effect curve of MA also showed an inverted U-shaped trend distribution . However, only the total intake dose of MA decreased at low MA doses  (P<0.01)  and infusions . However, post hoc comparisons showed a significant decrease in the active pokes and infusions following heroin substitution at doses of 50 or 200 μg/kg/infusion .When the rats were allowed to self-administer different doses of heroin instead of 50 μg/kg/infusion of MA, the statistical analyses showed a significant change in the number of active pokes , National Key Research and Development Program of China Grant (2017YFC1310403), and Ningbo Natural Science Foundation (2019A610294) of China.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


After adjusting for gender and time period, large institutions (> 3 residents per year) trended toward associations with more first-author publications (odds ratio (OR): 2.44; p = 0.066) and more any-author publications . No significant differences were observed by gender. (4) Conclusions: Canadian RO resident publication productivity nearly doubled over a 12-year period. The majority of publications are released in the last 2 years of residency, and larger residency programs may be associated with more publications. These findings serve as a baseline as programs transition to Competency Based Medical Education (CBME).(1) Background: Research productivity is a mandatory component of Canadian radiation oncology (RO) resident training. To our knowledge, Canadian RO resident research publication productivity has not previously been analysed. (2) Methods: We compiled a 12-year database of RO residents in Canadian training programs who completed residency between June 2005 and June 2016. Resident names and dates of training were abstracted from provincial databases and department websites and were used to abstract data from PubMed, including training program, publication year, journal, type of research, topic and authorship position. Residents were divided into four time periods and the linear trend test evaluated publication rates over time. Univariable and multivariable logistic regression analyses were performed to identify authorship predictors. (3) Results: 227 RO residents representing 363 publications were identified. The majority were first-author publications (56%) and original research (77%). Overall, 82% of first-author, and 80% of any-author articles were published in resident year 4 or higher. Mean number of publications for first-author and any-author positions increased significantly over time ( Scholarly pursuits during medical residency training have been a core part of the CanMEDs framework since its introduction in Canada in 1996 . In the While American RO resident productivity has been analysed, ,4 the prwww.scimagojr.com), by year of publication.We compiled a 12-year database of RO residents in Canadian training programs who completed residency between June 2005 and June 2016. Resident names and dates of training were abstracted from provincial physician databases , hospital and department websites, and online professional sites. Productivity was measured by the number of PubMed-indexed publications during residency and 6 months thereafter, in an attempt to include work completed primarily in residency. Abstracted data included training program, year of publication, publication journal, type of research, topic of research and authorship position. Journal impact factors were obtained from Scimago Journal and Country Rank (n = 41), 2008–2010 (n = 62), 2011–2013 (n = 65), and 2014–2016 (n = 59). Descriptive statistics were generated for all residents and stratified by first-author publication (yes versus no) and any-author publication (yes versus no), compared using the chi-square test, Fisher’s exact test or Wilcoxon rank sum test as appropriate. Linear trend test was used to evaluate changes in publication rates over time based on the pre-defined time period cohorts.Residents were divided into 4 cohorts based on 3-year time periods, representing graduates from: 2005–2007 (Univariable and multivariable logistic regression were performed to identify significant predictors of first-author and any-author publication based on the following characteristics: program (univariable only), gender, resident year (defined as postgraduate year (PGY) on publication date), time period, and size of program . Institutions and programs were anonymised for reporting. All statistical analyses were performed using SAS version 9.4 software  using two-sided statistical testing at the 0.05 significance level.n = 205) were first-author publications, with 18% as second authorships, and 26% representing later author publications. Eighty-four residents : 31–43%) co-authored at least 2 publications, with 45 of those  publishing at least twice as first-author. Nearly half of papers  were published in journals with an impact factor greater than or equal to 4.0 at the time of their publication. The most common journals (n = 72) and Radiotherapy & Oncology .A total of 227 RO residents graduating from 13 Canadian RO residency programs between 2005 and 2016 were identified, collectively co-authoring 363 publications across 116 journals . The disjournals  were Intn = 280), while case reports, reviews, systematic reviews and correspondence represented 10%, 8%, 4% and 2%, respectively  in 2014–2016. Similarly, total publications (with any-author position) increased from 1.24 (0.75–1.74) to 2.08 . This corresponded with increases in the maximum observed number of first-authored and total publications starting with 2 and 7 in 2005–2007 and increasing to 8 and 21 in 2014–2016, respectively.The results from the time trend analysis are shown