Striga hermonthica, a member of the Orobanchaceae family, is an obligate root parasite of staple cereal crops, which poses a tremendous threat to food security, contributing to malnutrition and poverty in many African countries. Depleting Striga seed reservoirs from infested soils is one of the crucial approaches to minimize subterranean damage to crops. The dependency of Striga germination on the host-released strigolactones (SLs) has prompted the development of the “Suicidal Germination” strategy to reduce the accumulated seed bank of Striga. The success of aforementioned strategy depends not only on the activity of the applied SL analogs, but also requires suitable application protocol with simple, efficient, and handy formulation for rain-fed African agriculture. Here, we developed a new formulation “Emulsifiable Concentration (EC)” for the two previously field-assessed SL analogs Methyl phenlactonoate 3 (MP3) and Nijmegen-1. The new EC formulation was evaluated for biological activities under lab, greenhouse, mini-field, and field conditions in comparison to the previously used Atlas G-1086 formulation. The EC formulation of SL analogs showed better activities on Striga germination with lower EC50 and high stability under Lab conditions. Moreover, EC formulated SL analogs at 1.0 µM concentrations reduced 89–99% Striga emergence in greenhouse. The two EC formulated SL analogs showed also a considerable reduction in Striga emergence in mini-field and field experiments. In conclusion, we have successfully developed a desired formulation for applying SL analogs as suicidal agents for large-scale field application. The encouraging results presented in this study pave the way for integrating the suicidal germination approach in sustainable Striga management strategies for African agriculture. Striga hermonthica, an obligate root-parasitic weed, is one of the major biotic constraints to cereal production in sub-Saharan Africa [Striga has infested about 50 million hectares of arable land in Africa [Striga infestation can vary from 40 to 100%, causing annual losses of around US $10 billion and threatening the life and food security of 300 million African people [Striga control strategies is crucial for not only reducing the extent of damage but also retaining further spread into the non-contaminant fields [Striga is challenging due to the production of ~0.1 million seeds per plant [Striga seed germination [n Africa ,2,3,4. An Africa . The cron people ,9,10,11.t fields . Howeverer plant , up to 2er plant , complexer plant , and hosmination . Striga seed requires favorable hot and humid conditions [Striga seeds should establish a connection to the root system of the host to survive due to very limited food reserve in tiny seeds for a short period of time [Striga life cycle leads to a basis for a promising control strategy, known as “Suicidal Germination” [Striga seeds can be triggered in the bare soil by direct application of synthetic germination stimulants [Striga, which can be exploited as a tool to eliminate the accumulated Striga seed bank [The germination of nditions  and, mosnditions ,19,20. T of time ,21. Thisination” ,23. The imulants ,25. Thiseed bank ,23,26. Aeed bank ,23,26,27eed bank . Indeed,Striga germination under different conditions [Striga in Africa.Several SL analogs and mimics were developed over the last three decades, but the problem of their efficacy, stability, and synthesis remains unsolved ,30,31. Tnditions ,32,33,34nditions ,32. Anotnditions . In addiStriga seed germination bioassays is depicted in Striga seed germination at a concentration of 1.0 µM, which was about 3–13% higher than AG formulation (49–57%)   as compared to seed populations collected from Burkina Faso and Niger (8–11%). However, these outcomes revealed that EC formulation of both SL analogs are still able to induce germination of various ecotypes of Striga seeds throughout African countries, depending upon seed viability and dormancy.Structure of SL analogs and packing of Emulsifiable Concentrate (EC) formulation of MP3 27EC and Nijmegen 34EC are shown in (49–57%) B. We als.036 µM) C. Importmulation C. Moreovmination . The StrStriga germination. EC formulation exhibited 60–64% germination when compared to AG formulation 52–57% ; whereas EC formulation of Nijmegen was much more stable and remained active up to week 6 with ~29% Striga germination  (Striga emergence (99%) than Nijmegen 34EC (89%). In addition, a higher reduction in Striga emergence led to a better growth of the host plant, indicated by an increase of 61–99% in plant height of the host crop  were further evaluated by applying at 1.0 µM concentration to nditions A,B. Intr(85–96%) C. Howeveost crop D.Striga, the efficacy of the two SL analogs MP3 27EC and Nijmegen 34EC was tested under mini-field conditions (Striga germination (Striga germination upon the application of MP3 27EC and Nijmegen 34EC (at 1.0 µM) compared to AG formulation. EC formulation of both SLs showed about 15–31% Striga germination and the Nijmegen 34EC appeared more active than MP3 27EC . Additionally, Nijmegen 34EC showed better activity than MP3 27EC . Moreover, MP3 in EC formulation showed a significant increase in grains per panicle over blank treatment   . AlthougStriga, an obligate parasitic plant, attaches to the root system of most cereal crops in Africa while its subterranean nature of damage has made its control very difficult [Striga in the infested soil [Orobanche ramosa [Striga infested pearl millet and sorghum farmers field in Burkina Faso, showing a promising impact on reduction in Striga emergence [ifficult ,35. Deveifficult ,36. Howeted soil . The “Suted soil ,39. We hted soil ,9. In adted soil . A good ted soil ,40. Atlated soil ,25,26. Pe ramosa ,41. Moremergence ,25. HoweStriga germination and EC50 over AG formulation. The induction of germination of various batches of Striga seeds by EC formulation of both SL analogs suggested that this formulation can be equally effective against all ecotypes of Striga in various parts of Africa  in Sudan batch and lowest germination (11%) in Niger batch. This variation among various populations might be attributed to seed viability, dormancy, as well as response to germination stimulants. The bioactivity of EC formulated MP3 for a longer period of time also indicates its potential as a good suicidal agent for field application in African soil. The EC formulated SL analogs possess longer shelf life and stability that is the desired characteristics for real field applications  and to give enough time for suicidal death after Striga germination. Indeed, when we increased the number to six applications under naturally infested farmer fields in Burkina Faso, we observed very encouraging results, particularly in the sorghum field  or the whole rainy season for maximum induction of suicidal germination of Striga seeds. In spite of this, reduction in Striga infection led to better yield of both sorghum and pearl millet crops  and pearl millet grain yield (>200%) as compared to blank treatment. The new EC formulation of the two SL analogs appeared to be very bioactive in terms of Striga reduction and host yield increase. In addition, the other advantages of EC formulation are simplicity, large-scale easy synthesis, stability, friendly use, easy packing/transportation and storage at normal room temperature. The development of proposed EC formulated simple SL analogs is the first step towards the large-scale synthesis of suicidal agents for field application and we believe this product will bring a breakthrough in suicidal technology to combat Striga in Africa.In summary, our results clearly demonstrate the effectiveness of the newly developed EC formulation of two potent and simple synthetic SL analogs as suicidal agents for practical field application. The new EC formulation of the two SL analogs appeared to be very bioactive, showing significant Striga hermonthica seeds were collected from a sorghum (Sorghum bicolor) field during 2020 in Sudan (provided by Prof. A. G. Babiker), a maize (Zea mays) field during 2018 in Kenya , a pearl millet (Pennisetum glaucum) field during 2020 in Burkina Faso  and a pearl millet field during 2019 in Niger . Seeds of rice IAC-165 were obtained from Africa Rice, Tanzania (Courtesy of Dr. Jonne Rodenburg).The SLs analogs MP3 and Nijmegen were synthesized and provided by Prof. Binne Zawanenburg, Radboud University, The Netherlands. Atlas G-1086  was mixed with cyclo-hexanone (1:4) to make conventional formulation of SL analogs, used previously in the field. The new formulation “Emulsifiable Concentrate” (EC) of the two SL analogs  were prepared by UPL, India and Safety Data Sheet (SDS) has been attached . MP3 27EStriga germination bioassays was conducted by following the procedure as described before [Striga seeds  were first pre-conditioned before treating with SL analogs. For this purpose, the seeds were surface sterilized with 50% commercial bleach for 6–7 min and washed subsequently six times with MiliQ water in a laminar flow cabinet. The surface sterilized seeds (~50–100) were spread uniformly on a glass fiber filter paper disc (9 mm). Then 3 mL of sterilized MiliQ water was added in a plastic Petri plate containing one sterilized Whatman filter paper and 12 discs with Striga seeds. The Petri plates were sealed with parafilm, wrapped in aluminum foil, and incubated at 30 °C for 10 days. On the 11th day, the discs were dried in a laminar flow cabinet and the SL analogs (50 μL) were applied on each disc with various concentrations ranging from 10−5 M to 10−11 M. After application, the Striga seeds were induced to germinate in the dark for 24 h at 30 °C. The discs were scanned under a binocular microscope and germinated, and non-germinated seeds were counted by SeedQuant [First of all, the two formulations of both SL analogs were tested under lab conditions. d before . The StreedQuant  and germStriga seeds were added in each plate and incubated at 30 °C for 24 h. The discs were scanned under a binocular microscope and germinated and non-germinated seeds were counted by SeedQuant [The stability of both the formulations of two selected SL analogs was observed in an in vitro bioassay. Five filter papers were added in plastic Petri plates (9 cm). Then, 10 mL of MP3 or Nijmegen with EC- and AG formulations at 1.0 μM concentration were added in each Petri plate and sealed with parafilm to incubate in the dark at 30 °C for two-week intervals for up to 12 weeks. On the final week, five glass fiber filter paper discs, containing 50–100 pre-conditioned eedQuant  and germStriga