The aim of the research was to check the possibility of using the non-destructive method of acoustic emission to assess the condition of concrete without dispersed reinforcement and with various additions of curved steel fibres, during three-point bending. An important aspect of the research proposed in the article is the use of a hybrid method of analysis, which involves complementing the results of strength tests, the results of numerical calculations and the results of strain distributions recorded with a digital image correlation system . The operation of the concrete material under load, depending on the amount of fibres added, is reflected in the recorded acoustic emission (AE) signals. The differences concern the number of signals of individual classes and their distribution over time. The differences exist for both low and high load values, which confirms the possibility of using the acoustic emission method to monitor the condition of the material. It was shown that the numerically determined effective stress levels decreased as the proportion of steel fibres in the concrete increased, while the maximum levels of the first principal stresses increased. During the analyses, a preliminary comparison of the deformation results obtained using the finite element method and the DIC System was also carried out. Steel fibre reinforced concrete (SFRC) is a composite material made of cement, mineral aggregate, sand, water and steel fibres. Unlike conventionally reinforced concrete, it is a homogeneous material with evenly distributed reinforcement. The reinforcement is made of kilometres of fibres in one cubic meter of concrete. The basic parameters of the steel fibres that affect the properties of composite concrete are fibre length, diameter, the tensile strength of the steel used for its production and its geometry. The slenderness ratio, defined as the relation of fibre length to its diameter, was introduced a long time ago. The slenderness ratio of the fibre used as reinforcement should not be less than “50”. Fibre with lower slenderness is always technologically questionable. Another very important feature of the fibre that undeniably affects the characteristics of concrete is its shape. The fibre shape must be selected so that the fibre tips are anchored as securely as possible in the concrete structure ,2,3.The primary function of steel fibre in concrete is to reduce stress concentration. When the fibres are evenly distributed in concrete, they transfer loads like bridges through the existing discontinuities of the concrete structure, such as cracks or fractures, taking over the forces resulting from the load. These forces are transferred through the fracture from one side to the other and reduce the stresses at the end of the fracture as a result of the much greater Young’s modulus for steel in relation to the matrix of the surrounding concrete. The described phenomenon prevents the transformation of internal microcracks into larger cracks leading to concrete destruction ,5.The main feature of steel fibre reinforced concrete is its resistance to cracking after the appearance of the first structural crack resulting from the load. Contrary to conventional concrete, fibre concrete behaves then not like a brittle material that is subject to destruction but like a flexible object. It is springy and capable to withstand a higher load .The degree of its plasticity, defined in the case of steel fibre reinforced concrete by “fracture resistance”, can be controlled by selecting an appropriate type and amount of fibre. The load–deformation curve shows a very different way of behaviour of concrete composites with steel fibres compared to normal concrete ,6,7.There is also a large difference in strength at certain deformations depending on the shape of the fibres. Straight fibres provide worse results than fibres with curved ends, even at higher contents .As a result, concrete that is normally hard but brittle becomes strong and elastic, which translates into many other advantages. An example of this is a fibre concrete floor , which tVarious research and studies on the use of non-destructive techniques to assess the technical condition of devices and structures operating under high loads have been carried out for at least a dozen years. The method of acoustic emission plays a special role in this respect, as it allows for assessing the overall technical condition of the structure, both in the case of a single load and long-term monitoring of a facility operating under load ,11,12.The term acoustic emission (AE) is defined as momentary elastic waves caused by the sudden release of energy stored in the material. These waves are generated in places called AE sources and are usually the result of several phenomena overlapping one another. As a result of an applied external stimulus , elastic waves propagate from the source to the material boundary surface, where they can be recorded by special receiving transducers ,14.In composite materials, which undoubtedly should be considered concrete reinforced with dispersed steel fibres, the basic source of acoustic emission is the formation and development of microcracks. Under load, microcracks can propagate, becoming active sources of AE. Their size and place of occurrence are important factors in the analysis of the threat to the integrity of the structure, as unstable defects usually propagate long before structural failure. In this way, the developing discontinuities become active sources of AE, making it possible to detect emerging hazards ,16,17.The values of the parameters of the recorded AE signals allow grouping the signals into classes, each of which is characterised by different dominant destructive processes and a different degree of hazard to the element or the structure. The signals characteristic for each class form “reference” databases enabling the identification of the destruction process, e.g., “concrete crushing” corresponds to the database grouping selected signal parameters assigned to this process ,17,18,19Databases for individual processes (or their groups) are determined using material samples, models in special laboratory tests (where a given destructive process or a group of processes dominates) and full-size structural elements during strength tests and the operation of objects ,14,15,16Having a database of AE reference signals, it is possible in this way to identify active destructive processes occurring in the entire tested volume. By carrying out long-term measurements, it is possible to determine the propagation of damage under the conditions of real load, taking into account the external conditions. An appropriate arrangement of AE sensors allows for the measurement of the entire tested element and the location of the emission source (location of damage) ,20,21.NOESIS software is often used to classify reference signals. NOESIS is based mainly on the pattern recognition method in two versions: with an arbitrary division into classes (unsupervised—USPR) and self-learning, in which the division into classes was performed with the use of reference signals (supervised—SPR) ,16,22,23In the first case, the analyses of arbitrary patterns are used mainly to create a database of pattern signals, if the number of classes is unknown. The second method is used when reference signals characterising given destructive processes are available. The reference signals are signals previously collected in databases, generated during independent experiments ,22,23,24In the case of statistical methods used to recognise objects, an important issue is the optimal selection of the recorded acoustic emission parameters. Many parameters of the acoustic emission show a strong mutual correlation, which means that they can provide the same information about the AE source. The degree of correlation between the AE parameters is determined by the so-called dendrograms that are created during the grouping of signals with the use of various algorithms depending on the model used ,21,22,23An important issue that can affect the accuracy of the calculations, which should also be taken into account, is the number of iterations needed to obtain satisfactory results. A sufficient number of iterations is 10.000, as proved by experiences in the analysis of concrete elements and structures. Reducing this number caused a significant decrease in signal matching in individual classes while increasing this number slowed down the process of analysis and the obtained results improved the matching to a small extent ,24,25.k-means algorithm provides accurate results in terms of matching. It belongs to the group of non-hierarchical group algorithms. The algorithm is based on the initial random selection of the location of the centres of the groups. In the subsequent iteration steps, after calculating the function of belonging to individual points to group centres, they are each time recalculated. Such a procedure causes the groups’ centres to search for their correct positions [The NOESIS program uses various grouping methods, but the user’s manual of the application does not provide guidelines for selecting one of them. The fuzzy ositions ,21,22.In the case of this algorithm, it is obligatory to impose the number of groups. However, the speed of computation and matching make up for these inconveniences.While the USPR method classifies the AE sources on the basis of the similarity of signals without assigning appropriate mechanisms to the groups, the SPR method assigns specific processes to groups, provided that a database of reference signals is available.So far, the AE method has been applied to concrete composites reinforced with equally distributed steel reinforcement, primarily to monitor various stages of the cracking process. The analyses focused mainly on the observation of changes related to single parameters. Attempts were made to extend the analyses to the observation of energy and frequency parameters, but as a rule, the values were maintained at the level of 2–3 and were not statistically correlated with each other ,24,25,26k-means algorithm. The individual classes were linked to the destructive processes taking place in the material under load. During grouping, 14 signal parameters listed below in this paper were taken into account.In this paper, the grouping of recorded signals into classes was performed using the The developing direction of the loaded concrete behaviour analyses is numerical calculations