Static Concentration Research Articles

Modeling gas holdup in a multiphase oxygen slurry bubble column reactor for Cu-Cl hydrogen production using CFD

The hydrodynamics of the oxygen bubble column reactor is investigated numerically using CFD analyses to predict the values of the gas holdup using Eulerian model and k−ε turbulence method. It is shown that, at any given static liquid height and solid concentration, increasing the superficial gas velocity leads to a higher gas holdup. Also, the gas holdup reduces when the static liquid height increases and/or the solid concentration increases at any given superficial gas velocity. All gas holdup findings were verified by experimental results from prior literature, showing excellent agreement and validating the models' applicability to this kind of a slurry bubble column system. Profiles of gas holdup obtained from CFD simulations were shown to generally under-predict the experimental data. Also, it is shown that CFD models accurately anticipated the experimental effects of the superficial gas velocity, static liquid height, and solid concentration on gas holdup.

Microseismic comprehensive evaluation method for coal burst: a case study in the Zhaolou Coal Mine

To explore the multiparameter precursor characteristics of pre- and post-coal burst. Based on a coal burst of LW 1305 in the Zhaolou Coal Mine, an early warning method combining stress‒strain curve and microseismic multiparameter is proposed. The research results show that coal burst was induced by the intrinsic static high-stress concentration and the strong external impact loading generated by fracturing of the key stratum. The precursors mainly characterize the enhancement trend of the S value, the sudden and sharp increase in the A(t) value, the continuous and abnormal decrease in the b value, the increasing absolute value of Z sharply and larger than 2, the continuous and abnormal decrease in the Qt value, and the dominant frequency moving to the low-frequency band. Essentially, many micro-fissures inside the key stratum initiated, converged and connected to form macro-fractures, which was verified by the attenuation rate of the K value. Considering the time-varying effect of the overlying stratum movement, the curves of the six parameters agree well with those of stress vs. strain, which indicates that it is reasonable to take the observed zone as a whole system to investigate the variation in the multiple parameters and fracturing of the key stratum. The research results can be applied to the monitoring, early warning and control of coal burst so that effective safety measures can be taken in real time.

Obavezno osiguranje vlasnika motornih vozila od odgovornosti između slobode ugovaranja i prinudne kartelizacije

The European Union enacted directives on motor vehicle liability insurance to accomplish the goals of free movement of persons and equal protection of third parties against damages caused by using motor vehicles. Serbia has been harmonising its legislation with the EU insurance acquis for several decades. Regarding motor vehicle liability insurance, market liberalisation has been prevented by the Law on Compulsory Insurance in Transport – LCIT 2009. LCIT authorised the Association of Insurers of Serbia to determine minimal premium prices with the consent of the National Bank of Serbia – NBS and stipulated mandatory Bonus-Malus System – BMS. Effectively, the NBS laid down minimal premium prices applicable within the BMS grades and conditions for the application of bonuses and maluses. The author analyses EU legislation and the case law of the Court of Justice related to fixing insurance premiums, mandatory BMS and competition law issues in the motor vehicle liability insurance market. The BMS in several EU member states has been compared with the BMS in Serbia. Competition in the motor vehicle liability insurance market in Serbia has been prevented as a consequence of the fixed premium prices and mandatory BMS. The author has also analysed the negative effects of the current legal framework on the motor vehicle liability insurance market structure, pointing out the static market concentration level and the substantial share of motor vehicle liability insurance premiums in the total insurers’ income. It is essential to amend LCIT without delay to liberalise the Serbian motor vehicle liability insurance market.

Fatigue load spectrum generation of Indonesian high-speed trains

The high-speed trains designed and constructed in Indonesia will use Aluminum alloy Al 6061-T6 as a structural material. Aluminum alloys are prone to fatigue failure due to the absence of endurance limit of the material, hence fatigue life prediction has to be carried out. Fatigue cracks could initiate at the defects of welded joints. Analyzing the fatigue load spectrum of critical locations in the train structures is crucial to predicting fatigue life. These critical locations are selected from areas with high static stress and stress concentration. The loads are analyzed using the multibody dynamic with rigid body assumptions and track roughness following UIC Standard Code 518. The finite element method is used to calculate the stresses from the loads generated by the multibody dynamic. The load sequence is further analyzed with rainflow counting method, and the load exceedance curve can be constructed. Finally, the Miner Linear Cumulative Damage Model is used to predict fatigue life.

The Influence of Time-Varying Sea Ice Concentration on Antarctic and Southern Ocean Numerical Weather Prediction

Abstract Although operational weather forecasting centers are increasingly using global coupled atmosphere–ocean–ice models to replace atmosphere-only models for short- and medium-range (10 day) weather forecasting, the influence of sea ice on such forecasting has yet to be fully quantified, especially in the Southern Ocean. To address this gap, a polar-specific version of the Weather Research and Forecasting Model is implemented with a circumpolar Antarctic domain to investigate the impact of daily updates of sea ice concentration on short- and medium- range weather forecasting. A statistically significant improvement in near-surface atmospheric temperature and humidity is shown from +24 to +192 h when updating the daily sea ice concentration in the model. The forecast skill improvements for 2-m temperature and dewpoint temperature are enhanced from June to September, which is the period of late sea ice advance. Regionally, model improvement is shown to occur in most sea ice regions, although the improvement is strongest in the Ross Sea and Weddell Sea sectors. The surface heat budget also shows remarkable improvement in outgoing radiative heat fluxes and both sensible and latent heat fluxes. This idealized research demonstrates the nonnegligible effect of including more accurate time-varying sea ice concentration in numerical weather forecasting. Significance Statement The purpose of this study is to understand how a more realistic Antarctic sea ice field may influence the skill of short- and medium-range weather forecasts. Many operational atmospheric numerical weather prediction (NWP) models use a static forecast field through the time frame of the model’s forecast—often 3–10 days. In this study, we updated the sea ice concentration field daily and compared the forecast outcomes with those from model runs using a static sea ice concentration field. We found the forecast skill of near-surface temperature and humidity show the most significant improvements in our idealized experiments. This indicates the importance of incorporating improved dynamic sea ice representation in Antarctic short- to medium-range operational weather forecasting.

Model-based learn and confirm: designing effective treatment regimens against multidrug resistant Gram-negative pathogens

Over the last decade, there has been a growing appreciation for the use of in vitro and in vivo infection models to generate robust and informative nonclinical PK/PD data to accelerate the clinical translation of treatment regimens. The objective of this study was to develop a model-based “learn and confirm” approach to help with the design of combination regimens using in vitro infection models to optimise the clinical utility of existing antibiotics. Static concentration time-kill studies were used to evaluate the PD activity of polymyxin B (PMB) and meropenem against two carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates; BAA2146 (PMB-susceptible) and BRKP67 (PMB-resistant). A mechanism-based model (MBM) was developed to quantify the joint activity of PMB and meropenem. In silico simulations were used to predict the time-course of bacterial killing using clinically-relevant PK exposure profiles. The predictive accuracy of the model was further evaluated by validating the model predictions using a one-compartment PK/PD in vitro dynamic infection model (IVDIM). The MBM captured the reduction in bacterial burden and regrowth well in both the BAA2146 and BRKP67 isolate (R2 = 0.900 and 0.940, respectively). The bacterial killing and regrowth predicted by the MBM were consistent with observations in the IVDIM: sustained activity against BAA2146 and complete regrowth of the BRKP67 isolate. Differences observed in PD activity suggest that additional dose optimisation might be beneficial in PMB-resistant isolates. The model-based approach presented here demonstrates the utility of the MBM as a translational tool from static to dynamic in vitro systems to effectively perform model-informed drug optimisation.

Early decrease of ionized calcium and static symmetric dimethylarginine concentration in a model of renal tubular necrosis in corn snakes (Pantherophis guttatus).

To determine if plasma concentrations of symmetric dimethylarginine (SDMA), N-acetyl-beta-d-glucosaminidase (NAG), GGT, ALT, AST, lactate, total calcium, and ionized calcium (iCa) and the calcium:phosphorus ratio are clinically relevant biomarkers to detect early stages of tubular lesions in snakes. 6 adult corn snakes (Pantherophis guttatus). Corn snakes were administered 11 injections of gentamicin at 50 mg/kg, SC, q 24 h in an experimental model of induced tubular necrosis. Plasma biochemistry and blood gas analyses were performed at baseline and after the 3rd and 11th injections. Parameters were compared between time points using a paired Wilcoxon test. In 3 individuals, renal biopsies were collected at baseline before starting injections and at the 3rd and 11th injections, while renal tissue samples were procured after euthanasia in all individuals. Renal proximal and distal tubular necrosis and hepatic steatosis were present in all individuals at necropsy. Compared to baseline, decreased blood concentrations of lactate, ionized calcium, and total calcium and a decreased calcium:phosphorus ratio were noted. A significant decrease of lactate and ionized calcium was observed after 3 days. Conversely, no changes in SDMA, NAG, ALT, AST, GGT, and sodium were detected. Ionized calcium and lactate concentrations were the earliest parameters to decrease compared to baseline values in this experimental model. While SDMA is a sensitive indicator of renal disease in mammals, this biomarker did not increase in a model of induced acute tubular necrosis in corn snakes.

Experimental and Computational Research on the Shear Performance of Partially Filled Narrow-Width Steel Box-UHPC-Combined Girders under Negative Moment Action

To examine the vertical shear behavior of narrow-width steel box-UHPC (Ultra-High Performance Concrete) composite beams with partial filling under negative bending moments, a total of six test beams were created and constructed in this study. The variables considered during the design and fabrication process included the flange thickness of UHPC, the amount of steel fibers in UHPC, and the height of the concrete filling. Reverse static concentration loading was applied to the beams. Compared to the C40 concrete flange, the cracking load of the 1/2 plate thickness UHPC flange and pure UHPC flange increased by 55.6% and 66.7%, respectively. The yield load witnessed a rise of 17.3% and 22.7%, while the ultimate load experienced an increase of 7% and 13.1%. This suggests that incorporating steel fibers can regulate the formation of cracks, enhance the flexibility of the flanges, and improve the overall shear capacity of the composite beams. When steel fibers were used in the amount of 2% of the concrete volume, the cracking resistance of the flange plate was increased by 16.7%. Partially filled and fully filled composite beams exhibited a 7.7% and 30.8% augmentation in cracking load, a 35.3% and 49.9% increase in yield load, and a 41% and 83.2% elevation in ultimate load when contrasted with composite beams devoid of concrete infusion within the steel box. The above observation implies that the incorporation of concrete within the steel box significantly improves the yield strength and ultimate shear capacity of the composite beams. The shear strength of the narrow-width steel box-UHPC composite beams, which are partially filled, shows a significant relationship with the experimental results when applying the principle of component superposition.

The Effects of Undercut Depth and Length on Weldment Mechanical Properties

Undercutting is a fusion welding defect that appears as a groove at the weld metal's toe. An undercut discontinuity forms when welding, particularly when the current is applied at an extremely rapid rate. It decreases the static and fatigue strength of the weld and produces stress concentration at the welding zone. The height of the reinforcement, the weld bead's contact angle, the undercut's breadth, depth, length, and root radius, as well as other factors, affect the stress concentration factor's size. In this study, two mild steel plates with a 20 mm thickness were welded together using gas metal arc welding. Each test plate was machined to have a 30° single bevel groove angle prior to welding. The butt welded plate underwent radiographic NDT testing. A weldment free of defect was created. The weldment was machined into typical test specimens for tensile strength. An undercut defect was simulated by drilling a groove through each tensile test sample. Grooves had different depths and lengths. After that, samples were put through a tensile test. The test findings allowed for the identification of the impacts of groove shape on tensile strength, ductility, and static stress concentration factor.

Determination of Stress Concentration Factor for a Stepped Bar Under Bending Loading: An Artificial Neural Networks Approach

Even today, charts and formulas derived from experimental determinations are used to obtain the stress concentration factor.Stress concentration factors from charts can be converted into numerical values using computational techniques. Stress concentration factor values were collected in a database and an Artificial Neural Network (ANN) model can be developed for improving the database. ANN model provides accuracy in obtaining the stress concentration factors. Using the static stress concentration factor for a stepped bar under a bending load we can quantify the impact of notches in fatigue.

Scattering of plane compressional waves by a variable thickness circular lined tunnel

The determination of the dynamic stress concentration factor (DSCF) associated to a circular lined tunnel with variable thickness liner incident upon by compressional P-waves is of particular interest. Due to the lack of symmetry, the treatment of such a problem via the traditional wave-function expansion method is not possible. To circumvent this dilemma it is proposed to employ the dynamic equivalent inclusion method (DEIM). As it will be shown, this method which is based on the notions of the eigenstress and eigenbody-force fields provides an accurate solution for the problem under consideration. In the simple special case where a tunnel with a concentric liner is subjected to plane compressional P-waves the exact wave-function expansion solution given in the literature is recovered. The effect of liner thickness variability on the static and dynamic stress concentration along the interior surface of the liner and along the liner-matrix interface is studied in detail through numerical examples. The maximum value of the DSCF for the concrete and steel liners with positive and negative values of eccentricity is obtained and compared with those of the corresponding concentric cases. It is observed that the eccentricity of the liner results in different behaviors of the stress concentration for the hard (steel) and soft (concrete) liners.

Translation of the efficacy of antibody-drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88.

Three semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) models, Simeoni, Jumbe, and Hybrid, were used for the efficacy translation of RC88 from preclinical to clinical. RC88 is a mesothelin-targeting antibody-drug conjugate for malignant solid tumor. In the preclinical study, the relationship between PKs and PDs was determined using the xenograft mouse model derived from ovarian cancer and lung cancer cell lines. A secondary parameter representing the efficacy index of the drug, termed as tumor static concentration (TSC), was calculated using the three semimechanistic PK/PD models. A mechanism-based target-mediated drug disposition model was used to predict the human PKs. TSC from mice and predicted human PK were integrated to predict human efficacy dose. Results showed that 2 cell lines were sensitive to drugs, and the predicted efficacy dose was between 0.82 and 1.96 mg/kg q1w.

Study on strength characteristics and thickening characteristics of classified-fine cemented backfill in gold mine

For some new mines, the utilization rate of tailings is not satisfactory when using unclassified tailings as backfill aggregate for cemented backfill. At the same time, with the progress of mineral processing technology, the tailings discharged by the concentrator gradually become finer. Therefore, cemented filling with fine-grained tailings as aggregate will become the development direction of filling technology in the future. In this paper, the feasibility of fine particle tailings backfill is studied by taking the particle tailings of-200 mesh as aggregate in Shaling gold mine. The calculation shows that the utilization rate of tailings is increased from 45.1% to 90.3% by using-200 mesh tailings as filling aggregate. The response surface central composite design method (RSM-CCD) was used to study the strength of backfill with alkali-activated cementitious material as binder by taking the mass concentration of backfill slurry and sand-binder ratio as input factors. The results show that the 28-day strength of the backfill with graded fine-grained tailings as filling aggregate can reach 5.41 MPa when the sand-binder ratio is 4, which can fully meet the needs of the mine for the strength of the backfill. The thickening test of-200 mesh fine particle tailings was carried out by static limit concentration test and dynamic thickening test. In the case of adding 35 g/t BASF 6920 non-ionic flocculant, the concentration of 64.74% tail mortar can reach 67.71% after 2 h of static thickening, and the concentration can reach 69.62% after 2 h of static thickening. The feeding speed of thickener should be controlled between 0.4 and 0.59 t/(m2 h). In this case, the underflow concentration of thickener is relatively high, which is 64.92–65.78%, and the solid content of overflow water is less than 164 ppm. The conventional full tailings thickening process was improved by using the design of high-efficiency deep cone thickener and vertical sand silo. The feasibility of fine-grained tailings as filling aggregate was demonstrated by combining the filling ratio test of fine-grained tailings, the data of thickening test and the improved thickening process. The research results can provide reference for other mines to use fine-grained tailings as filling aggregate to design filling system.

Theoretical model to predict the seismic drift concentration effect for self-centering-braced frame

This study is motivated to predict such drift concentration effects for SCB frames with the perfect flag-shape hysteretic behavior. Nonlinear time history analyses are conducted to compare and elucidate different deformation mechanisms between BRB and SCB frames. An elastic-plastic static model is established to predict the static drift concentration factor (DCFS) for the SCB frame under static lateral loads, where influential parameters include the column-to-frame stiffness ratios, α, and the SCB's post-yielding stiffness ratio, βk,2. To capture the dynamic loading effect, a regressive formula is further developed as the dynamic amplification factor by normalizing the dynamic drift concentration factor (DCFD) with the DCFS under static loads. The results show that unlike BRB frames with drift concentrated in the bottom story, SCB frames often feature peak story drifts in the top story. As opposed to BRB frames, the equivalent lateral loads do not feature an inverted triangle distribution but a parabolic distribution along the building height. The drift concentration effect for the SCB frame is reliably predicted by multiplying static DCFS with the corresponding closed-form formula for the dynamic amplification factor. The predicted DCFD is also utilized to identify a design range of βk,2 (i.e., 0.2–0.4) to effectively control the peak story drift and drift concentration for SCB frames.

Silk/Polyamidoamine Membranes for Removing Chromium VI from Water.

Polyamidoamine hydrogels prepared by the radical post-polymerization of α,ω-bisacrylamide-terminated M-AGM oligomers, in turn obtained by the polyaddition of 4-aminobutylguanidine with N,N'-methylenebisacrylamide, were reinforced with raw silk fibers, which can establish covalent bonds with the polyamidoamine matrix via reaction of the amine groups in the lysine residues with the acrylamide terminals of the M-AGM oligomer. Silk/M-AGM membranes were prepared by impregnating silk mats with M-AGM aqueous solutions and subsequent crosslinking by UV irradiation. The guanidine pendants of the M-AGM units imparted the ability to form strong but reversible interactions with oxyanions, including the highly toxic chromate ions. The potential of the silk/M-AGM membranes to purify Cr(VI)-contaminated water down to the drinkability level, that is, below 50 ppb, was tested by performing sorption experiments both in static (Cr(VI) concentration 20-2.5 ppm) and flow conditions (Cr(VI) concentration 10-1 ppm). After static sorption experiments, the Cr(VI)-loaded silk/M-AGM membranes could easily be regenerated via treatment with a 1 M sodium hydroxide solution. Dynamic tests performed using two stacked membranes and a 1 ppm Cr(VI) aqueous solution reduced Cr(VI) concentration down to 4 ppb. Remarkably, the use of renewable sources, the environmentally friendly preparation process, and the goal achieved meet eco-design requirements.

Failure mechanism and control of coal bursts triggered by mining induced seismicity in steeply inclined and extra thick coal seam

With the increase in mining depth, coal bursts have become a major challenge in the safe mining of steeply inclined and extra thick coal seams (SIETCSs). Based on a typical mining induced seismicity triggered coal burst (MSTCB) in SIETCS, a large-scale numerical model was developed using the Universal Distinct Element Code. The numerical model was calibrated and validated by laboratory results and field observations. The stress evolution, crack development and ejection velocity patterns in the MSTCB were analysed, and the effect of mining induced seismicity vibration velocity on the MSTCB was discussed. The results show that a triangular static stress concentration zone is formed in the coal on the roof side. And the high-energy mining induced seismicity leads to high dynamic stresses in the coal at the roof side rib and top of the headentry. Coal bursts occur under the superposition of static and dynamic stresses. The MSTCB results in tensile failure near the headentry surface and shear failure in the depth. The vibration velocity has a significant effect on the roof side rib and top of the headentry, while it has only a slight effect on the working face rib and bottom of the headentry. The dynamic stress and ejection velocity in the roof side rib and top of the headentry are positively correlated with the vibration velocity. Finally, measures for MSTCB prevention were proposed. The findings presented in this study can provide guidance for the prevention and control of MSTCBs in SIETCSs.

Evaluation of Fosfomycin-Sulbactam Combination Therapy against Carbapenem-Resistant Acinetobacter baumannii Isolates in a Hollow-Fibre Infection Model.

Static concentration in vitro studies have demonstrated that fosfomycin- or sulbactam-based combinations may be efficacious against carbapenem-resistant Acinetobacter baumannii (CRAB). In the present study, we aimed to evaluate the bacterial killing and resistance suppression potential of fosfomycin-sulbactam combination therapies against CRAB isolates in a dynamic infection model. We simulated clinically relevant dosing regimens of fosfomycin (8 g every 8 h, 1 h infusion) and sulbactam (12 g continuous infusion or 4 g every 8 h, 4 h infusion) alone and in combination for 7 days in a hollow-fibre infection model (HFIM) against three clinical isolates of CRAB. The simulated pharmacokinetic profiles in the HFIM were based on fosfomycin and sulbactam data from critically ill patients. Fosfomycin monotherapy resulted in limited bacterial killing. Sulbactam monotherapies resulted in ~ 3 to 4 log10 kill within the first 8 to 32 h followed by regrowth of up to 8 to 10 log10 CFU/mL. A combination of fosfomycin and continuous infusion of sulbactam led to a ~2 to 4 log10 reduction in bacterial burden within the first 24 h, which was sustained throughout the duration of the experiments. A combination of fosfomycin and extended infusion of sulbactam produced a ~4 log10 reduction in colony count within 24 h. This study demonstrated that fosfomycin in combination with sulbactam is a promising option for the treatment of MDR A. baumannii. Further studies are needed to further assess the potential clinical utility of this combination.

Foundations of static and dynamic absolute concentration robustness.

Absolute Concentration Robustness (ACR) was introduced by Shinar and Feinberg (Science 327:1389-1391, 2010) as robustness of equilibrium species concentration in a mass action dynamical system. Their aim was to devise a mathematical condition that will ensure robustness in the function of the biological system being modeled. The robustness of function rests on what we refer to as empirical robustness-the concentration of a species remains unvarying, when measured in the long run, across arbitrary initial conditions. Even simple examples show that the ACR notion introduced in Shinar and Feinberg (Science 327:1389-1391, 2010) (here referred to as static ACR) is neither necessary nor sufficient for empirical robustness. To make a stronger connection with empirical robustness, we define dynamic ACR, a property related to long-term, global dynamics, rather than only to equilibrium behavior. We discuss general dynamical systems with dynamic ACR properties as well as parametrized families of dynamical systems related to reaction networks. We find necessary and sufficient conditions for dynamic ACR in complex balanced reaction networks, a class of networks that is central to the theory of reaction networks.

Laboratory Protocol and Pilot Results for Dynamic Interference Testing of Continuous Glucose Monitoring Sensors.

Testing the potential influence of interfering substances on the measurement performance of needle sensors for continuous glucose monitoring (CGM) is a challenging task. For proper function, the sensors need an almost stable fluidic environment. Previously published in vitro interference experiments were measuring under static concentration conditons. Our experimental setup allows for interference testing with dynamic changes of the interferent concentrations. We designed a macrofluidic test stand that is fueled by several high-pressure liquid chromatography (HPLC) pumps generating programmable glucose and/or interferent gradients in phosphate-buffered saline (PBS). After optimizing experimental parameters (channel dimensions, temperature, flow rates, gradient slopes, buffer, pH etc.), we validated the setup using Dexcom G6 (G6) and Freestyle Libre 2 (L2) sensors with/without interferents, and using YSI 2300 Stat plus as the reference glucose device at room temperature. Both sensors tracked the programmed glucose changes. After calibration, G6 results closely matched glucose reference readings, while L2 routinely showed ~50% to 60% lower readings, most likely because of the factory-based calibration and temperature compensation. Gradients of maltose, acetaminophen, and xylose were employed to further validate the setup. As expected, both sensors were not affected by maltose. We confirmed previous findings regarding susceptibility of G6 readings to acetaminophen and L2 readings to xylose. Signals from both sensors are influenced by temperature in a linear fashion. Our experimental in vitro setup and protocol may provide a useful method to dynamically test CGM sensors for interfering substances. This may help to improve the accuracy of future CGM sensor generations.

In vitro activity of imipenem/relebactam plus aztreonam against metallo-β-lactamase-producing, OprD-deficient Pseudomonas aeruginosa with varying levels of Pseudomonas-derived cephalosporinase production

BackgroundTreatment options for metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa infections are limited. Imipenem/relebactam (I/R) plus aztreonam (ATM) may be an option. MethodsTen OprD(-) P. aeruginosa isolates (3 parent strains; 7 MBL-producers) were evaluated using checkerboard methodology and Fractional Inhibitory Concentration Index (FICI). Isolates exhibiting synergy in checkerboard studies (FICI ≤0.5) were evaluated using 24-h static concentration time-kill. Bacteria in late log-phase growth were diluted to 1 × 106 cfu/mL and incubated at 37°C for 24 h. Samples were drawn at 0, 2, 4, 6 and 24 h. Physiological fCmax, fCss,avg and fCmin of imipenem (26.7, 5.6, 0.5 mg/L), relebactam (REL; 13.1, 4, 0.8 mg/L) and ATM (62, 29, 8 mg/L) were used. Synergy in time-kill studies was defined as >2 log10 cfu/mL reduction compared with the most active individual agent. ResultsSynergy was observed in five isolates in checkerboard studies, including three of seven MBL-producing isolates. Isolates that were OprD(-) and harbored inducible Pseudomonas-derived cephalosporinases (PDCs) did not show synergy as defined by FICI; however, ATM minimum inhibitory concentrations (MICs) were significantly reduced with the combination. In time-kill studies, ATM alone was as active as combination regimens for MBL-producing isolates with deleted or inducible PDC production. For strains exhibiting constitutive PDC production, I/R plus ATM was synergistic at fCss,avg concentrations but exhibited similar activity to ATM at fCmin and fCmax concentrations. ConclusionsI/R plus ATM appears to exhibit synergy for some MBL-producing P. aeruginosa at physiological concentrations. Further study of the effect of dynamic concentrations is needed to fully understand the utility of this combination.