Additionally, the transfer length of the aramid fiber reinforced polymer (AFRP) depends on its surface conditions. Therefore, new coefficients αt = 1.5 and αt = 4.0 are also proposed for the transfer lengths of smooth braided and sanded and rough AFRP bars, respectively. Furthermore, the proposed coefficients αt = 2.6, αt = 1.9, and αt = 4.8 found in the literature were validated with the analysis of a larger database of the transfer lengths of glass fiber-reinforced polymer (GFRP) bars, carbon fiber-reinforced polymer (CFRP) bars, and gradually released CFCC strands, respectively. Moreover, the main existing theoretical models are presented, and the comparison of theoretical and experimental transfer length results is discussed. However, the low number of specimens prestressed with basalt fiber-reinforced polymer (BFRP) bars prevented the deeper analysis of the results. the analysis of the transfer length and the proposed new values of the coefficient αt provides possibilities for adapting it to design codes for engineering applications and performing additional research that fills the missing gaps in the field.The main aim of this paper is to provide a broader analysis of the transfer lengths of different types of fiber-reinforced polymers (FRPs) and to provide corrections to the existing theoretical models. Therefore, this paper presents a description of the main factors that influence the transfer lengths of different types of FRPs based on experimental results found in the literature. A database of more than 300 specimens was compiled with the results of the transfer lengths of different FRPs and the main influencing parameters. The analysis of the database results showed that the transfer length of the carbon fiber composite cable (CFCC) strands depends on the type of prestressed reinforcement release. Therefore, in this article, the new coefficient α There has been increasing concern about the durability of prestressed concrete structures due to the corrosion of prestressed steel strands, especially in corrosive environments such as parking garages, bridges, marine structures, and railway sleepers ,2,3. SteFRP consists of strong glass, carbon, aramid, and basalt fibers embedded in a resin matrix. Hybrid fiber reinforced polymer (HFRP) combines CFRP and GFRP ,7. The qFRPs have additional important properties that make them particularly attractive for prestressed concrete applications: high strength, which is similar to or greater than that of steel and low modulus of elasticity, which results in lower concrete prestress losses due to concrete creep and shrinkage as well as the relaxation of the prestressing element.The major difficulty in using FRP reinforcement for prestressing is that anchorage systems require greater attention than those for steel strands. Therefore, three types of anchorage systems are developed for FRP reinforcement: mechanical, bonded, and composite .The mechanical anchorage of reinforcement consisting of a steel barrel and wedges is ensured by friction between the reinforcement surface and the inner conical anchorage surface. Therefore, compressive stresses appear perpendicular to the reinforcement. However, FRP is an anisotropic material that has weak material properties perpendicular to the fibers. Therefore, practitioners suggest enhancing the mechanical anchorage of the FRP reinforcement using a small slope angle between the inner surface of the barrel and the outer surface of the wedges, the rounded edges of the wedges, and a soft metal sleeve  around the FRP. Other mechanical anchorages were described in ,15 such The bonded-type anchorage consists of a steel barrel with a bonding material (cementitious or resin) surrounding the FRP bar. The inner part of the barrel can have three different shapes: straight; conical with decreased length but larger diameter; or straight and conical with increased length and similar diameter with the purpose of relieving the stress concentration. The bonded-type anchorage depends on the bonding force between the CFRP cable and the bonding material to balance the tension of the cable. The performance of the bonded-type anchorage is mainly influenced by the dimensions and configuration of the steel barrel, the material type and surface condition of the FRP, and the properties of the bonding material. The main drawbacks are a large size, long curing time, creep of the bonding material, sensitivity to moisture, and high temperature.The composite anchorage takes advantage of mechanical and bonded-type anchorage. In , the strThe use of FRP reinforcement in prestressed concrete structures is highly dependent on the reliability of the reinforcement anchorage zone. That is, the behavior of concrete members is mainly dependent on the bond between reinforcement and concrete ,22,23. IIn pretensioned members, the length from the end of the member where the tendon stress is zero to the point along the tendon where the prestress is fully effective is called the transfer length . Ref. 11 definedOne of the most important factors that affect the transfer length of prestressed reinforcement is the Hoyer effect, which is caused by the swelling of the strand in the transfer zone after release as a result of the Poisson ratio. During the transfer, the induced confining stresses normal to the tendon enhance the bond strength at the interface, as the lateral deformation is resisted by the surrounding concrete. Enhancement of the bond caused by the Hoyer effect is directly related to the strength of the concrete and the coefficient of friction between the two materials. Additionally, according to , the disKnowledge of the transfer length is essential to maintaining the integrity of the structure and to preventing the bond slip failure of the member. Additionally, an accurate estimate of the transfer length is important for checking the stress limit at the serviceability limit state, determining the actual bond stress in the anchorage zone of the pretensioned reinforcement, and designing the shear of the prestressed members. The underestimation of the transfer length leads to unconservative shear calculations, while overestimation leads to unconservative stress calculations at the serviceability limit state.The simulation of the anchorage zone of FRP reinforcement introducing the finite element method (FEM) allows for performing a deeper analysis of the transfer length results that are difficult to measure in real experimental research. The simulation of the transfer lengths of BFRP , CFCC, aIn the last 30 years, numerous experimental researchers have investigated the transfer lengths of prestressed FRP. The transfer length is a function of several factors that depend on the properties of both the prestressing reinforcement and the concrete. Therefore, many studies were performed to investigate the influence of concrete compressive strength ,37,38,39The transfer length is an important parameter for the anchorage zone of prestressed reinforcement. In addition, it depends on various mechanical and geometric properties of the material. Therefore, this section presents an overview of the influence of different parameters on the transfer length of different prestressed FRP reinforcements . Unfortunately, only a few studies on the transfer length of BFRP bars were found in the literature ,55,56. Tci.min) and higher (fci.max) concrete strength correspond to higher (Lt.max) and lower (Lt.min) transfer length, respectively.Many authors investigated the influence of concrete compressive strength at the time of reinforcement release on the transfer length of concrete specimens pretensioned with different types of FRP reinforcement. Zou  concludeThe authors of ,37 conclThe FEM model of Motwani and Laskar  showed tBased on ,38,39, iAccording to pi/fpu) of different types of FRPs with the transfer length instead of the initial stresses (fpi). pi/fpu (min)) and higher (fpi/fpu (max)) prestress levels correspond to the lower (Lt.min) and higher (Lt.max) transfer lengths, respectively.The FRP reinforcements for prestressed concrete members can have different tensile strengths and initial stresses. Therefore, it is better to compare the ratios between initial stresses and tensile strength  and higher (Ømax) reinforcement diameters correspond to the lower (Lt.min) and higher (Lt.max) transfer lengths, respectively.Several authors have investigated the influence of reinforcement diameter on the transfer length of pretensioned FRP reinforcement. Domenico and colleagues ,30 and MNanni and colleagues ,38 calcuIn ,37, it wThe FEM model of Motwani and Laskar  showed tThe results for the influence of reinforcement diameter on the transfer length of pretensioned CFRP, CFCC, AFRP, and GFRP reinforcement showed that it is generally consistent with the literature and that the transfer length is directly proportional to the diameter of the prestressed FRP reinforcement. However, expressing the transfer length in terms of the bar diameter only can result in inaccurate results, as it also depends on the prestressing level and the concrete compressive strength.The effect of concrete cover is important for the durability of prestressed concrete structures. However, the FRP reinforcement covers this aspect. Therefore, a sufficient concrete cover is more relevant to controlling concrete splitting during the release of pretensioned reinforcement. Additionally, it is more relevant to analyze the influence of concrete cover on the cracking of the anchorage zone and the transfer length of the FRP reinforcement through the ratio between the concrete cover and the reinforcement diameter (c/Ø).In ,30, it wTaerwe and Pallemans  calculatKhin et al.  performeMotwani and Laskar  performeThe small concrete cover could lead to the splitting of the concrete at transfer due to the insufficient confinement of the concrete. Therefore, the additional confinement of the concrete can reduce the risk of splitting the concrete during reinforcement release.As stated in the previous section, additional concrete confinement can reduce the risk of concrete splitting during the release of pretensioned FRP reinforcement and therefore have a positive effect on the transfer length. Several authors have investigated the different types of concrete confinement at the anchorage zone of pretensioned FRP reinforcement. Saeed  tested cNanni et al.  investigDespite the low difference between prestress level and concrete compressive strength, it