seeds was added in the bottom of a 3 L perforated plastic pot. Then about 20 mg (Approximately 8000) Striga seeds (collected from a sorghum field during 2020 in Sudan) were thoroughly mixed in 1.5 L soil mixture and added on the top of clean soil in the same pot. The pots were given light irrigation under greenhouse conditions at 30 °C for pre-conditioning of Striga seeds for 10 days. Then each pot was treated with 500 mL (1.0 μM) of various treatments to allow Striga seeds to germinate without host for another 10 days. Then one week old three rice seedlings (IAC-165) were planted in the middle of each pot. The rice plants were allowed to grow under normal growth condition . After 70 days of sowing, Striga emergence was observed in each pot and compared with mock treatment. The biological activity of the two formulations of the SL analogs was further tested in pots under greenhouse conditions as described ,32,44. AStriga germination and emergence in response to SL treatments. The top 10 cm of soil in the box was infested with 50 mg of Striga seeds. Moreover, nine eplee bags containing surface sterilized Striga seeds (30–50 on average) were buried at a 10-cm depth in the box in an equidistant position and allowed them to pre-condition under hot and humid conditions for 10 days. At the end of the pre-conditioning of Striga seeds, both formulations of the SL analogs were applied (at 1.0 µM) and blank treatments (AG-1086 and EC) were included for comparison. Three eplee bags were taken out at 3, 6, and 9 days after SL application to count germinated and non-germinated seeds. After two weeks of application, pearl millet was sown in each box and emerged Striga plants were counted at 80 days after sowing (DAS).The selected two SL analogs with both formulations were also evaluated in mini-boxes at INERA, Burkina Faso and at ICRISAT, Niger. At INERA, a 1 m × 1 m and 40 cm deep wooden box was used while in ICRISAT, Niger a mini-field, made of cemented bricks measuring 1 m × 2 m was used to assess Striga-infested fields located near Kouaré research station  of INERA were selected. In each field trial, the plots (4 × 4 m2) with various treatments were laid out by following randomized complete block design (RCBD) with six replications. Each plot comprised of five ridges spaced 80-cm apart. All of the plots were spaced with four (4) blank ridges to avoid any contamination of the treatments. The two formulations (EC vs. AG) of MP3 and Nijmegen were applied (25 mL/m2 at 400 µM) for six times, after onset of rainfall (≥10 mm) to make the final concentration of 1.0 µM. We included blank treatment as a control to compare the treatment effects. In the blank, we added the same amount of EC or AG emulsifier without SL analogs (active ingredients). Pearl millet  and sorghum  crops were sown at 2 weeks after the last application. Striga emergence was counted at 110 days after crop planting. In ICRISAT, Niger the field was prepared with ploughing and planking and ridges with 80-cm spaces were made. Each plot consisted of 4 ridges (4 × 4 m2) and each ridge was infested with ~1.0 g Striga seeds. The trial was laid out by following RCBD with six replications. The field was artificially irrigated for pre-conditioning of Striga seeds for 10 days. All of the plots were treated with various treatments for six times and pearl millet (SOSTA-C88-P10) was sown at two weeks after the last application. Striga emergence was counted at 103 days after host planting.The two formulations of the candidate SL analogs were further assessed under naturally infested farmers field conditions in Eastern Burkina Faso and artificially infested field in ICRISAT, Niger. In Burkina Faso, two highly t-test were used for analyzing the effect of two formulations of the SL analogs on Striga infestation. All of the data were collected by following standard procedure and collected data were analyzed statistically using statistical software package R (version 3.2.2). One-way analysis of variance (ANOVA) with Least Significant Difference (LSD) multiple range test and unpaired


In order to study the durability of concrete materials subjected to sulfate attack, in a sulfate attack environment, a series of concrete tests considering different fly ash contents and erosion times were conducted. The mechanical properties and the micro-structure of concrete under sulfate attack were studied based on the following: uniaxial compressive strength test, split tensile test, ultrasonic impulse method, scanning electron microscopy (SEM) and X-ray diffraction (XRD). The mechanical properties were compressive strength, splitting tensile strength, and relative dynamic elastic modulus, respectively. Additionally, according to the damage mechanical theory, experimental results and micro-structure analysis, the damage evolution process of concrete under a sulfate attack environment were studied in detail. Finally, according to the sulfate attack time and fly ash content, a damage model of the sulfate attack of the binary surface was established. The specific results are as follows: under the action of sulfate attack, the change law of the rate of mass change, relative dynamic modulus of elasticity, corrosion resistance coefficient of compressive strength, and the corrosion resistance coefficient of the splitting tensile strength of concrete all increase first and then decrease. Under the same erosion time, concrete mixed with 10% fly ash content has the best sulfate resistance. Through data regression, the damage evolution equation of the sulfate attack was developed and there is an exponential function relationship among the different damage variables. The binary curved surface regression effect of the concrete damage and the erosion time and the amount of fly ash is significant, which can predict deterioration of concrete damage under sulfate attack. During the erosion time, the combined expansion of ettringite and gypsum caused micro cracks. With an increase of corrosion time, micro cracks developed and their numbers increased. Sulfate attack is an important factor affecting the service life and durability of concrete buildings and structures ,2,3,4. SEr as the damage quantity and found that it could better reflect the evolution law of erosion damage. Wu et al. [At present, scholars at home and abroad have primarily studied the change law and erosion mechanisms of the macroscopic mechanical properties of concrete under sulfate attack ,23. At tu et al.  studied u et al.  carried u et al. , as suchIn this paper, fly ash content and erosion time are taken as the main variables, while the uniaxial compressive strength test, split tensile test, ultrasonic testing test, scanning electron microscopy (SEM) and X-ray diffraction (XRD) were carried out on concrete under sulfate attack. First, the rate of mass change, relative dynamic modulus of elasticity, corrosion resistance coefficient of compressive strength, and the corrosion resistance coefficient of splitting tensile strength of concrete of different erosion times were analyzed. The erosion damage of concrete caused by sulfate attack was defined by the strength damage and wave velocity damage. Considering the superimposed effect of fly ash and erosion time, the influence of fly ash and sulfate erosion time on the expansion of concrete damage was discussed. Based on fly ash content and sulfate erosion time, a concrete composite erosion damage model was established. Finally, our study reveals the microstructure change law of concrete subjected to sulfate attack, aiming to provide theoretical support and an experimental basis for durability research of concrete structures in areas where sulfate attack occurs.ψ, mass fraction) of the total cementitious material, respectively. The coarse aggregate used in the test was continuous grading crushed rock of 5–25 mm. The fine aggregate was river sand with fineness modulus of 2.6. The water used was fresh, potable laboratory tap water. In the experiments, 6-mm basalt fiber with a volume ratio of 0.1% and 12-mm polypropylene fiber with a volume ratio of 0.2% were used. Their appearances are shown in This study used Portland cement (P•O 42.5) produced by Bagongshan Cement Plant , which conforms with the standard for Common Portland cement . The cheAccording to the JGJ 55-2011 specification for the mix proportion of ordinary concrete , concretThe types and dosages of concrete and fiber designed in this paper were all carried out on the basis of the research done in ,37. Basa2 solution with a relative humidity of 95% and a temperature of 20 ± 2 °C to cure for 28 days. The specific steps are shown in First, the sand, gravel, fly ash, and cement were batched and evenly mixed in a mixer for 60 s, and then the right proportion of water was added to the mixer for another 60 s. Second, blended fibers were evenly distributed into the solid mixture to prevent agglomeration which was mixed for 120 s. After mixing, the mixture was put into a cubic mold with side lengths of 100 mm × 100 mm × 100 mm, distributed evenly around the mold with a spatula to ensure compacting, and finally put on a vibrating table to seal all pores. The specimen was left for 24 h after loading into the mold, and then removed. The specimen was numbered and put into a saturated Ca(OH)After curing for 28 days under standard conditions, the concrete test block was placed in a sodium sulfate solution at a concentration of 5% for long-term immersion. The liquid level was 10 mm above the surface of the test block. In order to ensure the stability of the pH of the solution, the solution is replaced once a month, and the concrete was completely soaked and eroded. The times of sulfate attack were 0 d, 30 d, 60 d, 90 d, 120 d, and 150 d, respectively. The whole test was carried out at 25 ± 2 °C.n, and the initial mass (g), respectively.When a specified erosion time was reached, concrete samples were taken from the solution and then dried in a constant temperature room at 22 °C until the mass was constant. At the same time, the sample surface was gently wiped with a towel to remove crumbs. The sample mass was then weighed and recorded using an electronic scale with an accuracy of 0.01 g. There were 3 parallel concrete samples in each group when weighing, and the results were averaged. Next, to calculate the rate of mass change Equation (1) was used :(1)φi=; l is the path length (mm); t is the average ultrasound time (μs); t1, t2, t3, t4, and t5 are the ultrasound time values of 5 pairs of measuring points, respectively.The longitudinal wave velocity was calculated using Equations (2) and (3).rE(n) according to the