using the finite element method (FEM) ,31,32,33The currently available computer programs support the interpretation of the results obtained in the experimental tests of the fracture mechanics parameters. An example is GOM Suite optical analysis software used to analyse the results of non-contact measurements of displacement and deformation of flat and spatial elements subjected to loads ,43,44.GOM Suite is a program for preparing shape and dimensional analysis, 3D inspection and processing of meshes from 3D point cloud data and CAD data obtained by fringe projection technique using laser scanners, coordinate measuring machines (CMM) and other measurement systems .GOM Suite software is used, among other things, in the crack analysis of concrete samples, enabling the creation of detailed analyses of crack propagation. It allows us to understand the mechanics of fracture and to observe the directions of complex stresses inside the material.The problem of failure under load of concrete elements is a current issue being taken up by researchers. Intensive work is underway on the introduction of concrete additives to improve its characteristics, including by using steel fibres or other materials/measures. The number of studies covering the issues of determining the strength characteristics of concrete is associated with the complexity of the destruction process and many factors influencing the process of damage development and final destruction. The source of information about the concrete destruction process is experimental tests carried out in laboratories. Along with the development of new research methods, experimental research is supplemented, among others, by non-destructive testing  ,49,50,51A1 did not contain any fibres. Sample A2 contained fibres in the amount of 40 kg/m3. Sample A3 contained fibres in the amount of 60 kg/m3. The compositions of samples are given in Three samples with dimensions of 150 × 150 × 700 mm were used in the tests. The samples were different in terms of the steel fibre content. Reference sample Fibre concrete samples were subjected to three-point bending using a, v . During the tests, the following signals were recorded: test time, traverse displacement and the force loading the specimen. The distance between the supports in the machine was 600 mm. Samples were loaded to destruction. The diagram and view of the test stand are shown in AE signals were recorded during the tests. For this purpose, an AEWin acoustic emission processor  and two VS75-SIC-40dB sensors by Vallen  were used. Due to the measurement sensitivity of AE sensors, the AE sensors calibration procedure was carried out before the start of target measurements. For this purpose, readings of the AE signal parameters were performed, generated by a reference source—broken graphite of a Pentel pencil with a diameter of 0.3 mm and a hardness of 2H, set at an angle of 30 degrees to the surface of the tested element (Hsu-Nilsen source). The length of the extended graphite was about 2.5 mm. Breaking graphite was associated with the emission of signals with an amplitude above 95 dB. On this basis, it was found that the signals are recorded correctly ,16,19.During the study, an image of the front of the sample was recorded for later analysis using a digital image correlation system . The use of the DIC System made it possible to determine the level of strain present in the analyzed component. The front of the sample was properly prepared before the test by applying a layer of paint .Fourteen parameters of AE signals were used to create a base of reference signals for destructive processes in the fibre concrete samples:k-means algorithm, one of the fourteen acoustic emission parameters, which is the signal energy, was used as an illustration of the processes taking place. The individual classes of EA signals, on the basis of preliminary studies, were assigned to the processes taking place in the structure of the tested material:Class 1 (blue)—microcrack initiation;Class 2 (green)—crack formation and propagation;Class 3 (red)—crack development, concrete crushing;Class 4 (purple)—plastic deformation, material failure.After dividing the recorded AE signals into four classes, using the A1 . Knowledge of the stress–strain curves drawn during the compression and tensile tests of fibre concrete was required. The results found in professional studies served as support in determining the individual parameters of the model ,55,56,57As a result of numerical calculations, selected values of the mechanical fields developing in the analysed fibre concrete elements during loading were determined. The results obtained for: effective stress (according to von Mises) and maximum principal strain  are presented , Table 4A3, 60%) was about 35%. In contrast, the highest level of maximum principal strain was recorded for the analysed concrete specimen with steel fibre participation at 60%. It was about 1/3 higher than for the sample without the share of steel fibre reinforcement (A1).The highest level of effective stress (according to von Mises) occurred for the fibre concrete specimen without the addition of reinforcing steel fibres. As the percentage of steel fibres in the concrete increased (40% and 60%), a decrease in the maximum effective stress level was observed. The decrease in the level of effective stress for the sample without reinforcement and with the proportion of steel fibres (A1) and the other materials analysed . The differences took place due to the proportion of steel fibres in the concrete marked A2 and A3. The nature of the distribution of effective stresses in the cross-section of the analysed specimens was similar for the three materials included in the numerical analysis.In the case of the distributions of the fields of maximum principal strains , some diA2 material of around 3.6%. The results of the GOM system analysis were strongly influenced by the careful application of the paint layer on the sample and the careful positioning of the video recording device during testing in the laboratory.Three-point bending tests on specimens made of the analysed fibre concrete were accompanied by recording the deformation process of the material using the GOM system. In the next step of the analyses, this allowed us to confront the distributions of the first principal strains determined: as a result of numerical calculations and those determined using the GOM Correlate software , Table 5Three-point bending of fibre concrete samples is associated with the emission of acoustic signals characteristic of various destructive processes occurring in the material.The addition of curved steel reinforcing fibres in the form of equally distributed reinforcement changes the number and distribution of acoustic emission signals of individual classes.The differences in the number and distribution of acoustic emission signals of individual classes are observed at a low level of load and deformation.The acoustic emission method is very useful for monitoring elements or structures made of concrete reinforced with equally distributed steel fibres under load.In this paper, a hybrid method of analysis is proposed, which consists in complementing the results of strength tests, the results of numerical calculations and the results of deformation distributions (through the use of the GOM system). The proposed test method allows the determination of the characteristic values of the mechanical fields in the material, the knowledge of which makes it possible to assess the strength of concrete in its initial state and with reinforcement in the form of steel fibre participation.A3).It was shown that the numerically determined effective stress levels decreased as the proportion of steel fibres in the concrete increased. However, the maximum levels of the first principal stresses increased . Based on the conducted research and analyses, the following conclusions were drawn:Based on the analyses and the conclusions drawn from the research, the authors planned further tests on the monitoring of the condition and deformation of fibre concrete. It is planned to extend the analyses of the recorded acoustic emission signals towards the evaluation of changes in the time–frequency spectra of the recorded acoustic waves. It is also planned to extend the analyses with the use of FEM  and the GOM system.


A capillary zone electrophoretic (CZE) method was developed, validated, and applied for the assay of metformin (MET) and pioglitazone (PIO) in pharmaceutical formulations. The optimum running buffer composition was found to be 75 mmol/L phosphate buffer containing 30% acetonitrile (ACN) at pH 4.0. The optimum instrumental conditions were found to be injection time, 10 s; applied voltage, 25 kV; hydrodynamic injection pressure, 0.5 psi for 10 s, capillary temperature, 25 °C; and the detection wavelength, 210 nm. The quantifications were calculated based on the ratio of the peak areas of analytes to atenolol as an internal standard. The CZE method was validated in terms of accuracy (98.21–104.81%), intra- and inter-day precision of migration time and peak area (relative standard deviation ≤ 5%), linearity (correlation coefficients ≥ 0.9985), limit of detection (≤0.277 μg/mL), and limit of quantitation (≤0.315 μg/mL). The proposed method was applied for the analysis of PIO and MET both individually and in a combined dosage tablet formulation. All electrophoretic parameters were calculated and evaluated. A previously reported high-performance liquid chromatographic (HPLC) method was also applied to the same samples. A comprehensive comparison was then carried out for the analytical features of both methods CZE and HPLC. Comparable results were obtained with the advantage of reagent consumption and separation efficiency of CZE over HPLC and shorter analysis time by HPLC compared with CZE. Diabetes mellitus is a serious metabolic disorder characterized by high blood glucose levels and occurred when the body is not able to produce enough insulin or cannot use insulin effectively ,2. It haChemically, metformin (MET) is 1,1-dimethyl biguanide a. It is 1c) of ≥9 or glycemic target is not achieved after three months of treatment with MET [It is recommended to use a second agent along with MET if patients suffer from a high level of glycated hemoglobin  has evolved into a highly mature analytical technique. After its instrument commercialization, CZE has taken its place among well-established analytical