in p = 0.013). Another (institution B) was associated with fewer first-authored publications than all others . A trend towards significance was noted comparing large versus small institutions , but this was less predictive overall when including all institution sizes (p = 0.135). Neither gender (p = 0.410) nor time period (p = 0.365) were predictive. Multivariable analysis did not identify any significant predictors of more first-author publications, however large vs. small institutions predicted for more first-author publications .On univariable logistic regression analysis for predictors of first-author publications shown in p = 0.044), although this was not significant when including medium institutions (p = 0.130) (p = 0.043). Correspondingly, neither gender (p = 0.371) nor time period (p = 0.351) were predictive. Similarly, multivariable analysis did not identify any significant predictors of more any-author publications. Large vs. small institutions  and 2011–2013 compared to 2005–2007  non-significantly predicted for more any-author publications.For authorship at any position, large versus small institutions was significantly predictive  . One insp = 0.016) in 2014–2016, while mean any-author publications increased from 1.24 (0.75–1.74) to 2.08 . The majority of publications were authored by residents in PGY-4 or higher. These findings provide a benchmark for medical students interested in pursuing a career in RO, for RO residents in training, for program and research directors, for potential employers and can serve as a baseline for CBME implementation.Canadian-trained RO resident publications have significantly increased over the past 12 years. Mean first-author publications per resident during residency increased from 0.61 (95% CI: 0.35–0.87) in 2005–2007 to 1.17 , suggesting that the increase in publications detected herein is most attributable to a near doubling of publications among publishing residents, rather than an increase in the percentage of residents who publish. This implies some inertia with non-publishing residents that has yet to be overcome despite the overall trend in increasing publications. This may represent a population of focus for program or research directors going forward.Two institutions were associated with a significantly higher likelihood of publication (first-author publication for institution A and any publication for institution C) whereas one institution (institution B) was associated with a significantly lower likelihood of first-author publication, suggesting that local factors may play a role in resident productivity. Residents at large institutions  may also be more likely to publish. Institutional support systems, library and data analysis supports, staff research mentors, clinical workload for residents, and cultural factors may all be drivers.First-author productivity in United States RO residency programs was studied by Morgan et al. for the years 2002–2007, and by Verma et al. for 2014–2015 ,7. A simOverall, limited data exist on academic productivity of Canadian resident physicians. Canadian otolaryngology residents published a mean of 3.35 any-author publications during residency training between 1998 and 2013 .While the mandatory completion of an academic project during residency has existed as a Canadian RO Royal College requirement since at least 2012, the 2019 introduction of the CBME curriculum has changed the education landscape . The reqDebate remains about whether increased focus on scholarly productivity is beneficial to trainees. Resident productivity has been associated with increased departmental costs, and a reduced clinical caseload . HoweverShould continued productivity increases be desired by programs or residents, there are several interventions that have shown benefits for resident productivity. Lack of designated time, mentorship, interest, funding and technical support have been identified as challenges in research productivity during residency . GutovicThe findings of this study should be considered in the context of its limitations. While our estimated capture rate of RO trainees exceeds 90%, potential issues with data sufficiency and completeness may impact results. Resident demographic data were not available in a standard, centralised format. The degree of detail available in provincial physician databases was variable and thus the number of eligible residents in certain regions  may be underrepresented. Furthermore, Canadian-trained ROs who are not currently employed in Canada were not easily identified. Valuable academic activities outside of PubMed-indexed publications (such as grant applications) were also not captured. Several studies correlated simultaneous or previous completion of advanced degrees with increased productivity in residency ,20,21. UWhile studies have found resident productivity to be a mixed predictor of future publication rates, further work is required to determine the impact of resident publication rate on research productivity during later years, and to assess interventions to provide additional research mentorship and support if needed.Canadian RO resident publication productivity nearly doubled over a 12-year period. Year of graduation was significantly related to both first-author and total publications during residency and larger institution size for total publications. A single institution was associated with higher rates of first-author publications, while another institution correlated with higher rates of any-author publications. Future directions include analysing productivity outside of publications, and exploring initiatives to facilitate academic output in centres or among residents that wish to do so.