GB/T 50082-2009 standard for both test methods, for long-term performance and durability of ordinary concrete [n, and the initial dynamic elastic modulus, respectively; n and the initial longitudinal wave velocity (m/s).According to the relationship between the dynamic elastic modulus of the material and the ultrasonic sound velocity, the relative dynamic elastic modulus concrete , can be n, and the uncorroded compressive strength (MPa), respectively; n and the split tensile strength (MPa) without sulfate attack, respectively.When each set of sulfate erosion times was reached, the concrete sample was taken out of the solution and dried at room temperature. According to the GB/T 50081-2019 standard for test methods for the physical and mechanical properties of concrete , a CSS-YSEM and XRD tests were carried out using an S-3400N scanning electron microscope and a SMARTLAB9KW X-ray diffractometer from Yunnan Langlue Technology Co., Ltd. The microstructures, morphologies, and erosion products of minerals in the eroded samples were tested. The purpose was to analyze the erosion damage mechanism from a microscopic point of view. When a specified time of sulfate attack was reached, the concrete sample was taken out of the solution, left to air dry at room temperature, and broken into smaller parts for testing. After being placed in an oven and dried at 40 °C for 24 h, some samples were taken out, their surfaces were plated with gold on the surface, and then subjected to SEM tests. At the same time, the remaining test samples were crushed into powder and analyzed using XRD.The appearance and damage patterns of the concrete samples with different fly ash contents that were completely immersed in 5% sodium sulfate solution for different times are shown in The surface of the concrete specimens changed during erosion in the sodium sulfate solution with the increase in erosion time. The surface of various concretes eroded by 0-d sulfate were relatively flat and smooth. After 30 d of sulfate attack, minor defects began to appear on various concrete surfaces. After 60 d of sulfate attack, the surfaces of various concrete samples went from being relatively smooth surfaces to rough surfaces, and the mortar gradually peeled off. After 120 d of sulfate attack, the corners of the concrete of the FA0 group and FA10 group fell off dropped slightly and the surface mortar peeled off, while the surface mortar of the concrete specimens from the FA20 group appeared to have mostly peeled off. After 150 d of sulfate attack, cracks occurred at the corners and ends of the concrete in the FA0 and FA10 groups and the mortar peeled off; the corners of the concrete specimens in the FA20 group developed cracks. The more mortar completely peeled off of the surface of the entire concrete specimen, the more severe the deterioration. The reason for this is that the structure of a concrete test block was seriously damaged by sulfate erosion and the surface became brittle. A large amount of sulfate gathered in the concrete, and sulfate crystals precipitated after water evaporation ,41.According to Formulae (1) and (4)–(6), the relationships among the rate of mass change, relative dynamic elastic modulus, and corrosion resistance coefficient of strength of concrete specimens under the action of sulfate erosion and erosion time were obtained, as shown in 2 in concrete, which reduced the content of Ca(OH)2 in the concrete, reduced the production of gypsum and ettringite, and also alleviated the expansion of crystals. At the same time, because of the micro-aggregate effect of fly ash, fly ash particles filled the space between the unhydrated cement particles, which reduced the internal porosity of concrete, improving the pore structure and compacting the internal structure of concrete; this improved the durability of concrete [The change law of the rate of mass change, relative dynamic elastic modulus, and corrosion resistance coefficient of strength of different erosion times of sulfate attack are shown in concrete . At 30 dck), the corrosion resistance coefficient of splitting tensile strength (tk), and longitudinal wave velocity (v) were selected as damage variables. The damage caused by sulfate attack is shown by Equations (7)–(9).D1, D2, D3 are the sulfate erosion damage variables and are the corrosion resistance coefficient of compressive strength, the corrosion resistance coefficient of splitting tensile strength, and the longitudinal wave velocity, respectively.It can be seen from the sulfate attack test that the mechanical properties of concrete changed with the increase in erosion time, and the changes in the macrophysical properties can reflect the degree of internal changes in concrete materials. In order to quantitatively reflect the change law of the mechanical properties of concrete under the action of sulfate erosion, and comprehensively evaluate the state of concrete change, using damage mechanics, the corrosion resistance coefficient of compressive strength –(7), the amount of erosion damage under each evaluation index was calculated, as shown in 2, which reduces the content of substances that react with SO42−, thereby reducing the generation of erosion products [It can be seen from products ,37. Undeproducts ,45.n is the erosion time; a, b, and c are the coefficients in the fitting formula, as shown in At the same time, it can also be seen from D2 and D1 is established, as shown in Equation (11).a1, b1, and c1 are the coefficients in the fitting formula, as shown in The relationship between the sulfate erosion variables D1 of the corrosion resistance coefficient of compressive strength and ultrasonic velocity damage amount D3 of the non-destructive testing, as shown in There is also a good exponential relationship between damage amount To better study the influence of sulfate attack times and fly ash content on the corrosion coefficient of concrete’s compressive force, a sulfate damage prediction model using both sulfate attack time factors and fly ash content was examined. The scatter diagram results of sulfate erosion times, the amount of fly ash, and the corrosion resistance coefficient of compressive strength of the concrete specimens are shown in It can be seen from When concrete is subjected to sulfate attack, the change in its performance is, not only reflected in the process of macroscopic properties, but also in the process of microstructure changes.2), calcium hydroxide (Ca(OH)2), and calcium silicate hydrate (C-S-H). In addition to C-S-H, ettringite (Aft) could also be observed in groups FA0, FA10, and FA20 after being eroded for 30 days. At that time, ettringite production was limited, which filled the micro pores and cracks in the concrete specimens, optimizing the pore structure and making the concrete structure more compact. With the increase in erosion time, ettringite, and gypsum generation, when the erosion age reached 150 d, the content of Ca(OH)2 in the pores of concrete decreased continuously, decreasing the alkalinity and causing the erosion degree to intensify. A large amount of gypsum and ettringite was generated in the concrete, which increased in volume and produced expansion stress. When expansion stress exceeds the tensile stress of internal concrete, microcracks will form and the internal pore structure of concrete will be destroyed [estroyed ,46. At testroyed . More etestroyed . The proestroyed  and Zhaoestroyed .The microstructures of concrete at different time under the action of sulfate attack were observed using SEM, as illustrated in 42− entered the concrete and reacted with its internal hydration products to form acicular ettringite crystals and flake-like gypsum, which was continuously generated in the microcracks and pores, thus making the pores inside the concrete compact. However, with the continuous diffusion and reaction of SO42−, the generated needle-shaped ettringite and flaky gypsum gradually increased and crossed each other to form a network, which caused the pores of the concrete to be subjected to expansion forces. When the expansion forces reached a certain level, the number of microcracks and pores in the concrete specimens increased and expanded continuously [As can be seen from inuously . Accordiinuously  and Li einuously  observedinuously  and Li einuously .According to the results of this paper, the following conclusions can be drawn:(1) With an increase in sulfate attack time, the change law of concrete mass, relative dynamic elastic modulus, and strength corrosion resistance coefficient are similar, as they all initially increase and then decrease. Compared with other fly ash contents, concrete durability is better when fly ash content is 10%. The reason for this is that fly ash can fully react with the internal composition of concrete to produce C-S-H gel and other substances, enhance the internal cohesion of concrete, reduce the porosity of concrete, improve the density, and improve sulfuric acid erosion resistance.(2) The corrosion resistance coefficient of compressive strength, the corrosion resistance coefficient of splitting tensile strength, and the change in wave velocity were taken as damage variables. Concrete sulfate erosion damage was comprehensively evaluated using various damage variables. The evolution equation of concrete sulfate erosion damage based on each damage variable was obtained by data regression, and the exponential function relationship between different damage variables was established.(3) A composite sulfate erosion damage model between the corrosion resistance coefficient of compressive strength as a damage variable, erosion phase, and fly ash content was established. This model was used to predict concrete damage and erosion time after sulfate erosion. The model was used to predict the quantitative relationship between concrete damage, erosion time, and fly ash content after sulfate erosion to evaluate the resistance of concrete to sulfate attack in saline areas. The damage model is only suitable for concrete with a water–binder ratio of 0.6, fly ash dosage range of 0–20%, and mixed with 0.1% basalt fiber and 0.2% polypropylene fiber simultaneously.(4) Sulfate attack changes the internal microstructure of concrete, and sulfate ions react with hydration products in concrete to produce expansive crystal ettringite and gypsum. With an increase in erosion products and expansion force, microcracks and damage appear inside the concrete, which is aggravated continuously, inducing the expansion and penetration of cracks and pores, and the deterioration of the microstructure reduces the macro performance of concrete.


Current researches on the mechanical properties of concrete are mainly concentrated on the aggressiveness of sulfate, chloride ion, acid and freeze–thaw cycles. However, the evolution of concrete mechanical properties aggressived by landfill leachate remains to be revealed. As the micro-nano indentation test is a new method to measure the fine/micro mechanical behavior of materials, it is used in this research to evaluate the micro-mechanics of the landfill leachate of the concrete sample surface and different aggressived depths. In addition, the evolution of the macro-mechanical properties of concrete aggressived by the landfill leachate was studied through uniaxial compression tests. The results show that the hydration products with high elastic modulus are consumed by the aggressiveness of landfill leachate, which results in a large number of microscopic cracks on the surface of the concrete. Moreover, the longer the aggressive time, the shallower the aggressive depth, and the more severe the deterioration of the micromechanical properties of the sample surface. It is also notable that the uniaxial compressive strength of the concrete samples aggressived by landfill leachate showed a linear increase and then gradually decrease. Comparing with the sodium chloride and sodium sulfate solutions, the landfill leachate has the most significant weakening effect on the elastic modulus of concrete. So far, very few researches have been concentrated on the mechanical properties of concrete after being aggressived by the landfill leachate, and most researches have been focused on the study of the mechanical properties of concrete aggressived by the sulfate6, chloride ion8 and freeze–thaw cycles10. However, researches on the evolving of the mechanical properties of concrete aggressived by landfill leachate remains to be done.Generally, the mechanical properties of concrete behave a positive correlation with the strength of its anti-aggressived ability. The better the mechanical properties, the stronger the ability of resisting aggressive ions, and the harder the internal structure to be destroyed11. Even though the ultrasonic detection method has poor accuracy, it is suitable for determining sample with large aggressived depth13. And the strength degradation method assumes that the aggressived area does not bear force, which is inevitably inconsistent with its actual features.Generally, concrete aggressiveness is a process evolves from surface to inside, which can be divided into aggressived area and non-aggressived area. Since aggressived depth is one of the important parameters to distinguish the aggressived and non-aggressived areas, and traditional methods measuring concrete aggressived depth includes chemical analysis, ultrasonic detection and strength degradation, which have a certain degree of deficiencies. For example, the chemical analysis method has high accuracy, but it is not suitable for the detection of a variety of aggressive ions15. Actually, the mechanical properties at different aggressived depths are different, and the test results are greatly affected by the sample size and degree of aggressiveness. Therefore, it is necessary to study the mechanical properties of concrete at different aggressived depths.Past researches took the aggressived and unaggressived area of concrete as a whole to evaluate its mechanical properties, and then determine the degree of deterioration and establish the constitutive relationship of the aggressived concrete16. The emerging nanoindentation technology effectively solves the defect that the traditional indentation measuring method is only suitable for larger size sample. The continuous changing of the load is controlled by the computer, and the indentation depth is measured in real time. Because of the ultra-low load characteristic, the monitoring sensor has a displacement resolution smaller than 1 nm. Therefore, it can detect a pressure depth as small as nanometers (0.1–100 nm), which is especially suitable for measuring the mechanical properties of ultra-thin materials such as thin films and coatings, as well as measuring mechanical properties of a material on the nanometer scale17.Recently, a new method of micro-nano indentation test was invented to measure the fine/micro mechanical behavior of materials, which has been widely used in the metal materials and cement-based materialsTherefore, the micron indentation test was conducted to study the micro-mechanical properties of the concrete sample surface and different aggressived depths for different time by high-concentration landfill leachate aggressiveness group HLLN (High concentration—Landfill leachate—No osmotic pressure), landfill leachate original solution aggressiveness group NLLN , landfill leachate original solution plus osmotic pressure aggressiveness group NLLO . At the same time, the uniaxial compression test is also used to study the evolution of macro-mechanical properties of the concrete suffering aggressiveness of high-concentration landfill leachate group HLLN, sodium sulfate solution group NSSN  and sodium chloride solution group NSCN . Moreover, related test results can be used for providing scientific basis for understanding the evolution of macro/micro mechanical properties of concrete structures under the aggressiveness of landfill leachate.18. At the same time, considering the differences in aggressiveness environments, five groups including high-concentration landfill leachate aggressiveness group HLLN (High concentration—Landfill leachate—No osmotic pressure), sodium sulfate solution aggressiveness group NSSN , sodium chloride solution aggressiveness group NSCN , landfill leachate original solution aggressiveness group NLLN , and landfill leachate original solution plus osmotic pressure aggressiveness group NLLO  were prepared. Since the contents of sulfate ion and chloride ion in the landfill leachate are relatively high18 and has greater impact on the concrete, the total concentrations of sulfate ion and chloride ion in group HLLN were increased to 50 g/L, respectively, which can accelerate the aggressiveness effect. The concentration of the remaining components was the same as that in group NLLN. In order to study the difference of aggressiveness conditions under high-concentration landfill leachate and single sodium sulfate plus sodium chloride solution, the concentrations of sulfate ion and chloride ion in group NSSN and group NSCN were set 50 g/L.Because of the limited aggressiveness rate of the landfill leachate on concrete under natural conditions, the concentration of sulfate ion and chloride ion were increased in the landfill leachate to accelerate the aggressiveness effect19, and the composition ratio of each group of solutions are shown in Table The indoor configuration of landfill leachate was used in this study to ensure the unity of the experimental variables, which can effectively avoid the influence of the composition of landfill leachate on the experimental results. The composition ratio of landfill leachate was selected according to20. In addition, the ordinary silicate cement and primary fly ash were used for the tests, and the fine aggregate was medium sand with a fineness modulus of 2.6, and the coarse aggregate was 5–25 mm continuously graded gravel. The chemical composition of cement and fly ash can be seen in Table As the aggressiveness effect of the landfill leachate develops, the hydration products in the concrete reaction with the harmful substances in the landfill leachate, which inevitably influence the concrete durability. Aggressive ions such as sulfate ions and chloride ions in the landfill leachate will chemically reaction with the C–S–H gel and calcium hydroxide in the concrete hydration products, thereby causing aggressiveness to the concreteThe cylindrical specimens (φ150 mm × 150 mm) were cured under standard curing conditions . After the maintenance was completed, the standard cylindrical specimen of φ 50 mm × 100 mm is prepared by coring, cutting and grinding. And then they were put in the high-concentration landfill leachate aggressiveness group HLLN and landfill leachate original solution aggressiveness group NSSN, respectively, so as to simulate the aggressiveness of concrete structure under different environments. Considering the underground concrete structure on the landfill site is occasionally aggressived by the flowing landfill leachate with certain pressure, the high-concentration landfill leachate aggressiveness group HLN, sodium sulfate solution aggressiveness group NSSN, sodium chloride solution aggressiveness group NSCN, landfill leachate original solution aggressiveness group NLLN, and landfill leachate original solution plus osmotic pressure , it is concluded that no deformation damage occurred on the surface of the indentation point when the concrete suffered a maximum load of 15 N, whose indentation depth was 35 μm and indentation diameter was 0.25 mm. When the load is small (5 N), the indentation depth is shallow and generally affected by the surface roughness. However, large loads  led to the collapse of the surface of indentation point, which eventually caused errors in the measurement results.21, the maximum force of 15 N was determined in the indentation tests, and the distances from the indentation center to the boundary of the cubic sample and coarse aggregate are 2 mm, respectively. The test temperature was maintained at 24 ± 2 °C, and the micro-indentation test system is shown in Fig. According to the test results and standardh is the indentation depth of the indenter, vertical axis P denotes the load, hm means the maximum indentation depth during tests, hp indicates the depth of the residual indentation after unloading, hr represents the intersection between the tangent line and the horizontal axis at the maximum load of the unloading curve, and Pmax is the maximum testing load. Based on the Oliver-Pharry principle22, the elastic modulus E of a material can be calculated according the following formula:Er is the indentation modulus, Ei means the elastic modulus of the indenter, vi denotes the Poisson's ratio of the indenter. The elastic modulus and Poisson's ratio of the diamond are 1141 GPa and 0.07, respectively. v is the Poisson's ratio of a material and generally valued 0.2–0.3 for cement-based cement hardened paste, which was valued 0.25 in this study23. S means the contact stiffness and hc the contacting depth between the indenter and sample. A(hc) represents the projected area of contact between the indenter and sample, which is related to the contact depth hc. β is a constant related to the geometry of the indenter with a value of 1.012, and Figure μ is the arithmetic mean of the test value of hydration products, s means the standard deviation. μ is determined asN is the number of test data for each group, which is 90 in this study, and xk is the elastic modulus obtained from tests.Because of the significant difference among the concrete hydration products, the aggressiveness products of the reaction between landfill leachate and concrete are complicated, which makes the elastic moduli measured by the indentation tests are discrete. In order to obtain the distribution law of the meso-mechanical parameters of the samples, it is necessary to calculate and statistically analyze the 90 measuring points obtained from each group of experiments, so as to get the normal distribution curve and cumulative distribution curve. The normal distribution density function isThe maximum vertical force of the uniaxial compression test apparatus used in this research can reach 1000 kN and maximum confining pressure 50 MPa. In addition, both displacement controlling mode and force controlling mode can be applied in this apparatus. Therefore, the displacement controlling mode was chosen in this study. A small axial force of preloading is applied to the sample before loading, and a loading rate of 0.002 mm/s is then kept until the specimen is damaged.24. And the aggressive products of concrete due to the landfill leachate are ettringite and Friedel salt (whose elasticity modulus is similar to that of C-SH gel25). Based on the micron indentation tests, the distribution of the elastic modulus at different aggressived depths can be obtained, and hence the distribution of different hydration products at different corrosion sites can be effectively judged.Past researches revealed that the main phases of concrete hydration products are CSH gel (12.6–35.3 GPa), calcium hydroxide (33.0–44.5 GPa) and ettringite (40.0–52.0 GPa)Table Figure In addition, the elastic moduli of the hydration products before aggressiveness were greater than 11 GPa, most of which in the range of 27–39 GPa. It is attributed to rare pore and crack (elastic modulus in the range of 0–12.2 GPa) existed in the samples, which contained a large amount of hydration products such as C–S–H gel and calcium hydroxide with large elastic moduli (as shown in Fig. Local meso-mechanical properties at different aggressived depths aggressived by the high-concentration landfill leachate group HLLN, landfill leachate original solution group NLLN and landfill leachate original solution plus osmotic pressure group NLLO for 180 days were obtained through micro-indentation tests. The probability distribution of the elastic moduli of the hydration products at corrosion depth of 0–5 mm, 5–15 mm and 15–25 mm by group HLLN and group NLLN, and the elastic modulus of hydration products at samples depth 0–2, 2–4, 5–11 and 11–16 mm corroded by group NLLO are shown in Tables Figure As shown in Fig. Seeing from Fig. The mechanical parameters of the surfaces and different aggressived depths can be accurately measured through micro-indentation tests. As Fig. Seeing from Fig. According to Fig. In order to study the degradation law of the macro-mechanical properties of concrete in the landfill leachate, sodium sulfate and sodium chloride solutions, the concretes were aggressived by the high-concentration landfill leachate group HLLN, sodium sulfate solution group NSSN, and sodium chloride solution group NSCN, and the uniaxial compression test results are as follows.Figure According to Fig. 26, the trends of elastic modulus for the three groups are shown in Fig. According toAs the aggressiveness of the landfill leachate continues, a large number of microscopic cracks generated on the surface of the samples. At the same time, the hydration products with high elastic modulus such as C–S–H gel and calcium hydroxide in the concrete were consumed by the landfill leachate. The longer the aggressiveness of the high-concentration landfill leachate, the more severe the deterioration of the micromechanical properties of the sample surface.The shallower the aggressived depth, the more severe the deterioration of the local meso-mechanical properties of the samples, the more severe the change in the mechanical properties, the less the content of hydration products with larger elastic modulus such as calcium hydroxide, and the more aggressive products with smaller elastic modulus such as pore and cracks.The uniaxial compressive strength and elastic modulus of the concrete samples aggressived by landfill leachate showed a linear increase first and then slowly decrease with time. Compared with the sodium chloride and sodium sulfate solutions, the landfill leachate has the most significant weakening effect on the elastic modulus of concrete.In order to study the evolution of the macro/micromechanical properties of the concrete aggressived by landfill leachate, this research focused on the behavior of the surfaces and different aggressived depths aggressived by high-concentration landfill leachate group HLLN, sodium sulfate solution group NSSN, sodium chloride solution group NSCN, landfill leachate original solution group NLLN and landfill leachate original solution plus osmotic pressure group NLLO. The main conclusions are as follows:


Antimicrobials are the most frequently prescribed drugs in long-term care facilities (LTCF). Antibiotic stewardship programs (ASP) are coordinated interventions promoting the responsible use of antibiotics to improve patient outcomes and reduce antibiotic resistant bacterias. The objectives are to evaluate the effectiveness of a pharmacist-led ASP in a LTCF, to characterise antibiotic therapy and assess the appropriateness of antibiotic prescriptions. A prospective quasi-experimental study to implement an ASP in a LTCF. Antibiotic prescriptions for suspected infections initiated in any setting for LTCF residents were included. We assessed appropriateness and prospective audits and feedback of each inappropriate antimicrobial prescription were carried out. Associations of variables with appropriate antibiotic prescribing were estimated using logistic regression. A total of 416 antibiotic prescriptions were included. The mean consumption of antibiotics was reduced from 63.2 defined daily doses per 1000 residents-days (DRD) in the preintervention period to 22.8 in the intervention period (− 63.8%), with a signifcant drop in fluoroquinolones (81.4%). Overall, 46.6% of antibiotic prescriptions were judged inappropriate, mainly because of a use not recommended in treatment guidelines (63.2%). Multivariable analysis showed that empirical therapy, some classes of antibiotics  and prescription initiation in the emergency department were independent predictors of antimicrobial inappropriateness. Pharmacist-led ASP in a LTCF has being effective in reducing consumption of antibiotics by improving appropriateness of treatment decisions. However, ASP should include interventions in the emergency department because of the high inappropriate use in this setting. Roughly between one-half and two-thirds of LTCF residents are prescribed antimicrobials each year2. The particular characteristics of elderly contribute to difficulties in diagnosing and treating infections in LTCF residents, including the lack of typical signs , the presence of concurrent illnesses with associated nonspecific symptoms and the high prevalence of cognitive impairment that make it difficult to communicate symptoms3. In addition, most of LTCF do not have on-site laboratory and radiological facilities. It may lead to unnecesary, suboptimal or inappropriate antimicrobial prescription in LTCF. In fact, up to 75% of antibiotic prescriptions may be unnecessary, even when necessary, the antibiotics prescribed are often excessively broad spectrum or longer duration4. The overuse and misuse of antibiotics are associated with increased rates of adverse drug events and future infections such as those caused by Clostridium difficile and antimicrobial resistance (AMR)5. Furthermore, given that one-third of residents are estimated to be colonised with multidrug-resistant organisms (MDRO), LTCF serve as reservoirs6. Thus, there is an immediate need to optimise antibiotic use in this population to slow the emergence and spread of antimicrobial-resistant organisms7.As a result of the increase in the population age, the number of long-term care facilities (LTCF) beds has raised. Residents in LTCF are at high risk of infections due to multiple comorbidities, frailty and immunosenescence that lead to frequent antibiotic prescribing8. Although, it is less likely that LTCF can implement a formal ASP within this resource limited environment, growing attention has been given to improving antibiotic use in LCTF12. However, little is known about the contribution and appropriateness of antibiotic therapy initiated in other settings such as the emergency department (ED)13. As recommended by guidelines published by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA), ASP teams should include an infectious disease (ID) physician and a clinical pharmacist with ID training14. LTCF may not have access to the traditional ASP team given resource restraints. In this environment, where ID physician support is not available, the clinical pharmacist who has a consistent presence in LTCF can play a key role in promoting the optimal use of antimicrobial agents, monitoring and auditing the prescriptions, and educating health professionals16.In the acute care hospital, antibiotic stewardship programs (ASP) have been successful at improving the quality of patient care and safety, reducing potentially inappropriate prescribingTherefore, the objectives of this study are to evaluate the effectiveness of a pharmacist-led ASP in optimising antimicrobial use in a LTCF by educational interventions, to characterise antibiotic therapy for LTCF residents and assess the appropriateness of antibiotic prescriptions.17 was approved on February 2013. It was implemented in the Andalusian Public Healthcare System (SSPA) at both primary and hospital healthcare levels. However, LTCFs were out of this ASP. In January 2016, the Decree 512/2015 on dispensing and pharmaceutical care in the LTCFs of the SSPA was published18. It established that public LTCFs of Andalusia depended on the nearest hospital pharmacy service.In Andalusia, the most populated autonomous region in Spain, with 8.4 million inhabitants, an ASP called the PIRASOA programme19 and provide educational materials  and antimicrobial consumption corresponding to the preintervention period. The educational interventions and the provision of antimicrobial consumption data were repeated during the intervention period. Furthermore, during the intervention period, the ID pharmacist identified residents with prescriptions of drugs belonging to Anatomical Therapeutical Chemical (ATC) class J01  for suspected infections through the electronic prescribing. Then, pharmacist made weekly site visits to LTCF to collect data by review of the medical records. We only included antibiotics associated with a diagnosis of lower respiratory tract infection (LRTI), skin and soft-tissue infection (SSTI) or urinary tract infection (UTI), given their high prevalence compared with other infections in LTCF. We excluded confirmed positive COVID-19 infections without suspected bacterial or fungal co-infection and also prophylactic antibiotic prescriptions . ID pharmacist interacted directly with the prescriber in person or by phone to discuss the treatment and formulate recommendations to improve antimicrobial therapy in next prescriptions, focused specially in fluoroquinolones and amoxicillin-clavulanic acid.A prospective quasi-experimental study was conducted to implement an ASP in a public 264-bed LTCF in Spain. The ASP team consisted of an ID physician, an ID trained clinical pharmacist, the facility medical director and a microbiologist. ASP team and also LTCFs physicians were engaged in the programme. The study period was divided into two periods of 18 months each. During the pre-intervention period , baseline information of local patterns of antibiotic resistance and antimicrobial utilisation were collected. Second phase, aimed at improving appropriate antibiotic use, took place from July 1, 2019 to December 31, 2020. The development of the intervention began with sessions between ASP team and LTCF physicians to present the guidelines on antibiotic prescribing for the most commonly encountered infections in LTCFWe obtained demographic and clinical characteristics of residents including sex, age, allergic reactions to antibiotics, comorbidities, Charlson comorbidity index age-adjusted score, functional status  and medical devices, including urinary catheter, vascular catheter for dialysis, tracheostomy and feeding tube. Also, other risk factors such as a surgery in the last 30 days and antibiotic exposure in the last 6 months were identified. Variables related to infection and antibiotic prescription were collected: type of treatment , indication for antibiotic , antibiotic start and end date, antibiotic class, dosage, route and frequency, signs and symptoms on day of prescription and tracking, previous antibiotic therapy (last 2 weeks), microbiology data and setting of prescription initiation classified as ED, hospital or primary care (HPC) and LTCF and 30-day clinical outcome.21.The primary outcome was change in antibiotic use measured as total consumption for preintervention period versus intervention period. Total consumption of antibiotics was measured as the mean defined daily doses (DDD) per 1000 residents per day (DRD). DDD were calculated using World Health Organization (WHO) definitions. Occupied beds were used in the denominator. Secondary outcomes were change in costs of antimicrobials, hospitalisation and mortality, as well as appropriateness of antibiotic prescriptions classified as unnecessary, inappropriate and suboptimal antimicrobial useQualitative variables are presented with their frequency distribution and percentages. Quantitative variables were summarised with mean and standard deviation or median and interquartile range in case of asymmetry. Chi-square or Fisher’s test was used to compare categorical data and Student's t-test for normally distributed continuous variables and Mann–Whitney U Test for non-normally distributed continuous variables. To identify independent predictors of appropriateness, we performed an univariable logistic regression. We also analysed the collinearity between the variables. Subsequently, variables that showed statistical significant in the univariable analysis and those with p-value < 0.2 were included in a multivariable model. Relative risks were expressed as odds ratios (OR) and 95% confidence intervals. All reported p-value < 0.05 were considered as statistically significant. The area under the receiver operating characteristic (ROC) curve was calculated to assess the discrimination of the prediction score. For the statistical analysis, the software SPSS Statistics for Windows, Version 21.0  was used.The study was designed and permormed according to the the Helsinki Declaration and approved by the Ethics Committee of Jaén Province. The patients who participated in the study signed and informed consent for data collection. In case of incapacitated persons, close family members or legal guardians gave informed consent.The mean of occupied beds during the 18-months intervention period was 214. A total of 416 antibiotic prescriptions were included in this period , followed by cephalosporins (18.8%), amoxicillin-clavulanic acid (15.9%) and fluoroquinolones (13.0%). Polytherapy was only used in 2.6% of episodes. The most common indication for antibiotic use was UTI (43.3%), followed by LRTI (34.6%), and SSTI (22.1%). For UTI, fosfomycin-tromethamine was the most commonly prescribed antibiotic (57.8%), followed by cephalosporins (11.1%). LRTI was treated with cephalosporins (36.8%), amoxicillin-clavulanic acid (24.3%) and fluoroquinolones (21.5%). Penicillins (amoxicillin or cloxacillin) were the most often prescribed class of antibiotics for SSTI (43.5%), followed by amoxicillin-clavulanic acid (17.4%). Targeted therapy involved 16.8% of prescriptions, UTI being the most frequent (62.9%). Intravenous route was used only in 4.8% of cases. Median treatment duration was 5 (IQR: 1–7) days. Only 9.4% prescriptions were for longer than 7 days of duration. Sample collection was carried out in 29.6%, the majority (88.6%) before initiating antibiotic therapy: 74.0% uroculture, 16.3% exudate culture, 4.1% sputum culture. A positive result was found in 82.9% of cultures . The most prevalent microorganisms isolated were the Gram-negative bacteria (87.3%). The majority of antibiotic prescriptions were initiated within the LTCF (84.1%), while 12.7% by the ED and 3.2% by HPC.21 in 194 unsuitable antimicrobial prescriptions:Unnecessary : use of antimicrobials for non-infectious syndromes or non-bacterial infections , days of therapy beyond the indicated duration of therapy absent any clinical reason for a lengthened course , use of redundant antimicrobial therapy and/or continuation of empiric broadspectrum therapy when cultures have revealed the infecting pathogen .Inappropriate : use of antimicrobials in the setting of established infection to which the pathogen is resistant , use of antimicrobials not recommended in treatment guidelines .Suboptimal : use of antimicrobials in the setting of established infection that can be improved in one of the following categories: drug choice , drug route , drug dose .Considering that antibiotic prescriptions may be inappropriate for one or more types, we found 231 different types of inappropriatenessTable Subsequently, multivariable analysis showed that empirical therapy, some classes of antibiotics  and prescription initiation in the ED were independent predictors of antimicrobial inappropriateness Table . DatasetClostridium difficile infections, rates of hospitalisations or mortality12. However, the studies indicate that ASP can reduce the number of antibiotic prescriptions and improve adherence to guidelines. This review included fourteen studies, but only three are developed in Europe. Other later narrative review aimed to provide data about antibiotic consumption included ten studies carried out in Europe and four in other countries, all proposing educational interventions22. To the authors’ knowledge, our study is the first in Spain evaluating the role of a pharmacist-led ASP in elderly patients residing in a LTCF. Educational interventions and weekly prospective audits and feedback have resulted in significant decreases in antibiotic use and costs of antibiotics, but no changes in hospitalisation and mortality have been found. In the pre-intervention period, mean total use of systemic antimicrobials is 63.2 DRD, in concordance with data reported in another Europe country, Netherlands (73 DRD)23. We found that total consumption of antibiotics has reduced by 63.8%, more than the decreases reported in other studies with educational interventions (12–30%) focused on appropriate diagnosis and treatment of common infectious syndromes25.Although data are limited, there are several studies that have begun to characterise the status of ASP in LTCF. In contrast to findings of ASP in hospitals, a recent systematic review did not find evidence that these programs in LTCF change the incidence of 26. They are the class of antibiotics with the largest DRD reduction, being one of the targets in our study for two reasons. First, although ciprofloxacin is one of the most effective antibiotic in UTI, there is a significantly high rate of UTI caused by E. coli and Klebsiella spp. resistant to fluoroquinolones in our area, so fosfomycin-tromethamine is the election treatment in the guidelines for UTI19, antibiotic with a slight reduction between periods. This fact is explained because of treatment cessation of some asymptomatic bacteriurias. Cefixime and sulfonamides are also an effective alternative in the guidelines for these infections. Second, amoxicillin-clavulanic acid is the first line therapy for LRTI, while levofloxacin is the recommended treatment if allergy to beta-lactams antibiotics and/or history of COPD19. On the other hand, amoxicillin-clavulanic acid, the other focus antibiotic, is the second with greatest diminution. Penicillins are the first election therapy for SSTI instead penicillins with beta-lactamase inhibitors. The corresponding decrease in both classes suggests that our pharmacist-led ASP successfully improve their use.Fluoroquinolones account for 13% of antimicrobial prescriptions in our LTCF, in contrast with 30–44% documented in other studies, likely because of their oral bioavailability and broad spectrum of activity21, as well as identify predictors of antimicrobial appropriateness and specifically the influence of the setting of prescription initiation . The proportion of appropriate antibiotics prescribed in our study (53.4%) is consistent with other studies conducted in other LTCF28. Some classes of antibiotics  are negatively associated with antibiotic prescription appropriateness in the multivariable analysis. We assume that it is correlated with reasons explained before. Cephalosporins and fluoroquinolones are often prescribed for LTCF infections instead of first line antibiotics and they are relationated with Clostridium difficile infection. In this facility, fosfomycin calcium has been used for UTI with longer durations than guidelines recommendations in place of fosfomycin-tromethamine. In the case of macrolides, they have been prescribed for suspected respiratory tract infections possibly caused by virus or for syndromes in which initiation of an antibiotic is not recommended. On the other hand, antibiotic prescription for LTCF residents initiated in the ED is an independent predictor of antimicrobial inappropriateness. To our knowledge, this is the first description of this association. Probably this result can be explained by two main arguments. First, unlike LTCF physicians, those working in the ED usually treat patients of different ages. Elderly patients, specially those living in LTCF, are medically complex patients with multiple comorbidities that increase the risk of infection . Besides, it can be difficult to recognise infections because of the presence of atypical signs and symptoms and the cognitive impairment. So, the dread of a clinical worsening can result in an earlier initiation of the antibiotics prescription, even in absence of clear evidence of bacterial infection29. Second, there is not a formal ASP in the ED of the corresponding hospital. Therefore, LTCF ASP must consider also interventions focus on prescribers who are working outside of the facility.Furthermore, this study is the first to assess appropriateness of antibiotic prescriptions classified as unnecessary, inappropriate and suboptimal antimicrobial use31, firstly because different studies descibe an excessive and inadequate use of antibiotics associated to COVID-19 infections, second, due to ASP having been completely disrupted during this pandemic. In our case, the most frequent antibiotic prescribed was azithromycin because it is associated with potential antiviral effect. Although there has been a significant increase in the consumption of this antibiotic during the COVID-19 outbreak, we found no differences in consumption of macrolides for preintervention period versus intervention period  and this may have had a negative effect on antibiotic use. Despite the potential limitations previously mentioned and although the conclusions of this study