Escherichia coli (ETEC) challenge.Sialyllactose (SL) is one of the most abundant oligosaccharides present in porcine breast milk. However, little is known about its effect on growth performance and intestinal health in weaned pigs. This study was conducted to explore the protective effect of SL on intestinal epithelium in weaned pigs upon enterotoxigenic Thirty-two pigs were randomly divided into four treatments. Pigs fed with a basal diet or basal diet containing SL (5.0 g/kg) were orally infused with ETEC or culture medium.P < 0.05). SL also improved the digestibilities of dry matter (DM), gross energy (GE), and ash in non-challenged pigs (P < 0.05). Moreover, SL not only elevated serum concentrations of immunoglobulins , but also significantly decreased the serum concentrations of inflammatory cytokines  upon ETEC challenge (P < 0.05). Interestingly, SL increased the villus height, the ratio of villus height to crypt depth (V:C), and the activities of mucosal sucrase and maltase in the jejunum and ileum (P < 0.05). SL also elevated the concentrations of microbial metabolites  and the abundance of Lactobacillus, Bifidobacterium, and Bacillus in the cecum (P < 0.05). Importantly, SL significantly elevated the expression levels of jejunal zonula occludins-1 (ZO-1), occluding, and fatty acid transport protein-4 (FATP4) in the ETEC-challenged pigs (P < 0.05).SL supplementation elevated the average daily gain (ADG) and feed efficiency in the ETEC-challenged pigs (SL can alleviate inflammation and intestinal injury in weaned pigs upon ETEC challenge, which was associated with suppressed secretion of inflammatory cytokines and elevated serum immunoglobulins, as well as improved intestinal epithelium functions and microbiota.The online version contains supplementary material available at 10.1186/s40104-022-00673-8. Escherichia coli (ETEC) has been considered to be the main bacterial cause of PWD and intestinal injury (accounts for more than 45% of piglet diarrhea). Previous study indicated that ETEC can adhere to intestinal epithelial cells and cause intestinal injury through endotoxin and exotoxin [Weaning is one of the most stressful events for neonatal pigs, as weaning deprives their protections from maternal passive immunity and may contribute to intestinal and immune system dysfunctions that lead to reduced growth and feed intake, particularly during the first week after weaning . Post weexotoxin , 3. In pBifidobacterium and Bacillus) [Breast milk has been considered to be the most ideal food for neonatal animals including pigs, as it contains nearly all necessary nutrients for neonatal animals . Moreoveacillus) , servingacillus) , and proacillus) . Moreoveacillus) .Although, there are many studies on milk oligosaccharides, the effect of SL on growth performance and intestinal epithelial functions in weaned pigs is just beginning to be explored. This study was conducted to explore whether SL supplementation could attenuate intestinal inflammation and epithelium injury in weaned pigs induced by ETEC. This study will also provide convincing evidence on the beneficial effect of milk oligosaccharides and offer key insights into its potential mechanisms of action.Escherichia coli (ETEC) was purchased from China veterinary culture collection center . The serotype of ETEC was o149: K91, k88ac, and the strain number of CVCC was 225. It was a vacuum freeze-dried strain. The ETEC with strong toxicity was produced through resuscitation and proliferation culture in our laboratory. Luria-Bertani (LB) and LB agar broth were prepared  and sterilized under 121 °C, 0.11 MPa for 20 min (pH = 6). The bacteria were resuscitated in 3 mL of Luria Bertani (LB) broth at 37 °C with shaking for 24 h and inoculated on LB agar. A single colony was inoculated into 50 mL of LB broth, cultured overnight at 37 °C and 250 rpm, then subcultured and serially diluted on LB agar for bacterial counts [Pathogenic l counts .10 CFU/mL of ETEC by using an orogastric tube last for 3 d, whereas the non-challenge groups were orally treated with equivalent amount of culture medium [2 metabolism cage and were given ad libitum access to feed and fresh water with the room temperature controlled between 25 and 28 °C, relative humidity 65% ± 5%.A total of 32 male Duroc × Landrace × Yorkshire pigs weaned at 21 days of age (with an average body weight of 6.66 ± 0.14 kg) were selected and randomly allotted into a 2 (SL) × 2 (ETEC) factorial experiment of four treatments composed of CON , CSL , ECON , ESL . Sialylactose  was obtained from Glycom A/S. SL is produced via microbial fermentation and is a trisaccharide made from glucose, galactose and N-acetylneuraminic acid. The concentration of SL in the diet is 5 g/kg, which was decided according to the oligosaccharides content in the mature milk of sow’s (5 to 10 g/L) and previous study on piglets . Pigs wee medium . The base medium . Pigs we2SO4 solution to per 100 g of fresh fecal. The feed and fecal samples were dried at 65 °C for 2 d, and ground to pass through a 1-mesh screen, and then stored at − 20 °C until measurement for nutrients digestibility. Blood samples were obtained on d 22 by jugular vein puncture and placed in two 10-mL vacuum tubes. One for blood parameters analyzed and the serum was collected after centrifugation of another tube at 3500 × g and stored at − 20 °C until the serum indexes analysis. Pigs were anesthetized by intravenous injection with sodium pentobarbital (200 mg/kg BW), and the tissues of the duodenum, jejunum and ileum were immediately isolated at the end of the trial. At the same time, the duodenum, jejunum and middle ileum (4 cm from the middle of each intestine) were gently rinsed with cold phosphate buffered saline (PBS), and then fixed in 4% paraformaldehyde solution for morphological analysis. In addition, the cecal digestive products were collected, and the intestinal mucosa was obtained from the residual intestinal segments with a scalpel blade and placed in a freezing tube, then frozen by immersion in liquid nitrogen, and stored at − 80 °C until analysis.Feed samples were collected at the beginning of the experiment and stored at − 20 °C for nutrient analysis, during the d 22–25 of the experiment, fresh fecal samples were collected immediately after excretion from pigs in each cage, weighed, and adding 10 mL 10% HThe frozen dried and milled feed and fecal samples were used for nutrient digestibility analysis, which uses acid insoluble ash (AIA) as endogenous indicators. The dry matter (DM), crude protein (CP), ether extract (EE) and ash contents were determined according to AOAC , whereasThe concentration of proinflammatory cytokines  and immunoglobulin  in serum were determined followed by the instructions of a commercial available porcine Enzyme-Linked Immunosorbent Assay (ELISA) kits . All procedures were guided by manuals of the kits. For quantification, the standards provided in the kits were used to generate standard curves.The fixed with 4% paraformaldehyde intestinal segments were dehydrated through a graded series of ethanol and then embedded in paraffin . Cross-sg for 10 min at 4 °C and the supernatant was used to determine the enzyme activities. The activity of alkaline phosphatase (AKP) was determined using the alkaline phosphatase assay kit (A059–2-2) purchased from Nanjing Jiancheng Biotechnology Co., Ltd. . The enzyme-linked immunosorbent assay (ELISA) kits purchased from Shanghai Enzyme-linked Biotechnology Co., Ltd.  were used for detections of lactase (Porcine Lactase ELISA Kit ml712060), sucrase (Porcine Sucrase ELISA Kit ml712026), and maltase . All procedures were carried out according to the instructions of the kits. The absorbance of each reaction was determined using the spectrophotometer  at a wavelength of 450 nm. Enzyme activity was defined as hydrolysis of 1 mol of the substrate per mg of protein tissue per minute under the condition of 37 °C, pH = 6.0.The frozen duodenal, jejunal and ileal mucosa were homogenized in chilled saline at a ratio of 1:9 (w/v) for 15 min. The homogenate was centrifuged at 3500 × 2O. The SuperReal PreMix (Probe) kit  was used for Lactobacillus, E. coli, Bacillus and Bifidobacterium detection and primers and fluorescent oligonucleotide probes presented in 2O. All reaction protocol was composed of one cycle of pre-denaturation at 95 °C for 15 min; forty cycles of denaturation at 95 °C for 3 s; annealing and extension at 60 °C for 30 s. The Cycle threshold (Ct) values and baseline settings were determined by automatic analysis settings, and the copy numbers of the target group for each reaction were calculated from the standard curves, which were generated by constructing standard plasmids by a 10-fold serial dilution of plasmid DNA (1 × 101 to 1 × 109 copies/μL).Approximately 200 mg caecal digesta was weighed and treated using the Stool DNA Kits  following the manufacturer’s instruction to extract total DNA for quantification real-time PCR, which was performed by conventional PCR on the Opticon DNA Engine (Bio-Rad). Total bacteria were detected by the reaction which runs in a volume of 25 μL with 1 μL of forward and 1 μL of reverse primers (100 nmol/L), 12.5 μL SYBR Premix Ex Taq (2 × concentrated), 2 μL template DNA, 1 μL 50 × ROX Reference Dye*3 and 7.5 μL of RNase-Free ddHg), and the supernatant (1 mL) was then transferred into an Eppendorf tube (2 mL) and mixed with 0.2 mL metaphosphoric acid. After 30 min incubation at 4 °C, the tubes were centrifuged at 4 °C for 10 min  and aliquots of the supernatant (1 μL) were analyzed using the GC with a flame ionization detector and an oven temperature of 100–150 °C. The polyethylene glycol column was operated with highly purified N2 as the carrier gas at 1.8 mL/min.The SCFA  concentrations were determined using a gas chromatograph system  following previous method . After vThe frozen duodenal, jejunal and ileal mucosa samples (about 0.1 g) were ground in liquid nitrogen and homogenized in 1 mL of RNAiso Plus  to extract total RNA followed the manufacturer’s instructions, and the purity and concentration of total RNA were detected by using a spectrophotometer , samples which OD260/OD280 ratio ranged from 1.8 to 2.0 were deemed appropriate. Subsequently, a volume equivalent to 1 μg total RNA from each duodenal, jejunal, and ileal sample was used for reverse transcription into cDNA, which based on the protocol of PrimeScript™ RT reagent kit with gDNA Eraser . This process consists of two steps: I: 37 °C for 15 min, II: 85 °C for 5 s.–ΔΔCt method [The expression level of the target gene in intestinal mucosa was quantified using q-PCR, the oligonucleotide primers sequences used in q-PCR were presented in t method .The minimal sample size was calculated based on the experimental design  determining the SL × ETEC effect to the intestinal health as the primary outcome measure. We used G*Power software (version 3.1.9.2) for the power analysis with following variables; the power = 0.8, significant level = 0.05, and effect size = 0.35 in the experiment. The effect size was estimated based on the results from a preliminary study. Hence, the required minimal sample size was five pigs per group.P-value < 0.05 was deemed to be significant and the P-value between 0.05 and 0.1 to show a significant trend. Duncan’s multiple range test was used based on the analysis of ANOVA, which showed a significant difference. All data were analyzed by SPSS 24.0  and GraphPad (version 9) software . Results are expressed as means with their standard errors.The data collected before the ETEC challenge was analyzed by one-way ANOVA. After the challenge, the data were analyzed by two-way ANOVA with the General Linear Model (GLM) procedure of SPSS as a 2 (SL) × 2 (ETEC) factorial design. P < 0.05). Moreover, we observed a trend toward an interaction effect of SL and ETEC, when this trend toward an interaction effect was investigated with post-hoc test, we found that while the ETEC increased the F:G, this effect was prevented by the SL treatment. SL increased the digestibilities of DM, Ash, and GE in non-challenged pigs (P < 0.05). The digestibility of Ash was also higher in the ESL group than in the ECON group (P < 0.05) (Table As shown in Table 5) Table .Table 2P < 0.05). However, SL supplementation increased their concentrations in the non-challenged pigs (P < 0.05). A trend toward an interaction effect of SL and ETEC was observed that the decreasing of IgA upon ETEC challenged was prevented by the SL treatment. The serum inflammatory cytokines such as the TNF-α and IL-1β were higher in the ECON group than in the CON group (P < 0.05). However, SL supplementation significantly decreased their concentrations in the ETEC-challenged pigs (P < 0.05) and increased the IL-6 concentration in non-challenged pigs.As shown in Fig. P < 0.05). However, SL supplementation significantly increased the jejunal villus height in ETEC-challenged pigs (P < 0.05). For the V:C, ETEC challenge significantly decreased ratio of V:C in the duodenum, jejunum, and ileum (P < 0.05). Moreover, two trends toward an interaction effect of SL and ETEC in ileum were observed, when these trends toward an interaction effect were investigated with post-hoc test, we observed that while the ETEC increased the crypt depth and decreased V:C, these effects were prevented by the SL treatment (P < 0.05). As shown in Table P < 0.05). Moreover, the sucrase activity in the duodenal, jejunal and ileal mucosa of the CSL group was significantly higher than that in the CON group (P < 0.05).As shown in Table E. coli in the cecum. SL supplementation significantly elevated the abundance of beneficial microbial populations such as the Lactobacillus, Bifidobacterium, and Bacillus in the non-challenged pigs (P < 0.05). Moreover, ETEC challenge decreased the concentrations of acetic acid and propanoic acid in the cecum. However, there is a trend that SL supplementation prevented the decreasing concentrations of acetic acid and propanoic acid. SL also elevated the concentration of butyric acid in the non-challenged (P < 0.05).As shown in Table ZO-1 and claudin-1 in the duodenal and jejunal epithelium (P < 0.05). SL also elevated the expression level of occludin in the jejunal epithelium (P < 0.05). Interestingly, ETEC challenge decreased the expression level of FATP-4 in the jejunal epithelium. Moreover, SL supplementation also elevated the expression level of jejunal GLUT-2 in the non-challenged pigs (P < 0.05).As shown in Fig. It is well known that breastfeeding is the gold standard for infant nutrition. It offers complete nutrients for the newborn as well as many bioactive components that contribute to healthy development of the newborn . BioactiImmunoglobulins, also known as antibodies, are glycoprotein molecules produced by plasma cells, which act as a critical part of the immune response by specifically recognizing and binding to particular antigens, such as bacteria or viruses, and aiding in their destruction . In the The small intestine is the main place for digestion and absorption, and its integrity determines whether it can function normally. However, ETEC infection can destroy the intestinal structure, and severely impair the intestinal digestion and absorption function . Villi aBifidobacterium species, a dominant species in breast-fed infants [E. coli to Caco-2 cells and increase the abundance of Bifidobacterium and Lactobacilli in the infants and adults feces [Lactobacilli, Bacillus, and Bifidobacterium in the non-challenged pigs. Importantly, SL not only decreased the abundance of Escherichia coli, but also increased the abundance of Lactobacilli, Bifidobacterium and Bacillus in the ETEC-challenged pigs. Previous study indicated that MOs including the SL are structurally similar to the polysaccharide on the surface of intestinal epithelial cells which can act as an analog of bacterial lectin ligand and block bacterial attachment [Lactobacillus and Bifidobacterium can increase the butyric acid production, which may contribute to reduced generation of pro-inflammatory cytokines such as the TNF-α [MOs are known to support the growth of beneficial microorganisms in the large intestine, especially the  infants . As one  infants , 44. Rects feces , 46. Simtachment . Moreovetachment . Nondigetachment . SCFA, etachment . In the he TNF-α . Moreovehe TNF-α .Tight junctions are composed of transmembrane barrier proteins , cytoplasmic scaffold proteins , and adhesion molecules, which play a key role in maintaining intestinal permeability . HoweverBifidobacterium and Bacillushis have a protective effect on the intestinal barrier and can downregulate the expression levels of inflammatory cytokines [In the present study, we found that SL has beneficial effects on intestinal morphology, expression of tight junction proteins and inflammatory cytokines, probiotic colonization and VFA production. Previous studies have shown that probiotics such as ytokines –58. Therytokines , and incDietary SL supplementation improves the growth performance and alleviates ETEC-induced intestinal injury in the weaned pigs, which was associated with suppressed secretion of inflammatory cytokines and elevated serum immunoglobulins, as well as improved intestinal epithelium functions and microbiota. The beneficial effects of SL on the intestinal integrity and epithelium functions could make it an attractive prebiotic in the use of animal nutrition and feed industry.Additional file 1 Table S1. Sequences of primers for genes and intestinal bacteria.


In the mechanics of concrete constructions, one distinguishes between residual and elastic strains. Cyclic loadings evoke changes mainly in the elastic strains; however, the total strains are decided by the sum of the residual and elastic strains. The knowledge of the ratio between the residual and total strains allows to predict the total deformations of a construction assuming it is made from an ideally elastic material. This paper presents the effect of the load level at the values of the residual strains for beams made of high-strength concretes and subjected to bending. The investigations showed that the share of residual strains for these concretes differed from the share of residual strains for concretes of lower classes. The investigations were made for cyclically loaded concrete samples and ferroconcrete beams for various relative load levels. The ratio between the residual and total strains was presented in the form of a dependence on the relative load level of the element. An important conclusion was that, after the crack formation, the share of residual stresses reduced, along with the increase in the concrete strength and elastic features of the construction which started to predominate. The investigations of the relation between stress and strain (σ−ε) are fundamental and are performed in order to precisely examine the material response to acting loads. In the case of concrete constructions, the detailed evaluation of the relation σ−ε enables the prediction of a behavior of the construction as a dependence on its stress state. In most cases, experimental tests are performed with statically increasing values of an acting force (compressing or tensile), from zero up to the value which destroys a sample. If only the most important quantities characterizing a material are sought, this is usually sufficient. However, if one takes into account that real engineering constructions work under loads varying in different ways  and that the loading–unloading cycles can repeat many times, then the investigations of the relation σ−ε should also be expanded by the aforementioned factors. In this regard, the constitutive material models should be created which consider the most important factors responsible for a material’s behavior.The first studies concerning this topic can be found in ; other rThe constitutive models of concrete, presented in the literature, are usually based on the theories of elasticity, plasticity or fracture mechanics. This latter approach is a good reflection of the material behavior but requires the determination of a large number of parameters which is cumbersome and limits the application of such models in the engineering practice; several works within this scope are accessible where a good agreement between the developed models and the experimental results was achieved ,6,7. TheWhen analyzing the aforementioned publications, one can note a distinct and continuous striving to upgrade the models and increase their rational applicability in an engineering practice. An important summary in this aspect was made by Aslani and Jowkarmeimandi ; their dAlong with the improvement of the research methods and constitutive models, a distinct progress in the widely understood concrete technology occurs in building construction as well. Due to this, high-strength concretes become increasingly common; according to the currently applied criteria, this designation denotes a material with a characteristic compressive strength of over 50 MPa. The range of this strength is wide and amounts to ca. 100 MPa. The concrete with such high-strength parameters provides huge possibilities for the design of engineering constructions. The research works concerning the development of the appropriate constitutive models describing the high-strength concrete can be found in the literature. Aslani and Nejadi  proposedRashid et al.  presenteThe stress–strain relation is not, in all cases, a basic topic of the experimental investigations. The possibility of the credible prediction of the strains of components in a construction allows for their adaptation to the aesthetic and usability requirements resulting from its purpose. The advanced (nonlinear) Finite Element Method meets such expectations ,17,18,19In high-strength concretes, a broader elastic range is observed in the relation σ−ε than in classical concretes. This paper presents how to experimentally separate the elastic and plastic part of a strain in a ferroconcrete beam subjected to bending. The results of the investigations presented below align with the subject undertaken in a previous work . This anfib Model Code 2010 [Many numerical models were developed in the literature, describing the nonlinear behavior of the concrete and using, i.a., the environments Abaqus ,17, LS-Dode 2010 , Adapticode 2010  as well ode 2010 ,9. Due tode 2010 ,16 and Tode 2010  are releode 2010 ,20,21. TThe paper presents the influence of a load level on the values of the residual strains for high-strength concrete beams subjected to bending. The aim of the investigation was to present, in the case of an experiment, how the share of the residual strains in relation to the elastic strains changed for different levels of the load acting on the construction. The studies so far undertaken concerned the mainly compressed elements. In the case of the bent elements, the behavior after the first cracks occurred in the construction was also important . The experimental investigations made for the compressed elements showed that the share of the residual strains for the high-strength concretes differed from the share of residual strains for concretes of lower classes ,21,22. SThe analysis of the relation σ−ε for concrete elements under multiple loading and unloading presents a good concordance between the calculational models and experiments. An important element of the analysis is the states in which plastic deformations