In this paper, the types, formation time, structural morphology, and influence of steel corrosion products in seawater and sea-sand concrete were studied, and the intermediate and final products of steel corrosion under different conditions were determined. The corrosion products of steel in these concrete specimens under two curing methods were studied separately by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). Due to the presence of a large amount of chloride ions in the concrete, the rust layer on the surface of a steel bar contained many intermediates, such as lepidocrocite (γ–FeOOH) and aka-ganeite (β–FeOOH). Under wet/dry cycles, with the addition and loss of moisture in concrete, various corrosion products were also dynamically converted into each other. In the specimens immersed in seawater for a long time, the intermediates of corrosion were lepidocrocite (γ–FeOOH) and aka-ganeite (β–FeOOH), which were substituted for oxygen as the new depolarizers of cathode reduction reaction, and consumed themselves to ensure smooth corrosion. With the continuous development of marine resources in China, the construction of islands is an unavoidable topic. Considering the cost of transportation and time, it is of great practical significance to use sea stones and sea-sand on reefs as concrete aggregates for materials in island engineering projects. Due to the large amount of chloride adhering to the aggregate surface of seawater and sea-sand concrete, the steel reinforcement in concrete is the first to be affected by corrosion ,3,4,5,6.For a long time, researchers have extensively studied the corrosion of steel bars in concrete caused by chloride ions, but most of the studies are focused on the corrosion rate of steel bars and the degradation of the structural properties of reinforced concrete ,10,11,12Refait et al.  found thd et al.  establisAlthough there are many studies on the effect of chloride ion on steel bars at home and abroad, in order to shorten the test period, most of them are simulated experiments of concrete simulated pore solution, accelerated corrosion of steel under current and artificial cracking. The study designs are single, and most of them investigated macro-mechanical properties, without the use of XRD, SEM, and other means from the micro perspective. However, the studies on phase composition and microstructure of rust layer in concrete are still lacking in systematic theory, which cannot accurately describe the mechanism of steel corrosion in seawater sand concrete. Therefore, the research on this aspect needs to be improved.In view of the main problems in the durability study of seawater and sea-sand concrete at present, several seawater and sea-sand concrete specimens and ordinary concrete specimens were prepared in this study, to simulate the corrosion of steel bar specimens under the conditions of continuous immersion in marine environment and dry-wet cycling, respectively, in order to study the corrosion of steel bar in the specimens. Scanning electron microscopy (SEM) was used to photograph and analyze the surface of steel bar rust layer, and the types, generation time and effect on steel bar matrix were judged according to the morphology of rust products. X-ray diffraction was used to obtain the diffraction patterns of corrosion products of different rust layers of steel bar, and the composition and internal structure of the products were obtained. According to the environment of the specimens, the main intermediate products of steel corrosion and the final oxidation products under different conditions were deduced, and the complex transformation relationship between various corrosion products was determined.Cylindrical specimens with dimensions of Φ × L = 52 mm × 320 mm were adopted to ensure that the corrosion of the embedded steel bar in all directions was identical. The cement used was P.O32.5. In the seawater and sea-sand concrete, sea stones, and sea-sand were used for aggregates, but ordinary gravel and natural medium sand were used in ordinary concrete. The fine modulus The steel bars used in the specimens were all made of the same batch of HPB235 ordinary low carbon steel with a diameter of 12 mm. The composition of the steel bars is shown in After the specimens were made, they were placed in the curing room in different groups. One group was immersed continuously in artificial seawater to simulate the underwater environment of the ocean. The other group used a wet/dry cycles device to simulate the tidal environment of the ocean. The specimens were immersed for two days and dried for two days. The water temperature was 20 ± 5 °C . The groFirst, the corroded steel bars in concrete were taken out. The corrosion layers can be divided into internal rust layer and external rust layer according to the structure. The external rust layer was loose and could be easily exfoliated. The internal rust layer with compact structure was closely connected with the reinforced bar matrix. The rust powder was grinded separately in grinding bowls until it passed through 330 mesh sieves. As shown in After the specimens were broken, the concrete was hammered into soybean-sized particles. Then, 1-2 pieces of cement paste flake particles were selected on the surface of steel bars with corrosion products on the outside of steel bars. The specimens were packed in sealed bags under vacuum to prevent the corrosion products from continuing to oxidize in contact with air. The prepared samples were analyzed by Nova NanoSEM450 field emission scanning electron microscope  . CorrosiX-ray diffraction spectra of powder samples of the inner rust layer and the outer rust layer of carbon steel rust products in the two concretes are shown in From ) is very unstable at the interface between concrete and steel matrix, and easily oxidizes into new corrosion products aka-ganeite (β–FeOOH). Misawa and others [Some scholars believe that green rust hydrochloride d others  reportedPrevious studies ,26 have The above chemical reaction not only solves the stagnation of cathodic reduction reaction caused by lack of oxygen, but also reduces the resistance of hydrated To understand the morphological characteristics of the corrosion layer of steel bars, samples A1, B1, A2 and B2 were broken and sampled, and the morphology of the corroded layer was observed by SEM. d by EDS , the corFrom Due to the long-term immersion of the specimens, it was difficult for oxygen to reach the surface of steel bars during the corrosion process. Thus, the other part of the specimens was oxidized incompletely and became black magnetite  and lepidocrocite (γ–FeOOH) dehydrate and transform into hematite  The passive film of reinforcing bar in concrete was destroyed mainly by electrochemical corrosion reaction. Under the action of oxygen and water, iron lost electrons and metal anodic dissolution occurred. The electrons obtained from oxygen and water underwent cathodic reduction reaction of depolarizer, resulting in the intermediate product (2) Due to the large amount of chloride ions present in the aggregate and mixing water of seawater sand concrete, the internal rust layer contained many transition products, including lepidocrocite (γ–FeOOH) and aka-ganeite (β–FeOOH).(3) Under wet/dry cycling conditions, steel corrosion products tended to form maghemite (γ–(4) The content of lepidocrocite (γ–FeOOH) and aka-ganeite (β–FeOOH) observed in seawater samples for a long time was relatively small. The reason is that they can replace


A multidrug crystal based on drug combinations was synthesized by the solvent evaporation method. This multicomponent crystal consisted of antidiabetic drugs Glimepiride (Gli) and Metformin (Met), which was performed by single crystal X-ray structure analysis. The results showed an enhancement of the pharmaceutical properties such as lower hygroscopicity and greater accelerated stability than the parent drug Met, and a higher solubility and dissolution rate than Gli. In the field of pharmaceutical chemistry, the method of designing multi-target drugs  is beingRecently, there has been an increasing number of applications to combine oral drugs. A common combination of the type 2 diabetes mellitus (T2DM) drugs Metformin (Met) and Glimepiride (Gli) was founded after the screening of marketed combination drug formulations. Met, a biguanidine hypoglycemic drug, is the first choice for T2DM ,10. AddiHowever, both Met and Gli have some disadvantages of physicochemical properties. Met is commonly available as hydrochloride salt to address the high hygroscopicity in the base form ,14. AddiIn this article, we designed the synthesis of a multicomponent crystal based on drug combinations of Gli and Met, which was performed by single crystal X-ray structure analysis. Additionally, the issue of the poor dissolution of Gli and the high hygroscopicity in Met was tackled by the formation of a multicomponent crystal. Last but not least, the preparation process of the Gli-Met is simple, and the reagent is cheap and easy to obtain, which can be used in industrial production.With the simple and fast method of solvent evaporation, Gli-Met was successfully prepared for three days, which yielded up to 84.2%. At the first stage, powder X-ray diffraction (PXRD) and thermal analysis were used for the preliminary detection of the difference among Gli-Met and two raw materials. The diffractograms of Gli-Met, Met and Gli were characterized by PXRD. Obviously, when compared with the patterns of Met  and Gli , those of Gli-Met exhibited differences that were characterized as 2θ at 9.4, 9.5, 11.2, 22.3, 23.6, 20.6 and 26.8 . The PXRThermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were employed to investigate the thermal properties of Gli-Met, Met, and Gli samples. Thermal analysis was a reliable method of characterization of APIs in terms of the structural and stability investigations. As shown in For further clarification, the micrographs of Met, Gli, and Gli-Met were characterized by polarized optical microscopy (POM). This technique allows for the easy identification of the presence of crystals. The three kinds of crystals exhibited different forms which are flake-shaped (Met), small block-shaped (Gli), and prism-shaped (Gli-Met). The images obtained are presented in 1/c: a = 30.9830 Å, b = 8.91714 Å, c = 11.8813 Å, α = 90°, β = 98.8439°, γ = 90°, T = 293 K, and the final R1 was 0.0470 (I > 2σ(I)) and wR2 was 0.1368 . There was one molecule of Gli, one molecule of Met, and one molecule of crystal water (H2O) in the asymmetric unit in The single crystal of Gli-Met was analyzed by single crystal X-ray diffraction (SCXRD). The corresponding crystallographic data and refinement details are summarized in carbonyl and N(8)-H(8D)…O(2)sulfonyl hydrogen bonds are responsible for the bonding between the Met and Gli ions. Additional hydrogen bonds between Gli and water, i.e. O(6)-H(6C)…N(1) and O(6)-H(6D)…O(3), strengthen the bonding of Met to the Gli molecules further. The interaction between every two molecules of Gli in the outwards was formed by the N(2)-H(2A)...O(1)sulfonyl and N(3)-H(3A)...O(5)carbonyl hydrogen bond.Gli-Met is characterized by complex 2D hydrogen-bonded layers parallel to (1 0 0), as illustrated in 2O molecules. This means that Met has the competence to become a first-line choice of the selection of the co-former during the preparation of the multidrug crystals. On the basis of these intermolecular interactions, the Met and H2O molecules were sandwiched by the Gli molecules and formed an infinite hydrogen bond chain along the b axis.From the prospective of hydrogen bonding analysis, all donor and acceptor moieties of hydrogen bonds in Met actually formed hydrogen bonds with the Met, Gli, and HInterestingly, the molecules of Gli and Met were connected not only by hydrogen bonds, but also by the ionic bond as shown in Fourier-transform infrared (FT-IR) spectrum analysis was used an auxiliary method to detect differences between the Gli, Met, and Gli-Met samples at a molecular level. In the first instance, the Gli-Met IR spectrum should be a juxtaposition of the IR spectra of the parent compounds, with slight shifts for groups involved in strong hydrogen bonding. Additionally, the removal of the H atom of the amino group makes nitrogen become anionic. This can enhance the conjugative effect, which causes the absorption of the surrounding groups moving to a high frequency. This indeed was the case, as shown in −1) from Met moved to a high-frequency and showed a novel absorption peak at 3381 cm−1, which was influenced by the H atom of N between sulfonyl and carbamide from Gli moving to a biguanide bond from Met. The C=O vibration of sulfonyl and lactam (1708 cm−1 and 1673 cm−1) from Gli moved to a low-frequency and showed novel absorption peaks at 1704 cm−1 and 1665 cm−1, which were influenced by producing a slight electron pair effect due to the formation of N anions. These results manifest that Gli-Met formed hydrogen bonds and ionic bonds between Gli and Met. Our conclusion from the analysis according to the FT-IR spectrum was consistent with that from SCXRD.In the infrared spectra of the Gli-Met, N-H vibration. As shown in Notably, the Met powder was directly soluble when it made contact with the acidic medium (pH = 1), and it was impossible to gain the data of the dissolution rate. Therefore, there was no group of Met in this test and we concluded that Met is an extremely soluble compound. In this context, the trend depicting the dissolution rates of these samples was as follows: Met > Gli-Met > Gli.The other physicochemical evaluation of this multidrug crystal was sensitivity to water. Dynamic vapor sorption (DVS) analysis was performed to compare the hygroscopicity of Gli-Met with that of the two raw materials in 2O molecules were located in the sandwich covered by the Gli molecules. Additionally, Gli, a less hydrophilic compound, could reduce the exposure of pure Met to water and the opportunities for the formation of hydrogen bonds Therefore, it is reasonable to conclude that the multidrug crystals showed a significant drop in hygroscopic property when compared with Met.This could be explained by the model of Gli-Met structure, as shown in Gli was purchased from Adamas Reagent Company  and used as received. Met was prepared by adding metformin hydrochloride  and sodium hydroxide  into 70 mL of ethanol and the suspension was filtered after stirring at 25 °C for 12 h, followed by removing solvent with the rotary evaporator. The obtained free base of Met was freshly used in the next experiments. Other chemicals were purchased from Adamas Reagent Company , and used without any further purification.The boiling ethanol (35 mL) containing Gli  was added to the same volume of ethanol containing Met  and vigorously stirred. The resulting solution was kept for three days at 25 °C, yielding colorless prism-shaped crystals that are suitable for single crystal X-ray diffraction. The obtained solids were filtered and dried under room condition for further characterization.PXRD data for the crystalline products were collected using a Bruker D8 Advance X-ray diffractometer , operating in transmission geometry with Cu Kα radiation (λ = 1.5406 Å), 40 kV/100 mA. The samples were prepared on silicon single crystal sample holders with a 20 mm depth. Data for each sample were collected from 2θ = 5° to 50° at 25 °C with a step and scan speed of 5°/min.Thermogravimetric analysis was conducted in a NETZSCH STA 449 C  using a nitrogen gas purge flow of 20 mL/min and a scan rate of 10 °C/min. The sample (10 mg) was placed into a hermetically sealed aluminum pan containing a pinhole. The sample cell was equilibrated at 25 °C and then heated to 500 °C. Indium metal was used as the calibration standard.Every crystal drug has its intrinsic melting point, and the novel absorption peak can be detected with the emergence of a novel crystal by DSC. Differential scanning calorimetry analyses were carried out on a NETZSCH-TA4 STA Instruments 449C differential scanning calorimeter . Each sample (5 mg) was placed into a hermetically sealed aluminum DSC pan containing a pinhole. The sample cell was equilibrated at 100 °C and then heated to 250 °C under a nitrogen purge at a rate of 10 °C/min. Indium metal was used as the calibration standard.Single crystal X-ray diffraction (SCXRD) data were collected on a Bruker SMART CCD diffractometer  using Cu-Kα radiation (λ = 1.54184 Å) with a graphite monochromator at 293 K. The integrated and scaled data were empirically corrected for absorption effects with spherical harmonics, implemented in the SCALE3 ABSPACK scaling algorithm. Using Olex2 , the str−1.Mortars and pestles were previously washed and placed in a dryer for 30 min. Then, each compound (1 mg) was ground into powder with dried KBr (50 mg) in a mortar. The mixture was pressed into a piece of slice and recorded on a Nicolet Spectrum FT-IR spectrometer  in the range of 4000–400 cmSeveral droplets of Met, Gli, and Gli-Met were deposited on a microscope slide for observation. Optical characterization of these samples were carried out at 22 °C by POM using an Olympus transmission microscope coupled with a Leica digital camera and Leica Application Suite Software.w/v) of sodium lauryl sulfate as a dissolution medium at 37.5 ± 0.5 °C. The powder equivalent to 100 mg of Gli was weighed and added into the dissolution medium. At specified times (every 10 min for 90 min), 10 mL samples were withdrawn by using a syringe with a nylon 0.45 µm filter . The content of Gli was measured at 273 nm for Gli and 224 nm for Gli-Met using a UV-Visible spectrophotometer . Fresh medium that was pre-warmed at 37 °C was added to maintain its constant volume. Dissolution rates were performed in triplicate.The dissolution rate of pure Gli and Gli-Met in powder form were studied by using a U.S. pharmacopoeia tablet dissolution test apparatus  at a paddle rotation speed of 100 rpm in 900 mL of 0.1 N HCl containing 0.25% . Samples were mounted on a balance and studied over a humidity range from 0 to 80% relative humidity (RH) at 25 °C. Each humidity step was made if less than a 0.02% weight change occurred in 10 min, with a maximum hold time of 3 h.In conclusion, we created a novel drug-drug pharmaceutical crystal, and the process of preparation of Gli-Met is simple and the reagents used in this experiment are cheap. This new multidrug exhibits dramatic changes in the physicochemical properties such as the hygroscopicity and solubility of the two raw materials. However, it is difficult to address the issue of solubility and hygroscopicity at the same time as these factors are contradictory in essence . For exaTo the best of our knowledge, this is the first report to show a drug–drug hydrous pharmaceutical crystal of Gli based on drug combinations. The work described above shows a promising method that can be used to overcome the poor physicochemical properties of the parent drugs by forming a sandwich crystal unit. Additionally the combination of these advantages makes it an alternative for use against type 2 diabetes as opposed to pure Met or Gli. Drug-drug pharmaceutical crystals based on drug combinations could be a major trend in the pharmaceutical field.


