Radiation shielding concrete is one of the most used materials in the construction of nuclear power plants and will be subjected to high temperatures for a long time during its service life. This study aims to investigate deterioration of radiation shielding concrete with multiple heating at different temperatures. A microwave oven was used as a heating apparatus to simulate irradiation, and 200, 300, and 400 °C were selected as experimental cycle temperatures. The apparent characteristics, mass loss, splitting tensile strength, and gamma ray shielding properties of the commonly used magnetite shielding concrete were investigated. The results showed that the splitting tensile strength and gamma shielding performance of concrete were dramatically reduced at first heating. Then, as the heating times increased, the splitting tensile strength and gamma shielding properties of the concrete continued to deteriorate, and the higher the increase in heating temperature, the more severe the deterioration of the concrete. During the service period of radiation shielded concrete, the magnitude of temperature under the service conditions will affect the deterioration degree of concrete, and the continuous change of temperature will continuously lead to the deterioration of concrete. Concrete is one of the most common and inexpensive materials used in facilities that contain radioactive sources and radiation generating equipment. In contrast to other construction materials, concrete has better shielding properties and good durability against nuclear radiation ,2,3. RadIn general, radiation shielding concrete is exposed to high temperature and high radiation environment for a long time. The temperature of radiation shielding concrete in nuclear power plant is between 60 °C and 120 °C under normal working conditions . In nuclHigh temperature is an essential indicator of the deterioration of the performance of radiation shielding concrete. Due to the poor thermal conductivity, the concrete is subject to internal temperature differences under the direct action of the reactor core, which ultimately causes concrete cracking and a decline in durability . NowadayThe thermal damage of concrete at high temperatures mainly consists of structural cracking  and hydride decomposition . There are at least 3 kinds of cracks in concrete at high temperatures including shrinkage cracking induced by hydride decomposition , by therThe patterns of apparent properties, mass loss, splitting tensile strength, and gamma shielding properties of magnetite radiation shielding concrete heated at 200, 300, and 400 °C for different times were investigated in this paper. It explores the deterioration of radiation shielding concrete at different temperatures with multiple heating cycles, which provides some reference significance for the application of radiation shielding concrete.In this section, the basic properties of the material, the preparation of the specimen, and the main experimental methods will be introduced.The test used P.O 42.5 ordinary silicate cement from Hengyang City, Hunan Province, whose chemical composition is shown in The magnetite ore came from Gongyi City, Henan Province. Reference JGJ 52-2006 for test measures and standards. After cleaning and drying, the raw stones were screened using a standard square-hole sieve with needle and flakes removed, and then placed in different containers according to different particle sizes. The coarse aggregates used in the tests had a maximum particle size of 20 mm and were mixed in accordance with a certain mass ratio in below 5 mm, 5–10 mm, 10–16 mm, and 16–20 mm sieve size range. Part of 5–20 mm coarse aggregate was obtained by crushing coarse aggregate larger than 20 mm and part of 0.16–1.25 mm fine aggregate was obtained by crushing fine aggregate of 1–5 mm. The chemical composition of magnetite aggregates is illustrated in The test required magnetite radiation shielding concrete. The initial mix proportion was calculated according to the iron ore radiation shielding concrete mix ratio calculation method specified in GB/T 34008-2017. The mix ratio of magnetite concrete is shown in According to GB/T 5001-2019 standard, concrete specimens were made with the size of 100 mm × 100 mm × 100 mm. The test specimens were demolded after one day of resting after pouring, and then put into the standard curing room for 28 d. After the test specimens were cured, the specimens were placed in a dry atmospheric area for 14 d.All concrete specimens were heated sequentially in a microwave oven  with an internal chamber size of 400 mm × 480 mm × 340 mm. The same loading power was used for each heating (6 microwave emitters) and the temperature was measured at the center of the left side of the concrete (the specimen will be marked on the front side) to ensure the consistency of each loading . We placThe 10 cm × 10 cm × 10 cm concrete specimens were tested for splitting tensile strength, and the specimens conformed to Chinese standard GB/T5001-2019. We performed splitting tensile tests on the specimens using WAW-EY600C electro-hydraulic pressure servo tester with load control and a load rate set at 0.05 MPa/s . Three mGamma radiation shielding tests on magnetite concrete were made in the BH1326 nuclear physics experiment platform with NaI (TI) scintillation detector, a counting system and a gamma radiation source. The 137Cs radioisotope was used as a gamma-ray source which has 0.662 MeV photon energy (the source of 137Cs was a cylinder with a diameter of 5 mm and a height of 1 cm. Its activity was about 10 millicurie). The 10 cm × 10 cm × 10 cm specimens was cut into test specimens with thicknesses of 2.5 cm, 5.0 cm, and 7.5 cm, respectively. The specimens used for the test with a thickness of 10 cm were spliced from 2.5 cm and 7.5 cm specimens. To reduce thickness inhomogeneities and differences in aggregate distribution, each concrete sample was repeatedly tested at nine test points . Under g0 is the count rates of blank control; x means the thickness of the test specimen (cm); μ is the linear attenuation coefficient of test sample (cm−1); μm refers to the mass attenuation coefficient of the test sample with gamma rays(cm2/g); ρ represents the density of the test specimen (g/cm3); the error of μ, I, I0, μm and x are Δμ, ΔI, ΔI0, Δμm, and Δx, respectively.In this experiment the linear attenuation coefficient (μ), half-value layer (HVL), ten-value layer (TVL), mean free path (Mfp), and mass attenuation coefficient (Mac) of test specimen was discussed. Equations (1)–5) is to calculate the μ, HVL, TVL, Mfp, and Mac of concrete, respectively. Equation (6) is the error calculation formula of linear attenuation coefficient  is to ca.I = I0 In this section, the deterioration of splitting strength with different number of heating at different cyclic temperatures and the effect of different number of heating at different cyclic temperatures on the linear attenuation coefficient and transmission rate are presented.The appearances of magnetite concrete at high temperature with repeated heating are shown in The concrete internal composition changes with the temperature increasing, which will result in variations in the quality of the test samples. Thus, the change in the quality of concrete repeatedly heated at high temperatures can be used to indirectly assess the degree of deterioration and the status of changes in the internal composition of concrete. The experimental results showed that the magnetite samples changed the most in relative mass loss at the first round of heating, and the higher the heating temperature, the greater the relative mass loss. With the increase in heating times, the relative mass loss of the magnetite samples at heating temperature of 200 °C gradually increased and the trend of change decreased. While the relative mass loss of magnetite samples heated at 300 °C and 400 °C tends to level off with the increase in heating times to a certain value. As the mass loss of magnetite concrete is largely due to the dissipation of water inside it and the decomposition of hydration products to a certain extent ,30,31. FMagnetite aggregates have excellent physical and chemical properties and good performance in thermal conductivity and thermal storage properties ,47,48,49The features of the magnetite splitting blocks repeatedly heated at high temperatures are shown in Damage morphological transformation of concrete samples has three main reasons. One is the mortar and aggregates decompose differently at distinct temperatures. The decomposition degree of aggregates and mortar will keep decomposing with the increase in temperature ,30,31,32t, T) of magnetite concrete samples at high temperature condition. The experimental results indicated that as the heating time and temperature increased, the splitting tensile strength of magnetite concrete decreased continuously.Combined with the changes in mass loss of the samples under the experiment and thermal decomposition law of the concrete cement matrix, thermal damage under repeated heating at high temperature can be classified into the following two periods. One is the period of combined damage of various factors within the concrete (major damage) ,22,23,500). The relationship curves between the test sample thickness and ln(I/I0) are shown in At 0.662 MeV energy level, the linear attenuation coefficient (μ) was derived as the slope of the regression line from the thickness of concrete specimen and ln and sample thickness is shown in The changes in the apparent characteristics and mass loss of magnetite concrete varied with the increase in heating temperature. It was shown that the crack width, length, and number of specimens increased with the increase in heating times and heating temperature.Magnetite concrete has good thermal stability, and its relative mass loss varies less with the number of heating times and temperature. The relative mass loss was only 2.67%, 2.93%, and 3.59% after heating the specimens at 200, 300, and 400 °C 10 times. The higher the heating temperature, the greater the relative mass loss of the samples, and the final relative mass loss of the samples tended to be constant for each heating temperature when the concrete was left more intact.The splitting tensile strength of magnetite concrete decreased as there was an increase in heating times and heating temperature. Additionally, the higher the heating temperature, the greater the variation in the splitting tensile strength of concrete, and the more serious the deterioration of mechanical performance of concrete. The greatest change in splitting strength of magnetite radiation shielding concrete was observed in the first heating. The relative splitting strength changes of the specimens under heating temperatures of 200, 300, and 400 °C were 19.99%, 31.23%, and 51.66%, respectively. As the heating temperature was 200, 300, and 400 °C, and heating times up to 10, the relative tensile strength reductions in the specimens compared to the first heating were 5.52%, 12.77%, and 18.84%.The linear attenuation coefficient of magnetite concrete gradually decreased with the increase in heating times and heating temperature, and its HVL, TVL, and Mfp gradually increased. When the gamma ray transmission rates were the equal, the minimal shielding thickness of magnetite concrete gradually climbs with the increase in the heating number and the heating temperature. In addition, with the increase in heating temperature, the greater the rate of change between different heating times. Therefore, the deterioration of physical, mechanical, and gamma shielding properties of the concrete is more severe the higher the temperature to which the concrete is subjected and the more drastic the temperature change during the service life of the magnetite radiation shielding concrete.The mass loss test, cracking tensile strength test, and gamma ray shielding test of magnetite concrete after repeated heating at 200, 300, and 400 °C are presented in this paper. The following conclusions can be drawn from the experimental results:


Immunoglobulin G4-related disease is characterized by dense fibrosis, obliterative phlebitis, and lymphoplasmacytic infiltration that contains abundant IgG4 positive plasma cells. It causes tumefactive lesions in the involved organs and is most commonly seen in the salivary glands, pancreas, and retroperitoneum. Ovarian involvement has been reported in only two cases. In our case, a 58-year-old female patient presented with abdominal distention and pain. Pelvic computed tomography revealed a soft tissue lesion compatible with the omental cake, several intraabdominal implants, and bilateral adnexal fullness. A laparotomy was performed under suspicion of peritoneal carcinomatosis secondary to bilateral adnexal mass. In the histopathologic examination, abundant lymphoplasmacytic infiltration and dense fibrosis were observed in both ovaries and the peritoneum. In the areas of greatest density, the density of IgG4-positive plasma cells was found to range from 40 to 50 per high-power field. The patient was accepted as suffering from probable IgG4-related disease because of the bilateral involvement of the ovaries and the histopathological findings. In conclusion, we present this case to draw attention to the fact that IgG4-related disease can also be seen in the ovary. Immunoglobulin G4-related disease (IgG4-RD) is characterized by dense fibrosis, obliterative phlebitis and lymphoplasmacytic infiltration that contains abundant IgG4-positive plasma cells . IgG4-RDIn this case report, we present probable IgG4-RD involving the bilateral ovaries in which a bilateral ovarian mass together with peritoneal and omental involvement mimicked advanced ovarian cancer.A 58-year-old female patient presented with abdominal distention and pain and underwent further investigations after a pelvic mass was detected at an external center. Ultrasonography (USG) revealed mass lesions on both ovaries; the mass on the right ovary was 4 × 3.5 cm, and the mass on the left ovary was 4.2 × 2.7 cm. The largest metastatic nodule in the omentum was 5.4 × 4.2 cm. Pelvic computed tomography (CT) showed a 15-cm long, 3-cm thick soft tissue lesion compatible with the omental cake, several intraabdominal implants suggesting increases in nodular thickness, bilateral adnexal fullness, and pelvic peritoneal implants . As a reWhen the tissues were examined in frozen section, it was observed that the lesion contained intense fibrosis. Disseminated peritoneal leiomyomatosis was considered in the differential diagnosis due to the diffuse peritoneal involvement. Although a benign lesion was considered first, the final diagnosis was left to examination of the permanent sections.Macroscopic examination of the specimen showed areas of gray-white discoloration, the largest of which was 3 × 2.5 cm in diameter, on the anterior-posterior wall of the uterus and around the right and left tuba uterina. The right ovary was 3.5 cm in diameter, and the left ovary was 4 cm in diameter; the cross-sectional surfaces were irregular. Also, multiple intraabdominal serosal implants were located on the intestine and the appendix and in the right and left paracolic regions.On microscopic examination, intense fibrosis in an occasional storiform pattern was seen in both ovaries and peritoneal implants. Significant lymphoid follicles and intense lymphoplasmacytic inflammatory cell infiltration on the fibrotic ground were noteworthy. An immunohistochemical study determined the density of IgG4-positive cells. In a high power field (HPF), 40 to 50 IgG4 positive cells were found in the area of greatest density. The IgG4+/ IgG+ cell ratio was more than 40% . In concBlood samples taken for IgG1, IgG2, IgG3 and IgG4 were within normal limits three weeks after the patient’s operation. No additional treatment was given to the patient following the operation.IgG4-RD is a relatively recently defined systemic fibroinflammatory process . It was When diagnosing IgG4-RD, clinical, serological, and histopathological features are evaluated. IgG4-RD can affect a single organ or multiple organ systems and can be found bilaterally in organs, and an increase in the size of the affected organs or impairment of organ functions occurs . Among tIf these three criteria are met, the diagnosis of IgG4-RD is definitive. Patients who meet only one of the serological or histopathological criteria and have organ symptoms probably have IgG4-RD. Patients with organ symptoms who do not meet the serological or histopathological criteria are unlikely to have IgG4-RD .There are very few cases of IgG4-RD with ovarian involvement in the literature. In our case, bilateral ovarian enlargement was accompanied by peritoneal and omental implants as in the case reported by Maruyama . In a caIn our case, IgG4 levels were within normal limits in the blood samples taken three weeks postoperatively. In Maruyama’s reported case, serum IgG4 concentration was 1,000 mg/dL on day seven postoperatively, and in Sekulic’s reported case, serum IgG4 concentration was not determined ,11.Histopathologically, intense lymphoplasmacytic infiltra-tion was observed in all three ovarian IgG4-RD cases. In Sekulic’s case, the inflammation was reported to be rich in eosinophils . In our In terms of histopathological features, multiple myeloma, lymphoproliferative diseases, spindle cell mesenchymal neoplasms, multicentric Castleman disease, and infections should be considered in the differential diagnosis of IgG4-RD. Therefore, when examining a sample with IgG4-RD-like histology, its clinical history should be considered. The evaluation of IgG4-RD in frozen section may also be difficult due to pronounced fibrosis. Disseminated peritoneal leiomyomatosis can be considered in the differential diagnosis in frozen evaluation.In our case, luteinized thecoma associated with sclerosing peritonitis was also included in the differential diagnosis due to the bilateral ovarian and peritoneal involvement. However, the absence of luteinized cells and the presence of intense lymphoplasmacytic inflammation with storiform fibrosis ruled out this disease.In conclusion, we reported the third case of ovarian IgG4-RD. In histopathological examinations, IgG4-RD, although very rare, should be considered in the differential diagnosis, particularly if marked lymphoplasmacytic inflammation with storiform fibrosis is observed in ovary. IgG4-RD responds well to prednisone therapy, which increases the importance of a correct diagnosis. Correct diagnosis also prevents unnecessary surgical interventions.The authors declare no conflict of interest.


Microbially influenced concrete corrosion (MICC) causes substantial financial losses to modern societies. Concrete corrosion with various environmental factors has been studied extensively over several decades. With the enhancement of public awareness on the environmental and economic impacts of microbial corrosion, MICC draws increasingly public attention. In this review, the roles of various microbial communities on MICC and corresponding protective measures against MICC are described. Also, the current status and research methodology of MICC are discussed. Thus, this review aims at providing insight into MICC and its mechanisms as well as the development of protection possibilities. The use of concrete has a profound impact on the development of a modern society . ConcretChemical, physical, mechanical and biological corrosions are the common types of concrete deterioration . Among tMicrobially influenced concrete corrosion (MICC) ,10,11 isConcrete has become an ideal building material because of its high strength, low cost, excellent processability and durability . Over thConcrete can be destroyed with various environmental factors. This affects not only the aesthetics of a concrete structure but also shortens its durability. Concrete corrosion can be sub-divided into physical, chemical and biological . PhysicaChemical corrosion means the breakdown of concrete caused by a chemical reaction with, e.g., acids, alkalis and salts . It resuThe composition of microbial communities involved in concrete corrosion needs to be studied to find effective ways of understanding the processes in MICC . The metAcidithiobacillus (A.) thiooxidans dominated the flora in heavily corroded concrete (pH about 1); T. intermedia (T. intermedius) and T. novellus dominated the flora in corroded concrete with a moderate pH (range of 3 to 6), and A. thiooxidans was not detectable if the pH of concrete was above 6. Zhou et al.   and found that the pH of the concrete surface remained alkaline under the attack of biological sulfuric acid, confirming that these coatings protect concrete from a microbial attack. De Muynck et al. [Protective concrete coatings are often classified into two types: inert coatings and antibacterial coatings ,158. Thek et al.  found thk et al. . The autk et al.  stated tk et al.  used elek et al.  modifiedDespite the widespread usage of coatings for concrete protection, certain drawbacks such as the bonding between a coating and the concrete and the impact of a coating on the performance of concrete warrant more research.The age of sewer systems worldwide is increasing. Thus, the problems caused by MICC are becoming more and more serious, and research on the mechanisms, influencing factors, corrosion models and protective measures for MICC is therefore becoming increasingly important. However, as MICC involves many disciplines , interdisciplinary research also poses numerous difficulties for researchers. There are fundamental and scientific problems that still exist with MICC. These subjects should attract more attention from researchers, in addition to the willingness to perform interdisciplinary work.(1)Although remarkable achievements have been made for MICC, further research is needed due to the diversity of microbial species and differing environments. This review focuses on MICC processes in sewerage systems. It is worthwhile to also study and investigate MICC involved in a marine environment using established protocols, considering the increased demand for concrete in marine engineering.(2)There is presently no established model for MICC prediction and no unified standard to incorporate the large number of data obtained in specific experimental conditions. Therefore, how to make the data obtained in a laboratory or the data obtained from field tests applicable to a wide range still awaits further efforts.(3)The fundamental purpose of research on MICC is to protect concrete, but there are some drawbacks or undiscovered effects of various protective measures. For instance, biocides have an excellent performance in inhibiting the growth of microorganisms, but their impact on the performance of concrete and the environment may be problematic. Modifications of concrete and concrete coatings can protect concrete to a certain extent, but there are still many inevitable challenges in the actual engineering application, such as the cost, construction process and environmental impact issues.


Ligneous conjunctivitis (LC) is a rare inflammatory lesion of the conjunctiva with an unknown etiology. It is easily confused with conjunctiva lymphoma or other diseases in clinical diagnosis, and the lesion is very difficult to treat.We presented a 41-year-old female patient presented with bilateral conjunctival masses for more than six months. The patient had no contributory history of ocular trauma, family history of tumor and drug allergy. Taking the patient’s clinical and pathological features together, we considered this was a case of IgG4 + LC. Completely surgical resection combined with local glucocorticoid treatment might be effective.This is a very rare case report of immunoglobulin G4 positive LC with only one published case in literature. The typical manifestations of LC are with the appearance of a hard, fibrin-rich, woody pseudomembranous lesion. A large number of lymphocyte and plasma cell are infiltrated in the pathological tissue. Inflammation of LC may cause immune abnormalities, resulting in IgG4 increasing. According to Japanese studies, the incidence of IgG4-RD is 0.28–1.08/100,000, and that of IgG4-related ophthalmic disease (IgG4-ROD) accounts for 4–34% of total IgG4-RD cases [Ligneous conjunctivitis (LC) is a rare, chronic, pseudomembranous form of conjunctivitis of unknown etiology that is more common in infancy and childhood . Its maiRD cases –8, this A 41-year-old female patient presented with bilateral conjunctival masses for more than six months, and the previous treatment with tobramycin eye drops was not effective. The patient had no contributory history of ocular trauma, family history of tumor and drug allergy. The mass on the conjunctival surface of the upper right eyelid was obvious, with telangiectasia and brown lesions on the surface, and was covered by a pseudomembrane Fig. . The pre+ cell count was approximately 100/HPF, IgG+ cell count was approximately 200/HPF, and the IgG4/IgG ratio was > 40%. Taking the patient’s clinical and pathological features together, we consider this is a case of IgG4+ LC. After surgery, the patient received tobramycin and dexamethasone eye drops at localized points in both eyes for 14 days. In the 10 months’ follow-up, the disease had not recurred in the patient’s eyes.The patient was worried that the lesion might be malignant and requested surgery to clarify its nature. Therefore, we performed conjunctival mass resection on both eyes at the same time and removed as much diseased tissue as possible. Histopathological results showed severe chronic inflammation of the polypoid mucosa of the conjunctival mucosa, infiltration by comprised predominantly of neutrophils, lymphocytes and plasma cells, fibrous-tissue hyperplasia, non-keratinized squamous epithelium or column epithelial papillary hyperplasia covering the fibrotic mucosa, and a great many visible inflammatory exudates in the lamina propria Fig. . ImmunohLC is a disease with an estimated incidence of 16 cases per 1,000,000 people, and consanguineous marriage may be a predisposing factor for it . It mighCases of LC complicated with IgG4-RD are extremely rare, and only one has been reported so far . BecauseLC is very difficult to treat. Tissue plasminogen activator, allogenic serum plasminogen, antibiotics, heparin, cyclosporine, and other drugs have been applied. The therapeutic effect of a single drug is usually poor; the combined application of multiple drugs has some therapeutic effect –17. StudThe first reported case of LC with IgG4-RD was still recurrent after multiple treatments involving large-scale excision, cryotherapy, local triamcinolone injection, anti-proliferation soak of mitomycin C, and amniotic membrane transplantation; treatment required two years . In the In summary, this is the second case report of ligneous conjunctivitis complicated with IgG4-RD. The main feature is conjunctivitis with the appearance of a hard, fibrin-rich, woody pseudomembranous lesion. When the drug treatment effect is poor, completely surgical resection combined with local glucocorticoid treatment might be effective. Conjunctival inflammation of LC may cause immune abnormalities, resulting in IgG4 increasing. The relationship between LC and IgG4-RD needs to be supported by more cases. Therefore, comprehensive and detailed eye and body examinations, as well as comprehensive laboratory, imaging, and histopathological examinations, are necessary.


In this paper, a series of experimental and numerical studies were carried out to investigate the effect of multiple cracks on concrete fracture behavior. Seven groups of double-crack concrete three-point bending (TPB) experiments with different crack lengths and different crack distances were carried out. The experimental results showed that the bearing capacity of double-crack specimens was slightly larger than the standard specimen with one central crack. Additionally, with an increase in the second crack length or with a crack distance reduction, the concrete’s bearing capacity increased correspondingly. Based on the experiments, a numerical meso-model was developed based on applying cohesive elements. The aggregate, mortar, interface transition zone (ITZ), and potential fracture surfaces were explicitly considered in the model. In particular, cohesive elements were used to characterize the mechanical behavior of the ITZ and potential fracture surfaces. A modified constitutive concrete model was developed by considering the potential fracture surfaces’ damage relation and friction effect. The accuracy of the developed meso-model was validated through a comparison between simulation and experiments. Based on meso-models, the influence of multiple cracks on the concrete bearing capacity was investigated by analyzing the energy evolution. The analysis results showed that the bearing capacity has a linear relation with the proportion of mode II energy consumption during the fracture process, which explains why specimens with multiple cracks have a slightly larger bearing capacity than the standard specimens. In summary, this study has found that in three-point bending fracture tests primarily characterized by mode I fractures, the presence of multiple cracks near the main crack slightly enhances the load-bearing capacity of the specimens. This is attributed to a slight increase in internal energy dissipation associated with the presence of these multiple cracks. Concrete’s fracture performance has a significant impact on the safety of bridges or other structures. When concrete cracks, it can affect the corrosion resistance of the bridge and its corresponding load-bearing capacity ,2,3,4. TSince the theory of fracture mechanics was first used to analyze the failure behavior of concrete, a series of research works on concrete fracture mechanics have been carried out. Researchers studied the influence of the size effect ,4,5,6,7,In practical engineering, concrete may have multiple cracks due to the construction technology and natural factors, and these cracks often affect each other. However, there are only a few papers about the fracture behavior of concrete with multiple cracks . EvaluatDue to the complexity of the multiple crack problem, it is hard to analyze the fracture behavior of concrete with multiple cracks using the mathematical analysis method. Thus, the mesoscopic numerical method is more suitable for studying this problem. Up to now, many mesoscopic methods have been proposed, such as the traditional finite element method ,18,19, tThis study conducted a series of TPB experiments to investigate the effect of multiple cracks on the mode I fracture behavior. Double-crack TPB beams with different second crack lengths and different crack distances were designed and tested. In addition, a meso-model was developed based on the CZM and the corresponding constitutive model. Finally, based on the experimental results and the developed meso-model, the fracture process and the inner energy consumption were analyzed.To compare with the standard mode Ⅰ fracture behavior of concrete, double-crack TPB concrete beams were designed based on previous works . The staIn every experimental group, four specimens were cast to eliminate random errors, and all beams were cast at once. A steel plate with a thickness of 3 mm was used to make the initial cracks. The particle size of aggregates was distributed in the range of 5~20 mm continually. P.O 42.5 cement, sand, and water were chosen to cast the mortar matrix of the concrete. The mix proportion is cement:aggregate:sand:water = 1:1.225:2.458:0.44. Through the material property tests, the standard compressive strength, tensile strength, and elastic modulus were determined to be about 49 MPa, 3.5 MPa, and 45 GPa, respectively.−3 mm/s. All measured parameters were recorded through a DH-5902 testing system (sampling frequency: 10 to 100 k Hz).The loading scheme of the beams is shown in The typical fracture pattern of the TPB beams is shown in P. The typical In this study, the CMOD of the main crack was called To conveniently compare the influence of the second crack length and crack distance on the bearing capacity of the beams, the peak load and the corresponding CMODs were extracted and shown in The meso-modeling method proposed earlier ,33 was a(1)Single-mode damage relationThe modified constitutive model ,33 basedThe damage relation in the tangential direction can also be similarly given as follows:(2)Mixed-mode damage relationThe quadric criterion ,32,33 waThe PL criterion defined the evolution of the damage, and it can be given as follows:Assuming that the loading path is monotonous, by substituting Additionally, by substituting Based on these calculated parameters, the total displacement Hence, the damage factor in the mixed-mode condition can be finally given as follows:(3)Friction effectWhen the interface is damaged, friction occurs at the interface when the interface is closed. For this reason, the friction effect should be considered precisely. In this constitutive model, the fiction stress is calculated according to the interfacial sliding condition.(a) Interfacial not slidingIn this condition, the friction stress (b) Interfacial slidingIn this condition, the friction stress equals the maximum static friction stress. In addition, the corresponding interfacial sliding displacement should be updated:(4)Stresses in the mixed modelFinally, combining the damage relation and friction effect, the stresses can be given as follows:(5)Internal energy calculationAccording to the stresses defined above, three corresponding kinds of energy can be extracted to analyze the internal fracture behavior, which are: (1) the normal stress work The meso-model was used to analyze the concrete double-crack problem, as shown in The mesh of the numerical model is shown in According to the experimental results, repeat trial computations, and the previous works on cohesive elements ,32,33,34The numerical models were solved in the ABAQUS/EXPLICIT solver , with thThe standard group’s numerical and experimental P-δ1 curves are shown in The distribution of maximum stress during the fracture process is shown in It should be noted that the crack does not extend along an ideal straight line due to the random distribution of aggregate. As a result, some fracture surfaces may not separate completely. Thus, a large stress still exists in some areas without complete damage, as shown in The final fracture pattern of the standard beam is shown in The typical (the group TPBSC80 or TPBCD80) numerical and experimental The maximum stress distribution of the double-crack beam (the group TPBSC80 or TPBCD80) during the fracture process is shown in To obtain more details of the fracture process of the double-crack specimen (the group TPBSC80 or TPBCD80), the deformation of the beam at the pre-peak stage a and theThe simulation and experiment comparisons of the other groups  increases, the peak force increases correspondingly. The peak force is highly relevant to the shear stress work proportion, and a linear relationship exists between these two parameters, as shown in To validate the statement above, a group of numerical tests with three parallel cracks  were also carried out, and the fracture paths are shown in In the mode Ⅰ fracture (or composite fracture dominated by mode Ⅰ fracture) condition, multiple cracks in a small zone will slightly increase the bearing capacity of the concrete. With an increase in the other crack’s lengths or with a decrease in the distance between cracks, the bearing capacity increases.In terms of energy consumption, the proportion of shear stress work (mode II) is highly relevant to the bearing capacity of multiple-parallel-crack concrete. Multiple parallel cracks change the proportion of mode Ⅱ fractures and finally cause an increase in the concrete bearing capacity.In this paper, a series of TPB experiments were carried out to investigate the influence of multiple cracks on concrete fracture behavior. Six groups of double-crack TPB beams were designed and tested. A numerical meso-model was developed to analyze the fracture behavior of double-crack concrete specimens. In this meso-model, cohesive elements were adopted to characterize the potential fracture surfaces, and the corresponding constitutive model combining the damage relation and friction effect was developed. Through comparison, all the numerical results agreed with the experimental ones. Based on this model, the influence of multiple parallel cracks on the bearing capacity of concrete was studied by analyzing the energy consumption. The conclusions can be summarized as follows:Based on the conclusions above, in the mode Ⅰ fracture (or composite fracture dominated by mode Ⅰ fracture) condition, multiple cracks in a small zone can be equally considered as one crack from the perspective of safety design.It should be noted that in this study, only the concrete fracture behavior with multiple parallel cracks was investigated. However, in practical engineering applications, the distribution of cracks is more random and the fracture mode is more complex. Therefore, in subsequent studies, it is necessary to further analyze the mechanical behavior of multiple cracks under a mixed-mode (mode I and mode II) fracture process.


IgG4-related disease (IgG4-RD) is an immune-mediated disorder that involves multiple organs and is characterized by the infiltration of lymphoplasmacytic cells, including IgG4-positive plasma cells, along with storiform fibrosis and obliterative phlebitis in the inflamed organs. The primary sites affected by this condition include the pancreas, bile ducts, salivary glands, aorta, lungs, kidneys, meninges, lacrimal glands, mediastinal lymph nodes, and retroperitoneum. The pathogenesis is linked to a type 2 T-helper-cell cytokine profile and the involvement of regulatory T cells. However, the exact mechanism is still unknown. Patients with IgG4-related disease are frequently misdiagnosed as having malignancies due to the resemblance of the lesions to infections or other immune-mediated diseases and certain tumors, such as pancreatic cancer and pseudo-renal pelvis tumor. Prompt identification of IgG4-related disease is essential as a delayed diagnosis until advanced stages can result in severe organ damage and potentially fatal outcomes, despite the disease being highly responsive to treatment. This report presents a highly unusual case of IgG4-related disease (IgG4-RD) with an atypical presentation in a 38-year-old female patient. The patient sought medical attention in the emergency department due to nasal septal erosions and an oral-antral fistula. Nasal cultures were conducted and indicated the presence of Klebsiella ozaena. Subsequent investigations, including a nasal biopsy, confirmed the diagnosis of IgG4-related autoimmune disease.  IgG4-related disease, also known as IgG4-related systemic disease or IgG4-RD, is a chronic autoimmune disorder that can affect various organs and tissues in the body. It is characterized by the infiltration of immune cells, primarily plasma cells, and the accumulation of IgG4 antibodies in the affected tissues. Elevated levels of IgG4 in the bloodstream distinguish IgG4-related diseases, and the presence of sclerosing inflammation is accompanied by a significant number of positive plasma cells for IgG4 . The preA 38-year-old woman arrived at the emergency department with complaints of progressive headaches, an observed cavity in her hard palate, and clear nasal discharge for five days. Her headaches were constant, affecting both sides of the head and resembling migraines, but without accompanying nausea and vomiting or focal neurological deficits. The opening in the roof of her mouth caused her discomfort when drinking liquids, leading to regurgitation through the nostrils. She also reported an altered ability to smell. She denies experiencing any pain in her nose or facial/maxillary region. There is no history of trauma, except for a full dental extraction she underwent two to three years ago. She mentions having a chronic scab over her upper right molars that has remained unchanged and painless. She has a past medical history of hyperthyroidism, hypocalcemia, chronic kidney disease, migraine, depression, and rheumatic fever. She also had a full dental extraction two to three years ago. Her home medications include benazepril, bupropion, zolpidem, paroxetine, buspirone, propranolol, and methimazole. She has a smoking history of half a pack of cigarettes per day, but denies alcohol use, and has a family history of diabetes on both her paternal and maternal sides. She also denied any drug use or any significant family history. Upon arrival at the emergency department, her vital signs were stable with a blood pressure of 133/57 mmHg, a temperature of 98.6 degrees F, a pulse of 94 BPM, and a SpO2 of 100% on room air. On physical examination, a minor hole measuring less than 1 centimeter was observed in the hard palate, located at the center of the roof of the mouth. The remaining aspects of the examination were unremarkable. Her initial laboratory results indicated the presence of microcytic anemia, with a hemoglobin/hematocrit (Hb/Hct) ratio of 9.4/30% and a mean corpuscular volume (MCV) of 69.6. Additionally, the CRP level was elevated at 23.52 mg/dL, while the remaining laboratory values fell within normal ranges. Please refer to Table As a result of the signs and symptoms, a CT scan of sinuses with contrast was ordered, which revealed the complete opacification of the maxillary, sphenoid sinuses, and anterior ethmoid cells and partial opacification of the bilateral frontal sinuses. The rest of the findings are described in Figure CT Scan of the head was negative for any acute findingsDue to concerns regarding significant nasal and septal erosion, along with a suspected oroantral fistula, empirical treatment was initiated with vancomycin, zosyn, and liposomal amphotericin B. Subsequent cultures were performed, revealing the presence of a mild growth of Candida glabrata, Candida dublinesis, and minimal growth of Klebsiella ozaenae. Moreover, ENT and infectious disease were consulted. A subsequent nasal cavity endoscopy was conducted, unveiling notable crusting and ulceration of the septal perforation and erosion within the nasal cavity. The ulcerated mucosa was covered with a copious amount of purulent discharge. The tissue was biopsied. The endoscopy findings confirmed the existence of an oronasal fistula. Initial differentials included Wegner's granulomatosis, rhinoscleroma, sarcoidosis, vasculitis, fungal infection, and IgG4-related disease. Rheumatology was consulted and recommended further investigation for autoimmune diseases, such as testing for antinuclear antibodies (ANA) to evaluate for systemic lupus erythematosus (SLE), immunoglobulin G subclass 4, and Sjogren's antibody., however, all the autoimmune workup was negative including ANCA, Anti-DNA negative, C3/C4 negative, ANA positive with titers of 1:40 with a nuclear homogenous pattern. Furthermore, the patient’s chest x-ray did not show any cavitary lesions and her urinalysis did not reveal any hematuria, which made Wegner’s granulomatosis more unlikely. IGG4 antibodies come back positive with levels elevated at 150.8mg/dl. Moreover, a serial CT scan of facial bones without contrast showed extensive paranasal sinus disease with large nasal septal perforation, as shown in Figure Further biopsy analysis reported an inflammatory infiltrate characterized by a combination of cells, primarily neutrophils and plasma cells, with occasional eosinophils. A periodic acid-Schiff (PAS) stain was conducted to detect fungal organisms, but none were found. Immunostaining was performed to assess IgG and IgG4, showing an IgG4 to IgG ratio of approximately 15-20%. Figures , 4, 5. Antibiotics were deescalated to ceftriaxone 2 grams once a day and oral metronidazole for six weeks as blood cultures were negative. The patient responded well to the antibiotics without the need for any steroids. She was discharged with outpatient follow-up appointments with Infectious diseases, Rheumatology and ENT for further management and follow-up for IgG4-related disease.IgG4-related disease is known to impact multiple organ systems, with it commonly associated with type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis . This caDiagnosing IgG4-RD is challenging based on clinical presentation due to the lack of typical findings . This neInvolvement of the skull in a confirmed case of IgG4-RD is relatively rare and can be compared to a 2015 case of IgG4-RD that showed a mass in the right nasopharynx, blocking the Eustachian tube and leading to symptomatic mastoiditis. The distribution of fibrosis was reminiscent of nasopharyngeal carcinoma and involved the base of the skull . When coThis patient was also found to have an infection of Klebsiella ozaenae, which presents with similar findings of foul-smelling nasal discharge, nasal congestion and crusting, anosmia, nasal dryness, epistaxis, and nasal deformities . HoweverIgG4-RD has an undefined etiology, with some studies reporting a genetic association between patients with specific HLA and non-HLA subtypes being at a higher risk . Other sIgG4-RD has frequently been shown to cause dense fibrosis in the affected tissues, such as eosinophilic angiocentric fibrosis, which presents with nasal obstructive symptoms . ConversThere are multiple possible renal manifestations of IgG4-related disease, including membranous glomerulopathy, tubulointerstitial nephritis, and obstructive nephropathy. Our patient has a history of CKD which may have been the result of chronic underlying, undiagnosed, IgG4-related disease-based fibrosis and lymphoplasmacytic infiltrate . Our patTreatment for IgG4-RD depends on the clinical severity of the patient at the time of diagnosis. All symptomatic patients must be treated with glucocorticoids, with the option of an additional immunosuppressive agent such as rituximab . AsymptoIn conclusion, IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that affects multiple organs and is characterized by a wide range of clinical presentations and diagnostic challenges. Patients typically experience a gradual emergence of an organ-specific mass or enlargement of the affected organ. This condition predominantly affects middle-aged and elderly males but can also occur in females, and pediatric cases have been observed. Measuring the concentration of IgG4 antibodies in the bloodstream is a valuable indicator for diagnosing and predicting IgG4-related disease (IgG4-RD). Glucocorticosteroids are the initial treatment for IgG4-related disease (IgG4-RD), and immunosuppressive medications can be beneficial if glucocorticoids alone are inadequate or cannot be successfully tapered off. The prognosis of IgG4-related disease (IgG4-RD) varies depending on the organs involved and the timeliness of diagnosis and treatment. Early identification and proper management can lead to positive outcomes, including improved organ function and quality of life. However, it is important to note that some patients may experience relapses or irreversible organ damage, emphasizing the significance of long-term monitoring and follow-up care.


The effects of long-term antibiotic use, including the frequency of recurrent infections and new-onset resistant infections, are not fully understood. The role of antibiotics in the disruption of the gut microbiota has been well-described, impacting insulin susceptibility and lipid deposition.Prolonged antibiotic use may have potential to be implicated in obesity, diabetes, and hyperlipidemia. There may also be an effect on the incidence of secondary infections with new organisms, the frequency of breakthrough infections from the index organism, and the selection for resistant infections.This retrospective study evaluated 78 patients seen at an outpatient infectious disease practice. Inclusion criteria were patients with prescription of an oral antibiotic for 90 or more consecutive days between 9/1/18 and 12/31/2019, who utilize a health system pharmacy. Data was collected from patient charts at baseline prior to antibiotic initiation, and at time of most recent follow up after the initiation of antibiotic.Cephalexin (37.2%), azithromycin (34.6%) and amoxicillin (12.8%) were the most common antibiotics prescribed. Mean patient age was 69.4 years. Indications for antibiotic use included NTM infections (34.6% of cases), prosthetic joint infections (21.8%), recurrent UTIs (10.3%), and prosthetic valve infection (7.7%). 23.4% of patients experienced breakthrough infection with the index organism, while 21.8% experienced new, unrelated infection during follow-up, of which 52.9% had a resistant organism isolated. Mean BMI at baseline was 26.9, and BMI at follow-up was 27.3. The difference between baseline and follow-up BMI was not statistically significant (p=0.177). A1C, LDL, and cholesterol rose from baseline to follow-up, but did not reach statistical significance.Patients on long-term antibiotics had a numerical increase in BMI, A1C, LDL, and cholesterol values following initiation, but those increases were not statistically significant. Recurrence of infection and emergence of resistance was common. The small sample size and limitation of studying patients from one practice within one health system pharmacy are limitations of the study. Further studies with larger sample sizes and comparative groups by diagnosis are needed.All Authors: No reported disclosures


Since 2020, England’s Pharmacy Quality Scheme (PQS) has incentivised increased antimicrobial stewardship (AMS) activities in community pharmacy. In 2020/21, this included the requirement for staff to complete an AMS e-Learning module, pledge to be an Antibiotic Guardian and develop an AMS Action plan. To build and embed these initiatives, in 2021/22, the PQS required the use of the TARGET Antibiotic Checklist (an AMS tool for use when patients present with a prescription for antibiotics to support conducting and recording of a series of safety and appropriateness checks against each prescribed antibiotic). This paper describes the implementation of the national PQS criteria from 2020 to 2022, and details community pharmacies’ AMS activities and barriers to implementation of the 2021/22 criteria. A total of 8374 community pharmacies submitted data collected using the TARGET Antibiotic Checklist for 213,105 prescriptions; 44% surpassed the required number for the PQS. Pharmacy teams reported checking the following: duration, dose, and appropriateness of antibiotics; patient allergies and medicine interactions (94–95%); antibiotic prescribing guideline adherence (89%); and the patient’s previous use of antibiotics (81%). The prescriber was contacted for 1.3% of TARGET Antibiotic Checklists (2741), and the most common reasons for such contacts were related to dose, duration, and possible patient allergy. A total of 105 pharmacy staff responded to a follow-up questionnaire, which suggested that some AMS principles had been embedded into daily practice; however, the necessary time commitment was a barrier. The PQS was able to incentivise mass AMS activities at pace over consecutive years for England’s community pharmacies simultaneously. Future research should monitor the continuation of activities and the wider impacts on primary care. Antimicrobial resistance (AMR) is a public health threat of global concern. In tackling AMR, a key modifiable factor is the behaviour of healthcare workers and patients towards antimicrobials ,2. AntimPrevious qualitative research with community pharmacy staff highlighted AMS roles in providing reassurance and setting patient expectations, in checking antibiotic prescriptions adhere to guidelines, in identifying allergies and interactions, and in discussing prescriptions with prescribers where clinically necessary ,6. ReporThe pharmacy antimicrobial stewardship intervention (PAMSI) was co-developed with pharmacy staff and other key stakeholders ,10. It iThe English Pharmacy Quality Scheme (PQS) is part of the Community Pharmacy Contractual Framework (CPCF) in England and supports delivery of the National Health Service (NHS) Long Term Plan ,17. The Following the positive findings of the small-scale evaluation in 2020, the aim of this study was to assess and describe the national implementation of the TARGET Antibiotic Checklist (which was developed as part of PAMSI) through the PQS incentive scheme, as well as the uptake of AMS e-Learning and the Antibiotic Guardian pledge in 2020/21. The clinical checks completed by the pharmacy team, as well as whether the prescriber was contacted to discuss the prescription, are reported. The accompanying patient data from the TARGET Antibiotic Checklist are reported separately . A folloBox 1Infection prevention and control and review of antimicrobial stewardship practice using the TARGET Antibiotic Checklist  On the day of the declaration (applies to ALL contractors): Contractors must have reviewed their current practice using the TARGET Antibiotic Checklist, in order to provide tailored advice to patients and promote antibiotic awareness and stewardship.  Using the TARGET Antibiotic Checklist, appropriately trained staff must discuss the antibiotic prescribed with the patient or representative to help ensure safe and effective use. Attempts should be made for this discussion to occur with all patients to promote antimicrobial stewardship.  It may be appropriate to speak to an identified patient representative, family member or member of care staff. If there is a potential risk of antibiotic related adverse effects  or concerns about the patient’s therapy, the prescriber must be contacted to suggest a review is undertaken and the details of this intervention recorded in the pharmacy PMR.  The pharmacy team should support the patient to reduce the risk of adverse effects arising from ongoing antibiotic therapy and optimise outcomes through education and advice as well as adopting principles of shared decision-making.The service evaluation of the AMS intervention for community pharmacies in England was conducted as part of a national incentive scheme. The PQS requirements were developed by NHS England (NHSE) in collaboration with internal and external stakeholders . The AMSThe setting of this study was community pharmacies in England and the AMS activities that formed part of everyday practice. All community pharmacies providing NHS services in England were eligible to participate in the PQS, providing they met the gateway criteria of the PQS scheme. This included providing an advanced service (the New Medicines Service) which requires them to meet their terms of service and essential service requirements. Exclusion criteria included any non-NHS community pharmacies. Distance selling pharmacies were not excluded. In March 2022 there were 11,232 registered community pharmacies on the NHS England pharmaceutical list. Information about the PQS, including requirements and guidance about the scheme was communicated to contractors through the NHS Business Services Authority via the Drug Tariff and NHSE’s Pharmacy Quality Scheme Guidance.Patient-facing pharmacy staff were required to pledge to be an Antibiotic Guardian and complete the UKHSA ‘AMS for community pharmacy’ e-Learning module, which was hosted on the Health Education England (HEE) platform ‘e-Learning for Healthcare’, between October 2020 and June 2021. HEE collected non identifiable data on e-Learning sessions launches, active learners and the job role of learners.Community pharmacy teams were asked to use the TARGET Antibiotic Checklist for four weeks to reach a minimum sample size of 25 patients or extend its use to eight weeks if the sample size was not met. Any patient presenting at an NHS community pharmacy with an antibiotic prescription was eligible for inclusion. Pharmacy teams could still declare for the domain if they had not reached the sample size after 8 weeks. Contractors needed to complete the domain between September 2021 and May 2022 and submit data from completed checklists on the UKHSA online SnapSurvey  platform .If the community pharmacy had not completed the requirements of the previous 2020/21 PQS, i.e., if they had chosen previously not to participate in PQS or they were a new pharmacy on the pharmaceutical list, they were required to fulfil all the historic PQS as well as the 2021/22 PQS to be eligible for the PQS payment.The SnapSurvey was a digitalised version of the TARGET Antibiotic Checklist, and pharmacy teams were required to complete a survey for each patient. It also requested the pharmacy ODS code and postcode for verification. The online tool was piloted with 30 pharmacy staff, of whom nine provided further feedback to improve the tool prior to the survey commencing.A follow-up questionnaire hosted on SnapSurvey  collected feedback from a sample of staff about their experience of using the TARGET Antibiotic Checklist as part of the 2021/22 PQS . QuestioDescriptive analysis of the quantitative TARGET Antibiotic Checklist and follow-up questionnaire data was completed using Microsoft Excel. To describe regional uptake, the postcodes of pharmacies were matched to regions and compared with the list of registered pharmacies from March 2022. For qualitative analysis of the open-ended responses, thematic content coding was completed line by line in QSR NVivo 2020, with each response labelled with codes. The codes were then structured into categories and subcategories, and the frequencies of each occurring theme were reported. Example quotes from the open-ended responses which best illustrated the meaning of the themes were reported.As a service evaluation and as patient identifying data were not collected, institutional ethical approval was not required, as confirmed through the UKHSA Research Ethics and Governance Group and the NHS Health Research Authority decision tool . The datThe AMS e-Learning module was launched on the e-Learning for Healthcare website at the start of 2020 and was freely available for any healthcare staff to complete . The 202Of the community pharmacies registered on the NHSE pharmaceutical list in England, 88.5%  committed to the AMS criteria for the 2021/22 PQS; 74.5%  submitted data to the online platform by March 2022. All postcode towns, local authorities and regions of England were represented in the data. There were differences in uptake of the PQS activity regionally, as shown in Data were submitted from 213,105 TARGET Antibiotic Checklists completed with patients collecting antibiotic prescriptions. There was variation in the number of Antibiotic Checklists submitted by the 8374 participating pharmacies (range: 1–181) . Of the Of 213,105 Antibiotic Checklists submitted, 83%  were completed in full with all sections completed by pharmacy staff and/or patients. The remaining 17%  were either partially completed , with at least one section missing data or not completed at all , with no data for any of the sections. For those partially or not completed, 81%  provided an explanation for why it was not possible to collect data in full. The main reasons were lack of access to patient information, i.e., a patient representative was collecting on behalf of the patient and therefore did not know the indication and subsequent information , or the patient declined to complete the checklist or sections of the checklist . See The TARGET Antibiotic Checklist prompted pharmacy teams to conduct and record a series of safety and appropriateness checks against each prescribed antibiotic, and these were completed for 212,124 prescriptions (99.5%). Pharmacy teams reported contacting the prescribing clinician to discuss the prescription on 2741 (1.3%) TARGET Antibiotic Checklists. Out of 845 queries about strength, dose, duration, quantity, and formulation, 197 were for cases where the prescription did not match the recommended licensed dose, and 101 of these specified the dose was incorrect for the patient age, weight, or gender, mainly where the patient was recorded as a child. There were 139 queries regarding the dose and duration of nitrofurantoin, often used to treat UTIs, and 43/139 (31%) specifically queried the duration not matching current guidance . Long term use and rescue packs were often reported for the prevention of UTI in women who suffer from chronic/recurrent UTIs and patients with COPD, respectively.There were 242 queries related to allergies, and 146/242 (60%) of these cases specifically stated the antibiotic was changed or not dispensed (clarithromycin was the most common antibiotic to replace a penicillin). The other 96 did not provide information on the outcome of the allergy query, but the majority were for penicillin antibiotics .Overall, of those who contacted a prescriber, 900 (33%) provided information on the outcome of the discussion. These outcomes were as follows: the prescription dose, formulation, directions, strength or duration was changed for 312 prescriptions (34%); the prescriber confirmed the prescription was appropriate and it did not need to be changed ; or an alternative antibiotic was prescribed for 197 prescriptions (21%). Other less reported outcomes included patient information being confirmed , referral of the patient back to the prescriber to reconsult or confirm information , and that the prescription was cancelled .There were 105 responses from pharmacy staff for the follow-up questionnaire on the 2021/22 PQS activities (2% response rate of the subset of 4628 of pharmacies invited). Most respondents were a pharmacist manager (40%) or pharmacist (37%), but a range of different types of staff participated. There were similar numbers of respondents who worked in a pharmacy chain and in independent pharmacies. All regions of England were represented. Most respondents  stated that they personally contributed to using the TARGET Antibiotic Checklist, and 85%stated they had updated their action plan to include the TARGET Antibiotic Checklist or planned to (7%) since the PQS.The participant demographics and a full list of qualitative themes can be found in The TARGET Antibiotic Checklist was designed so that patients would personally complete the patient section whilst waiting for the prescription to be ready. However, most respondents (75%) reported that staff would ask patients the questions verbally and input answers onto a hard copy and/or directly online. Only 25% reported exclusively asking patients to complete the sections themselves, and 30% used a mix of both approaches depending on the situation. It was reported by 88% of respondents that they aimed to use the TARGET Antibiotic Checklist with any patient with an antibiotic prescription, and 5% aimed to use it with specific patient groups .There was positive response about the overall value of the TARGET Antibiotic Checklist  for suppOpen-ended responses about the benefits included the staff development achieved by delivering the action plan and training on AMS, and patients benefiting from one-on-one discussions and a better understanding of their antibiotics. A minority found the PQS activities to be less valuable; this was due to the activities already being in place, or a belief that the AMS role should be fulfilled by GPs and other prescribers.“The aim is laudable, but this was a PQS hoop-jumping exercise. You’re targeting the wrong people, pharmacies are happy to help patients get best use out of the antibiotics they have been prescribed, but the real levers for change are in the hands of the GPs. We don’t have the time, staff or authority to makes a significant impact”Most respondents reported continued use of the resources. Only 11% and 13% reported not using the TARGET Patient Leaflets or TARGET Antibiotic Checklist, respectively, since their declaration of the PQS 2021/22. For the TARGET Antibiotic Checklist, fewer respondents reported that they use it daily, but more have embedded the principles into their daily practice (40%). In regards to the TARGET Patient leaflets, more respondents reported that they use them daily (24%) or sometimes (45%).While 12 (11%) individuals stated there were no barriers, many discussed the time commitment as a barrier to use of the resources and counseling each patient individually (mentioned 43 times). The respondents discussed a lack of staff and resources. It was stated that provision of printed resources or digital resources which can be used in the pharmacy setting would be favourable.“It is really valuable and important but like every part of community pharmacy, every resource is stretched. We are constantly just trying to keep the essentials done”Among the respondents, 17% reported issues contacting a prescriber to discuss antibiotic prescriptions; 35% did not need to contact a prescriber during the period of the PQS. Issues faced included the timeliness of contacting the prescriber when a patient was waiting for their medication. Some respondents also reported that the prescriber or staff at the practice did not engage in the discussion, or were dismissive or uninterested.“can’t get to speak to them in a reasonable time when patients waiting to take script”“Hard to get a phone back from prescriber and met with stubborn/rude response”The patient barriers were that some patients were not willing or were too sick to wait to receive their medication while the clinical checks were being completed, and some were not engaged in the checklist or expected to receive their antibiotics immediately. Another barrier was that some patients were not physically present; either a representative picked up their antibiotics or they were being delivered, and staff did not have the time to follow up on these patients.“Although all patients agree that antibiotics should be used appropriately—each individual is not keen to wait and see and prefers to use antibiotics in case they get worse and have to take time out of life to get well”A national incentive scheme led to 8374 pharmacies in England  actively participating in structured AMS activities whilst dispensing 213,105 antibiotic prescriptions to patients. The participation from every postcode town in England demonstrates the effectiveness of the PQS in achieving widespread national uptake of AMS activities and its respective criteria. The findings suggested high engagement with the scheme as 44% of participating pharmacies submitted more data than was required, and clinical checks by pharmacy teams were completed in high proportions. As of May 2022, there were 51,453 pharmacists and 20,901 pharmacy technicians registered in England across all sectors with the General Pharmaceutical Council (GPhC) [The reasons that prompt pharmacy staff to contact a prescriber to discuss aspects of prescriptions are varied and highlight the clinical role pharmacy teams have in optimising the use of antibiotics. Prescribing information can often be confirmed through the Patient Medication Record (PMR) and/or summary care record (SCR). Pharmacy teams were able to complete appropriate checks to identify possible safety issues, interactions, and treatment failure. Where the pharmacy team reported contacting a prescriber about a given prescription, and where the outcome of the discussion was provided, over half resulted in aspects of the prescription being changed due to involvement of the pharmacy team. This demonstrates the clinical interventions that pharmacy teams can make in antibiotic decision making as well as supporting the AMS efforts of other prescribers.The antibiotic most often dispensed where pharmacy teams intervened to contact a prescriber was amoxicillin, which is a narrow-spectrum antibiotic used to treat many conditions in primary care. Unsurprisingly, amoxicillin and other penicillin antibiotics were those most queried where an allergy was detected. In a small number of cases, the pharmacy team did not dispense the antibiotic , but the exact context for this was unknown. Community pharmacy teams also discussed possible unnecessary prescriptions which could be part of a delayed prescribing strategy protocol with prescribers, which is often used, for example, when prescribing antibiotics for sore throats .Some of the queries related to dose and duration were for UTI antibiotics; the guidance for prescribing in women aged 65 years or below is for 3 days, and pharmacy teams intervened, for example, when a patient received a prescription for 7 days . PharmacThe TARGET Antibiotic Checklist asked pharmacy teams to report the reason for querying a prescription, but in many cases the outcome  and the wider context was not recorded. More in-depth analysis is required to determine the extent of the intervention community pharmacies have made in promoting AMS through their role in discussing prescriptions with prescribers (beyond the scope of this paper).The follow-up questionnaire findings with a sample of participating community pharmacy staff found that, at least in the short term, most respondents continued to use the resources themselves or the principles introduced, since participating in the PQS. Staff reported improved confidence, development of staff members and a belief that patients benefitted from education. Several barriers to using the resources and participation in AMS in general were reported in the follow-up questionnaire, the main issues being a lack of resources (time and staffing), patient expectations, patients not being present to provide information, and difficulty contacting prescribers to discuss prescriptions.AMS in community pharmacy is a growing area of research. Qualitative studies in England, Wales, and Scotland published before 2020 highlighted a lack of awareness of AMS, the role of pharmacy staff and AMR campaigns and interventions ,7. In EnQualitative research in France and a UK survey of pharmacy professionals who had pledged to be an Antibiotic Guardian found good knowledge of AMR and motivation to engage in AMS initiatives ,27,28. TAn evaluation of PAMSI in 2020 with 66 community pharmacies found that 84–86% of antibiotic prescriptions were checked by the pharmacy team for allergies, risk factors, dosage, duration and if the antibiotic was appropriate for the indication, and 73% were checked against local prescribing guidelines . This isA survey in Cornwall found that 18% of pharmacy staff would routinely ask patients their indication as 70% were concerned patients would either not know the clinical name of their infection or would not want to tell the pharmacist . LikewisAllergies were the second most common reason for the pharmacy team to contact a prescriber in our study. The role of pharmacy staff in checking patient allergies and interactions is well recognised ,27. As tEffective communication, collaboration and teamwork between pharmacy teams and other healthcare professionals is imperative for AMS. Our follow-up questionnaire findings suggested pharmacy teams face challenges in obtaining prompt access to discuss prescription issues with prescribers whilst under pressure of patients waiting, and a minority reported a lack of ability to directly influence prescribing decisions. A meta-analysis found that antibiotic stewardship programmes that involve pharmacists are effective at improving adherence to antimicrobial prescribing guidelines; therefore, promoting collaboration is key . In someOur findings echo the previous evaluation of PAMSI in 2020 which found that pharmacy staff lacked time, resources and staffing to address AMS, and physical resources such as the TARGET Antibiotic Checklist were not feasible for patients who have their prescription delivered or picked up by representatives . Issues A strength of this paper is the large dataset collected through a national scheme, representing large proportion of community pharmacies in England. To date, this is one of the largest datasets investigating AMS activities in community pharmacies. The data give a snapshot of current pharmacy AMS activities in an uncontrolled setting, evaluating the impact of an intervention introduced into daily practice. However, a limitation is that the activities may not be comparable to usual practice as they were introduced through an incentivised scheme. Furthermore, as the data were inputted by pharmacy staff, there are likely to be errors in the data entry process, and it was not feasible to ask participants to double enter data. This required data cleaning, and responses that were ambiguous  were removed from the analysis. The data relating to reasons why pharmacy teams contacted a prescriber offer useful insights into interventions by the pharmacy team. An in-depth analysis of these reasons was beyond the scope of this paper and project but could be explored further in future work. The data provided do not include the full context, and in many cases, although the outcome was reported, a clear reason was not given by the pharmacy team when they inputted the data as to why decisions were made. A strength of this paper is the inclusion of follow-up questionnaire data which provide a wider context and understanding of implementation barriers. The responses were from a varied sample representing all regions of England, different pharmacy job roles and types of pharmacies. As the follow-up questionnaire was sent to a sample of participating pharmacies, a limitation is the potential for sampling bias, where it is possible that more enthusiastic individuals participated.Through a national incentive scheme, the PQS AMS activities in community pharmacy were promoted effectively. This was demonstrated through high engagement within the scheme, and follow-up questionnaire responses suggest that some AMS activities continued. Future PQS and other activities need to build on this to continue the momentum, and future research should monitor the impact on patient attitudes and behaviours through national public surveys. The PQS for 2022/23 built on the clinical role of pharmacies by embedding shared decision-making tools to support consultations for patients with respiratory and urinary tract infections, before an antibiotic is dispensed ,36. All Our findings further highlight and recognise the essential clinical role that community pharmacy staff have in tackling AMR through AMS interventions and collaborative work with other primary care colleagues, as well as ongoing and continued public education to ensure the safe and appropriate use of antibiotics. These findings add to the evidence that community pharmacy can play a vital role in AMS and support the NHS in England, and internationally, to tackle the significant threat of AMR to public health.


The decrease in the quality of recycled aggregate due to an increase in the number of recycling is a primary factor that limits the multi-recycling of concrete. This degradation adversely affects concrete performance; thus, the characteristics of recycled aggregate should be considered during the mix design stage, but little research has taken that into account. This study investigates the effect of the equivalent mortar volume (EMV) mix design on some physical, mechanical and durability properties of concrete made of multiple recycled coarse aggregates at 50% and 100% replacement ratios compared to concrete made by the conventional mix design (CMD). The results showed that the performances of concrete by the CMD decreased with an increasing number of recycling cycles. The properties of EMV-based concrete deteriorated with an increase in the number of recycling cycles at 100% replacement ratio due to poor workability caused by a shortage of fresh mortar. However, at 50% replacement, the EMV-based concrete exhibited similar performance across the three cycles of recycling, as well as improved properties over natural aggregate concrete. This study demonstrated that an appropriate mix design and optimal aggregate replacement ratio can offset the property loss of multiple recycled aggregate concrete. Extensive and diverse studies on recycled aggregate for green construction have led to the establishment of various technical guidelines and standards for its use in many countries and institutes ,3,4,5,6.To date, studies on multiple recycled aggregate concrete (MRAC) have been conducted by a limited number of scholars, but this topic is intriguing to many researchers, and the interest is clearly growing. In general, the multiple recycling of concrete progressively reduces its mechanical properties in proportion to the number of recycling cycles. In a study by Abreu et al. , the 28-The aforementioned studies have investigated the effect of multiple recycling of concrete and reported the progressive decrease in performance as the number of times of recycling increases ,12,13. ATherefore, this study aims to enhance the performance of MRAC. A series of MRACs containing once-, twice- and thrice-recycled coarse aggregates (RCA) were prepared by the conventional mix design (CMD) and the EMV methods, respectively, and their physical, mechanical and durability properties were analyzed. The obtained experimental data are expected to make an important contribution to complementing the lack of knowledge about MRAC. After all, the ultimate goal of this study is to explore true sustainability of concrete through multiple recycling.RCA1: it refers to the first generation RCA produced by multiple crushing precast concrete members made of natural aggregate in a recycling plant.RAC1: the first generation RAC containing RCA1 is denoted as RAC1, and it is subdivided into R1-C-100, R1-E-50, and R1-E-100 according to the mix design and replacement ratio of RCA1.RCA2: the second generation RCA, RCA2, was obtained by crushing RAC1 with 100% RCA1  with a laboratory jaw crusher after 35 days of curing. In particular, R1-E-50, which contains 50% of natural coarse aggregate (NCA), was excluded from RCA2 production in order to ensure the representativeness of being recycled twice.RAC2: the second generation concrete uses RCA2, and it is divided into R2-C-100, R2-E-50, and R2-E-100 based on the mix design and RCA2 replacement ratio.RCA3: this refers to RCA obtained from RAC2 with 100% RCA2 . For the same reason as in the RCA2 preparation described above, R2-E-50 was excluded from RCA3 production.RAC3: the third generation RAC. RAC3 was produced using RCA3 as a coarse aggregate, and it is classified into R3-C-100, R3-E-50, and R3-E-100 depending on the mix design and aggregate replacement ratio.The experimental procedure of this study is shown in In this experimental research program, ordinary Portland cement was used as a binder, and its properties are provided in In order to investigate the mechanical and durability properties of MRAC, a total of 10 concrete mixtures were designed by the CMD and the EMV design : referenThe mix proportion of each mixture is detailed in Reference concrete was prepared using natural aggregates, and the mix proportion provided by a ready-mixed concrete plant was adopted, which was set to achieve a 28-day compressive strength of 30 MPa and a slump of 180 mm.For RAC1, two mix designs were used: CMD and EMV. Concrete made by CMD was named R1-C, and the concrete made with the EMV mix design was divided into R1-E-50 and R1-E-100 based on the RCA1 replacement ratio.The RAC2 with the CMD was named R2-C, and RAC2 proportioned by the EMV design was divided into R2-E-50 and R2-E-100 depending on the RCA2 replacement ratio. Particularly, at 100% replacement ratio, the combination of RCA2 with adhered mortar content of 23% and the EMV design significantly reduced the amount of fresh mortar, making it nearly impossible to mold with the general compaction , thus the modified EMV design proposed by Yang and Lee  was applThe RAC3 was classified into R3-C, R3-E-50 and R3-E-100 according to the mix designs and RCA3 replacement ratios. As in the case of RAC2, the modified EMV design was applied for R3-E-100. The adhered mortar content was considered to be 16% instead of 32%.For all mixtures, the water-to-cement ratio was kept constant at 0.4, and the dosage of a polycarboxyl-based plasticizer was maintained at 0.8% of the cement mass as recommended by the manufacturer. The concrete mixing and specimen preparation were carried out in accordance with ASTM C192.Workability, several physical, mechanical and durability properties of hardened concretes have been carried out. Some tests and devices used are presented in The workability, a key performance indicator of fresh concrete, was determined by the slump cone test in accordance with ASTM C143.The density and water absorption were measured to investigate the degree of porosity of concrete. The density was determined by dividing the mass in the saturated surface dry (SSD) state by the volume of the specimen. The water absorption was determined by subtracting the SSD mass by the oven-dry (OD) mass and dividing it by the OD mass.The mechanical strength of the hardened concrete was measured using a hydraulic universal testing machine with a capacity of 1000 kN on specimens cured for 28 days. Compressive strength and splitting tensile strength were performed on cylindrical specimens with a size of 100 × 200 mm in accordance with ASTM C39 and ASTM C496, respectively. A load corresponding to a stress of 0.25 MPa/s for compressive strength and 1.0 MPa/min for splitting tensile strength was applied at a constant rate until failure a,b. FlexThe drying shrinkage was performed to evaluate the potential for concrete to shrink over time due to moisture loss in accordance to ASTM C157. The prism specimens with a size of 100 × 100 × 400 mm were mounted on a device with an electronic dial gauge after 24 h of curing, and placed in a chamber with controlled temperature and relative humidity set to 23 °C and 50%, respectively, for 100 days d.The rapid chloride penetration test was performed according to ASTM C1202 to evaluate the resistance of concrete to chloride ions. Concrete disk samples with a size of 100 × 50 mm for testing were obtained by cutting the center of 100 × 200 mm cylindrical specimen, and the sides of the disk samples were coated with epoxy. The specimens were then conditioned according to the procedures specified in the standard: the specimens were placed in a vacuum desiccator at an absolute pressure of 6.65 kPa for 3 h, and water was put through the water valve to soak the specimens in water for 1 h under vacuum. The vacuum was then removed by opening the air valve and left in the water for 18 h. The conditioned specimens were assembled in a cell and applied at 60 V for 6 h e.The slump values of the MRAC manufactured by the CMD and the EMV method are shown in 3 and 4.75%, respectively, and those of MRAC varied from 2208 to 2372 kg/m3 and from 2.87 to 7.61%.The test results for density and water absorption are presented in 3 for R1-C-100, 2349 kg/m3 for R1-E-50 and 2332 kg/m3 for R1-E-100. This is related to the quality of the aggregate used, i.e., the density of RCA1 is comparable to that of NCA.The RAC1s showed little difference in density compared to NAC (≥1%). Furthermore, the densities of the RAC1s are almost similar to each other: 2321 kg/m3 for RAC1, 2337 kg/m3 for RAC2 and 2372 kg/m3 for RAC3), whereas for the E-100 concretes, the density decreased by up to 5.3%. The combination of the EMV mix design with high volume and low-quality RCA often causes workability issues. Hayles et al. [As the number of recycling generation increases, the density of C-100 concrete gradually decreases. The densities of R2-C-100 and R3-C-100 were 3.5% and 4.4% lower than that of R1-C-100. This reduction is a result of the increased accessible porosity due to the higher adhered mortar content and lower density of RCA with increasing number of recycling . Unlike s et al.  noted ths et al.  reportedThe test results of the 28-day compressive strength, one of the most decisive properties of hardened concrete, are shown in The compressive strength of the first generation concretes, R1-C-100, R1-E-50 and R1-E-100, increased by 5% to 14% over that of NAC. This increase can be attributed to the quality of RCA1, which has low water absorption and high density. Concrete made with high-quality RCA exhibits comparable to or even better strength than concrete with NCA ,28. SpecThe effects of the mix design methods are noticeably observed in RAC2 and RAC3. For the concrete with CMD, the compressive strength progressively decreases as the number of recycling cycles increases, as reported in previous studies ,15. The The gradual decrease in mechanical strength observed in the CMD-based concretes is associated with changes in RCA characteristics. The RCAs experienced deterioration in quality, such as increased water absorption and decreased density, with the number of recycling cycles. This leads to a weaker ITZ between the RCA and cement paste, resulting in strength loss . In contThe mechanical strength test results indicate that high-quality RCA can replace natural aggregates in terms of concrete strength without any significant barriers. Furthermore, by combining the proper RCA replacement ratio and concrete mix design, strength loss caused by multiple recycling can be prevented.The results of drying shrinkage on various concretes for 100 days are plotted in The drying shrinkage of the CMD-based concrete increased with the number of recycling cycles. Compared to R1-C-100, the drying shrinkage of R2-C-100 and R3-C-100 was 28.0% and 36.2% higher, respectively. This increase can be attributed to changes in the physical characteristics of the RCA as the number of recycling cycles increases. Previous studies ,33 have The results of electrical conductivity tests performed on each concrete are shown in To verify representativeness and effectiveness, the experimental data obtained in this study were compared with those of previous studies ,10,26,34The degradation of MRAC is associated to the gradual increase in the adhered mortar content of RCA obtained from repeated recycling of concrete, resulting in RCA turning into a low-density, high-porosity material. In this study, various properties of MRAC designed by the CMD and the EMV method were investigated.Concrete that includes RCA1 with low water absorption demonstrated performance comparable or superior to NAC. The slump of R1 concretes ranged within ±20 mm, and properties such as compressive strength (5–11%), tensile strength (±3%), flexural strength (14–17%), chloride resistance (11–18%), and drying shrinkage (3–12%) were improved when compared to those of NAC. This indicates that the poor performance caused by RCA in concrete compared to NCA can be offset by the use of high-quality RCA.As the number of recycling processes increases, the quality of RCA gradually diminishes, leading to a significant deterioration in the properties of the resulting concrete. Compared to R1-C-100 and R1-E-100, the slump, mechanical strength, and chloride resistance of R3-C-100 and R3-E-100 concretes decreased by up to 69%, 25%, and 60%, while the drying shrinkage increased by 40%. However, in contrast to this trend, the E-50 concretes exhibited a similar level of performance across three generations of recycling. Therefore, it can be concluded that the use of multi-recycled aggregate may reduce the performance of concrete, but this performance degradation can be mitigated through a combination of appropriate mix design and RCA replacement ratio.The experimental results in this study also indicate that RCA, even multiple RCA, have no barriers to being used as substitutes for NCA in terms of concrete performance. This could be an important finding in achieving true sustainability, enabling repeated recycling of concrete.Irrespective of the mix design method, remarkable slump losses were observed as the number of recycling increased, particularly in case of the EMV-based concrete. For the E-50 concrete, despite the good hardened performance, it may not suitable for building concrete unless its workability is improved. On the other hand, due to its low slump, the E-50 concrete can be utilized for prefabricated concrete elements, such as road pavement, precast structural members, sewage pipes, bricks and blocks.Since the concept of multiple recycling of concrete has been discussed relatively recently, there are many unknowns compared to the ‘used once’ recycled aggregate concrete. Therefore, further research is needed from various perspectives. For example, an investigation could be conducted to overcome the observed slump loss of MRAC through an increase in plasticizer dosage or through the use of supplementary cementitious materials. In addition, chemical and microstructure analyses, which have not been performed in this study, are recommended. Particularly, the analysis on the economic viability and environmental impact of multiple recycling of concrete remains unexplored, which will make a significant contribution towards achieving true sustainability in the concrete industry.