The Virtual Doctors charity (VDrs)4 uses a bespoke smartphone app to give remote telemedical advice to clinicians throughout rural Zambia. This approach links primary healthcare workers with volunteer doctors, predominantly based in the UK. We propose that this approach may be a valuable tool to promote antimicrobial stewardship (AMS) in these locations, and consequently that telemedicine can play a key role in preventing a future AMR pandemic.Antimicrobial resistance (AMR) presents a challenge to clinicians globally, particularly in low- and middle-income countries (LMICs) which often have a high prevalence of infectious diseases, coupled with limited diagnostic, treatment and surveillance capabilities.We carried out a systematic review to investigate current antibiotic prescribing practices in LMICs within sub-Saharan Africa, specifically the indications for use, choice of antimicrobial, and prescribing rates. Three Africa-specific databases, EMBASE, MEDLINE, Cochrane Library, Web of Science, Scopus, CINAHL, IRIS and Global Health databases were searched. English language studies evaluating antimicrobial use in primary care in LMICs in sub-Saharan Africa published between January 2010 and July 2021 were included. Data on the prevalence of antibiotic prescription, choice of agent and appropriateness was collated. We then reviewed anonymized prescribing data from the VDrs database, investigating antibiotic prescribing in cases over a period between January 2019 and June 2020. We excluded non-adult (<18 years old) patients, and reviewed cases that had been coded as ‘InfectiousDiseases’, ‘RespiratoryMedicine’ or ‘MedicineGeneral’ to identify those in which antibiotics were prescribed acutely and the impact of consultations on antibiotic prescriptions.Systematic review: 29 eligible studies from nine countries were identified, with 18 (62%) undertaken in urban settings and 7 (24%) encompassing rural settings. The prevalence of antibiotic prescription was 32.7%–84.4% , with respiratory and genitourinary infections the most common indications. The most prescribed antibiotics were β-lactams (primarily amoxicillin), then quinolones and metronidazole. Only two studies assessed the appropriateness of prescriptions, with 13%–36.4% found to be inappropriate. Retrospective cohort analysis of VDrs database: 502 cases were reviewed. 154 (30.7%) were receiving 1–3 antibiotic agents at the time of consultation. The most prescribed agents were metronidazole and amoxicillin. Following consultation, 53 patients (10.5%) were initiated on antibiotics. Of those already receiving antibiotics, 29.2% had these actively continued, and 45.5% had antibiotics rationalized or stopped based on volunteers’ advice.Our systematic review confirms high rates of antimicrobial prescription in LMICs in sub-Saharan Africa, with a significant proportion being inappropriate. However, data are limited, and mainly from urban settings, hindering the generalizability of results. Our analysis of VDrs data reveals that 45.5% of antibiotic prescriptions were rationalized through our telemedicine-based approach. The VDrs model aims not only to deliver case-based guidance to rural healthcare practitioners, but also provide long-term educational gains to enhance local and global health. We suggest that the appropriate use of telemedicine can have short- and long-term benefits for AMS in LMICs.


Gbind and ΔGbind⧧. Here, we report the calculation of the Gibbs energy barrier andGibbs binding energy by means of explicit solvent molecular simulationsfor the [Ga4L6]12– metallocageencapsulating a series of cationic molecules. The ΔGbind⧧ for encapsulation was estimated by means of umbrella sampling simulations.The steps involved were identified, including ion-pair formation andnaphthalene rotation  during theguest’s entrance. The ΔGbind values were computed using the attach–pull–releasemethod. The results reveal the sensitivity of the estimates on theforce field parameters, in particular on atomic charges, showing thathigher accuracy is obtained when charges are derived from implicitsolvent quantum chemical calculations. Correlation analysis identifiedsome indicators for the binding affinity trends. All computed magnitudesare in very good agreement with experimental observations. This workprovides, on one side, a benchmarked way to computationally modela highly charged metallocage encapsulation process. This includesa nonstandard parameterization and charge derivation procedure. Onthe other hand, it gives specific mechanistic information on the bindingprocesses of [Ga4L6]12– atthe molecular level where key motions are depicted. Taken together,the study provides an interesting option for the future design ofmetal–organic cages.The encapsulationof molecular guests into supramolecular hostsis a complex molecular recognition process in which the guest displacesthe solvent from the host cavity, while the host deforms to let theguest in. An atomistic description of the association would providevaluable insights on the physicochemical properties that guide it.This understanding may be used to design novel host assemblies withimproved properties  toward a given class of guests.Molecular simulations may be conveniently used to model the associationprocesses. It is thus of interest to establish efficient protocolsto trace the encapsulation process and to predict the associated magnitudesΔ The capability for tailoring the cavitiesof the SOCs has led to develop a rich host–guest chemistrywith many applications such as recognition of specific molecular targets,9 the purification of product mixtures,10 gas sorption,12 biomedicine,13 and catalysis.5Host–guestinteractions play an essential role in supramolecularchemistry, a rapidly growing field of research.The rules governing the specificity and strength of molecular bindingevents for these systems are complex. Among key questions is the exactcontribution of the different physicochemical variables involved inthe process of encapsulation. From the thermodynamic point of view,the process is governed by the Gibbs energy associated with the encapsulatingprocess. However, a molecular description of the process consideringthe flexibility of the cage, size, and shape complementarities, inbetween others, is highly desired.4L6]12–  (either based on force fields or quantum approaches).20 These works were focused at decodingthe particularities of the host–guest catalytic mechanism comparedto the reaction taking place in solution. Among the most strikingresults was the identification that the few solvent molecules thataccess the host cavity are fundamental for the catalytic effect providedby the supramolecular assembly. In these studies, however, anotherfundamental aspect in host–guest chemistry—the encapsulationprocess—was not addressed.Among the families of SOCsthat are receiving considerable attention,the self-assembled tetrahedral metallocage, [Ga6]12– 1, 1, develo4L6]12– SOC deforms to enlargean entrance for the passage of the guest, instead of transiently breakinga metal–organic ligand bond.22 Previous MM3calculations in the gas phase in combination with experiments of theguest displacement from the cage have been reported, although thesecalculations are based on constrained searches on the potential energysurface that do not account for the full flexibility of the system.23 However, uncovering the dynamics and structuralfluctuations of these supramolecular assemblies in solution is fundamentalto properly describe the process and for the rational design of novelcages.24The experiments on guest-exchange dynamics showed that the 12– metallocage (1)  for the encapsulatingprocess was also investigated. The atomistic description of this processrevealed very interesting motions in the metallocage and rearrangementsin the system.Here, we report a study aimed at both, establishing a computationalframework valid to calculate both Gibbs binding energies (Δcage (1) 1, which 22.11, contains a Ga3+ metal centeron each vertex of the tetrahedron. A bondedscheme was employed to describe these centers, according to whichthe interactions between the metal and its ligands were modeled usingharmonic potentials for bonds and angles , while rotations around metal–ligand bonds were not explicitlyincluded . Theparameters were derived using the Python-based metal center parameterbuilder (MCPB)36 developed by Merz andco-workers and based on Seminario’s method.37 The parameters of the bonding terms for the organic moietiesof the metallocage and for the guests were taken from the generalAMBER force field (gaff).39 Van der Waals parameterswere obtained from the optimized potentials for liquid simulationsforce field (OPLS),41 except those of the metal (Ga3+) taken from the universal force field (UFF).42 Atomic charges were computed by fitting themolecular electrostatic potential computed at the quantum mechanics(QM) level  level, as described below. The antechamber44 program was used to assign atom types and to derive atomiccharges  using the Gaussian 09 program.48 The SDD pseudopotential49 and related basis set complementing with a set of d polarizationfunctions50 were used for gallium, whilethe 6-31G(d) basis set51 was used for allother atoms. Optimizations were performed separately for the metallocageand each ligand, both in the gas phase and using the SMD solvationmodel50 to account for solvation effects.Binding energy estimates at the QM level account for thermal effectsvia the quasi-rigid-rotor-harmonic-oscillator (quasi-RRHO) approach.52 The standard state correction53  was also included.DFTgeometry optimizations were performed with the B3LYP-D3 functional54 employingthe default probe radii. The molecular surface areas of the metallocagewere calculated using UCSF Chimera.55The cavity volumes for the metallocage were obtained using theCAVER Analyst 1.0 software tool2.356 The MD simulation box,of size 46 × 49 × 47 Å and treated under periodic boundaryconditions, contains metallocage 1, the guest, 11 potassiumcounterions, and ∼2500 water molecules (TIP3P).57 The simulations were performed at constant temperature and pressure . A cutoff of9 Å was used for nonbonded interactions, with long-range electrostaticsinteractions accounted by the PME method.59 A time step of 2 fs was used in plain MD simulations, whereas forGibbs energy calculations, different time steps were used accordingto recommendations from the literature.MD simulationswere performed using the CUDA version of the pmemd program from theAMBER 16 package.Gbind) of each ligandwere computed using the attach–pull–release (APR) method.60 This method allows for precise calculationsof supramolecular host–guest binding, and may thus also beused to evaluate and optimize force fields.60 Three dummy atoms were used to setup the restraints required bythe APR method, together with two atoms of the guest and three ofthe host . The distanceforce constant was set to 5.0 kcal/(mol Å2), whereasthe angle and torsional force constants were set to 100.0 kcal/(molrad2). The distance between one atom of the guest and onedummy atom placed at the bottom of the metallocage was increased by0.4 Å from 6 Å (guest inside the cage) to 24 Å (guestoutside) during the simulation. For each simulated window, equilibrationand accumulation included 500,000 minimization cycles, 1 ps NVT at10 K, 100 ps heating to 298.15 K, 250 ps NPT equilibration, and 2.5–25ns NPT production (depending on the standard error of the mean ofthe restraint forces). Hydrogen mass repartitioning allowed for atime step of 4 fs. Snapshots from APR simulation are shown in Figure S7.The absolute Gibbs energiesof binding (ΔGbind) werecomputed using alchemical transformations61 of guest 2 into guests 3, 4, 6, and 7 (ligand 5 was notconsidered here because of the spiro substituents).The transformations were performed for the bound and unbound statesusing 12 values of the alchemical coupling parameter . The windows were sampled sequentially (startingfrom λ = 0.00922), performing 10 ns NPT simulations each. SinceSHAKE was not applied during the alchemical transformation, a timestep of 1 fs was used. ΔΔGbind was estimated by thermodynamic integration. Averages of ∂H/∂λ for each window