can be stated that specimens with shear reinforcement can induce a reduction in the transfer length of CFCC strands and the CFRP Leadline bar ,32 Tabl. AdditioThe bond properties between the reinforcement and concrete are influenced by different surface roughnesses of the reinforcement. Furthermore, reinforcement surface conditions can enhance the anchorage zone behavior of pretensioned reinforcement. Ehsani et al.  investigAdditionally, in ,48, threNanni and colleagues ,38 calcuThe test results revealed that the ribbed surface of the GFRP bar ,37 and tThe test results of Khin et al.  showed tThe difference in the bond characteristics in the anchorage zone of reinforcement can be attributed to the different moduli of elasticity of different FRP reinforcements. A lower modulus of elasticity causes more longitudinal deformation during prestressing and consequently more transverse deformation due to the Poisson ratio during the release of reinforcement for the same prestress level. Higher transverse deformations of FRP reinforcement with a lower modulus of elasticity improve bond strength at the transfer zone due to the lateral expansion of the bar, creating a wedge action known as the Hoyer effect. According to ,52, the Zou  calculatEhsani et al.  calculatLu et al. ,54 calcuSince the modulus of elasticity of FRPs is generally less than that of steel, the transfer length of most FRPs is less than that of steel .Different transfer lengths may appear at two ends of the pretensioned concrete member. This can be attributed to more than one specimen prestressed with the same reinforcement. In this case, one end of the reinforcement is prestressed (Live end), while the other at the same time is fixed to the rigid support (Dead end). During the release of prestressed reinforcement, differences can appear in the transfer lengths of different FRP reinforcements.In , the meaThe experimental results provided in ,60,61 shThe results of Crossett et al.  showed tThe transfer of the prestressing force to the concrete during the release of reinforcement is a short-term effect. However, the prestressed concrete member is intended for long-term operation. After the release of the prestressed reinforcement, the concrete members are affected by many long-term effects  that can influence the anchorage zone and transfer length of the prestressed concrete member.Zou  stated tAccording to Zou , there iGrace  showed tSoudki et al.  calculatLu et al.  also detMahmoud et al. ,32 deterIn ,52, it wAccording to , the traIt is suggested that at the ends of the member, the concrete strain increased with an increase in time, mainly due to the shrinkage of the concrete . Away frpi and Ø) influencing the transfer length. Additionally, with an empirical coefficient (20.7) which is based on the large database of transfer length results, Equation (5) was developed for steel strands. Mitchell et al. [p) of the reinforcement and proposes an empirical coefficient CT = 80 for the CFCC strand. Additionally, it calculates t dependent on the type of FRP reinforcement. Therefore, the coefficient αt can be calibrated for different types of FRP reinforcement  with different surface conditions. Additionally, it presents the concrete strength as p).Equation (5) provided in  is evalul et al.  suggestel et al.  equationl et al.  replacesver, Zou  stated tver, Zou ,65, the ver, Zou ,66, the ver, Zou , who staver, Zou ,32, the ver, Zou ,12. The vided in ,68,69. Avided in  proposedt for different types of FRP reinforcement , modulus of elasticity (Ep), tensile strength (fpu), initial stresses (fpi) of reinforcement, the ratio between initial stresses and tensile strength of reinforcement (fpi/fpu), concrete compressive strength at transfer (fci), average transfer length (Lt) of pretensioned reinforcement.A literature review of the experimental results of the transfer lengths of different types of pretensioned FRP reinforcement was performed. In total, 318 specimens were found. t) of different types of pretensioned FRP reinforcement under the influence of different experimental parameters: concrete compressive strength at transfer (fci), the ratio between initial stress in pretensioned reinforcement, and tensile strength (fpi/fpu), reinforcement diameter (Ø), concrete protective cover (c), the ratio between the concrete cover and reinforcement diameter (c/Ø) and modulus of elasticity of FRP reinforcement (Ep). The ranges of influential parameters  presented in The experimental results for the transfer length sof different types of FRP reinforcement  found in the literature are analyzed in this chapter. The results show that the transfer lengths of different types of pretensioned FRP reinforcement decrease with increasing concrete compressive strength at the time of pretensioned reinforcement release a. In genpi/fpu ratio  increase with increasing diameter of reinforcement c. For thThe transfer lengths of different types of pretensioned FRP reinforcement  increase with an increase in concrete protective cover d. The reAs in the case of reinforcement diameter c and conA comparison of the transfer length and modulus of elasticity of different types of FRP reinforcement shows that in most cases, the transfer length of FRP reinforcement  increases with increasing modulus of elasticity f. In 3636,51,52,pi/fpu, Ø, c, c/Ø, and Ep) with respect to the transfer length are opposite compared to GFRP, CFCC, CFRP, and AFRP reinforcements. The results of only six specimens pretensioned with BFRP reinforcement are presented in the database of transfer length  influencing the transfer length is presented in The prestress force can be transferred to the concrete in two ways: gradually or suddenly. Therefore, the influence of the type of release of CFCC reinforcement  on the transfer length and parameters (fpi), reinforcement diameter (Ø), and concrete compressive strength at transfer (fci). Therefore, for a better analysis of the results based on Equation (1), a graphical comparison of the transfer length of different FRP reinforcements  and t.Previous analysis of the results  showed tt is 2.58 with the standard deviation (STD) of 0.33 and the coefficient of variation (COV) of 12.8%  and αt = 2.42 with STD = 0.67, COV = 27.7%, and R2 = 0.94 for sudden transfer of prestress  and αt = 3.99 with STD = 1.70, COV = 42.7%, and R2 = 0.86 for sanded and rough AFRP bars  on the transfer length could be the topic of future research.2 = 0.68   with STD = 0.32 and COV = 21.7% and [t,teor/Lt.exp = 0.62) with STD = 0.19 and COV = 31.2%. The models of Mitchell [t = 2.6) show similar results with Lt,teor/Lt.exp = 1.05, STD = 0.13, COV = 12.1% and with Lt,teor/Lt.exp = 1.0 STD = 0.13, COV = 12.6%, respectively. The models presented by [From 1.7% and  underestMitchell  and Mahmented by  are in tt,teor/Lt.exp = 0.30) with STD = 0.12, COV = 40.2%. Equation (6) also underestimates the experimental results with Lt,teor/Lt.exp = 0.82, STD = 0.28, COV = 34%, but Equation (5) overestimates the results with Lt,teor/Lt.exp = 1.17, STD = 0.55, COV = 47.2%. Despite the relatively high variation of the results the most accurate prediction of experimental results was received by Equation (1) (αt = 1.9) with Lt,teor/Lt.exp = 1.01, STD = 0.33, COV = 32.5%.In the case of CFRP reinforcement b, Equatit,teor/Lt.exp = 2.31, STD = 0.81, COV = 35%  in predicting the transfer length for the gradual transfer of prestress  provides a very accurate prediction of the transfer length for gradual (αt = 5.0) (t = 2.4)  coincide with the results of Equation (1) for sudden transfer of prestress. It shows that the combination of empirical coefficient (20.7) and t = 2.4 and OV = 35% a. Additi = 21.3% b. Howeve = 21.3% a and sud = 21.3% b prestrerestress a, Equatirestress b with Ltt = 5.0) a and sudt = 2.4) b types ot,teor/Lt.exp = 0.3, STD = 0.15, COV = 51.8%; Lt,teor/Lt.exp = 0.8, STD = 0.23, COV = 30.1%; and Lt,teor/Lt.exp = 0.6, STD = 0.21, COV = 34.3%, respectively (t = 1.5) is closer to the experimental results with Lt,teor/Lt.exp = 1.02, STD = 0.36, COV = 35.8%, and more values are on the safe side  and (6) significantly overestimate the transfer length with Lt,teor/Lt.exp = 2.9, STD = 1.4, COV = 48.9% and Lt,teor/Lt.exp = 1.8, STD = 0.77, COV = 42.3%, respectively. A similar trend can be observed for all results from the database (without grouping according to surface conditions)  for AFRP reinforcement with sanded and rough surfaces (αt = 4.0) (t = 2.9)  c calculat = 4.0) b and allt = 2.9) c with Ltt (used in Equation (1)) were proposed by other authors  of different types of FRP reinforcement for different values of αt is presented in The comparison of the ratio between theoretical and experimental results of the transfer length  and a similar inbound 61%. The αt = 4.0 proposed for the FRP reinforcement with sanded and rough surface shows a higher variation in the theoretical results (42%) compared with the results of the smooth braided AFRP bars (35%), but less than the results for all AFRP reinforcement with αt = 2.9. As the results of the sanded and rough AFRP bars provide about 49% inbound values, the amount of overestimated (OV = 20) and underestimated (UV = 19) values is similar.The proposed αd values e. HoweveThe analysis of the literature showed that the concrete compressive strength has a greater influence on the transfer lengths of CFRP and CFCC reinforcement, and the prestress level has a greater effect on the transfer lengths of AFRP and GFRP reinforcement. Additionally, most transfer lengths of FRP reinforcements  are directly proportional to prestress level, reinforcement diameter, and modulus of elasticity of reinforcement and inversely proportional to concrete strength.The minimum concrete cover to avoid concrete splitting in the anchorage zone of the FRP reinforcement is 1.9·Ø for the CFRP bar and 2.8·Ø for the AFRP and GFRP bars. Additional research is needed for the CFCC strand, but the sufficient concrete cover for the CFCC strand is 4·Ø. Therefore, the concrete cover of 3.5·Ø and above does not have a significant influence on the transfer length of FRP reinforcement.t for different types of FRP reinforcement. The results of this article confirmed that the coefficients αt = 2.6, αt = 1.9, and αt = 4.8 proposed by other authors are suitable for predicting the transfer length of the GFRP bars, CFRP bars, and CFCC strands , respectively.Equation (1) was determined to give the most accurate prediction of the