are limited by the quasiexperimental study design, it is plausible that the intervention is associated with a signifcant lowering consumption of antibiotics. Nevertheless, generalisability to other LTCF must be taken with caution. In relation with the impact of the COVID-19 pandemic on the practices of the prescribers or the pattern of infections diagnosed, there is a growing concern about the possible future growth of antimicrobial resistanceod Table  so the uThe findings of this study support the feasibility of implementing and sustaining an ASP in LTCFs to optimize the use of antimicrobials agents, reduce total consumption and improve prescribing practices and possibly to contribute to the reduction in the incidence of MDRO pathogens. However, this programme may not have the same results in other countries where the consumption of antimicrobials is more moderate.The main barriers encountered to implemented ASP could be the creation of multidisciplinary local teams and the acceptance of the culture of public evaluation and transparent results. This is inherent to the enormous complexity involved in implementing an ASP through nonmandatory measures. Nevertheless professional leadership the institutional support favoured by the regulations of the European Union and the existence of an organized Healthcare System could make the success of the programme possible.26, together with an audit and feedback32, improving prescribing habits and reducing unnecessary antibiotic prescriptions22. Due to the approach was strictly pedagogical, aiming to improve prescribers' knowledge rather than to change any antimicrobial treatment, ASP has been well accepted by the clinicians. Pharmacist-led ASP in a LTCF has been effective in reducing global consumption of antibiotics by improving appropriateness of treatment decisions. Inappropriate use is high in antibiotics initiated in the emergency department and it constitutes a small but not unimportant percent of all prescriptions. So, in attempts to improve antibiotic stewardship in LTCF, ASP should include interventions in this setting.Overall, almost half of antimicrobials prescriptions are inappropriate. Evidence shows that educational interventions consisting of providing an antibiotic prescribing guide combined with physician antibiotic prescribing profiles are the most effective published ASP strategies


This article presents an analysis of the uptake of the GPRC label (Guaranteed Peer Reviewed Content label) since its introduction in 2010 until 2019. GPRC is a label for books that have been peer reviewed introduced by the Flemish publishers association. The GPRC label allows locally published scholarly books to be included in the regional database for the Social Sciences and Humanities which is used in the Flemish performance-based research funding system. Ten years after the start of the GPRC label, this is the first systematic analysis of the uptake of the label. We use a mix of qualitative and quantitative methods. Our two main data sources are the Flemish regional database for the Social Sciences and Humanities, which currently includes 2,580 GPRC-labeled publications, and three interviews with experts on the GPRC label. Firstly, we study the importance of the label in the Flemish performance-based research funding system. Secondly, we analyse the label in terms of its possible effect on multilingualism and the local or international orientation of publications. Thirdly, we analyse to what extent the label has been used by the different disciplines. Lastly, we discuss the potential implications of the label for the peer review process among book publishers. We find that the GPRC label is of limited importance to the Flemish performance-based research funding system. However, we also conclude that the label has a specific use for locally oriented book publications and in particular for the discipline Law. Furthermore, by requiring publishers to adhere to a formalized peer review procedure, the label affects the peer review practices of local publishers because not all book publishers were using a formal system of peer review before the introduction of the label and even at those publishers who already practiced peer review, the label may have required the publishers to make these procedures more uniform. Several countries have adopted performance-based research funding systems (PRFSs) based on bibliometric indicators. At the same time, researchers and policy makers have realized that indicators need to be adapted to the specific nature of scholarly communication in the Social Sciences and Humanities (SSH). The specificities of much of the research in the SSH disciplines have made an all-too straightforward approach toward the counting of publications for evaluative purposes unsuitable for the SSH  indexes for the bibliometric part of the indicator. Mounting pressure from academics  coupled with a growing awareness of the limitations of the large citation indexes for assessing research in the SSH prompted the Flemish government to devise a new way for publications to be counted by creating a regional database: the VABB, which lists all peer-reviewed publications by researchers affiliated to an SSH unit at one of the Flemish universities  publishing houses that did appear on the list, thus creating a disadvantage for local publishers. Moreover, the situation created an inequality between the two Flemish publishers already on the list (Brepols and Peeters) and other Flemish publishers not on the list. The system could also mean a disadvantage for disciplines that publish more locally oriented books, such as Law or History. Furthermore, the inclusion of local publishers would contribute toward making the VABB database more comprehensive.The GPRC label offers a way for books to be included in the VABB on an individual basis. The procedure for the GPRC label is as follows. The publisher holds on to a peer review dossier that includes at least the following parts:(1) The table of contents of the publication(2) The affiliation of the reviewers(3) A chronological overview of the peer review process(4) A minimum of two reviews(5) A formal confirmation that the reviewer authorizes the publication with the label.The ultimate decision on inclusion in the VABB remains the responsibility of the GP. The publisher has to submit the peer review dossier to the GP when requested. The panel does not review all publications with the label, but a selection each year from a number of publishers. The panel does not read the actual reviews submitted by the reviewers, their judgement of the peer review dossier is based solely on the formal criteria. The procedure for the inclusion of book series is similar. Publishers still have to hold on to a peer review dossier, which can be requested by the GP.In their discussion of the GPRC label, Verleysen and Engels  already A quality label for scholarly book publications has also been established in Sweden: Kriterium, a label that was established in a bottom-up way  journal literature for many decades, peer review has historically not been the primary way to ensure the scholarly value of book publications. Scholarly books have often been published by university presses who upheld the quality through the editorial processes of choosing authors and topics carefully and guarding the scholarly nature of their publications. Pochoda  mentionsThe pressure on academics to exclusively publish peer-reviewed works is increasing, and this can potentially affect publication practices in SSH. As already mentioned, researchers in the SSH publish a variety of works, including peer-reviewed scholarly articles, but also books directed at a wider audience. Hicks  argues tToday, external review (or peer review) is the norm for academic journals, as well as for many scholarly book publishers. The GPRC label is an attempt to include all peer-reviewed literature written by local scholars, not only the publications indexed in the major citation databases or published by publishing houses with an international reputation. In this way, the label can help scholars to continue to have a diverse portfolio of articles in international journals indexed in the major indexes as well as locally relevant publications in journals and books, often in Dutch, provided that they have been subjected to peer review. However, we have to remember that the GPRC label was introduced in a local (Flemish) context, and was also made available to publishers that do not have an exclusively academic/scholarly portfolio. Even though peer review has become the standard quality criterion of scholarly work, it is not necessarily performed systematically at local publishers. Some of the publishers who now publish GPRC books, previously may not have performed peer review of scholarly books in a systematic way. As the GPRC is an element within a PRFS that recognizes peer review as the main delineating factor between scholarly and not scholarly, it may result in some disciplines using peer review for a larger portion of their publications and it may tempt Flemish publishers toward using peer review and standardizing their peer review procedures.Another important element to take into consideration is how peer review is being defined. A recent study by Giménez-Toledo et al.  looks atbibliodiversity was introduced by Giménez-Toledo  and interpret them as signals of what society values about their research”  until 2019. These data are part of the most recent version of the VABB, version 11  were chosen to include in a further analysis of the content. We conducted a categorization of publication titles in terms of local (Belgian/Flemish) or international orientation for these GPRC publications.For the qualitative part of the study, three in-depth interviews with academics who had come into contact with the GPRC label were conducted. The interviewees were selected because of their experience with the GPRC label as author, member of the GP and/or through their experience in research management. Not all Flemish SSH researchers are familiar with the GPRC label or have a deep understanding of what the GPRC label entails. We decided to interview in particular someone from the discipline Law because the data pointed toward Law as the discipline that made the most use of the GPRC discipline, both in relative and in absolute terms. The in-depth interviews focused both on the respondent's general experience with the GPRC label (as author or policy maker) and some of the empirical results from the first part of the study. The interviews were recorded and transcribed. An ethical clearance was obtained from the University of Antwerp's Ethics Committee for the Social Sciences and Humanities. To safeguard the anonymity of the interviewees, we are not mentioning the specific professional positions of the interviewees.We identify a few key points of interest for the analysis of the data. Firstly, we want to find out to what extent the label has been used in the past 10 years and whether it has contributed to a more comprehensive inclusion of book publications in the VABB. Secondly, we analyse the languages represented among the GPRC book publications. We analyse to what extent the GPRC label contributes to a “balanced multilingualism.” Dutch language publications are also expected to discuss local topics. Thirdly, we expect the label to be taken up differently by the different SSH disciplines. While some SSH disciplines gear more toward the publication practices of STEM fields, publishing mostly English-language articles in international journals, others have a substantial share of local language articles and book publications, this is especially true for Humanities disciplines.In this first part, we analyse the evolution of the number of GPRC publications. VABB distinguishes between five publication types, four of which are relevant in the context of GPRC . We use the term “book publications” to refer to individual publications, which can be book chapters, edited volumes, monographs and proceedings papers.As can be seen in The most recent information on how many GPRC books were reported by publishers for 2020 shows a more nuanced picture. The number of books submitted for the last year (books that are not yet included in the VABB and thus do not show on the graph) is 104, almost 30 more than the 77 books that were reported by publishers in 2019. It seems too early to speak of a permanent drop in the use of the GPRC label.In 2009, the year before the introduction of the GPRC label, 22.3% of book publications submitted by universities  were included in the VABB. In 2019, the last year for which we have final data, this figure was 43.1%. This means that the inclusion rate for book publications in the VABB has almost doubled in the past 10 years. We hypothesize that this is due to an increase in comprehensiveness of the database  as well as a stronger inclination to publish peer-reviewed books at the researcher level. The alternative explanation—that universities no longer submit publications they assume will not end up in the database—is unlikely as sorting the publications would be much more time-consuming for them and uncertainty over outcomes makes the responsible people opt for the safer option of submitting everything that might potentially be included. It is, however, possible that publications that do not fit neatly in any of the five publication types are not always submitted.As can be seen in In this section, we discuss two aspects concerning the local orientation of publications. The first is language and the second is the content of publications, with topics of local relevance.As expected, the GPRC label shows a higher proportion of publications in Dutch  when compared to the language of other publications in the VABB. For the total database, 78.4% of included publications are written in English, with only 16.3% in Dutch. The third language is French (2.89%), the other major national language of Belgium. Among book publications, 73.5% are written in English, and only 16.1% in Dutch. A relatively large proportion of book publications are written in French, 5.8%. English is especially prevalent among WoS-indexed publications, where 96.5% of publications are written in English. For book publications with the GPRC label, only 28.8% of book publications are written in English while the majority, 68.1%, are published in Dutch. 2.5% of GPRC publications are written in French. In this way, the label caters mostly toward local language publications and adds an avenue for Dutch language publications to be included in the VABB. Thus, the GPRC label contributes to a balanced multilingualism, whereby English-language publications in international journals exist alongside a national literature of local language publications, including book publications. With the VABB system, both types of publications are counted toward the PRFS, provided they have been subjected to peer review prior to publication.Another aspect to take into consideration, is the content of publications. While it was not possible to study all GPRC publications in detail, an analysis of the list of GPRC titles taught us that several publications in the field of Law concern expositions of parts of the Belgian system of law. We conducted a categorization of the titles of 224 publications in Law that were either classified as edited book publications or monographs. We assigned publications to the category of Belgian or local issues if they contained explicit references to the locality  or if they could reasonably be assumed to deal with a local topic . Publications were assigned to the category of EU or European Law if their titles referenced either the EU or Europe. Most publications that were categorized as dealing with local topics did not use a toponym in the title, probably because the fact that they discuss Belgian law was assumed to be self-evident. Of the 224 publication titles we analyzed, 110 publications were found to concern Belgian or local law or criminology subjects. Twenty-four publications were found to concern EU or European law. Our approach is probably an underestimation, since it was based on a “common sense” categorization, where only publications that were very clearly local in nature were assigned to the local category. While this is only a rough estimate, it gives an indication of the importance of local topics to GPRC publications in the field of Law and a general impression of which kinds of publications the GPRC label is being used for by Law researchers. As these types of publications benefit in particular the local law practitioners and students, it makes sense for them to be written in Dutch. Eleven of these publications contain the word “handbook,” which can be translated into English as “handbook.” While the Dutch Law publications tend to focus on local law, the English-language Law publications often cover EU law.Closer scrutiny was also given to publications in the field of History, because book publications have been singled out as important parts of the research output of historians . Moreover, many Law publications are book publications . However, the predominance of Law publications among GPRC publications is also related to the nature of scholarship in Law. In many countries, a debate has emerged in recent years about the nature and methodology of research in Law, and the position of so-called doctrinal research Stolker, . This deBecause the discipline Law seems to use the label most often, A second noticeable trend in the distribution between disciplines is that some disciplines use the GPRC label for a larger portion of their book publications. Disciplines such as Law, Political Science and Arts use the GPRC label for a relatively large portion of their book publications . MeanwhiWe now zoom in on the differences between the social sciences and the humanities in terms of how the GPRC label has been taken up. Because the humanities are typically seen as more book-oriented disciplines, we expect the GPRC label to be more relevant to the humanities. We disregard the discipline Law. Firstly because Law has an overwhelming presence in the data and secondly because Law is sometimes also classified as a humanities discipline . On the whole, the intuition that a larger proportion of publications from the Humanities would be book publications than for Social Sciences disciplines is confirmed for the VABB data. Thirty-seven percent of publications in the Humanities are book publications, compared to only 23% for social sciences publications. This is not unexpected and in line with previous studies on book publications in the SSH  and languages. The majority of publications were written in Dutch, which corroborates the idea that the GPRC label can contribute toward a “balanced multilingualism.” While the GPRC label will likely not convince authors to write their publications in Dutch, it will allow them to have their Dutch language publications published at local publishers to be counted in the PRFS.We also found that the GPRC label was unevenly distributed among disciplines, with Law publishing by far the most GPRC-labeled book publications. The reason is that the different disciplines don't have the same use for the label. The label is most interesting for disciplines that publish locally oriented books at publishers that are not already included in the VABB. It certainly does not create a drive toward the publication of Dutch language books in those disciplines that have a predominantly journal-oriented international profile. This is not very surprising, but it does point toward the fact that while the GPRC label is part of a PRFS, it does not seem to have causal effects on the choice of publication outlet or language.A final finding of this study concerns the aspect of peer review. The GPRC label has prompted publishers that previously did not have a formalized peer review procedure to adopt one in order to comply with the GPRC regulations. It remains to be seen whether publishers will continue to publish GPRC-labeled books, or whether some publishers may decide to publish fewer GPRC books because of the extra work involved in organizing the peer review procedure. Whereas the initiative for obtaining a GPRC label currently comes almost entirely from the author, publishers could become more interested in using the GPRC label if the label would be recognized within the scholarly community as a mark of quality. If the GPRC label would be reviewed, it would be helpful to take inspiration from other labels for peer-reviewed books that have recently been introduced. The Finnish and Swedish examples show that there are different uses of a label for books, the GPRC label's sole focus on approval in the VABB may be a limiting factor to its further uptake.Finally, a few limitations of this study as well as suggestions for further research can also be given. Firstly, we have not taken book series into account in our analysis. Secondly, only limited attention was given to comparisons with the whole of the VABB. Thirdly, the total number of publications was quite small and the time frame limited to 10 years which makes it difficult to identify long-term trends. Another limitation is that we could not make causal claims about the effects of the GPRC label. Finally, future research could focus on analyzing in detail the developments at the Flemish publishers. Further studies could also explore the content of GPRC publications. While we offered a first look at the publication titles of Law and History publications, a closer analysis of both GPRC and non-GPRC publication titles and abstracts would enhance our understanding of the local and international characteristics of GPRC publications as well as the intended audiences of GPRC publications. This study also did not include an international comparison, in particular a comparison with the Finnish and Swedish labels for peer-reviewed publications could be interesting. Lastly, interviews with a larger number of authors from different disciplines as well as publishers of GPRC publications could give helpful suggestions for improving the label.https://doi.org/10.5281/zenodo.4472810. Part of the dataset is not available online. Requests to access these datasets should be directed to peter.aspeslagh@uantwerpen.be; raf.guns@uantwerpen.be; tim.engels@uantwerpen.be.Part of the dataset is publicly available on: doi: The studies involving human participants were reviewed and approved by Ethics Committee for the Social Sciences and Humanities (EASHW) University of Antwerp. The patients/participants provided their written informed consent to participate in this study.EV: conception and design, drafting the work, and performing the analysis. RG and TE: conception and design, substantial critical revisions, and providing approval for publication. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.