Infection is the most common cause of mortality within the first year after lung transplantation (LTx). The management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices.We sent by email a survey dealing with 5 daily clinical vignettes concerning perioperative antibiotic therapy to 180 LTx centers around the world. The invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center during a 3-month period.n = 46) and the USA (n = 34). Systematic screening for bronchial recipient colonization before LTx was mostly performed with sputum samples (72%), regardless of the underlying lung disease. In recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains  were reported in 72% of the centers, and antibiotics with activity against methicillin-resistant Staphylococcus aureus (mainly vancomycin) were reported in 38% of the centers. For these recipients, the duration of antibiotics reported was 7 days (33%) or less (26%) or stopped when cultures of donor and recipients were reported negatives (12%). In recipients with previous colonization, antibiotics were adapted to the susceptibility of the most resistant strain and given for at least 14 days (67%).We received a total of 99 responses from 24 countries, mostly from Western Europe (Practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. The antibiotic duration reported was longer for colonized recipients. Infection is a significant complication following lung transplantation and represents the most common cause of mortality within the first year, but it is also a risk factor for chronic lung allograft dysfunction (CLAD) , 2. EarlClinical practice guidelines for antimicrobial prophylaxis in surgery recommend the use of cefazolin for heart and lung transplantations, but the evidence was mostly based on cardiac procedures . Cystic Clostridioides difficile infections  number of LTx per center was 28 (15–38) in 2017 , which represent more than 3617 LTx performed in 2017. Answers came from 24 different countries  (37.7%), mostly vancomycin (86%) , fourth-generation cephalosporins such as cefepime (21.2%), and antibiotics with activity against methicillin-resistant 2.3%, fouThe duration of prophylaxis in this context was very heterogeneous Fig. a but mosPseudomonas aeruginosa only susceptible to carbapenems, colistin and tobramycin. This colonization was not considered a contraindication in 94.9% of the centers, and there was no pretransplant decolonization strategy in 69.7%. The postoperative antimicrobial prophylaxis consisted of meropenem or imipenem (92.9%), tobramycin (45.5%), colistin (36.3%), and antibiotics with activity against MRSA pathogens such as vancomycin, linezolid or teicoplanin (25.3%). Combined antibiotics with a carbapenem  and tobramycin or colistin were proposed in 69.7%. The duration of this antibiotic treatment was very heterogeneous .The second clinical case was a LTx for cystic fibrosis with colonization with Pseudomonas aeruginosa) were isolated at least once and never found again on the last samples, the delay was widely heterogeneous: 15 days or less (14.2%), between 1 and 3 months (35.3%), 6 months (16.2%), and 1 year or more (28.2%). If the organism was an MDR strain, the duration to consider antibiotic prophylaxis targeting this bacteria was longer: 15 days or less (14.2%), between 1 and 3 months (27.3%), 6 months (22.2%), and 1 year or more (34.3%).The third clinical case was the definition of colonization with wild-type or MDR bacteria in a COPD recipient. The questions were related to the delay between the last bacterial isolation and the LTx to consider if the therapy should target these bacteria. In such cases, where wild bacteria  or linezolid (30.3%). An antipseudomonal beta-lactam associated with ciprofloxacin or amikacin was also used in 26.3% of the centers, ciprofloxacin associated with amikacin alone was used in 21.2% of the centers, and nebulized colistin was used in 35.4% of the centers regardless of the other antibiotics.The fifth case was a LTx for cystic fibrosis with a history of colonization by MRSA and MDR strains of Pseudomonas aeruginosa, with no clinical signs of infection, 60.6% of the centers did not perform de-escalation, and 17.2% proposed de-escalation with piperacillin + tazobactam.On day 5, if the organism retrieved in the recipient perioperative samples was a wild type p = 0.02). A team protocol for antimicrobial prophylaxis was more reported in larger volume centers . Pre-transplant Burkholderia species colonization was more considered as absolute contraindication in small volume centers and rather a contraindication only if pan-resistant in larger volume centers.We compared the practice on perioperative antibiotic therapy according to large and small volume centers . Our survey revealed that only one-third of the centers target MRSA. Antibiotics against MRSA were almost exclusively used by centers from the USA, which follows the direction of use in accordance with the local ecology of each institution. Vancomycin was the most commonly used molecule against MRSA (> 80%). The perioperative period of a LTx may be associated with hemodynamic instability and carries a risk of acute kidney injury, but higher nephrotoxicity for vancomycin compared to linezolid was never clearly demonstrated [The risk of nstrated . Howevernstrated . Thus, tColonization is usually described as the detection of at least two isolates of an organism separated by a certain amount of time . In thisDespite the risk of bronchial colonization, only one-third of the centers reported a pretransplant decolonization strategy. Candidates for a LTx with bronchial colonization have recurrent episodes of infection in their history despite repeated antibiotic cures. Thus, classical antibiotic strategies, such as parenteral or nebulized antibiotics, are probably considered ineffective. However, alternative decolonization strategies are emerging in the perioperative period of a LTx. Indeed, different solutions have been tested with interesting results, such as perioperative tracheobronchial lavage and/or pleural irrigation with antiseptic solutions , 35 or aClostridioides difficile infections in longer therapy [Burkholderia cenocepacia many studies reported an increased mortality after LTx and for that reason, this colonization has been considered a contraindication in some centers [Multidrug-resistant bacteria are a specific concern in lung transplantation. We observed different antibiotic strategies between non-colonization recipients and recipients colonized with MDR bacteria in our survey, even under similar clinical conditions. Indeed, the presence of MDR bacteria followed the direction of the highest “caution” and, as an example, longer antibiotic therapy and less de-escalation were the reported responses