transfer length by applying different values of coefficient αt = 2.4 was proposed to determine the transfer length of the suddenly released CFCC strand based on a collected database of the transfer length results. The proposed value is valid for a concrete strength of 37–48 MPa, prestress level 30–65%, and reinforcement diameter of 12.5–15.2 mm.The analysis of the database revealed that the transfer length of CFCC strands is highly dependent on the type of prestress transfer. Therefore, a new coefficient αt = 1.5 for smooth braided AFRP bars  and αt = 4.0 for sanded and rough AFRP bars .It was determined that there is a correlation between the surface conditions and the transfer length of AFRP bars. Despite the relatively high variation in the results, in this article, new values are proposed: αt provides possibilities for adapting it to design codes for engineering applications and performing additional research that fills the missing gaps in the field. In particular, additional research is needed on the effects of shear reinforcement, release type of the prestressed GFRP and AFRP reinforcements, and the surface conditions of the AFRP and CFRP bars. Furthermore, the influence of prestressing transfer method and other important parameters  on the transfer length of the BFRP reinforcement could be a subject of future research.The analysis of the transfer length and the new values proposed for the coefficient αA large database of the transfer lengths of different FRP reinforcements was collected, and the analysis of experimental results, description of theoretical models, and comparison of experimental and theoretical results led to the following conclusions and proposals:


Antibiotics have become a mainstay of healthcare in the past century due to their activity against pathogens. This manuscript reviews the impact of antibiotic use on the intestinal microbiota in the context of mass drug administration (MDA). The importance of the gut microbiota to human metabolism and physiology is now well established, and antibiotic exposure may impact host health via collateral effects on the microbiota and its functions. To gain further insight into how gut microbiota respond to antibiotic perturbation and the implications for public health, factors that influence the impact of antibiotic exposure on the microbiota, potential health outcomes of antibiotic-induced microbiota alterations, and strategies that have the potential to ameliorate these wider antibiotic-associated microbiota perturbations are also reviewed. Greater accessibility to antimicrobials has contributed to an estimated 65% increase in human antibiotic consumption from 2000 to 2015 , 4. NextVirtually every niche of the human body harbors diverse microbial communities , even siThe prevailing view holds that microbial colonization of the gastrointestinal tract begins at birth in full-term infants, after which the microbiome progresses through a succession of identifiable shifts in composition . ImmediaThe major initial sources of bacteria for colonization of the infant gut are the mother’s vaginal, fecal, and skin microbiota and the immediate environment , 26, 27.Bifidobacterium spp. are the most abundant bacteria . Fo. Fo79]. elopment  through obacilli .Bifidobacterium.Overall, these studies suggest reduced α-diversity in infant microbiota associated with maternal exposure to IAP and consistent compositional changes, including a higher relative abundance of Enterobacteriaceae and lower abundance of Recent reviews reported few studies that investigated factors which determine the impact of antibiotic exposure on microbiota composition , 82, 83.Bacteroides, Bifidobacterium, Clostridium), while other macrolides were associated with altered abundance of 2–6 genera . Beta-lactams, such as ampicillin and cephalosporin for example, were associated with changes in abundance of 8 and 12 genera, respectively, spanning a phylogenetically diverse range of phyla  that differed from other beta-lactams [A recent review of 55 human studies summarized changes in microbiota composition that were significantly associated with 68 different antibiotics grouped into 22 antibiotic classes [Bacteroides spp. and Bifidobacterium spp. grown in anaerobic culture [Bacteroides spp. and Clostridium perfringens, but its effect on Bifidobacterium spp. depended on bacterial growth rates [Clostridium difficile, on which they had no impact [These taxon-specific effects of different antibiotics are corroborated by culture experiments. For example, metronidazole strongly reduced the growth of  culture , while ath rates . A more th rates . For insth rates . Macrolio impact . Howevero impact . The impNevertheless, suppression of microbes that are susceptible to an antibiotic’s mechanism of action can disrupt colonization resistance and open an ecological niche for opportunistic pathogenic bacteria, increasing the host’s susceptibility to post-antibiotic infection , 87. AltBacteroides.Considering the variation in antibiotic effects by antibiotic class and bacterial clade, the initial composition of the microbiota may also determine the short and long-term effects of antibiotics. Analyses of data from five adult cohorts determined that the abundance of specific species with an increased functional capacity to degrade complex carbohydrates, particularly host mucins, accurately predicted microbiota recovery from antibiotic-associated reductions in α-diversity . The basPrevotella and Faecalibacterium enriched or a Bacteroides and Parabacteroides enriched human fecal microbiome, and both were treated with a 7-day course of amoxicillin-clavulanate [Bacteroides group was more resilient to antibiotic exposure after 18 days [Bacteroides spp. can facilitate enteric infection, which has been demonstrated for C. difficile, C. rodentium, and S. typhimurium in mouse models, and further community-level investigation in different age groups is required to translate the findings to human populations [This finding in humans is supported by evidence from germ-free mice. Two groups were colonized with either a vulanate . α-Diver 18 days . Howeverulations , 87, 100Bacteroides established a new equilibrium at the same or higher relative abundance within 2 weeks [Bacteroides genus and a subset of bacteria belonging to the family Lachnospiraceae increased during treatment and required 42 days to return to pre-antibiotic levels. By contrast, a group of bacteria in the family Ruminococcaceae was reduced to undetectable levels after a single treatment with no recovery after ten months [Two comprehensive analyses provide further insights into the temporal dynamics of microbiota response and recovery from antibiotic exposure , 102. Bon months . A seconn months .Although these studies included very few individuals, and may represent inter-individual heterogeneity at best, they explored a richly sampled time-series of microbiota abundance data, and their findings are supported by experimental work. In one such experiment, two groups of mice were assigned to either specific-pathogen free conditions or general animal conditions with exposure to soil, and both were treated with a 2-week course of vancomycin and streptomycin . Soil-exA third analysis used a separate dataset from a small, randomized perturbation experiment of adults to quantify the recovery time of the gut microbiota over a one-year period after exposure to different antibiotics . RecoverLachnospiraceae and Enterobacteriaceae [Lachnospiraceae is not clear, the presence of members of this family in the early gut microbiota has been associated with reduced risk of asthma [Enterobacteriaceae are the first colonizers of the infant gut. Although microbiota α-diversity did largely recover by one year of age, the impact on host health of reductions in these early colonizers due to neonatal exposure to antibiotics requires careful investigation.Long-term effects of antibiotic exposure have also been investigated in infants , 106. Ref asthma , and EntIn another study, infants treated with antibiotics from birth to three years had lower species α-diversity compared to infants who had no antibiotic-exposure during that time, but the reduction in α-diversity was modest and was only evident for year one . At the Altogether, these analyses suggest that microbiota recovery from antibiotic-exposure may depend on the antibiotic used, the initial microbiota composition and the specific bacterial taxa affected by the drug. Furthermore, longitudinal observational studies provide additional evidence that recolonization of the gut may potentially play a critical role in microbiome recovery from antibiotic-exposure. However, more studies are needed which are designed to test the specific hypotheses suggested by these few studies.It is important to note that recovery alone may not protect the host from potential long-term effects of antibiotic perturbations to the microbiome Fig. . EpidemiE. coli pathotypes, Shigella, Campylobacter spp.), but the prevalence of specific pathogens varies by country [Campylobacter spp. and pro-inflammatory microbiome metabolic pathways may partly explain the sustained reductions in child mortality due to diarrhea and dysentery observed in those settings [E. coli and viral infections in children were associated with increased Bifidobacterium spp. and more severe illness [Bifidobacterium longum inhibited rotavirus isolates from pediatric cases and reduced the duration of viral gastroenteritis in another study [Fifty percent or more of infants in LMICS carry at least one enteric pathogen by age 3 months and experience at least one diarrheal episode by age 24 months . The mos country , 110. Mo country  of diarrsettings –113. Gutsettings . Limitedsettings . For exa illness , but Bifer study .Bacteroides spp. after antibiotic perturbation of the gut microbiome can facilitate enteric infection, which has been demonstrated for C. difficile, C. rodentium, and S. typhimurium. [Additional evidence comes from murine models. For example, mucin foraging by imurium. , 87 Alteimurium. , 118. NeFurthermore, the increase in antibiotic resistance gene carriage by the gut microbiome that can result from MDA suggests the potential for the beneficial effects to become limited by decreased susceptibility of pathogenic bacteria. Once resistance in pathogenic organisms develop, efficacy may reverse, as has been observed for other antibiotics in high-income settings . In contAntibiotic use is associated with an increased risk of obesity. The association is greater with earlier (prior to 6 months of age) and with greater frequency of exposure –123. LowBifidobacterium spp. [Without a clear understanding of the causal mechanisms that link changes in microbiota composition to health outcomes, microbiota composition is often defined as “dysbiotic” based on associations with disease relative to healthy controls . In highium spp.  due to tium spp.  or formuium spp. , 76 infaium spp.  and incrium spp. . As suchBifidobacterium, as well as reduced α-diversity at 1 month, but greater α-diversity beyond age 12 months [Bifidobacterium genus remained decreased at 24 months [The timing of antibiotic exposure may provide further insight into context-specific effects. In a cohort of 12,422 full-term newborns in Finland, neonatal antibiotic-exposure (predominantly intravenous benzylpenicillin and gentamicin) was associated with impaired length growth among boys in the first 6 years of life. The association with growth in boys was confirmed in an independent cohort of 1707 newborns from Germany . Convers2 months . Notwith4 months .In the same study, when germ-free mice were colonized with fecal microbiomes from 1-month old antibiotic-exposed infants, male mice experienced reduced weight gain compared to mice colonized with an antibiotic-unexposed infant microbiome. However, female mice did not, corroborating the observational findings in the human cohorts . The resBacteroides spp. associated with microbiota recovery  are also associated with reduced BMI. This may be due to their increased capacity to degrade complex carbohydrates [While a causal effect of early-life antibiotic exposure on obesity is yet to be confirmed , and thehydrates . By conthydrates . Forty phydrates Lactobacillus spp., Allobaculum spp., Rikenellaceae spp., and Candidatus arthromitus [A recent study in mice demonstrated that low-dose penicillin delivered from birth elicited an increase in adiposity and exacerbated the effect of a high fat diet on increased body weight. The growth phenotype was induced in germ-free inoculated with fecal microbiota from antibiotic treated mice, showing that the altered microbiota plays a causal role . Antibiohromitus . The inchromitus . HoweverEarlier , 136 andBifidobacterium spp. and facilitate cross-feeding by other species [Lactobacillus, Enterococcus, Anaerostipes, Blautia and Roseburia within 18 days of treatment, while azithromycin alone caused an increase in the abundance of proinflammatory Streptococci up to 60 days after treatment [A few promising approaches have been suggested to mitigate the impacts of antibiotic use on the microbiome Fig. . Co-admi species . Breastf species . The ben species . In chilreatment .Co-administration of probiotics with antibiotics in adults has also shown some potential to mitigate antibiotic selection for genetic determinants of resistance . HoweverBacteroides vulgatus and Bacteroides uniformis). However, erythromycin’s impact on pathogenic bacteria  was not impacted [Escherichia coli, Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa) [Another strategy involves use of antibiotic-drug combinations to achieve more targeted species-specific effects than single antibiotic treatments. For example, one investigation screened > 1000 drugs to identify candidates that reduce the broad-spectrum activity of antibiotics without impairing their activity against relevant pathogens . The antimpacted . Anotheruginosa) . More thuginosa) .Lactobacillus gasseri showed strong inhibitory activity against common pathogens such as Streptococcus aureus and Gardnerella vaginalis, but not against commensals [Bacillus thuringiensis [Clostridium difficile without impacting microbiota composition in a fecal-culture system that models the human colon [Identifying narrow-spectrum antibiotic alternatives is another approach. The microbiome itself may be a source of such narrow-spectrum compounds. For example, investigation of 752 bacterial genomes from the human microbiome project identified a cluster of genes carried by commensal bacteria that encode thiopeptides . Lactocimmensals . Thuricingiensis . It has an colon . DevelopFinally, there may also be important microbial components in the environment that may help to prevent dysbiosis or restore physiologically important subsets of the gut microbiome during critical developmental periods , 156. IdThis is a narrative review restricted to studies of antibiotics given as part of a mass drug administration program or policy to reduce morbidity and mortality in specific at-risk target populations, rather than treatment for a specific infection. Due to current public health interest in MDA with antibiotics to reduce childhood morbidity and mortality in view of global targets, and longer-standing interest in trachoma and yaws elimination programs, I focused on antibiotics administered in these contexts. I also focused on antibiotic prophylaxis in persons-living with HIV and intrapartum antibiotic prophylaxis due to the existence of recommendations and guidelines for those uses. There are few such publications and they are limited to infants, children, and pregnant women, reducing generalizability to populations outside these risk groups or to other indications for treatment. Most of these studies only reported antibiotic impacts on α- and β-diversity metrics, precluding more in-depth analysis of antibiotic-associated taxonomic changes. To gain further insight into the results of these MDA studies, I also discussed studies that reported the factors which determine how gut microbiota respond to antibiotic perturbation and studies which investigated antibiotic use, gut microbiota, and health outcomes in the same study population. The number of such studies was also small, limiting the conclusions that can be drawn. Finally, most studies reviewed here used 16S amplicon sequencing, and did not provide any information regarding the functional capability of the microbiome, which could provide more insight into the effects of antibiotic-induced alterations on health and the mechanisms involved.Bifidobacterium spp. and an increase in Enterobacteriaceae with prenatal or neonatal exposure. The microbiome may not fully return to its initial composition, depending on the class of antibiotic used, the initial composition of the microbiome, or the sources and frequency of recolonization. The potential impact on host health may depend on the timing of antibiotic exposure and the specific context. Interventions to mitigate or monitor the impacts of antibiotic use on the microbiome show promise but require further testing. Microbiome alteration by antibiotics is a complex process, and more comprehensive studies are required to fully characterize the potential mechanisms of antibiotic-induced changes in the human gut microbiome and consequences for host health, and to inform their translation into alternative treatments and public health strategies.The most consistent reported impact of MDA with antibiotics has been a reduction in microbiota α-diversity in infants and children, in addition to a reduction in


While efforts have been made in the United States (US) to optimize antimicrobial use, few studies have explored antibiotic prescribing disparities that may drive future interventions. The objective of this study was to evaluate disparities in antibiotic prescribing among US ambulatory care visits by patient subgroups. This was a retrospective, cross-sectional study utilizing the National Ambulatory Medical Care Survey from 2009 to 2016. Antibiotic use was described as antibiotic visits per 1000 total patient visits. The appropriateness of antibiotic prescribing was determined by ICD-9 or ICD-10 codes assigned during the visit. Subgroup analyses were conducted by patient race, ethnicity, age group, and sex. Over 7.0 billion patient visits were included; 11.3% included an antibiotic prescription. Overall and inappropriate antibiotic prescription rates were highest in Black (122.2 and 78.0 per 1000) and Hispanic patients (138.6 and 79.8 per 1000). Additionally, overall antibiotic prescription rates were highest in patients less than 18 years (169.6 per 1000) and female patients (114.1 per 1000), while inappropriate antibiotic prescription rates were highest in patients 18 to 64 years (66.0 per 1000) and in males (64.8 per 1000). In this nationally representative study, antibiotic prescribing disparities were found by patient race, ethnicity, age group, and sex. Clostridioides difficile infections . In Data analyses were conducted using JMP Pro 16 . Data weights were used to extrapolate sample visits to national estimates for all conducted analyses. Baseline characteristics were compared between visits with and without a documented antibiotic prescription using the chi-squared or Wilcoxon rank-sum tests, where appropriate. Antibiotic prescribing rates were calculated as the number of visits that included an antibiotic per 1000 total outpatient visits by patient race, ethnicity, age group, and sex. Prescribing rates in each subpopulation were calculated using population-specific denominators. Appropriateness of prescribing was also described as the rate and percentage of antibiotic visits classified as appropriate, possibly appropriate, and inappropriate in each subgroup. Prescribing rates and appropriateness were compared within groups using the chi-square test.In this nationally representative study of ambulatory provider office visits, disparities in overall and inappropriate antibiotic prescribing were found by race, ethnicity, age group, and sex. This study demonstrated that patient characteristics are a potential way for healthcare providers to identify those at risk of inappropriate antibiotic prescribing. While the causes of these disparities are multifactorial, identifying where and why these disparities occur is imperative to further direct antimicrobial stewardship efforts in the outpatient setting. Consideration for the frequency that antibiotics are prescribed and additional socioeconomic and cultural factors will aid in the improvement of these disparities. Furthermore, this study may contribute to protocol development on antibiotic prescribing for patients with characteristics known to put them at risk of inappropriate antibiotic prescribing. Further studies are warranted to continue evaluating antibiotic prescribing trends among various patient populations.


Bifidobacteriaceae levels from 54.4% to 0.6% and from 23.8% to 2.3% in the simulated proximal and distal colon, respectively, coinciding with a marked reduction in butyrate concentrations. Treatment with lactulose enhanced acetate and lactate levels during antibiotic treatment, likely through lactulose fermentation by Lachnospiraceae and Lactobacillaceae. One week after cessation of antibiotic treatment, Bifidobacteriaceae levels re-increased to 20.4% and 7.6% in the proximal and distal colon of the 5 g lactulose/d co-administered unit, as compared with 1.0% and 2.2% in the antibiotic-treated unit, and were even further stimulated upon extension of lactulose administration. Marked butyrogenic effects were observed upon prolonged lactulose supplementation, suggesting the establishment of cross-feeding interactions between Bifidobacteriaceae and butyrate producers. Furthermore, a limited Enterobacteriaceae outgrowth following antibiotic treatment was observed upon dosing with 10 g lactulose/d, indicating inhibition of pathogenic colonization by lactulose following antibiotic therapy. Overall, lactulose seems to be an interesting candidate for limiting the detrimental effects of amoxicillin–clavulanic acid on the human gut microbiome, though further studies are warranted to confirm these findings.The validated SHIME model was used to assess the effect of repeated administration of two different lactulose dosages (5 g/d and 10 g/d) on the human gut microbiome during and following amoxicillin–clavulanic acid treatment. First, antibiotic treatment strongly decreased  Bifidobacterium and Lactobacillus species [Penicillin-class antibiotics are used to treat a wide variety of bacterial infections. While being effective towards killing disease-causing agents, they also cause collateral damage by adverse effects on indigenous microbes, such as health-related  species . The res species . There iBifidobacterium species to counteract the creation of a dysbiosed microbial community due to antibiotic therapy [One of the strategies to possibly improve human health through modulation of the gut microbiome considers supplementation with prebiotics, which are defined as non-digestible substrates that selectively stimulate specific gut microbes, consequently conferring a health benefit on the host . While p therapy ,9,10,11.Alistipes, Parabacteroides, Anaerostipes [Megasphaera [Faecalibacterium prausnitzii [Lactobacillus, Anaerostipes and Roseburia, providing evidence that lactulose could be an interesting compound for use in minimizing adverse effects induced by antibiotic therapy.Lactulose, a synthetic non-digestible disaccharide, is well-known for its therapeutic use in treating constipation  and heparostipes ,17, Megaasphaera  and the usnitzii . In addiusnitzii  have sho®). Furthermore, the impact of prolonged repeated dosing of lactulose following antibiotic treatment was investigated in terms of microbiome recovery.The aim of the current study was to evaluate the potential effect of different doses of lactulose (5 g/d and 10 g/d) in supporting the recovery of the activity and composition of the gut microbiota upon co-administration with the antibiotic amoxicillin–clavulanic acid at clinically relevant doses using the in vitro Simulator of the Human Intestinal Microbial Ecosystem (SHIMEShort-chain fatty acid (SCFA) levels were stable during the control period within the different SHIME arms. Similarly, the negative control incubations (CTRL) were characterized by stable levels during the entire experimental period .p < 0.001 in the proximal colon (PC)) of butyrate levels at the end of the antibiotic treatment period (Antibiotic treatment in the absence of lactulose supplementation (AB CTRL) resulted in a slight decrease in acetate levels in both colon regions , though t period . On the p < 0.001 and p = 0.008 for the 5 g/d and 10 g/d test dose, respectively) and DC . Overall, final acetate levels were similar for both doses of lactulose tested, though during antibiotic treatment a trend towards increased acetate levels, especially in the DC, was observed when administering the higher dose of lactulose . While the addition of lactulose during the antibiotic treatment resulted in a similar stimulation of propionate levels as observed for the antibiotic control, prolonged lactulose administration (at both doses tested) significantly reduced propionate levels during the follow-up period in the PC, resulting in an average decrease of 8.3 mM (−71%) and 0.6 mM (−10%) at 5 g/d and 10 g/d, respectively, when compared to the antibiotic treatment period.Addition of lactulose during the antibiotic treatment resulted in significantly enhanced acetate levels as compared to the control period, i.e., an average increase of 10.7 mM (or +57% as compared to the control period) and 20.7 mM (+53%) upon supplementation of 5 g lactulose per day and an average increase of 14.2 mM (+74%) and 31.0 mM (+78%) upon administration of 10 g/d lactulose in the PC and DC, respectively . While cIn terms of butyrate production, cessation of antibiotic treatment resulted in recovery of butyrate levels, with the final butyrate concentrations reaching similar levels to those observed during the control period in the absence of lactulose supplementation. The addition of lactulose during the antibiotic period resulted in similar trends, though administration of the higher lactulose dose during the antibiotic period showed faster recovery of butyrate levels. Prolonged administration of lactulose during follow-up, on the other hand, increased butyrate levels beyond concentrations observed during the control period, resulting in significantly higher levels at the end of the experiment in both colon regions, i.e., an average increase of 17.7 mM (or +109% as compared to the control period) and 21.6 mM (+118%) upon supplementation of 5 g lactulose per day and an average increase of 16.7 mM (+107%) and 47.3 mM (+262%) upon administration of 10 g/d lactulose in the PC and DC, respectively.Finally, the addition of lactulose resulted in a strong stimulation of lactate levels, followed by a reduction in lactate levels upon cessation of lactulose treatment. Prolonged lactulose administration resulted in a further increase in lactate levels in the PC during the follow-up period, with the strongest increases observed when supplementing the higher dose of lactulose .p < 0.001).With respect to markers for proteolytic fermentation , antibioThe reciprocal Simpson diversity index was calculated as a measure of diversity . AntibioAkkermansiaceae in the DC. The decrease in Actinobacteria levels seen after antibiotic application was mainly linked to large decreases in Bifidobacteriaceae abundance, which was compensated by increased abundance of Bacteroidaceae. Furthermore, antibiotic treatment specifically resulted in enrichment of Proteobacteria, as evidenced by increased abundances of several families belonging to the Proteobacteria phylum (except in the PC of the QuadSHIME that was dosed with 5 g lactulose per day). Dosing lactulose during the antibiotic treatment period resulted in increased levels of Firmicutes at the expense of Bacteroidetes. The increased Firmicutes levels were attributed to increased abundance of Lachnospiraceae and Lactobacillaceae. Co-administration of lactulose resulted in a strong recovery of Bifidobacteriaceae levels following antibiotic treatment  as compared to the control, with an additional strong stimulatory effect being observed for the prolonged lactulose application.With respect to microbial community composition , the antBifidobacteriaceae with the extended lactulose supplementation was accompanied by a decrease in Bacteroidaceae and Lachnospiraceae. Several other bacterial groups were also stimulated when lactulose was given during the follow-up period, including Rikenellaceae in the DC and Veillonellaceae in both colon regions. Tannerellaceae levels also increased in the DC, though only upon prolonged administration of lactulose at a dose of 5 g/d. Furthermore, following antibiotic treatment, increased abundance of Enterobacteriaceae was observed in the PC in the absence of lactulose treatment (observed to a larger extent in the QuadSHIME that was dosed with 10 g lactulose per day), while lactulose application limited this effect, especially when supplementation was continued.The strong stimulation of The main finding of the present study is that metabolite production was stable and reproducible within and between the different SHIME units, while the negative control incubation was also characterized by stable levels during the entire experimental period (5 weeks). These observations are in line with previous findings of Possemiers et al. which demonstrated that a stable microbial community was reached within 2 weeks after the inoculation of fecal material into reactors . FurtherBifidobacteriaceae levels in both PC and DC, thereby confirming previous in vivo studies, including antibiotic therapy [Lachnospiraceae and Ruminococcaceae families following amoxicillin treatment [Bacteroidaceae family was strongly affected by amoxicillin therapy in these former studies [In addition, our study demonstrated that amoxicillin–clavulanic acid treatment at clinically relevant concentrations strongly decreased  therapy ,9. Furth therapy . Similarreatment ,8,23. In studies ,25.Bacteroidaceae. Bacteroidaceae could potentially obtain a competitive advantage upon partial eradication of Bifidobacterium and butyrate-producing species with amoxicillin–clavulanic acid treatment.In the current study, propionate production was stimulated towards the end of the antibiotic treatment, which correlated with increased relative abundance of Lactobacillaceae. Similarly, studies performed by Bothe et al. [Lactobacillus species under healthy conditions in vitro, while Nikolaou et al. [Lactobacillus spp. even during antibiotic treatment.During the antibiotic treatment, the co-administration of lactulose resulted in significantly enhanced levels of acetate and lactate in both colon regions, which was associated with increased abundance of e et al. ,18 showeu et al.  reportedBifidobacteriaceae as compared to the antibiotic control , with an additional stimulatory effect being observed when the application of lactulose was continued. Furthermore, it was observed that, post-treatment with amoxicillin–clavulanic acid, butyrate levels recovered in both colon regions, with the strongest recovery upon prolonged administration of lactulose. The butyrogenic effect was optimal towards the end of the administration period, probably because of the establishment of cross-feeding interactions between Bifidobacteriaceae and butyrate-producing bacteria [Following amoxicillin–clavulanic acid treatment, co-administration of lactulose during antibiotic therapy resulted in a marked recovery of bacteria ,27.Bifidobacteriaceae abundance, the expanded supplementation with lactulose was accompanied by strongly reduced Bacteroidetes levels, while the higher dose of lactulose significantly increased Firmicutes levels towards the end of the follow-up period. This finding is in line with the observations of Ladirat et al. [Bifidobacterium species as well as butyrate-producing bacteria belonging to the Firmicutes phylum following amoxicillin treatment. Moreover, extended lactulose administration in our study resulted in increased abundance of Rikenellaceae in the DC, a finding that is supported by Duysburgh and co-workers [Lactobacillus and Bifidobacterium species, which in turn could stimulate cross-feeding interactions.At the community level, next to enhanced t et al.  which sh-workers . OverallEnterobacteriaceae in the PC. Lactulose supplementation during and after antibiotic treatment, on the other hand, limited ammonium and BCFA recovery, thereby controlling Enterobacteriaceae outgrowth. While the Enterobacteriaceae family contains many commensal gut microbiota, this family is mostly linked with enteric diseases as it also contains several pathogenic micro-organisms, such as Escherichia coli, Salmonella, Enterobacter and Shigella [Streptococcus) significantly increased following treatment with the antibiotic azithromycin in children, while co-administration of lactulose with azithromycin limited the outgrowth of these opportunistic pathogens. This suggests that lactulose supplementation promotes recovery of the gut microbiome following antibiotic therapy, thereby providing a protective role against pathogenic colonization.With respect to markers for proteolytic fermentation, antibiotic treatment reduced ammonium and BCFA levels in both colon regions. Following antibiotic treatment, recovery of ammonium and BCFA levels was observed in both colon regions, which was accompanied with an outgrowth of Shigella , indicatShigella  reported® model with a co-culture human cell model [Bifidobacterium and Lactobacillus species. This subsequently stimulated the recovery of butyrate, with a strong butyrogenic effect being observed upon prolonged lactulose supplementation after cessation of antibiotic administration, with the strongest effects being observed for the higher dose of lactulose (10 g) tested. The current study supports the view that lactulose is an interesting candidate in limiting the detrimental effects of amoxicillin–clavulanic acid on the human gut microbiome. Clinical studies are now warranted to confirm these promising findings.This study has some limitations that we would like to acknowledge. First, inter-individual variations were not evaluated. However, it is important to note that in vitro gut models depend on the microbiome present in human stool samples and that human microbial community composition is generally characterized by large inter-individual differences . Therefoll model  could hall model , and theAll chemicals were obtained from Sigma-Aldrich  unless stated otherwise. Fresenius-Kabi iPSUM S.r.l.  provided the lactulose crystals (Ph.Eur.), which were tested at two different dosages, i.e., an in vitro dose of 5 g per day and an in vitro dose of 10 g per day. While the highest dosage  corresponds to the (lowest) approved dose for medicinal application , the lower dosage  was selected to investigate whether this dose would still have the potential to support the microbiome while limiting the risk of gastrointestinal side effects .® model  as described by Molly et al. [In vitro simulation of the human gastrointestinal tract was derived from the SHIMEy et al. . The reay et al. . Each ary et al. . Upon iny et al. . Out of y et al. .Amoxicillin is generally administered together with clavulanic acid in a clavulanic acid:amoxicillin ratio of 1:4 or 1:7 in vivo. Out of this oral dose of clavulanic acid, around 73% is absorbed in vivo . If the Starting from the control period, samples for analysis of microbial metabolic activity were collected three times per week from each colonic vessel. SCFA levels were determined as described by De Weirdt et al.  and inclStarting from the final week during the control phase, samples for microbiota profiling were collected once per week from each colonic vessel. DNA was isolated as previously described by Boon et al. , using pt-test for pairwise comparisons. The normality of the dataset was confirmed based on historical data. Differences were considered significant if p < 0.05. Data are presented as means ± standard deviations. Statistically significant differences relative to the control period are indicated in bold.The comparison of normally distributed data for the different experimental periods on microbial metabolic markers was performed with a Student’s For the 16S-targeted Illumina sequencing analysis, read assembly and clean-up was largely derived from the MiSeq procedure as previously described ,41. In b


In order to investigate the effectiveness of polymer modification and fiber reinforcement on the cracking and impact resistance of concrete materials prepared for ultra-thin whitetopping (UTW), carboxyl butyl benzene latex and polyformaldehyde fibers were added to the conventional cement concrete mix. In addition, test methods that used an asphalt mixture performance tester (AMPT) and mechanical rammer were developed to evaluate concrete cracking and impact resistance, respectively. Results from the AMPT test revealed that the cracking resistance can be enhanced with polymer and fiber, especially the initial tensile load peak, which can be improved by more than 40% when fiber and polymer compound modification is applied. Meanwhile, the impact loading test revealed that the inclusion of both fiber and polymer results in a two-fold increase in the number of impacts before visible cracking occurs, and the number of blows to failure increased by 21.4%. Moreover, microstructures were investigated by scanning electron microscopy (SEM) to confirm the reinforcing mechanism of both polymer modification and fiber reinforcement. Thin concrete overlays bonded to hot mixed asphalt (HMA) with the typical thickness limited to 5–10 cm, also known as ultra-thin whitetopping (UTW), has been used for the repair of distressed asphalt pavement in the US since its introduction in Madisonville, Kentucky, in 1991 [Overall, UTW can perform well and be an effective pavement rehabilitation technique for highways, parking lots, and intersections. A full bonding can be achieved when the substrate is of good quality ,3,4. UnfHowever, the properties of UTW with the addition of both fiber- and polymer-compound-modified concrete (FPMC) have been seldom researched. Therefore, further studies are needed to shed light on their properties and guide their application in civil engineering, especially for UTW.Additionally, great efforts have been put into correlating laboratory tests results with field performance. Laboratory tests are conducted on most concerned properties of rigid pavement, such as flexural strength, modulus of elasticity, and drying shrinkage. In general, the surface layer of concrete is required to achieve the specified strength level to undertake the load from the environment and traffic. Traditionally, compressive and flexural strength are commonly used as the indicators of the life service of cement concrete. However, higher strengths lead to higher modulus of elasticity and coefficient of thermal expansion, thus increasing the curling stress of rigid pavement accordingly ,14. TherCompared with laboratory tests on strengths, full-scale tests are believed to evaluate the cracking resistance of different types of concrete under dynamic loading more effectively ,18,19. HOn the other hand, varieties of impact loading tests in laboratory were conducted to evaluate cracking durability of concrete, such as the procedures proposed by ACI committee 554 (ACI 1999). According to ACI 1999, a series of drop-weight impact tests were proposed ,21, as wThe objectives of this study are to further investigate the influence of fiber and polymer compound modification on the fracture toughness and impact resistance and improve the test efficiency for each of them. Firstly, polymer and fiber reinforcement were added to concrete mixes in order to improve the cracking and impact resistance. The compressive and flexural strengths were tested for conventional, polymer-modified concrete (PMC), fiber-reinforced concrete (FRC), and fiber- and polymer-compound-modified concrete (FPMC). Secondly, overlay tests by Asphalt Mixture Performance Tester (AMPT) were carried out to investigate the cracking propagation process, and the tensile peak loads were recorded. The procedure was set up as follows: (i) the controlled maximum displacement of the cyclic triangular tension loading was determined by experiment and (ii) cracking resistance and maximum tensile loads were recorded to evaluate cracking resistance.Lastly, drop-weight impact loading tests with a mechanical rammer in accordance with ASTM D1557 (Standard Test Method for Laboratory Compaction Characteristics of Soil Using Modified Effort) were carried out as follows: (i) Using mechanical rammer, a drop-weight impact loading test procedure was developed, including the determination of the proper height of the specimen cut from a standard cube specimen for testing the compressive strength of concrete. (ii) Drop-weight loading test was carried out, and the blow number was recorded.Ordinary Portland cement P∙O 42.5 produced locally in Yunnan Province, China, was used in the mix design. Its main properties can be found in The polymer-based modifier used in this research was carboxyl butyl benzene latex. As shown in Due to the surface activity of carboxylated styrene–butadiene latex, excess air bubbles will be produced in the mix, causing discontinuities within the concrete and resulting in a negative effect on the impermeability and compressive strength . TherefoIn addition, polyformaldehyde fibers see in b were ad3. The concrete specimens with polymer modification were prepared with the polymer/cement mass (P/C) ratio fixed to 7.5%; the determination of the P/C ratio was based on previous research in this project [All the mix designs were developed with constant water-to-cementitious-material (W/C) ratio of 0.36 and a cement amount of 420 kg/m project , at the 0 was the reference, without polymer modification or fiber addition; CP1 was modified by polymer only, while CP2 was polymer-modified as well as 3‰ defoaming agent. CF1, CF2 were fiber-reinforced concrete with the content of polyformaldehyde fiber 0.9 kg/m3 and 1.2 kg/m3, respectively; CPF was polymer-modified concrete with 1.2 kg/m3 of polyformaldehyde fiber.The mix proportion designs are given in 2:Ca(NO2)) = 1:1, was added as an accelerating admixture with a fixed content of 1.9% of cement mass.To minimize the disruption to the travelling public due to work zones, pavement repair jobs are required to open to traffic as soon as possible. It is necessary that the concrete overlay materials can gain enough strength more quickly than the traditional concrete product to cut the time on curing. Aiming to open to traffic within 3~7 days, a mixture of calcium chloride and calcium nitrite ; rm represents mass of the mechanical rammer (kg); g represents acceleration due to gravity (9.81 m/s2); N represents number of blows; and eh = H − T, effective drop height (m).As presented in In order to further understand the reinforcing mechanism of fiber reinforcement and polymer modification, SEM tests were conducted on the samples from groups with polymer modification only (CP), fiber reinforcement only (CF), and both fiber and polymer addition, as well as the conventional concrete. Prior to the observation, the samples should be dried and gold-plated in an ion sputter coater for 2 min. The microstructures, hydration meshes, and fiber distribution were examined with JSM-7800F scanning electron microscope; the accelerating voltage was from 2 to 15 V.1 and CF2 exhibited comparable compressive strength to the conventional concrete. Comparing test results of flexural strength of CP1 and CP2 with C0, it can be concluded polymer modification results in much higher flexural strength than ordinary PCC, by 36.8% on average for test results of 3-day age and by more than 38% for 7-day age. As for fiber-reinforced specimens, the increments were 6.3% and 27.5% on average for 3-day and 7-day flexural strength, respectively. By examining mixtures CP1 and CP2, it was found that adding defoaming agents can slightly improve compressive and flexural strength by approximately 7% and 4%, respectively. However, adding polyformaldehyde fiber to polymer modified concrete did not affect the improvement of compressive or flexural strength, which resulted in comparable compressive and flexural strengths for CP2 and CPF.The compressive strength was tested with cubic specimens (150 mm × 150 mm × 150 mm) according to ISO 4012-1978, and the load rate was set from 0.5 MPa/s to 0.3 MPa/s. The flexural strength tests were conducted according to ISO 4013-1978 or ASTM C78, and the loading rate was set from 0.05 Mpa/s to 0.08 Mpa/s. The compressive strength and flexural strength of the mixtures are shown in 0. However, the CP1 and CP2 with polymer modification did not achieve adequate compressive strength at the 3-day age due to the increase of macro porosity. UTW is often used as a repair material for existing asphalt concrete pavement. Therefore, its curing time is required to be as short as possible. The addition of polymer will prolong the setting time of cement concrete [The 3-day flexural strength for all the mix designs was larger than the required value, according to Harrington and Fick . The tesconcrete  and dela1, CF2, and CPF after cracking was attributed to the fiber reinforcement. The load reduction rate showed a similar trend. The load reduction rate of the mixture without the inclusion of fibers increased to more than 85% at the end of the first cycle and gradually reached 90% in the next few runs.The cracking resistance tests were carried out at maximum displacement of 0.2 and 0.1 mm. Test results for crack opening of 0.2 mm are displayed in In summary, it was found that at maximum displacement of 0.2 mm, concrete failed too quickly to recognize the difference in the cracking propagation process for each mix. Therefore, the maximum displacement was reset to 0.1 mm.0 and CP1 were almost the same after 60 runs, then the two lines overlapped. However, polymer modification prolonged the process of breaking down, and tensile load decreased sharply to a very low level, yet it cost the CP1 and CP2 almost 20 runs to achieve a significant load reduction rate , the rank of the peak load level of different mixtures is not necessarily consistent with that of the load reduction rate because the load reduction rate is a relative parameter that is highly dependent on the initial peak load level. Overall, the load reduction rate for the CConcrete fails under tensile loading at a much lower stress level compared with compressive loading. Cracking occurs at the first loading cycle, then propagates during the following loading cycles. In fact, stress concentration at voids, in other words, defects, becomes large enough to initiate micro-cracking within the concrete. At the end of the first loading cycle, the crack will appear, and the concrete will fail in a brittle manner. Therefore, the peak load level before concrete cracking can be taken as an indicator of the micro properties of concrete.0, the reference group, was defined as 100%, and the percentage of other groups could be easily determined with respect to the reference. Initial tensile loads for the two maximum displacements are shown in 1 and CP2, polymer modification could improve the initial tensile load peak, especially when the defoaming agent was added. In addition, fiber reinforcement improved the initial load peak by 15.6–23.2%. Additionally, suppose fiber and polymer compound modification was included. In that case, the initial tensile load peak can be improved by 45.7% on average, much higher than that with only polymer or fiber addition.To make an easy comparison, the conventional concrete maximum tensile load of CClearly, the fiber and polymer compound modification can improve the cracking resistance significantly. The improvement of the maximum tensile load is attributed to three influence factors. Firstly, the polymer can fill the voids inside the concrete; secondly, the introduction of fiber can obstruct the propagation of the microcracks; and lastly, the carboxylated styrene–butadiene latex was an adhesion agent, which can adhere both the high-efficiency hydroxylated carboxylic acids on the surface of concrete and the polyformaldehyde fiber.0 even with number of blows up to 5000 times. As it is shown in T mm, where T was the thickness of trimmed specimens under the rammer, which varied at 150 mm, 120 mm, 100 mm, 70 mm, 50 mm, and 35 mm.Impact resistance tests were performed after the concrete was cured for 28 days at 20 °C, 95% RH. In this study, the standard cube specimens of 150 × 150 × 150 mm were tested directly without trimming. Unfortunately, all the specimens for the seven groups sustained more than 500 impacts prior to cracking occurrence. Moreover, there was no cracking found for C0 are shown in Impact resistance test results for different thicknesses of CN is the impact loading times to failure and T is the thickness of the concrete specimens (mm).Number of blows is assumed to be a power function of thickness of the specimens for the specimens that has distressed, namely thickness ranging from 35 mm to 120 mm. Then, the following regression equation (Equation (2)) can be used to describe the relationship between the thickness and the number of impacts to failure.It can be seen that the impact loading times are a function of the 6.219th power of the thickness, which means a small amount increase in the thickness can increase the number of impacts to failure greatly. For instance, if the thickness is increased from 130 mm to 140 mm, then the impact times inducing it to failure will increase from 426 to 676, making the test much more time-consuming.As a result, 100 mm was adopted as the optimum thickness for trimming specimens due to its higher efficiency and lower variance level than 120 mm. The standard specimen with a thickness of 150 mm, and the trimming specimen with a thickness of 100 mm is displayed in 0 broke into pieces, shown in Impact loading tests were performed on concrete specimens of different mix proportions but of the same size (150 × 150 × 100 mm). During the test process, cracking behavior was monitored, and the test paused immediately when visible cracking was detected; the crack width was then measured and recorded. The impact loading restarted and stopped until the failure of the specimen. One of the major failure modes was corner cracking, a fissure extending from one side to the adjacent one, as shown in 0, reaching 0.9 mm. Corner cracks appeared in group CP1 which represented specimens with polymer only, and the average crack width reduced to 0.2 mm; average crack width of CP2 specimens with polymer modification and defoamer addition further reduces to 0.15 mm, indicating that the use of defoamer could increase the compactness of concrete, which was beneficial to the improvement of impact resistance of concrete. Fiber reinforcement was capable of reducing the crack width. The average crack width was reduced from 0.35 mm to 0.20 mm when the fiber content was increased from 0.9 kg/m3 to 1.2 kg/m3. The average cracking width of CPF was notably reduced, such as to 0.10 mm. The outstanding effect on the improvement of fatigue performance could be predicted based on crack width measurement.Once the crack initialed and could be observed, the drop-weight test paused, and the measurement of the cracks was carried out along the crack for four positions; the maximum reading was then recorded as the crack width for the specimen. The average values for the four specimens in each group are listed in The number of blows was recognized in two series. One was the number of blows when the first crack can be observed, indicating the initiation of cracking. The other was recorded when the specimen was broken into two or more pieces, indicating the failure of the specimen.0 with others, results indicated that the inclusion of polymer alone could significantly improve the impact resistance of cement concrete. In addition, fiber reinforcement could effectively delay the initiation of crack and prolong the life to failure, whereas it did not exhibit any improvement on the impact times to failure. Comparing CPF and CP1, the impact resistance improved most with the combination of polymer and fiber, which doubled the number of impacts to induce the first visible cracking and improved the number of impacts to failure by 21.4%. Although the number of impacts for initial crack was almost the same for CP1 and CP2, the addition of the defoaming agent did improve the life to failure by 27.8% compared with the specimens without it. Polymer latex significantly improved the interfacial bond between matrix and fibers, thus making the fibers more difficult to slide out during the impact loading and acting as crack-bridging, which was beneficial to the energy dissipation under impact loading conditions. The cracking resistance of cement concrete could be improved by simply adding fibers to conventional concrete. Due to the bridging effect of fibers in the previous section, the number of impacts until cracking came forth was significantly improved comparing CF1 and CF2 with C0. However, due to the small amount of fiber content and its adverse effect on the workability of fresh concrete, the impact resistance of concrete decreased.As shown in ASTM standards are widely adopted by many countries to determine optimum water content and maximum dry unit weight for compacting soil and gravels, and the equipment is easy to find. Thus, the testing procedures developed in this research have the potential to be a standard drop-weight impact loading test in the future since it is convenient and easy to obtain the test equipment.Test results above indicated that the polymer modification had advantages in improving the mechanical properties of UTW materials; this agrees with the findings of the literature ,31 that In spite of the adverse effect on compressive strength, carboxylated styrene–butadiene exhibited a larger improvement in flexural strength compared with polyformaldehyde fibers.AMPT overlay test was proven to be capable of evaluating the cracking resistance of concrete material. Since a 0.2 mm maximum crack opening caused a sharp drop of tensile peak within only a few runs, 0.1 mm was suggested as the controlled maximum displacement.Mechanical rammer, according to ASTM Standards D 1557, was effective in performing the impact loading test with only a minor revision, and the standard cube specimens needed to be trimmed from 150 mm to 100 mm thick to improve testing efficiency.Fiber reinforcement was beneficial to improving flexural strength and inhibiting the formulation of cracking formulation but did not exhibit any advantage on the improvement of the number of impacts to failure.Fibers and polymer compound modification could significantly improve flexural and tensile strength, both of which were increased by more than 40%. Notably, the impact times of FPMC for cracking formulation was eight times that of the conventional concrete, indicating a longer fatigue life compared with conventional concrete.The defoaming agent was essential to polymer-modified concrete, which had a positive influence on the mechanical properties—not only on the compressive and flexural strength but also on the cracking resistance and impact resistance.SEM results show that the polymer modification can fill the defects inside the concrete and make the fiber stick into hydration meshes much more firmly. Furthermore, it explains the mechanical properties improvement within this research.The influence of fibers and polymer on concrete cracking and impact resistance was investigated in this research. This research presents new test procedures for cracking and impact loading resistance. On the basis of the test results above, the following conclusions can be drawn:


Overfeeding during lactation has a deleterious impact on the baby’s health throughout life. In humans, early overnutrition has been associated with higher susceptibility to obesity and metabolic disorders in childhood and adulthood. In rodents, using a rodent litter size reduction model  to mimic early overfeeding, the same metabolic profile has been described. Therefore, the rodent small litter model is an efficient tool to investigate the adaptive mechanisms involved in obesogenesis. Besides central and metabolic dysfunctions, studies have pointed to the contribution of the endocrine system to the small litter phenotype. Hormones, especially leptin, insulin, and adrenal hormones, have been associated with satiety, glucose homeostasis, and adipogenesis, while hypothyroidism impairs energy metabolism, favoring obesity. Behavioral modifications, hepatic metabolism changes, and reproductive dysfunctions have also been reported. In this review, we update these findings, highlighting the interaction of early nutrition and the adaptive features of the endocrine system. We also report the sex-related differences and epigenetic mechanisms. This model highlights the intense plasticity during lactation triggering many adaptive responses, which are the basis of the developmental origins of health and disease (DOHaD) concept. Our review demonstrates the complexity of the adaptive mechanisms involved in the obesity phenotype promoted by early overnutrition, reinforcing the necessity of adequate nutritional habits during lactation. The global prevalence of obesity and its comorbidities during childhood has increased worldwide . In a reEarly obesity is a global concern since there is a strong correlation between childhood body weight and adult obesity and metabolic syndrome . This coThe Developmental Origins of Health and Disease (DOHaD) concept explains the correlation between the early life environment and increased susceptibility to diseases, such as obesity and metabolic syndrome, in adulthood . NeonataMany epidemiological and experimental studies have supported the DOHaD concept. These observations have increased the attention paid to the “The First Thousand Days of life” , which iIn this review, we explore the recent findings of adaptive mechanisms in the small litter (SL) model responsible for metabolic disorders in the offspring. In view of the importance of the endocrine system in metabolic control, we emphasize hormonal changes, especially changes in its specific tissue action. We also explored the potential epigenetic mechanisms involved in this adaptive phenotype of the SL model and the interference of sex dimorphism with the metabolic profile.Early postnatal overfeeding, promoting higher susceptibility to obesity and its metabolic disorders throughout life, is experimentally simulated in rodents by the litter size reduction model ,13,14. IBecause of this early overfeeding, the SL offspring have an accelerated body weight gain and increased adiposity before weaning, exhibiting a body weight 30% higher than the control offspring at weaning . Some exDuring the lactation period, the hypothalamic circuits that regulate energy homeostasis are still in development and are sensitive to the early hyperinsulinemia and hyperleptinemia exhibited by the SL model . These hThen, the metabolic phenotype of SL offspring involves peripheral changes, especially central changes in pathways involved in energy homeostasis control. Many authors have described central resistance to hormones such as leptin ,23, insuInterestingly, several hypothalamic changes occur before weaning, such as leptin resistance at postnatal day (PND) 12 , with a In mice, these early changes promoted by neonatal overfeeding could affect neural projections  and synaIn addition to hyperphagia, male SL offspring have a food preference for a high-fat diet, an alteration that could be associated with changes in the dopaminergic reward system . This foIn addition to central dysfunction, SL offspring exhibit several peripheral changes involved in their metabolic profile. The early energy and fat overload promoted by the SL model  has beenEarly postnatal overnutrition increases the susceptibility to diabetes development . Indeed,In addition to modifications of insulin secretion, adult SL offspring exhibit changes in peripheral insulin signaling, suggestive of insulin resistance. In adult SL male and female offspring, the downregulation of markers of insulin signaling, such as insulin receptor substrate-1 (Irs-1) and glucose transporter 4 (GLUT4) in white adipose tissue and skeletal muscle ,45, reduThese findings reveal the impact of postnatal overfeeding on offspring susceptibility to diabetes development and the potential mechanisms involved.Neonatal overfeeding also affects animal behavior throughout life. The SL offspring exhibits, in adolescence, reduced social play behavior  and chanIndeed, there is a precocious change in the HPA axis of the SL model, exhibiting higher corticosterone levels during early life (PND 14 and 21), together with central changes suggestive of early maturation of the HPA axis . HypercoAdditionally, in adult SL offspring, a higher adrenal weight with an increased content of corticosterone  and cateEarly postnatal overfeeding promotes increased body weight and adiposity since PND 10 , regardlThe SL offspring of both sexes at PND 10 exhibit higher adiposity and increased serum adipokines, such as leptin and adiponectin . InteresNeonatal hyperleptinemia per se can be responsible for high adiposity and altered food intake in adult mice . DespiteInterestingly, even in the presence of resistance to the central anorexigenic effect of leptin, SL offspring maintain central sensitivity to activate other central regions, such as the PVN, suggesting that leptin resistance is area-dependent . AdditioPostnatal overfeeding modifies energy metabolism, promoting lower energy expenditure at weaning  and duriCentral and peripheral thyroid hormone action increases the basal metabolism, promoting higher energy expenditure. Even with an adequate hypothalamic–pituitary–thyroid (HPT) axis response to leptin administration, SL offspring exhibit thyroid hormone adjustments throughout life. Interestingly, at PND 21, SL offspring show higher plasma 3,5,3′-triiodothronine (T3) and thyroxine (T4) levels in the presence of increased thyroid-stimulating hormone (TSH) levels . This neAlthough hypothyroidism occurs, the HPT response to leptin administration is preserved in SL offspring, reinforcing selective leptin resistance in the ARC, the nucleus involved in satiety behavior, but not in the PVN .Brown adipose tissue (BAT), a target of thyroid hormones for thermogenesis, shows reduced responsiveness to cold and lower expression of several transcriptional regulators in young adult male SL offspring , suggestEarly obesity can affect the endocrine system, modifying the time of puberty. Since the small litter is also a model of early obesity, the effects on sexual parameters have been investigated in male and female offspring. In SL male offspring, serum testosterone levels are higher at PND 10, without changes at weaning, puberty, or adulthood . AlthougOn the other hand, female SL offspring exhibit controversial changes at puberty. It has been described as normal , early , or delaOther reproductive disorders, such as dysregulation of estrous cycles, decreased fertility , reducedTherefore, in addition to impacting food intake, leptin could be responsible for the changes in the reproductive axis of the SL model . The incPostnatal overnutrition reduces the fertility index in SL females , even inEarly overfeeding affects lipid metabolism, modifying liver homeostasis and promoting dyslipidemia. During the preweaning period, SL mouse offspring have higher serum nonesterified fatty acids (NEFAs) and normal serum triglycerides . This prIn addition to the metabolic adjustments described above, liver dysfunction is another finding of SL offspring and is responsible for dyslipidemia. At weaning, despite the normal hepatic lipid content, the liver from SL offspring exhibits higher expression of lipogenic factors ,54 and eEpigenetic changes are the key mechanisms in developmental programming, causing differentiated pattern of gene expression and transgenerational features, without altering the DNA nucleotide sequence . DNA metTherefore, some epigenetic changes are involved in the SL offspring phenotype, promoting other adaptive mechanisms, such as hormonal changes. Together, these adjustments favor the increased susceptibility to metabolic disorders in the offspring subjected to early overfeeding. More studies about the epigenome in the SL model are necessary.The impact of postnatal overnutrition has been extensively explored in male offspring. Only in recent years has the female phenotype and the comparative response of both offspring to early postnatal overnutrition been explored. These findings have enriched our knowledge about sex-related differences in many developmental programming models ,82, whicSex-related differences were reported regarding the reproductive axis, highlighting the differentiated susceptibility to reproductive dysfunction and time of puberty in the male and female offspring. Postnatal overfeeding increases body weight during the pubertal transition in both sexes . HoweverRegarding energy metabolism, early postnatal overnutrition promotes an obesity phenotype in both sexes (PND 10), which can be maintained  or aboliEarly overnutrition reduces pituitary growth hormone (GH) mRNA expression in both sexes in response to a high-fat diet. While in the male SL offspring, GH suppression seems to be due to lower GHRH expression, in the female SL offspring, another mechanism is involved, such as reduced pituitary ghrelin action . Indeed,Firmicutes, lower abundance of Bacteroidetes), which per se may impair energy metabolism [Recently, our group pointed to the impairment of the gut-brain axis as another contributor to the obesity phenotype in the SL model, whose regulation is also sex-related. In adult SL males, the lower expression of the glucagon-like peptide 1 (GLP-1) receptor in the ARC may impair the satiety role of GLP-1. Despite the paradoxical CCK1-R overexpression in the ARC, the female SL offspring have lower acetate and propionate contents in their feces, which may impair PYY secretion . These dtabolism , appearitabolism  and beintabolism .The obesity phenotype of the SL female is also of special concern due to its transgenerational role. The offspring from SL female dams, even weaned with 6 pups by the dam, exhibit early obesity and cardiac remodeling in the F2 offspring of both sexes, with cardiac dysfunction only in the F2 male offspring. On the other hand, F2 female offspring show hormonal changes suggestive of polycystic ovarian syndrome, with lower blood estradiol levels and higher testosterone levels .The rodent litter size reduction model is an efficient experimental tool for investigating the impact of early postnatal overnutrition on the development of metabolic diseases. There are early and later adaptive hormonal and metabolic changes described in the literature, which are involved in hyperphagia, energy expenditure changes, insulin resistance, and reproductive changes, featuring the obese phenotype of the small litter model . In progIlex paraguariensis (yerba mate) [Litter size reduction model is an interesting model to study the late impact of early overnutrition. Due to this, the variable “litter size” must be taken into account in the development of any experimental study with animals, regardless of the outcome to be investigated. However, care must be taken to extrapolate the outcomes of this model to human beings, since mothers usually have one baby per pregnancy. Additionally, in humans during breastfeeding, the baby controls the amount of milk intake, self-regulating its energy intake . Therefoba mate) , cinnamaba mate) , and kefba mate) . These fba mate) . Epigene