were computed on uncorrelateddata after removing the initial nonequilibrated part of the time series.62The relative Gibbs energiesof binding (ΔΔ2 was computed viaumbrella sampling.63 The distance betweenthe center of mass (COM) of the host (defined by the four Ga atoms)and the COM of the guest was selected as the reaction coordinate.A total of 38 windows (spaced by 0.4 Å) were used to cover therange between 0.7 and 15.1 Å (one further window was added inthe transition-state region). A harmonic potential with a force constantof 5.0 kcal/mol was applied to sample configurations in each window.The production time was 2.5 ns for each window, and before the productionrun, every window was minimized and equilibrated as described abovefor the APR method.60 A time step of 4fs was used. The weighted histogram analysis (WHAM) method64 was used to reconstruct the Gibbs energy profile.The PMF for the bindingof guest 31 ,65 over its smallerNMe4+, 3 10 and larger NPr4+, 6 65 counterparts.The supramoleculartetrahedral metallocage 1 1 offers 1 was centered on NEt4+ andconsisted in assessing an optimal parameterization procedure for thedifferent molecular entities compatible with the AMBER force field.Once the benchmark on this system was performed, the same protocolwas applied for the calculation of binding Gibbs energies of othercationic guests, which we compared to experimental data. Next, theGibbs energy profile for the whole encapsulation process was investigated.The first step in the computational study of guest encapsulationin 3.14L6]12–. One of the first questions in terms of modeling is to assess howthe presence of the solvent could affect the physicochemical propertiesof the metallocage and how this could influence the step of forcefield parameterization. We started by optimizing the geometry of themetallocage at the QM level. We observed significant differences betweenvacuum and continuum aqueous solvent conditions in terms of size andshape  is 5.8 kcal/mol for guest charges derivedin the solvent (entry 4–entry 1), whereas this effect accountsfor 9.1 kcal/mol when guest charges are derived in the gas phase (entry3–entry 2), respectively. The effect of guest charges, in turn,is 1.4 kcal/mol for host charges derived in the solvent (entry 1–entry2) and 1.9 kcal/mol for host charges derived in the gas phase (entry3–entry 4). The effect of host charges on the ΔGcalc.° is clearly higher than the effectof guest charges.The valuesshown in 3+ bonding parametersderived in the solvent shows that the effect of host charges derivedin the gas phase and solvent  is 3.8 kcal/mol for guest charges derived in thesolvent (entry 8–entry 5), whereas this effect is 3.2 kcal/molwhen guest charges are derived in the gas phase (entry 7–entry6). The effect of guest charges, in turn, is null for host chargesderived in the gas phase (entry 8–entry 7) and 0.6 kcal/molfor host charges derived in the solvent (entry 8–entry 5).As in the previous case, the effect of host charges on the ΔGcalc.° is larger than the effect of guestcharges, but the differences obtained are reduced.The analogous analysis taking GaGcalc.°)are concerned, regarding bonding terms for Ga3+ calculatedin vacuum or the solvent, those obtained in vacuum tendto give lower binding energies (more negative) than their counterpartsderived in the solvent (except for the comparison of entry 3 withentry 7). When all parameters are derived in vacuum  derived from implicit solvent DFT calculations provides avery good agreement with experimental Gibbs binding energies.3.23.2.13, 4, 5, 6, and 7) with known experimental values were calculated.Calculated and experimental energiesof binding are in very goodagreement for all guests 2. For co70 Converting guest 2 into each of the remaining guests, both in solution and encapsulatedin the metallocage, we estimated ΔΔG2 → j . The ranking of guestsbased on the ΔΔG values is in line withthe experimental trend. For guests 3 and 6, the estimates are consistent with the APR results , whereas for compounds 4 and 7,the difference in the computed ΔΔG issignificant. For guest 4, the FEP estimate is closerto the experimental data, whereas for guest 7, the APRestimate is closer to the experimental result. The relative potentialenergies of binding were calculated, but they fail to reproduce theexperimental trend (see Table S2).The computation ofrelative free energies of binding using alchemicaltransformations is a convenient technique to compare the affinityof ligands for a given receptor.2 and 4), whereas the lowest binding energies correspond to species bearingfour Me or Pr substituents . The binding energies of compounds 5 and 7, bearing two cyclic butyl substituentsand either two Me and two Pr substituents, respectively, lie in between.Moreover, guests with linear alkyl chains, 2 and 4  have a higher bindingaffinity than their cyclic analogue 5 ,which is consistent with the experimental observations on relativebinding affinities between n-alkanes (C5–C8)and their cyclic isomers.71 This agreementfurther validates the computational protocol and suggests that molecularsimulations may provide access to the molecular features that controlthe binding of guests to the SOC host. This is extremely relevantbecause the energetic behaviors between the different host–guestpartners are somehow counterintuitive. Indeed, one would expect somecorrelation between the size and shape of the substituent such asmethyl < ethyl < propyl. The simulations offer therefore a uniqueopportunity to better understand the molecular grounds of the energeticsof encapsulation.Importantly, calculated binding Gibbs energies with APR reflectthe same trend between encapsulation of compounds than those foundexperimentally 2. Thus, 3.2.272 several variablescould relate to such prediction: (1) the cavity volume of the hostalone, (2) the volume of the guest, (3) the packing values, that is,the ratio between the volume of the guest in front of the volume ofthe cavity of the host, and (4) the possible involvement of solventmolecules. It is likely although that the real relationship lies asa combination of these different factors.Owning a computational protocol thatcould help in defining therelative affinities of different guests to the same metallocage iscrucial in supramolecular chemistry and constitutes one of the objectivesof this work. Computing reliable binding affinities can be a precioustool for designing supramolecular hosts. Based on previous studieson supramolecular systems,1 in solution without any guest. Thevolume for the free state of the cage ranges from void (meaning noteven one solvent molecule could fit) to 480 Å3. Thenumber of water molecules inside the cavity varies from 0 to 15 (73 The number of K+ counterions in theclose environment of the cage (up to 11 Å from the COM of thecage) mostly fluctuates between 3 and 6 , with up to two K+ inside the cavity .We started analyzingthe metallocage  0 to 15 3a, with  3 and 6 S1, with Figure S5). The same occurs when plotting thevolume of the cavity and the volume of the guest, meaning that thestructuring of the cage was not only a product of the size of theguest alone . The correlationbetween binding Gibbs energy and volume of the guest is surprisinglygood, especially if guest 6 is not considered . The larger the Vguest, the greater (more negative) the Gibbs binding energy.This is accomplished until the volume of the guest overcomes a certainthreshold: all the guests fitting the correlation have a volume inthe range 80–160 Å3, whereas 6 has a volume of ∼200 Å3. Further analysisof the 6 ⊂ 1 complex reveals thatthis guest tends to be partially outside the cavity , thus explaining the reason why the binding energydecreases dramatically despite having a larger volume. Overall, forthose guests with a volume below the threshold, Vguest is an excellent predictive indicator for bindingaffinity trends. Those with larger volumes are expected to lie partiallyoutside the cavity, consequently having lower binding energies.The large variability of the sizeof the cavity of the cage clearlyindicates a high flexibility of the host. Importantly, these MD simulationssuggest that the flexibility of the cage enables adaptation of itscavity to the guest to be encapsulated. Our purpose was to look fora correlation, if any, between some properties of the host and guestand the binding process. Interestingly, no correlation is observedbetween the binding Gibbs energy and the size of the cavity  for the six systems under study in this work S5. The sVguest/Vcavity ratio : for 3,there are four water molecules (Vguest ∼ 80 Å3), for 5, there are threewater molecules (Vguest ∼ 120 Å3), for 2, 4, and 7,there are two water molecules (Vguest ∼150 Å3), and for 6, there are no watermolecules (Vguest ∼ 200 Å3). The Vcavity, in turn, remainsaround 300 Å3 for all the guests, except for 6, where the volume rises up to ∼450 Å3 . A comparisonamong the guests indicates that the larger the Vguest, the lower the number of water molecules inside the cavity.This allows keeping the packing values ranging from 0.55 to 0.63 (Table S1). These values are close to the theoreticalvalue of 0.55 proposed by Rebek,74 constitutinga rule of the thumb in supramolecular chemistry: the closer the packingto 55%, the better the binding affinity. For the case of 6, the packing coefficient is 0.45, in line with this guest havingthe least binding energy.Next, we analyzed the packing coefficient of the guest in the internalcavity of the molecular cage. In order to be able to calculate packingcoefficients, the presence of solvent molecules inside the cavity,if any, must be taken also into account. For that, we performed additional200 ns MD simulation for each of the guests. The analysis of the structuresalong the MD could identify the average solvent molecules inside thecavity .Thus, these two parameters are potentially useful for virtual screeningof the ability of this metallocage to bind a guest. To satisfy Rebek’srule on the packing coefficient, the solvent molecules present insidethe cavity need to be also considered, which can conveniently be obtainedby performing explicit solvent MD simulations. Overall, pure volumetricanalysis of the guests could be already indicative of the bindingaffinity with the metallocage. This also highlights that computationalapproaches, such as the one we tested here, could be a good ally forboth metallocage and guest selection and useful for supramoleculardesign.The results obtained up to here clearlyindicate that the APR methodprovides with very relevant results for the prediction of Δ3.363 and calculated the PMF associated with the entranceof a guest in the metallocage 1. Such kind of simulationsare computationally much more demanding than those to obtain bindingGibbs energies, and we thus decided to focus on the encapsulationof NEt4+, 2, in the metallocage. The second event consists in the penetrationof the guest from exterior into the internal cavity of the metallocage.The flexibility of the metallocage has beendemonstrated by thelarge variability of the size of the cavity shown during the MD simulations,as well as by encapsulating guests with different sizes and shapesinside the cavity. During the guest release and encapsulation, thedeformation of the metallocage by movements of six naphthalene-basedbisbidentate catechol ligands has been proposed, but the process hasnot been yet described at the atomic level in explicit solvents forany guest. Therefore, we intended to discuss this process in an illustrativeway from MD with an explicit solvent and counter ions. The generalrepresentation of the process is shown by the most populated molecularstructures in 4+·[Ga4L6]12–) forms at a distance of ∼6.6 Å between their respectivecenters of masses interactions between the C–H bonds of the guest and the amideoxygen of the metallocage. Moreover, the overall charge is also atplay. Interestingly, the internal cavity of the metallocage at thisstage is surprisingly small, with a volume lower than 30 Å3 (average of the cavity volumes of the three most populatedstructures). This is due to the fact that the naphthalene rings rotateto accommodate the guest, provoking that the inside cavity shrinksconsiderably (with no other molecules inside the cavity). Nevertheless,as previously shown, the system is dynamic and this volume fluctuates.The calculated Gibbs energy associated with this ion-pair intermediatestate is −3.4 kcal/mol relative to the free guest state . This shows that therotation of the naphthalene rings significantly modifies the accessiblecavity of the metallocage.Thefollowing step is the encapsulation of the guest from the ion-pairstate into the internal cavity of the metallocage . At this point,we observed that one of the naphthalene rings of the metallocage rotatesin the closing direction of the guest-entering face of the tetrahedronhost . There is a solvent water molecule found inside thecavity of the metallocage along with NEt4+;the calculated packing coefficient is 58%, which is quite close toRebek’s 55% rule74 and the classicalplain MD result (56%). This shows that the cage is able to vary itsvolume, trying to keep the packing coefficient close to the Rebekrule.After the guest passes through the transition statefor encapsulation,the encapsulated state is observed at a distance of 1.1 Å betweenthe COM of the metallocage and the COM of NEt3 are shown in + with three solvent water molecules, while the other  and the transition state (3.3 Å). The two cavities,with volumes of 129 and 188 Å+ (inside the cage) withthe guest (outside the cage). Nevertheless, the analysis of the distributionof the K+ cations shows that during most of the simulationtime, there are no K+ cations inside the cavity  and that the presence of K+ in one of the cavities formed during migration of the ligand ismore likely to be due to the proximity of the ions from the cage duringthe simulation. Our work suggests therefore that the mechanism proceedsby a simple encapsulation of the guest to the metallocage more thanan ion–ligand exchange process.The presence of the potassium at this particular step of the encapsulationprocess prompted us to hypothesize a mechanistic role of this ionand a possible exchange between K75 Moreover, the encapsulation of NEt4+ within the metallocage is found to be a spontaneousprocess with a rather low barrier. This is in line with the displacementexperiment: encapsulated NMe4+ in the metallocage 1 is readily displaced by NEt4+, andthe process is too fast to be monitored by 1H NMR spectroscopy.9The Gibbs energy barrierfor encapsulation is calculated to be2.4 kcal/mol from the ion-pair intermediate 5, whereaFrom a computational point of view, thebinding Gibbs energy estimatedfrom the PMF  is consistent with the APRresult . The small difference is likely dueto the different sampling strategies, probably limited in the umbrellasampling simulation at large host–guest separation.4This study shows that classical MD in anexplicit solvent withproper parameters provides the level of accuracy required for analyzingthe encapsulation of cationic species by a supramolecular metallocage.Importantly, for the sake of future modeling experiments on such kindsof systems, here, the best results were obtained when deriving theforce field parameters using QM calculation, accounting for solventeffects implicitly. The binding Gibbs energies were calculated tobe in very good agreement with the experiment.Vguest) and the Vguest/Vcavity ratio. Interestingly, theseparameters are available with low computational efforts. These correlationsshowed an outlier among the guests considered. It is the one thatdoes not fit into the cavity, lying partially outside, despite showinggood packing predictions. Calculated packing coefficients for theguests are in the range of 0.55–0.63, close to Rebek’sproposal of 0.55, provided that the solvent molecules inside the cavityare included in their evaluation, as revealed by the MD simulations.This work also sustains the validity of Rebek’s rule as a generaltrend to predict favorable encapsulation and also that atomistic modelingsuch as the one performed here can provide with information on whenthis rule reaches its limitations (mainly related to the shape andsize host–guest complementarity).The binding energiesof different guests to the metallocage werefound to correlate very well with the volume of the guest (The simulations allowedobtaining the atomic description for theencapsulation process. The encapsulation of the guest into the metallocagetakes place in two steps. First, an outer surface ion-pair intermediateforms: the guest faces one of the tetrahedron’s sides of thehost, which turns concave due to the conformation adopted by the naphthalene-baseligands. Then, entering of the guest into the metallocage is regulatedby the rotational movements of three naphthalene ligands of the metallocage;rotation of a naphthalene ligand creates two separate cavities. Afterthe guest passes through the transition state, the metallocage closesthe aperture and interacts with the guest by its interior surface.In the guest-encapsulated state, water molecules can be encapsulatedalong with the guest depending on the guest’s size, shape,and interactions.Overall, properly derived force field parametersin combinationwith statistical mechanics methods allow computing host–guestbinding energies for SOCs along with providing an atomic descriptionof the encapsulation process. This offers an interesting option forfuture development in MOC design.


In addition, 33 specimens were designed to study the bonding properties of duplex stainless steel bars to concrete. In this paper, the effects of concrete strength, duplex stainless steel reinforcement diameter, the ratio of concrete cover to reinforcing steel diameter, and relative anchorage length on the bond stress were investigated, and a regression model was established based on the experimental results. The results show that, with the concrete strength concrete strength from C25 to C40, the compressive strength of concrete increased by 56.1%, the bond stress increased by 27%; the relative anchorage length has been increased from 3 to 6, the relative anchorage length has doubled, and the bond stress has increased by 13%; and, the ratio of concrete cover to reinforcing steel diameter increased to a certain range on the bond stress has no significant effect and duplex stainless steel reinforcement diameter has little effect on the bond stress. The ratio of concrete cover to reinforcing steel diameter from 3.3 to 4.5 and the bond stress increased by 24.7%. A ratio of concrete cover to reinforcing steel diameter greater than 4.5 has no significant effect on the bond stress, with the average bond stress value of 20.1 MPa. The duplex stainless steel bar diameter has little effect on the bond stress for the diameters of 12 mm, 16 mm, 25 mm duplex stainless steel bar, and their average bond stress is 19.9 MPa.In recent years, as a result of the large-scale use of stainless steel bars in production and life, people’s demand for stainless steel bars has increased. However, existing research information on stainless steel bars is scant, especially the lack of research on the mechanical properties of duplex stainless steel bars and the bonding properties of duplex stainless steel bars to concrete. Therefore, this paper selects 177 duplex stainless steel bars with different diameters for room temperature tensile test, and then uses mathematical methods to provide suggestions for the values of their mechanical properties. The test results show that the duplex stainless steel bar has a relatively high tensile strength of 739 MPa, no significant yield phase, and a relatively low modulus of elasticity of 1.43 × 10 The corrosion of steel is a common durability problem for reinforced concrete structures, especially for offshore, harbor and hydraulic structures, and bridges in coastal areas, which are under harsh environmental conditions, such as long-term wet or alternating wet and dry conditions. The corrosion of steel bars not only affects the normal use of the structure, but it also shortens the service life of the structure and even directly endangers the safety of the structure. Repairing these corroded structures not only requires huge capital investment, but it also generates a lot of construction waste, which, in turn, causes a series of environmental problems. Therefore, countries around the world attach great importance to the study of steel corrosion and its protection technology. Currently, the primary measures for improving the durability of reinforced concrete structures and preventing premature and rapid corrosion of reinforcing steel are ,2,3: useResearch on reinforced concrete structures has remained consistent: Yue Liu  investigMost scholars currently use high-performance concrete to study the bonding performance of reinforced concrete. The study of stainless steel reinforcement is also austenitic, as duplex stainless steel reinforcement is not common in daily life; it has only become popular in recent years due to its excellent corrosion resistance and mechanical properties. Therefore, there is a lack of research on the bonding properties of duplex stainless steel reinforcement to concrete ,23. In tIn this paper, the model of 1.4362 duplex stainless steel bars is selected for experimental research. Its China code is Ensuring that the mechanical properties and bonding properties of duplex stainless-steel bars can meet the requirements of reinforced concrete structures is the prerequisite for the application. The mechanical properties include yield strength, tensile strength, elongation after break, and elastic modulus. According to GB/T 228.1-2010 “Room temperature tensile test method for metallic materials” , room teIn accordance with GB/T 228.1-2010 “Room temperature tensile test method for metallic materials” in the determination of the original cross-sectional area of duplex stainless steel bars, and then they are marked by continuous dots.The test was loaded by the strain rate control, and the strain rate was selected as 0.00025/s. A pre-tension force was applied before the test in order to eliminate the influence of the inaccurate fixture alignment and the bending of the specimen in the test. The pre-load rate was 10 MPa/s, and it stops when the pretension reaches 4% of the yield force. After preloading, a pre-calibrated electronic extensometer is installed on the specimen and then the loading is started according to the set loading procedure. After the specimen yields, the extensometer is quickly removed and then the specimen is stretched according to the set loading procedure until the specimen breaks.The final breaking position of the tensile specimens is different. The breaking point of some specimens is very close to the upper and lower clamps, and the breaking point of some specimens is in the middle. Through the investigation and statistics of 177 tensile samples, it is found that the sample is more likely to break near the identification symbol if there is a steel bar identification symbol in the parallel length range of the sample, as shown in When this phenomenon occurs, it is considered that the cross ribs of the duplex stainless steel ribs have played a strengthening role. The normal cross-rib spacing is about 2 mm and the cross-rib spacing at the identification symbol is about 4mm, which is to say, within the influence range of the identification symbol, the relative rib area is one-half of the other parts, forming a weak surface, as shown in Perform statistical analysis on the test data, and then obtain the average value of the mechanical indexes of the duplex stainless steel bars of various diameters, as shown in From the data shown in Hypothesis that Sort the measured data from smallest to largest and calculate the measured frequency Calculate the theoretical distribution of the distribution function Calculate the theoretical frequency Calculate the k: number of groups; and,r: estimate the number of parameters, which is 2 in this article.Look up the table, calculate In order to facilitate engineering applications and scientific research, the tensile strength, elongation after break, modulus of elasticity, and yield strength of the H0 is accepted, and the statistical analysis is calculated by normal distribution; otherwise, hypothesis H0 is rejected, and the