The introduction of newly developed blended cements into the mass market is essential to ensure an effective reduction of the carbon footprint related to cement production. To facilitate this process, formulating mix proportions using pastes and/or mortars rather than concrete can be a great advantage. However, for the upscaling towards industrial concrete it is then essential to maintain the target rheological and mechanical properties, something that is all too often challenging. In this work, a procedure facilitating such an upscaling was illustrated in the form of a flow chart. Specifically, best practices to obtain a good correlation between concrete prepared in a laboratory and one prepared in a plant were presented. This includes new data showing how to accommodate for possible differences in temperature and/or water content between both situations. The dataset of state-of-the-art correlations between mechanical performance and heat of hydration, considering w/b ratios relevant to practice, were expanded. This greatly facilitates the mix design of concrete with particularly low clinker contents, which in this work were illustrated with a blended cement containing only 50% clinker.The online version contains supplementary material available at 10.1617/s11527-022-02040-5. Given tmissions , 3–5, coductions .In all cases, large scale tests using concrete prepared in a plant are ultimately necessary to ensure the robustness of new concrete mix designs. This can however be more problematic than suspected since mechanical and rheological performances can be affected by factors as:—the type of mixer and/or its energy,—the moisture of sand and aggregates,—temperature,—accuracy of water dosing (including possible washing water remaining in the mixer) and—possible residues in the mixer from previous concrete productions. In particular, it is well known that mixing energy affects the hydration and rheology of cement and its constituents –12. FurtMoreover, the simultaneous use of several admixtures is common practice nowadays, especially for low clinker cements, and may lead to competitive adsorption processes that affect the targeted rheological performance –19. For Considering all these factors, a proper predictability of rheological and mechanical performance from lab tests to plant production is called for.3 content, sand volume fraction and curing conditions , as well as for water to binder (w/b) ratios going from about 0.3 to 0.43. Above w/b of 0.43 they found that the relation becomes dependent on w/b, but did not investigate this feature further. One of the contributions of the present paper is to expand the dataset of such correlations between compressive strength and w/b towards higher w/b values. Such situations are indeed highly relevant to practice as they correspond to the largest volumes of concrete used and therefore also to the largest possible use of low clinker cements. Results presented in this paper also shed new light onto the underlying reason why strength correlates with the heat release per unit volume of water as reported by Bentz et al. [An important issue here is to be able to account for performance changes in case the water content differs in industrial production. In this sense, correlations between calorimetry and strength of cement pastes or mortars are useful –28. Specz et al. .Another important part of this paper is to establish that the relation between compressive strength and heat released does not depend on temperature. Thus, while hydration kinetics are temperature dependent, at equivalent cumulative heat release the same compressive strengths are obtained. This also represents a very useful result allowing to better anticipate how variability in production conditions may affect concrete properties in practice.Based on these results a mix design method, presented in the form of a flow chart in Sect. 5.4, was proposed. It is a framework that aims at facilitating the optimization of low clinker cements and concrete at realistic w/b ratios and in presence of several chemical admixtures, from cement pastes to mortar, lab concrete and plant trials, in terms of target rheological and mechanical properties. It is emphasized that the role of paste volume was not considered. This factor profoundly affects the rheology of concrete, but has little effect on most hardened state properties as shown in the broad review compilation by Hermida , 30. So,Before this and in the next section, recent work on the correlation between rheological and mechanical performance of a new binder and a commercial one prepared either in the laboratory or in a concrete plant were summarized .3) [a new low clinker blended cement with 50% Portland cement, 20% limestone, 20% burnt oil shale and 10% fly ash and activated by gypsum (abbreviated MF);a blend of a CEM II/A-LL 42.5 N  and an SCM blend  .Recently, Boscaro et al. established correlations between fresh and hardened properties of concrete prepared in the laboratory (maximum 35 L) and in industry (maximum 3 m3) . They teThey found correlations between lab and industry flow table spread (FTS) from 10 to 90 min and for compressive strength from 1 to 7 days  containing 50% CEM I 52.5R , 20% burnt oil shale (BOS), 20% limestone (LL) and 10% fly ash (FA)  and a coV50 and the specific surface area SSABET measured as described in [ Table ribed in . The minribed in .Table 1CThe aggregates  were composed of calcite (60–70%w/w), dolomite (10–15%w/w), quartz (5–10%w/w), feldspar  and sheet silicates . The water absorption coefficient (WA24) of the aggregates was 0.8%, according to EN 1097–6. The granulometry is reported in Fig. S2 .V50 of 16.73 μm and SSABET of 0.77 m2/g, was used as activator of concrete prepared with the MF binder.Commercial ground gypsum , characterized by DA commercial superplasticizer (SP) Sika® ViscoCrete®-5063 T (Sika Technology AG) was used for concrete prepared with the F4F binder. PCE4, a non-commercial polycarboxylate ether superplasticizer (Sika Technology AG) containing defoamer and biocide, was included in the concrete prepared with the MF binder. PCE4 is a methacrylic-based polymer synthetized by esterification. Its molecular parameters are reported in Table A commercial air entraining agent (AEA) Sika® Luftporenbildner LPS A-94 (Sika Technology AG) was used in all concrete formulations.Concrete was prepared using deionized water and 0–16 mm dried aggregates, using several w/b ratios  Table . The binGypsum as activator was added on top of the binder and aggregates following two modes of addition:—added as a powder and homogenized for 1 min at 60 rpm;—added as a paste (prepared as described in ), followCalorimetric measurements were performed at 10 °C and 23 °C using an isothermal calorimeter I-Cal 8000 HPC . Concrete was sieved under 4 mm prior to the beginning of the measurements. The tests started about 12 min after the beginning of the hydration. The first 30 min of the calorimetric data were not considered for all the measurements, with the exception of MF_I and MF_II samples where the first 1.97 h and 1.48 h were not evaluated.The initial FTS and the fluidity loss at 1 h were measured according to SN EN 12 350–5 using a tronco-conic mould of 20 cm height × 20 cm bottom diameter × 13 cm smaller diameter. The flow table was humidified prior to testing. After the removal of the mould, the flow table was shocked 15 times and two perpendicular diameters were measured.Compressive strength was measured on concrete specimens (15 × 15 × 15 cm), according to EN 196. Samples were demoulded after 1 day and stored at 10 °C/100%RH or 20 °C/95%RH prior to testing. 2—3 cubes were tested per formulation. Table  Figure with binder F4F, at w/b of 0.45 and 0.48;with binder MFwithout activator for w/b of 0.43 (noted MF_I and MF_II);with gypsum activator blended to the cement (MF_GB) for w/b 0.43with gypsum activator added as a paste (MF_GP) for w/b of 0.43 and 0.47.Following the approach proposed by Bentz et al. , the relThe initial FTS of these mixes is reported in Table  Figure It was shown that the temperature does not significantly affect the FTS of concrete from 10 to 90 min, confirming previous results by Boscaro et al. obtained on cement pastes . This emThe correlation between compressive strength and cumulative heat, in particular for the MF binder, does not depend on temperature. However, the time needed to release a given amount of heat and thus to reach a given compressive strength does depend on temperature  Fig. . The curFigure H per water volume relates to compressive strength Rc through:The meaning of the “ineffective heat” is discussed in the next sub-section. For now, the slopes of the regressions from Fig. H0 is the ineffective heat (here 118 J/mL), α and β are respectively the slope and ordinate of the regression line in Fig. where The compressive strength can therefore be given in relation to w/b by:β is negative, which implies that the relation leads to an infinite compressive strength for a finite and critical value of w/b. If the data are fitted in terms of heat per mass of binder that critical w/b is 0.362, while it is 0.326 otherwise . In both cases, the value of H0 = 118 J/mL, α = 172.5 J/mL and β = -56.2, the predicted compressive strengths versus the measured ones are reported in Fig. Using Eq.  with H0 The compressive strength can actually also be well fitted by Eq.  when theAs previously mentioned, the correlation of strength with cumulative heat of hydration has been reported by many researchers –28. HoweH0 should increase with w/b above that limit. Specifically, they reported this for a mix with w/b of 0.56 [H0 for a CEM I 42.5 having w/c between 0.3 and 0.5 [The broad range of compositions over which the normalization with respect to the volume of water provided better correlations suggests that there is an underlying common mechanism to consider. This may be that the space filling of the volume initially occupied by water controls the strength development . With re of 0.56 . However and 0.5 .H0 is 118 J/mL, rather similar but nevertheless different to the one of 180–200 J/mL reported by Bentz et al. [In the results presented here the value of z et al.  and Lootz et al. . This maz et al.  and Lootz et al. , but nevz et al.  includedz et al.  and this3S that must react to produce 150 J is about 0.28 g, thus about 0.10 cm3. Stated differently, it implies that about 10% of the initial porosity needs to be filled by the additional volume occupied by hydrates before substantial strength may develop. The amount of C3S that must dissolve is much higher than what is needed to saturate the pore solution (in the range of 2 mg), which adds weight to the percolation argument.As first order analysis, an average ineffective heat of 150 J/mL between both studies is considered. The amount of C3A increases the heat release but does not affect the compressive strength at 1 day [2O eq. increases the strength but does not significantly change the heat of hydration [3S content was increased, the compressive strength increased also [H0.In relation to cement composition and correlation between early strength and heat of hydration, other authors showed that an extra 4% of Cat 1 day . In contydration . Most imsed also . This ofThese results lead to the main contribution of this paper, which is to present a framework that encourages a more efficient optimization of low clinker cements and concrete to reach target properties for conventional construction. Such a strategy is presented in the flow chart in Fig. Define the target concrete properties as the slump flow, compressive strength and durability. At this stage, considerations of durability serve to define a range of w/b values and are not considered further in the chart.Define the main compositional parameters of the low carbon concrete: Type and amount of SCMs, paste volume and aggregate grading. Along with considerations on strength and durability, this largely determines the initial choice of the w/b, which is also decided at this stage.Select chemical admixtures, particularly activators and superplasticizers. A. Basic mix design decisions:From Eq. , determiUsing correlations between flow spread on paste (and mortars) and simple rheological tests in concrete , determine the target flow spread to be obtained in pastes (and mortars). Procedures building on  are detaB. Reformulate target properties in parameters to be achieved in paste and mortar:Using flow spread measurements and calorimetry, optimize the accelerator and superplasticizer dosages to reach the target flow spread and heat release. For practical purposes, the onset of the acceleration period would most often not be wanted prior to 2 h after mixing.In mortars, compressive strengths are measured, which along with calorimetry and flow spread measurements allow to refine the admixture dosages. Should the target properties be difficult to reach, modifications of the w/b and SCM proportions may be considered.Experiments on laboratory concrete are conducted and offer the possibility to carry out minor adjustments of the admixture dosages to reach the target strength and slump flow. In principle, properties determined here should match the ones of concrete prepared in industry, provided the w/b is the same  , 30. WitIn terms of obtaining a first estimate of the superplasticizer dosage for a target fluidity, it is noted that for PCEs, correlations reported in , 34 alloA critical step for expanding the use of low carbon concrete into the mass market is to minimize the amount of work needed to obtain robust mix designs that deliver the prescribed fresh and hardened properties. In this sense, correlations between compressive strength and heat of hydration are very useful because they make it possible to carry out most of the mix design by using pastes instead of concrete.In this regard, results presented in this paper expand the type of strength to heat of hydration relation proposed by Bentz et al.  to deal Building upon this, this paper proposes a chart summarizing how to best use paste and mortar tests to formulate concrete mix designs that will perform as expected when prepared in industry. It is mainly intended for low clinker concrete that are prepared with chemical admixtures and at realistic w/b ratios. Such a workflow reduces the work-load for formulating well-working low carbon concrete mix designs and should therefore facilitate a broader use of such concrete in industry.Supplementary file1 (DOCX 599 kb)Below is the link to the electronic supplementary material.


In the Mediterranean Sea, near the coast of Israel, two dolphin species reside; the common bottlenose dolphin and the common dolphin. These two have been observed by researchers over the last 20 years and have been sighted along different parts of the coast. The two species therefore have different preferences of habitat and in order to evaluate environmental characteristics that are important for each species, statistical models were used to evaluate patterns in their occurrence. Common bottlenose dolphins were found to inhabit the entire length of coast and often chose to swim near fishing trawler vessels. Common dolphins were found to inhabit only the southern section of the Israeli coast and typically chose to swim in shallower waters than the common bottlenose dolphins. It is evident that the two species choose different habitats and the common bottlenose dolphins adapt according to human presence and disturbances, while the common dolphins have more specific preferences that are still not fully understood.Tursiops truncatus  and Delphinus delphis . Ship-board surveys and sporadic sightings over the last two decades have shown that the two differ in distribution—T. truncatus is found along the entire coast and D. delphis only in the south. The environmental and anthropological factors affecting these species’ spatial distribution and determining their habitat preferences in this area are largely unknown. This work is a first attempt at summarizing 20 years of observations and studying habitat preferences for both species, by use of Generalized Additive Models. T. truncatus was found to be present in all areas of the continental shelf where survey effort coverage was sufficient, with a high affinity towards bottom trawlers. Model results showed D. delphis distribution to be associated to  water depths, though the factors driving their limited latitudinal distribution currently remain unknown. It is evident that T. truncatus and D. delphis are present in segregated areas of the Israeli continental shelf and T. truncatus currently sustains a delicate balance with continuously shifting human activities, while the drivers of D. delphis distribution are more specified, yet still not fully understood.Along the Mediterranean coast of Israel, two near-shore dolphin species are prevalent;  Tursiops truncatus (Common bottlenose dolphin) and Delphinus delphis (Common dolphin), which are sighted routinely along the shallow continental shelf of Israel and are the focus of this research.Across the Levantine Basin in the Mediterranean Sea, only a few studies have been performed on cetacean populations. Although a handful of research cruises have been executed, as well as a singular aerial survey during the ACCOBAMS Survey Initiative, no long-term ecological research has been conducted, with the exception of the Israeli coast. In 1998, IMMRAC  began a near-shore research program for coastal dolphins, under the academic umbrella of the University of Haifa. Based on the data that have been collected regularly in Israel on dolphin populations over the last 20 years, it has been established that the Mediterranean coastal shelf along Israel’s shoreline is home to two resident dolphin species—T. truncatus and D. delphis populations, their distribution and preferred habitats during this period.This paper aims to summarize 20 years of dedicated vessel-based dolphin surveys in Israel and outline the main findings on the T. truncatus can be observed along the entire coast and has been documented since surveying began in Israel, while D. delphis has been observed anecdotally in 2009 and 2011 near Herzliya and routinely since 2016, in the south of Israel [D. delphis is typically regarded as a pelagic species that feeds on small schooling fish such as anchovies and sardines [D. delphis displays much plasticity in terms of habitat and is found in coastal water and near the shelf edge, in addition to pelagic waters [T. truncatus and Stenella coeruleoalba, in mixed groups [D. delphis has been observed exclusively in shallow waters, close to shore and the most common prey item identified from stomach content analysis of stranded individuals is Ariosoma balearicum, which is also the most common prey item of T. truncatus in Israel and a common by-catch fish in trawler hauls [Though both dolphin species are sighted regularly in Israeli Mediterranean waters, sardines , though c waters ,5,6. Thid groups ,6,7,8. IT. truncatus has been difficult to gauge and estimations have ranged from 360 [D. delphis population is comprised of a distinct cohort, verified by photo-ID analysis, and estimation of abundance is therefore more accurate. Mevorach et al., 2022 [D. dephis was initially observed in Israel, this group included up to 37 mature individuals, though since 2020 only the same 15 adults have been observed.Abundance of from 360  to 135 il., 2022  has demoa in the vicinity of the Nile River delta extending as far north as the Gaza strip [The Levantine basin is the most oligotrophic, saline, and warmest part of the Mediterranean . Seawateza strip ,17.The eastern Mediterranean has been undergoing many changes in recent decades, including shifts in ecosystem composition due to the introduction of invasive species from the Red Sea arriving via the Suez Canal ,20,21,22Additionally, climate change is a well described phenomenon with various global effects, which is causing measurable increases in water temperature in the eastern Mediterranean (mean of 0.04–0.05 °C per year) ,28,29 thT. truncatus’ relationship and dependency on trawlers, both in Israel, in other parts of the Mediterranean and worldwide [T. truncatus have been found to utilize bottom-trawlers and their nets as mobile feeding points [T. truncatus in particular are opportunistic predators and can shift their dietary preferences, foraging methods and habitat preferences according to available prey [The Mediterranean trawler fleet of Israel is also an influential and dynamic phenomenon, as the number of active trawlers has decreased throughout the study period from 31 to 15 and the target species have shifted multiple times. Many previous studies have demonstrated orldwide ,34,35,36g points ,37. Dolpble prey ,39,40.In Israeli waters, considerable anthropogenic intervention has occurred over the last two decades—establishing Marine Protected Areas, fishing regulations, conducting of seismic surveys, construction of oil and gas facilities, increase in recreational maritime activities and more. All of these activities affect the marine environment and its inhabitants—marine mammals included ,42,43.T. truncatus and D. delphis foraging efficiency and strategies as well as distribution. Dolphins, being apex predators, are key indicators of the health of our marine eco-systems [It is unclear how these combined changes will affect -systems  and chanIn order to map distribution of cryptic animals, such as marine mammals, habitat models are being applied in many regions worldwide, particularly in areas that are difficult to survey (far offshore) or are heavily impacted by human disturbances ,46,47. MThis study was conducted along the Mediterranean continental shelf of the Israeli coast a. The MeThe exact boundaries of the study area are depicted in T. truncatus distribution and habitat preferences and data from the years 2009–2020 were analyzed to study D. delphis.Over the last 20 years, researchers from IMMRAC, Delphis (NGO) and the University of Haifa have been conducting half-day nearshore shipboard surveys focused on the coastal dolphin population. For this study, data from the years 1999–2019 were analyzed to study During the shipboard surveys, the ship’s track is continuously recorded, as well as the sea conditions  and information on species, group size, behavior and presence of calves/juveniles. Surveys are initiated only when sea conditions are less than Beaufort Sea State 3, with survey vessels traveling between 7–12 knots and performing a zig-zag search pattern. If a trawler is present near-by, the vessel leaves its planned course in order to search for dolphins that may be feeding around the net. When dolphins are sighted, the vessel follows the group as long as necessary to take photos for individual identification. Although the data input platform has changed between hand-written notes, a designated tablet program and a designated phone app , the corD. delphis because this species’ extent of occurrence only encompassed Israel’s southern region, which will be referred to from here on as ‘Dd Area’  survey status (active searching/dolphin sighting), (b) dolphin sighting parameters, , (c) searching type  , (d) vesa, bottom content, artificial submerged structures, rigs and fish cages, searching = trawlers, searching = fish-cages), some serve as proxies from anthropogenic effects  and many also serve as proxies for both prey and anthropogenic effects.A large array of environmental data was gathered from multiple sources, as detailed in a’ (as a proxy for primary production), When considering sea surface temperature in the context of this study, the majority of the variability across this parameter occurs over time (between days) and not over space, therefore a data model was used that provided daily means. When considering chlorophyll a measurements, the ultra-oligotrophic nature of the study area and high variability require the use of direct measurements. However, many measurements were missing from the data-set due to cloud cover and proximity to shore, causing reduced coverage. This reduced coverage was not able to provide meaningful results during modeling, therefore chlorophyll a was ultimately excluded from the modeling process  and seasonal (‘Hot/Cold Season’) subsets were utilized to explore the changes over time and seasonal patterns. Spatial subsets were utilized to explore differences in habitat use across sections of the study delineated by different characteristics with regard to environmental parameters and survey effort b. ‘Area T. truncatus and 40 sightings were of D. delphis . D. delphis group sizes ranged between 4–30, with mean group size 16.2 ± 5.1 (95% CI). Surveys were carried out year-round, with totaled-surveys-per-year ranging between 6–170 and totaled-sightings-per-year ranging between 2–45.Between the years 1998 to 2020, 1137 ship-board surveys covered a total of 45,384 km and recorded 346 dolphin sightings. 306 sightings were of  delphis . T. trunT. truncatus demonstrate that this species is sighted all along the Israeli-Mediterranean coast, in a variety of group sizes, latitudes, depths and distances from shore  that exceeded the threshold were retained in these subsets c,d. OverD. delphis are sighted regularly in Israel during recent years, mostly south of Ashdod, in large groups , including calves [D. delphis sightings in the area were in shallow water, at depths less than 40 m  that was associated with presence of a trawler. Prediction maps were created based on four different models from the ‘trawler excluded’ subset and these display the probability of occurrence for T. truncatus along the Israeli continental shelf, according to the findings of each model  are prohibited for trawling year-round, in addition to a seasonal no-trawling period along the entire coast in July and August. Due to the relative novelty of these regulations, there is not enough data to determine how the change in trawling patterns has affected T. truncatus distribution.Survey observations as well as visualized prediction maps derived from ‘non-correlated data’ models demonstrate that T. truncatus sightings from designated surveys became scarce from the year 2014 and onwards. This finding may be related to an existing acoustic disturbance in the north in recent years, though this speculation has yet to be proven with certainty. Additionally, sightings reported from the general public are also very rare between Akko and Achziv in recent years. Either way, it appears that T. truncatus currently displays a preference towards the area of the Israeli coast from the Haifa Bay and southwards.In the north of Israel, near Rosh Hanikra and the Achziv sub-sea canyon, T. truncatus during the ‘Hot Season’.The difference found across models from the ‘Hot Season’ and ‘Cold Season’ in regard to association with trawlers may be attributed to: (1) Differences in trawler patterns, (2) Differences in prey availability in the natural environment and therefore differences in foraging strategies, (3) Differences in energetic budgets between seasons, resulting in differences attributed to foraging strategies. Trawl haul has been shown to change across the seasons , with reT. truncatus display a preference towards a corridor, approximately 3–5 km wide, that runs parallel to shore, at a distance of 6–8 km. This spatial preference could be related to depth, distance from shore (both as determinants of prey concentration), or following typical trawling routes in anticipation of encounters, and currently there is not enough data to discriminate between these possibilities.Prediction maps based on modeling results indicated that D. delphis are sighted only in the south of Israel, between ‘Palmachim’ and ‘Ashkelon’ and only in shallow waters between 20–40 m depth. Model results also support these observations, as ‘Depth’ was found to be the most significant environmental parameter for D. delphis distribution. These findings do not fully align with previous findings from stomach content analysis, which indicate an association between D. delphis and trawlers. Furthermore, throughout designated surveys, D. delphis were only occasionally observed near trawlers, mainly while in their sorting process, and it is possible that the few individuals that were stranded (deceased) are not a good representation of the entire population but rather represent outliers that died of unnatural causes.Survey observations conclude that D. delphis tends to inhabit deeper water than T. truncatus in overlapped areas around the world and in the Mediterranean Sea in particular [D. delphis in Israel as well.Considering the limited survey effort in deep waters, as well as the variability in this species’ observed habitat in the Mediterranean Sea, and the fact that rticular ,5,73, itD. delphis sightings reported by the general public since 2015, occurred during the months of January-March, demonstrating that D. delphis is not completely absent during these months, though less prevalent. It should also be noted that these three months are some of Israel’s coldest and stormiest winter months, making surveying difficult and minimizing the time the general public also spends out at sea.Although according to survey results this species display a seasonal trend of absence during winter, 10% of D. delphis’s spatial distribution is affected by diurnal patterns overlooked by the data. Small delphinids, including D. delphis have been documented to exhibit changes in behavior and distribution (nearshore vs offshore waters) across different hours of the day [Lastly, it should be noted that nearly all surveys in this region were conducted during the day, with the vast majority of surveys setting out in the morning and ending by noon, therefore it is also possible that  the day ,75,76.This species is considered ‘Threatened’ in the Mediterranean  and the T. truncatus occur across the entire length of Israel’s coastline while D. delphis sightings are clustered and confined to the south region. Although the restricted distribution of D. delphis may be related to higher concentrations of nutrients from the Nile River delta, this speculation could not be confirmed due to constraints in the collection of environmental data. Although survey observations and model results were not robust enough to detect temporal or spatial trends related to industrial anthropogenic effects, habitat models did provide partial answers to differences in distribution between the two species, with their results matching survey observations, demonstrating that D. delphis prefers shallower depths and T. truncatus prefers association with trawlers and fish farms.Two decades of designated surveys have shown that sightings of T. truncatus and D. delphis are present in segregated areas of the Israeli continental shelf. Due to the distinct spatial separation (according to depth) and different foraging strategies presented by the two species in the south of Israel, it is likely that their co-existence in the region is made possible by niche separation, though additional research on the topic is currently underway. Furthermore, there are no recorded observations of mixed species groups or interactions between the two species.Across all maps created during this study, it is evident that


Mycobacteriumavium-intracellulare complex (MAC) is the most frequently involved NTM. The MAC-PD treatment is based on the administration of several antibiotics for long periods of time. Nonetheless, treatment outcomes remain very poor. Among the factors involved is the ability of MAC isolates to form biofilm. The aim of the study was to assess the in vitro activity of different antibiotics and potential antibiofilm agents (PAAs) against MAC biofilm. Four antibiotics and six PAAs, alone and/or in combination, were tested against planktonic forms of 11 MAC clinical isolates. Biofilm was produced after 4 weeks of incubation and analyzed with the crystal violet assay. The antibiotics and PAAs were tested by measuring the absorbance  and by performing subcultures . The clarithromycin/amikacin and clarithromycin/ethambutol combinations were synergistic, decreasing the MBECs values compared to the individual antibiotics. The amikacin/moxifloxacin combination showed indifference. The MBIC values decreased significantly when PAAs were added to the antibiotic combinations. These results suggest that antibiotic combinations should be further studied to establish their antibiofilm activity. Moreover, PAAs could act against the biofilm matrix, facilitating the activity of antibiotics.Nontuberculous mycobacteria (NTM) cause lung infections in patients with underlying pulmonary diseases (PD). The  Mycobacterium tuberculosis and Mycobacterium leprae. They are broadly found in the environment  and are generally non-pathogenic to humans [Mycobacterium avium-intracellulare complex (MAC) is one of the most clinically significant, slowly growing mycobacteria (SGM) and is frequently involved in NTM-PD [Nontuberculous mycobacteria (NTM) include over 200 mycobacterial species other than o humans . Howevern NTM-PD . Nonethen NTM-PD .M. tuberculosis, have the ability to form biofilms [MAC, as well as other NTM and biofilms . There ibiofilms . Biofilmbiofilms . They ofbiofilms ,9. The abiofilms . As a rebiofilms ,11. Howebiofilms .N-acetyl-l-cysteine (NALC) have proved to be effective in disrupting the biofilm matrix, and thus improving antibiotic penetration at the site of infection [Pseudomonas aeruginosa pulmonary infections. Further research of the MAC-PD biofilm could improve patient management and result in better treatment outcomes. Consequently, the objective of the present work was to study the in vitro activity of different antibiotics and potential antibiofilm agents (PAAs), alone and in combination, against MAC biofilm.Given the poor MAC-PD treatment outcomes, it is essential to develop novel treatments that not only target the planktonic forms, but also MAC biofilm. Unfortunately, there are limited clinically available options. However, a few studies have used novel approaches against MAC biofilm by targeting the biofilm matrix . For insnfection . Differenfection ,13. Ther90 of the following ten clinical isolates: four clinical isolates of M. avium and six clinical isolates of M. intracellulare, plus the reference strain M. avium ATCC 25291, for four antibiotics (amikacin (AMK), CLR, EMB and moxifloxacin (MXF)), and six PAAs . The different antibiotics showed MICs values ranging from 2 µg/mL to 16 µg/mL against the planktonic forms. The PAAs showed MIC values of >64 µg/mL. 90 of the biofilm forming forms (BFF) for all the antibiotics and PAAs tested. All of these showed a MBEC90 of 4096 µg/mL.90 and the fractional inhibitory concentration index (FICI)90 of three two-antibiotic combinations , against all of the 11 isolates (including the reference strain). In the planktonic forms, the fractional inhibitory concentrations (FIC)90 of the combinations were indifferent (ranging from 0.75 to 4). However, in BFFs, the combination CLR/AMK was synergistic in M. avium and M. intracellulare isolates and the combination CLR/EMB was synergistic in M. intracellulare and indifferent in M. avium. The combination of AMK/MXF was indifferent in both species.M. intracellulare isolates. Synergism was observed when combining CLR/AMK with the PAAs, except for NALC and Tween 80 in M. avium isolates.90) in BFFs. An overall correlation was observed between the MBEC90 and the MBIC90 for the individual antibiotics and for the three two-antibiotics combinations.In addition, The individual results of each clinical isolate are displayed as M. avium and six M. intracellulare clinical isolates. The antibiotic combinations were studied with and without PAAs.In the present work, we studied the in vitro activity of four antibiotics, alone and in combination, against planktonic and BFFs of five M. avium and CLR/AMK and AMK/MXF against M. intracellulare. The third combination, CLR/EMB, was indifferent against both species . Differences in the antibiofilm activity of antibiotics have been observed in RGM. For instance, Muñoz-Egea et al. [Mycobacterium smegmatis and Mycobacterium fortuitum, while in the planktonic forms, the opposite occurred. This fact could be related to the chemical properties of each antibiotic. Moreover, in the presence of biofilm, the concentrations required to eradicate mycobacteria can be up to 100 to 100,000 times higher than the MICs of the planktonic forms. However, the addition of detergents and mucolytics, such as Tween 80 or NALC, enabled the activity of antibiotics and reduced the MBECs in two dilutions [M. smegmatis biofilm. In recent years, several antibiofilm agents have been tested against different bacterial species, given that a high percentage of chronic infections are mediated by biofilm formation [There is a strong interest in studying the activity of antibiotics against biofilm forming infections. Respiratory infections associated with biofilm formation mainly occur in patients suffering from bronchiectasis and cystic fibrosis and most of the literature is about a et al.  observedilutions . In our ilutions  analyzedormation . In addiormation .In this paper, three combinations were studied, showing indifferent activity against the planktonic forms with FICs ranging from 1.25 to 2.25 . NonetheM. avium. These methods of antibiotic administration reduce side effects, by allowing the sustained delivery of high concentrations directly to the site of infection.Although the synergistic concentrations found are not low enough to be achieved in the bloodstream with the usually administered doses, it highlights the importance of exploring new strategies to treat mycobacteria . For insSalmonella tiphimurium and P. aeruginosa [On the other hand, in the present study, six PAAs were also tested. Two of these, NALC and Tween 80, had been previously studied, showing antibiofilm activity against RGM . Additioruginosa ,22.M. intracellulare and four of these  against M. avium . This fact suggests that these six agents could have activity against the biofilm matrix, and thus enabling the activity of antibiotics. The confirmation of this finding in future studies would allow for the possibility of including these agents in the current treatment compounds addressed to destroy the mycobacterial biofilm.Interestingly, when the PAAs were added to the antibiotic combination of CLR/AMK, we observed synergistic activity of the six PAAs against M. avium . This waLastly, from a methodological perspective, the lack of standardized methods for biofilm analysis is a limitation, given that it can lead to different interpretations and conclusions.In comparison with the absorbance determination, subculturing may correlate better to the antibiotic activity, as it directly reflects the number of mycobacteria present. Previous studies have used similar methodologies and/or confocal microscopy ,15.M. intracellulare isolates. A synergistic activity was observed when ASA, IBP, PCM and DADS were added to the CLR/AMK combination in M. avium BFF. Regarding M. intracellulare BFFs, all the potential antibiofilm agents had synergistic activity when added to the CLR/AMK combination.As a final conclusion, the combination of CLR/AMK displayed synergy against both MAC species. In addition, the combination of AMK/MXF also showed synergistic activity in M. avium and six M. intracellulare clinical isolates obtained from the Microbiology Department of the Hospital Clinic of Barcelona were used in the present study. The ten clinical isolates were obtained from the respiratory samples of ten different patients. All of the isolates had previously shown the ability to form biofilm in vitro. The reference strain M. avium ATCC 25,291 was also included.Four The four antibiotics were selected among those recommended in the empiric treatment against MAC infections. The three two-drug combinations studied were designed according to the following criteria: CLA-EMB for oral administration; CLA-AMK for the treatment of severe cases and AMK-MOX for macrolide resistant cases. According to the results obtained, the best combination studied included PAAs.AMK, CLR, EMB and MXF, as well as the PAAs, NALC, Tween 80, ASA, IBP, PCM and DADS, were obtained from Sigma-Aldrich . AMK, EMB, MXF, NALC, Tween 80, ASA and PCM were dissolved in sterile distilled water. CLR was dissolved in acetone and sterile distilled water. IBP was dissolved in dimethyl sulfoxide (DMSO)   and sterile distilled water. DADS was dissolved in absolute ethanol  and sterile distilled water. All the antibiotics and PAAs were sterilized by filtration and stored at −20 °C until use.The experimental design for the MAC clinical isolates studied is explained in 5 CFU/mL, were added  . The positive control wells contained 100 µL of Middlebrook 7H9 and 100 µL of inoculum. The negative control wells were also included, by adding 200 µL of Middlebrook 7H9. The microplates were incubated at 37 °C for 7 days. After incubation, the plates were read using the Vizion System . The MIC value was interpreted as the lowest antibiotic and/or PAA concentration inhibiting mycobacterial growth.The MCIs for AMK, CLR, EMB, MXF, NALC, Tween 80, ASA, IBP, PCM and DADS, alone and in combination, were determined in 96-well plates . In brief, 100 µL of Middlebrook 7H9 liquid media  were added to each well. Then, 100 µL of antibiotic were added to the first well and two-fold serial dilutions, ranging from 64 µg/mL to 0.5 µg/mL, were made. The same procedure and concentrations were used for the PAAs, except for Tween 80, which was tested in dilutions ranging from 12.5% to 0.09%. Finally, 100 µL of inoculum, at a concentration of 1.5 × 10A + FICB = (CICA/MICA) + (CICB/MICB), where the CIC value is the lowest drug concentration that inhibits bacterial growth when the antibiotic acts in combination, and the MIC value is the lowest drug concentration that inhibits bacterial growth when the antibiotic acts individually.MICs, in combination with two antibiotics, were determined by crossing the individual MIC and the two concentrations below the MIC for each antibiotic with the corresponding one of the other antibiotics. This antibiotic interaction was analyzed using the FICI method, as proposed by Den Hollander et al. . The FICThe results of the FICI analysis were interpreted according to the following criteria: a decrease of two dilutions under the individual MIC was interpreted as synergistic with a FICI of <0.5; indifference was determined from 0.5 to 4; and a FICI of >4 was considered as antagonistic activity.90 and the FICI90 values, shown in The CIC7 CFU/mL, using a nephelometer. Afterwards, 200 µL of inoculum (1 × 107 CFU/mL) were seeded in each well of non-treated polystyrene plates . The plates were incubated for 4 weeks at 42 °C in the case of M. avium and at 37 °C for M. intracellulare . The wells containing only Middlebrook 7H9 medium, as well as only antibiotics or PAAs, were used as blanks and their mean A580 values were subtracted from the wells containing biofilm. The A580 values from the wells without antibiotics and/or PAAs were considered 100%. The wells containing antibiotics, individually or in combination, and/or PAAs were interpreted as a percentage of these values. In the present study, the MBIC was defined as the lowest concentration of antibiotic and/or PAA, decreasing by ≥40% the A580 value [90, values were defined as the lowest concentration that decreased by ≥40% the A580 value in 90% of the isolates, respectively.After incubation for the biofilm formation, the plates were treated with different antibiotics and PAAs, by adding in each well 100 µL of the desired drug at concentrations ranging from 4096 µg/mL to 32 µg/mL, except for Tween 80, which was tested in dilutions ranging from 12.5% to 0.09%. The plates were incubated again for another week at 37 °C. Then, the supernatant of the plates was discarded, and each well was rinsed once with 200 µL of 1× phosphate-buffered saline (PBS) see . The pla80 value ,26. The 580 readings, subcultures of the plates were made in a second plate, by seeding 20 µL of each well in a new well containing 180 µL of Middlebrook 7H9. These plates were then incubated for 1 week at 37 °C. After incubation, the plates were checked for visual growth using the Vizion System.Before the A90, values were defined as the lowest concentration that eradicated the biofilm formation in 90% of the isolates. The calculation of FIC and FICI for biofilm formation analysis was performed as previously described for the planktonic forms.The MBEC was defined as the lowest concentration of antibiotic, individually or in combination, and/or PAA inhibiting biofilm formation. The MBECThe main conclusion of the present study is that antibiotic combinations are significantly better than individual antibiotics against BFF. Furthermore, the addition of PAAs to antibiotic combinations could increase their activity. The results lead the path for further studies with other combinations, including common and new antibiotics, as well as potential antibiofilm agents, as tested in this study. These data could also open new therapeutic options based on the clinical use of these compounds, particularly in inhaled formulations, by feasibly administering higher doses with lower side effects.


Mathur et al.  point ouP < 0.05 and hypothesis-consistent direction correlate at 0.55 (0.66 with not achieving significance and rejecting the hypothesis). This suggests that statistical significance testing was a key aspect in the teams’ own conclusion formation processes. The rate of significant results per team explained 25% of the variation in subjective conclusions, the largest predictive variable by far. It is problematic that conclusions like those found in each team often become the headline findings of individual publications. Headlines often promoted reliant only on p values and without justification or recourse to the size and meaning of effects  held that the hypothesis was supported—despite the consistently small effect sizes. Support of this hypothesis by the team and the number of their models with a  effects , 4. And


Immunoglobulin G4-related disease (IgG4-RD) is an uncommon immune-mediated disorder most commonly involving the pancreas, lacrimal, and salivary glands. Immunoglobulin G4-related sclerosing mesenteritis (IgG4-RSM) is a rare site of involvement that usually mimics the imaging characteristics of mesenteric malignancies. Herein, we report a case of IgG4-RSM followed by an updated and comprehensive review of the literature. A 73-year-old woman presented with colicky abdominal pain in the right hypochondrium. The findings on contrast medium computed tomography (CMCT) showed a swelling of the mesenteric root with vascular structures surrounded by slightly contrast-impregnated tissue and irregular margins. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET) showed an area of inhomogeneous and intense hypermetabolism of the mesenteric root. Hence, laparoscopic resection of the mesenteric root was performed to distinguish such masses from malignant tumors, obtaining specimens for histopathologic examination. The latter exhibited tissue infiltration with lymphocytes, IgG4-positive plasma cells, and fibrosis, indicating a diagnosis of IgG4-RSM in the presence of both elevated serum IgG4 levels and the aforementioned imaging findings. With steroid therapy, no clinical signs of re-exacerbation within a one-year follow-up were observed and serum IgG4 levels returned to normality. Aiming to evaluate the real frequency of IgG4-RSM in view of the 2017 Comprehensive Diagnostic Criteria (CDC) of IgG4-RD, we undertook a complete MEDLINE, EMBASE, Web of Science, and Scopus database search of all case reports of IgG4-RSM published so far. Such criteria were met in only six cases with a definite diagnosis. This case highlights the mesentery as a rare site of involvement of IgG-RD and allows us to advance knowledge of IgG4-RSM. Immunoglobulin G4-related disease (IgG4-RD) is a systemic, immune-mediated fibro-inflammatory disease characterized by tissue destruction of multiple organs. It was recognized as a systemic condition for the first time in 2003  and muchThe patient has given written permission for her details to be published. MA is a 73-year-old woman who underwent video laparoscopic cholecystectomy for gallbladder stones in May 2020. In the following two weeks, she began to experience recurrent episodes of abdominal colicky pain in the right hypochondrium, which subsequently radiated to the entire abdomen, along with nausea and vomiting. Her medical history was significant for an unprovoked pulmonary embolism for which she was treated with dabigatran 110 mg t.d. for six months one year ago. The patient denied fever, night sweats, and blood in the stool. Her physical examination was remarkable for abdominal distention with mild tenderness on deep palpation in the right quadrants with rebound tenderness. Hence, she promptly underwent an abdomen contrast medium computed tomography (CMCT), which showed a 9 cm × 8 cm swelling of the mesenteric root with vascular structures surrounded by slightly contrast-impregnated tissue and blurred and irregular margins with preservation of the fat around the mesenteric vessels and without bowel ileus or obstruction Figure . Ten dayThe patient underwent a series of blood tests, the most significant of which are reported in Table They showed moderate inflammatory anemia, an increase in acute phase reactants, and an increase in serum IgG4 levels. The levels of the main tumor markers were normal. As it was difficult to distinguish the mass from abdominal malignant tumors such as malignant lymphoma, peritoneal carcinomatosis, metastatic carcinoid tumor, gastrointestinal stromal, carcinoid tumor, desmoid tumor, and metastatic adenocarcinoma, laparoscopic resection of the mesenteric root was performed in order to obtain specimens for the histopathologic examination. The histopathological examination exhibited a conspicuous chronic, inflammatory lymphoplasmacytic infiltration and collagen deposition in mesenteric adipose tissue without signs of obliterative phlebitis Figure .When the immunohistochemical staining for IgG Figure  and IgG4The diagnosis of IgG4-RSM was made in one month and the patient was started on oral 0.6 mg/kg methylprednisolone, which was gradually tapered over six months and then stopped. The patient's one-year control of both abdomen CMCT and total body 18F-FDG PET/CT revealed no disease recurrence and the above-mentioned blood examinations reverted to normal range, namely IgG4 levels (85mg/dL). At the moment, the patient is still doing well.Our case report describes a patient with symptomatic sclerosing mesenteritis as the only manifestation of IgG4-RD. The above-mentioned abdominal symptoms along with the results of both the abdomen CMCT and total body 18F-FDG PET/CT initially made us suspect the presence of a malignant tumor. However, the increase of serum IgG4 levels and the histopathological results of IgG4/IgG ratio of 50% with 20 IgG4 positive plasma cells/HPF, allowed us to make a definite diagnosis of IgG4-RSM in accordance with the commonly accepted 2011 comprehensive diagnostic criteria (CDC) of IgG4-RD, updated in 2017 . The excEpidemiologic studies concerning IgG4-RD mainly come from Japan, where the incidence of this disease has been estimated to be 0.28-1.08/100,000 with 336-1,300 patients newly diagnosed per year ,8. IgG4-The 2017 CDC for IgG4-RD largely reflects that of 2011. The definitive diagnosis of IgG4-RD is made in patients when the following three items are all positive: (1) characteristic diffuse/localized swelling or masses in single or multiple organs; (2) a serum IgG4 concentration >135 mg/dL; (3) histological findings of marked lymphocyte and plasmacyte infiltration and fibrosis as well as IgG4-positive plasma cell infiltration: ratio of IgG4/IgG positive cell >40%, and IgG4-positive plasma cells/HPF >10. A diagnosis of IgG4-RD is probable when patients fulfill criteria 1 and 3, whereas a probable diagnosis of IgG4-RD concerns patients who meet criteria 1 and 2. Patients with a possible or probable diagnosis could be re-diagnosed by organ-specific IgG4-RD criteria, e.g., for the pancreas, bile ducts, kidneys, lungs, and ocular cavity .Keeping in mind the aforementioned CDC 2017, we undertook a complete MEDLINE, EMBASE, Web of Science, and Scopus database research of all case reports of IgG4-RSM published so far since 2003. Such criteria were strictly applied and, to the best of our knowledge, were met overall in five cases with definite diagnoses (Table Notably, based on the CDC 2017 for IgG4-RD, the definite diagnosis was excluded in a number of case reports of sclerosing mesenteritis because the minimum IgG4 serum level of 135 mg/dL was not reached, and/or the requirements for the aforementioned histopathologic findings were not met.With regard to treatment, the patient of case no. 3  refused Our case report highlights the mesentery as an uncommon site of involvement among IgG4-RD and stresses the central role of both imaging and surgery as there are many malignant mimics in the differential diagnosis. The imaging demonstration of a diffuse mesenteric swelling, along with the increase of serum IgG4 levels and the mesenteric histopathological evidence of IgG4-RD, proved decisive for the patient’s outcome. As IgG4-RSM usually mimics the imaging characteristics of mesenteric malignancies, its preoperative diagnosis remains challenging. The following excellent response to corticosteroid therapy was in agreement with literature data according to which such therapy is recommended as the first-line treatment for IgG4-RD, showing a favourable prognosis in most cases. Finally, our extensive and in-depth research on previously reported cases showed that IgG4-RSM is indeed rare, as only six cases with a definite diagnosis have been reported so far. Our paper is part of ever-increasing literature on IgG4-RD because three of the six cases have been reported in the last two years. IgG4-RD recognition is increasing around the world, and clinicians from nearly every specialty are now becoming confident with most of its manifestations.


Synthetic lethality (SL) is a form of genetic interaction that can selectively kill cancer cells without damaging normal cells. Exploiting this mechanism is gaining popularity in the field of targeted cancer therapy and anticancer drug development. Due to the limitations of identifying SL interactions from laboratory experiments, an increasing number of research groups are devising computational prediction methods to guide the discovery of potential SL pairs. Although existing methods have attempted to capture the underlying mechanisms of SL interactions, methods that have a deeper understanding of and attempt to explain SL mechanisms still need to be developed.In this work, we propose a novel SL prediction method, SLGNN. This method is based on the following assumption: SL interactions are caused by different molecular events or biological processes, which we define as SL-related factors that lead to SL interactions. SLGNN, apart from identifying SL interaction pairs, also models the preferences of genes for different SL-related factors, making the results more interpretable for biologists and clinicians. SLGNN consists of three steps: first, we model the combinations of relationships in the gene-related knowledge graph as the SL-related factors. Next, we derive initial embeddings of genes through an explicit message aggregation process of the knowledge graph. Finally, we derive the final gene embeddings through an SL graph, constructed using known SL gene pairs, utilizing factor-based message aggregation. At this stage, a supervised end-to-end training model is used for SL interaction prediction. Based on experimental results, the proposed SLGNN model outperforms all current state-of-the-art SL prediction methods and provides better interpretability.https://github.com/zy972014452/SLGNN.SLGNN is freely available at  Developing effective anticancer drugs is a high priority research topic at medical and health research institutions worldwide. Identifying biochemical pathways that can be therapeutically targeted is a key step in developing new compounds. Synthetic lethality (SL) is an interaction between genes that, when both genes are mutated, can lead to reduced cell viability or even cell death, while mutations in only one of the genes in the pair not lethal . SL can To overcome these limitations, computational approaches are gaining considerable interest. Current computational methods can be subdivided into two categories: knowledge-based methods, and supervised machine learning  polymerase 1 and breast cancer 1 represent a biologically and medically relevant SL pair, with both molecules being involved in DNA repair. The recognition of the interaction between these molecules in the same biological process led to the development of the first SL-based PARP inhibitor for the treatment of cancer . In thisIn this section, we introduce the data used and the formulation of the problem. Then, we describe the details of each module of SLGNN.SynLethDB  and  carry the highest weights. This suggests that relationships describing the interaction between genes and disease and the participation of genes in biological processes are the most likely to contain a factor leading to SL. As can be seen from the figure, by maintaining the independence between the factors, the KG relationship with the highest weight is different in each factor, improving the interpretability of the model.It is readily apparent that not all factors influence an interaction that results in SL. Thus, various combinations of factors in the model are weighted differently to reflect the importance of distinct factors. Of the possible relationships illustrated in 357 and gene33 124 result in a SL interaction that can be derived through the attention mechanism. In this example, factor 3p has the highest attention score indicating that 3p is the main factor that causes the SL interaction between gene357 and gene33 124. From the semantics of factor 3p, we can explore the specific mechanism of SL interaction between these two genes.We can explain the interpretability of our proposed model from another perspective. The importance of factors leading to SL interactions differs for each gene. In other words, genes have certain bias to given factors. As can be seen from the figure, geneIn this article, we propose a knowledge graph-based model SLGNN for the prediction of SL interactions, while also modeling the SL-related factors that lead to SL interactions to improve the biological interpretability of the results. First, the factors leading to SL interaction are modeled as weighted sums of different relationships in KG, and the independence of factors is maintained by minimizing the distance correlation between them. Then, the GNN-based message aggregation mechanism is used to obtain initial embeddings for the genes in KG. Finally, we conduct a factor-based message aggregation through the SL graph and use GATs to improve the performance of the model. The experimental results show that our proposed SLGNN is superior to five existing state-of-the-art methods in predicting SL interactions.Despite its remarkable performance, SLGNN still has some limitations. For example, gene embeddings obtained through the KG graph is coupled and this has an impact on both interpretability and performance. To further improve this drawback in future work, we will attempt to use the decoupling representation learning, similar to that described in DisenKGAT (This work was supported by the grants from the National Key R&D Program of China [2021YFA0910700]; Shenzhen Science and Technology University Stable Support Program [GXWD20201230155427003-20200821222112001]; Shenzhen Science and Technology Program [JCYJ20200109113201726]; Guangdong Basic and Applied Basic Research Foundation ; and Guangdong Provincial Key Laboratory of Novel Security Intelligence Technologies [2022B1212010005].Conflict of Interest: none declared.


Background: Antibiotic resistance is one of the most pressing public health problems. Health authorities, patients, and health professionals, including dentists, are all involved in its development. COVID-19 pandemic restrictions on dental care may have had repercussions on antibiotic prescribing by dentists. The aim of this study was to assess the impact of the COVID-19 pandemic on antibiotic prescribing by dentists, and to review antibiotic consumption according to the WHO Access, Watch, Reserve classification. We conducted a natural, before-and-after, quasi-experimental study, using antibiotic prescription data covering the period from January 2017 to May 2021. A segmented regression analysis with interrupted time series data was used to analyse the differences between the numbers of defined daily doses (DDD) of antibiotics prescribed monthly. The outcomes showed an immediate significant decrease in overall antibiotic prescribing by primary-care dentists during lockdown, followed by a non-significant upward trend for the next year. This same pattern was, likewise, observed for Access and Watch antibiotics. COVID-19 pandemic restrictions on dental care influenced the prescription of antibiotics. During confinement, an initial decrease was observed, this trend changed when in person consultations were recovered. It might be beneficial to analyse the prescription of antibiotics using the WHO AWaRe classification, in order to monitor their appropriate use. Antibiotic resistance is one of the most pressing public health problems worldwide due to its impact on mortality, morbidity, and healthcare costs . The excThe COVID-19 pandemic has had repercussions on dental care, due to the risk of cross-contamination in dental clinics due to the characteristics of dental procedures, during which aerosols are generated, and due to the close proximity of the professional to the patient . During Currently, the impact of the COVID-19 pandemic on the short-term prescribing of antibiotics is unknown. Hence, the principal aim of this study was to assess the impact of the pandemic on antibiotic prescribing by dentists whose practices come within the Spanish National Health System (NHS) in north-west Spain; the secondary aim was to try to assess the impact of COVID-19 on the prescribing of those antibiotic groups that are most closely related with the development of antibiotic resistance.Primary-care dentists prescribed a mean of 35344 DDD of antibiotics before confinement, approximately 6% of which belonged to the Watch group, as shown in p < 0.005) was observed during lockdown ), followed by an immediate non-significant decrease (B = −1363.82) with respect to the pre-pandemic period, and a subsequent upward trend in the long term (B = 142.74).The monthly antibiotic prescribing trend from January 2017 to May 2021 for primary-care dentists is shown in p = 0.0133) in antibiotic prescribing during lockdown  decrease) followed by an immediate non-significant reduction in prescribing (B = −991.28) and a non-significant upward trend in the long term (B = 136.05).p < 0.0001) in antibiotic prescribing was observed ). Whereas the emergence of COVID-19 had a significant impact (B = −688.91) on the trend, with a reduction in prescribing (p = 0.0002); in the long-term, a non-significant increase was evident (B = 29.15). The data yielded by this quasi-experimental study indicate that the COVID-19 pandemic had an important impact on antibiotic prescribing by NHS dentists in north-west Spain. In March 2020, coinciding with the Spanish Government’s declaration of a state of alarm and confinement, a significant decrease was observed in monthly antibiotic prescriptions, which was maintained during lockdown and followed by an upward trend across the following year. This pattern was, likewise, generally observed for antibiotics and for those in the Access and Watch groups, with 8.92%, 8.00%, and 20.16% respectively.The initial decrease observed may be a consequence of the measures adopted during the first phase of confinement, in which care was dispensed by telephone consultation and, in rare cases, in person . Hence, The sharp drop observed during confinement is consistent with that found in Australia , and conThe increase observed after confinement can be attributed to the delay in treatment arising from confinement (owing to the lack of in-person care and/or patient fear) ,28 whichBefore the pandemic, a downward trend was observed in antibiotic prescribing by this group of professionals, similar to that reported by studies undertaken elsewhere  and the C difficile infections. Some studies indicate that approximately 15% of community C difficile infections may be caused by odontogenic antibiotic prescribing [Amoxicillin is the leading antibiotic used by primary-care dentists, a finding in line with the results of other studies ,35,36,37scribing . Other mscribing . The usescribing . These fWe found no study that assessed the impact of the pandemic on antibiotic prescribing by dentists according to the classification proposed by the WHO, nor any study that applied this classification to analysing prescriptions in this field. This prevents us from comparing our results to those of previous studies and would indicate that this classification should also be used in studies on dentists.The principal advantage of this study is the methodology used. The ITS design makes it possible to analyse the impact of the COVID-19 pandemic on antibiotic prescribing ,44.By way of limitations, the nature of the study per se should be mentioned. The model used assumes a linear trend in the outcome, and this assumption may only hold over short intervals. Furthermore, the introduction of data broken down by month means that neither individual changes nor the impact of the pandemic on specific days (at the beginning or end of lockdown) can be shown. The study was carried out in one region of Spain; therefore, this geographical limitation could compromise the generalizability. Another study limitation lies in the fact that we do not know whether the initial decrease in the number of prescriptions might have been linked to an increase in the DDD of antibiotics prescribed by dentists working in the private sector or in hospital emergency services. Another study limitation is that the DDD of antibiotics are not correlated to the numbers of in-person consultations and telephone consultations during the pandemic.Lastly, it should be stressed that the type of data analysed do not record the reason for prescribing, which means that our design does not allow for the appropriateness of prescriptions to be assessed. Thus, there is a need for further studies that would enable long-term changes in trend to be analysed.The results of this study demonstrate the usefulness of using the WATCH classification to monitor appropriate antibiotic prescribing. These results could be disseminated through specific educational interventions for dentists to raise awareness for the prudent use of antibiotics.2 and a population of 2.7 million. Healthcare for close to 100% of the population is covered by the Galician Health Service . Dentistry forms part of primary care, with services including the examination of the oral cavity, treatment of acute processes and dental emergencies, oral surgeries, and preventative treatments. For the remaining dental procedures, such as root canal work or prosthetic rehabilitation, patients have to use a network of private clinics, which also provide the range of treatment offered by SERGAS dentists. This study was conducted using antibiotic prescription data relating to the dentists, some 100 in all, who work at SERGAS primary care buccodental health units [Galicia is a region situated in the north of Spain, with an area of 29,434 kmth units . In SpaiWe used a natural, before-and-after, quasi-experimental design, with monthly data for the period from January 2017 to May 2021. This design, which enables causal effects to be estimated after controlling for baseline levels and trends , is suitThe drug class targeted by this paper comprises antibacterials for systemic use  , prescriFor study purposes, antibiotic prescription data were obtained from the SERGAS Pharmacy Information System for Complex Pharmacy Service Analyses (Sistema Corporativo de Información de Análisis Complejos Prestación Farmacéutica). This shows all medications dispensed by community pharmacies in the health area, based on official prescriptions billed to the Public Health Service. Data from primary-care dentists were selected. There was no change in the system across the study period.We calculated the number of monthly defined daily doses (DDD), defined as the average maintenance dose per day for a drug for its main indication .The World Health Organisation (WHO) suggests the use of the Access, Watch, Reserve (AWaRe) classification issued in 2019 and updated in 2021, for an improved evaluation and monitoring use of antibiotics. This tool makes it possible to reduce antibiotic resistance and access to all medicines . The WatAn interrupted time series (ITS) analysis model based on a segmented regression approach ,51,52,53All analyses were performed using the free R statistical software environment (version 4.0.5) , except The COVID-19 pandemic led to a decrease in antibiotic prescribing by primary-care dentists during the initial months, followed by an upward trend. This change was likewise observed for Access and Watch antibiotics. Due to the high percentage of antibiotic prescriptions issued by these professionals, it may well be of interest if future studies that analysed antibiotic prescribing among dentists were to use the WHO AWaRe classification.


The role of searching for industrial waste management solutions in construction is key for environmental protection. Research in recent years has focused on solutions aimed at reducing the carbon footprint. This paper presents the results of tests conducted on concrete reinforced with treated recycled tyre steel fibres (RTSFs) compared to the same amount of manufactured steel fibres (MSFs). The effectiveness of concrete reinforcement with RTSFs was analysed using the fracture mechanics parameters of cementitious composites. Rheological tests, residual flexural tensile strength tests, work of fracture measurements, toughness indices, examinations of the fibre distribution in the concrete, and SEM observations of the concrete fractures with fibres were performed. Determining the work of fracture and toughness indices was an innovative aspect of this paper. As the amount of RTSFs increased, a decrease in the consistency was observed, although the distribution of fibres in the concrete was uniform, as proven by the results of computer tomography tests. Concrete reinforced with RTSFs that is purified and refined during the recycling process might have better properties than concrete reinforced with the same amount of MSFs. The application of RTSFs in construction has environmental and economic benefits in addition to the strengthening of cementitious composites. The dynamic development of transport infrastructure and the automotive industry has forced an increase in the number of vehicles and, thus, an increase in the production of rubber tyres, which when worn out pollute the environment. The disposal of tyres is a global environmental problem. About 1.5 billion tyres are produced annually worldwide . More thClimate change, environmental degradation, and an increasing amount of waste pose a threat to Europe and the rest of the world. In order to address these challenges, the European Commission has introduced a strategy called the European Green Deal , which iTyres are a type of waste that does not decompose naturally and must undergo one form of recycling . Apart fAccording to statistics published by ETRMA , in EU cThe use of secondary raw materials from the material recycling of tyres has been the subject of much research for many years. The recycled material that has proved to have the most widespread application is rubber waste , constit2/t [2 emissions per year. Every year, about 3.4 million tonnes of old tyres are disposed of in Europe [The search for a way to replace traditional steel fibre reinforcement in concrete is crucial for environmental protection for a number of reasons. The world is facing a threat of a shortage of natural resources, including raw materials for steel production; thus, conserving natural resources is being emphasised. In addition, the steel production process contributes significantly to the increase in greenhouse gases polluting the atmosphere—steel production generates a significant amount of greenhouse gases; the carbon footprint of steel production is 1900 kg eCO2/t . Steel i2/t , which mn Europe ,22. It hn Europe ,23,24,25In addition, numerous studies indicate that steel cord is an effective material for reinforcement, comparable to manufactured steel fibres. Over the past few years, one could spot the increasing interest of researchers in the use of recycled steel fibres from tyres as structural reinforcement for concrete and as a possible replacement for manufactured steel fibres. A literature analysis indicates that recycled tyre fibres were more effective in improving the flexural strength of concrete and improving its fracture properties compared to unreinforced concrete and concrete with steel fibre additions, provided that they were found in the appropriate quantity and purity in concrete ,31,32,33Studies of the effects of various types of tyre fibres and their mixture with manufactured steel fibres on the rheological and mechanical properties of concrete ,34,35,36Contaminants from rubber and textile cord as well as steel dust encase the steel fibres and reduce the effectiveness of the reinforcement. The authors of  investig3, respectively. The results indicated that the treated RTSFs were more effective in controlling microcracking than the originally obtained steel cord.In one paper , the mecDespite the good scientific evidence, there are still concerns about the use of RTSFs for concrete reinforcement. The reason for the lack of interest in the application of tyre steel fibres as concrete reinforcement is related to their geometric parameters. RTSFs are very different from all other manufactured steel fibres on the market and are commonly used as structural reinforcement in concrete structures, such as industrial floors and tunnel linings ,41. As tConsidering the geometry, hybrid fibres such as those from recycled tyres, i.e., blended fibres of different lengths, diameters, and shapes, can be more effective in terms of reinforcement than dimensionally homogeneous manufactured steel fibres, a fact which has been scientifically proven . The useTaking into account the above considerations, the attempt to use treated recycled tyre steel fibres as structural reinforcement for concrete, from the point of view of the conservation of natural resources, waste management, and the reduction of the carbon footprint, while effectively reinforcing the cement matrix, is justified and fits in with the ideas shaping the innovation challenges of construction technology .The purpose of this study is to analyse the effectiveness of concrete reinforcement with recycled tyre steel fibres that have been cleansed of rubber and textile contaminants. As part of the research, a comparative study on concretes with the addition of treated tyre steel fibres and concretes with the same amount of manufactured steel hooked-end fibres, commonly used as structural reinforcement for concrete, was performed. Rheological tests of the concrete mixture (consistency) and the concretes with the same amount of RTSFs as MSFs were performed. As a measure of the effectiveness of the reinforcement, residual flexural tensile strength tests and tests defining the fracture toughness were performed, i.e., work of fracture and fracture toughness indices.In this study, the fibre reinforcement effectiveness was determined by examining the works of fracture; no similar research studies were found in the literature. The reinforcement effectiveness measure was also determined by a fracture’s toughness indices. Moreover, the novelty of this paper is that the properties of concrete with purified RTSFs were compared with the properties of concrete containing the same amount (by mass) of industrial fibres used as scattered reinforcement for MSF concrete. In similar studies, RTSFs were typically added in higher quantities than MSFs. Recycled tyre fibre treatment technology contributes to their better adhesion and effective concrete reinforcement. The fibre purity grade was evaluated with microscopic analysis, while a modern 3D computer tomography method was used for evaluating the fibre distribution in the concrete. Two types of fibre were used in these tests: manufactured steel fibre (MSF) and recycled tyre steel fibre (RTSF). The characteristics of the fibres are presented in MSFs are used as structural reinforcement for concrete and meet the requirements of the standard . The typThe results of the study indicated that fibres (wires) from tyres, despite their years of use and the process of recycling and pulling from tyres, show approx. 30–50% higher tensile strength compared to manufactured steel fibres, demonstrating great potential for their future application. Literature data indicate that the steel matrix in the tyre, which is the structural frame on which all loads are applied, is produced from high-grade and high-strength steel, with an average tensile strength of 2500 MPa ,39. WireIn this study, concretes with the addition of manufactured steel fibres and the same amount of recycled tyre steel fibres were tested in order to compare and evaluate the reinforcement efficiency of both types of fibre. The concrete was made according to EN 14845-1 . Table 33;Maximum content of cement CEM 42.5 R 350 kg/mMaximum aggregate size 16 mm, natural, uncrushed, silica-based;Water/cement ratio 0.55;Flexural tensile strength 4.3 ± 0.3 MPa (min. concrete class C25/30);Consistency of mix tested with the Vebe V3 method (from 6 to 10 s).The composition of the selected reference concrete met the following requirements:3, there was an issue concerning the appropriate homogenisation in the concrete mix. In addition, a fibre content higher than 40 kg/m3 resulted in a decrease in the workability, while the reference concrete excluded the dispensing of a chemical admixture. For the tests, the concrete was made as stated in 3. Eight concrete beams of 150 mm × 150 mm × 550 mm were made for each type of concrete, which, after demoulding, were cured for 28 days in water at 20 ± 2 °C. The tested concretes are shown in For the concrete made as stated in The consistency of concrete mixes with contents stated in The residual flexural tensile strength after 28 days was tested according to EN 14651 , using aIn most cases, both RTSF and MSF beams tended to break vertically along the notch and branch, as shown in The work of fracture of fibre concrete was defined as the total area under the load–deflection curve. The load–deflection diagrams for each test specimen were converted from the load–CMOD curves using the deflection conversion factor δ = (0.85CMOD + 0.04) according to EN 14651 . For eacIn some papers, fracture resistance for fibre-reinforced composites was determined by the fracture energy ,59,60, wLOP was calculated according to EN 14651 [LOP load values, (FLOP corresponds to the highest load for the CMOD range from 0 to 50 µm), the σLOP deflection was determined, followed by the 3 × σLOP, 5.5 × σLOP, and 10.5 × σLOP deflections, and the loads corresponding to these deflections. The region under the defined areas in the load–deflection curve was then determined and the indices I5, I10, and I20 were calculated. The test result is the average of the eight specimens tested for each concrete mix with MSFs and RTSFs. The difference between the fracture toughness indicator tests and the work of a fracture is that the work of a fracture is determined as the total area under the load–deflection curve, up to 3.02 mm deflection for each sample. The fracture toughness indicators were in turn determined as the ratio of the 3 × σLOP, 5.5 × σLOP, and 10.5 × σLOP areas to the area of the deflection at the limit of proportionality σLOP. That is why the fracture strength indicators determine the material’s fracture characteristics only at the beginning of the sample’s cracking. Toughness indices were determined according to ASTM C1018-97  from theEN 14651 . For theMicroscopic analysis was performed in order to observe a fibre–grout contact boundary and the adhesion of the fibre to the concrete matrix. Concrete fractures with MSFs and RTSFs were observed after 28 days of curing. The test was performed using a ZEISS Sigma 500 VP scanning microscope.3 of RTSFs and MSFs. The test was performed to observe the distribution of recycled tyre steel fibres in cured concrete and check if the fibres were uniformly distributed in the concrete mix during mixing. The test was conducted using General Electric (GE V|TOME|X M300) computer tomography, rendering 3D images of the fibre distribution in cubic samples. The fibre distribution in concrete was analysed on cubic samples with 100 mm × 100 mm × 100 mm side size, cut out from 100 mm × 100 mm × 500 mm concrete beams. Tests were made from the same batch as for three-point fracture tests, but in different forms. The samples contained 10, 20, 30, and 40 kg/mThe results show that as the fibre content increased, both MSFs and RTSFs reduced the consistency of the mix. A higher reduction in consistency was shown by recycled fibres from tyres than standard steel fibres, but the decrease was not significant enough to conclude that there was a technological issue in this scope. One problem would be the inability to test the consistency by any method (Vebe or slump test). A chemical admixture is always added to industrial fibre concrete to improve its consistency. In this case, the reference concrete did not assume an addition of chemical admixture in order to determine the influence of only the fibres’ consistency.3 of fibres. The refining process of RTSFs cleans their surfaces of the residues of rubber and textile wastes, which helps in the proper homogenization of the concrete mix. To prove the proper distribution of fibres in the cement matrix, the CT (computer tomography) scanning tests were performed  indicated that at 10 and 20 kg/mWhile residual flexural tensile strength describes the mechanical properties of fibre concrete for specific fixed CMOD values, work of fracture describes the entire fracture process of cement composites containing fibres, and serves as a measure of fracture resistance and the effectiveness of concrete reinforcement by a given fibre. The work of fracture was calculated based on the measurement of the area under the load (kN)–deflection (mm) curve from the moment of the application of a load to the deflection of 3.02 mm for all analysed types of concrete with MSFs and RTSFs. 2 = 0.9574) than for RTSFs (R2 = 0.9869). An analysis of the results indicates that at 10 kg/m3 and 20 kg/m3, concrete with MSFs had higher levels of fractures than concrete with RTSFs, by 32 and 28%, respectively. At 30 kg/m3, however, the work of fracture for concrete with MSFs was only 5% higher, while for 40 kg/m3, it was 7% higher than that of concrete with RTSFs. Considering the material’s characteristics, the uncertainty, and the standard deviation, it may be concluded that work of fracture, i.e., the fracture resistance, for both comparable composites with 30 and 40 kg/m3 of fibres was similar. No papers that defined fracture resistance using the measured work of fracture for concrete containing recycled tyre steel fibres were identified as part of the literature analysis.The figure shows that the work of the fracture, i.e., the resistance to brittle fracture, for both concrete with MSFs and concrete with RTSFs increased as the fibre content in the concrete increased; however, this correlation was slightly weaker for MSFs  for each RTSF and MSF content; this was similar for the I10 index . For the I20 index, a slight increase in the value was observed with the increase in the amount of fibres, both for RTSFs and MSFs.Considering the material’s characteristics, the uncertainty, and the standard deviation, it can be concluded that the toughness index IMicroscopic analysis was performed in order to observe a fibre–grout contact boundary in concrete fractures. This observation is used to assess the extent to which the fibres anchor and adhere to the grout and the quality of the fibre surface, which affect the effectiveness of fibre reinforcement. The analysis of the microscopic images of concrete fractures reveals that both MSFs and RTSFs were anchored to the grout well, reflecting their good adhesion. The additional process of purifying RTSFs of rubber and textile impurities causes them to have a more developed surface and thus good adhesion to the cement matrix. The fibre–grout contact boundary was proper, compact, and nonporous in both cases. Cement hydration products can be seen on the surface of the MSFs and RTSFs. Additionally, The microscopic analysis serves as a confirmation and justification of the mechanical test results, pointing to the purity of recycled tyre steel fibres, their good adhesion to the grout, and their effective reinforcement of the brittle cement matrix. As a result, they can be an alternative to manufactured steel fibres (MSFs).3, and at higher contents, such as 40 kg/m3. The test was performed because of the concrete reference characteristics according to the EN 14845-1 [ 14845-1  requiremThis article compares MSFs and RTSFs of various shapes and dimensions, which may be debated. In the vast majority of cases, the steel fibres used for concrete are of a similar type to the MSFs used here as a reference. Fibres with a much smaller diameter are available but are very rarely used and are not dedicated to concrete, just like mixtures of fibers with different diameters. Nevertheless, regardless of the type of fibers used, it seems that the most important parameter is the effect of energy absorption during concrete fracture, because it is an advantage for users. In this work, we deliberately used toughness indices to compare the reinforcement effect, because they are universal and by using them, even very different composites can be compared.This study demonstrated that recycled tyre steel fibres contribute to a slightly higher consistency decrease than the same amount of industrial MSFs, and the higher the fibre content in concrete, the more significant the decrease is.A reduction in the consistency of fibre concrete with RTSFs has also been shown in previous works ,38,39, wIt needs to be emphasised that a reference concrete mix containing no plasticising admixture was used in this study, so the consistency decrease when fibres are added is natural. The RTSFs were uniformly distributed throughout the entire concrete mix volume during mixing, with no clusters formed. Computer tomography of the cubes was performed to observe the fibres’ distribution in the cement matrix, confirming the uniform distribution of the fibres in the concrete. The authors of  reached 3 of RTSFs achieved equivalent flexural strength to concrete types with the same amount of manufactured steel fibres. In [In reference to the residual tensile strength at bending, it was discovered that similar relationships were observed in a previous paper , accordibres. In , however3, this is equivalent to concrete containing MSFs. Determining the work of fracture as a measure of brittle fracture resistance and the effectiveness of concrete fibre reinforcement with RTSFs is an innovative aspect of this paper. No papers were found in the available literature which determined brittle fracture resistance by measuring the levels of fractures for concrete containing RTSFs. The studies on the levels of fractures revealed that when RTSFs are added, the level of fractures rises, and for RTSF contents of 30 and 40 kg/m5, I10, and I20 for concrete with 30 kg/m3 of manufactured fibres and recycled tyre steel fibres. In this paper, the I5, I10, and I20 indices were lower for concrete containing tyre steel fibres than for concrete with manufactured fibres.Previous studies on the determination of toughness indices for concrete with RTSFs were also analysed. The authors of  analysed5, I10, and I20 is equivalent to and, in some cases, higher than that of concrete with manufactured steel fibres (MSFs). These results may be attributed to the characteristic fracture process of concrete with RTSFs, in which the strength increases on the load–deflection curve after the cement matrix cracks, which is the area where the I5, I10, and I20 indices are defined. To sum up, it can be concluded that, in this paper, the toughness of concrete with additionally treated RTSFs measured on the basis of the toughness indices IThe good effectiveness of concrete reinforcement with RTSFs can be attributed to the hybrid geometric characteristics of the fibres, which are a mix of fibres of different lengths, diameters, and shapes, allowing the microcrack bridging effect to affect many planes of the cement matrix ,48,49,50All over the world, particular attention is paid to combating growing environmental degradation by limiting the generation of industrial waste, the sustainably managing the resulting waste, saving natural resources, and reducing greenhouse gas emissions that contribute to global warming and the pollution of our planet. Replacing manufactured steel fibres (MSFs) with treated recycled tyre steel fibres (RTSFs) as a concrete reinforcement material has many benefits from an economic and environmental standpoint. The management of large amounts of waste contributes to saving the natural resources used to manufacture steel, which is in line with sustainable construction and the European Green Deal. Further, the additional steel cord treatment technology required to manage RTSFs efficiently has more environmental benefits than the process of manufacturing new steel, which harms the environment and has a very high carbon footprint.This paper, which confirms the excellent effectiveness of concrete reinforcement with purified recycled tyre steel fibres and the possibility of replacing manufactured steel fibres with them, is in line with all of the above. The prerequisite for effective concrete reinforcement with recycled tyre steel fibres is their high purity, with the lowest possible amount of rubber and textile contaminants and steel dust. Such fibres may only be obtained after the purification of the original steel cord obtained from tyres.Recycled tyre steel fibres (RTSFs) were added to concrete in the same amount as industrial steel fibres (MSFs) used as scattered reinforcement for concrete, with all tests made and analysed comparatively.The geometric characteristics of recycled tyre steel fibres (RTSFs), which are a mix of hybrid fibres of different lengths, diameters, and irregular shapes, are advantageous and contribute to achieving effective microcrack bridging in the cement matrix even better than MSFs.The rheological properties of concrete mixes determined by a consistency test revealed that RTSFs had a slightly higher reduction in consistency than MSFs, especially at high fibre contents. Still, this reduction was not high enough to be considered a technological issue in this regard. Concrete mixes, even those containing large amounts of RTSFs and MSFs, were homogeneous in terms of fibre distribution, with no signs of segregation. The fibre distribution examination with computer tomography confirmed the homogenous and uniform distribution of fibres in concrete and no local fibre clusters.3, concrete with RTSFs had lower values than that with MSFs, although concrete with the addition of 30 to 40 kg/m3 of RTSFs received higher values by about 20 and 15%, respectively. For a CMOD higher than 0.5–1.5 mm, the residual flexural strength for concrete with RTSFs was lower than that for concrete with MSFs.The properties of residual flexural tensile strength showed that at 10 and 20 kg/m3 of the fibres, it was shown that concrete with RTSFs had lower fracture resistance than that with MSFs; however, at 30 and 40 kg/m3, the fracture resistance determined by work of fracture was similar for both types of concrete . The efficiency of concrete reinforcement as determined by fracture mechanics parameters increases as the content of recycled tyre steel fibres in concrete increases.The effectiveness of reinforcing the concrete might be measured by the fracture toughness, described as the work of fracture, referring to the total areas under the load–deflection curve, which is a new approach compared to other studies devoted to the subject matter. In the case of the work of fracture for 10 and 20 kg/m3, concrete with RTSFs revealed equivalent or even higher fracture toughness indicators than concrete containing MSFs.The identified fracture toughness indices, which are the measure of a fracture’s resistance at the initial stage, right after the first fracture, revealed that the higher the RTSF content in the concrete, the higher the fracture’s toughness indices. For the content of 20, 30, and 40 kg/mThe microstructure of fractures of concrete with MSFs and of concrete with RTSFs was proper, with the fibres being anchored to the grout well and cement hydration products being visible on the surface of the fibres. These observations confirmed the good adhesion of the fibres to the grout. The good adhesion of RTSFs to the cement matrix resulted from the additional purifying process, which made the RTSFs’ surfaces more developed.The following conclusions were formulated based on this study:The parameters describing the fracture mechanics of fibre-reinforced cement composites indicate that recycled tyre steel fibres, if treated well and added to concrete in the right amount, may replace manufactured steel fibres.


Background: Dentists prescribe ~25.7 million antibiotic prescriptions annually. Private practice dentists (PPDs) represent 80% of US dentists who need to implement dental antimicrobial stewardship. We conducted a prospective cohort study of PPDs comparing appropriateness of antibiotic use before and after dental AS education. Methods: PPDs were invited to participate in this study. In phase 1 (pre-education), we collected 3 months (June–August 2019) of retrospective antibiotic use data  and number of dental procedures. We also conducted a preliminary survey to assess baseline antimicrobial stewardship knowledge. In phase 2 (education), PPDs attended 4 televideo education sessions (March–May 2021) taught by an infectious disease– antimicrobial stewardship (ID-AS) pharmacist and physician. In phase 3 (posteducation), we prospectively collected 3 months (June–August 2021) of antibiotic use data (as in phase 1), using an online database with ongoing feedback. In phase 4, we conducted antibiotic use audit and feedback to PPDs after the survey, and we solicited recommendations to reach more PPDs. The Student t test was used for statistical analyses. Results: Study participants comprised 15 PPDs: 2 oral maxillofacial surgeons, 6 periodontists, 4 endodontists, and 3 general dentists. Among them, 10 had been in practice >20 years. The presurvey revealed that 14 were unfamiliar with dental antimicrobial stewardship. All prescribed clindamycin , and standard antibiotic duration ranged from 5 to 14 days based on dental school training. In phase 3, despite more procedures, overall antibiotic use and duration decreased, and the use of clindamycin, quinolones, and prophylaxis for joint implant patients, also decreased. Appropriate use improved from 22% to 95%. Postsurvey responses on perceived value of antimicrobial stewardship education were 100% positive, with recommendations to make antimicrobial stewardship a required annual continuing education, similar to opioid continuing education. Study participants invited the ID-AS experts to teach an additional 150 PPDs to date via established PPD study clubs to expand dental antimicrobial stewardship across the United States. Conclusions: After learning dental antimicrobial stewardship guidance from ID-AS experts, PPDs rapidly optimized antibiotic prescribing behavior. PPDs identified their established study clubs as a forum to quickly expand dental antimicrobial stewardship training by ID-AS experts throughout the United States.Funding: MERCKDisclosures: None