despite a well-known risk factor for multidrug-resistant (MDR) bacterial and  therapy –12. It i therapy . Althoug centers –40. Agua centers  recentlyMycobacterium tuberculosis is also not consensual. Less than half of the centers reported a systematic screening and a specific treatment when positive for latent tuberculosis in the pretransplant evaluation. Lung transplant recipients are at higher risk of tuberculosis, and recently, guidelines recommended systematic screening and treatment for latent tuberculosis in the pretransplant assessment [Risk management of sessment .Clostridioides difficile infections. The right balance to prevent infection risk with limited side effects is not known. The duration of gram-positive antimicrobials has been described to increase the risk of MDR and Clostridioides difficile infection in an analysis of 500 non-cystic fibrosis lung transplant patients [Antibiotic use is a well-known risk factor for MDR and patients . In our Our study has several limitations. Some respondents (mainly surgeons) were not in charge of antibiotic management, and thus, in those cases, the answers might maybe not reflect the real practice of these centers. The question of the survey is complex and the practice varies widely from one center to another. Thus it was really challenging to cover all aspects of the problematic and in order not to make the questions too long, we sometimes limited the choice of answers and certain situations may have been neglected. For instance, the route of administration was not always specified when asking for an antibiotic strategy. Moreover, not all 180 centers contacted have responded to the survey, but we received a global response rate of 55%. The response rate from Western Europe was the highest (62%), but some countries with experience in LTx, such as the United Kingdom and Germany, did not participate well in the survey . We received no answer from China. Because we did not screen centers in advance for eligibility, it is likely that some of the nonresponders would have been ineligible (because they do not perform LTx). Furthermore, some centers may be not used to complex infectious situations since most centers perform LTx for fibrosis (61%) and may not be used to cystic fibrosis, which entails a more complex risk.Clostridioides difficile infections on the other hand.Our study revealed high heterogeneity between centers. It could be interesting now to evaluate in further appropriate randomized studies the use of antibiotics in perioperative of a LTx. From our point of view, two major questions still remain to be evaluated. Firstly, the type and the spectrum of the antibiotic therapy used, particularly in no prior colonization. And second, the duration of the postoperative antibiotic use on the prevention of postoperative infections on one hand, and on the selection of MDR strains or the occurrence of These survey results suggest that practices vary widely around the world, but hospital-acquired bacteria are mostly targeted by perioperative antibiotic therapy even if no colonization occurs, probably in order to treat possible donor-derived infections. Furthermore, there is a trend to limit antibiotic duration if the results of the bacteriological screening in the donor and recipient are negative and show no sign of infection, but the duration reported was longer for colonized recipients, cystic fibrosis patients and MDR situations.Additional file 1. Survey sent to the lung transplantation centers.Additional file 2. Raw anonymized answers of the 99 participantsAdditional file 3. Answers to Case 1.Additional file 4. Answers to Case 2.Additional file 5. Answers to Case 3.Additional file 6. Answers to Case 4.Additional file 7. Answers to Case 5.Additional file 8 Answers according to large et small volume centers. The groups were defined on the median of lung transplants performed in 2017 (n = 28). LTx: lung transplantation.


The paper describes the mechanical behavior of fine recycled concrete aggregate (FRCA) concrete according to the mineral admixtures. Three types of the mineral admixtures, i.e., fly ash (FA), ground-granulated blast-furnace slag (GGBS), and silica fume (SF), are used and the replacement ratios of FRCA are 50% and 100%. The dosages of the admixtures of FA, GGBS, and SF are determined with the normal dosage  based on the ACI committee reports  and half-normal dosage. The mechanical performance is investigated with the compressive and splitting tensile strength, and elastic modulus. Additionally, the total porosity is measured in natural fine aggregate (NFA) and FRCA 100% replaced specimens by mercury intrusion porosimetry (MIP) for investigating the relationship with the compressive strength. Based on the experimental test results, the mineral admixtures improve the mechanical performance of FRCA concrete. The effective dosages of FA, GGBS, and SF for FRCA concrete are investigated according to the replacement ratio of the FRCA. In particular, FRCA 100% replaced concrete may be possible to be used for the structural concrete members with the specific dosage of the mineral admixtures. The prediction of the splitting tensile strength and the elastic modulus by the codes or previous formulas exhibits underestimated and overestimated results, respectively. The relationship between the total porosity and the compressive strength of the FRCA concrete should be modified with more experimental tests.  The depletion of natural aggregates in construction has been a significant reason to begin the use of substitutes, such as artificial aggregates, wastes, and recycled products. One of the promising materials is the recycled concrete aggregate (RCA) from demolition of the concrete members ,2. This The FRCA concrete is more difficult to incorporate into the structural concrete than coarse recycled concrete aggregate (CRCA) concrete, mainly due to FRCA’s water absorption that result in workability issues with fresh concrete . Many prThe inherent weakness of the FRCA has been a significant obstacle to extend the use of FRCA to concrete members so that an effective way to improve the mechanical performance has been researched. One possible way to overcome the adverse effect of RCA on its mechanical performance is by employing mineral admixtures. There are three representative mineral admixtures, i.e., fly ash (FA), ground-granulated blast-furnace slag (GGBS), and silica fume (SF). According to the ACI committee about the mineral admixtures in concrete ,14,15, tThere is a little previous research on the effect of the mineral admixtures for FRCA concrete. Fly ash addition, over 50% showed strength reduction of 7.5% of normal strength  and 60% From the literature, it was found that the mechanical performance of FRCA concrete could be reduced