The global emergence of antimicrobial resistance is driven by antibiotic misuse and overuse. However, systematic data in Indonesian hospitals to adequately inform policy are scarce.To evaluate patterns and quality indicators of antibiotic prescribing in six general hospitals in Jakarta, Indonesia.We conducted a hospital-wide point prevalence survey (PPS) between March and August 2019, using Global-PPS and WHO-PPS protocols. The analysis focused on antibacterials (antibiotics) for systemic use.Of 1602 inpatients, 993 (62.0%) received ≥1 antimicrobial. Of 1666 antimicrobial prescriptions, 1273 (76.4%) were antibiotics. Indications comprised community-acquired infections (42.6%), surgical prophylaxis (22.6%), hospital-acquired infections (18.5%), medical prophylaxis (9.6%), unknown (4.6%) and other (2.1%). The most common reasons for antibiotic prescribing were pneumonia (27.7%), skin and soft tissue infections (8.3%), and gastrointestinal prophylaxis (7.9%). The most prescribed antibiotic classes were third-generation cephalosporins (44.3%), fluoroquinolones (13.5%), carbapenems (7.4%), and penicillins with β-lactamase inhibitor (6.8%). According to the WHO AWaRe classification, Watch antibiotics accounted for 67.4%, followed by 28.0% Access and 2.4% Reserve. Hospital antibiotic guidelines were not available for 28.1% of prescriptions, and, where available, guideline compliance was 52.2%. Reason for the antibiotic prescription, stop/review date and planned duration were poorly documented. Culture-guided prescriptions comprised 8.1% of community-acquired infections and 26.8% of hospital-acquired infections.Our data indicate a high rate of empirical use of broad-spectrum antibiotics in Indonesian hospitals, coupled with poor documentation and guideline adherence. The findings suggest important areas for antimicrobial stewardship interventions. We assessed community and hospital-acquired infections as well as medical and surgical prophylaxis, by hospital, ward type and diagnosis.We conducted a hospital-wide PPS of antimicrobial use in a purposive sample of six hospitals across Jakarta, between March and August 2019. We followed Global PPS (2018)The study was approved by the Research Ethics Committee of the Faculty of Medicine of the University of Indonesia (1364/UN2.F1/ETIK/2018) and the Oxford Tropical Research Ethics Committee (559-18). The requirement for individual patient consent was waived. Permission was obtained from the hospital management or research/medical committee in each participating hospital.JAC-AMR Online).We developed a paper data collection form (DCF) comprising ward, patient and treatment sections, modified from Global-PPSWe included systemic antimicrobials coded on the basis of the WHO Anatomical Therapeutic Chemical (ATC) classification system as follows: antibacterials (J01), antimycotics (J02), antifungals (D01BA), antimycobacterials (J04), antivirals (J05), nitroimidazole derivatives (P01AB), intestinal anti-infectives (A07A) and antimalarials (P01B). We recorded the diagnosis/reason for the prescribed antimicrobial (what the clinician aimed at treating or preventing), according to a diagnostic code listWe used descriptive statistics to summarize the data, expressed as counts or percentages, by hospital, ward type, indication and diagnosis. The analysis focused on antibacterials (antibiotics) for systemic use (ATC code J01). Antibiotics were reported by drug names, chemical class (according to the fourth level WHO ATC classification) and AWaRe groups. We used RStudio Version 1.3.1093 for all analyses.The six participating hospitals varied by care level ; sector ; availability of hospital antibiotic guidelines ; inclusion in the national health insurance scheme . All hospitals had an antibiotic stewardship team. All 238 inpatient wards surveyed included 87 medical, 31 surgical, 95 mixed medical-surgical wards and 25 ICUs, of which there were 123 adult, 51 paediatric-neonatal and 64 mixed adult-paediatric-neonatal wards Table. On the Of 993 patients, 497 (50.1%) were women and 782 (78.8%) were adults, and the median age was 43 years  Table .Of 1666 antimicrobial prescriptions, 76.4% (1273) were antibiotics (J01), followed by 11.4% (197) antimycobacterials, 4.3% (72) antivirals, 3.7% (62) antimycotics, 2.6% (43) intestinal anti-infectives, 0.8% (13) antimalarials and 0.4% (6) nitroimidazole derivatives. Among 46 different antibiotic agents (J01), the five most prescribed  were ceftriaxone , levofloxacin , metronidazole , meropenem  and cefotaxime  Table. The topTableClostridioides difficile-associated diarrhoea was documented , followed by surgical prophylaxis , HAI , medical prophylaxis , unknown  and other . The top five CAI were pneumonia , skin and soft tissue infection , gastrointestinal infection , sepsis , and intra-abdominal infection  Table; top fivted Table. The topted Table.The top five reasons for medical prophylaxis were neonatal , general , gastrointestinal , respiratory  and unknown  Table; the topOf all 1273 antibiotic prescriptions (J01), 67.4% (858) were Watch antibiotics, followed by 28.0% (356) Access, 2.4% (31) Reserve and 2.2% (28) Unclassified . This paThe reason for prescribing was documented for 63.5% (808/1273) of all prescriptions. Documentation of diagnosis/reason was better for therapeutic use  than prophylactic use , and in ICUs  than non-ICUs . Stop/review date  and planned treatment duration  were poorly documented overall .Local antibiotic guidelines were not available for 28.1% (358/1273) of prescriptions; notably, including 76.2% (93/122) of prescriptions for medical prophylaxis. Guideline compliance for drug choice was 52.2% (478/915) overall, 44.8% (223/498) for empirical CAI treatment, 45.9% (79/172) for empirical HAI treatment, 28.5% (82/288) for surgical prophylaxis and 18.9% (23/122) for medical prophylaxis .In total, 85.1% (1084/1273) of prescriptions were parenterally administered, including 88.5% (208/235) for HAI, 89.5%% (486/542) for CAI, 75.4% (92/122) for medical prophylaxis and 82.3% (237/288) for surgical prophylaxis .Among 619 patients with ≥1 antibiotic for therapeutic use, 48.8% (302) had ≥1 sample taken for bacterial culture . Blood cultures were taken in 44.4% (88/353) of pneumonias, 45.6% (26/57) of intra-abdominal infections, 58.6% (17/29) of upper urinary tract infections and 95.8% (23/24) of sepsis. Sputum cultures were taken in 26.9% (95/353) of pneumonias. Urine cultures were taken in 72.4% (21/29) of upper urinary tract infections Table.Treatment was targeted in 8.1% (44/542) of CAI and 26.8% (63/235) of HAI; 13.0% (46/353) of pneumonias, 15.8% (9/57) of intra-abdominal infections, 44.8% (13/29) of upper urinary tract infections and 13.0% (6/46) of sepsis.,,This was the first contemporary hospital-wide survey in Indonesia that systematically evaluated patterns and quality of antibiotic prescribing, using the recommended PPS methodology.,,,,Consistent with other surveys in AsiaAntibiotic prescriptions for HAI , predominantly for pneumonia but also intervention-related and post-operative surgical site infections, were comparable to recent surveys in India (19%),A high proportion of antibiotic prescriptions were for surgical (23%) and medical prophylaxis (10%), for a range of indications. Prophylactic prescribing was unusually high for gastrointestinal infections. Prolonged (>1 day) surgical prophylaxis was very common (76%) in our survey, as has also been observed in other countries in Asia (Pakistan 97%,,We investigated five basic quality indicators, which could be used to set benchmarks for quality improvement of antibiotic useA systematic review and meta-analysis showed that guideline-adherent empirical therapy was associated with a relative risk reduction for mortality of 35%.,,The WHO AWaRe framework offers an attractive metric for LMICs in the absence of validated quality indicators for antibiotic appropriateness,Limitations of this study are inherent to the cross-sectional PPS design, providing a mere snapshot of the antibiotic situation in the hospital surveyed. Moreover, given that we used a convenient sample of six hospitals in metropolitan Jakarta, which are potentially better resourced than many other hospitals in Indonesia, data are not necessarily representative for all hospitals in Indonesia, urging caution in extrapolating the observed patterns. Indeed, antibiotic prescribing can be influenced by many factors, e.g. patient case-mix, prevalence of different types of infections, AMR patterns and institutional factors.,In conclusion, we observed high levels of parenteral, empirical use of broad-spectrum antibiotics in Indonesian hospitals, and inadequate performance on key quality indicators of prescribing. Despite important progress in AMS, supported by national policies,dlab047_Supplementary_DataClick here for additional data file.


Science, Lopatkin et al.1 used different in vitro evolution protocols and extensive sequencing data analyses to demonstrate that metabolic mutations develop in response to antibiotic treatment in clinically relevant bacteria  can simulate metabolism in genome-scale reconstructions of metabolic networks. In a preceding study using FBA, Lopatkin et al. studied the effects of varying concentrations of glucose and casamino acid on a genome-scale model of E. coli as a model pathogen, provided proof that metabolic mutations can develop in response to antibiotic treatment.1 This was achieved by applying different in vitro evolution protocols and subsequent sequencing analyses of entire populations and selected clones. In a first step, the authors used a traditional protocol of serial passaging and continuous exposure to increasing concentrations of three representative bactericidal compounds targeting DNA replication (ciprofloxacin), cell wall biosynthesis (carbenicillin) and protein synthesis (streptomycin) to induce growth-dependent selection. The subsequent comparison of the sequence data from entire populations and individual clones revealed that more mutations of metabolic genes were found at the population level than at the clonal level, albeit at low frequency, indicative of an underlying genetic network of mutations with a previously unknown impact on metabolism influencing the evolution of resistance to antibiotics. Lopatkin et al., therefore, drew the conclusion that classical experimental evolution together with the sequencing of candidate genes and/or a small number of clonal isolates per condition mostly reveals expected mutations, or those occurring at a higher frequency but masks those occurring more infrequently. Consequently, in order to increase the frequency of metabolic mutations during the evolution of antibiotic resistance, the authors cycled E. coli subjected to daily 1-h antibiotic treatment and 22 h of growth without antibiotics. Metabolic activity was modified by daily increasing the temperature by 1 °C over a period of 10 days starting at 20 °C. This new protocol generated predominantly metabolic mutations in the emerging strains that were solely attributable to the exposure to antibiotics and not to the alternating growth/no growth cycle conditions. In the next step, the authors compared the biological processes significantly affected by the classic and the metabolic evolution protocols and observed the occurrence of parallel metabolic mutations indicative of metabolism modulation as an adaptive strategy against antibiotic stress. In order to assess the clinical relevance of these mutations, Lopatkin et al. analysed a library of 7234 E. coli genomes from clinical and non-clinical origin deposited at NCBI using the gyrA gene as baseline for comparison. Approximately 20% of the strains from either clinical or non-clinical origin had a mutation in gyrA_S83 and 12% in gyrA_D87, indicating that mutation prevalence alone can have a potential clinical impact. In order to test if the found metabolic mutations conferred resistance, the authors then evaluated a representative subset of metabolism-related genes  and classic antibiotic resistance genes . Knockout and overexpression experiments, as well as measurement of growth inhibition confirmed that metabolic mutations indeed lead to an increase of the minimum inhibitory concentration to at least one antibiotic in all cases, and in some to more than one. Finally, by analysing a mutation in the 2-oxoglutarate dehydrogenase enzyme (sucA), the authors were able to show that metabolic mutations per se can result in a small but measurable increase in antibiotic resistance.In the presently discussed study, Lopatkin and co-workers, again using 1 Their findings could help to explain the occurrence of (multi-) drug-resistant bacterial strains isolated in regions without significant exposure to antibiotics or the observed increase in antibiotic resistance upon excessive application of herbicides or other environmentally toxic substances.5 Systematic monitoring and analysis of the metabolic response to bactericidal as well as bacteriostatic compounds can provide a means to optimise and possibly even personalize treatment regimens and to test the efficacy of new drugs or new drug combinations of known compounds. In view of the global rise of antibiotic resistance not only expected to cause millions of deaths in the next decades but also putting significant pressure on national economies, new treatment options are in dire need. Lopatkin et al.’s work has come at exactly the right time.The work of Lopatkin et al. has shed light on the intricacies of metabolic mutations and their direct influence on antibiotic resistance and has provided a fresh outlook on the development of antibiotic resistance.Publication and Licensing Rights


Recent research has revealed the promising potential of using waste glass (WG) as a binder or inert filler in cement and geopolymer concrete to deliver economic and environmental benefits to the construction sector. However, the outcomes obtained by different research groups are scattered and difficult to compare directly because of isolated process parameters. In this study, the roles and impacts of WG and process parameters on the performance of WG-added cement and geopolymer concrete are critically reviewed. This study reveals that the chemical and mineralogical composition, and particle size of WG, mix proportion, activation, and curing condition of concrete are the most important parameters that affect the dissolution behavior of WG and chemical reactivity between WG and other elements in concrete; consequently, these show impacts on properties of concrete and optimum WG level for various applications. These parameters are required to be optimized based on the guidelines for high pozzolanicity and less alkali–silica reactivity of WG in concrete. This review provides a critical discussion and guidelines on these parameters and the chemistry of WG in cement and geopolymer concrete for best practice and highlights the current challenges with future research directions. Glass is a widely-used material due to its attractive appearance, transparency, ease of molding, high durability, and resistance to abrasion . As a reIn 2019, the glass recycling rate in Australia was 57%, but the rest of the waste glass was discarded as waste . In the Concrete casting requires natural sand and natural stone aggregates, which are around 20–30% and 60–70% of concrete volume. Excessive extraction of natural sand and stone aggregates may also result in resource shortages ,19. MiniGeopolymers are a class of inorganic aluminosilicate-binding materials with an amorphous or semicrystalline three-dimensional structure . The pro2 emissions and construction costs. As reported by Islam et al. . Th. Th62]. e binder . The alkactivity . Thus, aactivity . The proactivity ,50.42− and OH− ions in the solution and produce ZnSO4.nH2O, CaSO4.nH2O, and other SO42− products, which can delay hydration reactions . Wi. Wi27]. WG of particle size around 45 µm does not improve the workability compared to ordinary OPC concrete , as the However, due to the high cement dilution and the formation of a low amount of hydration products in the early stages of WG hydration, high flowability is observed in concrete ,40. On t2 and C–S–H) are formed, and the microstructure of concrete is densified with the high pozzolanicity of WG powder when added at the optimum level of replacement (20–30%) [Pozzolanic reactivity and filler effects are the two most important roles of the WG particle packing density and porosity reduction of cement concrete. The density of concrete varies according to the fineness, amount, and type of WG. (20–30%) . The den(20–30%) .Beyond the optimum level (30%), the addition of WG causes a reduction in density and an increment in the porosity of concrete. This is because the production of CH and C–S–H products reduces due to the fewer opportunities for pozzolanic reactivity of WG and reduced amounts of CaO ,58. MoreScanning electron microscopy (SEM) images of a specimen are generally used to show the internal pores, connectivity of pores, and uniformity of final reaction products in concrete. The microstructure of WGC depends on the particle size, mix ratio, and pozzolanic reactivity of WG. Finer and highly amorphous silica containing WG is suitable for producing a denser concrete micro-structure. Glass particles (<1.18 mm) act as microfilters at the early age of curing, and at low temperatures, their reactivity is low. WG particles of size below <75 µm show high filler and pozzolanic activity within the concrete and help to increase the density of concrete with a dense microstructure of the hardened matrix ,55. As fWith the required fineness of WG and proper curing conditions, a dense microstructure of concrete can be formed with an optimum level of WG. This is evident in the research of Kong et al. . As depiFurther, by room temperature curing for up to 28 days only, a low amount of hydration products was captured, but for steam curing at 80 °C temperature, a remarkably dense matrix is produced with significant C–S–H products . These f2 and other ingredients  that affect the pozzolanic properties of the WG. For example, neon glass contains around 22.6% CaO and 68.2% SiO2; thus, it yields 9.5% greater compressive strength in WGC than green glass, which yields 13% cement replacement [The chemical composition and fineness of WG control its pozzolanic reactivity and filler effect, which are the main factors in producing high-strength WGC ,27. The lacement .The strength of concrete increases with the increasing fineness of WG ,58,79. THowever, agglomeration of unreacted silica can delay the pozzolanic reaction, and accelerated ASR may occur within the concrete when more than 30% of cement is replaced by WG ,57,58. FDue to its high silica content, if properly graded, WG powder can fulfill the requirement for fine aggregates in concrete . TherefoWG glass with particle sizes larger than 4.75 mm is considered coarse aggregates in concrete and is typically sized up to 16 mm . These tWG aggregates are generally angular, with a rough texture and sharp edges. When used to replace coarse and fine aggregates, these rough particles prevent the flow of concrete because of the high friction between them . TypicalThe size of the WG in concrete is an important parameter that substantially controls the properties of concrete. The fine WG powder helps refine the pore size and divide the ITZ into a very thin layer, which increases the density of the concrete . However3 [Further, due to the lower specific gravity of WG compared with that of conventional stone aggregates, the density of concrete reduces when WG (Particle size > 2.36 mm) is used as coarse aggregates . For a 23 . Moreove3 . Fewer h3 . Therefo2 dissolution occurs, and consequently, less C–S–H production takes place. Moreover, due to ASR susceptibility, a significant number of transitional C–H products may be destroyed and turn to expansive gels, which drives a significant strength reduction [Fine WG aggregates refine and redistribute pore sizes and strengthen the ITZ of concrete; thus, within finely ground WG, the strength of WGC increases. Olofinnade et al.  replacededuction ,55,94.However, there are no data available on the ASR susceptibility of coarse WG aggregate (>5 mm size). Coarse WG aggregate increases the volume of the concrete and reduces the unit weight, but the porosity in concrete increases due to trapped micro-voids ,89. Due The alkali content and silica in the WG powder react and form ASR gels. These gels are expansive and worsen when absorbing water or chemicals. Therefore, ASR of WG harms the strength and durability of concrete ,6,97. ThSince ASR expansion increases with the particle size of WG, keeping the WG particle size below the critical value of 600–1000 µm is recommended  44,55,9,955,94. Regardless of the amount and particle size, the type and chemical composition of WG and the concrete mix proportions can also affect the ASR. For example, binary glasses (sodium silicate) cause more ASR expansion than soda-lime glasses due to the higher alkali released from binary glasses ,41. BrowBased on current practice, up to 30% cement, 50% fine aggregate, and 20% coarse aggregate in concrete can be replaced by WG of specified particle size without compromising the strength and grade of concrete  65,69,7,769,78. 2 solution showed positive influences on the ASR reduction and strength in WGC [Although several advantageous uses of WG as a construction material are noted, the ASR challenges and bond strength limitations are critical issues for the future development of WGC . Consideh in WGC .2 solution enhance the pozzolanic reactivity of WG, and high bond strength concrete is developed. However, the chemical changes and optimum treatment conditions have not been identified, and the sustainability of this treatment process is not discussed in the literature. Studies on the addition of fibers, low-cost or recycled waste polymers, and proper milling processes to enhance the bond strength within WG concrete are lacking. Further, guidelines on the comparative and correlative descriptions of the internal chemistry, microstructure, strength, and serviceability properties in WG-incorporated OPC concretes need to be established through future research.The reaction products formed along the surface of WG during immersion in Ca(OH)2 and a small amount of Al2O3 and CaO depending upon its chemical composition to contribute to the geopolymerization process [2 content are formed after the complete geopolymerization of alkali-activated glass-based precursors, regardless of the curing condition [2-rich gels in a composite paste of alkali-activated WG and other precursors [Geopolymer formation starts from the dissolution of silica and alumina out of the precursors, followed by their gelation, reorganization, and polymerization into geopolymer binders . As a pr process ,112,113. process . Gels wiondition . Howeverondition . For higondition , whereasecursors ,109. How2 and Al2O3 during geopolymerization than coarser ones and result in good geopolymerization regardless of other chemical factors [Silica dissolution from WG precursors is dependent on the fineness and amount of WG, concentration, type of activator, mixing, and curing environment of the geopolymer mix with WG. Finer WG precursors (particle size < 75 µm) release more SiO factors ,117. Zha factors  compared factors ,119. Zeo factors  recommen2O3 in raw materials should be below 15–20% to obtain high-strength geopolymer concrete. Further investigation is needed to clarify the role of WG in early-age hydration products and the chemistry of the gels in alkali-activated WG.Moreover, WG prolongs the setting time of geopolymers. Regardless of the activator concentration, a prolonged setting time was observed with an increased amount of WG in the binder. The setting time generally correlates with the second peak of heat flow during hydration. A comparison of 2SiO3, and their combinations [2SO4, and Ca(OH)2 [A high concentration of alkaline activator is required to ensure the high dissolution of silica from WG . Howeverinations ,117. Givinations . The addinations . Some ot Ca(OH)2 ,124,125. Ca(OH)2 , the eff2 and Al2O3 from WG to complete the geopolymerization process [Moreover, mixing and curing temperatures can remarkably affect the geopolymerization reaction and the performance of the concrete. Toniolo et al.  claimed  process ,109,117. process  reported process . Therefo2/g) was used by Wang et al. [The workability of alkali-activated geopolymer concrete increases with the increasing content of WG powder . About 1g et al.  to replag et al.  reportedg et al. ,109. How2- and Al2O3-rich precursor. When metakaolin is replaced by a finely ground WG (3%), which is SiO2 rich and contains a low amount of CaO, a Na-aluminosilicate amorphous matrix is formed at room temperature  from precursors. WG effectively participates in the geopolymerization process by releasing silica in high alkali-activating media and improves the strength of geopolymer concrete, depending on the type and content of WG and its activation methods ,29,130. nd finer . The strnd finer  observednd finer  demonstrnd finer . Howeveromposite ,128.2, Al2O3, and CaO) from precursors  [There is a close relationship among the activator’s properties, Si/Al dissolution from precursors, and geopolymerization. Sethi et al.  found a  others) ,130. On The investigations of the mechanical properties of WG geopolymer concretes are listed in Fine aggregates create a distinct ITZ and increase the volume of geopolymer concrete . The finHowever, to develop high-strength bonding, the presence of many silanol groups in the solution is needed, along with a high silica dissolution . Thus, mThe density of geopolymer concrete increased with the addition of WG aggregate. 2CO3 solution can be effectively used as an activator for slag-based geopolymer concretes. For example, 10 M NaOH with 10–25 g of WG powder solution was used as an activator in a prior study by Torres-Carrasco and Puertas [WG-derived solutions can be effectively used as activators for geopolymer concrete. The WG releases a significant amount of alkalis and silica in NaOH and water solution when being heated, and the heat-treated solution meets the requirement of a water glass activator ,134. Sod Puertas   enhances the thermal, fire, and elastic properties of geopolymer concrete. Further, the optimum curing condition for WG-based geopolymer concrete needs to be standardized because current knowledge is not sufficient, and raised temperature or oven curing is not a sustainable solution. There is potential for developing WG activators for geopolymer concrete, but due to limited studies on this issue, no certain guidelines exist. Some additional challenges include the lack of guidelines and approval for the standards and the limited availability of admixtures and precursors that are compatible with WG in geopolymer concrete. These issues should be considered in future research, and guidelines should be established to widen the applicability of WGC in the construction sector.Glass powder acts as a source of pozzolanic silica for cement and geopolymer concrete. For best pozzolanic reactivity, the particle size of WG and optimum binder replacement level should be below 75 µm and 30%, respectively. Silica, calcium oxide, and the small amount of alumina in WG participate in the hydration reactions and accelerate the formation of hydration products. A high curing temperature of around 40–50 °C and a proper water-to-binder ratio (<0.5) are useful to increase the pozzolanicity and hydration of WG in concretes.Fine WG powder (particle size < 150 µm) acts as a filler and pozzolanic material, increases the density, and reduces the porosity of concrete composites. Consequently, the mechanical performance of concrete is reliably enhanced. The most suitable WG conditions for improving the pozzolanicity and mechanical performance of concretes are WG powder with particle sizes less than 75 µm and the optimum cement replacement level (20–30%). As fine aggregates, a replacement level of approximately 50% is feasible to yield optimum strength in WG concrete.The mechanical performance of geopolymer concrete with WG aggregates, precursors, and activators has been consistent. Silica dissolution takes place from the WG in an alkaline activator solution, which accelerates the geopolymerization process. The replacement of precursors in geopolymers has been widely investigated, and the optimum replacement level lies within 30–50% with a WG powder particle size less than 75 µm. The requirement of an alumina source is crucial for completing the geopolymerization of WG-based geopolymer concretes. However, the intermediate reaction products of calcium or sodium aluminosilicate hydrates also showed significant stability in WG-based geopolymer concrete.The highly reactive surface of fine WG aggregates reacts in activated media to create a high-strength geopolymer network. For sodium-silicate activator solution preparation, the particle size of WG powder could be reduced to under 45 µm for better dissolution of silica and alkalis from WG. For WG powder-based geopolymers, the solid-to-liquid ratio (0.5–0.6), additional alumina sources, curing temperature (50–60 °C), and alkalinity of activator (8–10 M) must be controlled to achieve optimum performance.The most critical issue of glass incorporation into concrete is the alkali–silica reaction and expansive gel formation within the composite. This issue is less critical for geopolymers than cement concrete, but it cannot be ignored. The microcracks in WG particles cause more ASR vulnerability. ASR expansion in concrete can be minimized by using an optimum level of around 10–30% fine WG powder (<75 µm) to replace cement rather than aggregates and by adding recommended by-products, such as silica fume, fly ash, and slag.This review includes a critical discussion of the current research progress and future potential of waste glass (WG) in concrete production. Glass can be effectively included in cement and geopolymer concrete, substituting for conventional raw ingredients. The chemical composition and physical characteristics of WG offer compatible performance within the concrete. Based on the reviewed literature, the following conclusions can be drawn:There are still some challenges related to the use of WG in cement and geopolymer concrete, but the current research outcomes have revealed the potential economic and environmental benefits of WG as a construction material. Future research should widen the application of WG to commercial fields. This review highlighted the lack of investigations on WG-based cement and geopolymer concrete, especially in the areas of critical exposure conditions and performance under short-duration vibration, impact, and fatigue loadings. Further investigations on these topics are required to develop widely applicable guidelines for the application of WGC in the construction sector.


Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory pathology that has been reported to affect principally the retroperitoneum, hepatobiliary system, salivary glands, orbital structures or lymph nodes. However, IgG4-RD with laryngeal involvement is a very rare entity. Our aims were to describe a case of subglottic stenosis as first and only manifestation of IgG4-RD and review the literature. A patient with IgG4-RD affecting the larynx that presented as subglottic stenosis is described. A MEDLINE database search of IgG4-RD cases with laryngopharyngeal manifestations was also conducted. A 30-year-old Caucasian woman was referred to a tertiary care hospital for dyspnea on exertion, which had been increasing for the last 4 months. Medical and surgical procedures revealed a subglottic stenosis, with a histological finding of IgG4 positive plasma cell infiltration. There was no evidence of other organ involvement. She was successfully treated with oral glucocorticoids and rituximab infusions. Glucocorticoids were rapidly tapered and the rituximab regimen was optimized, with no evidence of relapses. In the literature review, we found a total of 12 reported cases with laryngopharyngeal involvement, two of them with subglottic stenosis. IgG4-RD of the larynx is rare but should be considered after excluding more common disorders. Immunoglobulin G4-related disease (IgG4-RD) is an idiopathic fibro-inflammatory disorder characterized by the presence of swelling or masses in single or multiple organs, with specific clinical, serological and histopathological features , 2. The In this report, we describe the case of a young woman diagnosed with IgG4-RD, who had subglottic stenosis as the only manifestation. A literature review of patients with IgG4-RD with laryngopharyngeal involvement was also conducted.A 30-year-old Caucasian woman was referred to a tertiary care hospital (XXX) in June 2016 for dyspnea on exertion, which had been increasing for the last 4 months. She had been diagnosed of laryngitis and treated with a short course of oral glucocorticoids at her primary care center. She was not a smoker and had no relevant family or medical history or known allergies. She had never been intubated, but she underwent adenoidectomy in childhood.Her physical examination and chest radiograph were normal. However, when a laryngeal fibroscopy was performed, a membranous subglottic abnormality occluding 50% of the lumen was found. Subsequent computed tomography of the neck showed a decreased caliber of the proximal trachea beginning 5 mm below the cricoid cartilage and extending 6 mm distally between the thyroid lobes Fig. . The patIn light of these findings, the patient was evaluated in a combined Rheumatology-Pulmonology clinic, where it was confirmed that no additional organs were involved .Laboratory tests including full blood cell count, biochemistry profile and serologies  were within the normal range or negative, as appropriate for each case. Serum IgG4 was also normal at baseline (48.00 mg/dL) and during follow-up (maximum of 55.61 md/dL). Apart from glucocorticoids , intravenous rituximab (RTX) was started with a regimen infusion of 1000 mg on days 0 and 14 (previously administered intravenous methylprednisolone and dexchlorpheniramine). Before RTX initiation, the patient underwent a vaccination program and was treated with isoniazid/pyridoxine (300 mg/50 mg per day) the previous month and for a total of 9 months due to Quantiferon test positivity.Posterior medical assessments and fibroscopic examinations showed a remarkable improvement of the patient, with no further signs of subglottic stenosis or laryngeal inflammation and no systemic manifestations. Moreover, a 18F-FDG PET/CT (fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography) scan confirmed the absence of vascular or other organ involvement. Prednisone was gradually tapered up to complete discontinuation after 9 months since the onset of this therapy. Also, RTX therapy was optimized reducing half the dose to 500 mg on days 0 and 14 and subsequently to 500 mg every 6 months and later 500 mg annually. At present, 4 years after the diagnosis, she is on annual cycles of RTX with no relapses.A comprehensive search of biomedical literature until December 2020 about cases of IgG4-RD patients with laryngotracheal involvement was performed. The research sources consulted were from MEDLINE, life science journals and online books published primarily on PubMed. The search was conducted using the following terms: “IgG4-related disease” and “trachea” or “larynx” or “pharynx”. The references in each selected study were reviewed to identify other relevant articles. Scopus and Web of Science databases were also searched with no additional related articles found. Two authors reviewed the search results and agreed on the included articles. From each article selected, data were collected on publication year, gender, age, location of the IgG4-RD, treatment received and time of follow-up. Non-English articles were excluded for the review.We identified 11 reports describing cases of laryngotracheal involvement due to IgG4-RD –26, 2 ofIgG4-RD is a relatively recently recognized multi-organ disease that manifests with pseudotumoral masses of inflammatory fibrosis in the pancreas, salivary glands, hepatobiliary system or eye orbit, among others , 2. The The presence of high serum concentration of IgG4 immunoglobulins can be useful in reinforcing the diagnosis but is not required to be present or self-sufficient for the diagnosis . It is uGlucocorticoids are the first line of treatment and they should be administered urgently when vital organs are affected . HoweverIgG4-RD comprises a group of heterogeneous and complex entities. In this sense, the 2019 American College of Rheumatology/ European League Against Rheumatism classification criteria for IgG4-RD  have beeIgG4-RD can be mimicked by other conditions, such as vasculitis, malignancies, other types of pancreatitis, Sjogren’s syndrome, sarcoidosis. Because of that, the diagnosis is often incorrect or delayed. To establish a more accurate diagnosis, characteristics of IgG4-RD mimics are collected as exclusion criteria in the 2019 American College of Rheumatology / European League Against Rheumatism classification criteria for IgG4-RD . In our IgG4-RD is a rare inflammatory disease with a wide range of manifestations. Diagnosis is challenging, but evidence on clinical, serological, imaging and histological features is increasing. In addition, recent classification criteria have been developed to help standardize future research. We describe an uncommon presentation of IgG4-RD beginning in the larynx. We also highlight its excellent outcome after initiating adequate immunosuppressive therapy.


Spun concrete technology allows manufacturing the reinforced concrete poles, piles, and columns with a circular hollow core. This concreting method ensures higher concrete density and strength than the traditional vibration technique and self-compacting concrete. This technology defines an attractive alternative for producing steel-concrete composite elements, allowing efficient utilisation of the materials due to the confinement effect. This study experimentally investigates the material behaviour of the composite columns subjected to axial compression. The experimental results support the above inference—the test outcomes demonstrate the 1.2–2.1 times increase of the compressive strength of the centrifugal concrete regarding the vibrated counterpart; the experimental resistance of the composite columns 1.25 times exceeds the theoretical load-bearing capacity. The proposed mechanical-geometrical parameter can help to quantify the composite efficiency. The parametric analysis employs the finite element model verified using the test results. It demonstrates a negligible bond model effect on the deformation prediction outcomes, indirectly indicating the steel shell confinement effect and confirming the literature results. Steel and reinforced concrete are typical materials for compressive structural members. However, such a decision comes with additional costs because of certain advantages and drawbacks of these materials. For example, steel structures are lightweight, but their thin-walled cross-sections are susceptible to local buckling. Besides, the high thermal conductivity of steel and insufficient fire resistance make such structural systems unacceptable in many cases without additional fireproofing. On the other hand, concrete structures are resistant to buckling and fire, but they are heavy and massive, taking up much usable space. However, the combination of these materials in the composite can solve the above problems ,2. The cCombining different materials in the cross-section can further improve the composite properties. For example, fibre-reinforced polymers (FRP)  and staiSolid core composite columns were the object of most experimental programs reported in the literature, and only several studies investigated columns with the concrete hollow core sections ,2,3,7,17Spun or centrifugal casting is well-known concrete technology, producing circular hollow core cross-sections. When fresh concrete is compacted at high rotation speeds, centrifugal force separates water from the concrete, moving it to the rotation centre and decreasing the water to cement ratio, increasing the concrete strength. As a result, a circular cross-section form with a uniform thickness is shaped. The spun casting also increases the concrete density regarding vibration technologies, and self-compacting concretes ,19.Demolition and reconstruction of concrete structures produce large amounts of solid waste, which is expensive in landfills. Thus, the partial replacement of concrete aggregate with recycled concrete waste defines an attractive perspective . HoweverThis study experimentally investigates the material behaviour and structural performance of the hollow core steel-concrete composite columns. A finite element model is developed to illustrate the complex stress-strain state characteristic of the confined concrete. The model verified using the test results is also used for parametric analysis of the composite columns subjected to the axial compression.This test program includes 18 hollow section 450 mm long centrifuged concrete columns, 15 spun concrete hollow section cylinders, and 15 vibrated concrete prisms (100 mm × 100 mm × 400 mm). The concrete specimens were used to investigate the efficiency of the centrifugal concrete technology expressed in terms of compressive strength. The spun concrete cylinders had the same geometry and were identical to the composite columns; the external steel shell was removed from the concrete core on the testing day.ini and (W/C)res; the spun casting caused the water reduction in the concrete. A Portland cement 42.5 N and coarse quartz sand were used. Five different concrete mixtures were used to produce the test specimens. d = the tube external diameter; st = the shell thickness; Es = the elasticity modulus; σy and εy = the average steel yielding limit and corresponding strain; σu and εu = the average steel strength and corresponding strain.Two types of steel tubes were used as shell elements of the composite columns. Cold bended from a cold-rolled low-carbon steel sheet (EN 10130: 2006) and welding with a straight longitudinal butt weld produced the 250 mm diameter and 2 mm wall thickness tubes. Additionally, hot-rolled tubes having a diameter of 159 mm and wall thickness of 4.8 mm  were also tested. Five tension coupons longitudinally cut from the tubes determined the mechanical properties of the steel according to the standard (EN 10002-1) requirements. Kont-31 centrifuge with supporting rubber belts (A er belts  was usedprf) and concrete cylinders (cylf) and the ultimate axial load of the column (uN).exp/NthN) can describe the composite efficiency [thN. Reference [ρ = s/AbA and a mechanical-geometrical parameter ψ exp/NthN decreases with the increase of the parameters ρ and ψ.The ratio between the experimental load-bearing capacity and the theoretical resistance  are included in The ratio between the external and internal diameters of the concrete core cβ, meaning that concrete has filled a 25% of the core. The further increase of the ratio cβ can cause uneven distribution of the concrete inside the tube. Thus, this value was set for the graphs shown in From the centrifuging process standpoint, 2.0 is the typical maximum and most efficient value of the coefficient Armavir Machine-Tool Factory, Armavir, Russia ). Spherical hinges reduced the applied load eccentricity; the transversal restraining rings prevented the local failure of the supports  software ena V5.9 . This soena V5.9 ,25,26,27Atena is utilized. This fracture modelling approach is based on the classical orthotropic smeared crack formulation and crack-band model. It assumes the Rankine failure criterion and exponential softening [fib Model Code 2010 [The constitutive model for concrete is based on the fracture mechanics for the tensile failure and the plasticity for the compressive failure. The CC3 DNonLinCementitious2 model offered by oftening . The soloftening . The necode 2010  using reThe bilinear, elastic-plastic von Mises material model with hardening (CC3 DBiLinearSteelVonMises) describes the behaviour of the steel shell. tf and cohesion C strength of the bond are 0.3 MPa and 1.0; the normal nnK and tangential ttK stiffnesses are identically equal to 6.4 TN/m3; the friction coefficient u is 0.1. The second analysis adopts an ideal connection between the materials. The yielding of the composite section, i.e., significant deformation increase under small load increment, determines the failure of the FE models.The load-deformation response of the column is simulated incrementally, applying a 0.04 mm vertical displacement to the top steel plate, as shown in l/d ≤ 5.0) [Four FE models are created to investigate the effect of the hollow core thickness on the deformation behaviour of the composite columns. The simulations assume the same modelling principles as described in the previous section. This parametric study considers a standard CHS 219 × 3 tube having the 219 mm external diameter, 3 mm wall thickness, and 450 mm length. Such columns are considered short (d ≤ 5.0) . TherefoE = 210 GPa; the Poisson’s coefficient υ = 0.3; the yielding strength yf = 355 MPa; the tangential hardening modulus hE = 1 GPa) describes the material plasticity. The constitutive CC3 DNonLinCementitious2 model was adapted for the C40/50 concrete. This model includes non-linear behaviour in compression with hardening and softening, biaxial strength failure criterion, reduction of compressive strength and shear stiffness after cracking. Compressive strength of 40 MPa was set; the remaining input parameters of the concrete, i.e., tensile strength, the modulus of elasticity, and the fracture energy, were assessed by fib Model Code 2010 [A steel S355 was selected for the tube. The bilinear isotropic von Mises model , is observed.exp/NthN. Concerning the specimens with cold-bended shells, the efficiency of the S2 and S4 specimen groups agree with the theoretical model. The remaining composite columns  were not efficient.The specimens with hot-rolled shells demonstrate exceptional efficiency on average 1.45 times exceeding the theoretical estimation.The composite effect  approachThe composite specimen series S2, S4, and S5 exhibited a ductile failure. On the contrary, the local buckling of the shell caused the failure of the specimens of series S1 and S3. That explains the efficiency results of At a specific thickness, local buckling can appear before the steel strains reach the yield limit. Therefore, the design codes for steel and steel-concrete composite structures  introduAtena software. The study [These results align with the parametric analysis outcomes , though he study  supportsThus, developing a reliable constitutive model is of primary interest and should be the further development object. The study also demonstrates that the local buckling of the hollow core composite column is sensitive to the The concrete infill has a negligible effect on the local buckling capacity of the investigated circular columns, even for specimens with manufacturing imperfections exceeding the current tolerances bound defined by Eurocode 3 . NotwithFurther spun concrete applications aim at developing efficient and fire resilient building structures employing high-strength steel and UHPC. The study  describeSpun or centrifugal casting technology allows the development of efficient composite elements using high W/C ratio concrete. The spun concrete strength is 1.3–2.1 times higher regarding the same vibrated concrete. On the other hand, the composite effect can exceed 25%, i.e., 1.25 times the theoretical load-bearing capacity.The local buckling of the steel shell in the hollow core composite column is sensitive to the tube diameter to thickness ratio and the concrete core depth. Thus, elaboration of the failure prediction formulas of current design codes is necessary, considering the concrete thickness.The predictions by the experimentally verified FE model correctly define the above tendency. Furthermore, the simulation results demonstrated that the bond model makes no sense on the numerical outcome, indicating efficient adhesion between the composite column constituents. However, the efficiency prediction error (underestimation) was 10%. That is a consequence of the simplified material model of the steel assumed in the modelling. Thus, developing a reliable constitutive model is of primary interest and should be further investigated object.ψ  model suitable for solutions to engineering problems and the development of efficient composite elements. The following conclusions were made:


Antibiotic-resistant bacteria are an increasing concern both ineveryday life and specialized environments such as healthcare. Asthe rate of antibiotic-resistant infections rises, so do complicationsto health and the risk of disability and death. Urgent action is requiredregarding the discovery of new antibiotics and rapid diagnosis ofthe resistance profile of an infectious pathogen as well as a betterunderstanding of population and single-cell distribution of the resistancelevel. High-throughput screening is the major affordance of dropletmicrofluidics. Droplet screens can be exploited both to look for combinationsof drugs that could stop an infection of multidrug-resistant bacteriaand to search for the source of resistance via directed-evolutionexperiments or the analysis of various responses to a drug by geneticallyidentical bacteria. In droplet techniques that have been used in thisway for over a decade, aqueous droplets containing antibiotics andbacteria are manipulated both within and outside of the microfluidicdevices. The diagnostics problem was approached by producing a seriesof microfluidic systems with integrated dilution modules for automatedpreparation of antibiotic concentration gradients, achieving the speedthat allowed for high-throughput combinatorial assays. We developeda method for automated emulsification of a series of samples thatfacilitated measuring the resistance levels of thousands of individualcells encapsulated in droplets and quantifying the inoculum effect,the dependence of resistance level on bacterial cell count. Screeningof single cells encapsulated in droplets with varying antibiotic contentshas revealed a distribution of resistance levels within populationsof clonally identical cells. To be able to screen bacteria from clinicalsamples, a study of fluorescent dyes in droplets determined that aderivative of a popular viability marker is more suitable for dropletassays. We have developed a detection system that analyzes the growthor death state of bacteria with antibiotics for thousands of dropletsper second by measuring the scattering of light hitting the dropletswithout labeling the cells or droplets. The droplet-based microchemostatsenabled long-term evolution of resistance experiments, which willbe integrated with high-throughput single-cell assays to better understandthe mechanism of resistance acquisition and loss. These techniquesunderlie automated combinatorial screens of antibiotic resistancein single cells from clinical samples. We hope that this Account willinspire new droplet-based research on the antibiotic susceptibilityof bacteria. Rapid screening of antibiotic toxicityin an automated microdroplet system. Lab Chip2012, 12, 1629–1637.22422170Churski, K.; Kaminski,T. S.; Jakiela, S.; Kamysz, W.; Baranska-Rybak, W.; Weibel, D. B.;Garstecki, P.  are urgently needed. Droplet-based microfluidics maybe an alternative (or at least a supplement) to common low-throughputantibiotic resistance tests and could open new paths for researchinto antibiotic resistance at the population and single-cell levels.Antibiotic-resistant strains ofbacteria were discovered soon afterthe introduction of antibiotics. Alexander Fleming mentioned thisin his Nobel lecture in 1945: 6 and/or contain an individual object of interestsuch as a single cell or a single piece of target nucleic acid foramplification . Droplets can be controllably merged,split, or sorted on the basis of droplet fluorescence7 or absorbance.8 Run-of-the-milldroplet generators are straightforward in design and readily availablefrom commercial vendors; however, their proper use requires additionalequipment, such as pressure generators for pushing liquids aroundchannels  or custom-made opticalsetups.Droplet microfluidics, where droplets of one liquid are submerged in another liquid , enables large numbersof tests, because millions of droplets can be easily generated, andeach droplet can contain a slightly different reagent compositionIn this Account, we guide the reader through advancesin the fieldof droplet-based AST. We first describe how the AST routines can beautomated within microfluidic devices in a variety of ways. We thenproceed to how the AST can be brought to the level of single cellsby means of droplets. In this section, we highlight how the analysisof single cells can help avoid an error-generating inoculum effectand what additional information can be extracted from an AST assaywhen the assay is single-cell oriented in comparison to a classicalpopulation-level assay. We also describe the hurdles of bacterialgrowth detection in droplets at high throughput and what can be doneto avoid or overcome these issues. Then, we describe how long-termstudies of bacterial evolution can be run within droplets with automatedprotocols. We then arrive at the conclusions where we mention problemsto be solved within the field of droplet AST, and we draft possiblefuture research directions.2Droplet-based assays allow for high-levelautomation of liquidhandling protocols. Here, we describe two different approaches toautomating droplet-based antibiotic interaction screening: one basedon flowing droplets and another based on printing droplets containingdifferent antibiotics onto a microchamber array.2.19 After hours of incubation at 37 °C, samplesare analyzed and the lowest concentration of the drug in which nobacterial growth is recorded is established as the MIC of a pair ofa given antibiotic and a given bacterial strain. Screening bacteriafor resistance to two antibiotics by establishing the MIC in 10 differentconcentrations of each antibiotic requires the preparation of 100dilutions, a time-consuming task. Utilizing on-demand generation ofnanoliter-sized droplets,10 we designeda system that automatically prepared combinations of two drugs atvarious concentrations1  is measured by preparing a serial dilution of a tested antibioticand inoculating it with a known and constant density of bacteria.rations1 1.12 Samples were diluted by mixing an antibiotic sample with pure mediumso that after each mixing event the final volume of the droplet wouldbe the same. This assay allowed us to identify interactions betweenantibiotics at a high resolution of antibiotic concentrations .trations 1. The cotrations 1a. We qu2.214 When a bacterial solution is pipettedinto the chip with printed antibiotics, the liquid is sucked intothe chambers as the chip tries to refill its polymer structure withgas as the chip had been degassed before the experiment. As the channelsbranch fractally from the inlet, there is no pressure difference betweenchambers and the filling is accurate. We can monitor the reactionoutcome by absorbance readout. The current focus is on using disposablepumps that make the degassing of printed chips unnecessary. Printeddevices offer large experimental scale and multiplexing of reactionconditions versus other chamber-based systems in which each set ofchambers requires manual dilution of a drug.16Off-chip dilution for sample preparation allowsfor one to use large and precise equipment before placing the dilutedsamples onto a small and disposable chip. In our solution, variousnumbers of antibiotic molecules and different antibiotics were printedinto >1000 nanoliter-sized chambers to screen for resistance tococktailsof antibiotics 2.14 When317 or cells can be placed inindividual droplets.18 Fitting cells ina single-phase microfluidic device is similar to organizing objectsunder a microscope with the addition of excellent fluid control: cellsare immobilized, can be easily tracked, and can be fed with nutrientsor antibiotics. Tracking individual cells allows for a rapid phenotypicMIC assay, as the cells can be monitored to determine whether theydivide in the presence of an antibiotic.19 Scaling up such an assay with a mother machine enabled an even faster,statistics-based MIC assay.20 A mothermachine is a widespread microfluidic device that consists of a maindeep channel and shallow dead-end channels perpendicular to the mainchannel. Each of the shallow channels can trap a single bacteriumthat does not escape as the shallow channels are dead-end. After eachdivision of the trapped cell, the daughter cells appear closer tothe main channel, but the original mother cell stays always at theend of the shallow channel. A mother machine used for AST allows oneto monitor multiple individual cells and their growth dynamics underantibiotic stress.20 The addition of microvalvesto a mother machine’s shallow channels allows for one to distinguishbetween two species of bacteria used in an assay in addition to assessingtheir MIC.21 Although impressive, thesesingle-phase solutions are still orders of magnitude below the scaleof droplet-based cell assays .Microfluidics is perfect for single cell studies, as individualorganisms can either be placed in structures that would fit only asingle cell3.124 The drug-containing droplets were merged on-chipwith solutions of bacteria and a bacterial viability indicator. Aftermerging, the samples were emulsified into 50 droplets each and incubatedfor growth of the bacteria that would later be detected optically.The separation of the emulsions with air allowed for the identificationof reaction conditions in a given set of 50 droplets. Each dropletcontained at most a single bacterial cell at the beginning of theexperiment. While this work was promising in terms of studies of theantibiotic resistance of single cells, 50 droplets per experimentare not sufficient to achieve statistical power; to encapsulate singlecells in the droplets, one has to dilute the sample before emulsification.According to Poisson statistics, to distribute cells among dropletsso that only a very small portion of droplets with bacteria containmore than one cell, the majority of generated droplets has to be empty.25 If there are 10 cells in a sample that is dividedinto 100 droplets, there is only a small chance that any droplet willend up with 2 or more cells. Thus, in the assay described above,24 50 droplets per experiment yielded only 5 dropletswith single cells per experiment.The historicallyfirst system for AST in droplets used an off-chipdilution protocol: a series of drug concentrations was prepared witha pipet and then portions of these prepared solutions were aspiratedto a piece of tubing by a syringe pump, separated by an air spacer.26Serial dilutions that we performon-chip are prepared in large (submicroliter) droplets, but it isalso possible to prepare a series of dilutions of antibiotics off-chipand then emulsify the diluted samples 2. The la3.224 weexperimented with generating “libraries” of droplets.A series of large sample droplets (“mother droplets”)was prepared and then emulsified; each emulsion with a different setof reagents constituted a separate library.27 We developed systems for both active and passive formation of multipleemulsions.26 Active emulsification with a module called flow-focusing quickly generates hundreds or thousands ofdroplets but requires a large proportion of oil (the continuous phase)to water (dispersed) to generate an emulsion.26 Passive emulsification generates droplets more slowly but withoutthe excess of a continuous phase in a mechanism called microfluidicstep emulsification (MSE).28 We employedMSE to screen for antibiotic resistance of single cells2 by generating multiple emulsions in series, eachwith a different antibiotic concentration. The emulsions had to beidentifiable in order to link any given droplet with a particularantibiotic concentration. Although color-coding of droplets (markingdroplets with unique sets of concentrations of distinct fluorescentdyes) has been successfully used in a microfluidic AST,23 a label-free system like ours would be beneficialto reduce the cost of the method, as each color for coding requiresseparate excitation light.To improve on thehistoric system,24 using oil insteadof air to separate emulsions with proper oil and chip constructionmaterials ensured that emulsions did not wet the incubation channelwalls, preventing the droplets from traveling between emulsions duringexperiments and causing cross-contamination. As MSE was used to generatedroplets, each emulsion was densely packed. Emulsions separated fromeach other with oil are called tankers. Tankers wereincubated to let bacteria grow and give off a fluorescent signal thatwe could detect. The tanker-based system allows one to screen forresistance with multiplexing of the reaction conditions because arobotic positioning system is used to generate mother droplets withvarious antibiotic concentrations. Similar multiplexing can be achievedwith modified plates for running reactions,19 printing antibiotics on chip,14 or usingcomplex integrated systems.29 If the throughputof the tanker system is increased, the system should allow one toscreen dozens of reaction conditions per experiment, yielding screeningof antibiotic cocktails at the level of single cells, which has notyet been achieved in an automated way.We physically separated emulsionsof different drug concentrations from each other, which would be inefficientif every generated emulsion was kept in a separate well on a plate.To keep the emulsions in flow, after generating each emulsion of aqueousdroplets submerged in fluorinated oil, we injected a portion of hydrocarbonoil into our system to separate the emulsions 3. While 3.3Escherichia coli cells and populationswith >5 cells were tested against the antibiotic cefotaxime. Itwasassumed that, for an emulsion with no antibiotic, every droplet thatcontained cells provided for the growth of bacteria and gave off afluorescent signal from constitutively expressed yellow fluorescentprotein (YFP). The fraction of droplets that yielded a signal (positivefraction) was divided by the total number of droplets for each emulsionand then was normalized against the no-antibiotic control, thus generatingdata points for viability curves (the percentage of droplets thatprovided growth in the increasing antibiotic concentration). The MICwas higher for the higher initial concentrations of bacteria in thesample  for detectors to notice at high throughput.34 Other solutions use proxies of bacterial growth to asses bacterialviability . The DNA-based MIC assay is pheno-molecular,as it combines gold-standard phenotypic assays with a molecular approach.Without the phenotypic aspect, the genotypic MIC screen is ratherprone to errors, as the simple lack of resistance genes is not a validpredictor of antibiotic susceptibility.38 Pheno-molecular droplet assays were used to assess the antibioticsusceptibility of clinically acquired bacteria within 30 min of apatient’s sample collection.37The aim of microfluidic AST is to be used in a clinicalsetting, so ways to identify bacterial growth without labeling thebacteria must be determined. Individual cells can be tracked,3.5.139 weturned to optical detection of bacterial growth. Optical detectionmethods are compatible with high-throughput screening of droplets(thousands of droplets per second),41 and droplet-basedassays can be relatively easily multiplexed.29 Resazurin is a handy replacement for geneticallyencoded fluorescent proteins and is reduced by metabolically activebacteria to become resorufin. Resorufin becomes fluorescent when exposedto green light, as opposed to an unreduced resazurin. There are twoissues with resazurin/resorufin in droplet-based bacterial assays:resorufin requires oxygen-metabolizing bacteria to glow, and resorufintends to leak from aqueous droplets to surrounding oil , which isbetter suited for droplet assays than resorufin; C12R-supplied dropletsproduce a fluorescent signal above background after hours of incubation,as opposed to leaking resorufin.44Even though we have experience in assessingbacterial growth in droplets by measuring droplet oxygen concentrationas a proxy of bacterial metabolism,ding oil 5. The fi3.5.241 The light scattered by thebacteria in the droplets changes the direction of propagation andcan be gathered with an optical fiber perpendicular to the laser beam.The intensity of the scattered light increases with the number ofbacteria so we can distinguish between droplets in which bacteriadid not grow and droplets in which bacterial growth was present  AST read-outwas not phenotypic, but pheno-molecular, a hybrid of a genetic andphenotypic assay.


Natural fiber-reinforced concrete (NFRC) has the advantages of environmental protection, energy conservation and regeneration. However, studies conducted to improve the macro mechanical properties of concrete by pine needle fiber have achieved good results. In this paper, the deformation and compression damage of pine needle fiber-reinforced concrete (PNFRC) are analyzed by digital image correlation; a fractal dimension is used to quantify the shape of PNFRC after compression damage; and the results of scanning electron microscopy confirm the effect of fiber treatment on deformation and damage of concrete. The results showed that the horizontal strain field of PNFRC has strain concentration zones in the elastic deformation stage, indicating that the fiber enhances the deformation ability of concrete. The defined damage factor can reflect the damage of fiber-reinforced concrete (FRC). The damage curve of natural fiber concrete increases evenly and slowly compared to ordinary concrete. However, natural fiber-reinforced concrete (NFRC) has the advantages of environmental protection, energy saving and regeneration. In previous studies, natural fiber dramatically improved the macroscopic mechanical properties of concrete. The researchers observed that palm fiber  reduced nd Meyer .In particular, previous studies found that pine needle fibers  significDigital image correlation (DIC) technology has the advantage of measuring objects without contact, which can obtain higher measurement accuracy than the traditional method  and can In this paper, the deformation field and damage characteristics of PNFRC under compression are analyzed by DIC. All samples in this study contained a volume of 0–2% pine needle fibers treated with tap water soaking, boiling water, and diluted alkali, respectively. The time-varying evolution law of relative deformation field on the specimen surface, the initial cracking position of the specimen surface and the influence range of fiber on the deformation field were studied. Meanwhile, the failure mode and fractal characteristics of PNFRC were calculated. The influence of pine needle fibers on the deformation and damage of concrete is validated by the SEM results. Compared with different damage factor curves, the damage factor In this study, the coarse aggregate used for raw materials was 5–15 mm of continuously graded gravel, and natural river sand with fineness modulus of 2.95, conforming to the Chinese Standard GBT14685-2001 and GBT14684-2001, respectively. The cementitious material was 42.5 R ordinary Portland cement; The test water met the domestic water standard GB5749-2006 . The con3. The fiber contents added to the concrete were 0.5%, 1.0%, 1.5% and 2.0% of the volume of the test block, respectively. All test samples were prepared, poured, and maintained in strict accordance with GB50081-2019 . The samThe experimental system for studying the compression deformation and damage characteristics of pine needle fiber-reinforced concrete included a loading system and DIC acquisition system.The DIC acquisition system is shown in Hydraulic servo universal testing machine  was selected for the loading system, as shown in The fractal dimension is used to evaluate the failure morphology of concrete with three treatments. From the micro-level, the effects of different treatments of pine needle fibers on the deformation of concrete are demonstrated by SEM, as shown in At the early phase of loading (before A), the coordinated deformation of the corner part of the specimen and the indenter resulted in local breakage, causing a weak strain concentration. In the early loading stage A–C, the strain field of the CC sample is relatively uniform, as the samples are in the linear stage of the load-displacement curve under compression. However, the strain fields on the surface of the PNFRC specimen present an uneven shape. At the elastic stage, the relative deformation fields of PNFRC were formed, and fiber and concrete bear forces together.In the C–D stage, there are strain concentration areas on the surface of the specimens in the nonlinear part of the load-displacement curve, and the strain field shows the clear heterogeneity of zoning. Especially for the specimens containing 0.5–1.5%, the impact range of the fibers on the relative deformation field of concrete increases, and a large strain concentration area appears on the sample surface.DIC is an important tool for quantifying sample damage. S.P. Ma  proposedo et al.  and H. Zo et al.  proposedUnder a 10% load at the initial loading phase, the above three damage factors keep changing synchronously. Under the same deformation conditions, the more fiber content, the earlier the damage occurs to pine needle fiber-reinforced concrete specimens. The damage degree of diluted-alkali-treated samples is less than that of the boiling-water-treated sample when the load is in the elastic stage. The increase in the damage of PNFRC is relatively gentle compared to ordinary concrete.(1)The fractal dimension of fiber-reinforced concrete treated with tap water soaking, boiling water, and an alkali solution is consistent with the macroscopic results of damaged morphology. At the same time, it is proved that pine needle fiber can promote the deformation and damage of concrete from the micro point of view. The SEM results show that the surface of the alkali-treated fiber is wrapped with cement mortar, which produces cracks after the concrete is damaged.(2)At 50% of the peak load, the strain concentration zone of the 0.5–1.5% PNFRC appears, and the strain concentration zone develops to the maximum at 90% of the peak load. The “X” type strain concentration zone of other samples is irregular at the peak load, compared with ordinary concrete and 2% pine needle fiber concrete.(3)Adding natural fiber can change the damage growth rate of concrete and make the damage curve grow evenly and slowly. The samples A30C10 show the best deformation and damage performance. The damage degree of the samples treated with boiling water is greater than that of the samples treated with dilute alkali in the elastic deformation stage.(4)fa could accurately reflect the compression damage of PNFRC. In the process of compression deformation, the defined damage factor can characterize the details of the damage and deformation of each specimen.The damage factor DIn this study, DIC technology was used to study the compressive damage characteristics of PNFRC, and three damage evaluation methods were compared. The conclusions were as follows:Therefore, it can be concluded that the damage of NFRC is different from that of ordinary concrete, and the damage factor evaluation method proposed in this study can accurately recognize the evolution mechanism of the plant fiber concrete instability precursor response crisis, and realize the damage evaluation of concrete. As a new type of natural reinforced composite material applied in buildings, PNFRC still needs further research. PNFRC can also be used to control the degree of damage by manual intervention.


In the case of existing prestressed concrete structures, information about the actual state of prestressing is an important basis for determining their load-carrying capacity, as well as remaining service lifetime. This is even more important in the case of existing prestressed concrete bridges, which are exposed to a more aggressive environment than the other prestressed concrete structures. The level of prestressing is affected and reduced by prestress losses at a given time. In calculating the internal forces and stresses, required for the assessment of the Ultimate Limit State and the Serviceability Limit State, it is necessary to know not only the prestressing level but also the cross-sectional area of the prestressing steel , which can change in time due to corrosion. In practice, in the case of the pre-tensioned concrete members, it has often happened in the past that cable ducts have been grouted only partially, or not at all, due to poor grouting technology. Experts did not realize what this could cause in the future—the penetration of water with aggressive agents directly into the cable duct and consequently corrosion of the prestressing steel, which means not increased protection of the steel, but rather acceleration of degradation. On the other hand, in many cases, corrosion also occurs in ducts that are not grouted and no water has entered them. This paper deals with this phenomenon—the formation of corrosion of prestressing steel in cable ducts in ungrouted ducts due to moisture. This problem was investigated experimentally and numerically in the simulation program ESP-r. Experimental measurements and numerical simulations have shown that the water vapor condenses in the cable ducts, which can subsequently cause corrosion of the prestressing steel. Deterioration of structural materials is an inevitable and challenging fact in the field of engineering. Consequently, we are forced to deal with it from the moment of design and construction of structural members. One particular form of deterioration—corrosion of prestressing steel—affects the load-carrying capacity and remaining service lifetime of structures ,3,4,5,6.In terms of material deterioration, the prestressed concrete (PC) structures are not an exception. In the case of the post-tensioned structures, the prestressing force is applied by jacking steel tendons against an already-cast member, so the prestressing is transferred through built-in steel anchorages. Furthermore, if the area between the prestressing steel and the duct is injected with cement grout, the prestressing is transferred also through the bond between the steel strands or wires and concrete. This cement grout with plastic or steel duct also provides efficient protection of strands (or wires) from corrosion . Steel cEvaluation of corrosion losses of prestressing steel in ungrouted ducts was investigated in scientific work . This reThis paper deals with the problem of corrosion of prestressing reinforcement in long-term ungrouted cable ducts on real bridge structures. The aim is to present that even if water does not get directly into the ungrouted cable duct, corrosion of the prestressing steel can occur due to natural moisture in the duct.The pivotal object of the presented study is one of the post-tensioned bridges in Podbiel (north part of Slovakia) from the first generation of prestressed concrete bridges which were built in former Czechoslovakia in the middle of the previous century (in 1956). The investigated bridge is presented in At the time of erecting, similar bridges consisting of precast post-tensioned girders were built and they deal with the same problems—corrosion of prestressing steel due to ungrouted cable ducts. This structure was chosen as an example because the diagnostic survey provided reliable information about the state of grout in ducts which are crucial for the presented analysis. The bridge in question was located in northern Slovakia on an international road leading to Poland. At the time of the diagnostic survey, this bridge was in service for almost 60 years. Edge supports of the bridge were provided by abutments and middle support was represented by a pillar. The span No. 1 was crossing the river terrace, whereas the span No. 2 was crossing an adjacent creek. The analyzed bridge consisted of two simply supported spans with an identical effective length of 26.650 m. The structure consisted of ten individual precast post-tensioned beams with a spacing of approximately 1140 mm. Their height was 1350 mm. The overall width of the structure was 11,800 mm. In the 1950s and 1960s, the deck of this type of bridge was normally composed of a monolithic concrete slab, which was cast on the upper edge of the precast beams. Nevertheless, the rigid connection between the precast beams and the monolithic concrete slab was not ensured since the slab was designed only as the base of the bridge pavement to ensure a transverse slope. Thus, the concrete slab was considered as ballast and did not contribute to the load-carrying capacity of the investigated bridge. The transversal connection between the beams was established using the transversal prestressing which was typically located in their upper flanges (in this case the spacing was 320 mm) and transversal diaphragms . Longitudinal prestressing was transferred into the precast concrete girders by twenty-two tendons consisting of twelve patented wires with a diameter of 4.5 mm. Prestressing wires were placed in a cable duct of a diameter of 50 mm. Cable ducts were identified as metal tubes ,28. DetaThe investigated bridge was in a bad state at first sight, so it could be assumed that regular inspections were neglected. The view on the bridge prior to its demolition can be seen in A presented study should help to understand the reasons for such severe corrosion of prestressing wires in ungrouted ducts of post-tensioned bridges and describe the conditions which negatively contributes to its extensive propagation like in the case of an investigated bridge. Additionally, the performed analysis could provide important information for the operators of post-tensioned concrete bridges from the first generation which could be endangered by analogous issues. p depends on the temperature T (°C) and the relative humidity RH (%) according to the formula [Condensation on the surface of the air cavity can occur when the surface temperature of the material surrounding the air cavity is lower than the dew point temperature. If the air cools near a cold surface, its relative humidity in this area can increase significantly. If it cools too much, condensation will form, liquefying excess water vapor. The determination of a dew point temperature D formula :(1)Dp, its surface can cool very sharply and condensation can form on its surface ,31. The The relative humidity rate in the cavity is the most significant for the cavity with the most negligible concrete wall/slab thickness. Due to the unavailability of information on humidity conditions in closed cavities of concrete elements (ducts), it was necessary to perform an experiment to describe this phenomenon. The fundamental question was whether it was possible to achieve such humidity in the cavity that it began to condense and subsequently cause corrosion of the prestressing steel. The results from the experimental program will be compared to the simulations see . In the Samples of dimensions of 150 × 300 mm (concrete cylinders) served to describe the change in humidity in the duct with no airflow. The cavity in the specimen originated in the longitudinal drilling of holes of different diameters. The holes of diameter 107 mm in specimens with denotation “C21”, holes with a diameter of 72 mm in specimens with denotation “C40” and specimens with denotation “C50” with the holes of diameter 51 mm were created see . This mack,cube = 58.1 MPa and an average bulk density of 2295 kg/m3. The maximum aggregate size was 16 mm, and the cement CEM II BS 32.5/R was used.The concrete cylinders were 27 months old, with a concrete cube strength fThe temperature for the drying of samples was 110 °C (230 °F). After the drying process, they moved to an air-conditioning chamber. The ambient temperature in the air conditioning chamber was the lowest (8 °C), at which it can maintain a humidity of 90% for a long time. The temperature and humidity were independent controlled in the inside space of the chamber. To determine the water absorption, it was necessary to determine the weight of the samples, measured at selected time intervals. After reaching humidity of 75% inside the specimen denoted as C21, the experimental test was terminated. The experiment aimed to determine whether and for how long the moisture in the cavity will reach 75% under constant temperature conditions under the action of atmospheric humidity and what effect the concrete cover thickness of the sample has a. The saAdditionally, we dried identical samples at 110 °C (230 °F). After tempering to 8 °C (46.4 °F), the specimen moved in an 8 °C water storage (water bath). They have been placed in a climatic chamber in the water bath, while maintaining an ambient and water temperature of 8 °C. After reaching the desired humidity in the cavity, we measured the weight of samples to determine the water absorption b.Under atmospheric humidity, a 75% increase in moisture in the cavity of the C21 sample occurred after 469 h. In the case of a water storage, that time was 103 min. The significant difference in the length of the passive stage between samples C21 and samples C40 and C50, whether under atmospheric humidity or in water storage, is due to the fact that the maximum aggregate grain size of the concrete mix is 16 mm, with a concrete cover thickness of 21 mm in the case of C21.The following The inverse value (ratio) represents the rate of moisture penetration during the passive stage , it is 0The rate of moisture penetration during the passive stage  in this Whether the water vapor would condense on the surface of the duct is determined by its current surface temperature. It depends on the external climatic conditions  and the heat capacity of the concrete beam. The calculation considers the dynamic behavior performed in the simulation program ESP-r (release 12.0), developed as a research tool . When it3, the computing coefficient of thermal conductivity was 1.58 W/m.K, the specific heat capacity was 1020 kg/m3, the absorption of the surface for solar radiation is equal to value 0.6. The simulation does not include the moisture transfer. The orientation of the cavities meets the bridge girder in the east-west direction . That means that the sunlight in the simulation fell on the left-hand side. The numerical simulation used the reference climate year of the IWEC  database for Prague. The zone (duct) humidity was a constant value throughout the simulation period. As described in the previously mentioned experiment, it is problematic to determine the relative humidity of the air in the duct. The relative air humidity in the cavity is more affected by the moisture contained in the concrete than in the outside air. For example, the concrete can absorb air humidity by rain and so it can get wet. Water can enter the concrete beam through the leaky road pavement, as well. Therefore, the simulations considered several levels of relative humidity in the cavity: 65%, 70%, 75% and 80%. It is also expectable that the bridges over the river will be less favorable during the year than over the ground (land). The simulation model works with a square cross-section of the air cavity (duct) instead of the original circular shape, enabling creating an orthogonal network of these cavities (ducts). The model, representing the cut-out of a one-meter concrete beam, consisted of 20 air cavities (20 zones model) see  with denAs will be seen in the next section, the main potential for condensation is in the cavities Z3 and Z4. They are on the bottom edge of the beam, and, in addition, the sunlight is not incident at this side of the concrete beam. However, condensation can occur in several cavities, which can also be seen in According to the course for 75% RH of air in the cavity, condensation can occur, especially in the cold winter season. In general, the lower is the air temperature, the greater the condensation potential is. For this reason, the coldest week from 9–20 February, which occurred in the reference climate year, was selected for further analysis in the other cavities. During that period, the relative humidity of the outside air was high for a long time, fluctuating from 60% to 100% .In In In In In In addition, through the relatively thin sidewall between the cavity and outside environment the air in the cavity (duct) heats up or cools down rapidly. Still, the massive concrete part of the beam next to the cavity ensures thermal stability. In the long term, if condensation on the surface freezes, it may not melt during the day due to thermal stability. This can also affect the corrosion of the prestressing steel.Experimental measurements  have cleExperiment in climatic chambers shows that the humidity in the edge cavities will be very strongly dependent on the soaking of the concrete beam by the wind-driven rain. It would be interesting to extend research in this direction and to monitor experimentally, or by simulation, the amount of incident rain, as is done in buildings . The numerical simulation  showed tThus, experimental measurements and numerical simulations together proved why in real bridge structures with ungrouted cable ducts , an enviThe basic aim of the cable ducts in the post-tensioned prestressed concrete members is the possibility to prestress the concrete element even after stiffening and hardening of the concrete (unlike pre-tensioned prestressed concrete elements). This also makes it possible to trace the position of the cables before concreting, i.e., the possibility of a covered cable (in the ground plan or height). Another important task is to protect the prestressing reinforcement itself against the penetration of degradation factors from the surrounding aggressive environment in which the element is located (mostly bridges). However, it can only perform this function if the cable duct is also well and sufficiently grouted. Today, the plastic cable ducts currently in use perform this task well. However, in the past, metal cable ducts have been used, which could corrode on their own. In the case of post-tensioned prestressed girder bridges, often used in practice in the past (60s to 80s of the last century), it has been proven many times that these cable ducts were not sufficiently grouted—within the diagnoses of bridges from that period it was found that they are either only partially grouted or even not grouted at all.The presented research shows that in that case, the cable ducts do not protect the prestressing steel against corrosion, but on the contrary, create an environment that can cause corrosion due to moisture condensation without aggressive factors—moisture can get into the cable ducts and water condenses due to temperature, which creates an ideal environment for corrosion of the prestressing steel, which is not protected by the concrete passive layer around the steel as in the case of reinforcement in reinforced concrete structures or prestressing steel in the pre-tensioned prestressed concrete structures.The research presented in the paper proves that the cause of problems of the post-tensioned prestressed bridges in practice, in which the prestressed reinforcements were not grouted well was corrosion of prestressing steel, even without penetration of aggressive factors to the steel itself, which could subsequently cause sudden failure of elements much earlier than their planned lifetime (approximately after 40 to 60 years of the service lifetime). The failure is usually sudden without showing any previous indications that would point to a possibility of a sudden failure .For this reason, in the case of the post-tensioned prestressed bridges, it is necessary to pay increased attention to determining the actual state of grouting of cable ducts and the state of the prestressing reinforcement—whether it is corroded or not.