techniques, in general, and separation techniques, in particular ,26,27,28In this context, CZE was exploited for the assay of MET ,31,32,33Primarily, spectrum scans of both drugs MET and PIO were carried out by a UV/Vis spectrophotometer. The maximum absorbance of MET and PIO were detected at 210 nm. Therefore, the PDA detector coupled with the CZE system was set at 210 nm for the quantification of both MET and PIO. In addition, the preliminary investigation also showed that phosphate buffer recorded better electropherograms, in terms of resolution, migration time, peak shape, peak height, baseline noise, and the electric current produced, than borate and acetate buffers. The literature also reported that the use of phosphate buffer was appropriate for MET ,36 and PIn separation of ionizable molecules by CZE, pH has a significant role, as it controls the degree of ionization of solutes . The aciThe buffer concentration also plays an important role in controlling the EOF and the current produced in the capillary, baseline stability, and peak shape that affect affects separation efficiency. In the current study, the examined phosphate buffer concentrations were 20, 50, and 75 mmol/L. Better resolution and baseline was achieved with 75 mmol/L phosphate buffer concentration, therefore it was chosen as the optimum.Furthermore, the addition of an organic solvent to the running buffer was experimented because of its effect on viscosity, dielectric constant, and zeta potential, in addition to the low solubility of PIO in a buffered aqueous solution. Notably, ACN and methanol are recommended as non-aqueous solvents in CZE. Such solvents manipulate separation selectivity. The lower currents in non-aqueous solvents enable wide bore capillaries, which allows larger sample load, and enables the use of high electric field strengths. Detection sensitivity, in many cases, can also be enhanced . DiffereFor other instrumental conditions, voltage is an important parameter in CZE that greatly affects in both migration times and resolution. The effect of voltage on electrophoretic parameters was studied at 15, 20, and 25 kV. It was noticed that high applied voltage increases the EOF and thus leads to shorter migration time and higher efficiency. As a result, a voltage of 25 kV was set as the optimum. In addition, temperature of the capillary column affects the viscosity of the buffer and thus affects EOF and electrophoretic mobilities. The effect of temperatures on separation was investigated at 20, 25, and 30 °C. The 25 °C was chosen as the optimum temperature in terms of resolution and analysis time. Moreover, the change in injection time leads to the change in the height and width of the peaks. In the current study, the samples were injected hydrodynamically at 0.5 psi in different injection times 5.0, 10.0, and 15.0 s. By comparing the obtained results, it was found that at 5.0 s the peaks intensity is very low while at 15.0 s the peak of PIO was expanded and deformed. 10.0 s showed the best result and therefore it was set as the optimum injection time.From the above experiments, the optimum running buffer composition for the simultaneous analysis of MET and PIO was 75 mmol/L phosphate buffer containing 30% ACN at pH 4.0. On the other hand, the instrumental optimum conditions were injection time, 10 s; applied voltage, 25 kV; capillary temperature, 25 °C; and the detection wavelength, 210 nm.The proposed CZE method was validated with respect to linearity, limit of detection (LOD), limit of quantification (LOQ), precision, and accuracy. In this context, the calibration curves were plotted using calibrator concentrations against the peak area ratio  against the drug concentration. Five calibrators for MET  and six calibrators for PIO  were used. The method of least squares was used and, accordingly, the regression parameters were calculated. As a result, the correlation coefficients for MET and PIO were 0.9988 and 0.9985 respectively, indicating acceptable linearity ,42. The On the other side, the LODs (μg/mL) of MET and PIO were 0.091 and 0.277, respectively, whereas the LOQ (μg/mL) of MET and PIO were 0.104 and 0.315, respectively. It might be noticed that the LOD and LOQ of MET are slightly lower than those of PIO. Nevertheless, all levels are appropriate for the assay of both drugs in their pharmaceutical formulations as both drugs are active ingredients and present at high levels.The intra-day precision was assessed by injecting five times in a day a standard mixture of MET and PIO at three different concentrations within the linear calibration curve, at 20, 40, and 60 μg/mL. The inter-day precision was also assessed by injection over a period of six days with standard mixture containing both drugs at 20, 40, and 60 μg/mL. The results are all compiled in The accuracy of the CZE method was examined based on spiking in commercial tablet formulations. Several aliquots of the MET and PIO mixture at three different concentrations, namely, 20, 40, and 60 μg/mL, were added to a weighted, ground powder of the MET and PIO combination tablet. The proposed CZE method was applied to the determination of MET and PIO in the individual tablets and in a synthetic mixture as well as in their co-formulated tablets. The electrophoretic parameters including peak area, peak width, peak symmetry, and resolution are presented in ® tables (500 mg MET) was successfully separated in the presence of 50 µg/mL IS. ® tablets (30 mg PIO) in the presence of 50 µg/mL IS. These outputs demonstrate neither interference nor overlap of inactive ingredients of tablets formulations manufactures by different pharmaceutical industries with the single active ingredient of either MET or PIO. Furthermore, a synthetic mixture of 75 µg/mL MET, 50 µg/mL IS, and 30 µg/mL PIO exhibits successful separation as shown in ® included 75 µg/mL MET, 1.323 µg/mL PIO, and 50 µg/mL IS. Another sample solution of Actosmet® included 1698 µg/mL MET, 30 µg/mL PIO, and 50 µg/mL IS. These two electropherograms confirm the selectivity of the CZE assay method for MET and PIO in real tablet formulation including different concentrations of active ingredients.The electropherograms of the applications of the CZE method to pharmaceutical formulations are illustrated in in A previous HPLC method  was applIt is noteworthy mentioning here that the CZE method consumed volumes of reagents and samples in microliters (0.0785), while the HPLC method consumed > 8 mL. Therefore, the CZE method is more economical and environmentally friendly than the HPLC method. Notably, several recent studies reported green analytical CZE methods for a wide range of applications including pharmaceutical, medicinal, food, and environmental analyses ,44,45,463OH) and acetonitrile (ACN) were purchased from Merck . Deionized water was purified by a Milli-Q system  and was used throughout for the preparation of solutions. Orthophosphoric acid (85%), sodium phosphate dibasic heptahydrate, ammonia, hydrochloric acid, and sodium hydroxide were purchased from Sigma-Aldrich . Standard materials of MET hydrochloride and PIO hydrochloride were supplied from Toronto Research Chemicals INC . Atenolol standard material was supplied from Sigma Aldrich, . Glucophage® tablets (500 mg MET) were prepared by Merck Serono. Actos® (30 mg PIO) was prepared by Arab Pharmaceutical Manufacturing Co., Ltd., Amman, Jordan. Actosmet® tablets (15 mg PIO /850 mg MET) were prepared by Jazeera Pharmaceutical Industries (JPI).Analytical-grade methanol  and a temperature-controlled sample storage module. The system is controlled by 32 Karat Software configured on a desktop controller. A fused-silica capillary column  with a total length of 40 cm and effective length of 37 cm with an internal diameter (ID) of 52 μm was set up. The capillary was housed in a cartridge with a detector window of 100 × 800 µm (10 cm to the detector). Samples were hydrodynamically injected in the capillary at 0.5 psi for 10 s. The applied voltage was adjusted at 25 kV, while the temperature was set at 25 °C. The Thermo Scientific™ Orion™ 2-Star pH meter was used. The Shimadzu UV-1650, which is a calibrated double beam UV-visible spectrophotometer, was used as well. The Shimadzu prominence-A standard stock solution (1000 μg/mL) of MET was prepared in distilled deionized water, whereas a stock standard solution of PIO (1000 μg/mL) was prepared in methanol with the addition of few drops of HCl. Additionally, a standard stock solution of atenolol (1000 μg/mL), as an IS, was prepared in methanol. All solutions were sonicated and filtered through 0.45 μm PTFE Millipore filter. Mixed working standard solutions were prepared in the running buffer  in an appropriate way at different concentrations ranged from 5 to 120 µg/mL for calibration purpose.An amount of 200 mmol/L of sodium phosphate dibasic heptahydrate buffer was prepared as a stock solution, then diluted to different concentrations  with ACN and distilled water. All solutions were sonicated and filtered through a 0.45 μm PTFE Millipore filter. The pH was adjusted with orthophosphoric acid 85%. The optimized running buffer solution was 75 mmol/L sodium phosphate buffer at pH 4.0.Ten tablets of each MET, PIO, and PIO-MET combination as previously described were weighed and powdered. Appropriate amounts were accurately weighed and transferred to 50-mL volumetric flasks. A MET tablet was dissolved in water, while PIO tablet and PIO-MET tablet combination were dissolved in methanol with the addition drops of HCl. A blank solution was synthesized for each individual drug. All solutions were sonicated and filtered through a 0.45 μm PTFE Millipore filter.This study demonstrated the development of a CZE method for the separation and simultaneous determination of MET and PIO. All chemical and instrumental parameters presumed to be controlling the efficiency of the method were examined and optimized. Under the adopted optimum conditions, MET and PIO, besides the IS, were electrophoretic migrated and successfully separated in less than 4 min. After a rigorous comparison of CZE against HPLC, comparable features were obtained. Nevertheless, the CZE has the advantages of reduction of reagent consumption from milliliters to microliters and larger number of theoretical plates due to the use of capillary columns in electrophoresis technique. Therefore, the proposed CZE method is an appropriate alternative to be applied for routine analysis in pharmaceutical industry.


IgG4-related disease (IgG4-RD) was recently described in Japan. It is characterised by extensive organ involvement with tissue fibrosis. We assessed the performance of the 2019 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria and the 2020 revised comprehensive diagnostic (RCD) criteria as well as differences between patients with and without IgG4-RD. In this retrospective, single-centre study of 50 patients admitted with suspected IgG4-RD, we evaluated the sensitivity and specificity of both criteria. We also compared clinical characteristics and laboratory data of patients with IgG4-RD (n = 42) and patients without IgG4-RD (n = 8). The ACR/EULAR classification criteria had 88.1% sensitivity and 87.5% specificity for IgG4-RD diagnosis. The RCD criteria had 100% sensitivity and 50% specificity. Patients with IgG4-RD had significantly more affected organs (p = 0.002). Patients with a single affected organ and IgG4-RD had significantly higher serum IgG4/IgG ratios (p = 0.027), lower serum C-reactive protein levels (p = 0.020), and lower total haemolytic complement activity (p = 0.044) than those without IgG4-RD. The ACR/EULAR classification criteria have high specificity and the RCD criteria have high sensitivity for diagnosing IgG4-RD. The number of affected organs is important for diagnosing IgG4-RD. Although the Japanese IgG4-RD team established comprehensive diagnostic (CD) criteria for IgG4-RD in 20112, several issues with the 2011 CD criteria have been raised, such as difficulty in performing tissue biopsies in some patients with suspected IgG4-RD and concerns about the usefulness of serum IgG4 levels for diagnosis4. Because IgG4-RD and other diseases have overlapping clinical features, it is important to distinguish between them accurately. It is well known that some patients without IgG4-RD have high serum IgG4 levels and more IgG4-positive cells in affected tissues7.Immunoglobulin G (IgG) 4-related disease (IgG4-RD) was first described in Japan. It is characterised by extensive organ involvement with tissue fibrosis and IgG4-positive plasma cell infiltration8. However, there is concern about the exclusion criteria; patients positive for disease-specific antibodies are excluded from analysis for IgG4-RD before they are assessed for other autoimmune diseases. The revised comprehensive diagnostic (RCD) criteria for IgG4-RD were proposed by a team from the Ministry of Health, Labour and Welfare of Japan in 20209. The 2020 RCD criteria were a revision of the 2011 CD criteria. Definite IgG4-RD, which includes patients who meet the organ-specific criteria for IgG4-RD and pathological diagnoses including storiform fibrosis and obliterative phlebitis, was added. However, there are still few studies about the performance of the 2020 RCD criteria in diagnosing IgG4-RD.In 2019, the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) proposed criteria that can classify IgG4-RD with high specificity, without tissue biopsyIn this study, we evaluated the performance of both the 2019 ACR/EULAR classification criteria and the 2020 RCD criteria in diagnosing IgG4-RD. We also evaluated clinical differences between IgG4-RD and other diseases.2 or respective organ-specific criteria for IgG4-RD16 after excluding other diseases. We also did not include patients who were initially diagnosed with IgG4-RD but ultimately diagnosed with another disease. This study was approved by the ethics committee of Juntendo University Hospital  and conducted in accordance with the principles of the Declaration of Helsinki. The need to obtain informed consent was waived by the ethics committee of Juntendo University Hospital because of the retrospective design.We retrospectively evaluated patients who were admitted to Juntendo University Hospital with suspected IgG4-RD from April 2010 to March 2022. Rheumatologists certified by the Japan College of Rheumatology diagnosed IgG4-RD based on the 2011 CD criteria17. The sensitivity and specificity of the 2019 ACR/EULAR classification criteria and the 2020 RCD criteria were evaluated by rheumatologists.We collected clinical data, including patient demographics, laboratory data at diagnosis, and outcomes, from medical records. The number of involved organs was counted from 11 lesions, based on a previous studyThe 2019 ACR/EULAR classification criteria consist of a three-step process. Step 1 involved the entry criteria; a patient met the entry criteria if there were characteristic clinical or radiologic involvement in a typical organ. Step 2 involved the exclusion criteria; a patient met the exclusion criteria if they had any clinical, serologic, or pathologic exclusion items. If the patient met entry criteria and did not meet any exclusion criteria, Step 3 was initiated. Step 3 involved the inclusion criteria; a patient met the classification criteria for IgG4-RD if the total number of points over 8 domains was ≥ 20.16 were also regarded as having definite IgG4-RD. In addition to definite IgG4-RD, probable IgG4-RD and possible IgG4-RD also met the 2020 RCD criteria. The details of both criteria were provided in previous publications9.The 2020 RCD criteria contained three items: (1) clinical and radiological features, (2) serological diagnosis, and (3) pathological diagnosis. Patients who fulfilled all three items were diagnosed with definite IgG4-RD. Those who fulfilled items (1) and (3) were diagnosed with probable IgG4-RD. Those who fulfilled items (1) and (2) were diagnosed with possible IgG4-RD. Patients with a diagnosis of possible or probable IgG4-RD based on the CD criteria who fulfilled organ-specific criteria for IgG4-RDU test to analyse continuous variables and Fisher’s exact test to evaluate categorical variables. Sensitivity referred to the proportion of patients with IgG4-RD who met the diagnostic criteria. Specificity referred to the proportion of patients with other diseases who did not meet the diagnostic criteria. The Kappa coefficient was used for assessing agreement between the criteria 18. To evaluate the predictive performance of clinical data, receiver operating characteristic (ROC) analysis was performed. We calculated the cut-off point using Youden’s index. P-values < 0.05 were considered statistically significant.Statistical analysis was performed using SPSS version 23.0 software . We used the Mann–Whitney A total of 50 patients with suspected IgG4-RD were admitted to our hospital and we diagnosed 42 patients with IgG4-RD. Patients who were not diagnosed with IgG4-RD had multicentric Castleman disease (n = 2), non–IgG4-related idiopathic retroperitoneal fibrosis (n = 2), malignant lymphoma (n = 1), dedifferentiated liposarcoma (n = 1), urothelial carcinoma (n = 1), and undiagnosed disease (n = 1). The ACR/EULAR classification criteria had 88.1% sensitivity and 87.5% specificity for IgG4-RD diagnosis. On the other hand, the 2020 RCD criteria had 100% sensitivity and 50% specificity for IgG4-RD diagnosis. There were 21 patients diagnosed with definite IgG4-RD, 1 patient with probable IgG4-RD, and 20 patients with possible IgG4-RD. The kappa coefficient for the criteria was 0.43.We compared the clinical characteristics and laboratory data at admission of patients with versus without IgG4-RD. Only the number of affected organs differed significantly between these two groups Table . Figure 8. We also found that the 2020 RCD criteria enabled diagnosis with high sensitivity. The kappa coefficient between the 2011 CD criteria and the 2019 ACR/EULAR classification criteria showed poor reliability in a previous study19; however, this study showed moderate reliability between the 2020 RCD criteria and 2019 ACR/EULAR classification criteria. One possible explanation is that the 2020 RCD criteria allowed for the diagnosis of definite IgG4-RD with organ-specific findings or additional pathological findings, which allowed for the diagnosis to be made regardless of serum IgG4 levels, thereby increasing the agreement between the two sets of criteria.In this study, we evaluated the performance of the classification and diagnostic criteria for IgG4-RD in patients admitted to hospital with suspected IgG4-RD. We confirmed that the 2019 ACR/EULAR classification criteria enabled disease classification with high specificity, similar to the results of a previous study20 according to one study, but another study found them to be less useful4. These results also showed that it was difficult to differentiate IgG4-RD from other diseases based serum IgG4 levels and the IgG4/IgG ratio. However, we confirmed the usefulness of the IgG4/IgG ratio in a sub-analysis limited to patients with a single affected organ. Previous studies showed that many patients with IgG4-RD have multiple affected organs21 and as the number of affected organs increases, so do serum IgG4 levels22. However, patients with IgG4-RD who have relatively small and restricted lesions have been reported to have higher IgG4/IgG ratios, even in the absence of elevated serum IgG levels20. CH50 and serum CRP levels were also significantly lower in patients with IgG4-RD than patients without IgG4-RD among patients with a single affected organ. A previous study reported hypocomplementemia and low serum CRP levels in IgG4-RD23; we had similar results in this study. The mechanism underlying hypocomplementemia in IgG4-RD remains unclear, but it has been reported that IgG4-RD with hypocomplementemia is associated with more kidney or lung involvement and relapse17. Since serum CRP levels are often elevated in mimickers such as multicentric Castleman disease5, we might have identified a significant difference in serum CRP levels among patients with versus without IgG4-RD with a single affected organ. For the diagnosis of IgG4-RD, focusing on laboratory data such as the serum IgG4/IgG ratio relative to the number of affected organs is expected to help increase diagnostic accuracy.There were no significant differences in patients with versus without IgG4-RD in this study, other than in the number of affected organs. Serum IgG4 levels and IgG4/IgG ratio were considered useful for diagnosing IgG4-RDThis study has several limitations. It used a single-centre, retrospective design. Interpreting results for classification criteria may require caution, because the purpose of classification criteria is to create homogenous cohorts for clinical research and not for diagnosis. Due to the limited number of patients, multivariate analysis was not performed. The results of this study might need to be confirmed in larger studies.In conclusion, the 2019 ACR/EULAR classification criteria have high specificity and the 2020 RCD criteria have high sensitivity for diagnosing IgG4-RD. The number of affected organs is also important for diagnosing IgG4-RD, with particular attention to the serum IgG4/IgG ratio in the case of single organ involvement.


Machine-made sand instead of natural sand has become an inevitable choice for the sustainable development of the concrete industry. Orthogonal experiment and grey correlation analysis were used to investigate the performance of machine-made tuff sand concrete. The optimal concrete mix ratio of machine-made sand was obtained by orthogonal test and its working performance was verified. Grey correlation analysis was applied to compare the factors affecting the mechanical properties of the machine-made sand concrete. The test results show that the sand rate has the greatest degree of influence on slump and slump expansion. The mineral admixture has the greatest effect on the 7-day compressive strength of the concrete. Additionally, the water–cement ratio has the greatest influence on the 28-day compressive strength. The mechanical and working properties of the machine-made sand concrete reach the optimum condition when the mineral admixture is 20%, the sand rate is 46%, the stone powder content is 10% and the water–cement ratio is 0.30. Comparing different fine aggregate concretes of similar quality, we conclude that the mechanical and working properties of tuff sand concrete and limestone sand concrete and river sand concrete are similar. The compressive strengths of the mechanism concrete show the greatest correlation with roughness and the least correlation with stone powder content. The stone powder content has almost no effect on the compressive strength of concrete when the stone powder content does not exceed a certain range. The results of the study point out the direction for the quality control of concrete with machine-made sand. Concrete is the most widely used material for building structures today. As China invests more in infrastructure construction, concrete consumption is still on the rise. Fine aggregates account for about one-third of the raw materials for concrete. Fine aggregates can be divided into natural sand and artificial sand . River sThere are many methods for designing the proportioning of machine-made sand concrete, and different proportioning methods have their own focus ,6. They Today, the complexity of civil engineering has prompted the industry to develop a variety of new materials. In line with the concept of sustainability, the construction industry is trying to replace ordinary silicate cement concrete using geopolymer concrete ,24,25. STherefore, in this study, the research on machine-made tuff sand concrete is carried out through the following aspects. Firstly, the factors influencing the high-performance machine-made sand concrete mix ratio are analyzed. These factors to be optimized are used as influencing factors for orthogonal tests. The test results are analyzed to find the optimum level of concrete performance under each influencing factor. The optimal machine-made sand concrete ratio is obtained, and the performance of concrete under the optimal ratio is verified. We used the grey correlation analysis to calculate the correlation between fine aggregate stone powder content, clay lump content, roughness and compressive strength. The main factors affecting the mechanical properties of the machine-made sand concrete were analyzed. Then, we compare the correlation matrices of tuff and limestone machine-made sand. The magnitude and laws of different factors on the concrete properties are analyzed to show the direction for the quality control of the machine-made sand concrete.2/kg. Fly ash used Grade II fly ash with a fineness of 45 μm sieve margin of 15.2%, a burn-off of 1.78%, and a water demand ratio of 101%. Slag powder using S95 grade slag powder, specific surface area 411 m2/kg, 7-day activity index 83%, water content 0.85%, flow rate ratio of 98%. Water reducing agent is selected from a high efficiency water reducing agent. Polycarboxylic acid water reducing agent has the characteristics of low dosing and high water-reduction rate. The water reduction rate is 25%. In this study, the dosing range is 1.2%~1.8% of the cementitious material. The experimental mixing water is tap water, which meets the requirements of Chinese national standards. The fine aggregates are selected from machine-made tuff sand (number NH), machine-made limestone sand (number SH) and river sand (number HS). The physical index of fine aggregate is shown in 3 and bulk density of 1.52 g/cm3. The gradation curve of fine aggregate is shown in In this study, P.O 42.5 grade ordinary silicate cement was used for the cement. Its 28-day flexural strength was 7.5 MPa and compressive strength was 46.8 MPa, specific surface area was 348 mOrthogonal experimental design is a quantitative design analysis method for studying multiple factors and levels. This experiment method is commonly used to optimize mortar and concrete properties ,37. TherWe used the full calculation method to perform preliminary tests on the properties of the machine-made sand concrete. The mix ratio was optimized by considering the level of factors and the number of tests. Four levels were set for each factor, and a 4-factor, 4-level orthogonal test table was selected for the experiments. The parameter values under each level are shown in Three different types of fine aggregates, machine-made tuff sand, machine-made limestone sand and river sand , were selected and tested in different batches of the same fine aggregate. Additionally, the fineness modulus, bulk density, apparent density, clay lump content and roughness of each batch were measured. Four batches of machine-made tuff sand , four batches of machine-made limestone sand , and two batches of river sand  were sieved to obtain two types of stone powder to adjust the stone powder content of the sand. The stone powder content of each batch of the two types of sand was set to 3.0%, 6.5%, 10.0% and 13.0%. The clay lump content of the batches of the two types of machine-made sand fluctuated widely from 0.2% to 0.9%. The clay lump content of river sand was higher at 0.7% and 0.9%. The performance indicators of each batch of fine aggregate meet the corresponding national standards, and the main performance indicators are shown in The degree of influence of index properties such as stone powder content, clay lump content and roughness of the machine-made sand on the mechanical properties of concrete is different. The compressive strengths of concrete with different fine aggregates were tested and obtained through comparative studies of concrete with different batches of tuff and machine-made limestone sand and river sand. The correlation between the stone powder content, clay lump content, roughness of the machine-made sand and compressive strength of the concrete was also calculated by using the grey correlation analysis. The correlation matrix was analyzed to derive the magnitude and influence law of each factor on the degree of performance.The concrete strength grade in this study is C50, which is mainly applied to the T-beam in the bridge structure. The T-beam is the main component of the main structure of the bridge and has a design service life of 100 years. The concrete is required to have good working properties and mechanical properties, and the trial strength reaches 1.15 times of the design strength.The working performance test indexes are slump and slump expansion. Additionally, the specific operation is carried out in accordance with the Chinese standard GB/T 50080-2016 “Standard for Test Methods of Properties of Ordinary Concrete Mixes”. The mechanical performance test indexes are compressive strength at 7 and 28 days. Additionally, the specimen size is 150 mm × 150 mm × 150 mm concrete test block, the test method is conducted according to the Chinese standard GB/T 50081-2002 “Standard on Mechanical Properties of General Concrete”. The process of this study is shown in Sixteen sets of concrete test blocks designed for orthogonal experiments were tested for working properties and mechanical properties. The results of the concrete slump and compressive strength tests are shown in The orthogonal experimental design software Minitab 20  was used to perform a polar difference analysis on the experimental results. The extreme difference refers to the difference between the maximum value and the minimum value of the mean value of the test index corresponding to each level in each column. The effect of each level on the test indexes was ranked from largest to smallest by the extreme difference analysis. The results of slump and slump expansion analysis of concrete are shown in From The results of the 7-day and 28-day compressive strength extreme difference analysis of the machine-made sand concrete are shown in From Single factor analysis refers to the situation where the test results vary with a single factor when other factors are constant. The analysis of the effect of single factor on the slump and slump expansion of the machine-made sand concrete is shown in (1)The amount of mineral admixtureAs shown in (2)Stone powder contentAs shown in (3)Sand rateAs shown in (4)Water–cement ratioAs shown in In summary, the optimal working performance of the machine-made sand concrete is achieved at a mineral admixture of 20%. Although the corresponding compressive strengths of concrete are not the respective maximum values, they differ from the maximum values by a small margin. The concrete slump and slump expansion are at maximum, and the compressive strengths of concrete are maximum when the sand percentage is 46%. When the stone powder content is 10%, the working performance is better, and it is in the state of imminent deterioration of performance. At this time, the compressive strengths have great values. With the increase in the water–cement ratio, the concrete slump and slump expansion show a gradual increase in trend, which has a certain improvement effect on the work performance. The water–cement ratio has a significant effect on the compressive strengths of concrete, and the strength decreases significantly as the water–cement ratio increases. Therefore, in order to ensure that the concrete has excellent mechanical properties, a lower water–cement ratio should be used as much as possible.3B3C3D1. This is the optimal combination ratio of the machine-made sand concrete obtained from the orthogonal test. However, this group of tests was not available in the orthogonal tests. To further verify the accuracy of the results, three sets of tests were set A3B3C3D1, A4B3C3D1 and A3B3C3D2. The numbers are Y-1, Y-2 and Y-3. The working properties and mechanical properties of the machine-made sand concrete were tested. The matching ratio and test results of the verification experiments are shown in From the above points, it can be seen that the mineral admixture, sand rate and stone powder content are all at level 3 and the water–cement ratio is at level 1, i.e., AFrom NH1 denotes the first set of experiments, using fine aggregate of batch number NH1, and so on.)From Combining Grey correlation analysis is based on the similarity of the geometry of the series curves to determine whether they are closely related or not ,43,44. G1.Data column representation.kth case is denoted as Specify the reference data column, which is often noted as 2.Initialization process.Before calculating the correlation coefficient, the series needs to be primed. Each number in the series can be divided in turn by the maximum value in the series to obtain a dimensionless data series for easy comparison.3.Calculation formula of correlation coefficient and correlation degree.k comparison subsequences Referring to the parent sequence The degree of correlation is calculated by the following equation.4.Construction of the strengths analysis matrix.m parent factors and the corresponding n child factors are ordered in a row to obtain the correlation matrix R. The correlation matrix allows the dominance analysis of the parent and child series.The correlations of the R(1) and the machine-made limestone sand correlation matrix R(2).Based on the experimental results in R(1) and the limestone sand concrete correlation matrix R(2),i = 1, 2) indicate that the correlation between compressive strength and roughness at different ages is the largest. Additionally, the stone powder content has the least correlation. Among the three factors, roughness is the main influencing factor on the strength of the concrete of the machine-made sand. The greater the roughness of the concrete aggregate, the stronger the bond between the aggregates and between the aggregates and the cement paste. Concrete is about less prone to damage when compressed, and thus exhibits higher compressive strength. j = 1, 2, 3) indicate that the correlation between the 7-day compressive strength of concrete and roughness, stone powder content, clay lump content is greater compared to the 28-day compressive strength. As the early concrete fly ash has not been fully hydrated, the strength is low, and the enhancing effect of mineral admixture has not been fully developed. Therefore, the early strength of the machine-made sand concrete is more influenced by the roughness and mud lump content. I = 1, 2) indicate that there is no significant correlation between compressive strengths of concrete and stone powder content. When the stone powder t content does not exceed a certain range (about 10%), the stone powder content has little effect on the compressive strength of concrete. For ordinary concrete, the aggregate and cement paste interface is the high incidence of force damage. Additionally, it is dominated by damage to the bonding surface. The effect of stone powder on the bonding effect of aggregate and cement paste is small. Therefore, the stone powder does not improve the compressive strength of concrete significantly.A combined comparison of the machine-made tuff sand concrete correlation matrix NH2 indicates the 12th group of experiments, using NH2 batch of fine aggregates, others as well.)The performance of concrete specimens was determined by reducing the stone powder content and clay lump content of the machine-made tuff sand and blending the improved quality fine aggregate, Number NH5. Additionally, we compare it with NH2 batch of machine-made sand under the optimal combination of matching ratio. The results were also compared with the test results of groups 2 and 3. The apparent and bulk densities of the sand in groups 11 and 12 were not significantly different, and the fineness modulus was 2.7. The fine aggregates in groups 11 and 2 were from the same batch, and the performance index values were not significantly different. Other properties of fine aggregates and experimental results are shown in From the test results, it can be seen that the compressive strengths of the concrete tested in group 12 are greater than the corresponding values in group 11. The index value of fine aggregate roughness in group 12 is greater than that in group 11 and slightly less than that in group 3. In addition, the difference between the compressive strength values of concrete in group 12 and group 3 is small. The experimental results are consistent with the findings of the study.According to the concept of sustainable development, new environmentally friendly construction materials can protect the environment and save construction costs ,25. Qin With the scarcity of natural sand resources, replacing natural sand with machine-made sand has become an inevitable choice for the sustainable development of concrete industry. In this study, the concrete performance of machine-made tuff sand is studied by orthogonal test and grey correlation analysis. From the experimental and analytical results, the following conclusions can be drawn.1.The results of orthogonal tests were analyzed to study the degree of influence of each level on the test index. Among them, the sand rate has the greatest degree of influence on slump and slump expansion. The influence of mineral admixture dosing on 7-day compressive strength was the greatest. The water–cement ratio has the greatest influence on the 28-day compressive strength.2.The optimal mix combination was obtained from the orthogonal test results. The optimal working performance of the machine-made sand concrete was achieved at the mineral admixture of 20%, sand rate of 46%, stone powder content of 10% and a water–cement ratio of 0.30. The performance of the concrete under the optimal mix combination was also verified.3.We compared different fine aggregate concretes of similar quality. It is found that the mechanical properties of machine-made tuff sand concrete are similar to those of machine-made limestone sand concrete and river sand concrete.4.Grey correlation analysis was applied to compare the factors influencing the mechanical properties of tuff and machine-made limestone sands. The correlation between compressive strength of concrete and roughness was found to be the highest. Additionally, the correlation with the stone powder content is the smallest. This points the way to quality control of high-performance machine-made tuff sand concrete.Equal amounts of fly ash and slag powder were mainly considered as mineral admixtures in this study. We can analyze the effect of their different amounts on the properties of machine-made sand concrete in future studies. For the research of high-performance machine-made sand concrete, other environmentally friendly cementitious materials can also be considered.


The Centers for Medicare and Medicaid mandated that nursing homes implement antibiotic stewardship programs (ASPs) by November 2017. We conducted surveys of Wisconsin nursing-home stewardship practices before and after this mandate. Our comparison of these surveys shows an overall increase in ASP implementation efforts, but it also highlights areas for further improvement. Antibiotic stewardship programs (ASPs), which aim to optimize antibiotic prescribing, are critical to combatting antibiotic resistance. The Centers for Medicare and Medicaid services (CMS) mandated that all NHs must implement an ASP by November 2017. This ASP requirement is based on the core elements of antibiotic stewardship for NHs developed by the Centers for Disease Control and Prevention (CDC). Recent assessments of ASPs in NHs have reported high levels of adherence to the CDC core elements; however, knowledge of specific stewardship activities remains limited. In this study, we used survey data to detail the structure and process of ASPs in Wisconsin NHs before and after updates to CMS regulations.Antibiotic use in nursing homes (NHs) is high and frequently inappropriate.1–3). Wisconsin Department of Health Services (DHS) survey 1 was electronically distributed through the Division of Quality Assurance listserv to all licensed NHs from February to May 2015 to capture information on antibiotic stewardship practices before the CMS mandate. Survey 2, a semistructured telephone survey designed to further characterize the structure and process of NH ASPs, was administered between January and April 2016 to a subset of respondents of Survey 1 who volunteered for further contact. Following the mandate, the Wisconsin DHS distributed survey 3, a structured electronic survey, to all licensed Wisconsin NHs from November to December 2018. Completion by the infection preventionist (IP) was recommended. Survey 3 posed the same questions as survey 1 and included elements from survey 2 to capture changes in the structure and processes of NH ASPs following new CMS regulations. Survey elements were encoded, and results were compiled to aid in analysis, which was performed in R version 1.3.1073 software .Between 2015 and 2018, 2 electronic surveys and 1 telephone survey were used to study Wisconsin NHs; they were completed by a facility representative  reported engaging in stewardship activities; however, only 73 (49%) reported having a formally recognized ASP. Following the CMS mandate, all NHs participating in survey 3 reported having a formally recognized ASP.Overall, director of nursing , IP , medical director , and pharmacist  were the roles most involved in stewardship efforts in 2015. Survey 2 revealed that the director of nursing and the IP were responsible for most stewardship activities. However, beyond attending ASP meetings, the medical director and the pharmacist had limited roles in conducting stewardship tasks.Following the mandate, pharmacist  and medical director N = 100, 78%) involvement as members of the facility ASP team remained unchanged. Pharmacist involvement in stewardship tasks increased after the mandate  and/or following the return of culture results . Some less commonly reported strategies included standardized antibiotic formularies  and antibiotic preapproval .C. difficile infections rates , was less common.In survey 1, 126 NHs (73%) reported tracking antibiotic use, although 11 NHs (48%) in survey 2 reported the analysis of trends in these rates. For survey 1, 103 NHs (60%) reported tracking culture susceptibilities in some manner. In survey 2, only 9 NHs (39%) reported using a cumulative susceptibility report . Tracking of other antibiotic use-related outcomes, such as antibiotic adverse events  and Following the CMS mandate, antibiotic utilization tracking increased to 90% (N = 116). The proportion of NHs using rates increased to 63% (N = 72), and 66% (N = 76) reported trending antibiotic use over time. Tracking of antibiotic resistance using an antibiogram also increased . Other studies have reported significantly lower levels of stewardship activity among NHs prior to the new CMS regulations, although considerable geographic variation exists. The higher levels of self-reported stewardship activity identified in Wisconsin NHs in this study prior to the revised CMS regulations may reflect differences in survey design but may also be due to Wisconsin’s enhanced focus on medication safety education and survey activity since 2012. Similar to our findings, national levels of NH-reported antibiotic stewardship activity increased following release of the revised CMS regulations.These surveys show increased implementation of stewardship activities in Wisconsin NHs following the release of the new CMS regulations. Notably, a high level of antibiotic stewardship activities existed in Wisconsin NHs prior to the CMS mandate, although only half had a formalized ASP. In a 2016 national survey of facilities participating in the CDC National Healthcare Safety Network, only 42% of participating NHs reported implementing all 7 CDC core elements of antibiotic stewardship. Here, we built upon these findings by showing that nursing staff, particularly the director of nursing and IP, were primarily responsible for the conduct of specific antibiotic stewardship tasks in Wisconsin NHs. Importantly, pharmacist engagement in stewardship activities increased significantly following the release of the revised CMS regulations. However, the revised CMS regulations appear to have had a minimal effect on the engagement of medical directors in stewardship activities, which remained disappointingly low.Prior studies have identified significant relationships between the comprehensiveness of NH-reported antibiotic stewardship activity and IP certification and turnover. Our findings are consistent with these national trends but suggest areas for continued improvement. Specifically, many NHs continue to track antibiotic utilization using count rather than rate metrics and do not identify trends in utilization data over time. Moreover, the current study shows that antibiogram use in NHs is increasing; however, much about antibiogram structure and its roles in stewardship operations and empiric antibiotic decision making remains unknown.Most NHs participating in national surveys report tracking antibiotic utilization and antibiotic use–related outcomes in some manner. Consequently, comparisons and contrasts drawn with these studies should be viewed with a certain level of caution.This study had several limitations. First, responses were self-reported and potentially affected by normative influences. Second, participation was voluntary with low response rate of licensed NHs, and participating NHs may differ from nonparticipating NHs. Taken together, our results may paint a relatively optimistic view of antibiotic stewardship activity in Wisconsin NHs. Although questions were coded, some differences between survey questions and modalities across time may limit comparability. Additionally, the survey instruments employed in the current study differed from those employed in other studies.


Airport pavement concrete often suffers from freeze–thawing damage in high latitude and cold areas. In addition, the use of aircraft deicer makes the airport pavement concrete suffer from salt-freezing damage. To improve the durability of airport pavement concrete, modified polyester synthetic fiber (FC), cellulose fiber (CF), and basalt fiber (BF) reinforced concrete were prepared in this paper. The mechanical strength, pore structure, and frost resistance  of fiber-reinforced concrete were investigated. The effects of the combined action of fiber (fiber type and content) and surface treatment methods (spraying silane and impregnating silane) on the frost resistance of concrete were investigated. The results show that the flexural strength of concrete is positively correlated with the elastic modulus of fiber, but has little effect on the compressive strength. Fiber can reduce mass loss and dynamic modulus loss of concrete subjected to frost damage. FC more effectively improved the frost resistance of concrete than CF. After 30 cycles of salt freezing, the spalling amount of concrete sprayed or soaked with silane was decreased by 65.5% and 55.5%, respectively. Adding fiber and impregnating silane reduced the spalled concrete by up to 70.5%. Spraying silane treatment is better than impregnating silane treatment in enhancing the frost resistance of concrete because a better silane condensation reaction is achieved with spraying silane. As one of the most basic and important infrastructures of the airport, airport pavement has a significant impact on flight safety and airport operation efficiency. In addition to geometric factors such as length, width, and slope, airport pavement must also meet the requirements of strength, stiffness, flatness, and durability. Cement concrete pavement is the main structural form of airport pavement, which is affected repeatedly by various environmental climates. For example, the pavement concrete of some airports in high-latitude cold areas is damaged by freezing and thawing all year round, resulting in performance degradation, shedding, and failure ,2,3,4,5.In addition to the common failure form of gradual cracking, denudation, and structural failure under the action of repeated freeze–thaw cycles, airport pavement is also damaged by surface denudation caused by freezing in the presence of deicing salt (glycol aircraft deicing fluid). Some concrete with good water-resistant freeze–thaw damage tests will also suffer serious salt freeze–thaw erosion after being sprinkled with deicing salt for several winters, and the pavement aggregate will be exposed, which will seriously affect its use ,7. The tTo improve the flexural strength and frost resistance of pavement materials, fibers are often added to concrete to improve the brittleness and durability of concrete and prevent damage caused by various factors ,9,10,11.In addition to the durability of fiber-reinforced concrete, since the 1980s, the United States has used organosilane materials to spray and soak the concrete structures of roads and bridges to increase the durability of structures. Many durability technical standards also take surface silane impregnation as an effective surface protection measure ,18,19. WIn summary, at present, research on freeze–thaw damage of fiber-reinforced concrete and silane impregnation protection has been carried out, but research on the protection of concrete against freeze–thaw damage by different fiber types, dosages, and different surface treatment methods is still limited. This study attempts to fill this gap through the mechanical test, freeze–thaw test, and salt-freezing test, combined with SEM, XRD, and MIP measurements.2/kg [Cement: The cement is P.O 42.5 ordinary Portland cement  with a specific surface area of 335 m2/kg . The iniCoarse Aggregates: The coarse aggregates are subdivided into large (16–31.5 mm) and small (4.75–16 mm) gravel and both of them are well graded; the properties are shown in 3, fineness modulus was 2.3, sand mud content was 2.9%, and its sieving curve is shown in Fine Aggregates: The fine aggregates were natural sand (0–4.75 mm), whose apparent density was 2.655 g/cmFibers: Three types of fiber were used in this study . Ultra-high strength modified polyester synthetic fiber (FC) is a new material specially developed for airport road surface concrete. Cellulose fiber (CF) is a sheet-like monomer of fiber monofilament. Basalt fiber (BF) is a continuous fiber drawn from natural basalt. The morphology of the three types of fibers is shown in Additives and other chemical reagents: The superplasticizer is an air-entraining polycarboxylic acid water-reducing agent, which is in accordance with the provisions of GB8076-2008 Concrete Admixtures . The glyTo ensure the uniformity of the concrete mixture, concrete was mixed with a forced mixer. Test samples were manufactured in the laboratory. The mixing procedure of fiber concrete used in the test is as follows: first pour stones, sand, cement, and fiber into the mixer successively, mixing for 120 s, then pour the mixed liquid of water reducer and water into the mixer, mixing for another 120 s, and cast the test block after the fiber is evenly dispersed. The test samples were filled at one time when forming, and then placed on the vibration table for 10 s. After vibration, the surface was troweled, and the samples were water cured (20 °C) after demoulding at 24 h.3, was used in the concrete mixes except for G7. The concrete mix consists of eight mix groups according to different fiber content and fiber types, whether a water-reducing agent is used or not, and different sand ratios. Their mixed proportion and relevant composition information are shown in 3 were molded and compacted according to the GBT 50081-2019 [After mixing, prismatic specimens of 150 × 150 × 550 mm081-2019 . After 2081-2019 . The twoThe freeze–thaw cycle test was carried out according to a quick freezing method in GB 50082-2009 , which sThe salt-freezing test was carried out according to MH 5006-2015 , and theAfter the concrete samples were cured to the specified age, they were crushed with a small hammer. The selected pastes, particles about the size of soybeans, were soaked in sufficient absolute ethanol for 24 h to stop hydration, and then placed in a vacuum drying oven at 40 °C for vacuum drying for 3 days. After that, the pore structure was tested by the Autopore IV9510 mercury intrusion instrument . A selection of 3–5 g samples were taken for each test, the pressure range was 0.0036–414 MPa, and the measured minimum pore diameter was about 3 nm.XRD patterns were collected by using a Bruker D8 powder diffractometer  with a CuKα radiation source (λ = 1.5418 Å) at 40 kV and 40 mA to identify the variation in the crystalline phases. Scanning angles (2θ) were from 5° to 70° at a rate of 0.6 s/step and 0.02° per step. The samples for XRD were dried at 40 °C for 2 days and then ground to powder (≤75 μm).Field emission environmental scanning microscope  and a working voltage of 15.0 kV was used for the SEM test to observe the micromorphology of the samples under high vacuum mode. The sample preparation method is as follows: use the cutting machine to cut the large test piece into small pieces, and then crush it before observations. The fresh broken surface, which was the target surface, was coated with carbon before being placed into the measurement chamber.3, 1.0 kg/m3, 1.4 kg/m3, and 1.8 kg/m3), the effect of fiber content on the strength of concrete can be discussed. The compressive strength and flexural strength of the eight groups, G1–G8, at 28 days are shown in From the experimental results, the addition of superplasticizer (G3) increases the 28 d compressive strength of concrete but decreases the 28 d flexural strength of concrete. Compared with G3 and G8, the sand ratio is reduced from 0.3 to 0.28, and the compressive and flexural strength of concrete at 28 days is increased by 6.19% and 8.7%, respectively. The compression failure of concrete may include the failure of the aggregate itself in addition to the bonding interface between the cement paste itself and the aggregate. Then, a larger sand ratio could reduce the amount of coarse aggregate and the ability of aggregate in concrete to bear its damage, resulting in a reduction in compressive strength.When the fiber type changes but the fiber content is relatively low, the 28 d compressive strength of fiber concrete changes little, and the effect of improving the compressive strength of the fiber concrete is not obvious. Among the three fibers, CF (G5) showed the highest compressive strength. Compared with G1 (without fiber), the flexural strength of G3 (FC), G5 (CF), and G6 (BF) at 28 days increased by 4.36%, 1.17%, and 4.64%, respectively. After adding fiber, the 28 d flexural strength of the concrete is improved. The flexural strength of the high modulus fiber (FC) concrete G3 was the highest, the flexural strength of the medium modulus fiber (BF) concrete G6 was the middle one, and the flexural strength of the low modulus fiber (CF) concrete G5 was the lowest. The flexural strength of fiber-reinforced concrete was positively correlated with the elastic modulus of fiber. The 28 d flexural strength of all specimens was greater than 5.75 MPa, which meets the requirements of flexural strength of airport pavement concrete .3, 1.0 kg/m3, 1.4 kg/m3, and 1.8 kg/m3, respectively. From the experimental results, the 28 d compressive strength of concrete does not change significantly and fluctuates within a reasonable range, among which the 28 d compressive strength of G3 is greater. The flexural strength of the three groups with 1.0 kg/m3, 1.4 kg/m3, and 1.8 kg/m3 fibers increased by 2.65%, 4.36%, and 2.18%, respectively.The change of FC content from G1–G4 is 0 kg/mFrom the above mechanical results, three groups G1, G3, and G5 were selected for freeze–thaw cycle experiments. The mass loss and relative dynamic elastic modulus under different freeze–thaw cycles are shown in After 200 freeze–thaw cycles, the surface of the reference concrete (G1) specimen showed local peeling and dropping. The spalling phenomenon on the surface of fiber-reinforced concrete was not obvious. Compared with the FC concrete, the surface holes of the CF concrete were more obvious. After 300 freeze–thaw cycles, the surface of the reference concrete (G1) specimen showed flake falling, the number of new holes increased, and the denudation was obvious. Individual new holes appeared in the FC concrete. The original holes on the surface of the CF-fiber-reinforced concrete specimens increased, but there was still less spalling than the reference concrete specimens. The different trend from cycles 275 to 300 could be explained by the fact that after 275 freeze–thaw cycles, the mass peels off completely. Therefore, 275 to 300 cycles may cause the freeze–thaw water absorption icing mass to be greater than the peeling mass, resulting in a mass increase.In G1 without fiber, the mass loss of 300 freeze–thaw cycles was about 1%, and there was almost no mass loss in G3 and G5. It is obvious that the use of fiber can improve the frost resistance of concrete. Among them, compared with CF, FC is more effective in improving the spalling mass loss of concrete caused by frost resistance.Similar to the experimental results of mass loss rate, the relative dynamic elastic modulus of the two groups with fibers was greater than that of the control group without fiber. After 300 freeze–thaw cycles, the relative dynamic elastic modulus of the control group (G1) was reduced to 0.93, while the relative dynamic elastic modulus of G3 and G5 was reduced to 0.968 and 0.966, respectively. The improvement increment of the relative dynamic elastic modulus was 4.03% and 3.86%, respectively. Compared with the concrete with CF, the frost resistance of concrete with FC is better.2 silane; and silane impregnation means that the formed surface of the concrete specimen was soaked in the silane (5 mm) for one day.Since G3 had the highest resistance to freeze–thawing cycles, this mix and the control mix G1 were explored further to investigate the effect of surface treatment methods on the salt-freezing performance. Different surface treatment methods were considered and the results are shown in According to the requirements of high friction coefficient, the airport pavement needs to be roughened . In addiIt is obvious from the experimental results that no matter how the surface is treated and whether fibers are added or not, the total peeling mass of the three groups impregnated or sprayed with silane is less than that of the three groups not sprayed or soaked with silane. This shows that the use of silane can significantly improve the salt-frost resistance of concrete. Compared with S2, the spalling quality of concrete after 30 times of salt freezing was reduced by 65.5% and 55.5%, respectively, in S3 (silane is sprayed) and S4 (silane is soaked). Compared with S5 with S2, the spalling quality of concrete after 30 times of salt freezing was reduced by 8.54%. Compared with S6 with S4, the spalling quality of concrete after 30 times of salt freezing was reduced by 70.5%. It is obvious that fiber can increase the salt-freezing resistance of concrete, and this effect is more significant in specimens with impregnating silane.Compared with G1, the use of air entraining superplasticizer increases the total porosity (G3 and G7), and also increases the pore volume of <4.5 nm, 50–100 nm, and >100 nm except for the pore diameter of 4.5–50 nm. The characteristic pore size—the pore size corresponding to the highest peak value of pore size distribution—of the group without superplasticizer is smaller, which may be more favorable for the concrete to show better mechanical, but not frost, resistance.From When comparing G2, G3, and G4 groups with the G1 group without fiber, it was observed that the addition of fiber into the cement matrix improved the compactness of the matrix. This can be explained by the fact that these micro fibers penetrated into the pores of the pastes and thus reduced the porosity. The porosity of the three groups with fiber was less than that of the G1 group without fiber, and the reduction range was more than 10%. In terms of the fiber types, concrete with basalt fibers showed a lower porosity, which might not be a good option for frost resistance. BF is a typical silicate fiber, which is close to the density of cement concrete. It is easier to disperse and evenly distribute in the concrete during mixing, overcoming the shortcomings of uneven distribution such as agglomeration of other fibers. FC fiber has a large surface area, which restricts the micro-cracks so that they are not connected, but its density is small, the diameter of monofilament is small, and there is a thickening effect, which is not conducive to the vibration compaction of concrete. Therefore, the porosity of FC concrete was the largest among the three fibers, which could be beneficial to resist frost damage.The results of eight groups of XRD for paste sampling in concrete are shown in In addition, for G8 with a low sand ratio and G7 without a water reducing agent, the XRD results show that the peak value of calcium hydroxide, the hydration product of cement, is lower than that of their respective control groups. It was determined that the use of a low sand ratio without a water reducing agent affects the workability of concrete, and then affects the hydration degree of concrete. The G1 group was not mixed with fiber and the amount of calcium hydroxide was also lower than that of the corresponding control group. It can be considered that the use of fiber in concrete will not affect the hydration of cement, but may promote the hydration degree. According to the consistency of their calcium hydroxide content, it appears that the kind of fiber and the amount of fiber used in G2-G6 fiber-reinforced concrete will not significantly affect the degree of hydration.The test results show that after adding fiber, the frost resistance of the concrete is greatly improved. In order to study the modification mechanism of fiber in the concrete matrix, SEM was used to analyze the microstate of the interfacial transition zone (ITZ) of concrete specimens and the interfacial structure characteristics of the fiber-cement paste and the improvement effects were analyzed ,31,32. T3 in this study), it will lead to insufficient mixing and vibration of concrete, resulting in unconsolidated concrete and reduced strength. Therefore, the optimal fiber content recommended in this study is 1.4 kg/m3.The compressive and flexural strength of concrete are the basic mechanical indexes of airport pavement concrete. From the results in Frost resistance is another important technical index of airport pavement concrete. By comparing the test of the relative dynamic elastic modulus and mass loss of concrete mixed with CF and FC fiber and concrete without fiber, it can be concluded that adding fiber can improve the frost resistance of concrete, due to the creation of a mechanical bite between fiber and substrate. The stress suffered in concrete can be borne by the tensile and shear resistance of the fibers, so as to improve the strength of the interface between the fiber and the substrate, which is beneficial to alleviate the freeze–thaw temperature stresses in the concrete and improve the frost resistance . From thn ≤ 3 indicates the degree of silane hydrolysis. The hydrolysate hydroxysilane has high activity and the condensation reaction can continue in hydroxysilane. The equation is as follows:The results of salt-freezing indicated that silane spraying (S3) is more efficient than silane impregnation (S4). Compared with no silane treatment, the mass loss after 30 salt-freezing cycles in concrete can be reduced by 65.5% by spraying silane. Silane is a small molecular substance, and liquid silane has low viscosity and can penetrate to a certain depth through the open pores on the concrete surface. Under the action of water in the concrete, silane monomer molecules undergo a hydrolysis reaction to produce hydroxysilane .R-Si- surface is more conducive to reaction (2), and reaction (2) is easier to carry out. In this paper, three types of fiber  reinforced concrete were prepared. The physical properties, and freeze–thawing and salt-freezing performance were investigated, and the microstructure and pore distribution of different fiber-reinforced concretes were characterized by SEM and MIP. Some favorable measures to improve the frost resistance of pavement concrete are put forward. The main conclusions are as follows:3), the flexural strength of FC and BF concrete increased by 4.36% and 4.64% compared with that of ordinary concrete, but CF concrete increased by only 1.17%. The flexural strength of fiber-reinforced concrete is positively correlated with the elastic modulus of fiber.(1) All fibers improve concrete flexural strength but have little effect on compressive strength. Under the same mass fraction (1.4 kg/m(2) The use of fiber can improve the frost resistance of concrete, characterized by less mass loss and dynamic modulus loss. After 300 freeze–thaw cycles, the relative dynamic elastic modulus of the control group (G1) was reduced to 0.93, while the relative dynamic elastic modulus of G3 and G5 with fibers was reduced to 0.968 and 0.966, respectively, increasing the relative dynamic elastic modulus by 4.03% and 3.86%, respectively. Compared with CF, FC is more effective in improving concrete frost resistance.(3) Regardless of fiber types, the total peeling amount of concrete impregnated or sprayed with silane was less than that of concrete not sprayed or impregnated with silane. The use of silane can significantly improve the salt-frost resistance of concrete. After 30 cycles of salt freezing, the spalling amount of concrete sprayed or soaked with silane was decreased by 65.5% and 55.5%, respectively. Furthermore, adding fiber and impregnating silane reduced the spalled concrete by up to 70.5%.3 in the airport pavement concrete, and apply silane spraying on the exposure surface to protect the concrete. Spraying silane treatment was better than impregnating silane treatment in enhancing the frost resistance of concrete because the dry concrete surface is more conducive to silane condensation reaction in the spraying treatment. Proper surface treatment is more important than the effect of fiber when the concrete is subjected to salt freezing.(4) It is recommended to add FC with a content of 1.4 kg/m


In Alberta, Canada, we quantified the rate of potentially inappropriate oral antibiotic prescribing in emergency departments for viral infections or conditions not likely requiring antibiotics from 2010-2020 and assessed the impact of two Choosing Wisely Canada (CWC) campaigns (2015/2016 and 2018) discouraging inappropriate antibiotic prescribing in emergency medicine.We linked emergency department adult and pediatric records from the National Ambulatory Care Reporting System and medication dispensations from community-based pharmacies in the Pharmaceutical Information Network. From January 2010 to February 2020, we identified emergency department visits for 5 conditions that were potentially inappropriately treated using antibiotics per CWC recommendations . We used an interrupted time series design to detect changes in antibiotic prescribing by fitting Autoregressive Integrated Moving Average (ARIMA) models to account for secular trends and seasonality, allowing for change in slopes to measure the effect of each CWC intervention.Antibiotics were commonly prescribed in emergency departments for bronchitis (proportion of visits with antibiotics: 57%) and asthma (22%) in adults; bronchiolitis in children (43%); pharyngitis (39%) and acute otitis media (54%) in adults and children. Based on visual inspection, the proportion of emergency department visits for each condition where antibiotics were dispensed remained relatively consistent. The ARIMA models demonstrated mixed impacts on potentially inappropriate antibiotic prescribing associated with two interruptions: the 2015/2016 CWC recommendations and subsequent 2018 CWC Using Antibiotics Wisely campaign. Following each interruption, antibiotic prescribing was slightly reduced for bronchitis  and bronchiolitis (not significant) , but unchanged for asthma  and pharyngitis , and slightly increased for acute otitis media (not significant) .Rates of potentially inappropriate antibiotic prescribing remained constant over the past 10 years in Alberta. Campaigns to rethink antibiotic use in emergency medicine may have resulted in small decreases in antibiotic use; however, further initiatives building upon existing campaigns are required to substantially reduce rates of inappropriate antibiotic prescribing.