of the material occur. Such a level of the deformations where a construction deflects significantly, much more than under an initial load, can be observed both in the regions prone to earthquakes and in cyclically loaded constructions, as well as in rheological processes. There are many examples in the literature concerning investigations concerning a description of the behavior of high-strength concretes under loads of all kinds, e.g., fatigue ,27, monoConstitutive equations are applied for a description of the stress–strain relation in the concrete. Aslani and Jowkarmeimandi  describepl = 0.725εun (εun—unloading concrete strain) and the influence of a crack formation in the tension zone for a monolithic construction is controlled with the use of a stress value σf = cf/10 which corresponds to a full closing of the crack. The value depends mainly on the concrete strength and the kind of crack.Based on the experimental results, Bahn and Hsu  describeVon der Haar and Marx  describeThere were more models in the literature considering the relation σ−ε during cyclic loading and unloading in a parabolic way, e.g., according to the model of Karsan and Jirsa  the unloc ≤ εcl, did not consider energy dissipation or stiffness reduction, as well as the effect of confinement  by a reduction in the concrete’s compressive strength. In this model, the partial loading and unloading (lines IJ-JG and GH-HI), as well as the influence of the tension before the crack formation, (lines KL and DF) were described as linear.Blakeley and Park  applied finement . The stiA piecewise linear model of the relation σ−ε during cyclic loading and unloading was described by Yankelevsky and Reinhard . The stiA concrete model proposed by Mander et al.  describeWith the aim of analyzing the displacements to an appropriate extent, as well as to enable a numerical analysis, Martinez-Rueda  proposedLam et al.  describeKonstantinidis et al.  proposedSadeghi et al.  presenteA constitutive model of a compressed concrete proposed by Breccolotti et al. , based oA detailed explanation of the models of Sadeghi , BreccolThe high-strength concretes differed in terms of physical features from the concretes commonly applied in 20th century. They concerned not only such basic parameters as characteristic strength or Young’s modulus but also the plastic features, elongation, fatigue properties, cooperation between the concrete and reinforcement, and the σ−ε curve for loading and unloading, etc. In the presented models, the authors analyzed each of these parameters. For practical calculations, the models are often sought which allows for a simple description of the most important features and relations in the concrete. Below it is presented in the Borcz model , describThe model  describeThe static problem is reduced to a one-dimensional issue.If a beam has a constant second area moment, then a reference line covers the line of gravity at the center of the beam cross-section.If a beam has a variable stiffness, then the line of gravity at the center of the beam cross-section is not straight. In such a case, it is assumed that the longitudinal coordinates for the whole beam are measured on the one, straight reference line.A beam with a variable second-area moment is replaced by a beam with a piecewise constant second-area moment. The beam is divided into sections, of which each has a constant equivalent stiffness.It is assumed in this model that the directions of principal stresses during loading are constant.For repeatable loads, the model assumes the total reversibility of the elastic part of the strain after unloading a construction.ij in this model is described by a relation:The total strain tensor εThe basic assumptions of the Borcz theory are as follows:This theory was experimentally verified ,21,39,40The investigations to date primarily concerned a compressive load; no investigations concerning bent elements were found. Such investigations had a great practical meaning if the serviceability limit states were taken into consideration and cracks occurred in a beam subjected to bending. The studies so far undertaken concerning the ratio between the residual and elastic strains for concretes of lower classes showed that this ratio was not constant. There was no information in the literature on how to describe the ratio ck,cubef = 77.5 MPa  and theThe beams were loaded with two concentrated forces according to the scheme presented in The strains and deflections were registered on the induction and resistance sensors. The loads were applied in a continuous and interrupted way. The loading cycle during the investigations is presented in When the deflections were forced in a continuous and interrupted way, they enabled the registration of short-term rheological effects and the strains remaining after unloading . The layr = 〈0.5%, 1.5%〉 were performed. The good quality concordance between the results showing the ratio Seven series of tests on one-span ferroconcrete beams for the reinforcement ratios res/εE was observed in a critical phase. Such a variability of this ratio was also confirmed for other reinforcement ratios of the beams , and higher loads  without any long section of strains. In this respect, the shape  of the graph resembles the graph for the relation σ−ε for a steel with a small elongation.In the investigations presented above ,33,34,35The tangent of the slope angle for the dependence describing the loading and unloading, with the use of the relation σ−ε for various load levels, is almost constant. Its value approximately corresponds with the value of the elasticity modulus. The creep process is described by a horizontal line, whereas the cyclic loading and unloading could be qualified as creep . Such description of the phenomenon is partially confirmed by Martinez-Rueda  and Lam pl = 0.725 εun (εun—unloading concrete strain) and the influence of a crack formation in the tension zone for a monolithic construction with the use of a stress value σf = cf/10.The investigations performed by the authors of this paper confirm the results obtained by Bahn and Hsu , who appres/εE does not exceed the value of 0.5 [The investigations also allow the establishment of the ratio between the residual and elastic strain in the range of the short-term load. It is clearly visible that the crack formation affects changes in this regard. Before the crack formation, this ratio increases quasi-linearly and approximately reaches the values within the range 〈0.6, 1.0〉. Then, after the crack formation, it slowly decreases down to the level where the material begins to damage. In this respect, the high-strength concrete presents a higher share of the residual strains than the concretes with a lower strength, where the ratio εe of 0.5 ,42.res/εE for various levels of material effort are clearly visible in The differences in the character of the functions showing the ratios εres/εE allow for a fast prediction of the expected strains (and deflections) of ferroconcrete elements. However, the potential importance of the concrete class must be emphasized. For the high-strength concretes, the influence of the residual strains after the crack formation is reduced, contrary to the concretes of lower classes, where the ratio εres/εE is almost constant. Based on the performed experimental investigations, it can be concluded that after crack formation the share of the residual stresses reduces along with the increase in the concrete strength, and the elastic features of the construction start to predominate. Moreover, the ratio εres/εE is significantly higher for the high-strength concretes than for the concretes with a lower strength.The investigations of the ratio εThe development of computational methods based on linear elastic models is justified by the speed and ease of calculations.The approximate results of the experimental investigations from the linear elastic models have an accuracy of up to 5% which is sufficient for the design of most engineering constructions.These models allow the prediction of a strain state in pre-critical states, including accidental loads .The experimental investigations undertaken in this paper aim to verify the Borcz theory and show the advantages of this simplified method for the calculation of strains. One can distinguish the following benefits:res/εE. The knowledge of the share of residual and elastic strains allows a determination of the internal forces in a construction and its deflections based on the calculations made with the use of the methods applied for constructions made from elastic materials. The results, obtained in such a way, can be approximately corrected allowing for the calculation of the residual and elastic strains in the construction as well as an assessment of the influence of these strains on the total deflections.The next conclusion from the presented investigations concerns an experimental determination of the ratio εThe experimental investigation of these relations can be acknowledged as a valuable method for a fast determination of the expected strains, also in the case of more complex ferroconcrete structures. The potential to predict the total strains of the elements or whole constructions without performing very complicated numerical calculations allows for a more reliable design of structures  and the


Intelligent Reflecting Surfaces (IRSs) are emerging as an effective technology capable of improving the spectral and energy efficiency of future wireless networks. The proposed scenario consists of a multi-antenna base station and a single-antenna user that is assisted by an IRS. The large number of reflecting elements at the IRS and its passive operation represent an important challenge in the acquisition of the instantaneous channel state information (I-CSI) of all links as it adds a very high overhead to the system and requires equipping the IRS with radio-frequency chains. To overcome this problem, a new approach is proposed in order to optimize beamforming at the BS and the phase shifts at the IRS without considering any knowledge of I-CSI but while only exploring the statistical channel state information (S-CSI). We aim at maximizing the user-achievable rate subject to a maximum transmit power constraint. To achieve this goal, we propose a new two-phase framework. In the first phase, both the beamforming at the BS and IRS are designed based only on S-CSI and, in the second phase, the previously designed beamforming pair is used as an initial solution, and beamforming at the BS and IRS is designed only by considering the feedback of the SNR at UE. Moreover, for each phase, we propose new methods based on Genetic Algorithms. Results show that the developed algorithms can approach beamforming with I-CSI but with significantly reduced channel estimation overhead. Intelligent reflecting surfaces (IRS), also called reconfigurable intelligent surfaces , and sofThe optimization of the beamforming at the IRS and the BS has been studied in some works ,12,13,14In order to overcome this issue, recently, some works started exploring the statistical channel state information (S-CSI) ,23,24,25Currently, evolutionary computation techniques have attracted great interest due to their ability to solve complex optimization problems from different fields. These techniques are inspired by biological evolution process, swarm behavior, and physics . Among tTherefore, as continuous phases at the IRS are not feasible in practice, usually GA is the most suitable heuristic method to design phase shifts at the IRS. From this, some works started to explore this technique to design phase shifts at the IRS by considering S-CSI knowledge ,24,25. M1.We develop a novel framework based on meta-heuristic methods to design beamforming at BS and IRS without requiring I-CSI;2.We reveal that the proposed solution can achieve a close-to-ideal performance by considering only S-CSI knowledge with low training overhead.Motivated by the above challenges, in this paper, we consider a MISO (Multiple-Input Single-Output) communication system aided by an IRS. Then, we propose a new framework split into two phases in order to design beamforming at the IRS and BS by considering new methods based on the main GA features. We aim to maximize the system achievable rate while meeting a maximum transmit power requirement at the BS through beamforming optimization at IRS and BS. To achieve the main goal of this work, first, beamforming at the BS and the phase shifts at the IRS are designed based only on S-CSI and, secondly, such beamforming pairs are used as an initial solution of the proposed method in order to improve its convergence; the beamforming at BS and IRS are designed based only on the feedback of SNR at UE. Here, it is important to note that the proposed solution does not require any explicit channel estimation process. As we can observe, differently from ,23,24,25The rest of this paper is organized as follows. Notations: An Italic letter such as a denotes a variable, bold-faced upper case letters such as A denote a matrix, and a bold-faced lower case letter a represents a vector, where [a]i-th element of a. In addition,   N antennas and IRS is equipped with We consider a wireless communication system where an IRS is deployed to assist communication between a multiple-antenna BS and a single-antenna user equipment (UE), as shown in dance to , in thiss denotes the transmitted data defined as an independent random variable with zero mean and unit variance, and B denotes the number of bits per each element at the IRS. Moreover, in accordance to [The received signal at UE is as follows :(1)y=βchdance to ,9, we coIn this paper, we consider two different pathloss models; i.e., for the BS-UE direct link, pathloss (in dB) is provided by the following :(2)βd=Gtollowing :(3)βc=Gtposition .In addition, to compute the small-scale fading, we consider the Rician fading channel model for BS-UE and IRS-UE links, which are given by the following:dance to ,34,35,36The LoS components of all links are expressed by the antenna array responses at the IRS and at the BS, which are dependent on the array geometry. In this work, we consider that the BS is equipped with a Uniform Linear Array (ULA) as in ,37 and Iollowing :(5)aBSθBe vector . FinallyIn this work, we aim to optimize beamforming at BS and the phase shifts at IRS in order to maximize the achievable rate at the user by considering a maximum transmit power constraint. This optimization problem is provided by the following:Maximizew1.Randomly generate the individuals of the first generation;2.Compute the fitness of each individual;3.Elitism: Create a set with some of the fittest individuals of the current generation and perpetuate these individuals to the next generation;4.Selection Method), which will be submitted to the Reproduction Process (Crossover and Mutation Operators).Select some individuals (named parents) by the Tournament Method  have their features permuted to form descendants. In this work, we implemented the l coding , for whiReal Random Mutation Operator. This operator randomly selects a new value from the set of valid values of that optimization variable to replace the current one of the selected gene.The Mutation Operator is applied on individuals resulting from the crossover operator in order to add new features in individuals and increase their genetic diversity. This operator aims at reducing the likelihood that the GA becomes stuck at a local optimum. This operator follows a given mutation probability (pmut) ,43. In tElitism is a method that is used to ensure that the genetic material of the fittest individuals of the current generation will be perpetuated to the next generation, improving GA convergence. In Elitism, the best individuals of a population are selected and kept for the next generation without experiencing crossover and mutation operators. This method guarantees that the quality of the solution obtained by the GA does not decrease in the next generation. In addition, Elitism improves the performance of GA because this concept ensures that the GA does not waste time rediscovering good solutions that are previously analyzed ,44.In this paper, a solution based on GA is proposed to solve the optimization problem in . In the 1.Estimate S-CSI: In this phase, we consider that IRS is in the sensing mode and the S-CSI of all links chniques ,46.2.Compute : Based on the estimated S-CSI, in this phase, we consider Algorithm  1 to compute I.L beamforming vectors at the IRS Randomly generate g vector  given byII.Calculate the fitness defined by  of each III.Elitism: Select the IV.Selection Process: Select, from the Tournament Method, V.Crossover Operator: With crossover probability VI.Mutation Operator: With mutation probability VII.L beamforming vectors, The new population is generated by the union of the individuals generated in Steps III and VI VIII.Check whether the maximum number of iterations 3.Compute w and : In this phase, the beamforming vectors at BS and the phase shifts at the IRS to be tested are defined at BS and sent to IRS from the controller illustrated in I.The first population is generated by the following individuals: (i)  is generated following the basic principles of GAs . HoweverAlgorithm 1: Algorithm applied in Phase 2 to compute In addition, it should be noted that the proposed solution exploits S-CSI knowledge as an initial point of the beamforming search in order to improve its convergence. With this approach, as we show next, it is possible to reach a close-to-ideal solution with reasonable overhead.Algorithm 2: Algorithm applied in Phase 3 to compute Upper Bound . After this, the proposed optimization problem is converted to a convex problem following the steps described in [GA-without CSI  by the fact that the first generation of the proposed GA does not consider the beamforming pair computed based on S-CSI as an initial step), the beamforming at the BS, and the phase shifts at the IRS are computed by applying only Algorithm 1, which does not exploit the S-CSI knowledge; and (iii) GA-with S-CSI, the proposed solution presented in In order to show the performance of the proposed solution, we present the results achieved by considering the simulation setup in ribed in  and the ribed in ), the opribed in  Equationribed in , while tB) or ideal continuous phase shifts are not energy efficient and are difficult to achieve due to hardware limitations, it is important to achieve a close-to-ideal performance with a small number of controlling bits B [B by considering In this work, we consider discrete phase shifts at each reflecting element at IRS. As the high resolution (large number of controlling bits g bits B . Therefonowledge . From thM) for M does not increase the achievable rate at UE. Thus, in this case, the achievable rate is more dependent on beamforming at the BS; (ii) for M and the proposed solution reaches a close-to-ideal performance with discrete phases at each IRS element and only a few number of controlling bits. This can be explained due to the fact that, as UE is close to IRS, the UE can explore the IRS gain added to the system. In addition, from the results, we can verify that the position of UE has a considerable influence; this can be related to the gain of the beamforming at BS or at the IRS which the UE can exploit when it is close to the BS or IRS. This conclusion is ratified in M increases. However, from the results, we can also verify that, when we do not consider S-CSI knowledge (GA-Without S-CSI), the performance gap in terms of bits per second per Hertz  , then thThe previous results consider perfect S-CSI knowledge. Thus, in order to investigate the robustness of the proposed solution, we next consider the following model for imperfect S-CSI knowledge , taking L is the population size, and M and In this paper, we proposed a solution based on GA. Therefore, to compute the computational complexity of the proposed solution, it is necessary to consider the complexity of each genetic operator in each phase of the proposed solution. For the second phase, we have the following computation complexity: (i) For the importance of computational complexity analysis, for this work, we consider that the issue of training overhead is more relevant as this is one of the main challenges in IRS-assisted communication systems. Therefore, in the manuscript, we evaluate the amount of feedback from the user to the BS, NitL . If the  ((MN+1) , then thIn this paper, we evaluated two different solutions based on GA in order to design beamforming at BS and IRS, with a maximum transmit power constraint and discrete phase shifts at IRS. First, we proposed a solution that does not consider any knowledge of the CSI at BS, and a suboptimum design of the beamforming at BS and IRS was performed. Next, we proposed another solution to solve the beamforming problem only by exploiting S-CSI knowledge. The novel solutions were evaluated considering different setups, and from the results, we can conclude that they achieve a great performance considering discrete phases with a few numbers of controlling bits at each element and with a reasonable amount of feedback from UE. This shows that the proposed solutions are very attractive in practice. As future works, we intend to investigate the system overhead in a MIMO multi-user system.


It is now widely recognized that inappropriate use of antibiotics is a major driver of the emergence and spread of antibiotic resistance. This has resulted in the development of antibiotic stewardship programmes, which aim to optimize antibiotic use by maximizing the clinical benefits while minimizing adverse consequences including toxicity and resistance. As antibiotic resistance is a global threat, the formulation of stewardship programmes and assessment of their cost-effectiveness requires knowledge of the trends in antibiotic usage at local, national and international levels. For many years, a major contribution to the surveillance of antibiotic use has been provided by the European Surveillance of Antimicrobial Consumption Network , which comprises an international network of surveillance systems that collects data on antibiotic consumption across the EU/European Economic Area (EEA). This Supplement comprises a series of articles presenting data on antibiotic consumption in the community from 30 EU/EEA countries over two decades (1997 to 2017), and updates previously available information covering the periods 1997–2003 and 1997–2009. The articles review temporal trends, seasonal variation, presence of change-points and changes in the composition of the main antibiotic groups. Data outputs are presented as yearly antibiotic consumption aggregated at the level of the active substance, using the WHO ATC classification and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day, analysed using a range of non-linear mixed models. For those readers not fully conversant with such statistical methodology, the Supplement also includes a tutorial that describes and illustrates statistical methods for analysing time trends  in antibiotic consumption. These updated analyses of two decades of ESAC-Net data provide the most comprehensive and detailed description yet of antibiotic consumption in the community in Europe, which we hope will be of interest to JAC readers, and in particular those involved in informing and evaluating control strategies.None to declare.


Modern medicine is founded on the availability of effective antimicrobials, but antibiotic resistance is an inevitable consequence of widespread use of antibiotics. The rise in multidrug resistant organisms, and the increasing numbers of pan-resistant infections being identified, mean that antimicrobial resistance (AMR) is now a pressing global concern  in healthcare. The first article in the collection, by Rynkiewich's article goes further by challenging a common assumption of antibiotic stewardship approaches—that the problem lies in individual physician behaviors and habits. Based on vivid ethnographic case studies in two American hospitals, the author argues that decision-making about antibiotics is instead a collective practice, which happens between institutions, physicians, pharmacists, nurses, and other staff. The implications are that, rather than targeting “bad” physician practice, stewardship efforts should recognize the collective nature of antibiotic use.Tarrant et al. look in detail at the notion of “inappropriate” antibiotic prescribing in their interview study, involving hospital prescribers in the UK, South Africa and Sri Lanka. They identify that prescriber definitions of inappropriate antibiotic use are not purely objective. Inappropriate antibiotic use can't be pinned down by precise technical definitions. Instead, prescribers' judgements about the appropriateness of prescribing decisions reflect their moral position and the context in which they work.Chen et al.'s qualitative study provides another example of the complexities of antibiotic decision-making, this time in rural primary care. They find that physicians work to balance their understanding of rational use of antibiotics against the need to maintain good relationships and protect the safety of their patients. The idea of “suzhi” —respecting and protecting their patients—is drawn on by prescribers to explain their liberal prescribing of antibiotics.Shifting the focus to China, Saukko and Rousham's article focuses on patients' and health professionals' affective experiences related to diagnosis and management of urinary tract infections. Using the conceptual framing of illness narratives, they describe narratives of chaos and control, and point to the need for stewardship programmes to consider the affective dimension of decision-making about antibiotic use.How patients and professionals perceive suspected infection is consequential for antibiotic use. Jamie and Sharples, offers a refreshingly different perspective. The authors describe how natural materials such as clay may offer alternatives to antibiotic treatment. They provide some theoretical lenses through which sociologists could study how their materiality  might influence the use of these materials in healthcare.The majority of efforts to tackle AMR to date have focused on the preservation of existing antibiotics through stewardship, and investment in development of new antibiotics. The final article in this Topic, by Taken together, the articles illuminate the ways in which the use of antibiotics  are shaped by social and organizational infrastructures, individual meaning-making, as well as the materiality of the substances themselves. Addressing AMR will require us to think differently about the nature of the problem and about our possible futures (Chandler, The authors confirm being the only contributors of this work and approved it for publication. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


One commonly used cement type for thermal applications is CAC containing 38–40% alumina, although the postheated behavior of this cement subjected to elevated temperature has not been studied yet. Here, through extensive experimentation, the postheated mineralogical and physicochemical features of calcium aluminate cement concrete (CACC) were examined via DTA/TGA, X-ray diffraction (XRD), and scanning electron microscopy (SEM) imaging and the variation in the concrete physical features and the compressive strength deterioration with temperature rise were examined through ultrasonic pulse velocity (UPV) values. In addition, other mechanical features that were addressed were the residual tensile strength and elastic modulus. According to the XRD test results, with the temperature rise, the dehydration of the  Building materials such as cement and concrete play a key in construction sustainability, and that is why numerous studies ,2,3,4 haReviewing the literature indicates that increasing the temperature lowers the mechanical features of mortar, hardened cement paste, and concrete specimens ,11,12. AAmong non-Portland specific cement types, calcium aluminate cement (CAC) plays a significant role and can be a proper substitution for a fraction or the whole Portland cement volume. In situations requiring mortar or concrete to show specific properties ), the use of this cement is justified. Several aluminates with different volumes ranging from 40 to 90% make this cement . At pres2O3) and compared the postfire behaviors of this concrete and conventional concrete. It was reported that the alumina existing in the CACC considerably improved the mechanical features in comparison with conventional concrete. In this regard, the residual strength of the CACC was higher compared with that of the conventional concrete, especially for temperatures above 400 °C. It has been established that the mechanical features of this concrete are dependent upon the alumina content.Khaliq and Khan  exploredTherefore, exploring the postfire mechanical properties of CACs with different alumina contents is also required. One of the most common CACs is the one with 40% alumina that is produced by the Fondo factory, Isfahan, Iran, under the commercial name Iran Refectory Cement Co. Several studies have been conducted by the authors regarding the mechanical and fracture properties of calcium aluminate cement containing 38% alumina at the ambient temperature ,17.In the present research, the impact of changes in the microstructure of CACC after experiencing heat and on the mechanical features of this concrete was explored. Data about this subject are scarce in the literature. The impact of water-to-cement ratio on the mechanical features of CACC was explored in the previous work of the authors , where tIn addition, the heat-induced chemical processes leading to the deterioration and degradation of the cementitious matrix were explored via thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS) methods. Moreover, to obtain a better understanding of the postfire performance of CACC, the observed results for this concrete were compared with the results reported in the literature for other concrete types, especially with the results of Khaliq et al. .Here, refractory cement, commercially available under the name IRC-40 (Fondu), made by Iran Refractory Cement Co., Isfahan province, Iran, was used. Calcium aluminate cement was used with a 24 h mechanical strength of 45 MPa and an initial setting time of 200 min. Both coarse and fine aggregates were utilized. Washed river sand was used as the fine aggregate, with a specific gravity of 2.6, fineness modulus of 2.6, and water absorption of 0.7%. The coarse aggregate had a specific gravity of 2.5, a maximum particle diameter of 12 mm, and water absorption of 0.5%. Water used to make the mixtures was tap water. The gradation curves of coarse and fine particles obtained by passing them through a series of sieves in accordance with ASTM C33  are giveCa12Al14O33) also detected.For enhancing the workability of the concrete mix, a superplasticizer based on polycarboxylate ether was employed, which had a specific gravity equal to 1.11. The XRD patterns of CAC are seen in The X-ray fluorescence (XRF) spectroscopy was used to obtain the oxide composition of CAC, with the corresponding results shown in The mix proportion of CACC is shown in Standard concrete cylinders with a height and diameter of 300 mm and 150 mm, respectively, were manufactured to assess the elastic modulus and tensile strength based on ASTM C496  and ASTM3 in accordance with ASTM C78M [For three specimens made from each mix design, the average of the results was reported. The tests for measuring the compressive strength, tensile strength, and elastic modulus were conducted with a loading rate of 3, 2.1, and 5.2 kN/s, respectively, applying an automatic testing machine  with a load control strategy. Moreover, three beams were tested through the three-point bending test with the dimensions of 500 × 100 × 100 mmSTM C78M . Figure An ultrasonic nondestructive electronic machine was used to measure the UPV, complying with ASTM C597 . A transThe fresh CACC specimens were cured at perature  and the perature . For theBased on the literature, there are three approaches for evaluating concrete strength at high temperatures, which are called stressed testing, unstressed testing, and unstressed residual strength testing. In the stressed testing approach, the specimens are loaded before heating, and this loading continues during the heating phase. When the specimens reach the target temperature, the load/strain is increased up to the failure of the specimens. In the unstressed testing approach, specimens are heated without a preload to reach the target temperature and then tested at this temperature. In the unstressed residual strength testing approach, the specimens are heated without a preload to reach the target temperature and then left to cool to reach the room temperature at which the load/strain is applied to the specimens until failure. In this research, the unstressed residual strength testing approach was employed since it provides the best results for evaluating the postfire properties of concretes .In order to investigate the structure of the produced concretes, the X-ray diffraction (XRD) test was used, with the results shown in According to  studies ,33. As tMoreover, with increasing temperature, the peak located at an angle of around 2θ = 40.17° related to the In addition, as the temperature increases, it is seen in this structure that the intensity of the peaks increases, due to the increase in the crystallite degree of crystalline structures in the concrete.As 6.As can be seen in The energy-dispersive spectroscopy (EDS) analysis was performed to identify the type and semiquantities of the constituent materials of concretes. The results of this test for the CACC specimens are given in According to The above reaction shows that the carbon and oxygen in the structure of calcium carbonate are converted to gaseous carbon dioxide and exit the matrix.In order to examine the thermal properties of this concrete, the thermogravimetric analysis (TGA) was used, with the obtained results shown in By analyzing the TGA graph, the behavior of a specimen against the temperature can be investigated. However, sometimes it is needed to investigate the decomposition rate of a material, which is not shown in the graph. As a result, the weight loss rate is shown in the DTGA graph. In 3AH6).In the present study , the comAs the temperature increased further up to 400 and 600 °C, the compressive strength experienced a 37 and 60% reduction. Khaliq  conducteThe ultimate tensile strength of the cylindrical specimens exposed to heat was measured and recorded after cooling, with the associated results given in In this regard, Sakr  investigIn the present research, as the temperature was raised to 200 and 400 °C, the tensile strength declined by around 39 and 50%, respectively . A stren1 is the stress related to 2 is the strength associated with 40% of the ultimate load, 2.ASTM C469  proposedIn the present study, the elastic modulus decreased from 41.93 GPa at the ambient temperature to 24.63 GPa after exposure to 200 °C, showing a 41% reduction, as can be seen in As the temperature further increased to 400 and 600 °C, the obtained elastic modulus values were 15 and 8.05 GPa, respectively, indicating a drastic reduction. In this regard, Fares et al. [Ultrasonic wave velocity is a nondestructive method for measuring the velocity of sound in the materials considering that the velocity of a wave is a function of the porosity inside the material. The proper relation between the mechanical properties of the concrete and the velocity of the ultrasonic waves can be determined, and many of the mechanical properties, as well as the quality, of the concrete can be evaluated nondestructively. It is observed that before exposure to different elevated temperatures, UPV values in specimens vary from 4700 to 5000 m/s, indicating the good condition of concrete at the ambient temperature. This is because an ultrasonic pulse velocity higher than 4.575 km/s generally represents the excellent quality of concrete . The excMany investigations in recent years have focused on the thermal performance of different concretes. Note that regarding the thermal performance, in addition to common variables considered in different investigations under normal conditions, variables including the heating rate and time of exposure to the target temperature are factors notably affecting the microstructure and mechanical properties of concretes. In this regard, as the heating rate decreases and the time of exposure increases, the deterioration of the microstructure and mechanical parameters is exacerbated. Due to the importance of the different performances of various concretes against high temperatures, in this section, an attempt is made to provide a comparison between the residual mechanical properties of CACC with those of other concretes (investigated in the literature) after exposure to heat, with some parameters being variable. By comparing the residual compressive strength of different concretes shown in In In addition, Weight loss is a measure that can determine the governing process under high temperature ranges. Below 200 °C, the weight loss is merely due to the evaporation of the capillary water, which is a physical process. At 200–400 °C, weight loss is due to the gradual evaporation of the chemical water, and the concrete experiences a chemical–physical process. For temperatures above 400 °C, the weight loss is mainly due to the evaporation of the chemically bound water and decomposition of the compounds, which are chemical processes.Based on the results of the XRD and EDS tests, as the temperature increases, the structure of The mechanical properties of the concrete specimens  degraded with the increase in temperature. At 25–200 °C, due to the evaporation of capillary and gel waters, the reduction in the mechanical properties was significant. However, at 200–400 °C, the variation in the properties was not significant. At 400–600 °C, a severe reduction was seen in the mechanical properties, due to the conversion of hydrogarnet and increase in porosity.The aim of this study was to explore the microstructural changes and their effects on the mechanical and fracture properties of the CACC upon exposure to extreme temperatures of up to 600 °C. The results of this research are beneficial and significant for understanding the microstructural degradation and decomposition of chemical compounds in the cement matrix and the variation in the mechanical and fracture features of this concrete after the fire. The main findings are as follows:


Escherichia coli was the most frequently detected pathogen (75.6%), followed by Klebsiella pneumoniae (6.9%) and Pseudomonas aeruginosa (2.5%). Overall, 840 cases (46.7%) were due to antimicrobial-resistant uropathogens: 83 (4.7%) extended spectrum beta-lactamase (ESBL)-producing, 119 (6.7%) multidrug resistant (MDR) and 4 (0.2%) extensively drug resistant (XDR) bacteria. Empirical antibiotic therapy failed in 172 cases (9.6%). Having ESBL or MDR/XDR uropathogens, a history of recurrent UTI, antibiotic therapy in the preceding 30 days, and empirical treatment with amoxicillin or amoxicillin/clavulanate were significantly associated with treatment failure, whereas first-line therapy with third-generation cephalosporins was associated with protection against negative outcomes. In conclusion, the increase in the resistance of uropathogens to commonly used antibiotics requires continuous monitoring, and recommendations for antibiotic choice need updating. In our epidemiological context, amoxicillin/clavulanate no longer seems to be the appropriate first-line therapy for children hospitalised for UTI, whereas third-generation cephalosporins continue to be useful. To further limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be implemented.The development and spread of antibiotic resistance is an increasingly important global public health problem, even in paediatric urinary tract infection (UTI). In light of the variability in the data, it is necessary to conduct surveillance studies to determine the prevalence of antibiotic resistance in specific geographical areas to optimize therapeutic management. In this observational, retrospective, multicentre study, the medical records of 1801 paediatric patients who were hospitalised for UTI between 1 January 2012, and 30 June 2020, in Emilia-Romagna, Italy, were analysed.  Enterobacteriaceae family, of which Escherichia coli is the most frequent, causing more than 70% of UTIs. Other frequent pathogens of the same family are Klebsiella spp., Enterobacter spp. and Proteus spp. Although Pseudomonas aeruginosa is a less frequent Gram-negative pathogen, it is often associated with more severe UTIs. Among rare cases of UTIs caused by Gram-positive microorganisms, those caused by Enterococcus spp. are most frequent [Urinary tract infections (UTIs) are among the most common infections in children. Indeed, it is estimated that 11.3% of females and 3.6% of males develop at least one episode of a UTI within the first 16 years of life . Moreovefrequent ,5.E. coli resistance during the study period increased for ampicillin from 47.1% to 89%, for trimethoprim-sulphamethoxazole from 44.8% to 56% and for nitrofurantoin from 5.3% to 15.1% [E. coli. Furthermore, the prevalence of ESBL-producing pathogens in paediatric UTIs varies from 0.5% to 50% across studies [The development and spread of antibiotic resistance are increasingly important global public health problems, even in UTI, with variable prevalence in different geographical areas . In receto 15.1% . Neverth studies ,11. In lIn this observational, retrospective, multicentre study, medical records for paediatric patients of both sexes and under the age of 18 years who were hospitalised for UTI between 1 January 2012, and 30 June 2020, in the paediatric wards of Emilia-Romagna, Italy, were analysed. The medical records were extrapolated on the basis of the following diagnosis-related group (DRG) codes and/or International Classification of Diseases 9th revision (ICD-9) diagnosis codes: DRG 322, infections of the kidney and urinary tract, age <18 years; ICD-9-CM 590.1, acute pyelonephritis; ICD-9-CM 590.3, cystic pyeloureteritis; ICD-9-CM 590.8, pyelonephritis, unspecified; ICD-9-CM 590.9: kidney infection, unspecified. Patients with congenital or acquired immunodeficiencies, undergoing immunosuppressive therapy, or with neoplastic diseases were excluded. Only patients with positive urine cultures as defined in the Italian Society of Paediatric Nephrology guidelines  and febrAll medical records of subjects under the age of 18 years who met the inclusion and exclusion criteria were retrospectively reviewed. The data collection was focused on demographic characteristics, remote and proximate pathological history, blood and urinary laboratory parameters at onset, radiological findings  and laboratory data following the acute episode, uroculture and antibiogram results, antibiotic therapies administered before admission, during hospitalisation and prescribed at discharge, trends in vital parameters and any procedures carried out.5 CFU/mL. These cases were then analyzed by measuring frequency and describing the susceptibility/resistance of the individual pathogens. Pathogens that hydrolysed penicillin and first- to third-generation cephalosporins and aztreonam were defined phenotypically as ESBL [Positive urocultures were defined as the identification of a single pathogenic species present at ≥10 as ESBL . Criteri as ESBL . MDR patRisk factors as well as clinical, laboratory and renal ultrasound findings associated with UTI due to susceptible and resistant pathogens were investigated. All antibiotic molecules administered were recorded, and the clinical cure rate for therapies was evaluated in the entire study population using the clinical improvement of the patient with the resolution of fever and symptoms as a definition of therapeutic success.For data collection, a special form was used for each patient. In the case of patients with multiple accesses within the inclusion criteria, the last access was chosen.2 and Fisher’s exact tests were used to assess differences on all categorical variables and compare the two periods of analysis (2012–2015 vs. 2016–2020). Considering the eight-year study periods, we compared the first four years of enrollment with the last four years of the study period. Independent samples t-tests and Wilcoxon–Mann–Whitney tests were employed to compare the distribution of continuous variables. For all tests, an alpha <0.05 was considered statistically significant.Statistical analysis was conducted using R software v. 4.0.1. Descriptive statistics, as absolute and relative frequencies, means and standard deviations, were used to summarize the data. Pearson χUnivariable logistic regression models were then used to assess the effect of select risk factors and the onset of UTIs caused by resistant pathogens, as well as failure of empirical first-line treatment. E. coli  was the most frequently detected pathogen in both study periods, followed by K. pneumoniae  and P. aeruginosa . From 2012–2015 to 2016–2020, a significant increase in cases due to E. coli and a significant decrease in cases due to P. aeruginosa were observed.p < 0.001), though the prevalence of MDR uropathogens decreased. The most frequent ESBL pathogens were E. coli  and K. pneumoniae , and the most frequent MDR pathogens were E. coli , P. aeruginosa , K. pneumoniae  and Proteus mirabilis . XDR pathogens were E. coli (3/4) and K. pneumoniae (1/4).No significant differences in clinical findings, blood exams or urinary exams between the groups were observed. The empirical therapy administered to the study population is provided in Overall, empirical antibiotic therapy failed in 172 children (9.6%). This study shows that antimicrobial resistance among uropathogens is an increasing phenomenon in children hospitalised for UTI in Italy, with a remarkable prevalence of ESBL as well as MDR/XDR strains. In general, previous antibiotic administration, including for UTI prophylaxis, is associated with resistance to antibiotics. Interestingly, risk factors for empirical treatment failure included having ESBL or MDR/XDR uropathogens, history of recurrent UTI, antibiotic therapy in the preceding 30 days, and empirical treatment with amoxicillin or amoxicillin/clavulanate, whereas empirical treatment with third-generation cephalosporins was associated with protection against poor outcomes.E. coli and K. pneumoniae to be the most frequent uropathogens in children hospitalised for UTI and those most commonly observed in cases involving resistance [Awareness of upper UTI aetiology and variation in pathogen susceptibility to antibiotics is essential for the choice of an effective therapy. As previously reported, our study showed sistance ,14,15,16sistance ,18. The sistance ,20 and lsistance ,22,23. HTo assure the highest probability of bacterial eradication, official guidelines indicate which antibiotics must be used. Taking into account the increase in the incidence of ESBL cases, Italian guidelines were recently updated, and an amoxicillin/clavulanic acid combination was indicated as the drug of choice for paediatric UTI treatment, highlighting that first- to third-generation cephalosporins have no additional role in this regard, as they are, in many cases, ineffective against ESBL-producing strains . This exProper identification of patients at increased risk of antibiotic resistance can reduce the risk of ineffective therapy. In our study population, the previous use of antibiotics was the most important risk factor associated with antibiotic resistance. Antibiotics are among the drugs most commonly prescribed to children in hospital and community settings ,29. UnfoNevertheless, a number of studies suggest that resistant UTI can occur even in children without any risk factors . AlthougLimitations of the study included its retrospective nature, the different number of patients evaluated in the two study periods and the fact that the research is limited to a definite epidemiologic context. However, the strict inclusion criteria and the long duration of the study period permit to draw important results on what happens in real life.Despite being very common and well-studied, UTIs in paediatric patients remain challenging and this manuscript improves clinical knowledge on their management. We highlighted that the increase in resistance of uropathogens to commonly used antibiotics requires continuous monitoring of microbiological characteristics of UTIs and updating of recommendations for antibiotic choice. In our epidemiological context, amoxicillin/clavulanate no longer seems to be the appropriate first-line therapy for children hospitalised for UTI, whereas third-generation cephalosporins continue to be helpful. In order to selectively use cephalosporins so as to avoid increasing resistance to this class of antibiotics, in future studies using multivariate analysis it may be interesting to understand if a differentiated approach can be adopted using amoxicillin-clavulanate at the first UTI and cephalosporins in the presence of second and subsequent infections. The emergence of antibiotic resistance is an unavoidable phenomenon closely correlating with the use of antibiotics themselves. To limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be made. Increased use of antibiotic stewardship can be greatly effective in this regard.


Phytohormones are small chemicals critical for plant development and adaptation to a changing environment. Strigolactones (SLs), carotenoid-derived small signalling molecules and a class of phytohormones, regulate multiple developmental processes and respond to diverse environmental signals. SLs also coordinate adjustments in the balance of resource distribution by strategic modification of the plant development, allowing plants to adapt to nutrient deficiency. Instead of operating independently, SL interplays with abscisic acid, cytokinin, auxin, ethylene, and some other plant phytohormones, forming elaborate signalling networks. Hormone signalling crosstalk in plant development and environmental response may occur in a fully concerted manner or as a cascade of sequential events. In many cases, the exact underlying mechanism is unclear because of the different effects of phytohormones and the varying backgrounds of their actions. In this review, we systematically summarise the synthesis, signal transduction, and biological functions of SLs and further highlight the significance of crosstalk between SLs and other phytohormones during plant development and resistance to ever-changing environments. As signalling mediators, SLs regulate the coordinated development of roots and shoots, particularly under N- and P-deficient conditions . AccordiArabidopsis, MORE AXILLARY GROWTH1 (MAX1) encodes a cytochrome P450 monooxygenase (CYP711A1) that catalyses the conversion of CL to produce carlactonoic acid (CLA), which is then methylated to methyl carlactonoate (MeCLA) by an unknown methyltransferase  converts CL into 4-deoxyorobanchol (4DO), and finally another homologue, Os1400 (CYP711A3), further catalyses the 4DO to form orobanchol  (ent–5DS (Arabidopsis), resulting in the 26S proteasomal degradation of this repressor and thus the transcription of SL responsive genes  and F-box component (MAX2 in idopsis) . The D14idopsis) . KARRIKI under optimal growth conditions, whereas an opposite effect was observed under the P-deficient conditions  and SL biosynthesis-deficient mutant (D10) showed no adverse effects (D10 and D27) and SL signalling-deficient mutant (D3) in rice decreased under low-P conditions. By contrast, all these SL-related mutants presented increased LR density during P starvation compared with wild-type plants  and SL content decreased in tomato roots under drought stress  activity  through CK signalling components  following dehydration was observed in the SL signalling-deficient mutant MAX2 compared with wild-type plants , have led to increased grain yield with upregulated SL response pathways modulating tillering. Furthermore, ontogenetic modification of the SL transport signal, such as overexpression of the SL transporter PDR1, might be useful for obtaining a potential breeding stock. Applying SL analogues for shaping the plant architecture, improving their performance and resistance, and enhancing AM colonisation are of high potential value. Cheaper sources of SLs analogues are required for large-scale agricultural applications.Similar to other phytohormones, SL biosynthesis and activity are regulated by multiple levels of crosstalk in hormonal networks under suboptimal environmental conditions . As the FW, YG, and WY wrote the manuscript. NS and JZ edited the manuscript. All the authors discussed and created the review’s outline.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


We assessed staff’s beliefs and attitudes to antibiotic supplying for common infections ). Pharmacists  and pharmacy assistants (n = 55: 21%) responded. About 30% (80/265) had supplied antibiotics without a prescription for common infections, including common cold (15.8%), sore throat (13.6%) and diarrhoea (10.2%). Overall, pharmacists were less likely to supply than non-pharmacists. Pharmacy staff with more positive beliefs about their professional competency to supply and monitor antibiotic use were more likely to supply antibiotics without a prescription for common cold , wound infections , and UTI . Pharmacy staff who believed in the effectiveness of antibiotics against common infections were more likely to supply antibiotics for common infections. Supply of antibiotics without a prescription was associated with staff’s beliefs about antibiotics’ effectiveness and their professional competency. Our findings could be used to strengthen regulatory strategies to improve practice.Inappropriate antibiotic use is a problem in Sri Lanka. We investigated pharmacy staff’s attitudes towards antibiotic supply for common infections in Sri Lanka. A self-reported cross-sectional survey was conducted among a random sample ( Globally, antibiotic consumption has increased by 35% between 2000 and 2010 ,5, and rIn the majority of countries worldwide, there is a legal requirement for antibiotics to be supplied only on prescription from physicians. However, in many countries, antibiotics can be purchased from community pharmacies without a prescription . InapproEasy access to antibiotics without a prescription has been identified as an important contributing factor to self-medication with these medicines . Antibio2  = 26.85, p < 0.001). Among the pharmacists (n = 210), the majority had an efficiency (apprentice) pharmacy training  and about 2% (n = 5) had a formal university degree in pharmacy. Most of the demographic characteristics of the participants  completed the survey (response rate = 72%). Two incomplete questionnaires were excluded and 265 responses were included in the final analyses. Fifty-five (21%) respondents were categorised as pharmacy assistants  and 210 (79%) as pharmacists. No significant difference was observed between pharmacy assistants and pharmacists in terms of personal and professional characteristics assessed except for the years of working experience. Pharmacists had worked for a longer period than assistants  to supply antibiotics without a prescription and monitor people’s use of antibiotics  without a prescription. Factor 2, Shared responsibility, focused on pharmacy staff’s beliefs that promoting appropriate use of antibiotics is a shared responsibility of various stakeholders, including policy makers, patients, pharmacists and doctors. Factor 3, Beliefs about effectiveness of antibiotics, explained participants’ beliefs about the effectiveness of antibiotics against a range of common conditions presented by people to community pharmacy staff, such as wound infections, common cold and cough, diarrhoea, acute sore throat, fever and UTI. Factor 4, Access and availability, centred on pharmacy staff’s opinions about the ability of people to easily access and receive antibiotics without a prescription from pharmacies to meet their needs if they do not have enough money or time to see a doctor. Contributing to these beliefs were the pharmacy staff’s beliefs that antibiotics can cure all bacterial infections, ABR is not a problem, and they were sufficiently trained on antibiotics in their pharmacy training. Factor 5, Appropriate and legal supply and use, explained participants’ attitudes towards antibiotics supply control strategies, and included beliefs that antibiotic supply without a prescription should be controlled by authorities, and that patients’ demands and misuse of antibiotics and pharmacists’ contribution towards appropriate use of antibiotics should be stopped . All items loaded onto the expected factors with factor loadings greater than 0.4, except two items which loaded onto factor 4 (0.35 and 0.31) and one item onto factor 5 (0.37) with lower factor loadings. Weighted factor-based scales were calculated for all five factors . The midThe Cronbach’s alpha for Factor 1 was 0.95, indicating a very high level of internal consistency. The median score for each of the 10 items measuring beliefs in professional competency to supply antibiotics without a prescription and monitor antibiotics use (Factor 1) was 2  , indicatThe Cronbach’s alpha for Factor 2 was 0.83, indicating good internal consistency. Pharmacy staff agreed with all four items (median 4 or 5) regarding responsibility for appropriate use of antibiotics being shared by various stakeholders, including health professionals, policy makers and consumers (Factor 2). The data further indicated that the median weighted factor-based scale for Factor 2 was above the mid-point value. This demonstrated that the majority of respondents believed that promoting appropriate use of antibiotics is a shared responsibility of all stake holders . The Cronbach’s alpha for Factor 3 was 0.92, indicating high internal consistency. Overall, the respondents disagreed (median 1 or 2) with all of the six items measuring beliefs about effectiveness of antibiotics for different conditions (Factor 3) evaluated . The data also showed that the median weighted factor-based scale for Factor 3 was below the mid-point value. This demonstrated that the majority of the respondents did not believe in the effectiveness of antibiotics for the evaluated conditions . The Cronbach’s alpha for Factor 4 was 0.76, indicating acceptable internal consistency. The median score for each of the seven items which measured access and availability was 1 or 2 (Factor 4), indicating disagreement of the respondents with supply of antibiotics to the public without a prescription. However, the median weighted factor-based scale for Factor 4 was above the mid-point value. This demonstrated that the majority of the respondents supported people’s ability to easily access and receive antibiotics from pharmacies without a prescription . The Cronbach’s alpha for Factor 5 was 0.70, indicating acceptable internal consistency. The median score for each of the five items in Factor 5 was 4 or 5, indicating respondents’ overall high levels of agreement for the items measuring the appropriate and legal supply and use of antibiotics. The median weighted factor-based scale for Factor 5 was above the mid-point value, indicating that the majority of the respondents did support the appropriate and legal supply and use strategies . There were no significant differences found in the respondents’ attitudinal factor scores between the three different groups of respondents, i.e., the pharmacists with proficiency qualification, the pharmacists with efficiency qualification, and non-pharmacists . About 30% (80/265) of respondents reported that they had dispensed antibiotics without a prescription for the common infections, such as acute sore throat, common cold and cough, diarrhoea, wound infection and UTI, in the week prior to completing the survey. About 40% of the antibiotic supply without a prescription was for potentially viral infections, including common cold and cough (15.8%), acute sore throat (13.6%) and diarrhoea (10.2%). The reported antibiotic supply without a prescription for wound infection and UTI were 21.1% and 8.7%, respectively . No signp = 0.032), wound infections  and UTI . Pharmacy staff who believed that antibiotics were effective against the evaluated minor infections were more likely to supply antibiotics for acute sore throat , the common cold and cough , wound infections  and UTI . Pharmacy staff with any form of reported pharmacy qualification were less likely to supply antibiotics without a prescription for common infections, including acute sore throat , common cold and cough  and diarrhoea .The multiple logistic regression results are shown in These findings are part of the first national survey conducted among Sri Lankan community pharmacies aiming to evaluate pharmacy staff’s knowledge about antibiotics, and their attitudes towards antibiotics supply for common infections. The focus of the current study was to investigate attitudes towards antibiotic supply without prescriptions for common infections and to evaluate the association between attitudes and supply of antibiotics. This study included all different types of national retail community pharmacies, pharmacists with different professional qualifications, and staff responsible for managing pharmacies without any pharmacy qualification. The high response rate (78%) was also a strength of this study.Most of the respondents did not believe that they were professionally competent to supply antibiotics without a prescription and monitor people’s antibiotic use. They did not believe that antibiotics were effective against different infections, including viral infections. Whilst they had positive beliefs about the effectiveness of antibiotics, they lacked beliefs about their own competency. This is an interesting finding that may highlight their limited knowledge about antibiotics and limited clinical experience, which may be a reflection of the qualifications held by the pharmacy staff, where only 2% held a bachelor’s degree in pharmacy, and the majority of the pharmacists had efficiency and proficiency training. The adjusted multiple logistic regression models showed that pharmacy staff’s beliefs about their professional competency to supply antibiotics without a prescription and monitor antibiotics use by people, and their beliefs about the effectiveness of antibiotics for minor infections were strongly associated with staff’s behaviour of supplying antibiotics without a prescription for such infections. One explanation for this observation could be that those respondents who believed in their own professional competency and the effectiveness of antibiotics were more likely to provide antibiotics without a prescription. This observation may be further supported by the finding that a pharmacist with any form of recognised pharmacy qualification in Sri Lanka was less likely to supply antibiotics without a prescription for possible viral infections. However, supplying antibiotics without a prescription is an illegal practice in the country and supplying antibiotics inappropriately for possible viral infections is worrying, because it highlights pharmacy staff’s limited knowledge about antibiotics and their appropriate use. Comparable to these observations, pharmacists’ and non-pharmacist staff’s poor knowledge has been reported elsewhere . Barker The poor clinical knowledge of pharmacy staff in this survey could possibly reflect the extent of their pharmacy training, because most respondents (53%) reported that they had completed apprentice pharmacy training with no tertiary education or clinical training . PharmacWhilst our findings demonstrated that supply of antibiotics without a prescription from community pharmacies for common infections is widespread in Sri Lanka, these figures are lower when compared to our mystery shopper visits to the same pharmacies. The simulated client visits with direct antibiotic product requests and symptom-based antibiotic requests for four common infections  revealed a higher prevalence of antibiotic supply, at 61%  and 41% Availability of a pharmacist in the pharmacy significantly impacted antibiotic supply without a prescription. It was found that pharmacy staff with any formal pharmacy qualification recognised by the Sri Lankan government were less likely to supply antibiotics without a prescription for common infections, as they are more likely to be aware of the legal requirements of antibiotic supply. This finding was also supported by mystery shopper studies conducted in the same pharmacies ,19, and The findings of this study have identified a need for interventions to improve pharmacists’ and pharmacy staff’s knowledge related to appropriate antibiotic use and supply, and influence their beliefs about antibiotics and possibly behaviour (antibiotic supply). This will help to support appropriate antibiotic use in the community in the long run. An important limitation of this study was that the data were self-reported, and there was therefore the possibility for social desirability bias, and issues with recall. The proportion of pharmacists and non-pharmacist staff who reported supplying antibiotics without a prescription might be an underestimation of what is occurring in real practice. This was a cross-sectional national survey conducted among community pharmacy staff throughout Sri Lanka between December 2016 and September 2017. This study was part of a larger study, investigating knowledge, attitudes and dispensing practices regarding antibiotics among community pharmacy staff in Sri Lanka. A total of 369 community pharmacies throughout the country were selected for study participation. The sample size estimation has been described previously ,19,28. APharmacies included in this survey were randomly selected from all nine provinces (sampling frame) using a simple random sampling technique. The sample of pharmacies which had legal permission to function in each province was derived from the list of pharmacies from the Pharmacy Directory maintained by the National Medicine Regulatory Authority (NMRA) (as of April 2016) . A randoThe study questionnaire was developed based on the results of previous studies conducted in other countries ,39,40,41Data on: (i) pharmacy staff’s personal and professional characteristics; (ii) their beliefs and attitudes towards antibiotic supply without a prescription; and (iii) supply of antibiotics without a prescription, for five common infections—acute sore throat, the common cold and cough, diarrhoea, wound infection and urinary tract infection (UTI), were collected using the self-administered questionnaire.These included age, gender, geographical location, level of pharmacy education, years of working experience in community pharmacy, employment type, employment status, type of pharmacy, and number of pharmacists and pharmacy assistants working at a given time in the pharmacy.Community pharmacist was defined as a respondent with any of the following qualifications in pharmacy: graduate pharmacist (B.Pharm or BSc (Pharmacy)), proficiency certificate pharmacist, or diploma in pharmacy or efficiency certificate pharmacist (apprentice pharmacist). All groups of pharmacists have equal pharmacy practice rights in Sri Lanka. All other respondents who did not hold these qualifications were considered as non-pharmacist staff.Beliefs and attitudes were measured using 43 statements on a 5-point Likert scale with 1 = strongly disagree, 2 = disagree, 3 = neither agree nor disagree, 4 = agree and 5 = strongly agree. The supply of antibiotics without a prescription within the week prior to survey completion by pharmacy staff for common infections  were assessed using a five-point Likert scale .Completed questionnaires were coded, reviewed for accuracy and entered into a database. Statistical Package for the Social Sciences  was used for all of the analyses. Descriptive analysis: Personal and professional characteristics, beliefs and attitudes towards antibiotic supply (including latent constructs) and antibiotics supply for common infections were presented either using mean ± SD or median interquartile range (IQR) for continuous data, or frequencies and percentages for nominal data. Factor analysis was performed to identify latent attitudinal factors influencing antibiotic supply without a prescription. One-way ANOVA was performed to evaluate for any difference in the attitudinal scores between the three different groups of respondents .p < 0.05. The dependent and independent variables used in the regression models have been described below.Factors influencing antibiotic supply for common infections were assessed using multivariate logistic regression using the backward elimination method provided in SPSS. The attitude constructs, and all the personal and professional characteristics were introduced together in the regression model. The regression outcome, antibiotic supply without a prescription for common infections was reported by adjusted β and the corresponding 95% confidence interval (CI). The level of significance was set as n = 55) in the study.The pharmacist and non-pharmacist data were combined for the factor analysis and in the regression models because, as observed in this study  and in eThe 5-point Likert scale items assessing rate of antibiotic supply without a prescription in the week prior to the survey for acute sore throat, the common cold and cough, diarrhoea, wound infection and UTI were recoded into a dichotomous variable by treating responses from “25%” to “always” as antibiotic supplied , and “never” as it was and given a value of “0”. The “don’t know” responses were left out of the regression analyses. All five recoded dichotomous variables representing the five conditions were summed to create an overall summative score for non-prescription antibiotic supply for common infections (score 0–5), where “0” meant that no antibiotics were supplied without a prescription, and “1–5” meant that antibiotics were supplied without a prescription for one to five common infections.The association between pharmacy staff’s beliefs and attitudes related to antibiotic supply without a prescription and their professional characteristics with antibiotic supply for common infections was investigated. Exploratory factor analysis (EFA) was conducted to determine the dimensionality reduction of the variables measuring attitudes towards antibiotic supply without a prescription. In this study, there were 43 attitudinal items, and some were correlated with each other. EFA allows for the reduction of these items into meaningful factors and takes into account the correlation between the items. In EFA, relationships among sets of interrelated variables are examined and represented in terms of underlying factors. The construct validity was tested using the principal axis factor (PAF) method with oblimin rotation. Eigenvalue greater than 1 was used as a criterion to select the initial number of factors to be rotated. A cut-off value of 0.30 was set for factor loadings as inclusion criterion in a factor . VarimaxWhilst pharmacy staff are providing antibiotics to the public without a prescription, they appear to hold beliefs that antibiotics are ineffective against common infections, evaluated that they do not have the professional competency to supply and monitor the use of antibiotics provided without a prescription to people, and that supply of antibiotics should follow the legal requirements. However, they believe that the public should have an easy access to antibiotics.Pharmacy staff’s beliefs about the effectiveness of antibiotics for common infections and their beliefs about their professional competency to supply antibiotics without a prescription and monitor antibiotic use by the public were associated with the supply of antibiotics without a prescription.The findings highlight reasons that could contribute to inappropriate supply of antibiotics without a prescription and further emphasise an urgent need for educational and regulatory interventions to improve appropriate antibiotic dispensing practices in Sri Lanka.