goodness-of-fit test of the measured test data is performed again.Subsequently, hypothesis The measured tensile strength, elongation after break, modulus of elasticity, and yield strength of duplex stainless steel bars of each diameter from 16 mm to 32 mm were tested according to the steps, and the test results regardless of diameter are shown in The standard value of elastic modulus is calculated by Formula (8):The standard values of tensile strength, elongation after break, and yield strength are calculated using Formula (9):The standard values of tensile strength, elongation after break, elastic modulus, and yield strength of duplex stainless steel bars calculated by substituting the test data into Formulas (8) and (9), as shown in 5 MPa, 513 MPa.It can be seen from d) were chosen to be 12 mm, 16 mm, and 25 mm; the ratios of concrete cover to reinforcing steel diameter (c/d) were chosen to be 3.3, 4.5, 5.8, 7.3; duplex stainless steel bar relative anchorage lengths  chosen were 3, 4, 5, 6; the test protocol designed the specimens with these four factors as variables; and, the detailed parameters of the specimens are shown in The center pull-out test specimen size is relatively small when compared to the beam test, and the production cost is low, the test process is simple to operate, and it is suitable for the production of a large number of specimens to measure the duplex stainless steel reinforcement and concrete bond strength. The concrete strengths chosen were C25, C30, C40, and the concrete mix ratio is shown in The center pull-out test was carried out on a 1000 kN Xinsansi electro-hydraulic servo testing machine, and The duplex stainless steel reinforcement and concrete center pull-out test completed in this paper have two forms of damage: duplex stainless steel reinforcement pull-out damage and concrete splitting damage. The surface shape of the duplex stainless steel bars can significantly affect the form of damage, resulting in a rib height increase; rib spacing can be reduced to increase the bite of concrete and duplex stainless steel bars, in favor of increasing the bond stress. Some studies have shown that ,33: in tDuplex stainless steel bar pull-out damage2.Concrete splitting damageThe duplex stainless steel reinforced concrete bond stress is not uniformly distributed over its bond length, and the bond stress is calculated using Equation (10) to facilitate analysis.The bond stress between duplex stainless steel bars and concrete can be obtained while substituting various parameters into Formula (10), as shown in The effect of concrete strength on bonding performanceThere are three sets of specimens of the duplex stainless steel bar and concrete strength change in the concrete center pull-out test. In the specimens, the diameter of the stainless steel bar is 16 mm, the ratio of concrete cover to reinforcing steel diameter is 4.5, the relative anchorage length is 5, and the concrete strength is C25, C30, C40.In these three groups of a total of nine specimens, pull-out damage occurred in eight specimens, and the specimens in which splitting damage occurred were caused by improper test operations. It can be assumed that the concrete strength on the specimen damage form basically no effect. During the test, the stainless steel bar cross-rib will produce extrusion pressure on the concrete between the ribs; when the extrusion pressure reaches the limit of the concrete, the concrete in front of the stainless steel bar rib is crushed and the stainless steel bar is pulled out.The bond stress values for the concrete strengths of C25, C30, and C40 specimens were 17.4 MPa, 20.2 MPa, and 22.1 MPa, respectively, and the compressive strengths of the cubes that were poured simultaneously with the three groups of specimens were 28 MPa, 38.1 MPa, and 43.7 MPa, respectively. 2.The effect of duplex stainless steel bar diameter on bonding performanceThe duplex stainless steel bars and concrete center pull-out test in the stainless steel bar diameter changes in three groups of specimens: specimens in the concrete strength are C30, the ratio of concrete cover to reinforcing steel diameter are 4.5, and the relative anchorage length are 5; the duplex stainless steel bar diameters were 12 mm, 16 mm, and 25 mm.There are nine specimens in these three groups, and pull-out damage occurred in six specimens. Among them, splitting damage occurred in three specimens, C30R12T4.5L5-3, C30R25T4.5L5-1, and C30R25T4.5L5-3. This is because, during the test, the stainless steel bar cross-rib will produce extrusion pressure on the concrete between the ribs and, as the diameter of the stainless steel bar increases, the extrusion pressure increases when the concrete between the ribs reaches its limit. Splitting damage occurs when the tensile force on the surrounding concrete exceeds the tensile limit of concrete. Therefore, when the diameter of the duplex stainless steel bars increases, the specimens are more prone to splitting failure.The values of bond stress for duplex stainless steel bars with diameters of 12 mm, 16 mm, and 25 mm are 19.9 MPa, 20.2 MPa, and 19.6 MPa, respectively. 3.The influence of the ratio of concrete cover to reinforcing steel diameter on bonding performanceThe duplex stainless steel reinforcement and concrete center pullout test in the protective layer thickness changes in a total of four groups of specimens: specimens in the concrete strength are C30; stainless steel reinforcement diameter are 16 mm; the relative anchorage length are 5; the ratio of concrete cover to reinforcing steel diameter are 3.3, 4.5, 5.8, and 7.3; and, the four groups of specimens bond stress values are 16.2 MPa, 20.2 MPa, 20.1 MPa, and 20.0 MPa.These four groups of a total of 12 specimens; out of nine specimens with pull-out damage, splitting damage only occurred in the C30R16T3.3L5 group of three specimens. During the test, the duplex stainless steel bar will produce extrusion pressure on the surrounding concrete, so that the concrete is in a state of tension, as seen in the force schematic diagram presented in 4.Effect of relative anchorage length on bonding performanceThere are four groups of specimens in which the anchorage length of the duplex stainless steel reinforcement and concrete center pull-out test changes: the concrete strength is C30; the stainless steel reinforcement diameter is 16mm; the ratio of concrete cover to reinforcing steel diameter is 4.5; the bond stress values of the four groups of specimens are 18.9 MPa, 19.3 MPa, 20.2 MPa, and 21.3 MPa; and, the corresponding relative anchorage lengths are 3, 4, 5, and 6. In these four groups of a total of 12 specimens, pull-out damage occurred in all specimens. This indicates that the concrete around the duplex stainless steel reinforcement can provide a large enough tensile force to make pull-out damage occur in the specimens. The bond stress of duplex stainless steel bars is evaluated when considering the following influencing parameters: concrete strength, duplex stainless steel bar diameter, the ratio of concrete cover to reinforcing steel diameter, and relative anchorage length. The bond stress  shows the analytical expression that is derived for the bond stress of duplex stainless steel bars by using multiple linear regression analysis.Analyzing the above regression equation, it is found that the coefficient of The tensile process of duplex stainless steel bars is different from that of ordinary steel bars, which can be divided into three stages: elastic stage, strengthening stage, and necking stage. The mechanical properties of duplex stainless steel bars are stable, and their strength is high. Additionally, there is no significant yield strength, but the elastic modulus is low.Duplex stainless steel reinforcement center pull-out specimens have two forms of damage, respectively, pull-out damage and concrete splitting damage. In duplex stainless steel bars in the extraction process, its raised ribs will produce squeezing force on the surrounding concrete matrix. The squeezing force causes tension in the surrounding concrete. When this tensile stress exceeds the tensile strength of the concrete, the specimen cracks internally, which involves cracks developing from the inside out. When the tensile strength of the concrete specimen is small, the internal cracks develop to the surface of the specimen and splitting damage occurs. When the tensile strength of concrete is higher, no cracks are visible on the surface of the specimen, the concrete in front of the reinforcing rib is crushed, and the reinforcing bar is pulled out, at which time the specimen undergoes pull-out damage.The higher the strength of the concrete, the greater the bond stress between the duplex stainless steel reinforcement and the concrete, and the bond stress is proportional to the square root of the concrete strength. The change in the diameter of duplex stainless steel reinforcement has an effect on the damage form of the specimen: the larger the diameter of duplex stainless steel reinforcement the lower the bond stress. The increase in the ratio of concrete cover to rebar diameter can enhance the crack resistance of the specimen: when the ratio of concrete cover to rebar diameter is less than 4.5 and when the concrete has a small tensile strength, the specimen is prone to splitting damage and the bond stress increases with the ratio of concrete cover to rebar diameter; when the ratio of concrete cover to rebar diameter is greater than 4.5 and when the concrete has a higher tensile strength, the specimen is prone to pull-out damage and bond stress remains basically unchanged. Because the duplex stainless steel reinforcement has higher strength, which greatly enhances the bond strength with concrete and duplex stainless steel reinforcement, bond stress is more uniformly distributed along the anchorage length direction, so that, when the relative anchorage length increases, the mechanical bite between the duplex stainless steel reinforcement and concrete increases, and the bond strength increases accordingly.The duplex stainless steel bar bond stress expression that is established by regression analysis can better fit the test value and predicted value for different concrete strengths, the duplex stainless steel bar diameters, the ratio of concrete cover to bar diameter, relative anchorage length, and the formula established, and the test results are in good agreement. It shows that the bond stress formula is scientific and reliable.In this study, 177 duplex stainless steel bars of different diameters were fabricated for room temperature tensile tests, and mathematical methods were used to provide recommendations for the values of the parameters of the duplex stainless steel bars. The bonding performance of duplex stainless steel bars with concrete was tested by constructing 33 specimens, and the effects of four factors on the bonding stress of duplex stainless steel bars, namely concrete strength, duplex stainless steel bar diameter, the ratio of concrete cover to reinforcing steel diameter, and relative anchorage length, were investigated by controlling the variables. Finally, the analytical expression of the bond stress of duplex stainless steel bars was fitted by multiple linear regression. The research presented in this paper can be summarized, as follows.In this study, four factors affecting the bond strength of duplex stainless steel bars were considered, and the influence of the surface characteristics of duplex stainless steel bars on the bond strength need to be further considered. We look forward to discussing more influencing factors in future studies. Because only pull-out tests were used in this study to evaluate the bonding behavior of duplex stainless steel bars in concrete, future studies should use other test methods, such as pull-out tests and beam-sample tests, in order to obtain reliable results and develop design models. This paper only considers the bond strength of duplex stainless steel bars with ordinary concrete, and further studies of different types of concrete are needed to establish a more comprehensive relationship between the bonding performance of duplex stainless steel bars in concrete.