The corrosion of steel reinforcement in concrete often leads to huge unbudgeted expenses for maintaining, monitoring and renovating an infrastructure. This is mainly due to the presence of salts or chemical chlorides that pose a danger to the concrete structures. The determination of the existence of these corrosive salts is vital for defining the service life of concrete. This research looked at developing an electromagnetic induction (EMI) sensor for the detection of corrosive salts. The first design adopted a single-loop coil (SLC) concept, and the second was based on a multiple-loop coil (MLC) one using copper wire. Tests were conducted on these two techniques, and with the results obtained, the latter seemed more promising; thus, a prototype sensor was developed using the MLC concept. As this new prototype sensor was able to detect the manifestation of chemical contents in a concrete structure, it could be used as a non-destructive evaluation (NDE) technique for the detection of corrosive chemicals in concrete and has the further possibility of detecting corrosion in concrete. Corrosion is a destructive attack on a material’s surface caused by chemical or electrochemical reactions with the environment ,2,3. It Initiation and propagation, which are the two main stages involved in the corrosion process, are supported by various mechanisms,  . During To detect corrosion in a concrete structure, many solutions have been developed, including NDE techniques that are normally preferred ,17 becauEssentially, an appropriately configured electromagnetic induction (EMI)-based technique is capable of detecting moisture, determining the presence of cracks and estimating their sizes, determining the susceptibility of concrete to corrosion, identifying regions susceptible to chloride penetration, and mapping corrosion activity ,32,33. VElectromagnetic theory is based on a set of equations produced by Maxwell in 1865 that sum all the known results in the field of electricity and magnetism, with the basic law of electricity and magnetism. In Equation (1), In particular; Faraday’s law of EMI, which is the theoretical basis of many applications, is used in this research. The basic principle of the EMI method is followed, and its concept applied for the design of a concrete corrosion sensor. Normally, in EMI, a strong direct current is passed through a transmitter loop and a receiver coil is placed in its centre which produced induced voltage signal.The currents in conductive layers decay more slowly than those in resistive ones, with the relationship among the time-varying decay amplitude, time-layer conductivity and depth quite complex. Generally, longer decay times relate to deeper depths ,46. 1k = a constant, M = the product of the current (amps) and area (m2), σ = the terrain conductivity (Siemens/m), t = the time (s), and V(t) = the output voltage from a single turn of the receiver coil in a 1 m2 area.In this research, concrete is used as the only conductor between the transmitting and receiving loops to detect the chemical properties inside the concrete. The voltage response can be separated into three different stages of early (the response is constant over time), intermediate (the shape of the response varies over time) and late (the response is a straight line on a log-log plot), and varies according to the time and conductivity as where ρ = 1/σ, the resistivity with depth can be calculated byAs the measured voltage changes linearly with resistivity, the EMI is intrinsically more sensitive to small variations in conductivity than conventional resistivity determinations. The measured voltage can be represented with respect to the apparent resistivity, and, since rM) (the area multiplied by the number of turns) multiplied by the time derivative of the vertical magnetic flux density as where µ is the magnetic permeability and tM the transmitter loop moment (L2 × I). As V(t)/rM is inversely proportional to the time over which the current diffuses downwards, it is difficult to measure at great depths unless the transmitter moment is increased.The voltage induced in the receiver coil is the product of the receiver coil moment  and (3). However, before focusing on constructing the sensor with improved dimensional accuracy, the various SLCs were tested and observed, and imperial data indicated that SLCs produce very low-level output signals ; hence, an MLC design was taken into account. During the second stage of this research, a concentric MLC sensor was designed to counter the shortcomings identified in the SLC sensor design. The proposed sensor had the added advantage of providing a larger area of detection field and greater detection depth. It was basically constructed from Category 5 (CAT 5) cables, which can withstand frequencies of up to 100 MHz. A single sheathed strand extracted from the twisted-pair cable was then wound up with a coil winder. The outer coil (transmitter) and inner coil (receiver) were constructed using 12 and six turns, respectively.Before proceeding with the MLC design, it was necessary to carry out an analysis of the behaviour of the electromagnetic field (EMF) in the region of interest. The non-commercial finite element method magnetics (FEMM) software was used to perform the 2D simulations as shown in Three concrete blocks of the same mixture were tested. Standard Portland cement CEM I 42.5R  and a quick mix  were used to cast the block specimens, which were cured for 30 days at an air temperature of 18 °C and 60% relative humidity. A mortar box frame was machined into specific sizes of a frame with an inner dimension of 150 mm × 450 mm × 450 mm, as shown in Firstly, experimental tests were conducted on the SLC sensor using the coplanar setup shown in The MLC design was similar to that of the metal detection technique used by Nabighian  but applThe same setup and procedures for generating and obtaining signals as in the first set of tests for the blocks soaked in distilled water and a NaCl solution were used for the second set, except that the sensors were placed on opposite surfaces but on the same concentric centre point, as shown in In this Section, the recorded results, with the locations of the maximum and minimum outputs critical for determining corrosion, are tabulated and analysed. Three pulses were taken from each wave signal obtained from each block and then separated into three Sections, one for each pulse. In −4 s, the second from 53,334 × 10−4 to 10,666 × 10−4 and the third from 10,667 × 10−4 to 160,000 × 10−4, with the maxima and minima obtained within these ranges shown in The first Section ranges from 0 to 53,333 × 10From the results, it is evident that the concept of using EMI to detect the presence of corrosive chemicals is possible. The signals obtained from the different concrete specimens were different, as they were subjected to different environmental conditions, and research could results in the development of novel techniques to detect salts and predict corrosion in concrete. However, further research is needed in this area as this research was a proof of concept. Further research on different salts types, salt concentration, period of exposure to salts and the mortar ratio would further enhance the research methodology.−4 to 47,934.5 × 10−4 s from For the coplanar-placed sensors, the difference in the time delays between the pulses for the dry concrete block and the concrete block soaked in distilled water was approximately 0.25 s  than those placed on opposite surfaces. This was due to a decreased distance between the transmitter and receiver, which resulted in a larger EMI strength that satisfied Equation (4). It should be noted that the potential responses shown are as measured and they are strictly limited to qualitative interpretations. Further research with extended samples is currently being undertaken for a quantitative understanding on the origin of these signals.A sensor was developed based on EMI principles following Faraday’s law of EMI. The MLC design was successful to the extent that it was capable of displaying the differences between a dry concrete block and blocks submerged in distilled water and a NaCl solution. The differences observed among the three blocks were in the time delays between the pulses extracted from the data acquisition process, which, it can be stated, were due to the blocks’ different moisture and chemical contents, which changed their resistivity levels. Therefore, if a steel-reinforced concrete structure was suspected of containing any corrosive chemicals, , this chemical could be identified by the proposed sensor technology. The newly developed prototype proves the concept of detecting corrosive chemicals present in concrete through the use of EMI-based technology. This was evident, as the results depicted that the presence of salts alters the received signal. The time delay for the dry block, one submerged in distilled water and one submerged in NaCl are 0.45, 0.25 and 1.80 s, respectively, for the prototype.2, CaCl2, and BaCl2).Interesting topics for further research on the time delay between the EMI-induced pulses detected in each concrete block could be using various thicknesses for testing and acquiring signals from sensors placed on both coplanar and opposite surfaces; constructing coils with different numbers of turns, sizes and wire materials to identify the parameters for an optimum sensor design specification; and determining benchmark values for the time delay of other corrosive solutions (e.g., MgClThis research project is part of the patent work in the field of monitoring corrosion in reinforced steel. An EMI-based sensor for non-destructive corrosion estimation in concrete has been patented under IP Australia, 2,018,100,760, 2018.


Lactobacillus brevis is a major hop-resistance bacterium which poses significant challenge for the brewing industry, mainly due to the difficulty or incapability in detection by routine culturing methodology and its beer spoilage ability.This study aimed at investigating the VBNC state of a hop-resistance strain, L. brevis BM-LB13908. The culturable, total and viable numbers of L. brevis cells were calculated by MRS agar plate counting, acridine orange direct count (AODC) method and Live/Dead BacLight bacterial viability kit with fluorescence microscope. VBNC formation was induced by 189 ± 5.7 days under low-temperature storage or 27 ± 1.2 subcultures by continuous passage in beer, and VBNC cells induced by both strategies were recovered by adding catalase. In addition, insignificant difference in beer-spoilage ability was found in 3 states of L. brevis, including logarithmic growing, VBNC and recovered cells. This is the first study on the formation of VBNC state for L. brevis and beer-spoilage ability of both VBNC and recovered cells, which indicate L. brevis strain could cause beer spoilage without being detected by routine methodologies. The results derived from this study may support further study on L. brevis and other hop-resistance bacteria, and guidance on beer spoilage prevention and control, such as improvement for brewers on the microbiological quality control by using the improved culture method with catalase supplementation. Lactobacillus strains have been verified for formation of VBNC state, including L. lindneri  and carbon dioxide concentration (approximately 0.5% w/w), low pH (3.8–4.7), low concentrations of nutritive substances and extremely low oxygen content (<0.1 ppm), as well as hop bitter compounds (approximately 17–55 ppm of iso-α-acids) . Hop comlindneri , L. caseL. casei , L. planlantarum , L. parainocides  and L. atolerans , which hLactobacillus brevis is capable of producing end or by products of carbohydrate fermentation including lactic acid and acetic acid as significant influential factors on the flavors of beer, as well as biogenic amines which are associated with food intoxication, blood pressure increasing, migraines, dystonias, Parkinson’s disease, schizophrenia, drug addiction, mental disorders and neurodegenerative disease  responsible for hop resistance have been previously studied in L. brevis strains  had been isolated