Thus, either c-Met activation triggers integrin activation and cell adhesion or integrin adhesion to its extracellular ligand triggers c-Met activation. These two modes of cooperation require the adhesive function of integrins and mostly lead to cell migration and invasion. In a third, less conventional, mode of cooperation, the integrin plays the role of a signalling adaptor for c-Met, independently from its adhesive property, leading to anchorage independent survival. Recent studies have revealed the influence of endocytic trafficking in c-Met-integrin cooperation including the adaptor function of integrin occurring on endomembranes, triggering an inside-in signalling, believed to promote survival of metastatic cells. We present the evidence of the cooperation in vivo and in human tissues and highlight its therapeutic relevance. A better understanding of the mechanisms regulating c-Met-integrin cooperation in cancer progression could lead to the design of new therapies targeting this cooperation, providing more effective therapeutic approaches than c-Met or integrin inhibitors as monotherapies used in the clinic.c-Met is a receptor tyrosine kinase which upon activation by its ligand, the hepatocyte growth factor, mediates many important signalling pathways that regulate cellular functions such as survival, proliferation, and migration. Its oncogenic and tumorigenic signalling mechanisms, greatly contributing to cancer development and progression, are well documented. Integrins, heterogeneous adhesion receptors which facilitate cell-extracellular matrix interactions, are important in biomechanically sensitive cell adhesion and motility but also modulate diverse cell behaviour. Here we review the studies which reported cooperation between c-Met and several integrins, particularly β1 and β4, in various cell models including many tumour cell types. From the various experimental models and results analysed, we propose that c-Met-integrin cooperation occurs  Structudomains) . For an domains) . HGF/c-Mdomains)   . Activatdomains) . Anotherdomains) . Interesdomains)  prior todomains) . Dependidomains) . Moreovedomains)  and c-Me in vivo . Further in vivo . Given t in vivo . Resulta in vivo . C-Met i in vivo .Integrins are a large family of cell-surface adhesion receptors, which are fundamental in facilitating interactions between cells and their extracellular matrix (ECM) . Thus, Epecific) . Specifipecific) . Some inpecific) . Importapecific) . The lespecific) .via inside-out signalling -MAPK pathways  receptor and platelet derived growth factor receptor , whereasin vivo and in human tissues and highlight its therapeutic relevance.Here we review the studies which have reported c-Met and integrin cooperation and their role in cell migration, invasion, anchorage-independent growth and tumorigenesis. Through carefully analysing the experimental conditions and results of each publication, we propose that c-Met-integrin cooperation mainly occurs through the conventional inside-out or outside-in signalling mechanisms. Thus, either c-Met activation triggers integrin activation and cell adhesion or integrin adhesion to its extracellular ligand triggers c-Met activation. Furthermore, we also describe a less conventional mechanism in which an integrin acts as a c-Met signalling adaptor, which appears to be independent from its adhesive property. Recent studies have revealed the influence of endocytic trafficking in c-Met-integrin cooperation including the adaptor function of integrin occurring on an endosome following the co-trafficking of the two molecules, triggering an inside-in signalling. Although here we focus on the evidence pertaining to each mode of signalling cooperation, it is likely and indeed in some studies apparent that these types of cooperation are not mutually exclusive. We also present the evidence of the cooperation One form of cooperation appears to occur through the inside-out signalling, whereby c-Met, dependently or independently of HGF, acts upstream of the integrin receptor, inducing its activation and triggering downstream signalling and cell function.Early studies reported that HGF stimulation of normal and cancer cells increased their adhesion to integrin ligands such as collagen, laminin-1, vitronectin, fibronectin or vascular cell adhesion molecule-1. Moreover, the adhesion was inhibited by relevant blocking antibodies of integrins, including αvβ3, and β1 and its partners α2, α3, α4, and α5 . More reFurther studies reported the role of integrins in HGF-dependent cell migration. HGF triggered cell migration on laminin, the β4 ligand . Moreovein vitro and in vivo  of its activator, the guanine exchange factor general receptor for 3-phosphoinositides 1, impaired HGF-stimulated β1 integrin recycling as shown using biotin-labelling and immunostaining, with no change in total β1 expression . HGF-depecycling , the sigvia siRNA transfection in ovarian cancer cells, which overexpressed c-Met, triggered a reduction in β1 and α5 expression and reduced cell adhesion on fibronectin and vitronectin, and to the peritoneum of mice  was increased upon c-Met activation. Furthermore, p52Shc siRNA KD impaired c-Met-β1 co-IP. These results suggested that β1, through its NXXY domain in the cytoplasmic tail, also functioned as an adapter linking c-Met to p52Shc, subsequently allowing sustained activation of ERK1/2. Importantly, this signalling occurred in adherent and detached cells, and β1, as well as its NXXY domain, were found to be required for c-Met-dependent anchorage growth in soft agar, protection against anoikis and peration .in vivo. Similar phenotypes were seen with the loss of β1 -specific computational model of HGF/c-Met axis supports the findings of experimental studies reporting enhanced inhibition of phosphorylated AKT and ERK1/2 upon c-Met-α5β1 dissociation and highlights the importance of previously identified c-Met-β1 co-trafficking .Several of the studies reviewed here have reported the association of c-Met and integrin in a complex predominantly through co-IP and co-immunofluorescence experiments. Interestingly, complex formation is observed across the different signalling cooperation mechanisms.c-Met-β1 , c-Met-αA detailed analysis using PyMOL modelling  identifiThe association of c-Met and β1 integrin detected by proximity ligation assay, which typically detects molecules at less than 40 nm distance, strongly suggests they interact directly . HoweverThere are also reports of glycoprotein cluster of differentiation isoform six involvement in c-Met-α6β4 binding . c-Met-βThe induction or disruption of c-Met-integrin complex formation has functional consequences. The functional role of c-Met-β1 complex was further demonstrated with the engineering of an artificial heterodimerisation system where the rapamycin-derived drug AP21967 induces the heterodimerization of fused c-Met-FKBP (FK506-binding protein) and β1-FRB (FKBP-rapamycin-binding). The dimerization promoted wound healing and invasion of breast cancer cells . A theraIntriguingly, integrin-c-Met cooperation may also be mediated by the binding of HGF to an ECM integrin ligand, such as vitronectin or fibronectin, as seen in adhesive endothelial cells. HGF binding domains were identified on these two integrin ligands . Thus, sin vivo is scarce. Using proximity ligation assay one group has shown c-Met-integrin association in patient breast tumour tissue with elevated levels of c-Met-β1 complex in brain metastases compared to the primary tumours (Although high levels of c-Met or integrin in patient tumour tissue have been shown to correlate with poor prognosis , direct  tumours . In addi tumours .The artificial heterodimerization of c-Met-FKBP and β1-FRB by the rapamycin-derived drug AP21967 promoted breast cancer cell extravasation out of circulation as shown through a tail vein metastasis assay . c-Met-βin vivo tumorigenesis in mice and cell invasion in zebrafish embryos required the expression of β1 and the presence of its intact NXXY domain (in vivo invasion and tumorigenesis, in vivo evidence of an independence from β1 adhesive property was not provided. However, the requirement of the autophagy regulator autophagy-related gene five in the HGF-driven invasion of lung cancer cells in zebrafish was shown using siRNA, suggesting that the inside-in c-Met-β1 cooperation in ARE vesicles support the invasion (in vivo evidence that c-Met-β4 integrin cooperation can occur independently from the adhesive property of integrin. Thus, cells expressing WT c-Met and extracellularly truncated β4 integrin resulted in the formation of tumours in mice, whereas cytoplasmic β4 mutants did not form tumour masses (One study reported a significant reduction of phosphorylated c-Met and total c-Met expression levels in HCC xenograft tumour tissue upon siRNA-mediated KD of β1, and a notable inhibition of HCC tumorigenic progression . SimilarY domain . Althouginvasion . Furtherr masses .in vitro and reduced tumour growth in HCC xenografts (As c-Met-integrin cooperation appears therapeutically important in diverse tumour contexts, it may be exploited in improving anti-tumour effects and modulating drug resistance. There has been a limited benefit of c-Met or integrin inhibition in the clinic . Integrinografts .Further, integrins and c-Met cooperation may be a potent mediator of resistance to therapeutics modulating the behaviour of other molecules . Thus c-in vivo (Histone deacetylase inhibitor suberanilohydroxamic acid reportedly leads to an upregulation of α5β1 which mediates c-Met phosphorylation associated with poor sensitivity in prostate and lung cancer cells in vivo . AlthougHaving reviewed in detail the literature on c-Met and integrin cooperation, we propose that the two molecules utilise three main mechanisms of signal integration which include inside-out  and outsAlthough our review highlights these three main mechanisms of cooperation, they are not necessarily mutually exclusive and a few studies have shown elements of inside-out and outside-in c-Met-integrin cooperation in the same cells .Although the studies reviewed here show some elements of evidence for mainly c-Met-β1 cooperation, many did not dissect the mechanisms of cooperation including whether the two molecules form heterodimers. Therefore, the level of specificity and mechanistic diversity of c-Met-integrin cooperation remains poorly defined. In light of the studies reporting spatial facilitation and regulation of cooperation predominantly between c-Met and β1, we believe that the true scope and importance of spatially controlled c-Met interaction with a range of integrins is yet to be revealed.Signalling events induced by c-Met-integrin cooperation are poorly defined, with limited evidence on the exact signalling mechanisms that induce tumorigenic functions. Interestingly, c-Met-integrin cooperation appears to contribute to more global changes in transcriptional cell profiles , potentiMechanical ECM properties may also regulate c-Met-integrin crosstalk. ECM stiffness may modulate c-Met-β1 interaction, as increased matrix rigidity results in upregulated c-Met, β1 and FAK, and associated cell proliferation, epithelial-mesenchymal transition and resistance to tyrosine kinase inhibitors . Differein vitro cell migration and invasion models do not fully recapitulate the physiological conditions, posing a challenge to understand the specific functional role integrin-c-Met interaction may play in the tumour microenvironment. Encouragingly, evidence of viable therapeutic manipulation of c-Met-integrin signalling systems in vivo suggests potential exploitation of their cooperation which could enable more effective treatment strategies than c-Met or integrin inhibitors used as a monotherapy.Other oncogenic partners may enhance c-Met-integrin cooperation as exhibited by mutant NRP1 co-receptors . MoreoveTherefore, we must strive for a greater understanding of c-Met-integrin cooperation, aiming to thoroughly elucidate their signalling networks and the associated tumorigenic effects. Understanding the mechanisms of cooperation, signalling cascades and their functional effects on tumour cell behaviour in a tumour microenvironment context would potentially provide novel therapeutic avenues direly needed to improve clinical outcomes.