Co-amoxiclav treatment, the antibiotic most commonly administered, decreased from 66.6% to 33.3%. Among outpatients’ bronchiolitis episodes, a statistically significant decrease in beta2-agonists’ use  and a quasi-significant decrease in corticosteroid use (from 8.0% to 0% pre and post periods) were observed. An evidence-based CP supported by educational lectures was associated with significant changes in the physicians’ prescribing habits.Despite the lack of evidence that bronchodilators, corticosteroids, and antibiotics are useful in treating bronchiolitis, their use is still widespread. This study aimed to determine the consumption of antibiotics for bronchiolitis before and after a procalcitonin-guided clinical pathway (CP) implementation. In December 2019, a CP for lower respiratory tract infection management was implemented at the Department of Women’s and Children’s Health at Padua University Hospital. This was a pre-post, quasi-experimental study that assessed the changes in the treatment of bronchiolitis during two bimesters preceding the CP implementation (pre-period: January 2018–February 2018 and January 2019–February 2019) and during the bimester after CP implementation (post-period January 2020–February 2020). After the CP implementation, there was a significant reduction in antibiotic prescriptions from 36.2% to 12.5% ( Bronchiolitis is the most common lower respiratory tract infection (LRTI) in children less than one year of age and has a mainly viral etiology ,2,3. It In the presence of bacterial infection, the biomarker procalcitonin (PCT) is produced in the parenchymal tissues mediated by cytokines IL-6, TNF-α, and IL-β, and the degree of PCT rise correlates with the severity of the infection. Conversely, PCT production is attenuated by interferon-γ primarily secreted in response to viral infection ,8,9,10.The success of PCT guidance in adults with LRTI also triggered pediatric research and proved to be effective in reducing antibiotic exposures in primary care and hospital settings ,12,13. DThe primary aim of this study was to determine the consumption of antibiotics for bronchiolitis before and after the implementation of a PCT/PCR-guided clinical pathway (CP). As a secondary aim, we determined the prescription rates of inhaled beta-agonist, corticosteroids, and epinephrine before and after the CP implementation.This was a quasi-experimental study that assessed the changes in antibiotic prescribing for bronchiolitis during two bimesters before  and one bimester after CP implementation . The study was conducted at the Pediatric Emergency Department (PED) and Pediatric Acute Care Unit (PACU) of the Department of Women’s and Children’s Health (DWCH) of Padua University Hospital. This hospital provides primary and secondary care for a metropolitan area of 350,000 people and tertiary care for a regional and extra-regional population, with approximately 24,000 PED visits per year and an overall hospital admission rate from PED of around 7%.In December 2019, the CP for the management of LRTI was implemented and presented to physicians and residents working in the PED and PACU .The CP is a one-page decision support algorithm designed to assist providers in determining whether antibiotic treatment should be started or not. This PCT/PCR-guided algorithm summarizes international guidelines and was developed by a multidisciplinary group  at the DWCH at Padua University Hospital, where it is in place for more than four years an efficient antibiotic stewardship program based on CPs.Although bronchiolitis diagnosis is clinical, and blood tests and chest X-ray exams are not routinely necessary, for children hospitalized with severe bronchiolitis with a suspicion of co-infection it is suggested to add PCT to the classical blood exams.CP indicates that with: (i) PCT < 0.25 μg/L in addiction to C-reactive protein (CRP) < 100 mg/L—a bacterial infection is unlikely and the initiation or continuation of antibiotic is strongly discouraged; (ii) PCT > 0.25 μg/L and CRP >100 mg/L—a possible bacterial infection and the initiation or continuation of an antibiotic therapy is encouraged; (iii) PCT > 0.25 μg/L and PCR < 100 mg/L or PCT < 0.25 μg/L and PCR > 100 mg/L—the decision to start or continue the antibiotic therapy should be based on clinical examination.Antibiotic therapy can be considered in critically ill patients . If antibiotics are given, early discontinuation after 1, 3, or 5 days should be endorsed if PCT levels remain < 0.1 μg/L.All patients aged between 1 and 12 months with an International Classification of Diseases, 9th Revision, Clinical Modification code, or descriptive diagnosis of bronchiolitis were included.Patients with a concomitant bacterial infection, ongoing antibiotic therapy , immunodeficiency or immunosuppressive therapy, chronic disease (including cystic fibrosis and diabetes), sickle cell anemia, Down’s syndrome or congenital cardiac disease, or chronic lung disease (except asthma) were excluded.Admissions for bronchiolitis occurring in the same patient greater than 30 days apart were analyzed as separate events.® and manually collected from electronic medical records through the Redcap® data collection form.All clinical, demographic, diagnostic, and prescription data were retrieved from GalileoThe following information was considered: date of birth, admission and discharge dates, the reason for discharge, descriptive diagnosis, sex, body weight, a previous visit to the primary care pediatrician , antibiotic allergy, and vaccinations. Illness severity was assessed as mild, moderate, or severe by SR and DD according to respiratory rate, respiratory effort, oxygen saturation, feeding rate, and apnea. Other data required were diagnostic exams  and treatments .Privacy was guaranteed by assigning each patient a unique study-specific number and not collecting personally identifying data.https://www.wma.net/what-we-do/medical-ethics/declaration-of-helsinki/ accessed on 14 January 2021), revised in 2013. This study was approved by the Ethical Committees of Padova University Hospital (3737/AO/16). Due to the nature of the study,  no informed consent was required.The investigations were carried out following the rules of the Declaration of Helsinki of 1975 .Results were summarized as frequencies and percentages  and as means with standard deviations (SD) or medians with interquartile ranges (IQRs) (continuous variables) for both inpatients and outpatients. Comparison of categorical variables in the pre vs. post-periods was conducted with χ2 or Fisher exact test. Continuous variables were compared with the non-parametric Mann–Whitney U test or one-way ANOVA. A Overall, 82 inpatients (58 in the pre-period and 24 in the post-period) and 145 outpatients (100 in the pre-period and 45 in the post-period) were included. Three children were excluded due to the presence of concomitant disease and because of ongoing antibiotic therapy.Demographic characteristics, signs and symptoms, and microbiological and laboratory-related data are shown in No difference was found in sex prevalence nor age, but in the pre-period cohort, in 15% of cases, children were born < 37 weeks of age. Not surprisingly, most of the patients were not vaccinated (72.4% and 45.8% in the pre- and post-periods). Patients had a previous visit with their primary care pediatricians in 39.7% and 35.5% of inpatient episodes in the pre-period and post-period, respectively; in 39.1% (pre-period) and 33.3% (post-period) of cases, the primary care pediatricians requested an ER visit .p = 0.001). Median PCT values did not change in the periods considered , followed by rhinovirus and parainfluenza virus. Clinical analysis requests and results were similar in the two cohorts, except for PCT requests, which increased significantly in the post-period . Co-amoxiclav alone was the most prescribed antibiotic in the pre-period (76.2%), followed by ceftriaxone and the combination of ceftriaxone with a subsequent shift to co-amoxiclav (9.5% each) and azithromycin (4.7%). The three antibiotic therapies administered in the post-period were: co-amoxiclav, ceftriaxone/co-amoxiclav, and ceftriaxone/ampicillin  was administered in 6.9% and 20.8% of cases in the pre- and post-periods, respectively. Inhaled epinephrine was administered just in three cases in the pre-period .The cohorts in the pre- and post-periods were similar with respect to sex and age . Around p = 0.001), resulting in four swabs positive for rhinovirus and four swabs positive for RSV. Other diagnostic test requests and results were similar in both periods, except for PCT requests, which increased in the post-period, with no changes in median value results. . Inhaled beta2-agonist prescription significantly decreased in the post-period  of pediatricians included in a study set in a UK primary care setting were prescribed medication to treat potential differential diagnoses, reflecting the clinical challenge of differentiating between bronchiolitis and other conditions  . In our Another challenging fact that should be taken into account when discussing patient care in children with bronchiolitis is the vaccination status; indeed, in our study we found very few children had received complete immunization, including pneumococcal vaccine.Among outpatients, a decrease in antibiotic prescriptions was not significant, but it was expected. In the PED of Padua University Hospital, an antimicrobial stewardship program was implemented, which resulted in a significant decrease in broad-spectrum prescription rates that might have an impact on clinicians’ behaviors toward antibiotic prescribing for outpatients ,24. MoreEven though decreasing inhaled beta2-agonists was not the primary aim of this study, a statistically significant decrease in salbutamol prescription rates for outpatients was noted after the CP implementation. The first part of the CP is designed to help clinicians assess a correct differential diagnosis that is subsequently categorized according to illness severity as mild, moderate, or severe. Beta2-agonists seem ineffective in the resolution of the disease, when used without evidence, as already reported in the Italian outpatient setting . Thus, tFurthermore, a quasi-significant decrease of corticosteroids prescribed among outpatients was observed. Systemic and nebulized steroids did not decrease the incidence and duration of hospitalization or improve short and long-term prognosis.Our study has strengths and limitations. It is one of the first studies evaluating the effectiveness of an Antimicrobial Stewardship Program (ASP) based on a CP in an Italian hospital. This intervention was designed to be feasible and was developed by a multidisciplinary team to guarantee a high quality and level of coordination, with cooperation between the infectious diseases and PED teams. To our knowledge, it was the first study in which a CP was used to lead pediatricians’ decisions to a correct diagnosis and treatment of children with bronchiolitis.Limitations of this study include the quasi-experimental design, the fact that just one center was involved, and the short period of observation. Despite the randomized controlled trial representing a better study design in terms of reduced bias, it is also known that is costly and time-consuming; hence, we believe that implementing a stewardship policy or quality initiative could be a valid alternative. Indeed, our results were similar to a randomized control study conducted in Switzerland to assess PCT-guided treatment, which resulted in a decrease by 28 percentage points in antibiotic prescribing rate for non-CAP LRTI . On the Differently from guideline publications alone,  stewardsThe unnecessary use of antibiotics in patients with LRTI having mainly a viral cause, such as bronchiolitis, impacts patient care and the development of antibiotic resistance worldwide.The evidence-based CP supported by educational lectures has proved to be an efficient strategy to disseminate best practices to reduce antibiotic use in hospitalized patients and via inhaled beta2-agonist prescriptions for outpatients, and the adherence to bronchiolitis guidelines increased. To avoid unnecessary use of diagnostic testing, particular emphasis should be placed in the development of the clinical pathway algorithm.


