FRP (fiber-reinforced polymer)-reinforced concrete members have larger deflection than reinforced concrete members because of the low modulus of elasticity of the FRP bar. In this paper, we proposed a new effective moment of inertia equation to predict the deflection of FRP-reinforced concrete members based on the harmony search algorithm. The harmony search algorithm is used to optimize a function that minimizes the error between the deflection value of the experimental result and the deflection value expected from the specimen’s specifications. In the experimental part, four GFRP (Glass Fiber-Reinforced Polymer)- and BFRP -reinforced concrete slab specimens were manufactured and tested. FRP-reinforced concrete slabs were reinforced with GFRP and BFRP rebars on spiral rib surfaces. The effects of the FRP reinforcement ratio and balanced reinforcement ratio ( Reinforced concrete structures are economical, can freely manufacture the shape and size of members, and are efficient in terms of maintenance. Therefore, concrete and steel rebar are recognized as the most essential materials in the construction industry . As reinFRPs have excellent advantages such as high tensile strength, non-corrosiveness, and light weight compared with steel rebars. When FRPs are used as a steel rebar substitute, it is possible to prevent the deterioration of concrete structures caused by the corrosion of steel and increase their durability ,8,9. TheFRP rebars do not have a yield point, but rather exhibit complete elastic behavior until failure. In addition, FRP rebars have a relatively low modulus of elasticity compared to steel rebar ,12,13. FIn addition, FRP rebar-reinforced concrete members have brittle failure modes in flexure, either due to concrete crushing or sudden ruptures in the FRP rebar . ConcretIn this study, a modified effective moment of inertia equation was proposed, and a comparison was performed with the flexural test results of FRP-reinforced concrete slabs. The proposed effective moment of inertia was developed based on Branson’s equation. The harmony search algorithm was used, where 135 data points were used to minimize the test deflection value when the proposed equation reached the final strength. In order to examine the validity of the effective moment of inertia equation proposed through the harmony search algorithm, a comparative analysis was performed with the flexural stiffness results using concrete slabs reinforced by GFRP and BFRP. In the remainder of this paper, first, the previous model of the effective moment of inertia proposed by other researchers was analyzed. Next, the effective moment of inertia was proposed using data collected from other from other literature. FRP-reinforced concrete specimens with GFRP and BFRP rebar were manufactured and compared with the experimental results in order to verify the proposed effective area moment of inertia.The relationship between the flexural moment and a curvature is defined as shown in Equation (1), wherein the flexural stiffness of a member changes depending on the magnitude of the force acting on the member, the modulus of elasticity actually changes depending on the stress level, and the moment of inertia also changes depending on the presence or absence of cracks. λ is a modification factor reflecting the reduced mechanical properties of concrete, When the service load or a greater load is put into action, a flexural tensile crack is formed in the center of the member, and the position of the neutral axis in the cracked section is shifted to the compression side. At that time, only the cracked transformed section, excluding the concrete crack surface, becomes valid for determining the stiffness of the member, and the moment of inertia of the central section of the member is changed to the moment of inertia of the cracked transformed section. However, since the moment of inertia outside the central section where the flexural crack does not occur and the moment of inertia of the section with a low stress impact is assumed to be the same as the area moment of inertia, the effective moment of inertia is located between the moment of inertia of the cracked section and the area moment of inertia. According to ACI 318 , the effHere, Branson’s equation overestimates the stiffness of the members when the  members ,28. TherIn the study of Benmokrane et al. , the comToutanji and Saafi  found thHall and Ghali  and the nd Ghali  is shownnd Ghali  is shownACI 440.1R-03 , Yost etACI 440.1R-03  set βd=αt et al. , the pre40.1R-06  proposedRafi and Nadjai  compared40.1R-06 :(14)Ie=MThe parameter γ is a relationship obtained via a linear regression analysis of the test results, where Bischoff ,37 propoBischoff and Gross  modifiedIn Equation (17), γ is a parameter in four-point flexural beams.Mousavi and Esfahani  used theNeuyen et al.  proposedIn this study, FRP-reinforced flexural test data obtained by various researchers using four-point loading methods was collected to evaluate the accuracy of the effective moment of inertia equations presented in the literature and to present a new equation of the effective moment of inertia. The collected data comprised a wide range of test data, including 135 data points, and these data points were obtained from the load–deflection relationships of approximately 112 FRP-reinforced concrete members. Details of the various experimental studies are summarized in the The midspan deflection of the concrete member of the four-point loading method can be calculated as shown in Equation (20), and the effective moment of inertia is the main factor in determining the deflection along with modulus of elasticity:To derive the value of parameter m, the correlation between the The harmony search algorithm applied in this study is the most optimized algorithm that mimics musical harmony. This is the process by which each tone harmonizes to create an optimal chord. The harmony search algorithm is characterized by the fact that it does not require mathematical differentiation processes as in other algorithms and that it is optimized by approaching it from a probabilistic perspective. The harmony value generated in the initial full set range is stored in harmony memory, and the ranking is continuously improved to derive the optimal harmony value. In this process, the HMCR (Harmony Memory Considering Rate), which is the probability of randomly generating new chords, provides the possibility of finding a better optimal value without falling into the local solution . In addition, the PAR (Pitch Adjusting Rate) improves the performance of the HMS (Harmony Memory Size) by considering it as a value adjacent to the existing solution in order to find a good solution .In this paper, Mousavi and Esfahani’s  approachThe harmony search algorithm continues until the error converges to the lowest point. For optimization, the size of HMS was set to 50, the number of interactions was set to 100,000, and the HMCR and PAR values were set to 0.70 and 0.25, respectively. The values of obtained by the harmony search algorithm through this optimization are as follows:In this study, the FRP rebar used consists of individual fibers and epoxy resins and has a spiral ribbed surface type. The FRP rebar’s diameter was 13 mm. The FRP-reinforced concrete member was designed as a one-way slab in which the FRP rebar was laid transversely. The deflection was analyzed according to the effective moment of inertia in terms of the FRP rebar type and the FRP reinforcement ratio. As shown in In this paper, various proposed models for the effective moment of inertia of FRP-reinforced concrete members were reviewed. Data were secured by listing 12 existing proposal equations of the effective moment of inertia and collecting literature reporting results of the four-point flexural test. The collected data used a wide range of test data, totalling 135 data points, and these data points were obtained from the load–deflection relationship of approximately 112 FRP-reinforced concrete members. Based on the collected data and experimental results, a new equation of effective moment of inertia was proposed using the harmony search algorithm. The proposed equations of the effective moment of inertia were derived to minimize the difference between the deflection of the experimental results and the calculated value. The effects of the FRP reinforcement ratio and the balanced reinforcement ratio (The proposed model considering the ratio of the reinforcement ratio and the balanced reinforcement ratio, the ratio of the moment of inertia of the transformed cracked section and the gross moment of inertia, and the ratio of cracking moment and the maximum service load moment were confirmed to have a higher accuracy than previous models.In the case of GFRP specimens, Mousavi and Esfahani  and the The proposed model using the harmony search algorithm showed a low error in the deflection of FRP-reinforced concrete slabs. The accuracy of the proposed model was verified by experimental results and showed good agreement.It is necessary to verify the suitability of the proposed model for calculating the effective moment of inertia of FRP-reinforced concrete members, such as in the presence of various surface geometries, mechanical properties, and types of FRP rebar.