in the specific amount of the mineral admixtures in 28 days, while long-term strength can be improved as well. Due to the significant difference in FRCA’s quality, the relationship between the type of the mineral admixtures and the FRCA needs to be further investigated . The lacThe purpose of this study is to investigate the mechanical performance of concrete with commercially produced FRCA employing the three types of the mineral admixtures, namely FA, GGBS, and SF. The replacement ratios of FRCA are 50 and 100% regarding high volume and complete usage of the FRCA. The amount of the mineral admixtures in FRCA concrete considers two types of dosages; normal dosages by the ACI committee and half-normal dosage. Mechanical performances are investigated using compressive strength, splitting tensile strength, and elastic modulus at 28 days. Additionally, a mercury intrusion porosimetry (MIP) test is employed to investigate the relationship between the mechanical strength and porosity of FRCA concrete using high amounts of the mineral admixtures. The aggregates used for this study are classified as natural coarse aggregate (NCA), natural fine aggregate (NFA), and fine recycled concrete aggregate (FRCA). NCA is prepared by using crushed gravel, and NFA is river sand. FRCA is provided by a domestic manufacturer in Korea , which has produced good quality of FRCA ,25,26. FThe water absorption is a significant issue to determine the quality of the FRCA. The measured water absorption by ASTM C128 2015)  indicate  indicatThere are four binders, including three types of the mineral admixtures such as fly ash , granulated blast furnace slag , and silica fume . The chemical compositions of the binding materials were measured using X-ray fluorescence , and the specific surface area was evaluated according to ASTM C204 (2011) , which aefW/C) is the same with the total water to cement ratio . The water to binder ratio is 42.5% in volume and the target compressive strength is 27 MPa for the normal strength concrete specified by the standard of recycled aggregate concrete [The aggregates are prepared for the saturated surface dry (SSD) condition by ASTM C128 2015) . Accordiconcrete  for fly concrete  for GGBS . AccordThe slump of FRCA concrete can be influenced by the rough surface so that the slump may decrease with the increase in amount of FRCA. In order to keep the high slump property, the polycarboxylate-based superplasticizer (SP) is used in the mixing design with the dosage of 1% to the amount of cement. This is because of the possible use of the FRCA concrete to the filled concrete to the steel tube. The three stage mixing process are employed. It is to mainly overcome the high porous nature of FRCA. First, the SSD coarse and fine aggregates are mixed during the 30 s. Next, the cement and the mineral admixtures are added and mixed for 30 s without water. Lastly, water and chemical admixture are added and mixed during the 90 s and 180 s. This mixing process was motivated by previous studies to improve the ITZ characteristics for recycled aggregates .3 are fabricated from the five mixing proportions of R0, R100, R100FA30, R100GGBS40, and R100SF5.0, respectively.Six test cylinders with Φ100 × 200 mm were produced for each specimen, hence, a total of 126 cylinders were fabricated for measuring the compressive strength, splitting tensile strength, and elastic modulus. One day after casting, cylinder specimens are demolded and cured for 28 days in an air-dry laboratory. According to the national weather service, the average temperature and the average relative humidity (RH) were 23.1 ± 8.6 °C and 68.7 ± 18.4%, respectively, during the curing period. This was under outdoor conditions so that the curing room condition would be much more stable with less variations on temperature and RH. For the porosity measurement, the FRCA specimens of 50 × 50 × 50 mmThe compressive strength test was conducted according to ASTM C39 (2015)  at 28 d.It should be noted that the ratio slightly increases with increase in FRCA. This may be caused by the roughness of the FRCA to make better resistance to the tensile failure. Note that the failure mechanism of concrete with the mineral admixtures is affected by the strength of aggregate, the strength of the paste, and ITZ property. The increase in the amount of the FRCA leads to increase the possibility of existence of weak strength of aggregate and the porosity of ITZ on the old cement paste of FRCA. Furthermore, the increase in the amount of the mineral admixtures brings the higher retardation of the hydration of cement paste at 28 d. The addition of the mineral admixtures improved the elastic modulus for R0, R50, and R100 concrete as shown in The pore size of hardened concrete is an important factor to determine the material property. The common boundary of size of the micro- and macropore is 0.05 μm . Figure A previous study  demonstrFor the GGBS effect on strength, the literature with water absorption of 3.6% , which hFor SF effect on strength, the literature with water absorption of 2.1%  which waIncrease of porosity in concrete leads to decrease of mechanical property. There are some of the porosity-strength relationship of previous researches ,45,46,47The study investigates the effect of the mineral admixtures on the mechanical performance of FRCA concrete, which includes the compressive strength, splitting tensile strength, and elastic modulus. Based on experimental results, the effective dosages of the mineral admixtures are discussed for FRCA concrete with normal strength and moderate water absorption of 5.86%. The key findings of this study are as follows:1. The mineral admixtures enhance the mechanical performance of FRCA concrete as compared with NFA concrete with no mineral admixtures. For FRCA 50% replaced concrete, every mineral admixture and dosage can bring better mechanical performance. FRCA 100% replaced concrete, however, the half-normal dosages, thus, FA 15%, GGBS 20%, and SF 2.5% are available for enhancing the mechanical performance. 2. The admixture additions improve the measured elastic modulus of FRCA concrete with about 45%. The strength enhancement of FRCA concrete by the mineral admixtures can be good for improving the predictability of the elastic modulus predicted by the code equations. 3. The relationship between the total porosity and the compressive strength of the FRCA concrete does not comply with those of cementitious materials using natural aggregates and the CRCA concrete. Due to FRCA concrete has inherently higher porosity than that of CRCA, the strength shows less at the same level of porosity. Extra datasets of the FRCA concrete will be able to be used for developing proper relationship between the strength and the total porosity.


To assess variation in antibiotic prescribing practices among village doctors in a rural region of Shandong province, China.Almost all outpatient encounters at village clinics result in a prescription being issued. Prescriptions were collected over a 2.5-year period from 8 primary care village clinics staffed by 24 doctors located around a town in rural Shandong province. A target of 60 prescriptions per clinic per month was sampled from an average total of around 300. Prescriptions were analysed at both aggregate and individual-prescriber levels, with a focus on diagnoses of likely viral acute upper respiratory tract infections (AURIs), defined as International Classification of Diseases, 10th Revision codes J00 and J06.9.Proportions of prescriptions for AURIs containing (1) at least one antibiotic, (2) multiple antibiotics, (3) at least one parenteral antibiotic; classes and agents of antibiotics prescribed.In total, 14 471 prescriptions from 23 prescribers were ultimately included, of which 5833 (40.3%) contained at least 1 antibiotic. Nearly two-thirds 62.5% (3237/5177) of likely viral AURI prescriptions contained an antibiotic, accounting for 55.5% (3237/5833) of all antibiotic-containing prescriptions. For AURIs, there was wide variation at the individual level in antibiotic prescribing rates (33.1%–88.0%), as well multiple antibiotic prescribing rates (1.3%–60.2%) and parenteral antibiotic prescribing rates (3.2%–62.1%). Each village doctor prescribed between 11 and 21 unique agents for AURIs, including many broad-spectrum antibiotics. Doctors in the highest quartile for antibiotic prescribing rates for AURI also had higher antibiotic prescribing rates than doctors in the lowest quartile for potentially bacterial upper respiratory tract infections .All village doctors overused antibiotics for respiratory tract infections. Variations in individual prescriber practices are significant even in a small homogenous setting and should be accounted for when developing targets and interventions to improve antibiotic use. We investigated whether significant variations exist in antibiotic prescribing patterns among village doctors working in a small, homogenous setting in rural China.We included over 14 000 prescriptions sampled across a 2.5-year time period.Uniquely, we analysed prescriptions both according to clinical diagnosis, focussing on acute upper respiratory tract infections, and at the level of individual prescribers.We could not verify diagnoses clinically, so variations between the village doctors in terms of diagnostic ability could not be assessed.Irrational antibiotic use is an important and modifiable driver of antibiotic resistance.3 4et al found that variability in prescribing patterns for antibiotics at primary care centres in the UK could not be adequately explained by variations in patient consultation rate or pre-existing comorbidities,10Previous studies in China strongly indicate that there is widespread antibiotic overuse in outpatient clinics in rural areas, particularly for respiratory tract infections (RTIs).We investigated patterns of antibiotic prescriptions at the individual prescriber level in eight village clinics in rural Shandong province, China, over a two-and-a-half-year time period. Village clinics are the first place that most rural residents seek healthcare, and almost all consultations result in patients receiving a prescription, in part because prescriptions are a way in which reimbursements for healthcare expenditures are calculated and administered. The clinics are staffed by village doctors who typically have a high school level education and additional vocation-related training; many of the older village doctors were trained under the barefoot doctor programme.12We conducted a prospective observational analysis of outpatient prescriptions from January 2015 to July 2017 at eight village clinics clustered around a single town in Z County, Shandong province. This county is in the middle level in Shandong province in terms of economics, health indicators and population size. As previously described in the full study protocol,The prescriptions of all village clinics in Z county are included in an e-prescription system that records for each visit the patients’ name, sex, age, date of visit, diagnosis, medicines prescribed, total cost for the visit and name of the doctor. For each village clinic, a target of 60 prescriptions per month  was collected using a random sampling method in which every fifth consecutive prescription was selected, beginning with a randomly generated starting number between 1 and 10. The prescription details were exported one by one from the e-prescription system in XPS format and entered into a Microsoft Excel database. In addition, in July 2015, the doctors completed a short face-to-face questionnaire concerning their demographic information .Prescriptions from one doctor who did not complete the questionnaire were removed . Data from prescriptions from the remaining 23 doctors were then anonymised with patient names being removed and each doctor assigned a three-digit code representing the village clinic at which they worked (1XX–8XX) and a unique number (X01–X23).likely viral AURIs was created by grouping diagnoses of J00 (acute nasopharyngitis (common cold) and J06.9 .All diagnoses on prescriptions were coded where possible according to the International Classification of Diseases, 10th Revision (ICD-10) by an independent researcher from China with a background in clinical medicine and public health: first, a list of unique diagnoses included on the prescriptions was created; second, these were matched with the standard ICD-10 Chinese translation provided by the National Health Commission of China that is used in hospitals; finally, these diagnoses