Most concrete studies are concentrated on mechanical properties especially strength properties either directly or indirectly (fresh and durability properties). Hence, the ratio of split tensile strength to compressive strength plays a vital role in defining the concrete properties. In this review, the impact of design parameters on the strength ratio of various grades of Self-Compacting Concrete (SCC) with recycled aggregate is assessed. The design parameters considered for the study are Water to Cement (W/C) ratio, Water to Binder (W/B) ratio, Total Aggregates to Cement (TA/C) ratio, Fine Aggregate to Coarse Aggregate (FA/CA) ratio, Water to Solid (W/S) ratio in percentage, superplasticizer (SP) content (kg/cu.m), replacement percentage of recycled coarse aggregates (RCA), replacement percentage of recycled fine aggregates (RFA), fresh density and loading area of the specimen. It is observed that the strength ratio of SCC with recycled aggregates is affected by design parameters. In recent days, the boom in urban development and industrialization has resulted in the high consumption of natural aggregates apart from other materials. And also, due to demolition of the second largest consumption material (concrete) by humans, leads to the generation of construction and demolition waste (C&DW), which is to be relocated, reused, or recycled. The constant population growth and modernization of regions imply a daily increase in the generation of concrete waste . ResearcAccording to data from the European Statistical Office, Eurostat, each European citizen produces an average of 2000 kg of waste per year, excluding mining waste  . Of thisSelf-compacting concrete (SCC) is used to facilitate proper filling and structural performance of constrained and/or reinforced areas ,10. This2) emissions [A decrease in the carbon footprint for concrete could be achieved, effectively reducing carbon dioxide  reduction of waste generated; (b) increase in recycling and reuse; (c) limitation of incineration; (d) limitation of the use of landfills . With thThere are so many parameters in determining the SCC properties, in which the influenced parameter is design parameters . Most ofDue to the ease of casting and testing in actual site requirements, most construction sites are casting cubical or cylindrical specimens to determine the compressive strength and split tensile strength . ConcretBy utilizing waste material from the construction sector, without harming the environment  in larger proportions, natural aggregates should be replaced by RA. However, some international standards allow usage of RA in SCC up-to a certain limit and they more often discuss fresh concrete properties only. Most hardened properties of concrete depend on strength (compressive and split tensile strength) properties at any age. These mechanical properties mostly depend on the design parameters as discussed earlier . Many reThe review methodology used in this review is reported in 3), W/S ratio (%), % of RFA, % of RCA, the fresh density of mix, compressive load area and split tensile strength load area were different design parameters considered for the current study. Total aggregates are the sum of fine aggregate, coarse aggregate and recycled aggregates, from which is given total aggregates to cement ratio. Overall solid contents in the mix like aggregates, recycled aggregates, cement and binders from which the water to solid ratio were estimated. The articles without mixed proportions, or any one of the required ingredients were omitted from the review process.From available literature on SCC with recycled aggregate, the design parameters were estimated using mix design (based on various methods). The collected literature should contain the SCC mix design as various ingredient weights in a given volume to satisfy the SCC properties (fresh and hardened). Since most of the literature did not concentrate on the powder particle in RFA or the natural fine aggregate, it was neglected for this study. Binder content included the cement and mineral admixtures i.e., binder material to bind aggregates together. W/C ratio, W/B ratio, TA/C ratio, FA/CA ratio, SP  at a decreasing rate as observed and already reported in literature . It can The strength ratio initially increases with an increase in W/C ratio as observed in Initially the decrease in strength ratio is due to lower split tensile strength and higher compressive strength at 28 days. A lower W/C ratio results in the lesser formation of hydration products, the particle packing playing a key role in increasing density, thereby increasing compressive strength and split tensile strength. On further increasing the W/C ratio, compressive strength is decreased at a higher rate when compared to split tensile strength. Therefore, the strength ratio goes higher for the lower grade of SCC for a W/C ratio of 0.40 to 0.60. Water available in the cement matrix is the adequate amount for the W/C ratio lying between 0.30 to 0.45 to form hydration compounds which make the cement paste matrix denser and bind the aggregates . Due to To achieve minimum fresh properties, there is a need for a substantial amount of fine particles in the concrete. However, to obtain the minimum requirement for hardened properties there is no compromise in the aggregate content in SCC. If we increase the cement content in the mix, the cost of the mix increases and other problems are created alongside high energy consumption and carbon dioxide emissions. Without compromising the minimum quality with respect to both fresh and hardened properties of SCC, the increase in fine particles is achieved by the addition of admixtures. Admixture not only reduces the cost of the mix but also enhances the concrete properties and its environmental protection . MineralIn literature, various types of admixtures like fly ash, lime stone, ground granular blast furnace slag, etc., are used as a mineral admixture for the replacement of cement content ,66,68. STotal aggregate plays a vital role in determining the dimensional stability apart from fresh and hardened properties of concrete, which occupies 65% to 70% in total volume . The ingA lower grade of concrete results in a higher strength ratio because the change in compressive strength is at a higher level when compared to the change in split tensile strength. For the lower TA/C ratio, a higher strength ratio is observed from The fresh concrete state of SCC requires the appropriate proportion of coarse aggregate and particle size distribution within the specified limit to promote the movement of ingredients and the filling of the voids in between them . The rheFamily I, II, III and IV show a FA/CA ratio in the range of 1.5 to 2.5 from The governing factor for fresh concrete properties of SCC is ingredients used in the mixes and their proportion. An appropriate proportion of ingredients, specifically particle size distribution of aggregates to fill the voids in between them by use of both aggregates and paste . The totThe strength ratio for family I and II is lowest among all the families and it is in the range of 0.045 to 0.05 for TA/C ratio, lying in the range of 3 to 5 from Particle friction between coarse aggregate, fine aggregate and binder content increases the internal resistance to flow, hence limiting the deformability and speed of flow. Chemical admixtures dissolve through the cementation of particles through surface activating action among solid and liquid states, reducing the water quantity. Few groups of chemical admixtures offer the negative potential to cement and cementation particles; thus, the binding particles become electrostatically repelled from each other and fluidize the cement mortar paste . To imprFamilies I, II, III and IV have SP content up-to 9 kg in the mix resulting in a lower strength ratio in the range of 0.04 to 0.07, as observed from The fluidity and packing characteristics of SCC depend on the W/S ratio of the mix, because the solid content of the mix is suspended in the fluid system i.e., water and SP. Coarser ingredients like coarse aggregate are one type of solid along with finer ingredients like fine aggregates and binder content. These finer ingredients should be in proper proportions to form the paste with appropriate viscosity and flowability. The minimum water content present in the cement matrix is used for hydration reaction along with wetting the finer ingredients’ surface completely so that it fills voids . Cement A lower W/S ratio results for the families II and III but strength ratio is in the range of 0.065 to 0.095 from RFA contains finer hydrated or non-hydrated particles that form a weak link in new hydration product formation. This leads to a decrease in the density of the cement matrix. Loss in strength is due to an increase in drying shrinkage which is due to more amount of paste volume in the mix . The preFrom The presence of more amounts of RCA content results in greater porosity and the larger gap between aggregate paste interface which could be due to the presence of debris attached to the surface of RCA . Due to Most of the literature state that 20% replacement of NCA by RCA shows higher strength than control concrete, due to good adhesion between the new mortar and the adhered mortar of recycled aggregate as well as the quality of RCA . Most ofThe strength ratio for all the families lies in the range of 0.05 to 0.115 for most of the cases, as observed in The lower density of recycled aggregates and an excessive amount of paste leads to a weak interface zone and low-density matrix generating a poor matrix . ITZ in The microstructure of ITZ in concrete is extremely different from the ITZ found in cement paste due to longer portlandite crystals, higher porosity and ettringite content in it . The mic3 to 2400 kg/m3. Lower fresh density may be due to lower water content for the mix. Family II and III show a slightly higher strength ratio in the range of 0.050 to 0.095 mostly with a fresh density range of 2100 kg/m3 to 2500 kg/m3. Fresh density is decreased for family IV with an increase in strength ratio is observed. For family V and VI, the fresh density is maintained between 2100 kg/m3 to 2400 kg/m3 but the strength ratio is increased. The higher fresh density is due to an increase in the water content of the mix. The higher strength ratio has been already described earlier.From The most common experiment carried out on concrete is the compressive strength experiment. Because of ease of experiment procedure and cost effectiveness, the most recommended experiment is compressive strength. As per various international standards, the most used geometrices are cyclinders with slenderness ratio as two and cubes. The effect of specimen shape on compressive strength has been studied widely and different relationships obtained for these geometrical shapes have been proposed in the literature . For cubFor cylindrical specimens, when the height of a cylinder is less than the diameter of the cylinder, then the type of failure when subjected to uniaxial compression in the concrete is crushing. If the height of the cylinder is greater than the diameter of the cylinder then the type of failure when subjected to uniaxial compression is cracking. If the diameter of the cylinder is equal to the height of the cylinder, then the type of failure when subjected to uniaxial compression in concrete is mostly cracking at 45 degrees . Stress Van Vliet and van Mier., 1996  determinGonnerman (1925) experimentally exhibited that the ratio of the compressive failure stress to the compressive strength decreases as the specimen size increases. This phenomenon of reduction in strength dependent on specimen size is called the “reduction phenomenon”. When a member is subjected to pure tension loading, the failure is caused by a relatively narrowed localized zone and in the case of compression loading, the failure is caused by a larger damage zone . For botCubical and cylindrical specimens are used to determine split tensile strength of concrete frequently. Various international codes across the globe contain the formula that does not consider size and shape effect