The interest of researchers in UHPC has increased over the past decade. It is crucial to understand the structural behavior of reinforced UHPC (R/UHPC) components under various loading conditions before they can be used as a replacement for conventional concrete. Although several studies on ultra-high-performance concrete (UHPC) have been conducted, the knowledge is scattered, and no one can easily judge the performance and methodology of UPHC. Therefore, the purpose of this study was to review the research studies already carried out on UHPC. The review focuses on the materials’ physical and chemical composition, mechanical and durability characteristics, fire resistance, and environmental benefits of UHPC. Design considerations for effectively utilizing UHPC in structural elements are also presented. The best UHPFRC mixture is obtainable with a steel fiber content of 2–3% and a water-to-cement ratio of 0.2–0.3. The review also discusses the essentials recommendation for future research on UHPC. Conventional concrete is strong in compression and weak in tension, and fails when brittle without any deformation. Ultra-high-performance concrete (UHPC), which is a cutting-edge concrete, may be able to resolve these problems. According to the Federal Highway Administration (FHWA) of the United States, UHP cement is a cementitious material formulated by combining Portland cement, fine silica sand, silica fumes, quartz flour, high-range water reducers, and discontinuous internal combustion steel or organic fibers, and a water-to-cement ratio less than 0.25. The strength of UHPC is greater than 21.7 ksi (150 MPa) compressive strength and greater than 0.72 ksi (5 MPa) tensile strength sustained post-cracking . In postFibers can also provide UHPC with strain-hardening properties in tension and convert brittle failure to ductile failure . Several2 content and the ability to increase the packing density of the matrix. It has small, glassy, and spherical characteristics of a ball bearing that can create the ball-bearing effect and help replace water entrapped between the fine and coarse particles [Silica fume is a SCM that serves as a critical component in the production of UHPC. It plays a significant role in affecting its overall performance because of its high amorphous SiOarticles . There carticles . As a coarticles .Furthermore, it can also improve the interfacial transition zone (ITZ) between aggregate/fiber and matrix to eliminate large preferentially oriented CH crystals, ultimately leading to improved homogeneity . The optAs a result, UHPC is an ideal material to provide greater strength and durability to components or structures at the same time as it increases their strength and durability. However, knowledge is scattered and no one can easily judge the benefits of UHPC. Therefore, this review paper examines the mechanical properties, durability properties, and thermal properties of UHPCs. It also discusses the environmental and cost benefits of UHPC.The choice of a brand and type of cement is probably the most important factor in selecting material for high-strength concrete mixtures. In the case of high-strength concrete, cement variation causes the concrete compressive strength to fluctuate more than any other single component. In fact, cement variation seemed to have a greater influence than any other individual concrete component. The cement should be selected based on its water demand; the normal consistency in the cement paste determines the water demand. It is observed that the highest water demand results in the lowest compressive strength. This cement also exhibits good workability and admixture compatibility, and does not possess false setting characteristics. Good quality cement is required to produce uniform high-strength concrete consistently .Polycarboxylate-based high-range water-reducing agent was used since ultra-high-strength concrete’s composition has a low water-binding material ratio. Polycarboxylate-based superplasticizers are suitable in the range of 2.0–3.5 wt.%, based on the amount of the binding material.The shape, surface texture, and mineralogy composition of coarse aggregate must be considered when designing UHPC. The shape and surface texture of the aggregate, together with the mineralogy of the aggregate, affect the overall mixing water required for the concrete. Thus, they play a greater role in the strength-producing qualities.Cubical-shaped coarse aggregate is the preferred satisfying requirement of IS:383 . The graIt is strongly recommended that the fine aggregate fineness modulus is at 2.8–3.0, as it assures the concrete’s derivable fluidity and reduces the viscosity of the final mix. It should satisfy the IS:383  limit of2 (silicon dioxide) should be 85%; maximum C (carbon) allowed = 2.5%.Micro silica or silica fume are exceptionally fine micro particles of amorphous silica, which are included in concrete mixes. They are pozzolanic highly reactive silica, which increases the durability and strength of the concrete. The micro silica/silica fume should satisfy the requirements of ASTM C-1240 . MinimumDue to its very high strength and homogeneity, UHPC is very brittle; yet it can be made ductile by adding steel fibers . Fibers 3 [The mix design of UHPC should be economical and sustainable to achieve a denser matrix, reduce porosity, and improve the internal microstructure to produce superior mechanical and durability properties. The mixture design should also promote economics. The use of mixture designs for UHPC has been reported under various models. The main parameters considered within the initial design process to achieve an improved homogeneous microstructure with dense and ductile properties are optimization of granular mixtures, elimination of coarse aggregates, and proper integration of fibers with the granular mixtures . Conside3 .Furthermore, a few statistical models were proposed that could simulate the mixture design of UHPC. In the case of UHPC, an adaptive neuro-fuzzy interface system (ANFIS) was used for proportioning the ingredients of the mixture  to calcu2 that is replaced with cement has a much higher reaction capacity, so it is easier to attract surrounding water molecules to form chemical bonds. The fast reaction of SiO2 can be attributed to its high specific surface area and many unsaturated bonds. Therefore, there is no water separation or obvious exudation of water from the nano-SiO2 mixture [Yu et al.  studied  mixture . Further mixture . A decre mixture  made UHP mixture . As a re mixture . Besides mixture . Table 3Mo et al.  used 0–2A study also reported that maximum compressive strength was obtained at 15% substitution of metakaolin . This re2 and calcium hydroxide, which promotes the formation of hydrated calcium silicate. Concrete without nano-silica can only hydrate to a very small amount of calcium silicate hydrate if the cement does not contain nano-silica. Calcium silicate hydrate is one of the vital elements that provide strength to concrete. Because of this, concrete without nano-SiO2 has a low compressive strength [2 particles [Additionally, CH gels are removed during the hydration of cement with metakaolin and are actually responsible for accelerating the cement–cementitious hydration process . Yu et astrength . Accordiarticles . It is iarticles . Researcarticles  as well articles . The resarticles . The 3-darticles . Accordiarticles . Table 4The inclusion of metakaolin in cement-based composites enhances compressive strength through the filler effect in the interfacial transition zone between the cement paste and aggregate particles. In addition, CH gels are quickly removed during the hydration of cement with metakaolin and actually accelerate cementitious hydration . Mo et a2 value approximately equal to 90% (83%).It is well known that concrete with high water permeability can become a barrier that allows chemicals, such as chloride ions, to diffuse into it and eventually result in corrosion of steel rebars and/or fibers. UHPC is characterized by much smaller porosity and a much denser microstructure than both conventional concrete (CC) and high-performance concrete (HPC). The low porosity makes UHPC a superior permeability-resistant material. The water absorption capability of concrete can easily provide information on factors such as the porosity and quantity of permeable pores and the interconnectedness of those pores . The dur−8 mm, respectively, as determined by a single pressure method [−19, which is three orders of magnitude lower than the gas permeability coefficient of conventional concrete. When the porosity of the pores is low, and the pore connectivity is restricted, water absorption is greatly reduced. With the addition of mineral admixture to UHPC, the microstructure of UHPC becomes more homogeneous, and the thickness of the ITZ is significantly reduced. In such a case, it reduces the UHPC’s water absorption capacity because it partially blocks its water transport pathway [In comparison to HPC, UHPC’s potential absorption of water is about ten times lower, and it is 60 times lower than NSC’s potential absorption of water . The rede method . Compare pathway .–13 m2/s [It has been identified that chloride ion penetration resistance is one of the most critical factors in concrete strength. It is known that concrete that has a higher tolerance to chloride has a higher ductility. A series of variables such as the w/b ratio, exposure conditions, curing regime, and exposure duration determine the degree of chloride penetration . Chlorid–13 m2/s . A study–13 m2/s . It was –13 m2/s .The damage caused by freezing–thawing occurs in concrete when water molecules freeze and expand beyond the volume limitations of the concrete. As a result, concrete becomes distressed, especially when the pressure develops higher than its tensile strength, eventually resulting in dilation and rupture of the cavities within. In most cases, concrete deterioration is caused by freeze–thaw action, including random cracking, surface scaling, and joint deterioration due to cracking . It has Concrete shrinks when it dries out, which leads to cracking, which is caused by the loss of water due to evaporation. The low w/c ratio facilitates the self-desiccation of UHPFRCs. In the self-desiccation process of concrete, the internal relative humidity of the concrete decreases during the hydration process, thus reducing the size of the pores and resulting in increased capillary tension inside each individual pore. The presence of self-desiccation condition induces the rapid development of the autogenous shrinkage of UHPFRC at an early stage. However, only a very small amount of moisture exchange occurs in the environment due to this condition. As a result, no shrinkage occurs after drying. However, a substantial part of shrinkage occurs within the first few minutes after setting . There aCreep is the propensity of a substance to permanently distort under sustain load. Concrete produces an instantaneous elastic strain when compressed . A lower3. The density of concrete also plays a vital role in its durability. A higher density of concrete results in more durable concrete as the water or harmful chemicals cannot penetrate into the concrete. Generally, UHPC has a higher density as compared to conventional concrete. The typical range of UHPC density is 2400 to 2500 kg/mThe increase in density for the 15% silica fume mix is about 1% larger than that of the 0% mix. The increase in density with silica is due to micro filling and the pozzolanic reaction; micro filling the voids in concrete ingredients leads to more dense concrete while the pozzolanic reaction of silica fume form secondary cementitious materials, i.e., calcium silicate hydrate, improves the binding properties of cement paste, leading to more dense concrete. Furthermore, UHPC concrete typical contains fibers, which also play an important role in the density of concrete. A study reported that the density of concrete increased with fiber. The increase in density of concrete due to addition of fibers can be attributed to crack prevention. Fiber prevents the propagation of cracks, resulting in more dense concrete . AnotherA major problem for ultra-high-performance concrete is the presence of fire or high temperatures (UHPC). After being exposed to 800 degrees Celsius, UHPCs may suffer a strength loss of up to 80% . UHPC stGenerally, the preliminary material cost of UHPC is greater than that of normal strength concrete and high-strength concrete because of its extremely high cement content and steel fiber addition. As a consequence of the use of UHPC, more sustainable building may be achieved, with potentially superior economic, social, and environmental benefits. Construction costs are closely related to the cross-sectional dimensions of structural parts. The usage of UHPC structural parts aids in the reduction of cross-sectional dimensions, hence allowing for the creation of more usable space in structures . As a coOne of the most important factors in producing UHPC is to improve mechanical and durability performance. A detailed review of the literature regarding the distinctive features of UHPC was conducted in this study. The following conclusions can be drawn based on the summary and discussion.UHPC should contain only fine aggregates like natural sand, silica sand, recycled glass cullet, quartz sand, etc., and not coarse aggregates because they will weaken the ITZ.UHPC normally exhibits lower workability as compared to normal strength concrete. UHPC normally contains fiber, increasing the internal friction between concrete ingredients, leading to lower workability.The best mechanical characteristics were obtained for UHPFRC mixtures when the water-to-binder ratio was less than 0.20.Maximum mechanical and durability performance was achieved at 2.0% addition of steel fiber by volume and hook-type fiber, further enhancing the performance of UHPC.Low water absorption, porosity, carbonation depth, freezing and thawing action, and dry shrinkage of UHPC make it usable in all types of aggressive environments.Thermal conductivity of UHPC is higher than that of conventional concrete due to higher density.UHPC is not recommended for use in high-temperature applications due to its low heat absorption capacity.Finally, the overall performance of UHPC depends on the optimum percentages of each ingredient. Most researchers focus on the quality of UHPC ingredients, while a limited number of researchers have focused on optimization by performing statistical analysis such as using the response surface methodology or artificial neural networks for optimization of UHPC ingredients. Therefore, further study is recommended to optimize UHPC ingredients using statistical tools. Furthermore, limited studies are available on the durability aspects of UHPC.


Aberrations in the preterm microbiome following antibiotic therapy have been reported in previous studies. The objective of this study was to probe potential underlying mechanisms between this observation and susceptibility to adverse prematurity-related outcomes.Metagenomic shotgun sequencing was performed on 133 stool and 253 skin samples collected at 1 and 3 weeks of age from 68 infants born at <36 weeks postmenstrual age and birth weight <2000 g. After accounting for gestational age and maternal antibiotics, the distribution of organisms in all samples and the corresponding metabolic pathway abundance were compared between infants exposed to postnatal antibiotics and antibiotics-naïve infants.p< 0.001). Butyrate-producing genera, including Clostridium and Blautia, were significantly more abundant in antibiotic-naïve neonates at 3 weeks postnatal age. Correspondingly, metabolic pathways required for short-chain fatty acid synthesis were significantly increased in antibiotic-naïve infants, but not in antibiotic-exposed neonates, at 3 weeks after birth.In antibiotic-naïve infants, gestational and postnatal age imparted similar trajectories on maturation of the microbial community and associated metabolic functional capacity, with postnatal age exerting greater contribution. Antibiotic exposure was associated with reversal in maturation trajectory from the first week to the third week of age (Early brief antibiotic exposure markedly disrupts developmental trajectory of the neonatal microbiome and its corresponding functional capacity. Our findings may provide a mechanistic explanation for the known associations between antibiotic use and adverse outcomes in preterm infants.Video AbstractThe online version contains supplementary material available at 10.1186/s40168-022-01300-4. Infants’ microbiomes undergo a major transition during the perinatal period –3, from In order to increase insight into the ontogeny of the microbiome in preterm infants, especially as it relates to modifiable environmental conditions, such as antibiotic exposure, we assessed the microbiome in a prospective cohort of preterm infants, from birth till 3 weeks of age using shotgun metagenomic sequencing. We compared between three body sites , as the organization of the microbiota in term  and pretSamples from the skin (axilla and groin) and stool were collected from 68 preterm infants, median (range) birth weight 1384 (648–1940) g and gestational age 30.5 24.0–35.0) weeks .To understand the ontogeny of the microbial community of the stool and skin in the preterm infant during the first 3 weeks of age, we focused on infants that did not receive postnatal antibiotics during this 3-week period. Microbial DNA from a total of 89 stool and 169 skin swabs (86 from the groin and 83 from the axillae) from 46 antibiotic-naïve infants was sequenced and data from week 1 were compared with week 3. We found, as expected, that at all three body sites examined, the number and diversity of genera increased from week 1 to week 3 . Several other genera, Klebsiella, Veillonella, Serratia, and Escherichia, were also significantly increased . Conversely, Staphylococcus demonstrated the greatest decrease in abundance from week 1 to week 3  and declined with advancing gestational age . The other body sites and time points were not significantly different with respect to gender  between antibiotic-exposed and antibiotic-naïve groups from week 1 to week 3  received < 48 h of ampicillin and gentamicin, and predominantly during the first 3 days of age. We first compared microbiome diversity across body sites at week 1 and week 3 between antibiotic-exposed and antibiotic-naïve groups. Stool samples showed a decrease in diversity during the first and third weeks and skin samples from the groin demonstrated decreased diversity by the third week post-antibiotic therapy , indicating the metabolic capacity demonstrated significant functional maturation in these infants. However, the change from week 1 to week 3 in antibiotic-exposed infants was not significant (p=0.064), indicating that antibiotics impaired maturation of metabolic functional capacity. On PCA analysis, antibiotic exposure was associated with a shift to a more immature metabolic pathway abundance at week 3 compared to antibiotic-naïve infants. These two features of the PCA plot reveal that antibiotic exposure is associated with stunting of functional maturation of the preterm infant microbiome. To specifically address the role of antibiotic exposure and account for differences in gestational age and maternal antibiotic exposure between groups, we employed generalized linear mixed modeling (GLMM) with fixed and random effects. We found that genes encoding a total of 20 metabolic pathways were significantly different from week 1 to week 3 in the stools of antibiotic-naïve infants. In contrast, 34 metabolic pathways were significantly different in infants that received antibiotics  and acetate (PWY.6588.pyruvate.fermentation.to.acetate) . Infants born at <36 weeks postmenstrual age and birth weight <2000 g admitted to the Neonatal Intensive Care Unit (NICU) at the University of Cincinnati Medical Center (UCMC) from February 2019 to October 2019, with anticipated length of stay of >21 days, were enrolled on admission. Infants were stratified into (1) antibiotic-exposed or (2) antibiotic-naïve groups, based on any postnatal antibiotic therapy. Stool and skin samples were collected at 1 (5–9 days) and 3 (15–21 days) weeks of postnatal age following written consent from parents. Skin samples were obtained with a soft cotton swab moistened in normal saline from infants’ groins and axillae. Swab tips were snapped off into sterile 1.5-ml polyethylene tubes, transferred immediately to a −80°C freezer for storage. Stool samples were scrapped from diapers and immediately frozen at −80°C until analysis. Maternal and neonatal demographic data, labor complications, and NICU courses, including postnatal antibiotic therapy, were extracted from electronic medical records.Briefly, genomic DNA was isolated from stool samples using the Qiagen QIAamp® PowerFecal® Kit, per the manufacturer’s protocol. For skin samples, MasterPure yeast DNA purification kit  and Genomic DNA Mini Kit , lysis buffer with the addition of 1ul (3500 U) of diluted Ready Lyse solution were used according to the manufacturer’s protocol . Yield aU test or Kruskal-Wallis test), followed by the Bonferroni correction for multiple testing. Effect size of the statistically significantly different genera was determined using shrinkage linear discriminant analysis (SLDA). We performed generalized linear mixed modeling with parameterization for (NBZI-GLMM), then performed false discovery rate (FDR) correction followed by calculation of effect size using SLDA as we described previously [Raw sequence reads were extracted and demultiplexed using the Illumina program bcl2fastq. Raw reads were then filtered and trimmed for quality control using the program Sickle with default settings . Trimmedeviously . All datAdditional file 1: Table S1. Detailed information on all infant antibiotic exposures.Additional file 2: Table S2. Summary sample size by body sites, postnatal ages, gestational ages, antibiotic treatment groups, and collection times.Additional file 3: Table S3. Raw genus count data.Additional file 4: Table S4. Raw species count data.Additional file 5: Table S5. Microbial pathway abundance data.Additional file 6: Figure S1. A Impact of gestational age on microbiome structure, using PCA. B Impact of postnatal age on microbiome structure. Figure S2. The contribution of gender to microbiome composition at all body sites and found the only time point with difference in gender was groin at Week 1 . Figure S3. Antibiotic exposure was associated with altered abundance of several genera. Figure S4. Microbial metabolic pathway abundance and enrichment from Week 1 to Week 3 were compared between antibiotic-exposed and antibiotic-naïve preterm infants using MRPP and GLMM, as described in the text.


H  has been studied in water/dmso (98 : 2) and CD2Cl2. These guests have essentially identical molecular surfaces, volumes and external functional groups to interact with the cage interior surface; but they differ in polarity with dipole moments of ca. 7, 4 and 0 Debye respectively. In CD2Cl2 guest binding is weak but we observe a clear correlation of binding free energy with guest polarity, with 1,4-DCB showing no detectable binding by NMR spectroscopy but 1,2-DCB having −ΔG = 9 kJ mol−1. In water (containing 2% dmso to solubilise the guests) we see the same trend but all binding free energies are much higher due to an additional hydrophobic contribution to binding, with −ΔG varying from 16 kJ mol−1 for 1,4-DCB to 22 kJ mol−1 for 1,4-DCB: again we see an increase associated with guest polarity but the increase in −ΔG per Debye of dipole moment is around half what we observe in CD2Cl2 which we ascribe to the fact the more polar guests will be better solvated in the aqueous solvent. A van't Hoff analysis by variable-temperature NMR showed that the improvement in guest binding in water/dmso is entropy-driven, which suggests that the key factor is not direct electrostatic interactions between a polar guest and the cage surface, but the variation in guest desolvation across the series, with the more polar (and hence more highly solvated) guests having a greater favourable entropy change on desolvation.Binding of a set of three isomeric guests  inside an octanuclear cubic coordination cage host  The three dicyanobenzene isomers have obvious similarities but differ in their dipole moment: effects on binding in a coordination cage host in different solvents are discussed. Knowing binding constants is of course important but this information alone falls short of providing detailed insight into the factors that are responsible for guest binding in the way that has long been routinely applied to understanding biological or organic host/guest systems.8 An early quantitative analysis was based on relative sizes of host and guest by Rebek and became the basis of the so-called ‘55% rule’.9 Beyond that, systematic analyses of thermodynamic factors responsible for guest binding in cage hosts are rather limited, with the work of Raymond and co-workers providing the most prominent examples.10The factors responsible for binding of guests to hosts in supramolecular assemblies have been extensively reviewed.8L12]16+ host H . All three have essentially the same molecular volume and are comfortably small enough to bind inside the cage cavity, as crystal structures show. They all have essentially the same surface area, meaning that the surface matching with the interior of the cage will liberate the same number of water molecules from both surfaces, leading to similar hydrophobic contributions to binding. And all have two nitrile functional groups which are weak hydrogen-bond acceptors. However, the differences in polarity – as expressed in their dipole moments – are significant with calculated gas-phase dipole moments of 7.1 , 4.3  and 0 Debye .18 Comparison of the three guests should therefore reveal the extent to which a molecular dipole influences guest binding in the cage different solvents – water and CH2Cl2 – as this variable is the main difference across this guest series. Overall the work we describe here contributes to our understanding of optimising guest binding in synthetic hosts with a view to increased predictability.To pursue our understanding of guest binding further we were interested to examine the effects of guest polarity in different solvents, as manifested in the guest dipole moment. This is quite different from the effects of specific (charge-assisted) hydrogen-bonding interactions between cage and guest which are highly dependent on the local functional groups involved in the interaction.H that we reported originally,19 which was soluble only in polar organic solvents, can be functionalised with differing external substituents to control solubility. For this paper we have used H  for the crystallographic studies. The cage Hw incorporates hydroxymethyl substituents at the C4 position of every pyridine ring, conferring improved water solubility due to the set of 24 externally-directed OH groups.12 The cage HPEG similarly has a set of 24 tri-ethyleneglycol monomethyl ether substituents, which confer much improved solubility compared to H in both water and organic solvents such as CH2Cl2 because of the flexibility of the PEG chains which allows them to adopt both polar or non-polar conformations as required.20 The structures of these are summarised in The unsubstituted cage 21,22 recently popularised by Fujita and co-workers,21 that we have employed recently with considerable success.23 Growing crystals of the cage H from solvent in the presence of guests generally leads to crystals of empty H; however, pre-preparing good-quality crystals of H solvothermally, and then immersing them in a concentrated solution of the desired guest (or the pure guest if it is a liquid) for a few hours, affords a good chance of the guest being taken up into the cage crystals without loss of crystallinity. Using this method we were able to perform single-crystal structural determinations of all three cage/DCB complexes which we denote H·12DCB, H·13DCB and H·14DCB with 1,2-, 1,3- and 1,4-DCB respectively as the guests.The crystal structures of the cage/guest complexes with each of the three guests were obtained using the crystalline sponge method,H·12DCB  gives a cavity occupancy of 67%. As usual in cases where the guest has one or more externally-directed lone pairs, weak hydrogen-bonding interactions with the cage interior surface serve to orient the guest in the cavity ] where several C–H hydrogen atoms converge: as these are close to a Co(ii) centre in a region of positive electrostatic potential they carry a higher δ+ than a neutral CH group and participate in CH⋯N interactions,11 and N22G makes contacts of <3 Å with six CH protons from the methylene (CH2) or naphthyl protons in the surrounding pocket. The other N atom (N32G) makes a smaller number of contacts, with two significant CH⋯N interactions of 2.70 and 2.82 Å with naphthyl and pyrazolyl CH groups, respectively, close to the adjacent metal centre Co(2)  . The lowH·13DCB likewise contains a stacked pair of guests, with unit site occupancy each and no positional disorder, lying astride an inversion centre such that their local dipoles cancel  projects into the convergent pocket of CH hydrogen atoms close to the fac tris-chelate metal centre Co(4), with four CH⋯N contacts in the range 2.51–2.84 Å. The other nitrile N atom N7G forms CH⋯N interactions of 2.52 and 2.84 Å with naphthyl and pyrazolyl CH protons in the vicinity of the adjacent metal ion Co(3)  .H·14DCB  or six MeOH molecules (the other 50% of the time). Short O⋯O contacts  are indicative of the presence of OH⋯O hydrogen bonds between the methanol molecules. The most significant feature of the structure is the orientation of the 1,4-DCB guest which lies along a long diagonal of the interior cavity (fac tris-chelate sites [Co(4) and its symmetry equivalent; 26 The resulting array of CH⋯N contacts between the guest and the cage interior surface (2) and naphthyl protons in the binding pockets. Guest atom N(20G), which lies further into the pocket and closer to Co(4), has five CH⋯N contacts in the range 2.47–2.54 Å; guest atom N(18G), which lies slightly further out of the other pocket, has two comparably short interactions (2.46 and 2.55 Å) and a larger number of slightly longer ones.The crystal structure of H·14DCB  is fundaH·14DCB , implyinr cavity  such tha surface  involvesca. 67%. In contrast the more elongated shape of 1,4-DCB seems to preclude this, with 1,4-DCB needing to lie along a long diagonal of the cavity to fit – an orientation which results in hydrogen-bonding interactions at both ends of the guest but which prevents the presence of a stacked pair. The cavity is therefore less efficiently filled by 1,4-DCB which may explain why only half of the cages contain a 1,4-DCB guest, with the other half containing a hydrogen-bonded network of MeOH molecules.The set of three structures has some obvious similarities in respect of the CH⋯N contacts between guest and cage interior surface. The relatively compact shapes of guests 1,2-DCB and 1,3-DCB allows a π-stacked pair to occupy the cage cavity giving a cavity occupancy in the solid-state of Hw as the water-soluble host.12 To get an initial idea of binding constants – to allow us to determine whether we should be using NMR or UV/vis spectroscopy, for example – we first calculated binding constants using the molecular docking programme GOLD with our customised scoring function that was obtained from a large training set of empirical data.16 This afforded estimated log K values for 1 : 1 host/guest complex formation of 3.2, 3.1 and 1.8 for the 1,2-, 1,3- and 1,4-DCB isomers respectively, with a significantly lower binding constant predicted for 1,4-DCB compared to the other two. Binding constants in the region 102–103 M−1 ideally require mM concentrations of host and guest to get a high degree of binding, which means that NMR spectroscopy was selected as the most appropriate analytical technique.We next measured the binding constants of three guests in water using the hydroxymethyl-substituted cage 27Initial tests showed that the DCB isomers are not sufficiently soluble in water for this to be possible, however inclusion of a small amount of dmso  cured the problem. We have avoided as far as possible using mixed solvent systems because selective solvation effects can have consequences for supramolecular interactions which are highly non-linear with solvent composition, as Hunter and co-workers have thoroughly demonstrated.However use of just 2% dmso in water fixed the solubility problems and still gave binding constants of the same order of magnitude (and in the same relative ordering) as those predicted using GOLD (see below).1H NMR titration experiment involving addition of portions of 1,2-DCB to a solution of Hw is shown in ii) ion disperses the signals over the range ±100 ppm,11–14 making it easy to see spectroscopic changes associated with a guest that is binding in slow exchange: the steady replacement of signals associated with free Hw (highlighted in green) by shifted signals associated with the formation of the Hw/1,2-DCB complex during the titration (highlighted in orange) is clear. The value of K was determined by integration of these separate signals for free and complexed host, and knowledge of the concentration of all species present at each point.An example of a i.e. the error values in ‡‡1H NMR spectra that is the main source of error in this work. This is shown by the fact that we see significantly smaller errors associated with K values when they are derived from e.g. fluorescence measurements, or NMR measurements when the guest is in fast exchange: in such cases a large number of data points can be included in a conventional curve which is fit to a 1 : 1 isotherm  can actually vary during a titration as more guest is added, to an extent depending on the solvent and the nature of the host and guest involved. Piguet and co-workers have looked at this in detail, see ref.  28We note that accurate deconvolution and integration of broad, overlapping signals from a paramagnetic complex can be difficult, so multiple individual integration measurements at different points in the spectra were averaged to reduce the experimental error. Moreover, the standard deviation from this averaging of multiple integration ratios has been doubled to provide an appropriately cautious estimate of experimental uncertainty, K values of 7000(±3000), 2700(±1400) and 620(±340) M−1 for the 1,2-, 1,3- and 1,4- isomers of DCB in water. The experimental uncertainties are high for the reasons given above, but (i) the values are in reasonable (order of magnitude) agreement with those predicted using GOLD, and (ii) the general trend is clear – and also as predicted by GOLD – with the binding constant decreasing in line with the reduced dipole moment across the series of guests. A plausible interpretation is that the δ- regions of the guests are those that lie closest to the positively charged cage surface, as the crystal structures all show, affording favourable electrostatic interactions. We know from other work with surface binding of anions that the high positive charge of the cage surface results in strong anion binding,29 which is the basis for the catalytic effects that we have seen.4 A similar favourable electrostatic interaction of the cage surface with a δ- part of a molecular dipole is quite possible here. Note that, although crystal structures show that two guests  can occupy a cage cavity under forcing and non-equilibrium conditions, we assume that binding of a second guest will be much weaker than the first, such that at the concentrations used the assumption that the speciation will be dominated by 1 : 1 host : guest complex formation is reasonable.23From similar experiments with all three guests we obtained 2Cl2 rather than water. This necessitates use of the cage HPEG with the same octanuclear core structure and cavity as H and Hw but bearing more solubilising substituents.20 It was immediately apparent that a far larger excess of the DCB guests was required to be able to observe new signals for the cage/guest complex  were deconvoluted and integrated, and the resulting calculations of K were averaged over multiple measurements in different parts of the spectra and at different points during the titration. The resulting K values for 1 : 1 host/guest complex formation with the 1,2- and 1,3-DCB isomers were 45(±8) and 9(±3) M−1 respectively: with 1,4-DCB we observed no significant change in the NMR spectrum of HPEG even after addition of >100 equivalents of 1,4-DCB . Given the much less significant solvophobic contributions to guest binding in CH2Cl2 compared to water (see below), the effect of guest polarity dominates the binding constants more obviously.We see the same effect of guest polarity, but with the background hydrophobic effect removed, by performing binding constant measurements for the three isomeric guests in CD complex . Again d 1,4-DCB , top, meG = 16 kJ mol−1) increases to 20 and then 22 kJ mol−1 for the 1,3- and 1,2-isomers respectively as the dipole moment increases from 0 to 4.3 to 7.1 Debye, i.e. an increase in −ΔG of 0.8 kJ mol−1 per Debye in this solvent. The second observation is that the effect of guest polarity is more pronounced in CD2Cl2 than in the aqueous solvent, with comparison between 1,3- and 1,2-DCB binding free energies showing an increment of 1.5 kJ mol−1 per Debye, nearly double the coefficient obtained in water/2% dmso. This likely reflects the fact that the dipoles of 1,2-DCB and 1,3-DCB are better stabilised by water than by CD2Cl2, meaning that binding of the more polar guests inside the cage cavity will carry a higher desolvation penalty in water/2% dmso than in CD2Cl2.From the binding constants in different solvents we can extract two interesting pieces of data associated with the effects of guest polarity. We assume that the similarity between the guests in other respects means that the dipole differences are the major factor in determining the binding constant differences – the assumption that underpinned the choice of guests. Firstly we note that, for the three measurements in water, the contribution to guest binding arising from polarity is approximately linear with dipole moment. The binding free energy of 1,4-DCB in water/2% dmso  must be cancelled out by any desolvation costs and the free energy costs associated with combining two species into one supramolecular complex which restricts relative molecular motions.8It is also interesting that 1,4-DCB shows no detectable binding to 11 This is clearly not the case here, and we note that nitrile groups are significantly poorer hydrogen-bond acceptors, with a lower β parameter, than the functional groups such as amides and N-oxides that allowed H-bonding to be a significant contributor to guest binding in those earlier cases.30,31 Given this absence of significant binding of 1,4-DCB in CD2Cl2, and the relative lack of solvophobic effects in CD2Cl2 compared to water, one could reasonably conclude that the binding that we observe with more polar 1,3- and 1,2-DCB isomers in CD2Cl2 can be attributed to the additional polar contribution of a δ– region of the guest surface interacting with the 16+ cage surface.In earlier work to quantify different contributions to binding with a range of guests we noted a significant contribution, in MeCN as solvent, from H-bonding between the guest and the cage interior surface in some cases.HPEG in CD2Cl2 due to cancellation of the various favourable and unfavourable effects as described above, it follows that the binding free energy in water (−ΔG = 16 kJ mol−1) is ascribable solely to the change in solvent, i.e. a combination of the hydrophobic effect and any additional desolvation costs that apply in water. In previous work in which guests containing the same functional groups but zero or one additional fused aromatic rings were compared for their binding, we observed a consistent increment associated with binding of an additional aromatic ring in water compared to MeCN of ca. 10 kJ mol−1 due to the additional hydrophobic surface.12 The hydrophobic effect scales with surface area: 1,4-DCB (surface area 157 Å2) is significantly larger than one aromatic ring, and also is not purely hydrocarbon, but we just note here that the binding free energy of −ΔG = 16 kJ mol−1 for 1,4-DCB is approximately consistent with expectations based on previous work on the expected magnitude of hydrophobic contributions to binding of aromatic units.12In addition, given that there is no detectable binding of 1,4-DCB inside 2Cl2 which means that binding is undetectable by NMR spectroscopy, (ii) the strength of the hydrophobic effect which drives binding in water, and (iii) the incremental consequence of guest polarity on binding free energy which is present in both solvents but is more pronounced in CD2Cl2.Overall the binding constant measurements in two different solvents clearly illustrate (i) the weakness of binding of non-polar 1,4-DCB in CDK changed with temperature. Standard van't Hoff plots of ln K vs. 1/T then allow the ΔH and ΔS contributions to guest binding to be separated. Given the magnitude of the binding constants this experiment only gives reasonable data in the water/2% dmso solvent system.To probe further the contributions to guest binding in water we performed variable-temperature NMR measurements on cage/guest mixtures which allowed us to see, through steady changes in the relative values of integrals associated with free and guest-containing cages, how the values of G between the three guests are masking more substantial changes in ΔH and TΔS which tend to oppose each other: this illustrates the phenomenon of ‘enthalpy/entropy compensation’32 whereby (in simple terms) a favourable change in enthalpy associated with a strong intermolecular interaction forming is offset by a loss of entropy associated with two independent species joining together. Here, the opposing changes do not quite cancel out. As the guest increases in polarity from 1,4-DCB to 1,2-DCB we see the modest steady increase in −ΔG that has been discussed earlier arises because of positive shifts in both ΔH (unfavourable) and TΔS (favourable) that do not cancel, with the favourable increase in TΔS more than compensating for the unfavourable ΔH change, so we can say that the increased guest binding associated with guest polarity is actually entropy-driven.The results are summarised in H and TΔS changes on guest binding in water is counter-intuitive: the polarity effect that we proposed earlier, viz. that an increased dipole on the guest provides the opportunity for δ– regions of the guest to interact favourably with the cationic cage surface, would constitute a favourable ΔH contribution to guest binding. Whilst this remains a likely contribution to the binding of the more polar guests, it appears to be small  and masked by larger and less predictable changes in the ΔH and ΔS contributions to the hydrophobic effect associated with structural changes in the guests. Specifically the polar guest 1,2-DCB is expected to be more strongly solvated in water than non-polar 1,4-DCB, resulting in a greater enthalpy penalty for desolvation compared to 1,4-DCB: conversely, liberation of the tighter-bound solvation sphere from around 1,2-DCB will result in a larger entropy gain than occurs from more weakly-solvated 1,4-DCB. This is enthalpy/entropy compensation again,32 but the opposite way around to the simple example described earlier, and the entropy effect wins in controlling changes in binding free energies across this series of guests in water.Based on the preceding discussion, this direction for the Δ8 and the number of water molecules liberated from the cavity following guest binding will be similar in each case given that the molar volumes of the three isomeric guests are so similar. This leaves desolvation of the guests on binding as the main variable to account for the trend in K values that we observed.Importantly we can expect that the entropy decrease associated with a guest binding inside the cage cavity will be similar with each guest;33 much recent work has shown that it can have a substantial enthalpy contribution,14,34 with the balance between the two effects being unpredictable. We observed a while ago that the improved binding free energy of guests inside Hw associated with addition of a hydrophobic CH2 group to the guest skeleton was mostly enthalpic in origin.14 We also note that the ΔΔH and Δ(TΔS) values associated with the change from 1,3-DCB to 1,2-DCB are much larger than those associated with the change from 1,4-DCB to 1,3-DCB despite the slightly smaller dipole moment increment, for which there is no simple explanation.We note that whilst the hydrophobic effect was originally considered as primarily entropic in origin,G between CD2Cl2 and water. The different ΔH/TΔS contributions to guest binding across the guest series in water arise principally from changes in solvation of the guest when it binds, and cannot be rationalised simply by considering direct cage/guest electrostatic interactions. We note that Raymond and co-workers came to similar conclusions regarding the dominance of guest desolvation on controlling binding affinities for a wide range of guests inside a coordination cage host in protic solvents.10Overall, in this guest series, it is clear that the hydrophobic effect is the dominant thermodynamic contribution to guest binding in water, as shown by differences in −Δ2Cl2. Overall it is clear that increases in guest dipole moment results in increased binding free energies −ΔG, but the magnitudes of any polarity-induced changes in binding strength are small compared to the hydrophobic effect which dominates guest binding in water. In water, in terms of ΔH and TΔS components, the increased free energy of guest binding for the more polar guests is entropy-based, with the enthalpy changes associated with binding of the more polar guests being unfavourable but less significant. We ascribe this to the effects of guest desolvation, with the more polar guests that have a tighter solvation sphere in water needing a higher enthalpy penalty to desolvate them, but also showing a greater favourable entropy change when those solvent molecules are liberated to allow guest binding to occur. In water/2% dmso, any favourable direct interactions between polar guests and the cage  are therefore less significant in determining the pattern of guest binding free energies across the series than is guest desolvation which is the dominant effect.This set of isomeric guests provides changes in dipole moment whilst keeping as fixed as possible molecular volume, surface area, and the functional groups involved in hydrogen-bonding, allowing us to evaluate the effects of guest polarity on binding inside a coordination cage host in water/2% dmso, and CDH ,19Hw (used for guest binding studies in water/2% dmso)12 and HPEG (used for guest binding studies in CD2Cl2)20 were prepared according to published methods. The three isomers of DCB were purchased from Sigma-Aldrich and used as received. Calculated binding constants for the DCB isomers (assuming pure water as solvent) using the GOLD programme were performed as outlined in ref. Samples of 23 by immersing pre-grown crystals of H 19 into a concentrated MeOH solution of the relevant guest. Information on the crystal properties, data collections and refinements associated with the structure determinations of the cage/guest complexes of H are collected in Table S1 of ESI.35 using methodology, data processing and software described previously.23The crystalline sponge experiments were performed as described in a previous paper,C. M.: Synthesis and NMR measurements of cage/guest binding constants. A. B. S. and C. G. P. T.: crystalline sponge experiments and X-ray crystallography. B. S.: calculations of predicted binding constants using GOLD. M. D. W.: project conception and supervision, manuscript preparation.There are no conflicts to declare.DT-051-D2DT02623F-s001DT-051-D2DT02623F-s002


To determine the coarse aggregate contribution to the overall concrete performance, lean and rich concrete mixtures (Mix 1 and Mix 2) were used. Mix 1 (lean mixture) consisted of a ratio of water to cement (w/c) of 0.5 and cement content of 300 kg/m3, whereas a higher quantity of cement of 500 kg/m3 and a lower w/c ratio of 0.3 were used for Mix 2 (rich mixture). The results showed that while the compressive strength for different aggregate types in Mix 1 was comparable, the contribution of aggregate to concrete performance was very significant for Mix 2. Heavyweight aggregate produced the highest strength, while the lightweight and recycled aggregates resulted in lower mechanical properties compared to normal weight aggregates. The modulus of elasticity was also substantially affected by the coarse aggregate characteristics and even for Mix 1. The ACI 363R-92 and CSA A23.3-04 appeared to have the best model for predicting the modulus of elasticity, followed by the ACI-318-19 (density-based formula) and AS-3600-09. The density of coarse aggregate, and hence concrete, greatly influenced the mechanical properties of concrete. The water absorption percentage for the concrete produced from various types of aggregates was found to be higher for the aggregates of higher absorption capacity.Concrete is classified as a multi-composite material comprising three phases: coarse aggregate, mortar, and interfacial transition zone (ITZ). Fine and coarse aggregates occupy approximately 70–85% by volume, of which coarse aggregate typically constitutes more than two-thirds of the total quantity of aggregate by volume. The current study investigates the concrete performance produced using various recycled construction and by-product industrial waste coarse aggregates. Six types of coarse aggregates: manufactured limestone, quartzite, natural scoria, by-product industrial waste aggregate, and two sources of recycled concrete aggregates with densities ranging from 860 to 2300 kg/m Concrete is considered the highest utilized and consumed construction material worldwide. Concrete is a heterogonous and multiphase composite material comprised of coarse aggregate, mortar, and interfacial transition zone (ITZ). Fine and coarse aggregates occupy approximately 70–85% of the total quantity of concrete mixtures by volume . The worThe failure mechanics of normal weight aggregate concrete (NWAC) is dependent on the three phases of concrete: coarse aggregate, cementitious matrix, and ITZ. In normal strength concrete (NSC), which is recognized to have a higher ratio of water to cement (w/c), less cement contents, and assuming rigid coarse aggregate, the failure is initiated at the weakest link of ITZ in the form of micro-cracking, causing a separation between the matrix and coarse aggregate particles and leading to crack propagation around the aggregate particles ,5,6. NevThe modulus of elasticity of HSC is also greatly influenced by the coarse aggregate quality, and the literature indicates that a stronger aggregate tends to produce stiffer concrete ,7,9. ThiOver the last few decades, lightweight aggregate concrete (LWAC) structural components have attracted the attention of the concrete industry owing to the reduced self-weight of structural members, lower building cost, ease of construction, better thermal properties, and fire and acoustic resistance ,12,13. T3 to 3840 kg/m3 has been classified in the literature as heavyweight concrete [Heavyweight aggregate concrete (HWAC) has been widely employed in nuclear power plants, military impact-resistant facilities, medical laboratories, shielding applications, and radioactive facilities due to its ability to provide a protection material and its ability to absorb neutron energy ,17. Whilconcrete . Althougconcrete . De Domeconcrete  reportedconcrete  reviewedRisks of natural aggregate resource depletion and moving towards sustainable and environmentally green concrete have promoted the utilization of industrial waste and recycled concrete aggregate (RCA). However, while the concrete performance at the fresh and hardened states appears to be negatively influenced at the full replacement level, its adequacy and compliance with international concrete specifications are met when used at an appropriate replacement level or when treatments are applied. The characteristics of adhered mortar, which is composed of unhydrated and hydrated cement paste, play a major role in the concrete performance at the fresh and hardened states. The adhered mortar typically results in inferior concrete performance, higher porosity, higher water absorption, lower density, lower specific gravity, higher fine content, and lower resistance to abrasion and impact ,22. Conc3 and with different strength properties were studied. The applicability of the available equations for predicting the elastic modulus of concrete produced using these aggregates is also verified. It is evident that the effect of coarse aggregate characteristics on concrete performance has been previously investigated and shown to have an enormous impact on concrete performance. Nevertheless, a great deal of these studies considered aggregates of the same density category or looked at the effect of replacement levels with normal aggregates. Limited studies have investigated the performance of concrete produced using various sources of recycled construction and by-product industrial waste coarse aggregates at a full replacement level, and compared the performance with natural or manufactured lightweight and normal weight coarse aggregates. Additionally, there are limited studies on the stress–strain relationships of concrete produced using recycled construction and by-product industrial waste coarse aggregates, especially with a wide range of densities. The current study investigates concrete performance in terms of compressive strength, splitting tensile strength, stress–strain characteristics, and water absorption produced using various recycled construction and by-product industrial waste coarse aggregates. The novelty of the study is covering a wide variety of commonly used coarse aggregates: manufactured limestone, quartzite, volcanic scoria, by-product industrial waste aggregate, and two sources of RCAs with densities ranging from 860 to 2300 kg/mType I Portland cement of Yamama cement factory, Riyadh, Saudi Arabia, conforming to the ASTM C150 requirements  with a sThis study used six types of coarse aggregates covering a broad range of mineralogy and densities, as shown in The RCA-1 was produced from low porosity and HSC specimens with compressive strength of roughly 60 MPa collected from the concrete plants. On the other hand, the RCA-2 was prepared from low-strength, highly porous concrete specimens whose compressive strength did not exceed 20 MPa. It should be pointed out that the virgin coarse aggregate source utilized in the concrete specimens of the RCA-1 and RCA-2 was manufactured limestone aggregate (LS), and the primary difference between the two RCAs lies in the quality of adhered mortar in terms of porosity, water absorption, surface texture, and abrasion resistance. The maximum nominal size of coarse aggregate was 20 mm for all aggregate types except for the LWA, with a maximum nominal size of 10 mm. The gradation curves for the various coarse aggregate types satisfied the ASTM C33 requirements . 3 for the LWA to 2300 kg/m3 for the HWA. These aggregate densities are translated into concrete densities ranging from 2025 to 2918 kg/m3. The LWA and RCA-2 had very high-water absorptions of 10.6% and 8.2%, respectively, whereas the other aggregates appeared to be in the range of 1.3% to 4.7%.The physical properties of aggregates, determined in accordance with the ASTM C127 [3, whereas a higher cement quantity of 500 kg/m3 and a lower ratio of w/c of 0.3 was used for Mix 2 (rich mixture). The concrete mixture proportions for both mixtures were designed in accordance with ACI 211.1 [The concrete mixture design considered lean and rich concrete mixtures, referred to throughout the paper as Mix 1 and Mix 2, respectively, to determine the coarse aggregate contribution to the overall concrete performance created using various coarse aggregate types. Mix 1 (lean mixture) consisted of a 0.5 w/c ratio and cement quantity of 300 kg/mCI 211.1 , as show® 51, a water-reducing admixture in compliance with the ASTM C494 Type F [Since the current study is intended to evaluate the effect of various coarse aggregate types on the performance of concrete, several precautions were taken. First, the coarse aggregate-to-fine aggregate ratio by volume was kept fixed at 1.48 for the two concrete mixtures. Second, the relative coarse aggregate volume was maintained fixed at 45% for Mix 1, whereas a lower percentage of 41.3% was used for Mix 2. The minor reduction in the coarse aggregate volume of Mix 2 was due to having a slightly higher quantity of cement compared to Mix 1. These modifications in the concrete mixture design resulted in concrete in which the total aggregate volume occupied was 75.5% for Mix 1 and 69.1% for Mix 2. The concrete mixtures considered the extra water needed for each type of coarse aggregate since they had a wide range of water absorption. In order to address the workability issues related to the mixtures of higher cement quantity and a lower ratio of w/c, especially with the aggregates of higher water absorption, it was essential to utilize MasterGlenium4 Type F , which i3 for the lean mixture, and 2311 to 6932 mL/m3 for the rich mixtureThe concrete mixtures were all designed to have a slump within a workable range of 75 to 100 mm, which is consistent with the recommended slumps for various types of construction adopted by ACI 211.1 . Therefo2 cylinders with proper vibration to reduce air voids. Following the casting process, concrete specimens were removed from the molds one day after the casting day. They were cured for 28 days under a laboratory-controlled environment (24 ± 2 °C) by submerging in curing water tanks until the testing day.Concrete was poured into 100 × 200 mmThe coarse aggregates  were tesThe quality of coarse aggregates with respect to the abrasion resistance was assessed using the Los Angeles testing described in the ASTM C131 , as illuThe compressive strength determined at 28 days for Mix 1 and Mix 2 was performed in accordance with the ASTM C39/C39M-20 , and theThe superior performance of RCA-1 compared to RCA-2 was owing to the quality of mortar attached on the surface of coarse aggregate particles, which was characterized by the lesser volume of porous attached mortar, lesser water demand or absorption, and better abrasion resistance. Nevertheless, the existence of a high volume of porous mortar attached to the surface RCA-2 particles introduced an additional phase to concrete, and the failure mechanics were controlled by the bonding strength of the new ITZ to the old ITZ adhered. This zone was considered the weakest link, owing to the high volume of the porous adhered mortar and high absorption level of 8.5%. Consequently, microcracks initiated and propagated around that zone caused a separation between the matrix and RCA particles. The lowest compressive strength was recorded for LWA (21 MPa). It should be noted that the LWA aggregate was very porous, had substantially higher water absorption of 10.6%, and substantially lower abrasion resistance with a mass loss of 45%. The compressive strength drop of the LWA was attributed to a very low coarse aggregate strength compared to the mortar. As the LWA was subjected to the axial compressive loads, stress redistribution within the concrete specimen occurred, and due to the lower stiffness of the LWA, the matrix attracted more stress. The compressive strength of the LWA concrete specimen would be less than the strength achieved if this specimen contained only mortar. This phenomenon has been generally cited in the literature as the limit strength, which corresponds to concrete compressive strength assuming the elastic modulus of both the mortar and coarse aggregate is similar ,4,7,9,103 and when the ratio of w/c ratio was reduced from 0.5 to 0.3, the degrees of compressive strength improvement for LS, MK, LWA, HWA, RCA-1, and RCA-2 were 20%, 28%, 103%, 48%, 10%, and 65%, respectively. The compressive strength values ranged from 41.7 MPa to 81.1 MPa. It was generally observed that a stiffer coarse aggregate produced a higher compressive strength. The LS and MK specimens, which comprised normal weight coarse aggregates, had an almost similar compressive strength of 70 and 68 MPa, respectively. While the MK aggregate had slightly higher abrasion resistance than that of the LS, the surface of the LS aggregate was rough and more angular than that of the MK, whose texture was somewhat smooth. The HWA achieved the highest compressive strength of 81 MPa, owing to its higher mechanical characteristics. The failure mechanism for the concrete produced using LS, MK, and HWA was controlled by the mechanical properties of coarse aggregate. The cracks go through the aggregates instead of moving through the ITZ due to the inherently stronger matrix in the case of Mix 2. As for the RCA-1, there was a slight improvement of 10% in compressive strength. This can be justified because of the adhered mortar, which introduced an additional phase to the composite phases. It is hypothesized that the adhered mortar still had an effect even though the recycled aggregate was obtained from HSC. Ideally, if RCA-1 had no adhered mortar, it would behave as LS since the HSC specimen from which RCA-1 aggregate was acquired was the same as LS aggregate. The role of coarse aggregate types and their contribution to the concrete compressive strength can be noticed for Mix 2, as presented in On the other hand, if the adhered mortar is very porous and has a higher absorption rate, it would typically act as RCA-2. Therefore, the characteristics of adhered mortar would generally dictate the performance of concrete. Even if the RCAs were procured from HSC, micro-cracking would initiate at the interface between the new ITZ and the old ITZ. The micro-cracks would then propagate until failure. The performance of RCA-2 was improved when the mix was rich . However, this improvement was limited because of the low quality of adhered mortar. It should be noted that the coarse aggregate used in RCA-2 was obtained from low-quality concrete of a strength of about 20 MPa. The strength limitation was attributed to the properties of the RCA-2 aggregate, which had low abrasion resistance, high water absorption, and porous adhered mortar. While the compressive strength of the LWA concrete specimen was approximately doubled in Mix 2 compared to Mix 1 due to the richness of the concrete mixture, the LWA had the lowest compressive strength of 40 MPa. Unlike Mix 1, the bonding between the LWA and matrix was greatly improved, and hence the axial stresses were redistributed, and the interface could carry the higher compressive stress. As long as the tensile strength of LWA was reached, which typically occurred early for LWAs as opposed to NWAs, the failure occurred without substantial cracking in the matrix. At this stage, the concrete reached its ceiling strength, and no further gain in strength could be attained even with the rich mix (Mix 2). The splitting tensile strength of concrete specimen tests was carried out in accordance with the ASTM C496/C496M-17  for Mix The uniaxial compressive stress–strain curves for Mix 1 and Mix 2 are displayed in The strain at peak stress is the main parameter of the stress–strain response of concrete. The strain at peak stress for Mix 1 and Mix 2 is shown in The modulus of elasticity obtained in accordance with the ASTM C469  for Mix The experimentally measured elastic modulus was compared with the predictive expressions available in the literature and adopted by various design codes to assess their validity for predicting the modulus of elasticity of concrete made using different coarse aggregate types. 3. Moreover, there were no correction factors to account for the unit weight of lightweight concrete or the toughness of LWA. For instance, the elastic modulus of the LWA concrete of Mix 1 and Mix 2 predicted by the CEB-FIP-90 model [oK, which was taken as 20 kN/m3 for normal weight concrete). It should be noted that a range of oK values is provided, but the appropriate selection of a oK value is entirely left to the experience of designers. The ACI-318-19 [It can be seen from 90 model  compared90 model  formula 90 model  equationI-318-19  overestiThe density-based formula of ACI-318-19  generallWhile the modulus of elasticity computed by AS-3600-09  appearedThe quality of the RCA is typically expressed in terms of water absorption, abrasion resistance, adhered mortar, and quality of original concrete from which RCA was obtained. Therefore, a valid model for concrete produced using RCA should consider these parameters in future studies.Water absorption, which represents the maximum value of water ingress, is considered an indirect measurement of water-accessible porosity and has been used to give some indication of the permeability and durability of concrete. The water absorption test of concrete specimens was carried out as per the ASTM C1585-20  for Mix The study is expected to serve as a benchmark for comparing the performance of different types of coarse aggregates covering a broad range of mineralogy and densities. The test results indicated that HSC (compressive strength > 40 MPa) could be produced using rich mix even with the LWA and poor-quality recycled concrete-based normal weight aggregate RCA-2. Additionally, water absorption can also be considerably reduced for these highly porous aggregates. The test results are also expected to serve as a guide for optimizing the mixes using different available aggregates.3 was investigated. Compressive strength, splitting tensile strength, stress–strain relationships, and water absorption were used to assess concrete performance. To determine the coarse aggregate contribution to the overall concrete performance, lean and rich concrete mixtures (Mix 1 and Mix 2) were used. Mix 1 had a water-to-cement ratio (w/c) of 0.5 and a cement quantity of 300 kg/m3, whereas a higher quantity of cement of 500 kg/m3 and a lower ratio of w/c of 0.3 were used for Mix 2. Based on the outcomes of the experimental study results, the following conclusions can be drawn:The contribution of coarse aggregate towards the concrete strength is more pronounced for Mix 2 as the coarse aggregate characteristics controlled the failure mechanics. While the LS, MK, HWA, and RCA-1 had comparable compressive and tensile strengths for Mix 1, the elastic modulus was greatly influenced by the abrasion resistance and strength of coarse aggregates. The combined effect of reducing the ratio of w/c and increasing the quantity of cement improved (Mix 2 vs. Mix 1) the mechanical performance of concrete irrespective of the coarse aggregate type. The rate of increase in compressive strength for Mix 2 relative to Mix 1 was more pronounced than splitting tensile strength and the modulus of elasticity. The density of coarse aggregate was found to have an influence on the concrete mechanical properties. It should also be noted that the stiffer the aggregate, the more likely to enhance concrete performance.The mechanical characteristics of concrete with recycled aggregates were greatly dependent on the quality of attached mortar on the surface of coarse aggregate. However, the existence of attached mortar may have some impact on its mechanical properties.The LWA resulted in lower mechanical performance than LS, MK, HWA, and RCA-1 due to the higher volume of porosity, higher mass loss, and weaker mechanical strength of coarse aggregate. While the rich mix (Mix 2) improved the matrix and ITZ characteristics, the strength of the concrete reached a ceiling limit beyond which no further increase would be expected. The low quality of adhered mortar significantly resulted in a drop in the concrete performance. The drop in RCA-2 compressive strength compared to RCA-1 was 49% for Mix 1 and 31% for Mix 2.The experimentally measured modulus of elasticity was compared with available formulas of design codes. ACI 363 R-92 and CSA A23.3-04 were the best prediction models, followed by the density-based formulas of ACI-318-19 and AS-3600-09.Irrespective of w/c ratios, the water absorption of concrete was high for concrete whose coarse aggregates had high water absorption. 3), the modulus of elasticity of HWA concrete correlates well with the design equations of ACI 363R-92 and CSA A23.3-04. Thus, the modulus of elasticity of HWA concrete can be appropriately computed using the equations of these codes.While the density of concrete is considered an essential factor in predicting the modulus of elasticity, the mechanical characteristics of coarse aggregate also appear to have a great influence. Although a majority of design codes impose an upper limit on the density of concrete (2500 kg/mFuture research is needed to evaluate the effect of steel and synthetic fibers on the performance of concrete with recycled construction and by-product industrial waste coarse aggregates.The performance of concrete produced using various recycled construction and by-product industrial wastes, manufactured limestone, quartzite, and volcanic scoria with densities varying from 860 to 2300 kg/m


Clostridium difficile and resistant organism infection were not increased. This multi-institutional study demonstrated no difference in the rate of PJIs between patients who received extended antibiotic prophylaxis and those who did not in aseptic revision arthroplasty. The risk of C. difficile and resistant organism infection was not increased with prolonged antibiotic use.The use of extended antibiotic (EA) prophylaxis (> 24 h) remains controversial in aseptic revision arthroplasty. We sought to determine whether EA prophylaxis reduces the risk of periprosthetic joint infection (PJI) in aseptic revision hip and knee arthroplasty. A total of 2800 patients undergoing aseptic revision hip and knee arthroplasty at five institutional databases from 2008 to 2017 were evaluated. One to two nearest-neighbor propensity score matching analysis was conducted between patients who did and did not receive extended antibiotic prophylaxis. The matching elements included age, sex, body mass index, Charlson comorbidity index, hospital distribution, year of surgery, joint (hip or knee), surgical time, CRP, preoperative hemoglobin, albumin, and length of stay. The primary outcome was the development of PJI, which was assessed at 30 days, 90 days, and 1 year following revision and analyzed separately. A total of 2467 (88%) patients received EA prophylaxis, and 333 (12%) patients received standard antibiotic (SA) prophylaxis (≤ 24 h). In the propensity-matched analysis, there was no difference between patients who received EA prophylaxis and those who did not in terms of 30-day PJI , 90-day PJI  and 1- year PJI . For revision hip, the incidence of PJI was 0.2% vs 0% at 30 days (p = 0.482), 1.6% vs 1.4% at 90 days (p = 0.837), and 3.4% vs 5.1% at 1 year (p = 0.305) in the EA and SA group. For revision knee, the incidence of PJI was 0.4% vs 0.9% at 30 days (p = 0.63), 1.8% vs 3.4% at 90 days (p = 0.331), and 4.4% vs 7.8% at 1 year (p = 0.203) in the EA and SA group. A post hoc power analysis revealed an adequate sample size with a beta value of 83%. In addition, the risks of  Some literature and recent guidelines even suggest one dose of preoperative antibiotic prophylaxis before incision without any additional antibiotic prophylaxis following primary TJA postoperatively6. However, in the revision setting, the risk of infection is substantially higher than during primary TJA, with rates reported as high as 7% in most literature8. This is often because of longer operative time, more complex nature, and the unexpected positive intraoperative cultures of the revision surgery compared to primary TJA9. Therefore, up to 60% of orthopedic surgeons continue antibiotic prophylaxis more than 24 h in their practice in a recent survey10.The use of perioperative antibiotics remains one of the important practices for reducing the rate of infection following total joint arthroplasty. In primary TJA, antibiotic prophylaxis is often administered for a maximum of 24 h, as this was the maximum time allowed by previous guidelines13. However, in the revision TJA setting, the use of extended prophylactic antibiotics therapy has demonstrated conflicting results in the literature18. While some have found that prolonging antibiotic prophylaxis is a protective effect against PJI18, other studies found no association regarding a reduction in PJI17. Furthermore, the 2018 International Consensus Meeting on Musculoskeletal Infection stated that the evidence behind extended prophylactic antibiotics therapy for patients undergoing aseptic revision is limited2. Currently, we are aware of no strong evidence to suggest that extended antibiotic prophylaxis more than 24 h is beneficial for aseptic revision TJA. In addition to the conflicting literature regarding the benefits of extended antibiotics17, there is limited literature regarding the antibiotic stewardship implications and possible increase in antibiotic-related side effects such as the development of Clostridium difficile infection1 and resistant organisms19.The use of extended prophylactic antibiotics therapy in primary total hip (THA) and knee arthroplasty (TKA) has shown no decrease in the rate of periprosthetic joint infection (PJI) compared to those who received prophylaxis for 24 hThe aim of this study was to evaluate the rate of PJI and antibiotic-related complications with the administration of extended antibiotic prophylaxis (> 24 h) compared to standard antibiotic prophylaxis (≤ 24 h) following aseptic revision hip and knee arthroplasty.21 for a consecutive series of revision TJA (hip and knee) between 2008 and 2017 in Taiwan. Using the International Classification of Diseases, Ninth Revision, and 10th Revision (ICD-9 and ICD-10) procedure codes, electronic medical and operative notes were queried to identify aseptic revision TJA for a non-infective indication . Patients, who were younger than 18 years, underwent septic revision , less than 1 -year follow up after index revision surgery, and those with one or more positive intraoperative culture during revision, and those without documented post-operative antibiotic duration, were excluded.This study was approved by the Institutional Review Board (IRB) of Chang Gung Memorial Hospital, Taiwan (IRB No. 201901016B0C601) and carried out in accordance with the pertinent guidelines and regulations. Following IRB approval of the waiver for informed consent, we retrospectively reviewed the five institutional standardized electronic medical records from Chang Gung Research Database (CGRD)A total of 2800 aseptic revision cases were identified for analysis. Of those, 333 (12%) received standard antibiotic prophylaxis (≤ 24 h) and 2467 (88%) received extended antibiotic prophylaxis (> 24 h). Patient demographic factors , comorbidities , hospital distribution, joint (hip or knee), year of procedure, American Society of Anesthesiologists (ASA), the use of antimicrobial incise drape, component revision , surgeon volume (high or low), surgical time, blood transfusion, and length of stay (LOS) were queried. Preoperative lab data, including erythrocyte sedimentation (ESR), C-reactive protein (CRP), hemoglobin, platelet, creatine, and albumin were also queried within 2 weeks before revision surgery. Serological markers were obtained in all revisions followed by aspiration if ESR and/or CRP were high. The infection organisms were also recorded from cultures taken preoperatively and intraoperatively. Because the cutoffs for revision TJA volume are not defined in the literature, we considered low volume as less than 1 revision case per month and high volume as 1 or more cases per month.15. Briefly, one gram of first-generation cephalosporin was prescribed within 1 h of skin incision. If patients exceeded 80 kg, 2 g of preoperative antibiotics were given. The antibiotics were re-dosed when the surgical time was longer than 4 h or if intraoperative blood loss exceeded 1500 ml. For patients who demonstrated an anaphylactic allergy to cephalosporin or penicillin, 1 g of clindamycin or vancomycin was administered. After aseptic revision surgery, patients received the standard antibiotic prophylaxis for an overall duration of 24 h. However, the extension of post-operative antibiotic prophylaxis for more than 24 h was based on the surgeon's discretion.All patients who underwent aseptic revision hip and knee arthroplasty received standard antibiotic prophylaxis protocol according to the respective policy of the institution22. The operative reports were then manually reviewed to confirm that surgery had been performed for PJI. The secondary outcome was the occurrence of resistant organisms and C. difficile infection.The primary outcome was the development of PJI at the following time points: within 30 days, 90 days, and 1 year after index aseptic revision surgery. PJI was defined using the definition from the 2013 ICMt-tests and categorical variables were analyzed using the chi-square test or Fisher’s exact test. Missing data were filled by five imputations using multiple imputations by chained equations23. To provide the association of extended prophylactic antibiotic prophylaxis and PJI, covariates associated with PJI at p < 0.2 in the univariate analysis were added to a second multivariate logistic regression model. To mitigate the baseline differences between the two groups, a 1:2 ratio propensity score matching (PSM) technique was performed. We fitted a logistic regression model to estimate the propensity score using the following variables: age, sex, BMI, CCI, hospital distribution, year of surgery, joint (hip or knee), surgical time, CRP, and preoperative Hb, albumin and LOS. A nearest-neighbor matching procedure was applied, with the restriction of a caliper width of 0.25 units of each other. The difference of primary outcome between the matched group was calculated with conditional logistic regression. Post hoc power analysis using the difference between two dependent means (matched pairs) was performed to compare the PJI at 1 year in the matched group to determine the likelihood of a type 2 error (missing a significant difference between the standard and extended antibiotic groups when one in fact exists). Based on current information (beta = 0.83), the sample size was adequately powered at 83% to detect no difference between the treatment groups. A forest plot presented an adjusted odds ratio (OR) with 95% confidence interval (CI). The Kaplan–Meier survival curve was analyzed to calculate the cumulative incidence of PJI in two groups of the matched cohort. The group difference was assessed using the log-rank test. A p-value < 0.05 was considered statistically significant. All analyses were assessed using SPSS Statistics  and NCSS Statistical Software .Statistical analysis was performed for continuous variables using Student The mean duration of antibiotic use was 3.9 ± 1.8 days  in the extended antibiotic (EA) group. Compared to patients in the standard antibiotic (SA) prophylaxis group, those with EA prophylaxis were hip predominant  and with a longer surgical time , 1.7% vs 2.1% at 90 days (p = 0.657), and 3.7% vs 6.0% at 1 year (p = 0.051) in the EA and SA group , 90-day PJI , and 1-year PJI  between the EA and SA group. Results from a regression analysis of the PSM cohort showed no significant association between 30-day PJI and EA prophylaxis . The 90-day PJI  and 1-year PJI  risk remained non-significant in patients with EA prophylaxis , 1.5% vs 1.4% at 90 days (p = 1.0), and 3.2% vs 5.1% at 1 year (p = 0.16) in the EA and SA group. For revision knee, the incidence of PJI was 0.7% vs 0.9% at 30 days (p = 0.59), 2.3% vs 3.4% at 90 days (p = 0.52), and 5.0% vs 7.8% at 1 year (p = 0.26) in the EA and SA group. When stratified by hips and knees in the matched cohort, the incidence of PJI remained with no statistical difference between the two groups .In patients who developed PJI within 1 year, there were no significant differences in the infecting organisms between the 2 groups Table . The incC. difficile infection and no differences in the infecting organisms, including resistant organisms. There is limited evidence to support extended antibiotic prophylaxis for patients undergoing aseptic revision hip and knee surgery in the published literature. Our multicenter study, with a larger sample size, statistical methodology, and adequate follow-up, improves the evidence on the previous literature.The results of the present study demonstrate no difference in 30-day, 90-day, and 1-year PJI between patients who received extended antibiotic prophylaxis and those who received routine antibiotic prophylaxis (maximum 24 h). This was present even after controlling for potential confounders with multivariate logistic analysis and PSM. Among those who received extended antibiotic prophylaxis, we found no increased rates of 14. Bukowski et al. demonstrated that extended antibiotic prophylaxis with a mean duration of 11 days was associated with a sevenfold decreased risk of any infection at 90 days compared to those without extended antibiotic prophylaxis after aseptic revision TKA 18. However, studies from Kuo et al. demonstrated that extended antibiotic prophylaxis have shown no added benefit on the risk reduction of 5- year PJI in aseptic revision knee 15 and 1-year PJI in aseptic revision hip 16. Recently, Villa et al. reported the incidences of PJI rate were not significantly different in the EA group (2.2%) versus in the SA group (3.5%) after aseptic total hip or knee arthroplasty revisions in a minimum follow-up of 1 year among 86% of their cases17. Our study evaluated three different time points  of PJI and revealed that EA prophylaxis did not positively affect any evaluation time point compared to those with SA prophylaxis. Although a longer follow-up is better to avoid bias in the results, prior studies have shown that 1-year follow-up is reliable because most subsequent infections occur within 1 year after revision arthroplasty24. Besides, the effect of reduction of PJI with extended antibiotics prophylaxis did not continue at 1 year and 5 years18. Based on these reasons, we did not follow up on these patients for more than 2 years after aseptic revision.The current literature is mixed regarding the utility of extended antibiotic prophylaxis for reducing PJI in the setting of aseptic revision TJA. Claret et al. reported prolonged post-operative antibiotic treatment up to 5 days was marginal significantly associated with a lower rate of 90-day PJI  after aseptic revision knee arthroplasty25. Furthermore, after two-stage exchange arthroplasty for PJI, chronic suppression with extended antibiotic prophylaxis has demonstrated a clinically meaningful reduction in the infection and treatment failure rate29. However, we could not demonstrate the utility of extended antibiotic prophylaxis in aseptic revision TJA, unlike the studies in high-risk primary TJA or two-stage exchange arthroplasty. Studies have demonstrated an unexpected positive intraoperative culture (PIOC) is associated with the risk of subsequent PJI in the presumed aseptic knee and hip revisions32. The prevalence of unexpected PIOC in presumed aseptic revision ranges from 7.9 to 28%33, leading to the duration of extended antibiotics. In a large multicenter cohort evaluating the outcome of PIOC, the failure rate was 8.4% after an antimicrobial treatment for a median time of 56 days (IQR 42–90)34. The duration of antibiotic use for PJI treatment usually takes 6–12 weeks35. However, our study initially excluded patients with one or more positive intraoperative cultures during revision and the mean duration of antibiotic use was 3.9 ± 1.8 days  in the EA group. Therefore, we could not evaluate the extended antibiotics' role in patients with PIOC.In the primary TJA literature, recent literature suggests that extended antibiotic prophylaxis provides some benefit. Inabathula et al. demonstrated that patients with 1 week of oral antibiotics were 5 times and 4 times less likely to develop 90-day PJI in high-risk patients than those who did not take antibiotics postoperatively in primary total knee arthroplasty and total hip arthroplasty, respectivelyClostridium difficile infection36. The incidence of C. difficile infection is estimated to range from 0.4% after revision TKA37 to 1.7% after revision THA38. The incidence rates of C. difficile infection increase gradually from 1.6 to 2.1 times following 1–3 to 7–11 days of antibiotic exposure compared to those without prior antibiotic exposure39. The overall incidence of C. difficile infection in our study was 0.25%, which was similar to prior studies38. Although C. difficile infection is an uncommon complication following revision TJA, it can increase hospital stay, costs, and in-hospital mortality following revision surgery38. Surgeons should pay attention to high-risk patients and manage perioperative antibiotics judiciously.Long-term antibiotics utilization increases antibiotic resistance and Staphylococcus aureus. Third, our database did not have socioeconomic status and education level, which has shown to be associated with PJI. Finally, we did not perform synovial fluid and histopathologic analysis during the revision in this study, and the diagnosis of aseptic revision was using ICD code rather than standard criteria (like ICM). This could under-diagnose septic revision in presumed aseptic revision and affect the antibiotic duration and the outcome.Our study has several limitations that should be considered. First, the study was retrospective and non-randomized, which introduced the possibility of selection bias. For example, a higher CRP level was observed in the EA group, and surgeons may lead towards extended antibiotic use after revision surgery. Besides, CCI was calculated as a numerical variable based on the ICD diagnosis codes to represent comorbidity. Therefore, a lower CCI distribution was found in the EA group. Given that the duration of antibiotics administered was based on the surgeon's discretion, the comorbidities and complexity of the surgery may have influenced this decision. However, we utilized propensity-score matching analysis and multiple logistic regression to control for possible confounding factors. Besides, a post hoc power analysis revealed a beta value of 83%, indicating the sample size is adequate, and the likelihood of a type 2 error is low. Moreover, the reason for a surgeon selecting extended antibiotic prophylaxis was not recorded. Second, we could not control for factors that may have influenced the use of extended antibiotic prophylaxis, such as a positive nasal colonization screening for methicillin-resistant Extended antibiotic prophylaxis may not reduce the PJI rate up to 1 year following aseptic revision TJA. Efforts are needed with evidence-based approaches regarding the duration of antibiotic prophylaxis. This supports current and previous guidelines that do not recommend extended antibiotic prophylaxis.