Despite the advantageous benefits offered by self-compacting concrete, its uses are still limited due to the high pressure exerted on the formwork. Different parameters, such as those related to concrete mix design, the properties of newly poured concrete, and placement method, have an impact on form pressure. The question remains unanswered on the degree of the impact for each parameter. Therefore, this study aims to study the level of impact of these parameters, including slump flow, T500 time, fresh concrete density, air content, static yield stress, concrete setting time, and concrete temperature. To mimic the casting scenario, 2 m columns were cast at various casting rates and a laboratory setup was developed. A pressure system that can wirelessly and continuously record pressure was used to monitor the pressure. Each parameter’s impact on the level of pressure was examined separately. Casting rate and slump flow were shown to have a greater influence on pressure. The results also demonstrated that, while higher thixotropy causes form pressure to rapidly decrease, a high casting rate and high slump flow lead to high pressure. This study suggests that more thorough analysis should be conducted of additional factors that may have an impact, such as the placement method, which was not included in this publication. The formwork pressure exerted by self-compacting concrete (SCC) is considerably higher than that of normal concrete due to its high flowability . This hPrevious studies have shown that form pressure is affected by several parameters, and these parameters are generally classified into parameters related to mixture design and material properties, the fresh concrete properties of the mix, and the placement method and speed of casting . HoweverThe parameters that affect the amount of pressure and its distribution over the form’s height are relatively interrelated. For example, mixture design affects the flowability of the concrete and has an influence on the pressure and its reduction over time. To understand that phenomenon,  conducteA different study by  investigThe important effect of reinforcing bars has also been demonstrated, as shown in congested reinforcement where pressure was rather lower than it was when few reinforcing bars were used ,18,19. TCasting rate and placement methods have a significant effect on pressure, with a higher casting rate leading to higher pressure ,26,27,28A laboratory setup was developed to simulate the casting process. A 2 m plastic pipe was vertically fixed to the column and given rigid support to avoid any tilt, trembling, or collapse . PressurWith the help of cutting-edge sensors and the Internet of Things, a system developed by PERI was used in the experiments with the idea of turning cast-in-place concrete into a digital process. The sensor system consisted of data transmitters that provided readings from the sensors to the cloud. As seen in The mixture used for casting was a commercial mixture with fixed proportions, and only the type of cement and superplasticizers were altered depending on the required slump flow. Different variations were then used to study the significance level of different parameters, such as slump flow, T500 time, fresh concrete density, air content, static yield stress, concrete setting time, and concrete temperature.For all batches, the water-to-cement ratio was kept at 0.59, and the superplasticizer (SP) used was MasterGlenium 592. A small mixer was used in the laboratory to mix the concrete in various batches. New batches of concrete were created for each layer of casting while preserving the same characteristics. To ensure the same flowability, the measurement of the slump was kept track of and maintained for each batch. Two cement types were used. The first cement was Bascement (BAS) CEM II/A-V 52.5 N Portland-fly ash, which is recommended for use in normal concrete work, per the supplier Cementa. This cement has a different setting time. The second cement, known as Anläggningscement FA (ANLFA), is a Portland-fly ash cement type (CEM II/A-V 42.5 N MH/LA/NSR) used in mass concrete which has mild heat requirements in terms of hydration (cementa.se).Casting rate is a significant parameter that affects the amount of lateral pressure when casting with SCC. In the laboratory plan, casting rate was set at 0.25 m/h, 0.5 m/h, 1 m/h, and 4 m/h. Using these diverse rates, the effect of casting rate was then investigated. Different types of slump flow were created by controlling the amount of superplasticizers so as to produce the desired slump flow diameter, with the first interval being 700–750 mm, the second 600–650 mm, the third 500–550 mm, and the fourth interval 400–450 mm.Before casting, the concrete was tested for different properties, including slump flow, T500 time, air content, fresh density, setting time, and static yield stress. The tests were performed according to the guidelines specified for each test in the European guidelines for SCC , except The setting bag test was conducted as specified by  using a For each concrete recipe, the portable vane test or torque test was performed instantly to measure static yield stress. This was used to investigate the structural behavior of SCC at rest and involves using four-blade vanes and a torque gauge to measure the torque required to break the structure. The static yield stress (in Pa) of the concrete at rest can be determined from the measured torque value and vane geometry. The method is explained in detail in . An example of pressure monitoring is shown below for one of the tests of SCC with a casting rate of 0.25 m/h. Pressure was monitored over 8 h of casting, as demonstrated in hydro = ρgh, where ρ is concrete density in kg/m3, h is casting height (m), and g is gravitational acceleration (9.8 m/s2).3 for BAS concrete and 2382 kg/m3 for ANLFA concrete. The suppliers of the concrete claim that BAS takes 150 min to set, whereas ANLFA takes 170 min. The impact of employing various types of cement on pressure is demonstrated in Concrete temperature affects the amount of form pressure reduced but not maximum pressure , with coSetting time was documented according to DIN18218 , which iThe effect of static yield stress at 15 min is crucial to understanding the effect of concrete viscosity as well, with high-viscosity concrete leading to lower form pressure. From Correlation denotes the form of relationship between variables, which in this case includes either inputs such as density, height, and casting rate or the output, which is pressure. A negative coefficient denotes that when one variable decreases the other increases, while a positive coefficient denotes that when a variable increases the other associated variable also increases.The results in Casting rate has a significant effect on the amount of pressure, with faster rates resulting in more pressure.Flowability, as measured by slump flow, also has a significant effect on pressure.Cement type (ANLFA and BAS) had a minimal effect on form pressure during casting, though a larger impact was observed when examining pressure reduction.Higher density results in higher pressure.Higher air content causes early fresh concrete to have lower initial form pressure, and this impact lessens as the concrete begins to solidify.It can be challenging to determine how concrete temperature affects pressure.The temperature of the concrete affects the amount of form pressure that can be reduced but does not affect maximum pressure; higher temperature concrete tends to harden more quickly than lower temperature concrete due to the hydration rate of previously cast concrete.Concrete that sets more slowly leads to higher pressure, whereas concrete that sets more quickly leads to lower form pressure.Concrete with high viscosity has less form pressure, which is supported by evidence that, after 15 min, pressure is lower in concrete with increased stress.The correlation matrix demonstrated that air temperature and density both have a greater correlation with maximum pressure, as shown by measurements recorded throughout the entire testing period.This study explored the degree to which slump flow, T500 time, fresh concrete density, air content, static yield stress, concrete setting time, and concrete temperature have an impact on form pressure when casting with SCC. Extensive laboratory experiments were conducted with a newly developed pressure system to monitor pressure and study the effects of these parameters. Several conclusions are made:


To evaluate the clinical impact of the BioFire FilmArray Pneumonia Panel (PNA panel) in critically ill patients.Single-center, preintervention and postintervention retrospective cohort study.Tertiary-care academic medical center.Adult ICU patients.Patients with quantitative bacterial cultures obtained by bronchoalveolar lavage or tracheal aspirate either before  or after  implementation of the PNA panel were randomly screened until 25 patients per study month (75 in each cohort) who met the study criteria were included. Antibiotic use from the day of culture collection through day 5 was compared.P = .0006). Also, 56 postintervention regimens (75%) were eligible for change based on PNA panel results; actual change occurred in 30 regimens (54%). Median antibiotic days of therapy (DOTs) were 8 before the intervention versus 6 after the intervention (P = .07). For the patients with antibiotic changes made based on PNA panel results, the median time to first antibiotic change was 10 hours. For patients who were initially on inadequate therapy, time to adequate therapy was 67 hours before the intervention versus 37 hours after the intervention (P = .27).The primary outcome of median time to first antibiotic change based on microbiologic data was 50 hours before the intervention versus 21 hours after the intervention (The PNA panel was associated with decreased time to first antibiotic change and fewer antibiotic DOTs. Its impact may have been larger if a higher percentage of potential antibiotic changes had been implemented. The PNA panel is a promising tool to enhance antibiotic stewardship. Respiratory samples are commonly obtained in the diagnostic workups of pneumonia and are utilized to guide antibiotic therapy. Identification and susceptibility testing results from respiratory cultures may take up to 72 hours. During this time, patients often remain on broad-spectrum antibiotics, increasing the risk of developing adverse events or antibiotic resistance. Pathogen identification in patients with pneumonia allows for targeted antibiotic therapy and has been associated with reduced mortality.Lower respiratory tract infections, including pneumonia, are the fourth leading cause of death worldwide, with ∼19% of pneumonia hospitalizations involving intensive care unit (ICU) admission. The BioFire FilmArray Pneumonia Panel  uses multiplex polymerase chain reaction (PCR) technology to identify 18 bacterial and 8 viral pathogens as well as 7 antibiotic resistance genes from respiratory specimens within 75 minutes of testing. Previous studies have shown the overall percentage of positive agreement between the PNA panel and respiratory cultures to be 90%–96.8% and the negative agreement to be 96.8%–98.1%. Our institution implemented the PNA panel in November 2021. Rather than the test being ordered by a provider, our microbiology laboratory automatically tests all respiratory specimens from adult ICU patients with quantitative cultures obtained by bronchoalveolar lavage (BAL) or tracheal aspirate (TA) with the PNA panel unless they had a PNA panel test within the preceding 72 hours. Theoretically, the more rapid identification of potential pathogens and key resistance markers would promote earlier tailoring of antibiotic therapy compared to using standard respiratory cultures alone. Although several studies have demonstrated the potential impact of the PNA panel on antibiotic therapy, the actual effects of the test are less well established. Therefore, we evaluated the clinical impact of the PNA panel at our institution.The use of rapid diagnostic tests in healthcare settings has increased in recent years due to their timely pathogen identification, which has allowed for a decrease in broad-spectrum antibiotic use, quicker time to adequate therapy, and decreased healthcare costs.This retrospective, single-center, pre-post cohort study was approved by the institutional review board at an 885-bed academic medical center in the southeastern United States where it was conducted. This study included 2 cohorts based on date of respiratory specimen collection: a preintervention cohort  and a postintervention cohort . The following ICUs were included in the study: medical (including oncology), neuroscience, surgical, cardiothoracic, cardiovascular, trauma, and burn. During the 2-month implementation period, educational sessions and written communication were provided to critical care providers and pharmacists in these ICUs. Education included a description of pathogens and resistance genes detected by the PNA panel, the location of results in the electronic health record (EHR), and instruction on how to interpret and apply the results to guide therapeutic management. No targeted stewardship interventions were implemented with the initiation of the PNA panel. However, as with all microbiologic data, PNA panel results were reviewed daily by critical care clinical pharmacists who were available from 07:00 to 22:00 and who routinely participate in clinical decision making regarding their patients’ antimicrobial therapy.Because we sought to determine the overall impact of the PNA panel as used at our institution, we evaluated the entire population of patients meeting criteria for the PNA panel, whether or not they had pneumonia. Patients were included in the study if they met the following criteria: age ≥ 18 years, admission to an adult ICU, and collection of a quantitative specimen obtained by BAL or TA. Patients with another bacterial infection treated inpatient or outpatient with antibiotics (other than bacteremia with the same causative pathogen) in the 14 days prior to specimen collection through 5 days after specimen collection, those who died within 5 days after specimen collection, and those who had another quantitative culture obtained by BAL or TA within the previous 72 hours were excluded.A query of the microbiology laboratory information system identified patients admitted to an adult ICU with a quantitative BAL or TA sample obtained during the preintervention and postintervention periods. These patients were retrospectively reviewed in random order until 25 patients who met study criteria from each study month (75 patients in each cohort) were identified based on the calculation that 141 total patients would be required to detect a median difference of 30 hours between cohorts. Patients were included only once per admission.Pseudomonas was detected). Regarding the correlation between culture and PNA panel results, an exact correlation was defined as an exact match between pathogens identified on respiratory tract culture and those identified on PNA panel results . A sample with no growth on culture and a negative PNA panel result was also considered an exact match. Antibiotics included in DOT calculations included all systemic antibiotics administered during the 5 days following specimen collection.The primary outcome was the time to antibiotic change based on microbiologic test results within 5 days of specimen collection. Secondary outcomes included potential and actual antibiotic changes made based on culture and PNA panel results, time to adequate therapy in patients who were not on adequate antibiotic therapy, number of occurrences in which therapy that was de-escalated based on the PNA panel results was re-escalated based on culture results, correlation of the PNA panel results with culture results, days of antibiotic therapy (DOT), and vancomycin serum concentration monitoring. Hospital and ICU length of stay up to 30 days from the date of culture and in-hospital mortality within 30 days of culture were also compared between the 2 cohorts. De-escalation was defined as modification of antibiotic therapy by discontinuing antibiotics or changing to an agent with a narrower spectrum of activity. Escalation was defined as switching to an antibiotic that was active against a pathogen detected that was not covered by the patient’s previous antibiotic regimen. Adequate therapy was defined as the receipt of antibiotic therapy with in vitro activity against all identified pathogens. Antibiotics were determined suitable for change if the PNA panel detected an untreated organism requiring escalation of therapy or did not detect an organism such that therapy could be de-escalated . Initial antibiotic therapy was deemed inadequate for 4 patients in the preintervention cohort and 6 patients in the postintervention cohort. The median time to antibiotic change to provide adequate therapy in this subset of patients was shorter in the postintervention cohort (37 hours) than in the preintervention cohort . In 8 instances, antibiotics were never initiated in the preintervention cohort, and in 12 instances antibiotics were never initiated in the postintervention cohort.Time-to-event outcome analyses are reported in Table P = .07).In the postintervention cohort, 56 (75%) antibiotic regimens were suitable for change based on the PNA panel results. Actual changes occurred in 30 (54%) of these regimens. Of the antibiotic regimens that were changed based on the PNA panel, the median time to change was 10 hours . Antibiotic de-escalation occurred in 23 cases, with vancomycin discontinuation being the most common change. Antibiotics were initiated in 7 cases, and gram-negative antibiotic coverage was initiated in 6 of these cases (Table Staphylococcus aureus (n = 10), Pseudomonas aeruginosa (n = 7), and Klebsiella pneumoniae (n = 7). An exact correlation between the PNA panel and culture results was found in 45 samples (60%). In 14 instances, the PNA panel identified organisms that grew on culture plus additional organisms that did not grow out on culture. In 11 cases, the PNA panel identified organisms at a low concentration that did not subsequently grow on culture. In 5 instances, organisms not included in the PNA panel grew on culture: Stenotrophomonas maltophilia (n = 2), Providencia stuartii (n = 2), and Ewingella americana (n = 1). In no case was an organism identifiable by the PNA panel identified by culture but not by the PNA panel. No statistically significant differences in ICU length of stay, hospital length of stay, or in-hospital mortality were detected between the 2 cohorts . Rapid diagnostic tests can provide accurate and early pathogen identification, decreasing the time to targeted therapy compared to using traditional culture data alone. Although many studies have been conducted to determine the potential impact of the PNA panel, data on its actual impact in clinical practice are limited. In this study, we sought to obtain real-world data on the impact of the PNA panel at our institution.Current pneumonia guidelines recommend using respiratory cultures to guide targeted antibiotic therapy.The PNA panel significantly decreased the time to antibiotic change in critically ill patients, with the greatest impact on the de-escalation of MRSA antibiotic coverage. Furthermore, when exclusively looking at patients in whom the PNA panel result was used to prompt antibiotic change, the median time to antibiotic change was reduced to 10 hours. The use of the PNA panel was also associated with fewer days of antibiotic therapy. In our study, the PNA panel led to a quicker time to adequate therapy in patients who were initially on inadequate therapy. By facilitating a more rapid change to targeted therapy, rapid diagnostic tests, such as the PNA panel, can aid in decreasing broad-spectrum antibiotic use and decreasing the time to adequate antibiotic therapy. These efforts by antibiotic stewardship clinicians can help decrease the initial hesitancy of some providers to embrace these new technologies and assist with their appropriate application to antibiotic use.Although the PNA panel had a significant impact on antibiotic optimization in adult ICUs, opportunities for improvement were identified. Although the PNA panel had the potential to influence 75% of the therapy courses, it only led to antibiotic changes in approximately half of these patients. To understand these cases further, an analysis was conducted that evaluated patients in the postintervention cohort who could have had therapy modified based on PNA panel results but did not. In approximately half of these cases, antibiotics were subsequently changed based on the culture results, which may indicate a lack of trust in the PNA panel. With more time and experience, confidence in using this new test to modify antibiotic therapy may increase. In the other half of the patients, therapy was not modified even after culture results were reported, potentially indicating a general reluctance to de-escalate therapy in these patients. The panel may also have had a greater effect if stewardship interventions beyond the actions of critical care clinical pharmacists, which occur predominantly during the day shift, had been implemented. Multiple recent studies have shown the positive effects of real-time, active methods to assist with optimizing antibiotic stewardship practices using rapid diagnostic tests. 46.3%, and 47.4% concordance rates. The number of discordant PNA panel and culture results were anticipated given that the number of pathogens detected by the PNA panel is not exhaustive and that the panel can detect both nonviable and viable organisms at very low quantities. Therefore, it was expected that the PNA panel would detect organisms from a respiratory sample that did not grow on culture. No instances occurred in which an organism detectable by the PNA panel was not identified by the PNA panel but subsequently grew on culture, supporting the high negative predictive value of the test. Based on these results, clinicians should feel confident in de-escalating anti-MRSA or antipseudomonal antibiotic therapy if the respective pathogens and resistance genes are not identified on the PNA panel in critically ill patients with pneumonia. As with all tests, the PNA panel is a tool that must be used in conjunction with an assessment of patient-specific factors to optimize care.In our study, exact agreement occurred between the PNA panel and culture results for 60% of samples, which is similar to previous studies that reported 53.6%,This study had several limitations. Owing to its retrospective design, the data collected were limited to those recorded in the EHR. This study was conducted at an institution that did not consistently use MRSA nasal screening to de-escalate anti-MRSA coverage. Therefore, the impact on anti-MRSA therapy utilization may not translate to an institution with more universal MRSA screening practices. As more rapid diagnostic tests become available and are used together, it may be beneficial to evaluate the impact of each test individually and when used in concert. In addition, our study was conducted during the coronavirus disease 2019 (COVID-19) pandemic, and it is unknown how the differences in severe acute respiratory coronavirus 2 (SARS-CoV-2) variants, treatments, and vaccine reception may have affected the different study groups. Also, we did not control for confounding factors, such as patient comorbidities , severity of illness, and hemodynamic instability, which could have influenced de-escalation decisions. Finally, our postintervention cohort was studied shortly after the implementation date of the PNA panel; therefore, our results may not represent the application of this new test after providers became more familiar with its use.In conclusion, the PNA panel was associated with a significant decrease in the time to the first antibiotic change and fewer antibiotic days of therapy. The PNA panel may have had a greater impact on antimicrobial use if more antibiotic changes had been implemented at the time of PNA panel result. The PNA panel is a promising antimicrobial stewardship tool.


The recoveries in urine samples were reported to be 97.0 and 105.6% for both MOR and MET, respectively.For the first time, a sensitive electrochemical sensor using a glassy carbon electrode modified with CMK-5 Ordered mesoporous carbon was fabricated for simultaneous analysis of morphine and methadone. Modern electrochemical FFT-SWV techniques and partial least-squares as a multivariable analysis were used in this method. CMK-5 nanostructures were characterized by field emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction analysis, and Raman spectroscopy. Variables such as accumulation time and pH for the proposed sensor were optimized before quantitative analysis. To train the proposed sensor, standard mixtures of morphine (MOR), and methadone (MET) were prepared in the established linear ranges of the analyzes. The results obtained from training samples were used for PLS modeling. The efficiency of the model was determined using test and real matrix samples. The root mean square error of prediction and the squared correlation coefficients (R It is also classified as a banned doping agent for athletes2. Methadone (MET), also known as 6-dimethylamino-4, 4-diphenyl-3-heptanone, is a potent synthetic analgesic used as an opioid for maintenance therapy in the treatment of heroin and morphine addicts and for the treatment of chronic pain management4. However, research has also shown that MET can be addictive, and addiction to MET is increasing in various societies6. According to the study results, MOR and MET have almost similar pharmacological properties, and overdose of MOR and MET can lead to premature death in people7.Morphine (MOR) is an analgesic of the opiate family commonly used to relieve acute pain. However, it can become habit-forming and lead to physical dependence14. Electrochemical techniques are emerging as promising alternative methods for pharmaceutical analysis because of their rapid results, simple operation, accuracy, and cost-effectiveness15. Furthermore, the fast fourier transform square wave voltammetry (FFT-SWV) technique has been used as a sensitive and accurate method for the analysis of various compounds. FFT-SWV uses Fourier transform filtering combined with electrochemical methods to eliminate instruments' stationary noises, which helps to improve sensitivity17.In the last decades, researchers have developed a variety of methods for the analysis of MOR and MET, such as high-performance liquid chromatography, supercritical fluid chromatography, gas chromatography coupled with mass spectroscopy, chemiluminescence, spectrophotometry, which are generally time-consuming, prohibitively expensive, complicated, and often require pretreatment20. For example, Behzad Rezaei et al.21 have developed an electrochemical sensor based on carbon nanotubes and carbon quantum dots to detect methadone. Also, Maccaferri et al. have used exfoliated graphene oxide to fabricate an electrochemical detection of morphine22. The results show that carbon nanotubes and graphene can improve the electroanalytical performance of the sensor due to their large surface area, electrical conductivity, and electrocatalytical properties23. CMK-5 is a group of ordered mesoporous carbon with high porosity and a large surface area. Recent research has shown that ordered mesoporous carbon has lower electron transfer resistance than carbon nanotubes24. Due to the extremely well-ordered pore structure, the high specific pore volume, the high specific surface area and the good electrochemical conductivity, OMCs are suitable for use in fields of electrochemical sensor technology25. For example, OMCs have been used electrochemical detection of glutathione, dopamine, glucose, and morphine28. Moreover, the high ability of these OMCs to adsorb and accumulate analytes can lead to very sensitive electrochemical sensors29.However, electrochemical detection of MOR and MET with bare electrodes has several limitations, such as slow electron transfer, low sensitivity, and impurities. The development of nanotechnology has provided a variety of nanomaterials as electrode surface modifiers to improve the electrochemical detection of MOR and MET. Carbon nanostructures such as carbon nanotubes and graphene have been widely used to fabricate electrochemical sensor for MOR and METBased on previous studies, the oxidation mechanism of MOR and MET substances can be written as Fig. 132. MET is oxidized by the mechanism shown in Fig. 33. A review of previous articles shows that the second peak of MOR, appears at a higher potential and overlaps with the electrochemical peak of MET34.Figure 37. Compared to other types of multivariate calibrations, the partial least-squares (PLS) technique has many advantages as a linear model has many advantages, such as providing high performance, use of all response profiles, reduction of interference effects, and ignoring concentrations of components other than the desired analyte41.Multivariate calibrations can be used to solve the problem of signal overlap. Unlike univariate calibration methods, which evaluate the signal of one analyte, the responses of several combinations are considered simultaneouslyThis work focuses on the synthesis of CMK-5 mesoporous carbon nanostructures to modify the surface of a glassy carbon electrode (GCE/CMK-5) for simultaneous measurement of MOR and MET. CMK-5 was characterized by X-ray diffraction analysis (XRD), Raman spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). In addition, the electrochemical properties of the modified GCE/CMK -5 electrode were investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The FFT-SWV technique was used for quantitative analysis. The digitized response profiles were used as input for the multivariate calibration can be observed in Fig. pluronic P123, tetraethyl orthosilicate (TEOS), aluminium chloride, furfuryl alcohol (FA), trimethylbenzene (TMB), oxalic acid (OA), N, N-dimethylformamide (DMF) were purchased from Sigma-Aldrich. All other reagents were of analytical grade with maximum purity. Morphine (MOR) and methadone (MET) were supplied by the Darou Pakhsh Holding Company (DPHC). All the solutions were prepared using high purity water from a Millipore system (> 15 M cm). Phosphate buffer solution  was employed as a supporting electrolyte. The stock solutions of MOR and MET were made separately at concentrations of 1 mM in PBS and stored in the refrigerator. Also, the working solutions used for analyses were obtained by diluting the stock solution with PBS.42. briefly a liquid crystal template was prepared by dissolving 4 g of P123 surfactant in 150 mL of HCl (2 M) aqueous solution. Then 9.6 mL TEOS was added drowsily to the above solution under stirring at 40 °C stirring for 20 h and then heated in an autoclave at 100 °C for 24 h. The obtained solid product was separated, washed, and dried at 60 °C. Finally, the dried powder was calcined at 550 °C for 8 h to remove the template. For the synthesis of Al-SBA-15, 2.0 g of SBA-15 was ultrasonically dispersed in an ethanolic solution of 16.6 mM AlCl3 for 2 h. The ethanol was then evaporated in a vacuum oven and the remaining solid was calcined at 550 °C for 3 h43. CMK-5 was synthesized in a template of Al-SBA-15. To prepare CMK-5, a solution mixture of furfuryl alcohol (FA) and trimethylbenzene (TMB) as carbon sources and oxalic acid (OA) as catalyst was prepared at a molar ratio of 200:185:1. This solution was mixed with Al-SBA-15 and stirred at a temperature of 80 °C for 1 h. The suspension was dried in an air oven at 150 °C for 12 h. Consequently, aluminum silicate and oxalic acid catalyzed the polymerization of furfuryl alcohol on the pore wall of Al-SBA 15.The obtained dark brown powder was carbonized in a furnace at 300 °C with a heating rate of 1 °C min−1 and then 800 °C with a rate of 5 °C min−1 for 4 h under nitrogen atmosphere. Finally, the product was treated with 20 mL of HF (1 M) aqueous solution to remove the silicate template.The synthesis of CMK-5 mesoporous carbon is shown in Fig. GCE/CMK-5 was prepared as follows: First, the GCE (2 mm) was polished to achieve a mirror-like surface with 0.3 and 0.05 μm alumina. Then, the electrode was sonicated in a mixture of water and ethanol (50:50) for 5 min to clean the electrode surface and finally dried under high purity nitrogen flow. Next, 1 g of CMK-5 was weighed and dispersed in 1 mL of DMF by sonication for 15 min. Eventually, about 2 µL of the prepared suspension was dropped onto the surface of the GC electrode and dried under the IR lamp. The GCE/CMK-5 electrode was obtained.X-ray diffraction analysis (XRD) was performed on a Philips diffractometer of X'pert company device with monochromatic Cu Kα radiation (λ = 1.5406 Å). The Raman spectroscopy was recorded by a device of Takram N1-541 model (laser wavelength 532 nm) produced by Teksan Company. Transmission electron microscopy (TEM) image was obtained by Philips CM30 with an accelerating voltage of 200 kV. Scanning electron microscopy (SEM) images were obtained by TeScan–Mira III as well as energy-dispersive X-ray spectroscopy . The pH meter (Metrohm 744 pH Meter) was used. The sonication bath  was used for ultrasonic radiation.44. It has a three-electrode system, including a GCE (2 mm in diameter) as the working electrode, a platinum wire as the auxiliary electrode, and an Ag/AgCl electrode as the reference electrode. fast fourier transform square wave voltammetry (FFT-SWV) is a modified technique based on the square wave voltammetry (SWV) technique using the discrete fast fourier transform (FFT) method for background subtraction and two-dimensional integration of the electrode response over a selected potential range and time window. As shown in Fig. All electrochemical experiments were performed by μStat-i 400 s as a portable Potentiostat/Galvanostat/Impedance Analyzer  controlled by a personal computer with DropView 8400 softwarePartial least squares (PLS) were employed to construct a predictive model based on the voltammetric profiles for different MOR and MET concentrations. Solutions of binary mixtures of MOR and MET ranging from 0.1 to 4 µM were prepared, including 14 training samples and 6 test samples.1 and u1 are latent score vectors of the first PLS factor, p1 and q1 are corresponding loading vectors, and E1, F1 are error matrices46.Briefly, PLS consists of an input matrix X and an output matrix Y, following the general formula.2), root mean square error of calibration (RMSEC), root mean square error of prediction (RMSEP), and root mean square error of cross-validation (RMSECV). The R2 value was calculated asyi is the actual concentration of the analyte in sample i, i, n is the total number of samples used in the calibration set. The RMSEC, RMSEP and RMSECV were calculated as:Since the number of latent variables should be neither too high nor too low, as this leads to overfitting or underfitting when modeling the data, the evaluation of the multivariate model by statistical parameters to determine the correct number of LVs is of high importance. The statistical parameters include squared correlation coefficient  and crystalline graphite (G-band), respectively.The powder X-ray diffraction (XRD) patterns of Al SBA-15 and CMK-5 are shown in Fig. The morphological properties of CMK-5 were studied via SEM and TEM images. Figure ct) for GCE and GCE/CMK-5 are 189.28 and 88 Ω and Cdl for GCE and GCE/CMK-5 are 36.3 and 113.2 µF, respectively. The obtained the equivalent circuit values indicate CMK-5 can provide an excellent electron passage at the electrolyte/electrode interface and a high surface area for absorption of MOR and MET.The electrochemical feature of CMK-5 surface was evaluated by electrochemical impedance spectroscopy. Figure Cyclic voltammetry was applied to investigate the electrochemical behavior of MOR and MET on the GC and GC-CMK5 electrode's surface. Figure 47. However, Fig. The effect of buffer pH as an important variable on the response of the electrode in the simultaneous determination of MOR and MET was evaluated. As shown in Fig. One of the variables that can improve the electrochemical signal of MOR and MET on the electrode modified with CMK-5 is the accumulation time due to the strong adsorption properties of CMK-5. Here, the effect of accumulation time for MOR and MET from 0 to 180 s was separately investigated. The results showed , and LV4 was chosen as an optimal condition. All statistical parameters for the final model are can be found in Table To obtain the linear calibration range of current as a function of concentration for both analytes, their electrochemical behavior was first studied in a univariate manner using the FFT-SWV technique. The linear equations obtained are shown in Table Furthermore, a comparison of the present method with methods described in the literature is presented in Table To investigate the effect of interference on the simultaneous measurement of MOR and MET, common interfering species in the urine matrix were evaluated by spiking solutions with 0.5 µM MOR and MET under optimal conditions. A maximum amount of 5% of the relative prediction error for each species was determined as the tolerance limit. However, the results showed that none of the common interferences significantly affected the PLS prediction. The data obtained are shown in Table The reusability of the GCE/CMK-5 sensor was investigated with 10 times measurement by FFT-SWV in a mixture of 0.5 µM MOR and 0.5 µM MET in PBS solution (pH = 8.5). The sensor was washed with deionized water after each measurement. The relative PLS prediction error was studied as a reusability parameter. Figure Samples were prepared as follows. First, 3 urine samples were collected from healthy volunteers. Then, a certain amount of each of the drugs MOR and MET was added. To induce protein precipitation and protonation, 20 μl of a 5 M HCl solution was added to the samples. The sample was then filtered using a 0.2 um filter. To reduce interference and control pH, samples were diluted 5 times with phosphate buffer solution (pH = 8.5). Figure In conclusion, CMK-5 was successfully synthesized in a hard templated Al SBA-15 by chemical and thermal treatment methods. Investigations showed the electrocatalytic effect of CMK-5 double-pore systems on the oxidation of MOR and MET. Also, electrochemical and structural characteristics showed that CMK-5 has a high ability to absorb both drugs in its structure. The result of FFT-SWV indicated the good sensitivity of GCE/CMK-5 the detection of MOR and MET. Furthermore, Combining FFT-SWV with the partial least squares (PLS) method was used to decrease interference MOR and MET. the model obtained by this method successfully detected the concentrations of MOR and MET with the mean square error values of the validation values were 0.00772 and 0.00892 respectively. In addition, an as-fabricated sensor was applied to detect MOR and MET in the urine samples. MOR and MET detection recovery in urine samples ranged from 95.6 to 105.6. The sensor illustrated an excellent ability to tolerate real sample matrix interferences. The present work proved that CMK-5 mesoporous carbon is a suitable candidate for the construction of sensors. Besides, multivariate calibration methods allow simultaneous detection of multiple analytes with reasonable precision for use in complex matrices.Supplementary Information.


To the editor,Overuse and/or misuse of antibiotics has long been a public health problem, particularly in many Low-or Middle- Income Countries (LMIC). Antibiotic overuse is a main contributor to increasing rates of antibiotic resistance (AR) which is a real challenge for infectious disease control in coming years.A recent paper in the Lancet Regional HealthFirst, the antibiotic overuse comes from patients. The recent Lancet Regional Health study,Second, the antibiotic overuse is contributed by GP overprescribing. Unfortunately, data on characteristics of prescribers (GPs) were not available in the recent Lancet Regional Health studyIn conclusion, in Vietnam, an alarmingly high rate of overprescribing of antibiotics at primary care settings coupling with a high rate of antibiotic self-medication leads to overuse and misuse of antibiotics and their associated consequences including antibiotic resistance. While Vietnam is accelerating its capacity in primary care with a focus on increasing the role and numbers of family doctors, tackling the issue of overprescribing should be seriously considered in parallel. A multimodal intervention strategy addressing issues related to multi-stakeholders including consumers, prescribers, pharmacies, regulators and inspectors, is urgently needed.None.


Background: Improved patient safety for those undergoing treatment of head and neck cancers depends on prompt identification of warning indicators from severely critical patients and appropriate treatment. As a result, many hospitals all around the world have implemented quick response techniques, including medical emergency teams (MET), which have systems and personnel that are highly trained to deal with patients who are deteriorating. Nowadays, automated activation and alert programs are also being discussed.Aim: To compare the patient outcomes in two conditions: one before the application of the automated MET alert and activation program and the other after the application of the automated MET alert and an activation program was used.Methods and Materials: There was an examination of clinical data on MET-managed patients before and after the computerized alert and activation approach was put in place. The study comprised all adult head and neck cancer patients who were treated by the MET between March 1, 2017, and December 31, 2021. The physiologic abnormalities of the patient at the moment of the MET initiation were recorded as causes for MET activation when the MET was alerted by the computerized alert, and activation system. From activation through deactivation, the MET intervention lasted. Hospital mortality served as the study's primary outcome. The duration of stay at the hospital and unscheduled ICU hospitalizations were secondary outcomes. Medical records from hospitals were examined retrospectively to get information on clinical outcomes.Results: The percentage of unplanned admissions in ICU was greater in the pre-implementation stage (22.34%) as compared to that in the post-implementation stage (13.56%) . The duration of stay of patients at the hospital also got reduced in the post-implementation phase (13.23 ±1.47 days) as compared to the pre-implementation stage  (p<0.001). The median time of derangement of activation of MET was greater in the pre-implementation stage (62 minutes) as compared to the post-implementation stage (34 minutes) . The most common complications leading to MET activation in a pre-implementation phase were neurological and respiratory complications. On the other hand, overall deterioration was the most common cause of MET activation. The mortality rate of patients in the pre-implementation stage was 36.23% as compared to 22.12% in the post-implementation stage (p<0.001).Conclusion: The hospital experienced improved clinical outcomes with the adoption of an automated alarm and activation system using a cumulative weighted scoring methodology, which significantly reduced the time from disruption to MET activation. Head and neck cancer patients in hospital wards frequently display atypical physiological symptoms hours before complications take place . ImproveAfter the MET program at Raj Hospitals in Ranchi, Jharkhand, was launched, all head and neck cancer patients who received MET care were prospectively registered. We examined clinical data on MET-managed patients before and after the computerized alert and activation approach was put in place to answer the core research objective of whether the application of the computerized alert and activation approach for MET is connected with health outcomes in head and neck cancer patients admitted to the critical care and anesthesiology departments and then transferred to the general ward. Because this study is an observational one, the institutional reviewing board approved it and waived the need for informed consent with IRB number IEC/2016/1245. Before analysis, patient data was also de-identified and anonymized.Study populationThe study comprised all adult head and neck cancer patients who were managed in the general ward by the MET between March 1, 2017, and December 31, 2021. A prior study  containeThose patients with a Modified Early Warning Score (MEWS) of seven or above at the moment of MET activation were considered for the main study to address the major research objective of analyzing the impact of the computerized alert and activation approach with the MEWS . The finImplementation of the automated alert and activation systemThe computerized alert and activation approach based on the MEWS was used by the MET to launch an active screening program across all ward patients. When nurses entered the patient's vital indicators into the electronic health care record, the MEWS was generated automatically, employing five physiological signals (systolic blood pressure (SBP), heart rate, respiration rate, body temperature, and degree of awareness). An automated alarm was delivered to members of MET in the form of a text in actual time, 24 hours a day, seven days a week, whenever the MEW score was seven or greater, and the Medical Emergency Team engaged automatically. Patients who agreed to a do-not-resuscitate command were omitted from the active screening, and the hospital's digital medical record was used to capture information on the patient's code status. While MEWS was color-coded in the patient profile in the computerized medical record system, alerts were not shown to the ward's doctors and nurses. As a result, the ward's medical personnel could identify the patient's MEWS status: green color code for MEWS 0 to 2, yellow color code for MEWS 3 and 4, orange color code for MEWS 5 and 6, and red color code for MEWS 7 or higher. When feasible, vital signs of the patient were captured at the bedside quickly following examination using only a laptop or transportable device. Without a set hospital policy, the number of vital sign measurements was determined by the attending physician. However, vital signs were often recorded at least four times each day and sometimes more frequently if the patient's clinical condition changed. Every time a patient's vital signs were recorded for the first time, MEWS was updated right away.Data collection and clinical outcomesAs quickly as feasible after the event, a MET member entered the required information into a registry for all MET activations brought on by calls and automated alerts. Patient demographic characteristics, the method that activated the MET , the causes of the MET activation, the time of the first substantiated physiological disorder, MEWS, the times the MET was activated and deactivated, the vital signs at those times, the interventions the MET provided, and the patient's state following the clinical episode were all collected and recorded. This data was added the next day to check hospital medical records before registering for registration data quality control. The physiologic abnormalities of the patient at the moment of the MET initiation were recorded as causes for MET activation when the MET was alerted by the computerized alert and activation system. From activation through deactivation, the MET intervention lasted. Hospital mortality served as the study's primary outcome. The duration of stay at the hospital and unscheduled ICU hospitalizations were secondary outcomes. Medical records from hospitals were examined retrospectively to get information on clinical outcomes. Because self-imposed limits on treatment could affect the clinical outcomes, patients who cut back on therapy after MET intervention were not included in the analyses of outcomes.Statistical analysisTo compare the traits and clinical results between the two stages before and after the computerized alert and activation program was put in place, descriptive statistics were used. A Mann-Whitney U test was used to examine the median values and interquartile ranges of continuous variables. Where appropriate, chi-squared tests, as well as Fisher's exact tests, were used to assess categorical variables, which were reported with numbers and percentages. The odds ratios of active screening using the computerized alert and activation methods were calculated using the logistic regression approach, and the risk variables for hospital mortality in patients in general wards who had clinical deterioration were identified. The OR (odds ratio) of every predictor with 95% confidence intervals was used to represent the results (CIs). For all analyses, a 2-tailed P-value of equal or below 0.05 was regarded as statistically significant. The statistical program SPSS Inc. SPSS for Windows, Version 14.0. Chicago, SPSS Inc. was used to examining the data .In this study, the total number of patients with head and neck cancer managed by MET was 586. Among them, 46 patients were out of the general ward, and the medical records of the other 14 patients were able to be retrieved. Therefore, they were excluded from the study . Most of the patients in both groups were from the medical department (79.9% and 78.2%).The percentage of unplanned admissions in the ICU was greater in the pre-implementation stage (22.34%) as compared to that in the post-implementation stage 13.56%) . Patients' hospital stays were also reduced in the post-implementation phase (13.23 days) compared to the pre-implementation stage (24.76 days) (p = 0.001). The median time of derangement of activation of MET was greater in the pre-implementation stage (62 minutes) as compared to the post-implementation stage (34 minutes) . The most common complications leading to MET activation in the pre-implementation phase were neurological and respiratory complications. On the other hand, overall deterioration was the most common cause of MET activation. The mortality rate of patients in the pre-implementation stage was 36.23% as compared to 22.12% in the post-implementation stage (p = 0.001) , cardiopulmonary pulmonary resuscitation, High-flow nasal cannula (HFNC) and noninvasive ventilation (NIV), respiratory system as a cause for MET activation, and delay in the time of activation of MET were significantly related to an elevated risk of patient mortality, while implementation of the automated activation and alert system of MET and medical and surgical therapy given by MET was significantly related to reduced risk of patient mortality Tables -5.According to the authors' knowledge, this is the first study to evaluate the role of automated activation and alert systems for MET in head and neck cancer patients at a tertiary-level hospital of Raj Hospitals in Ranchi. In our study, patients were divided into two categories: One category included patients managed by MET before the application of the automated activation and alert system for MET, and the other included patients managed by MET after the application of the automated activation and alert system for MET. It was found that the percentage of unplanned admissions in the ICU was greater in the pre-implementation stage as compared to the post-implementation stage. The duration of stay of patients at hospitals was also reduced in the post-implementation phase as compared to the pre-implementation stage. The median time of derangement of activation of MET was greater in the pre-implementation stage as compared to the post-implementation stage. The most common complications leading to MET activation in the pre-implementation phase were neurological and respiratory complications. On the other hand, overall deterioration was the most common cause of MET activation.A reduced proportion of ICU admissions is associated with automated stimulation of the MET employing electronic medical record-based screening criteria , althougThe use of a computerized prediction model to identify high-risk subjects for whom therapies by rapid-response teams are linked with decreased mortality was recently discovered by major multicenter cohort research , althougObjective evaluations have been suggested to enhance the early detection of unexpected declines. The most common grading method is an overall weighted approach based on variations in vital signs. In this investigation, the MEWS, which was calculated and used automatically, was used to turn on the MET automatically -22. DuriAdditionally, compared to single factors, aggregate scoring methods are more accurate at identifying the risk of unfavorable outcomes . To helpBut calculating cumulative weighted scoring systems manually is difficult and susceptible to inaccurate measurements . As a reAlthough both doctors and nurses were permitted to contact the MET at our center, in reality, doctors made practically all of the MET calls. This shows that when aberrant vital signs were discovered, nurses first informed the junior doctor of the patient's clinical state. After examining the patient, the resident doctor called the MET. The interval between deterioration and MET activation was greatly reduced since the automatic alarm and activation system avoids this procedure. In many clinical settings, it has been shown that acting quickly when a patient is very sick is helpful, and shortening the time between deterioration and MET activation helps skilled medical professionals evaluate and treat the patient sooner.The study had some limitations. First, the study's inherent retrospective observational design posed limitations. Even though all MET participants were taught how to record each variable, some information may have been missed, and recollection bias may have affected how accurate the results are.The hospital experienced improved clinical outcomes with the adoption of an automated alarm and activation system using a cumulative weighted scoring methodology, which significantly reduced the time from disruption to MET activation. If clinical impairment is found, automatic alarm and activation software make sure that the MET is turned on quickly. This helps avoid delays that could happen with a system that isn't automated.


Optimal duration of empiric antibiotic therapy in hospitalized patients with febrile neutropenia of unknown origin (FN-FUO) remains controversial. Emerging evidence suggests that early discontinuation of antibiotics at 48-72 hours of apyrexia is safe regardless of neutrophil count. However, in the U.S., the adoption of this and other antibiotic use practices in these patients remains unstandardized and understudied, particularly in community hospitals. In this pilot study, we sought to evaluate current antibiotic prescription practices in our large community hospital in admitted patients with AML and FN-FUO.th, 2021. All patients admitted with a diagnosis of AML and febrile neutropenia (FN) were screened and those with FN-FUO, defined as no microbiological growth on blood, respiratory or urine cultures at 48 hours of first fever were included. Data on initial antibiotic choices, use of vancomycin and its congruence with IDSA guidelines, mean days of therapy (DOT), mean days of “excess” therapy (DOET), defined by days of antibiotics after >72 hours of apyrexia and total DOET were obtained by medical record review and descriptive analysis was performed.We conducted a retrospective cohort study from January 1st, 2020 to December 16A total of 65 patients with FN were screened. After screening, 27 patients met criteria for inclusion and data from their hospital stay was obtained (Table 1). Cefepime was the preferred choice of initial intravenous β-lactam in 85% of cases and piperacillin-tazobactam was used in the remainder of cases. Vancomycin was used initially in 55% of cases out of which its use was considered to be incongruent with IDSA guidelines in 25% of cases. The most common reason for IDSA incongruent use of vancomycin was lack of documentation for its use. Mean DOT was 10 and mean DOET was 3 (Table 2). In total, we identified 87 excess days of antibiotic therapy in this cohort.Little is known about antibiotic prescription practices in high risk FN-FUO patients in community hospitals. Our findings highlight potential concrete antibiotic stewardship targets and shortening this knowledge gap may help guide the development of interventions that have been previously shown to improve clinical outcomes in this overall underrepresented population.All Authors: No reported disclosures.


Planting concrete, an eco-friendly concrete in which plants can grow directly, has been widely used in roof greening and the slopes of rivers. Porosity and compressive strength are important indicators for evaluating the properties of planting concrete. By preparing planting concrete with different aggregate gradations  and water–cement ratios , the effect of aggregate gradation and water–cement ratio on the porosity and compressive strength of the planting concrete was analyzed, the intrinsic relationship between aggregate gradation and plane pore parameters was studied, the strength growth pattern and microscopic strengthening mechanism were studied, the relationship between porosity and compressive strength of the planting concrete were explored, and a tall fescue planting experiment was carried out to evaluate the plantation performance of the planting concrete. The results show that under the same conditions of water–cement ratio, the smaller the particle size of the aggregate, the smaller the porosity of the plane, and the denser the structure. The average diameter of the planting concrete shows an exponential relationship with the porosity of plane. The early growth of the compressive strength of the planting concrete is rapid; the compressive strength has a linear relationship at the ages of 7 days and 28 days. Compared to polynomial and logarithmic functions, the exponential function gives a better insight into the relationship between the porosity and compressive strength of the planting concrete. Tall fescue seeds germinate and grow well; height, cover, and leaf rootstock and element content of plants can be used as indicators to assess the performance of vegetated concrete planting. Planting concrete is a porous concrete and its products that can satisfy the requirements of green plants, with continuous internal pores that allow water, air, etc., to pass through easily. It not only guarantees its basic function as a material structure, but also reduces the load on the environment and plays an important role in enhancing moisture and heat exchange in the ground, regulating temperature and humidity, and absorbing noise, with significant eco-benefits ,2,3,4,5.Despite the many important benefits of planting concrete, the efficient growth of plants is still influenced by porosity. The greater the porosity of the planting concrete, the more space there is for plant growth and the better the plants will grow; however, higher porosity leads to lower strength for concrete . The typIn this study, planting concrete was prepared with two aggregate gradations and five water–cement ratios, the effect of aggregate size and water–cement ratio on the porosity and compressive strength of planting concrete was studied, the effect of different aggregate sizes on the two-dimensional pore characteristics of planting concrete was explored, and the intrinsic link between planar pore parameters was investigated. This study also explored the relationship between water–cement ratio, porosity, and compressive strength, establishing a relationship equation between porosity and compressive strength. By optimizing the design of the mixing proportions, parameters for a planting concrete formulation to support the growth of tall fescue are proposed. A system of evaluation indicators for plant growth in planting concrete was constructed by testing the growth status, above- and belowground biomass, and the total nitrogen and phosphorus content of tall fescue plants with different planting methods and different sowing densities.Cement: The test was performed using Hai Luo brand ordinary Portland cement of strength grade 42.5. The chemical composition and physical properties are shown in According to literature research, the suitable aggregate–cement ratio of planting concrete is between 3.75 and 5.33, and the water–cement ratios were selected as 0.25, 0.27, 0.29, 0.31, and 0.33 ,16,17. IFirst, 30% cement, 70% water, and all aggregates were mixed together in a forced single-shaft mixer for 60 s. This process allows the slurry to be fully mixed and evenly wrapped on the surface of the coarse aggregate. Then, 70% cement and 30% water were added and mixed for 120 s until the slurry layer was uniformly wrapped around the surface of the coarse aggregate and had a metallic luster. Finally, the well-mixed concrete mix was loaded into the test mold in three layers, with each layer being 1/3 of the overall test mold volume, and 15 poundings were inserted in sequence from the edge to the inside. After one layer of plugging and pounding was completed, the next layer of molding was carried out, and finally the specimen was manually compressed and the surface of the specimen was repaired and leveled, as shown in (1)Compressive strength: Compressive strength is an important indicator of the mechanical properties of planting concrete. To test the compressive strength of the planting concrete, cubic samples of planting concrete with dimensions of 150 mm × 150 mm × 150 mm were used . There wcf is compressive strength at 7 days and 28 days (MPa), F is the breaking load of theplanting concrete sample (N), and A is the cross-sectional area of the specimen (mm2).(2)W1 was weighed. After the mass was soaked in water for 24 h and saturated with water, its mass in water W2 was weighed. The connective porosity is given in Equation (2).Porosity: The porosity of planting concrete can be classified into connective porosity and gross porosity. The connective porosity is an important indicator for positive plant growth in planting concrete (porosity in the subsequent text refers collectively to connective porosity). The specific test is as follows : After laP is the connective porosity of the specimen, W1 is the mass of the specimen in air after 28 days of curing, W2 is the mass of the specimen in water after 24 h of immersion, V is the volume of the specimen, and ρw is the density of water. The connective porosity of the planting concrete is taken as the average of three specimens.(3)Surface porosity analysis: A rock cutter was used to slice the cubic standard specimen into layers, and the specimen was evenly cut into 5 pieces with a slice thickness of 30 mm. The upper and lower surfaces of the cut section should be parallel and the surface should be smooth. The cut surfaces were polished with 150-grit sandpaper for more than 20 min to eliminate the scratches caused by the cut sections so that the surface of the section was smooth and flat and the structure of the hole was visible. A digital camera was used to photograph the concrete slices, and the images were equalized and grayscale-processed. Combined with the histogram image features, the pore grayscale values were judged to be in the range of 50–80, and the image binarization was achieved using the im2bw function in the mathematical software. The processing result is shown in bP is the porosity of the specimen section plane, iA is the area of pore number i, and tA is the area of the plane.(4)SEM microscopic experiment: For SEM specimen preparation, concrete specimens of 20–40 mm grade with 0.29 water–cement ratio were cured to 7 days age and broken. A block with a section of about 1 cm × 1 cm × 1 cm was taken and the section was left untreated; the specimen sections were left untreated and then put into anhydrous ethanol for 48 h to end hydration. A small piece of the specimen was glued to the sample table and surface gold plating was performed to increase the electrical conductivity, and the thickness of the gold spray was about 20 nm. The sample was tested by SEM using a Gemini SEM300 scanning electron microscope  for SEM testing of the sample morphology, and the test was performed using a secondary electron SE2 detector.(5)Planting experiment: Tall fescue was selected for planting in the experiment, and the seeds are shown in (6)2SO4–H2O2 decoction method, and the total phosphorus content was determined by the alkali fusion molybdenum antimony anti-colorimetric method.Determination of biomass and elemental levels in plant leaves and roots: After 50 days of growth, tall fescue plants grown with different planting methods and planting densities were taken as samples. The tall fescue plants were removed from the planting concrete completely; the stems and leaves were separated from the root system with scissors, and the root system was rinsed with distilled water. Each pot of stem and root samples was separately placed in a 115 °C oven for 15 min to inactivate the enzymes and then dried at 75 °C. Three tall fescue plants were taken for measuring the biomass of stems, leaves, and roots, and another three plants were taken for measuring the total nitrogen and phosphorus content in tall fescue. The total nitrogen content was determined by the HThe effect of the water–cement ratio on the porosity of the planting concrete is shown in 2. At an aggregate size of 20–40 mm, the planar porosity of the planting concrete is 29%, with a low number of planar pores but the existence of large pores.The area of each pore in the plane of the planting concrete is shown in The average diameter distribution of the pore space in the plane of the planting concrete is shown in 2 of the exponential relationship equation The average diameter of planting concrete versus planar pore area is shown in A reasonable porosity has a positive effect on plant growth, but porosity and compressive strength are in inverse proportion to each other. Therefore, it is necessary to study the relationship between water–cement ratio, porosity, and compressive strength at the same time.The development of the compressive strength of the concrete is shown in This is due to the existence of a great number of pores within the planting concrete, which allows the cement and water to come into full contact at an early stage, and thus the hydration is adequate. As shown in 2 of 0.97. This indicates that it is best at describing the correlation between porosity and strength and therefore expresses the relationship more appropriately. It shows that the model can effectively describe the relationship between the compressive strength and the porosity of the planting concrete.Experimental studies have been carried out on the relationship between porosity and strength of different porous materials. Hasselmann et al.  proposed2 [According to the results of the porosity and compressive strength tests, the porosity and compressive strength of the planting concrete specimens with 20–40 mm aggregate gradation and 0.29 water–cement ratio are 29.7% and 8.1 MPa, respectively, which can satisfy the needs of plant growth and are suitable for practical projects. Therefore, the planting concrete with these proportions was selected for the planting experiment, and the seeds were spread by hand at an amount of 30–40 g/m2 . After sSelected planting concrete specimens with the gradation of 20–40 mm and the water–cement ratio of 0.29 were sown with 4.5 g and 9 g, and the sowing method was mixed with surface sowing. Mixed planting consists of placing concrete blocks on the surface of the soil and then pouring soil and seeds with water into the holes of the concrete blocks; surface sowing consists of placing concrete blocks on the soil surface and then spreading the seeds on the surface over the holes in the concrete blocks. After sowing, the surface is covered with a layer of loose soil 0.5–1 cm thick and sprayed with water to avoid soil loss. After the planting is completed, daily watering is performed to ensure that the top and bottom of the concrete blocks are saturated with water.(1)The porosity of planting concrete decreases with increasing water–cement ratio, and the larger the aggregate particle size, the greater the porosity at the same water–cement ratio.(2)With the same water–cement ratio, the porosity of the planting concrete prepared with 10–30 mm aggregates is lower than that of the planting concrete prepared with 20–40 mm aggregates. The average diameter of the planting concrete shows an exponential relationship with the porosity of the planes; the exponential relationship equation is (3)With an aggregate gradation of 10–30 mm, the optimum water–cement ratio should be controlled at 0.31–0.33, when the compressive strength ranges from 6.90 to 7.10 MPa and porosity is 30.8–31.0%. With the aggregate gradation of 20–40 mm, the optimum water–cement ratio should be controlled at 0.28–0.30, at which point the compressive strength ranges from 7.75 to 8.10 MPa and the porosity ranges from 29.8 to 30.5%.(4)2 was calculated, and it was found that the exponential model The growth of the compressive strength of the planting concrete is rapid in the early stages, with a linear relationship between the 28-day compressive strength and the 7-day compressive strength: (5)Tall fescue can adapt to a degree of acidity and salinity and is a resilient growing plant, suitable for planting on planting concrete. The height of all 10-day plants was around 10 cm, the root system reached 7 cm in length, and the roots were entering the internal pores of the concrete. The roots of the 25-day plants reached a length of 12 cm and were able to puncture a 10 cm thick planting concrete test block.(6)The effectiveness of planting concrete is influenced not only by its own properties, but also by the way in which the plants are planted and the density at which they are planted. The selection of surface planting methods with a reasonable seed density can achieve excellent planting results. In addition, plant height, cover, number of individuals and root condition around and at the base of the concrete block, leaf rootstock element content, and aboveground and belowground biomass can be used to assess the vegetation performance of the planting concrete.


The sensitivity, specificity, positive, and negative predictive values of mPCR were 93% (95% CI 84–100), 99% (95% CI 99–100), 68% (95% CI 54–83), and 100% (95% CI 100–100), respectively. The overall coefficient of agreement between mPCR and standard culture was 0.80 (95% CI 0.68–0.89). Intensivists changed empirical antimicrobial therapy in only 14% (18/125) of cases. No new antibiotic was initiated in more than half of the CAP/HAP pneumonia-suspected cases  and in more than one-third of those suspected to have VAP without affecting or delaying their antimicrobial therapy. Conclusions: Rapid mPCR was feasible on blinded PTC with good sensitivity and specificity. New antibiotics were not initiated in more than half of patients and more than one-third of VAP-suspected cases. Further studies are needed to assess mPCR potential in improving antibiotic stewardship.Background: Diagnosis of co/superinfection in patients with Acute Respiratory Distress Syndrome (ARDS) is challenging. The FilmArray Pneumonia plus Panel , a new rapid multiplex Polymerase Chain Reaction (mPCR), has never been assessed on a blinded protected telescope catheter (PTC) samples, a very common diagnostic tool in patients under mechanical ventilation. We evaluated the performance of mPCR on PTC samples compared with conventional culture and its impact on antibiotic stewardship. Methods: Observational study in two intensive care units, conducted between March and July 2020, during the first wave of the COVID-19 pandemic in France. Results: We performed 125 mPCR on blinded PTC samples of 95 ARDS patients, including 73 (77%) SARS-CoV-2 cases and 28 (29%) requiring extracorporeal membrane oxygenation. Respiratory samples were drawn from mechanically ventilated patients either just after intubation ( The test is a semi-quantitative approach to detect a panel of 15 bacteria and a qualitative approach to detect three atypical bacteria, nine viruses, and seven antibiotic resistance genes within 1.5 h from sputum, endotracheal aspirate, or bronchoalveolar lavage (BAL) specimens draw. The performance of mPCR has not been assessed on samples of a protected telescopic catheter (PTC), although the latter is the most commonly employed tool to diagnose nosocomial pneumonia in many countries, including France  known colonization, chronic obstructive pulmonary disease, bronchial dilatation, dialysis, solid organ transplant recipients).We conducted a monocenter retrospective analysis on 95 critically ill patients admitted to two ICUs of Henri-Mondor University Hospital between March and July 2020. During that period and in compliance with the recommendations of the French Society of Microbiology , Gram st3 colony forming units/mL). PTC was performed as previously described  , and nine bacteria that the culture failed to detect . Four of those nine bacteria were identified by culture in previous samples (Staphylococcus aureus (n = 1); Streptococcus agalactiae (n = 1); Pseudomonas aeruginosa (n = 1); and Legionella pneumophila (n = 1). In seven of the thirteen mPCR-detected cases, the patients had already been on an antibiotic active against the causative bacteria at the time of respiratory sampling.The 13 bacteria identified by mPCR (in 11 patients) included four bacteria which were equally isolated by culture but below the threshold [Burkholderia cepacia, Citrobacter spp., Staphylococcus lugdunensis, Corynebacterium accolens, and Enteroccocus faecalis) and two covered by the panel yet only revealed by conventional culture (Klebsiella aerogenes and Staphylococcus aureus).The seven bacteria identified above the threshold by culture included five bacteria not spanned by the panel .Overall, eight bacteria were identified below the threshold, four by both methods (see above), and four by culture alone (3 CFU/mL).Five CAP/HAP were documented , and nineteen VAP were diagnosed , 99% (95% CI 99–100), 68% (95% CI 54–83), and 100% (95% CI 100–100), respectively . The senblaCTX-M, one blaOXA 48, and one blaNDM), and two false positives for Methicillin resistance of Staphylococcus aureus (mecA/C with MREJ).mPCR test detected eight antibiotic-resistant gene carriers, including six true positives (four n = 29) and more than one-third of VAP-suspected patients .Based on the results of mPCR alone, the intensivists did not initiate any antibiotic therapy in ten (8%) cases, did not change ongoing antibiotic therapy initiated before  or after , suspecting pneumonia in them, but did modify empirical therapy in 18 (14%) cases  (to a narrower spectrum), whereas the negative results led mainly to no change in antibiotic therapy   than to escalation , whereas the negative results more often led to no change in antibiotic  than to de-escalation  (to a narrower spectrum)  . In the pectrum) . All ninWe herein showed that mPCR has an overall good performance upon using PTC as the diagnostic sampling technique. mPCR seems to be a useful tool to guide antibiotic stewardship in ARDS patients in the absence of direct smear examination. No new antibiotic was initiated in nearly half of the patients suspected to have pneumonia and more than one-third of those suspected to have VAP.mPCR performance with PTC is consistent with the findings of previous studies that examined mPCR with other sampling methods where a direct examination was available ,15. ThisCitrobacter spp., Hafnia alvei, and Morganella morganii) and some opportunistic non-fermentative Gram-negative bacteria species . For all those reasons, in a strongly suspected case of VAP, albeit with negative mPCR, empiric broad-spectrum antimicrobial therapy must still be administered.According to the guidelines, antibiotic therapy should be started as soon as possible in severe cases suspected to have VAP or HAP. However, in the recent surviving sepsis campaign guidelines, in adults with possible sepsis and not in shock, a time-limited, rapid investigation is advised . MoreovemecA/C and MREJ were not exceptional [A potential concern of PCR-based methods is that they may detect residual nucleic acids rather than viable material. In our study, four samples were mPCR-positive and culture-negative, and showed the same microorganisms that had already been found in the culture of previous samples, i.e., mPCR detected their residue . Detectieptional ,15.Our study has the following limitations. First, it was conducted in a single center on ARDS patients. The number of patients was relatively small. A higher number of patients could have increased the reproducibility and statistical relevance of this study. However, the rate of documented CAP/HAP is consistent with that found in multicenter studies of coinfection at ICU admission ,20. SimiWe herein report the feasibility of mPCR on PTC samples. mPCR offers good potential to improve antimicrobial stewardship. A solid step that opens the door widely for randomized control trials where patients either receive treatment guided by results of the mPCR test or standard care.


The increase in steel fiber volume content slightly enlarged chloride penetration depth, while the higher concentration of sodium hydroxide solution was beneficial as it improved chloride penetration resistance. The results suggest that although ultra-high compressive strength can be achieved, the durability issues of steel fiber reinforced slag/metakaolin-based geopolymer concrete still need considerable attention.Ultra-high performance geopolymer concrete (UHPGC) has been favored due to its excellent sustainability and outstanding mechanical properties. This study was conducted to explore the mechanical and durability properties of slag/metakaolin-based UHPGC with steel fibers reinforcement. The uniaxial compression test and rapid chloride migration test were conducted to measure the compressive strength and chloride penetration resistance of UHPGC. A total of nine groups of mixture proportions were designed and tested to investigate the influences of steel fiber dosage and sodium hydroxide (NaOH) solution concentration. The results showed that an increased steel fiber dosage and alkali concentration can improve compressive strength, and the maximum compressive strength can reach more than 140 MPa. In addition, the rapid chloride migration test showed that the chloride penetration resistance of the slag/metakaolin-based concrete was moderate, with a non-steady chloride migration coefficient ranging from 6.5 × 10 The increasing need to improve the performance of concrete materials has resulted in the invention of ultra-high performance concrete (UHPC), which has been favored due to its superior compressive strength, high blast-resistance, excellent abrasion resistance, and good durability ,2. HowevIn terms of geopolymer concrete, Thomas et al.  summarizIn recent years, ultra-high performance geopolymer concrete has been proposed by adding steel fibers into geopolymer concrete, which can reach comparable and even better properties compared to those of UHPC ,24. Liu Contrary to the extensive studies focusing on mechanical properties, durability issues of UHPGC have received relatively less attention. Researchers have studied the chloride resistance of UHPGC since chloride is a major deleterious ionic species that can cause corrosion in embedded steel reinforcement ,29,30,31As summarized in the literature review, remarkable progresses have been made regarding the mechanical properties of UHPGC, and various influence factors, such as fiber dosage, fiber type, and alkali molarity, have been investigated in previous research. However, most of the studied materials were based on single-phase precursors, such as slag and fly ash, while the mechanical performance of slag/metakaolin-based UHPGC were seldom reported. In addition, although the durability aspects of UHPGC have attracted attention in academia, the research on both the mechanical and durability performances of UHPGC, especially for slag/metakaolin-based UHPGC, is inadequate, and understandings of different influence factors on both aspects are also insufficient.Regarding the abovementioned knowledge gap, an experimental study concerning both the mechanical and durability properties of slag/metakaolin-based UHPGC was conducted. Firstly, the influence of steel fiber dosage and molarity of sodium hydroxide solution on the compressive strength of UHPGC was investigated. A total of nine groups of specimens with three different fiber volume contents  and NaOH solution concentrations  were designed. Then, a rapid chloride migration (RCM) test was conducted to determine and compare the chloride penetration resistance of UHPGC with different fiber dosages and NaOH solution concentrations in the alkali activator solution. Summaries and conclusions derived from the obtained test results are provided after the methods and results discussions.3, respectively.Ground granulated blast furnace slag, metakaolin, and silica fume were adopted as precursors to prepare the geopolymer binder, and their chemical compositions and loss on ignitions (LOI) are listed in Nine groups of specimens were designed with different fiber dosages and sodium hydroxide concentrations to investigate the influence of steel fiber dosage and the molarity of sodium hydroxide solution on both compressive strengths and chloride penetration resistance. The detailed mixture proportions are provided in The alkaline activator solution was prepared in advance and cooled for 24 h due to the exothermic effect when dissolving sodium hydroxide solids. The precursors, including ground granulated blast furnace slag, metakaolin, and silica fume, were mixed in a mixer for about 2 min. Subsequently, the river sands were added with the mixer continuously working for 1 min. The alkaline activator solution was then gently and uniformly poured into the mixture within 1 min and mixed for 3 min. Then, the steel fibers were added into the mixture and mixed for 2 min in order to obtain a uniform distribution. Finally, the mixture was poured into molds and covered with a plastic film to avoid moisture evaporation. The specimens were demolded after 24 h and cured in laboratory condition with a temperature of 20 ± 2 °C and a relative humidity of 72 ± 3%.The compressive strength of cubic specimens sized 70.7 mm × 70.7 mm × 70.7 mm were tested using the universal testing machine. The loading rate was set as 1 mm/min, and the averaged compressive strength of three specimens in each group was calculated.nssmD signifies the non-steady chloride migration coefficient (×10−12 m2/s); T represents the average value of the initial and final electrolyte temperature (°C); L represents the thickness of the sample (mm); U represents the applied voltage (V); t represents the test duration in hours; and dx represents the average penetration depth of the chloride ions (mm).In addition, a RCM test was conducted following the NT Build 492 standard . The cylThe typical failure modes of the UHPGC specimens under the uniaxial compression test are shown in In addition, the failure modes were also different for the specimens produced using the alkali activator solution with the same molarity of sodium hydroxide  where strength , and botstrength . TherefoChloride induced corrosion has always been a deleterious factor influencing the durability performance of concrete structures serving marine and saline environments ,39. The −12 m2/s to 14.1 × 10−12 m2/s. According to a recent study by Noushini et al. [−12 m2/s and 79 × 10−12 m2/s, which were approximately 5 times higher than chloride migration coefficients of slag/metakaolin-based geopolymer concrete. The relatively lower chloride penetration resistance of the fly ash/slag-based geopolymer concrete may be caused by the reduced chloride binding capacity due to the addition of low calcium fly ash.The non-steady chloride migration coefficients measured using the RCM test are listed in i et al. , chloridThe impact of the steel fiber volume content in the geopolymer matrix is shown in The joint influence of steel fiber volume content and NaOH solution concentration on the non-steady chloride migration coefficient is plotted in It should be noted that NT Build 492 was originally proposed based on ordinary Portland cement concrete. The influence of pore solution pH on the color contour of white silver chloride depositions cannot be comprehensively considered for geopolymer concrete in which the chemistry of the pore solution would be different from ordinary Portland cement concrete . In otheIn this study, the mechanical and durability properties of slag/metakaolin-based UHPGC were investigated by conducting uniaxial compression tests and rapid chloride migration tests. The influence of steel fiber dosage and NaOH concentration in alkali activator solution was analyzed. Based on the experimental results, the following conclusions can be made.The addition of steel fibers can effectively limit cracks propagation because of the bridging effect. The maximum compressive strength of geopolymer concrete without steel fibers can reach 100 MPa, and adding steel fibers up to 2% can further increase the compressive strength to 140 MPa.Increasing the molarity of alkali activator solution within the range of 12 mol/L can improve compressive strength due to the facilitated geopolymerization reaction. More significant improvement in compressive strength was observed when the sodium hydroxide concentration increased from 8 mol/L to 12 mol/L.−12 m2/s to 14.1 × 10−12 m2/s. A higher steel fiber dosage slightly decreased the chloride penetration resistance, which is possibly attributed to steel fibers corrosion, current enrichment, and rising temperatures due to fiber segregation.The non-steady chloride migration coefficient measured using the RCM test ranged from 6.5 × 10A higher alkali concentration in the alkali activator solution could significantly mitigate chloride penetration, which is mainly because the facilitated geopolymerization reaction in a higher alkali environment can result in a lower porosity and decrease chloride penetration depth.