in the calculation of split tensile strength of concrete. To determine the split tensile strength of concrete, cylindrical specimens are proposed by  and wereThe strength ratio is in the range of 0.085 to 0.105 for family IV and V, and has a lower split tensile load area due to splitting force decreasing with a decrease in the size of the specimen. A lower split tensile load area is observed for families III, IV and V from Reduction in extraction of raw materials, especially aggregates and processes associated with them ,103Reduction in the negative impact on the environment through removal and disposal processes Introduction of circular economy Reduction in the dependence on resources from nature Reduction in the requirement for safe disposal sites of C&DW ,105Reduction in the cost of construction ,106Creation of new employment fields Development of a sector based on recycled aggregates manufacturingThe limited availability of natural resources and their continuous usage will lead to depletion with respect to time. To preserve natural resources, needless wasting of natural resources in any form should be restricted and regulated. Formulation and implementation of proper waste management along with appropriate knowledge on concrete properties manufactured with recycled aggregates can minimize the waste generated from C&DW. In order to promote the sustainable construction associated with using recycled aggregates in construction, some advantages are listed, such as:Accomplishment of recycling process of C&DW necessitates promotion by means of education and information in addition to legal rules from the governing body. Hence, in order to support the above, a database gathering the usage of recycle aggregates based on mechanical properties would provide concrete evidence.A comprehensive review of the influence of design parameters on the strength ratio is required in the current scenario to understand the role of various ingredient proportions on strength requirements. This will help budding engineers or researchers who work on SCC with recycled aggregate as standard requirements of ingredients proportions in SCC mix.Increase in W/C ratio, decrease in strength of SCC (or increase in the family from I to VI). A lower W/C ratio results in a lower strength ratio for a higher family .Increase in W/B ratio, decrease in strength of SCC (or increase in the family from I to VI). A lower W/B ratio results in a lower strength ratio for a higher family . A higher W/B ratio results in a higher strength ratio for lower families .FA/CA in the ratio of 1.5 to 3.0 is observed for all the families. Lower the strength ratio higher the family and higher the FA/CA ratio lower families .TA/C in the ratio of 3.0 to 7.0 is observed for all the families. Higher TA/C ratio, lower families  are observed for higher strength ratio. Lower the TA/C ratio, higher families  are observed for lower strength ratio.Lower strength ratio results for higher families  result in the usage of SP from 2.0 kg to 7.0 kg and in similar usage of SP, there is a higher strength ratio for lower families . Hence, there is no clear relationship between strength ratio and usage of SP in kg.W/S ratio is lower (in the range of 3.0 to 8.0) resulting in a lower strength ratio for higher families . Higher W/S ratio, above 9.0, results in lower families .Lower level of replacement of NFA by RFA is observed for all families. A 100% replacement is observed in higher families only.A 50% replacement of NCA by RCA is observed for all the families, showing a lesser difference in strength ratio. A 100% replacement is observed for all the families.Lower fresh density for higher families  results in a lower strength ratio and higher strength ratio is from higher fresh density for lower families .Higher compressive load area results in a higher strength ratio for lower families  and a lower strength ratio is from higher families  leading to the lower compressive load area.Similar to compressive load area results, the higher the split tensile strength load area, the higher the strength ratio for lower families . A lower split tensile load area, the lower the strength ratio from higher families .Hence, this overall review may be helpful for researchers, scientists and academicians to develop standards for SCC with recycled aggregates based on the strength properties. It also guides budding engineers and builders to utilize different ingredients combinations impact on compressive and split tensile strength for various grades.


The aim of this study was to analyze the effect of discontinuation of antimicrobial stewardship programs (ASP) activity on the antibiotic usage pattern.An interrupted time series analysis assessing the trends in antibiotic use and incidence of antimicrobial resistance in major pathogens was conducted between March 2017 and April 2019 in an 859-bed university-affiliated hospital in Korea, where all ASP activities were discontinued in February 2018. The major activity of the ASP was a restrictive measure for designated antibiotics. We defined antibiotics as medication with the Anatomical Therapeutic Chemical class J01, and the antibiotic consumption was measured as days of therapy (DOT), which was then standardized per 1,000 patient-days. The use of antibiotics against multidrug-resistant pathogens increased immediately after the discontinuation of restrictive antibiotic program . In addition, there were positive changes for the GW and ICU . The use of broad-spectrum antibiotics in patients in the ICU significantly decreased . For non-broad-spectrum antibiotics, there were positive changes for the GW and ICU (18.17 and 22.69 DOT/1,000 patient-days per month, respectively. In conclusion, after discontinuation of ASP, antibiotic usage patterns rapidly returned to the patterns prior to ASP implementation.All Authors: No reported disclosures


In order to better predict the development of shrinkage deformation of steam-cured concrete mixed with slag, a deformation-temperature-humidity integrated model test, a hydration heat test, and an elastic modulus test were performed. The effects of the steam-curing process and the content of slag on shrinkage deformation, hydration degree and elastic modulus of concrete were studied. The results indicate that during the steam-curing process, the concrete has an “expansion-shrinkage” pattern. After the steam curing, the deformation of concrete is dominated by drying shrinkage. After the addition of slag, the shrinkage deformation of steam-cured concrete is increased. The autogenous shrinkage increases by 0.5–12%, and the total shrinkage increases by 1.5–8% at 60 days. At the same time, slag reduces the hydration degree of steam-cured concrete and modulus of elasticity. A prediction model for the hydration degree of steam-cured concrete is established, which can be used to calculate the degree of hydration at any curing age. Based on the capillary tension generated by the capillary pores in concrete, an integrated model of autogenous shrinkage and total shrinkage is established with the relative humidity directly related to the water loss in the concrete as the driving parameter. Whether the shrinkage deformation is caused by hydration reaction or the external environment, this model can better predict the shrinkage deformation of steam-cured concrete. With the improvement of current standards for building industrialization, environmental protection and low-carbon concepts cannot be ignored. Traditional cast-in-place concrete technology has a series of shortcomings, such as environmental pollution, an unstable quality of concrete, high resource consumption and being labour-intensive . HoweverConcrete is a typical hydrophilic material with a large number of tiny pores and cracks inside. when the environmental relative humidity is lower than the internal relative humidity of concrete, the moisture inside the concrete will evaporate and cause concrete to shrink. This kind of shrinkage is called drying shrinkage. Another type of shrinkage is caused by the consumption of water due to the hydration of cementitious material during the concrete setting and curing process at early ages and is called autogenous shrinkage. As is known, the shrinkage strain of concrete is positively correlated with the relative humidity inside concrete ,14,15. HIn this paper, the effects of the steam curing process and addition of slag on hydration, deformation, pore size distribution and elastic modulus of concrete were studied. Based on the experimental results, an integrated model of autogenous shrinkage and total shrinkage of steam-cured concrete based on changes of internal relative humidity and temperature will be established. The results are helpful for understanding and predicting the shrinkage and deformation of concrete after steam curing.2/kg and 0.8%, respectively. The fine aggregate was river sand, and its fineness modulus was 2.6. The coarse aggregate was basalt, and its continuous gradation was 5–20 mm. The water reducing agent is a polycarboxylic acid-based superplasticizer with a water-reducing rate of 30%. The mixing water was tap water. The water-binder ratio of the cement paste is 0.32, and the mix proportion of the concrete segment of the typical coastal subway is shown in Portland cement type of P.I 52.5 and slag type of S95 with chemical composition were used Cf. . The speThe TAMAir eight-channel isothermal calorimeter  was used to test the heat of hydration of the pure pulp samples S0 and S25 at 20 °C and 50 °C. The data collection interval was 30 s, and the test time was 7 days. This uses water as the reference group. It puts the weighed sample into an ampoule and weighs 4 g of the gelling material sample. They are stirred at low speed in the ampoule.The capillary negative pressure test system is based on physics and combined with the Laplace equation to develop a comprehensive test system for capillary negative pressure. It can realize real-time unattended monitoring of the capillary negative pressure of cement-based materials by managers ,22,23,24The test piece uses a steel mold of 100 mm × 100 mm × 400 mm. Before the start of the test, the sensor device and the water potential probe are exhausted first, and then the microporous ceramic head is buried in the sample to be tested, and the initial value of the test is 0 ± 0.5 kPa through change. After the test piece is poured, it is moved into the steam curing box. The test collection instrument will automatically record the capillary negative pressure value of the entire process, and the collection frequency is 0.5–2 min/time.A vibrating wire strain gauge with a range of ±1500 με is used to measure the deformation of concrete. Its accuracy is 1 με, the measuring gauge length is 150 mm, and the applicable ambient temperature is −20–125 °C. The strain gauge can automatically perform temperature compensation. The fresh concrete is poured into a steel mould of 100 mm × 100 mm × 400 mm. The strain gauge is pre-embedded in the centre of the test piece, and the temperature and humidity sensor is inserted at half the height of the concrete specimen. It is necessary to calibrate the temperature and humidity sensor with the salt solution before the test. ρ2 is the surface relaxation rate, which is 12 nm/ms [T2 is the lateral relaxation time of water molecules in the pore, ms.Low-field nuclear magnetic resonance (LF-NMR) is a new technique for rapid measurement of rock physical parameters. It has the advantages of fast measurement, simple operation, no damage to the core, no pollution, and quick acquisition of reservoir physical parameters, which provides a novel way to evaluate the pore structure of the reservoir. This paper uses this technology to obtain the pore distribution characteristics of the cement paste after steam curing. Because of the short setback time of this technology, the relaxation of free water can be ignored ,27. Assu12 nm/ms ; T2 is tThe test selects cement paste samples with ages of 8 h, 7 days and 28 days for testing. Before the start of the test, the sample was crushed, then placed in absolute ethanol for 7 days to end the hydration