from finished beer sample  and maintained as a glycerol stock stored at −80°C. Whole genome sequencing was performed for this strain and the draft genomic sequence was deposited in GenBank under accession number LTDY00000000. L. brevis BM-LB13908 shows strong hop resistance and contains the hop resistant gene horA in its genome. A small amount of stock was spread onto MRS agar  and incubated at 26°C for 3 days to obtain isolated colonies. A single colony was transferred to 1 mL of MRS broth and incubated anaerobically at 26°C for 24 h prior to further experiments.The present L. brevis BM-LB13908. Low temperature or cold treatment have also been frequently reported to induce the VBNC formation of various bacteria in previous studies (L. brevis BM-LB13908 in logarithmic growth phase were harvested at 4°C (centrifugation at 5000 rpm for 15 min) and washed twice with phosphate buffer (PBS). Then the washed cells were filtered through a 0.22 μm Millipore membrane filter and resuspended in 10 mL of degassed beer at a final density of 107 cells/mL. The bacterial cells were further maintained at 0°C for the formation of VBNC state.Based on the environment beer-spoilage bacteria encountered during beer brewing (continuous passage) and storage (low-temperature), two strategies, including low-temperature storage and continuous passage in beers were selected to conduct the formation of VBNC state of strain  studies . For the7 cells of L. brevis BM-LB13908 in logarithmic growth phase were harvested at 4°C (centrifugation at 5000 rpm for 15 min) and washed twice with PBS. Then the washed cells which marked as 0# subculture were resuspended by 10 mL of degassed beer at a final density of 107 cells/mL and anaerobically cultured at 26°C. After 7 days incubation, the cells were marked as 1# subculture and harvested, washed, and resuspended in 10 mL of fresh degassed beer. The process was repeated every 7 days.Continuous passage in beer was performed as described previously , with slIn the current study, the definition of “VBNC state” is the incapability of microbial growth on MRS agar until 3 days of incubation at 26°C. For both induction processes, the culturable cell number was accessed by inoculating 100 μL of bacterial culture on MRS agar according to a conventional plate culture procedure . After 3Number of total cells was determined every 7 days by AODC method . In brieCellular viability determination was further conducted by the Live/Dead BacLight bacterial viability kit , followed by observation under fluorescent microscope . In brieL. brevis cells. Oxidative stress was encountered by the VBNC L. brevis cells under low temperature and harsh beer condition  at final concentrations of 0.1%, 0.1%, 5 g/L, 5 g/L, and 800 U/plate. Simultaneously, MRS agar with no supplements and addition of heat (60°C for 15 min) denatured catalase were controls. After incubation at 26°C, daily examination for the microbial growth and colony formation on agar plate was performed, with the day of first observation of colonies recorded as detection time.After the VBNC state induction process, chemicals addition was performed for recovery of VBNC ondition , adding ondition . Tween aondition , were alL. brevis BM-LB13908  and quantified by external standard method  of three independent biological replicates. Statistical comparisons were made by one-way analysis of variance followed by Tukey’s comparison test (XLstat software). The 5 cells/mL, whole population of L. brevis cells were no longer culturable after 189 ± 5.7 days . According to the continuous passage in beers, formation of VBNC state of L. brevis strain BM-LB13908 was found with 27 ± 1.2 subcultures . The present results had verified the induction on VBNC state of L. brevis by simulating conditions during beer brewing. It was also found that the culturability of L. brevis declined significantly during conditions induced by beer subculture or low temperature, indicating the VBNC L. brevis could be potentially neglected in brewery environments due to incapability of detection by traditional culture methods. As Lactobacillus strains were concerned, up to date, a total of five species have been validated for VBNC state formation, including L. lindneri  appeared on MRS agar supplemented with catalase at day 3. Thus, VBNC L. brevis cells regained culturability on media containing catalase. Importantly, no colony appeared on the MRS agar plates with no supplementation and addition of heat-denatured catalase. Heat denaturation of catalase deferred the recovery process, verifying catalase addition is capable of recovery of VBNC L. brevis cells. Such finding suggested the potential improvement for brewers on the microbiological quality control by culture methodology with catalase supplementation. It has been reported that transfer of cells to nutrient-rich environment initiates a metabolic imbalance, thus leading to a rapid production of superoxide and free radicals , suggesting its maintenance of beer-spoilage capability in both VBNC and recovered state. No turbidity was observed in the non-inoculated beer. In addition, higher level of both lactic acid and acetic acid were found after incubation for 30 days, which may eventually lead to beer acidizing (Table 1). It indicates both VBNC and recovered cells retained as similar level of viability and metabolic activity as logarithmic cells, which was in accordance with previous studies (L. brevis is capable of VBNC formation under common food storage condition (low-temperature), recovery by addition of catalase, as well as maintained production of lactic acid and acetic acid, which may be the leading cause for a wide range of beer spoilage cases. In addition, it indicated that the normal, VBNC, and recovered L. brevis cells are capable of causing spoilage within the storage life of beer.According to the results, the logarithmic, VBNC, and recovered cells of  studies . As the L. brevis, as well as beer-spoilage ability of both VBNC and recovered cells. For L. brevis strain BM-LB13908 in the present study, VBNC formation and recovery, as well as maintenance of beer spoilage capability have been verified, which indicated L. brevis strain could cause beer spoilage due to incapability of detection by routine methodologies. The results derived from this study may aid in further study on L. brevis and other hop-resistance bacteria, and guidance on the prevention and control of beer spoilage, such as improvement for brewers on the microbiological quality control by using the improved culture method with catalase supplementation.In conclusion, this is the first report on the VBNC induction and recovery of ZX and YD conceived of the study and participated in its design and coordination. JL and YD performed the experimental work. LL, JS, and BL analyzed the data. JL, YL, BP, MS, and ZX prepared and revised this manuscript. All authors reviewed and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MC and handling Editor declared their shared affiliation.


The unnecessary use of antibiotics and concomitant rapid growth of antibiotic resistance (ABR) is a widely acknowledged threat to global health, development, and sustainability. While the underlying cause of ABR is undoubtedly the overall volume of antibiotic use in general, irrational antibiotic use, which is influenced by several interrelated factors, is a major contributory factor. Here, we aimed to present and describe selected main drivers of irrational use of antibiotics in Europe. We performed a broad search of the current literature in databases such as PubMed, Google Scholar, Cochrane, as well as various institutional websites  to provide a new perspective on selected drivers of irrational antibiotic use in Europe. We also searched for relevant literature using snowballing, i.e., using reference lists of papers to identify additional papers. In this narrative review, we present that major factors among the general public driving antibiotic resistance are lack of public knowledge and awareness, access to antibiotics without prescription and leftover antibiotics, and knowledge attitude and perception of prescribers and dispensers, inadequate medical training, pharmaceutical promotion, lack of rapid and sufficient diagnostic tests, and patient–doctor interaction as major factors among healthcare providers. We further discuss initiatives that, if taken and implemented, can have an impact on and improve the current situation in Europe. Antibiotics are one of the most cost-effective, life-saving medicines and contribute to an extended lifespan . HoweverAntibiotic resistance in common pathogens is consistently reported to be higher in countries that have a higher use of antibiotics . The EurDuring the period 2012–2016, a statistically significant decreasing trend in antibiotic use was observed in Finland, Luxembourg, Norway, and Sweden, while an increasing trend was observed in Greece and Spain. In 2016, antibiotic consumption for systemic use in the community  in Greece was 36.3 defined daily doses (DDD) per 1000 inhabitants per day (DDD/TID). Meanwhile, in the Netherlands, less than a third of this volume was used (10.4 DDD/TID).Klebsiella pneumoniae is strongly associated with carbapenem consumption. Therefore, data showing that more than one million carbapenem prescriptions are issued in Europe each year is a major concern.Although only 10–20% of all antibiotics are used in hospitals, the intensity of use is far higher than in the community. Hospitals are key locations in which final recourse antibiotics—such as carbapenems and polmyxins—are used ,6,7,8. FThe health and economic consequences of ABR are severe. Today, drug-resistant infections lead to approximately 700,000 deaths per year globally. This is projected to increase to 10 million by 2050, with associated costs as high as US $100 trillion worldwide if no action is taken . Each yeAlthough the absolute consumption of antibiotics is the largest in high-income countries, antibiotic consumption increases the fastest in low- and middle-income countries (LMICs)  which alKlebsiella pneumoniae isolates overall did not increase in Europe between 2014 and 2017 (20.8% to 20.5%), increasing national trends were reported from several countries. In 2017, 7.2% of Klebsiella pneumoniae isolates were identified as resistant to carbapanems, with an enormous variation across Europe from 0% in several countries, such as Croatia, Estonia, Iceland, Luxembourg, Norway, and Slovenia, to 64.7% in Greece. At the same time, 14.9% of Escherichia coli isolates were identified as resistant to third-generation cephalosporins, ranging from 5.9% in Norway to 41.3% in Bulgaria. For Escherichia coli and Klebsiella pneumoniae, combined resistance to several antimicrobial groups was frequent, and extended-spectrum beta-lactamase (ESBL) production was common. A majority (87.4%) of the third-generation cephalosporin-resistant isolates from 2017 were extended-spectrum beta-lactamase (ESBL)-positive. Methicillin-resistant Staphylococcus aureus (MRSA) invasive isolates reached a proportion of 16.9%, with large variations across Europe (1.0% in Norway to 44.4% in Romania) ’.Pharmaceutical promotion is also believed to increase irrational prescribing. The EU regulation on pharmaceutical promotion states that advertising must be consistent with the approved product information and cannot be misleading. It also states that Member States shall ensure that there are adequate and effective methods to monitor the advertising of medicinal products. However, it has been argued that, globally, even countries with adequate resources for regulatory oversight vary greatly in the extent to which they effectively monitor pharmaceutical promotion and enforce laws with adequate sanctions . PharmacA core problem behind the incorrect prescribing and use of antibiotics is the lack of sufficient diagnostic tests to rapidly identify the pathogen and its antibiotic susceptibility profile, guide antibiotic prescribing at the point of care, and reduce the need for broad spectrum antibiotics . ConventThe availability of regional antibiotic susceptibility data for most common bacteria to inform medical practitioners vary across European countries. Many countries report the data only from a small number of hospitals in a specific geographical location. Therefore, the sample cannot be representative and may not show variations at the regional level within a country . The samIn 2015, the WHO launched the Global Antimicrobial Resistance Surveillance System (GLASS) , the firMany studies have shown the relevance of the patient-doctor relationship and communication for the prescribing of antibiotics. A qualitative study from UK showed that doctors overestimated patients’ expectations for antibiotics and prescribed antibiotics to maintain a good patient-doctor relationship . A surveThe consequences of antibiotic misprescribing and/or overprescribing are severe and have a major impact on the development of ABR, the medicalisation of patients’ symptoms, and increasing healthcare costs . The vasAs part of the standard dispensing process, pharmacists in community and hospital settings provide counselling  on the safe, effective, and rational use of medicines . A studyIn some countries, dispensing without a prescription is still a common practice. A study from Spain showed that pharmacists attributed the problem of antibiotics dispensed without a prescription—and its relationship to ABR—to the attitudes and/or factors, such as the external responsibility of doctors, dentists, and the National Health Service, acquiescence, and lack of continuing education . A studyA study from Romania evaluating the perceptions and attitudes of pharmacists toward their role in respect to antibiotic consumption and resistance showed that pharmacists encounter many barriers in their activities related to antibiotic management, such as when they see how the healthcare system impacts the patient’s ability to seek care . The finTo minimise further increase in ABR, we hereby propose immediate and effective actions needed to improve use of antibiotics, from all stakeholders, including international organizations, governments, researchers, and private and public sector clinicians. Providing education at all levels  is essential to ensure rational use of antibiotics and to suppress the spread of ABR. Public education campaigns have been shown to be effective in changing attitudes and knowledge regarding antibiotic use and resistance ,56 and sImproving education for healthcare professionals has recently been widely promoted as a potential method for optimising antibiotic use . SpecialClinicians should support the education of patients regarding antibiotic use and resistance. For example, they could use effective strategies, such as shared decision making, to alert people to the actual risk of acquiring antibiotic-resistant bacteria following antibiotic use. Patients need to stay informed and receive independent information on antibiotics, as better health literacy and a higher degree of knowledge and awareness about the appropriate use of antibiotics are associated with decreased consumption. Preventing leftovers from previous courses of antibiotics may be one effective way to prevent self-medication with antibiotics. This can be done through technical measures, such as promoting the dispensing of the exact number of tablets, or by educating patients not to use leftover medications. Moreover, take-back programmes, including the return of unused or excess drugs to pharmacies, are recommended by the WHO . Most peSurveillance is one of the cornerstones of combating ABR. Lack of surveillance can lead to misdirected and inefficient policies and waste of resources. It is essential to understand trends in antibiotic use and resistance, inform treatment guidelines, identify priorities for intervention, tailor and target interventions, and monitor the impact of interventions. In a very recent draft opinion on ABR, developed by the European Parliament, it was emphasised that routine collection and submission of monitoring data at the EU level should be mandatory . The WHO has recently undertaken many initiatives to map information regarding antibiotic use and resistance. The implementation status of countries’ action plans to address ABR across all sectors can be monitored via the WHO website . In EuroThere is a shortage of a coordinated priority setting in antibiotic research and development spending. The current pipeline demonstrates a lack of truly valuable new antibiotics, vaccines, and diagnostics. Moreover, most publicly funded research and development initiatives in this area target the basic research phase. Much less funding is available for later stages of antibiotic development, clinical studies, and post-marketing surveillance, which require continuous financial support. Focused research is needed to help to develop new, effective treatment principles. The pharmaceutical industry has an important role in the overall effort to ensure the just and prudent use of antibiotics. Product development partnerships (PDPs) have the potential to address the lack of development of new antibiotics and to focus on unmet medical needs and should always include stewardship principles of any treatments that result from collaboration.Innovative, affordable, and easy-to-use rapid diagnostic tests are needed to allow immediate identification of potentially infective organisms and to support doctors in deciding whether or not to initiate antibiotic therapy and thus improve the management of infectious diseases. It is also crucial to identify novel therapies that do not drive resistance. Numerous monoclonal antibodies have shown the potential to treat infectious diseases in preclinical evaluation, both in vitro and in animal models. As of November 2016, there were at least 38 monoclonal antibody products in active clinical development for 14 infectious diseases .Research and development incentives based on the principle of delinkage should be applied in lieu of the traditional reward of market exclusivity (such as patents) to ensure the affordability of end products. The WHO and Drugs for Neglected Diseases initiative project on the Global Antibiotic Research and Development Partnership (GARDP) is a good example of an alternative, public health-driven model of innovation. More stewardship from governments regarding research and development agendas is needed. In the EU-supported Driving Reinvestment in Research and Development for Antibiotics and Advocating their Responsible Use (DRIVE-AB) project conducted from October 2014 to December 2017, several incentives have been determined to be the most effective in stimulating the antibiotic pipeline and ensuring that critical antibiotics continue to be accessible and can be used sustainably . Grants Governments should ensure proactive and effective control of pharmaceutical promotion, taking into account the threat to public health of antibiotic overuse and misuse. At a minimum, all promotional material on antibiotics should undergo a system of pre-vetting. Pharmaceutical products with antibiotic components should only be available as prescription only (PO), except where the healthcare system requires otherwise. Political will and coherence at the European level is needed to achieve an ambitious plan to reduce the emerging growth of ABR.The EU has taken several actions to mitigate the growing problem of ABR. After a revision of its Action Plan against the rising threats from antimicrobial resistance, implemented during 2011–2016, on 29 June 2017, the EU launched a new, more comprehensive One Health Action Plan. It contains 75 actions aimed at supporting the EU and its Member States in delivering effective and sustainable responses to ABR. The new EU One Health Action Plan takes a multisectoral approach, links EU and international actors, and mentions the possibility for funding Member States’ actions against ABR and boosting research and innovation. However, a number of shortcomings, such as the lack of a precise description of actions to support Member States and the engagement of various stakeholders that threaten this ambitious EU goal, have been identified. It was acknowledged that in order to achieve the common goal of reducing ABR, support for the development and implementation of national action plans and the allocation of adequate funds must be provided to the countries with the highest prevalence of ABR—and probably the lowest level of resources —and that strong national organisational structures are essential. The successful adoption and implementation of the Action Plan depends on the input of various actors—such as NGOs—who should be involved. The available and newly generated data should be used through the Action Plan as a benchmark for national reduction targets . The severe health and economic consequences of ABR are well-recognised. The described drivers of irrational antibiotic use show the complexity of the problem that needs to be tackled from different angles. Although the number of initiatives and actors working on ABR is massive, they all emphasise the importance of urgent action to combat ABR, the need for international, cross-sectorial collaboration, education of the public and healthcare professionals, and foremost, the importance of a One Health approach. Humans, animals, the food chain, the environment—and the interconnectedness among them—should be treated as one entity to enhance public and animal health, and to benefit European and national economies.


The applicability of mesoscopic models plays an important role in studying the mesoscopic mechanical properties of concrete. In this study, the computerized tomography (CT) test of concrete under uniaxial compression conditions is conducted using a portable dynamic loading equipment developed by Xi’an University of Technology and a medical Marconi M8000 spiral CT scanner. On the basis of damage partition theory, a probabilistic statistical method for determining threshold values is proposed, and a CT test images is obtained and divided into aggregate, hardened cement and hole-crack areas. A ‘structural random numerical concrete model’ is also established on the basis of the coordinates of each pixel unit in CT images. Uniaxial static compression and tensile numerical simulation tests are conducted. Results show that the structural random numerical concrete model can not only reflect the microscopic composition of concrete but also the interfacial transition zone (ITZ) between aggregate and mortar. The ITZ thickness is approximately 0.04 mm, which is close to the real concrete sample ITZ thickness (approximately 10–50 μm). In the two tests, the specimen damage starts from the initial defects, and the damage crack expands through the weaker ITZ around the aggregate. No matter under the action of static tension or compression load, the damage cracks of the sample almost never pass through the aggregate. Most of the many cracks in uniaxial compression are shear cracks. However, many cracks form at the beginning of uniaxial tension, and only one main crack, which is roughly perpendicular to the loading direction, exists in the end. Since the proposal of ‘numerical concrete’ by Roelfstra et al., meso-scale numerical models based on finite element (FE) analysis have been widely used in the research of rock and concrete . HoweverTo date, a number of efforts have been devoted to generating realistic aggregate shape, size distribution and spatial distribution in numerical simulations of concrete behaviour. Many methods have been developed based on advanced computer technology to realistically simulate aggregates in 2D and 3D. In 2D numerical models, aggregates are often simulated as having circular shapes ,5,6,7, aAlthough the virtually-generated numerical concrete by the methods mentioned above may have the same internal structure as real concrete in terms of size distribution and volume of aggregate, its limitations are also obvious in terms of the spatial distribution and shapes of aggregates. Therefore, it is necessary to develop innovative methods to more accurately model the micro/meso structures of concrete.However, CT scanning techniques can obtain the 3D internal structure of objects using X-rays. Thus, these techniques have been routinely applied in hospitals. CT scanning technology has become a powerful tool for describing the mesoscopic structure of materials due to its high-resolution, non-destructive and clear 3D visualisation properties. In the past decade, researchers have successfully applied this technology to characterise mesoscopic structure and study damage evolution of various materials, such as Man and Mier ,20,21 maIn fact, according to the CT imaging principles , variousTo this end, a CT test of concrete under uniaxial compression conditions is conducted. In accordance with the test results, a concrete scanning pattern is quantitatively partitioned on the basis of damage partition theory. The method of determining partition threshold is studied. Then, ‘structural random numerical concrete model’, a 2D mesoscale FE model, is developed. By using the secondary development of ANSYS software, the numerical simulation of concrete under uniaxial compression and uniaxial tensile stress is performed by introducing the double-fold damage constitutive model. Finally, the crack evolution of concrete under tensile and compressive stress is studied. This test adopts the newly developed portable power loading equipment of Xi’an University of Technology, which is the first power loading test equipment with CT scanners in China . The CT This test uses a first-grade C15 concrete cylinder test piece with a size of Φ60 mm × 120 mm, a water-cement ratio of 0.4 and an aggregate particle size of 5–20 mm. Samples are cured for 28 days under standard conditions, and the test is then conducted.During the test, the concrete specimen is placed between the two pistons in the loading device, and a small force is initially applied. In this manner, the specimen does not slip. Then, the portable loading device is placed in the centre of the CT scanner through the hospital bed, and the initial scanning is performed. The initial scan results are used as a comparison between the loading stages of the scan. The loading is stopped every scan, and the loading is repeated in accordance with the loading, scanning, reloading and scanning sequences until the concrete breaks. Displacement loading method is adopted, and the loading rate is 0.002 mm/s. The scanning is performed 11 times. The number of scanning layers of the sample is 70 longitudinal layers and 24 transverse layers. Each scanning layer is evenly arranged in accordance with the sample. The scanning position and the stress–strain curve are shown in The larger the CT number in the CT image, the higher the brightness, and the greater the density of the representative material. The brighter areas in the x, y, z)| is an arbitrary point on the study object space area}. Any point in the whole field is complete, but the integrity is different. On this basis, the integrity can be defined as follows [H is the CT number of the space point , which can be defined as follows:On the basis of fuzzy mathematics theory, the entire CT scan image is called the whole field, which is represented by a set as Ω = {( follows :(1)P area, which is recorded as When The division is based on the CT number. Thus, the fine aggregate in the mortar is also divided into the aggregate area in the division, whereas only cement hydration and hardening products remain in the cement mortar. In this study, these products are called ‘hardening cement’.λ1 and λ2. For homogeneous rocks, λ1 and λ2 can be obtained using maximum-minimum method. However, for concrete, this method cannot be used. This method is proposed based on homogeneous materials. Hence, its applicability to heterogeneous materials, such as concrete, is limited. Therefore, the method of probability statistics is used to determine the threshold.The focus of the partition is how to determine reasonable partition thresholds Concrete is a composite material composed of aggregates, mortar and ITZ. The idea of partition indicates that a component of its resolution unit should be continuous and gradually distributed to avoid large jump changes. The distribution of the resolution units among different components is bound to a certain jump. Therefore, a total of 137,027 resolution units are required to select a CT scan as a universe Ω. The statistical relationship between the threshold and the resolution unit is shown in λ1 and λ2 are preliminarily 0.7 and 0.84, respectively.As shown in λ1 and λ2, whose threshold centres are on 0.7 and 0.84, respectively. As shown in λ1 and λ2 are set as 0.698 and 0.843, respectively.To improve the accuracy of the threshold selection, two sub-areas are selected for the statistical analysis of The reconstruction of the structural random numerical concrete model is based on the initial CT scan image of the uniaxial compression CT test, as shown in P), the extracted CT numbers are normalised. Then, following the concept of intercepted sections, the CT scan image is divided into aggregate, hardened cement and hole–crack areas, which are marked as P0–λ1, Pλ1–λ2 and Pλ2–1, respectively.The first task of modelling is to perform image localisation. Then, the CT number of CT images is extracted. The coordinates of the resolution unit in the CT scan image were used to determine the location of the modeling image, and the selection point of the graph coordinates was judged according to the CT value of the resolution point, The positioning accuracy of the image is one CT pixel (approximately 0.009 mm). Following the concept of integrity D={0 ε0 is the main tensile strain corresponding to the tensile strength, εris the tensile residual strain:εu is the ultimate tensile strain:According to literature , λ is seFor brittle materials, such as concrete, both tensile failure and compressive failure are ultimately due to the fact that the tensile stress exceeds its ultimate tensile strength. Therefore, the maximum tensile strain strength criterion is adopted in this paper, that is, the element starts to damage when the maximum principal tensile strain value of the element exceeds the given limit tensile strain threshold, and the element still has a certain bearing capacity. The damage evolution model is shown in Equation (6).Generally, material parameters determine the accuracy of the numerical test results. Hence, to maintain consistency in physical and numerical test results, reasonable physical test parameters must be used. In accordance with the physical tests, the material parameters as shown in When the unit’s maximum tensile strain reaches To match the numerical simulation test results with the physical CT test, the constraint conditions in the numerical simulation are the same as those in the physical test. As such, the bottom surface is fully constrained and the top surface is horizontally constrained. Displacement loading is used for loading.−4 m, and the loading stops when the sample is broken.Displacement loading method is adopted in this test, and the loading steps were consistent with CT test. Each loading is 2 × 10The results of the tests based on the above conditions are shown in As shown in The change law of horizontal displacement  is similThe main stress nephogram of each loading stage of sample under uniaxial compression loading is shown in The law of crack propagation has always been a topic of interest in the research on concrete, and its analysis can reveal the intrinsic mechanical properties of concrete from the root. As shown in In accordance with the above analysis, simulating the damage evolution process of concrete under uniaxial compression by using the structural random numerical concrete model and the damage evolution equation of double broken line is suitable. This method can also effectively reflect the damage and failure mechanism of the interior of concrete under compression.In the uniaxial tensile test, except for the loading direction, the other conditions and parameters are the same as that of uniaxial compression test. A total of 10 loading tests are performed with the displacement as the loading method. The test results are shown in In view of the stress, the stress distribution of the specimen under uniaxial tensile load is similar to that under uniaxial compression loading The method of determining the threshold using probability statistics method is proposed. The concrete CT scan is divided into aggregate, hardened cement and hole-crack areas  in accordance with different thresholds. The integrity of CT image information is ensured, thereby giving full play to the value of CT numbers of each resolution unit.(2)On the basis of the coordinates of each pixel unit in the CT scan, the structural random numerical concrete model is established using the secondary development of ANSYS software. The model is similar to the actual concrete sample. It not only can reflect the mesoscopic composition of concrete but also the bonding ITZ between the aggregate and the hardened cement. The thickness of the ITZ established by the model is approximately 0.04 mm, which is close to the real ITZ thickness (approximately 10–50 μm) and considerably smaller than the ITZ (greater than 1 mm) formed by using the random aggregate model. As such, the numerical tests show that the simulated mechanical properties of concrete are authentic.(3)The numerical simulation tests results show that in all tests, the damage crack of concrete sample experienced the process of initiation, slow expansion, slow penetration and sudden rapid penetration, the damage of the specimen begins from the initial defect and the damage cracks then propagate along the weak ITZ around the aggregate. Most of the many cracks that form in the uniaxial compression test are shear cracks. In the uniaxial tension test, many cracking points form at the beginning and multiple cracks develop simultaneously. However, only one major crack is present at the end of test, which is roughly perpendicular to the loading directions. No matter under the action of static tension or compression load, the damage cracks of the sample almost never pass through the aggregate, which is consistent with the results of physical CT test.(4)This study results can provide a certain methods and theoretical basis to static and dynamic characteristics research of mass concrete. The study only established the mesoscopic structure of concrete from a two-dimensional perspective, cannot study the concrete from the three-dimensional perspective. The next study should be establish three-dimensional concrete numerical model based on two-dimensional concrete structure, and study the effect of material heterogeneity to the static and dynamic characteristics of mass concrete based on CT number.(5)The calculation results of the traditional model have significant mesh size dependence in the numerical simulation study, and the regularization method is often used to correct it. However, the mesh dependence problem is not considered in the numerical simulation, which is a defect of this study, the authors are going to focus on the analysis and solution of this problem in subsequent research.This study uses the damaged partition method to reconstruct the structure random numerical concrete model, with the pixel points of the CT scan as the unit. The numerical simulation test is compared with the physical CT test. The following conclusions can be drawn:


L-shaped concrete filled steel tube (L-CFST) columns are used frequently in civil engineering, and the concrete damage inside the L-CFST column is difficult to monitor. This research aims to develop a new method to monitor the internal concrete damage in the L-CFST column by using embedded piezoceramic smart aggregates (SAs) under low frequency cyclic loading. The SA enabled active method is used to monitor the concrete damages near the bottom of the L-CFST columns, and the wavelet packet analysis is used to establish a damage index, which is used to analyze the acquired data. During the experiment, three L-CFST columns with different wall thickness of the steel tube were tested. The experimental results find that the structural damage indices under the low-frequency cyclic loading are basically consistent with the results of the hysteretic curves and the skeleton curve of the specimens, and are in good agreement with the experimental phenomena. We conclude that the use of smart aggregate can directly and clearly reflect the damage process of the concrete core, demonstrating the feasibility of using piezoceramic smart aggregates to monitor the internal concrete damage of the L-CFST column. In recent years, high performance and multi-functional materials and structures have received much attention ,2,3,4. AAt present, the methods of structural damage detection include X-ray, acoustic emission, and ultrasonic methods ,17, amonIn recent years, smart materials, such as optical fibers and piezoelectric materials ,24,25, hPiezoelectric transducer based structural damage detection methods include two major categories: the electromechanical impedance method ,49,50 anThe active sensing method using piezoceramic smart aggregate is commonly used for monitoring concrete structural damage. The active sensing method uses a smart aggregate as an actuator and another smart aggregate as a sensor. Using the inverse piezoelectric effect, the smart aggregate actuator generates a stress wave, which propagates along the interior of the structure to the piezoelectric smart aggregate sensor. Using the direct piezoelectric effect, the sensor converts the received stress wave into an electrical signal effect. Once there are cracks inside the structure, the signal received by the piezoelectric smart aggregate sensor will attenuate. Therefore, the internal damage of the structure can be analyzed. Gu et al.  used SA From the above applications, it can be found that the existing smart aggregate-based damage studies are mostly conducted under static loading, however, less experimental studies are carried out under dynamic loading. Gu et al.  embeddedAt present, the study of structural damage detection under dynamic loads using SAs is mainly about reinforced concrete structures, and there is little research on the internal concrete damages of concrete filled steel tube structures. CFST structure is a structure filled with concrete inside the steel tube, and its bearing capacity is shared by the steel tube and the internal concrete. The damage of the concrete core will greatly impact the bearing capacity of a CFST. In this research, three L-CFST columns with different wall thicknesses of steel tube were used in this experiment. Piezoelectric smart aggregates were embedded inside the L-CFST columns. The active sensing method based on SA was used to monitor the concrete damage inside column base of L-CFST columns under low-frequency cyclic loading, and wavelet packet analysis was used to establish a damage index, which was then used to analyze and process the monitoring data. The experimental results find that the structural damage index under the low-frequency cyclic loading is basically consistent with the results of the hysteretic curves and the skeleton curve of the specimen. The use of smart aggregate enabled active sensing can directly and clearly reflect the damage process of the concrete core in the L-CFST specimens.λ is the slenderness ratio of the specimen, which is defined asL is the effective length of the test specimen and i is the radius of revolution of the test specimen, and is defined asI is the moment of inertia of the specimen and A is the cross-sectional area of the specimen. Please note that the Q235 steel is used to fabricate all the specimens.Three L-CFST columns were designed and fabricated in the research with the consideration of the cost. The limb length of all of the columns is 200 mm with the length of 1300 mm and the width of 100 mm. The wall thicknesses of the columns are 3 mm, 4 mm, and 5 mm, respectively. The shop drawings of the specimen are shown in As the first step to fabricate the L-CFST specimens, two smart aggregates (SAs) were tied to steel bars, as shown in yf and the ultimate strength uf are shown in The steel plates used in the tests were processed into standard test specimens, each with different thicknesses of 3 mm, 4 mm, and 5 mm, for tensile testing. The test method is carried out according to the relevant provisions of the Chinese standard (GB/T228-2002), and the yield strength cuf = 48.35 Mpa on the 28th day, and the mechanical properties of the concrete are shown in The C45 commercial concrete was poured into the tube, and three standard concrete cubes with the dimensions of 150 mm × 150 mm × 150 mm were prepared at the same time. The test blocks and L-CFST column were naturally cured under the same conditions. The compressive strength of the concrete cube in the steel tube is measured by a cube test block. The mean value of the compressive strength of the concrete standard test block measured was The schematic and physical diagram of this test device are shown in Before the test, preloading along the axial direction was applied twice to stabilize the load and deformation of the specimen, and then the vertical axial force is increased to the full load. Preloading was also applied laterally twice to eliminate the non-uniformity in the steel column and to check the performance of the instrumentation. The displacement control loading method was used in this test. First, the yield displacement of the specimen was estimated. At the initial stage of loading, when the displacement did not exceed the yield displacement, the loading displacement was loaded in incremental increments of less than 5 mm, and each load was performed once. When the displacement exceeded the yield displacement, the control load was applied with a multiple of the displacement, and each loading displacement was repeated three times until the lateral loading force of the specimen fell below 85% of the peak loading force, and then the loading was stopped. The specimen was considered to have been totally damaged at this stage. The test loading schedule is shown in In the three specimens of this research, two SAs were embedded inside each specimen. The SAs are named SA1–SA6 according to the serial number of the components and are shown in During the loading process, the anterior side of the test specimen is defined as the negative direction and the posterior side is defined as positive. The cross-section of the specimen is numbered to facilitate the description of the test phenomenon of the specimens, as shown in The test phenomenon of the specimen L-CFST2 is described as follows, and the test phenomena of other specimens are basically similar. During working conditions 1–6, the specimen has no obvious change, and during working condition 8, side 1 of the specimen appears slightly buckled. During working condition 13, the side 3 of the specimen appears slightly buckled, and during working condition 14, the negative lateral load of the specimen reaches the peak (Pmax = −102.272 kN). At working condition 20, side 2 of the specimen appears slightly buckled, and at working condition 25, side 4 of the test piece specimen appears buckled and the lateral load reaches its peak (Pmax = 110.920 kN). At working condition 32, side 6 of the test specimen appears buckled and the weld of the specimen is cracked. At working condition 35, the weld of the specimen is cracked, and the lateral load of the specimen has dropped to 85% of the peak value, and the experiment stops loading. In the test, the buckle locations of the specimen side are found to be about 5–9 cm above the stiffener, and the buckle of the side increases with the subsequent load. The images of the buckle on the side are shown in The lateral force-displacement curve under the low-frequency cyclic loading clearly shows the hysteretic effect. The hysteretic loops effectively reflect the seismic performance of the specimen, including the energy dissipation performance of the specimen. A skeleton curve refers to an envelope curve of hysteresis loops and is drawn by concatenating the peak points of the first cycle. The skeleton curve shows the peak point trajectory of the horizontal force of the CFST column under various displacements, and it reflects the ductility and strength change of the specimen during the entire loading process.The trends of the hysteresis loops and corresponding skeleton curve development of the three test specimens are basically the same in the tests. The hysteresis curves and skeleton curves of all the three specimens are shown in The skeleton curve and hysteresis loops of L-CFST2 specimen are described here, and the other specimens are basically the same. The skeleton curve and hysteresis loops of the L-CFST2 specimen are shown in The three cycles of the skeleton curve of each amplitude of the specimen L-CFST2 are plotted in The skeleton curves of the three specimens are shown in S output by smart aggregate sensor is processed by wavelet packet analysis. The signal S is decomposed with n-level wavelet packet into 2n wavelet packet signal sets j is the frequency band index . m represents the number of sampling data. In addition, the energy In order to monitor the internal damage degree of the specimen, the signal 2,⋯,S2n} , Sj is ti, the energy vector of the signal can be expressed asAt time DI) of the specimen asj band index at time i.In this paper, the root mean square index is used to define the internal concrete damage index , we can see that when the energy vector approaches The wavelet packet-based damage indices of the sensors SA2, SA4, and SA6 are shown in The first cycle damage index graphs of the three test specimens are shown in Taking the L-CFST2 as an example, the internal concrete damage during the test is analyzed in detail with the help of the DIs. According to The positive peak displacement damage index curves of the three test specimens are plotted in The high cost of fabricating the specimens prevented us from making more specimens. Though this research involves only three specimens of L-shaped Concrete Filled Steel Tubes (L-CFSTs) with different wall thickness, the results of the three specimens are very consistent, which demonstrates that three specimens are enough to demonstrate the proposed method to monitor the internal concrete damages using embedded smart aggregates.This research develops a new method to monitor the internal concrete damages in the L-shaped concrete filled steel tube (L-CFST) columns by using embedded piezoceramic smart aggregates (SAs). The SA enabled active method is used to monitor the concrete damages near the bottom of L-CFST columns, and the wavelet packet analysis is used to establish a damage index. Three L-CFST columns with different wall thickness of the steel tube were designed, fabricated, and tested. The analyses of the test results of three L-CFST columns show that the damage index value of the specimen initially increases linearly with the increase of the loading displacement, and then gradually approaches 1, and then it will remain basically unchanged. The displacement-damage index histogram shows that the damage of the concrete inside the specimen increases with the increase of the loading displacement. With the increase of the number of cycles, all three specimens show no significant changes in the concrete internal damage of the specimen under the same displacement amplitude loading. Comparing the positive-negative peak displacement and the 0-displacement index histogram of the damage index, the value of the damage index continuously changes with the loading of the low-frequency cyclic load, which is well reflected by the phenomenon that repeated opening and closing of concrete cracks in the core area in the low-frequency cyclic loading process. The analysis result of the data monitored by the smart aggregate under the low-frequency cyclic load is basically consistent with the analysis results of the hysteresis curve and the skeleton curve of the specimen. The test results demonstrate that the use of smart aggregate can directly and clearly monitor in real-time the damage process of the concrete core, which is not directly visible. It can be concluded that it is feasible to use smart aggregate enabled active sensing to monitor the internal concrete core damage of a concrete filled steel tube structure.


Antibiotics are one of the most commonly prescribed medications in hospitalized patients, with up to half of prescriptions being irrational. This study aimed to assess the quality of antibiotic use among surgical inpatients at our institution.A one year  retrospective chart review on antibiotic use for patients admitted to the surgical department at AIC Litein Hospital, a faith based non-governmental health institution in Western Kenya, was conducted. Data were collected from medical and nursing patient charts with a standardized questionnaire. The criteria applied to assess inappropriate antibiotic use focused on the choice, duration and indication of the antibiotics prescribed.A total of 394 cases were evaluated, with a mean age of 44.8 years and a mean duration of hospitalization of 7.2 days. Antibiotics were initiated either for prophylaxis  or treatment  for a mean duration of 6 days (range 1-37). The predominant route of administration was intravenous . Most antibiotics started at admission were continued till discharge and the duration of antibiotics was indicated in only 11% of the treatment sheets. At discharge, 321 (81.4%) cases had antibiotics prescribed for a mean duration of 5.7 days (range 1-60). Inappropriate prescriptions were noted in 45.4% of prophylactic antibiotics, 33.4% treatment antibiotics and 52.6% of discharge antibiotics. The most common reason for inappropriate antibiotic use during hospitalization was inappropriate duration (45.9%).Proper documentation, daily antibiotic review and preparation of a local antibiotic policy guideline could help improve the appropriate use of antibiotics. Antibiotics are one of the most commonly prescribed medications in hospitalized patients, accounting for up to 50% of total drug cost -4. Ratiost to December 31st 2015 were included in the study. Patients with incomplete/missing data were excluded from the study. Data concerning patient demographics, diagnosis, surgeries, name and duration of antibiotics prescribed, complications, outcome and duration of hospitalization were recorded from the individual case records. The data was then entered into a preformed data sheet and analyzed using descriptive statistics. An antibiotic given was considered to be inappropriate by the following criteria: 1) The antibiotics were prescribed for a condition that does not need treatment with antibiotics (inappropriate indication). 2) The antibiotic chosen was too broad, too narrow or ineffective for the particular condition (Inappropriate choice). 3) Wrong duration of therapy (Inappropriate duration). Permission to carry out this study was granted by the Institutional Research Board (IRB) at AIC Litein Hospital.This retrospective review was undertaken at AIC Litein Hospital, a referral faith-based facility in Western Kenya, Kericho County, Litein town with 200-bed capacity, serving a population of up to 400,000 people. All in-patients admitted to the surgical department during the period of January 1A total of 430 files were retrieved for analysis, with 36 being rejected due to inadequate information (n = 10), missing treatment sheets (n = 10) or admission to other wards (n = 16). The 394 cases represented 368 patients as 24 patients were admitted twice during the duration of the study, and one patient was admitted three times. The group had a mean age of 44.8 ± 22.2 years and a male predominance at 71.3%. The mean duration of hospitalization was 7.2 ± 6.2 days, with most patients  being admitted for 1-7 days. The rest were distributed as 78 (19.8%) for 8-14 days, 18 (4.6%) for 15-21 days and 17 (4.3%) for > 22 days. At discharge, 18 patients were referred for further management and while 7 patients died.Antibiotic use: Antibiotics were initiated in 92% of cases, either for prophylaxis  or treatment . The mean duration administration was 6±4.7 days, with most patients being on antibiotics for 1-3 days  or 4-6 days . The antibiotics were prescribed at admission , in the ward  or post-operatively . Most patients received one  or two antibiotics , with only 43 (11.8%) patients receiving three or more antibiotics simultaneously. The mean number of antibiotics was 1.6 ± 0.6 per patient. The route of administration was intravenous in 332 (91.2%) cases and oral in 32 (8.8%) cases. Ceftriaxone and floxacillin, either alone or in combination with metronidazole, were the most common antibiotics prescribed  cases had antibiotics prescribed for a mean duration of 5.7 ± 3.4 days. One antibiotic was prescribed for 284 (88.5%) cases, two for 35 (10.9%) cases and three antibiotics for two cases. The most common duration prescribed were 5 days , 7 days  and 3 days . Floxacillin , ampicillin-cloxacillin , metronidazole , cefuroxime , and amoxicillin-clavulanate  were the most common antibiotics prescribed , frequency , and dose of antibiotics ; the duration of antibiotics  was only rarely indicated. Only 29 (8%) patients had one or more antibiotics stopped, while 49 (13.5%) patients had one or more antibiotics added or changed. The proportion of prescriptions judged to be inappropriate was 45.4%  of antibiotics for prophylaxis, 33.4%  of antibiotics for treatment, 40.1%  of antibiotics administered during hospitalization and 52.6%  of antibiotics prescribed at discharge  patients admitted received one or more antibiotics, with the drugs being invariably 91%) administered intravenously (IV). In addition, the drugs were mostly continued till or just prior to discharge. The mean length of stay (7 days), differed from the mean duration of antibiotic administration by just one day. The percentage of patients receiving antibiotics for 1-7 days was similar to the percentage of patients whose length of stay was between 1 and 7 days, with only 8% of the patients having an antibiotic stopped prior to discharge. While prior studies have revealed a much a lower rate not only of total antibiotic administration 14-32%), but also proportion of IV formulation used 60-75%), we believe studies from other resource-limited settings may show a picture similar to ours [% adminis2%, but a0-75%, we% patientMcCallum et al noted poor documentation of antibiotics prescribed with the stop dates and indication for the antibiotics indicated in 14% and 18% respectively . SimilarThe task of documenting the discharge summary is commonly delegated to the most junior members of the team. In resource limited settings, however, there is significant variation in the training, competence and skill of the junior team members, who only passively participate in the overall patient management. There may be a strong desire on part of the team members to routinely send the patient home on a course of antibiotics, irrespective of the duration of antibiotics given while in the ward. In this review, the delegation or poor supervision of the medical staff  writing the discharge summary and belief on routine prescription of antibiotics on discharge contributed greatly to the findings of 81% of patients being discharged on antibiotics, with 92% of these having a 5-7 day course. Interestingly, more than one-third of the patients who had not been on any antibiotic during their hospitalization were discharged with antibiotics for a median duration of 5 days. Antibiotic use can be improved by frequent audits, active surveillance, preparation of local antibiotic use guidelines, legislation about antibiotic restriction and initiation of antimicrobial stewardship programs ,7,9. TheThis audit found antibiotic prescription to be mostly inappropriate. Too many patients were placed on intravenous antibiotics that were continued for too long, with the patients then being discharged needlessly on more antibiotics. In addition, there was minimal review on the indication for and the need for an antibiotic switch or stop. Improved documentation, serial evaluation of the need for antibiotics, development of local antibiotic guidelines and better supervision of prescriptions at discharge may help improve the appropriateness of antibiotic use at AIC Litein Hospital.Antibiotics are one of the most commonly prescribed medications in hospitalized patients, with a significant proportion used irrationally;The volume of antibiotic use is one of the most important factors driving the emergence of antibiotic resistance;Despite the dangers of antibiotic resistance, there continues to be misuse, overuse of antibiotics in many low and middle income countries where resources are limited.Poor antibiotic prescription documentation and lack of frequent antibiotic prescription review leads to prolonged use;While irrational use of antibiotics within the hospital is important, this can continue when the patient is discharged on unnecessary antibiotics.The authors declare no competing interests.


Prenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants.In this prospective study , we examined in 454 infants the association of prenatal antibiotic exposure  with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses  at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months.Compared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21  higher WFL-z at 12 months, and 0.28  higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association  with infants exposed to ≥ 3 courses having 0.41  higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z  and subscapular skinfold thickness  at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months .Prenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months.The online version of this article (10.1186/s12941-019-0318-9) contains supplementary material, which is available to authorized users. Despite efforts to prevent obesity, the prevalence of childhood obesity has more than tripled in the past 40 years . It reacz score (WFL-z) or skinfold thickness at 12 months.Nurture is a prospective birth cohort that recruited mothers from 2013 to 2015 in Durham, North Carolina, US. A detailed description of the cohort and data collection process is provided elsewhere , 10. We We determined maternal and infant oral antibiotic intake from questionnaires and confirmed for those with medical records data. We categorized antibiotics based on the Anatomical Therapeutic Chemical classification system : tetracy2, continuous variable). Other covariates included delivery method , infant sex , birth weight (continuous variable), and gestational age (continuous variable). All covariates were extracted from or calculated based on questionnaires at recruitment and during home visits.Confounders were defined as variables both related to the exposure and the outcome but not in the causal pathway. Pre-selected potential confounders included maternal age at delivery (continuous variable), race , marital status , education , annual household income , smoked during pregnancy , and maternal pre-pregnancy body mass index /[height (m)]The primary outcome was infant WFL-z. Secondary outcomes included subscapular, triceps, and abdominal skinfold thicknesses, SS + TR, and SS/TR. We used multivariable linear regression models to estimate the difference in these outcomes at 12 months by any prenatal antibiotic exposure , timing of exposure (trimester of pregnancy), number of courses, and types of antibiotics, adjusting for potential confounders (Model 1). We then added infant birth weight and gestational age (Model 2), and further added infant delivery method into the regression models (Model 3). We conducted sensitivity analyses by further adjusting for infant antibiotic intake in the first year of life in Model 1, and by examining if maternal antibiotic use in the first year after delivery associated with infant WFL-z at 12 months. We considered a two-sided P-value < 0.05 as statistically significant.We also collected fresh stool at 3 months (in 68 infants) and 12 months (in 50 infants) and conducted 16S rRNA sequencing of the V4 region  took ≥ 1 course of antibiotics during pregnancy; 77 (16.96%) took ≥ 3 courses; and 60 (13.22%), 69 (15.20%), and 146 (32.16%) took antibiotics during the first, second, and third trimester, respectively. Mothers who took antibiotics during pregnancy had higher pre-pregnancy BMI and were more likely to take antibiotics in the first year after delivery. Their infants were also more likely to have received antibiotics in the first year of life  or infant antibiotic intake in the first year of life . When we further added delivery method to Model 2, only second-trimester antibiotic intake remained associated with infant WFL-z at 12 months  (Model 3). The second trimester was also the only period in which antibiotic exposure was associated with higher 12-month subscapular skinfold thickness [0.50  mm increase].Given the persistent association of second-trimester antibiotic exposure with infant 12-month WFL-z, we next examined in a subsample of infants whether second-trimester antibiotic exposure was associated with the infant gut microbiome. Infants exposed to antibiotics in the second trimester versus not exposed had significantly different relative abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months . Moreover, we were not able to confirm maternal compliance with these prescriptions, thus misclassification of the prenatal antibiotic exposures might exist. However, such misclassification would most likely to be non-differential by outcome and, if any, bias the association towards the null. Furthermore, we only collected stool from a subsample of infants, and we did not collect stool or vaginal samples from the mother to test whether antibiotic-induced changes to the microbiome mediated the observed associations with measures of adiposity.Our findings suggest that prenatal antibiotic exposure in the second trimester is associated with an altered infant gut microbiome composition at 3 and 12 months and higher infant WFL-z and subscapular skinfold thickness at 12 months. Larger birth cohorts with repeated microbiome measures are needed to confirm our findings.Additional file 1. Materials for full microbiome methods.Additional file 2: Table S1. Adjusted association  of prenatal antibiotics and infant skinfold thicknesses at 12 months.Additional file 3: Table S2. Associations of second trimester antibiotics and bacterial ASV (microbiota) abundance as shown in Fig.