were translated into English. In cases of uncertainty, a shortlist of potential diagnoses was discussed between the first author  and the independent researcher until either agreement was reached or no ICD-10 code was assigned ; in total, these cases of uncertainty accounted for <10% of all prescriptions, and did not include any prescriptions that were ultimately classified as likely viral acute upper respiratory tract infections (AURIs). A category of Prescriber-level analyses were limited to the 20/23 doctors with ≥50 AURI prescriptions during the study period, to ensure that the antibiotic prescribing rates (APRs) calculated for each individual doctor were sufficiently representative of their practice. Of the three doctors with fewer than 50 AURI prescriptions, two retired from clinical practice near the beginning of the study period (616 and 720), and one newly started working at the specific village clinic at the end of the study period (618). We further identified an error in the coding of prescriptions in village clinic 1 which was due to one doctor (101) being responsible for entering the majority of prescriptions onto the electronic system using their account, irrespective of who the actual prescriber was, because of the low computer literacy of the other doctor (102). We therefore could not be confident of which doctor was responsible for which prescription, so all 433 prescriptions from the two doctors working at this clinic were excluded from prescriber-level analyses. This error was not present at other village clinics. All prescribed antibiotics were coded using the Anatomical Therapeutic Chemical (ATC) classification systemFor each prescriber, antibiotic prescribing was analysed using three indicators: (1) Antibiotic prescribing rate (APR)=number of prescriptions that included at least one antibiotic/total number of prescriptions × 100%, (2) multiple antibiotics prescribing rate (MPR)=number of prescriptions that included at least two antibiotics with different ATC codes/total number of prescriptions that included at least one antibiotic × 100%, (3) parenteral APR (PAPR)=number of prescriptions that included at least one parenteral antibiotic/total number of prescriptions that included at least one antibiotic × 100%. Comparisons were also made against antibiotic prescribing quality indicators developed in Europe2 tests and Pearson correlation. The Kruskal-Wallis H-test was used to assess whether there were statistically significant variations between the individual doctors in terms of APRs for likely viral AURIs. Pairwise Mann-Whitney U-tests were used post-hoc to assess for differences in all pairwise comparisons between doctors, using the Benjamini-Hochberg procedureAll analyses were conducted in Microsoft Excel and SPSS (version 24). Descriptive statistics were calculated and comparisons were made using χ10.1136/bmjopen-2019-036703.supp2Supplementary dataPatients or the public were not involved in the design, conduct, reporting or dissemination plans of this specific study, but have been involved in the dissemination plans for results of the overall IMPACT research programme.In total, 14 471 prescriptions from 23 prescribers from January 2015 to July 2017 were included in the analyses. This included an average of 58 prescriptions per month per village clinic (mean range from 56 to 60). There was a total of 222 diagnoses in Chinese, with 20 diagnoses accounted for nearly 90% of all prescriptions (12 811/14 471). The 5 most common diagnoses overall were: J00 (acute nasopharyngitis (common cold), 34.1%, 4938/14 471), I10 , K29.7 , M13.9  and I25.1 . Overall, 40.3% of the prescriptions (5833/14 471) contained at least 1 antibiotic.likely viral AURIs, and 62.5% (3237/5177) of these prescriptions contained at least 1 antibiotic, accounting for 55.5% (3237/5833) of all antibiotic-containing prescriptions. Fifteen per cent (491/3237) of AURI antibiotic prescriptions included two or more antibiotics and 24.3% (785/3237) included at least one parenteral antibiotic.Sixteen classes of antibiotics and 27 antibiotic agents were prescribed for AURI . The thr10.1136/bmjopen-2019-036703.supp1Supplementary data14r=0.65). The mean absolute individual variation in AURI APRs between 2015 and 2016 was ±13.1% (SD=6.7%). Eleven prescribers had lower AURI APRs in 2016 compared with 2015, and six had higher APRs in 2016 , amikacin (1), lincomycin (1) and azithromycin (1). For each doctor, their three most commonly prescribed antibiotic agents accounted for a mean of 64.4% (range 45.3%–86.4%) of all the antibiotics they prescribed for AURI .r=0.47, p=0.05) and PAPRs , but there was no association between doctors’ APRs and the prescription of at least one analgesic or anti-inflammatory medicine . Village doctors’ MPRs were also positively correlated with their PAPRs .The Kruskal-Wallis H-test showed that the variations in APRs for AURI prescriptions were statistically significant among the 18 prescribers (p<0.001). Pairwise Mann-Whitney U-tests were used as post-hoc tests to assess for differences in all possible pairwise comparisons between prescribers. This involved 153 pairs of prescribers, and the difference was statistically significant in 93 of these.We prospectively investigated patterns of antibiotic prescriptions over a two-and-a-half-year period at village clinics in rural Shandong province in order to assess evidence of irrational antibiotic use and variability in prescribing practices at the level of the individual village doctor.The patterns of diagnoses recorded on the prescriptions in our study are broadly similar to those in previous studies conducted in rural China,5 7 16 20 21Although the antibiotic prescription rate is high in absolute terms, supporting clinical information is required to better understand the quality of the prescribing. We found that two-thirds of all antibiotic use occurred in patients with a diagnosis of an RTI, and that likely viral AURIs accounted for over 80% of the total antibiotic use for RTIs. This is despite there being very little evidence of benefit of antibiotic use for such AURIs, and a considerable number of strong recommendations that they should be avoided.27Antibiotic prescribing quality indicators were recently developed in Europe to assess both the decision to prescribe an antibiotic in specific clinical conditions and the actual choice of antibiotic agent.Clinical treatment guidelines are not in widespread use in village clinics in China31Interestingly, we found that antibiotics were used less frequently than recommended for adult patients with a diagnosis of pneumonia (73.3% compared with a target of 90%–100%),Understanding what variations exist in clinical care, and why, is important for developing targets as well as context-specific interventions capable of reaching these targets. It is also essential for working towards individuals having equitable access to healthcare, regardless of where they reside.Our study design has enabled us to investigate variability in antibiotic prescribing at the prescriber-level while keeping several factors relatively constant: the villages served by the clinics are limited to a small geographical region and are quite homogeneous in terms of socioeconomic levels; the patient populations in the villages are likely to have similar consultation behaviours when ill, in particular for a common diagnosis such as AURI; the doctors all have the same medical qualifications and at least 14 years of clinical experience; the village clinics are all subject to the same reimbursement systems (including zero markup on antibiotics) and regulations concerning antibiotic use.35 36et al investigated APRs for upper respiratory tract infections (URTIs) among 84 primary care practitioners in the Netherlands, finding that these ranged from 15% to 27%.et al examined antibiotic prescribing for RTIs at a single outpatient practice in the USA and found variations depending on the provider type from 55% (residents) to 84% (nurse practitioners).et al found an IQR of 27%–60% in APRs for RTIs among 109 prescribers in a large healthcare network in the USARelatively few published studies have assessed variations between prescribers concerning antibiotic use in primary care settings, with most studies analysing aggregated data and presenting averages. In 2001, Akkerman Future studies should explore why such variations exist, as well as what the consequences are for efforts to improve antibiotic use. For example, qualitative studies with individual prescribers could help understand why some doctors already have very low rates of parenteral and multiantibiotic use, and why prescribers have used such a wide range of antibiotic agents for patients with a single diagnosis. It is possible that structural factors such medicine shortages might contribute to changes in antibiotics prescribed. We did find that high antibiotic AURI prescribers were more likely than low antibiotic AURI prescribers to prescribe antibiotics for the group of URTI diagnoses that are most likely to have bacterial causes . One possible explanation is that these prescribers could be more risk averse, and so are more likely than other doctors to prescribe antibiotics in cases where the cause could be bacterialOur study has several strengths, including the long length of data collection and the high number of prescriptions included by individual village doctors. Furthermore, almost all patients that visit doctors at a village clinic receive a prescription. A common limitation of studies using prescription data is the inability to verify diagnoses. To reduce the impact of this limitation, we restricted the individual-level analyses to AURI diagnoses, but we cannot guarantee that misclassifications did not occur, particularly given there is currently no incentive for doctors to correctly classify diagnoses. AURIs accounted on average for 86% of RTI diagnoses by individual doctors, but this ranged from 58% to 100% which strongly suggests that there were variations in how doctors classified different infections, and this warrants further investigation, particularly if diagnosis-based antibiotic prescribing targets are ever introduced. Indeed, a recent study concluded that deficits in diagnostic knowledge are a major driver of unnecessary antibiotic prescriptions in clinics in rural China.Together our results provide evidence that even in a small homogenous setting in rural China, variations in individual prescriber practices are significant, and they need to be accounted for in the development of targets and interventions to improve antibiotic use. We suspect that this finding is likely to be generalisable to other areas in rural Shandong province as a minimum, but also to other areas in eastern rural China, where the healthcare system is very similar in terms of structure, regulations and staffing. We show that there is a need for all prescribers to reduce their APR for AURIs, but the extent of this reduction varies widely between prescribers. For some prescribers, reducing the proportion of prescriptions that contain fluoroquinolones and third-generation cephalosporins may be more important goals, both for their patients and for public health. Finally, it is possible that interventions that incorporate individual-level feedback will have a more directed and effective impact on improving antibiotic use. A promising recent example in Anhui province, China, was able to provide ‘just-in-time’ individualised information and feedback to doctors in village clinics which improved antibiotic prescribing practices.43