process, and finally dried in an oven at 50 ± 2 °C for 3 days before the NMR test. During the NMR test, the magnetic field intensity of the instrument was set to 0.42 T, the magnet frequency was set to 18 MHZ, and the magnet temperature was maintained at 32 ± 0.02 °C. The temperature in the laboratory was controlled at 20 ± 1 °C through air conditioning and other equipment, and the sample was placed in a cylindrical glass tube with a diameter of 25 mm and a length of 200 mm for testing. The standard oil sample was calibrated by the free induction attenuation sequence to obtain the frequency deviation (O1) and 90° pulse width (P1) of the RF signal. The transverse relaxation time (T2) of the sample was obtained by the Can–Purcell–Meiboom–Gill pulse sequence , and finally the pore size inside the cement paste was obtained.dE is the dynamic elastic modulus; sE is the static elastic modulus; L is the length of the specimen, m; ρ is the concrete test piece density, kg/m3; υ is Poisson’s ratio; t is the age of the test piece in full immersion solution; K, c are fitting parameters.The modulus of elasticity reflects the relationship between the stress and strain on concrete, and it is an important parameter for establishing a concrete shrinkage model . Researc3S and slows the hydration rate, and the cement still maintains good plasticity. It can be seen from 2+ in the pore solution and releases more SiO44−, which reduces the Ca/Si ratio in the pore solution, so unstable C–S–H is formed [3S and C2S [s formed ,37. It t and C2S . From th2. Ca(OH)2 plays the role of an alkali activator. Under the action of the alkali activator, slag will react with the Ca(OH)2 in the pore solution. Meanwhile, slag will hydrate under high temperature. The above processes result in the release of more heat.It can be seen from − can destroy the Ca–O bond, Al–O bond and Si–O bond in slag, which promotes the hydration of slag. Therefore, the amount of Ca(OH)2, Mg(OH)2 and ettringite in the hydration product increases faster than concrete just with cement, which increases the expansion level [The development of deformation during the steam curing stage is caused by a combination of many factors, including the thermal expansion of each phase of concrete, chemical shrinkage caused by hydration, and autogenous shrinkage caused by lower internal humidity. Relationship between deformation of concrete and the internal temperature and relative humidity during the steam curing stage is shown in on level . In the on level ,40.As is known, the precast concrete samples are always steam cured in the factory, and then transported to the construction site. The steam curing process completed in the factory does not affect the application of the precast concrete samples in the construction site, so it is reasonable to use the time of demould as the zero point of shrinkage.2 and Al2O3, the autogenous shrinkage will increase significantly. Mainly due to the active SiO2 and Al2O3, the hydration products are more complicated, including C–S–H gel , C–A–S–H gel , C–A–C–H gel, hydrotalcite-like material, and C–A–H . Compared with hydration products of cement, these hydration products contain more bounded water, which affects the autogenous shrinkage of concrete [42− and generates more ettringite, which makes the concrete expand more, so it plays a supplementary role in autogenous shrinkage. Therefore, in the actual project, we tried not to mix mineral powder alone, and it could be mixed with fly ash. The internal shrinkage of the concrete specimen increases with the decrease of relative humidity. The shrinkage curve and the relative humidity curve show good correlation and synchronization during the test period. The relationship between autogenous shrinkage and relative humidity is mainly manifested in the fact that when cement undergoes hydration, it absorbs a large amount of free water inside concrete to form voids, which causes the internal balance of unbound water to be lost, so the relative humidity continues to drop. For concrete, which is in a completely sealed state, the relative humidity of concrete continues to decrease, resulting in the presence of gas-phase in the pores, so that the water vapour in the pores is no longer saturated. As the cement hydration reaction continues to intensify, according to the principle of minimum energy, water must migrate from large pores to small pores driven by capillary action, and form a meniscus at the largest pore to reach a thermodynamically stable state. At a certain moment of the hydration reaction, there is a critical radius r0, and there is a meniscus in the capillary pores with a diameter of r = r0, which then generates capillary stress. This will produce negative pressure on concrete, which will eventually cause concrete to shrink automatically. The drying shrinkage of concrete is mainly manifested in two aspects: on the one hand, the hydration process consumes internal water and reduces the relative humidity of concrete. On the other hand, the relative humidity inside the concrete is constantly changing after exposure to the environment with different temperature and relative humidity, which leads to the loss of moisture inside the concrete to the environment. Through the above analysis, it can be found that both autogenous shrinkage and drying shrinkage are caused by the drop in relative humidity of concrete. Therefore, from the Kelvin equation [concrete ,42,43.  and sulfate ions, and gradually increases the elastic modulus. At the same time, the components in slag react with Ca(OH)2 to form C–S–H, which reduces the content of Ca(OH)2 at the interface between hydrate and coarse aggregate. As a result, the interface transition zone is improved [improved . This ima and b are constants and their values are shown by the fitting curves. The results in a, b are fitting parameters.BS EN  shows thα(t) can be calculated based on the cumulative heat release Q(t) and the heat release Q(u) to achieve complete hydration, as shown in Equation (5). The ultimate heat release Q(u) can be determined according to the Q-FHP model as shown in Equation (6), where Q(u) = a1 + a2 [Q(u) of the samples with the same mix proportion is almost the same at different temperature. This is because Q(u) is just related to the mix proportion of the samples. The average Q(u) of S0 and S25 is 353.61 J/g and 446.27 J/g, respectively. Furthermore, the change curve of the hydration degree of the cement paste at 20 °C and 50 °C is shown in 1, a2, τ1, τ2, β1, and β2 are parameters.The temperature is constantly changing during steam curing. In order to analyze the influence of temperature on the hydration of cementitious material, the concept of hydration degree is introduced. The hydration process of cementitious materials can be quantified by the degree of hydration, and the degree of hydration is an important parameter of the shrinkage model of concrete. The degree of hydration  a1 + a2 ,54,55. TrT is the reference temperature, K, taking 293 K; aE is the activation energy of the material, kJ/mol; R is the gas constant, J/mol∙K, taking 8.314 J/mol∙K; T is the average temperature in Δt, K.The steam-curing process is a temperature-changing process. In order to eliminate the influence of temperature history on the analysis of the hydration degree of cementitious material, researchers have established the equivalent age equation, as shown in Equation (7) . ThroughEa in Equation (7) is the only parameter that reflects the sensitivity of concrete to temperature. Wade et al. [Ea of S0 and S25 is 36 kJ/mol and 47 kJ/mol, respectively, compared with the measured hydration degree, the calculated hydration degree based on equivalent age has the highest accuracy, as shown in et is the equivalent age; a and b are constants. Parameters a and b of S0 and S25 are, respectively, 0.67, −2.25 and 1.35, −1.56. Then the hydration degree of the cementitious material at any age can be calculated.The apparent activation energy e et al. ,57 foundIn order to study the effect of steam curing on the hydration process of concrete, the establishment and verification of subsequent shrinkage models, the internal temperature change of concrete was measured as shown in E is the elastic modulus;In this section, the change of relative humidity in concrete is used as the internal cause, and an integrated model of autogenous shrinkage and total shrinkage of steam-cured concrete is established based on elastic modulus, hydration degree and pore diameter. Since the model defaults to the zero time as the starting value, the calculated value of the model should be compared with the test results after demould to verify the applicability of the model. According to the self-consistent method, the shrinkage strain caused by the internal tensile stress tion (9) ,62:(9)εHion (10) :(10)KT =ewV and pV are functions of the hydration degree.ewV is the vaporizable water in the hardened cement paste; pV is the total pore volume; P is the water-cement ratio function; K is the ratio function.The saturation coefficient ectively ,64. Vew P of pure cement and cementitious material mixed with slag is calculated according to Equations (13) and (14), respectively.3, 1000 kg/m3 and 2850 kg/m3, respectively; W/C is the mass fraction ratio of each component.K of the cementitious material mixed with slag is calculated according to Equation (15):RH is the relative humidity, %; T is the Kelvin temperature, K; 3/mol.According to the Kelvin–Laplace equation , The steε measured by the test should be composed of the deformation hε caused by the change of relative humidity and the deformation tε caused by the change of temperature, as shown in Equation (17).Except for the deformation caused by the change of relative humidity, the temperature deformation caused by the change of temperature is another important part of the early deformation of concrete. In order to accurately predict the overall deformation, the deformation caused by temperature must be considered. The total deformation tβ and temperature T of concrete. et is the equivalent age of the cement hydration process; C, λ and β0 are constants, the values of which are 132, 0.3 and 7, respectively.The early temperature deformation is mainly affected by the thermal expansion coefficient During the steam curing process, the concrete shows an “expansion-shrinkage” pattern. After the mould is removed, the relative humidity and concrete deformation have good consistency, no matter in the fully-sealed or semi-sealed conditions. Shrinkage of concrete increases continuously with the decrease of the relative humidity. After steam curing, the main shrinkage of concrete is drying shrinkage. At 60 days, drying shrinkage accounts for over 65% of the total shrinkage. Compared with pure cement concrete, the addition of slag increases the autogenous shrinkage of concrete by 0.5–12%, and the total shrinkage increases by 1.5–8%.Compared with pure cement steam-cured concrete, the addition of slag reduces the hydration degree and elastic modulus of concrete. At the same time, the addition of slag increases the most probable pore diameter of cement paste, evacuates the hardened structure, and makes the pore distribution more reasonable.The hydration degree prediction development model of steam-cured concrete is established, and the hydration degree at any age can be calculated.An integrated model of concrete autogenous shrinkage and total shrinkage under steam curing conditions based on internal factors of the change of relative humidity was established. Whether shrinkage deformation is caused by cement hydration or drying, this model can better predict the deformation of concrete. In particular, the shrinkage of early age concrete is predicted. The deformation of early-age concrete is much more complicated than that of later mature concrete. This stage cannot be ignored.In this paper, the development characteristics of shrinkage deformation of steam-cured concrete with and without slag are studied, and an integrated predictive model of autogenous shrinkage and total shrinkage is established. According to the research results, the following conclusions are drawn: