The direct microscopy illustrated diagnostic accuracies of 60.4% (sensitivity), 99.77% (specificity), 98.9%  and 88.3% , respectively (against culture) for the detection of Mycobacterial species. The pancreatin-CPC DDM showed competitive diagnostic accuracies (against NALC-NaOH DDM) of 99.32% (sensitivity), 94.07% (specificity), 85.05% , and 99.76% , respectively, for the isolation of Mycobacterial species. In conclusion, pancreatin-CPC DMM was a highly sensitive, technically simple, and cost-effective method, suggesting its competence to substitute the currently used NALC-NaOH DDM.The present study evaluated the performance of newly developed pancreatin-cetylpyridinium chloride (pancreatin-CPC) digestion and decontamination method (DDM) with N-acetyl L-Cysteine-sodium hydroxide (NALC-NaOH) DDM for isolation of Mycobacteria from clinically suspected pulmonary tuberculosis (PTB) patients. For the study, sputum samples ( Mycobacterium tuberculosis (MTB) in culture is necessary for accurate detection of tuberculosis (TB). However, isolation of MTB and other non-tuberculous mycobacteria (NTM) are hindered due to the presence of microbial flora in the patients’ samples resulting in delayed confirmation of tubercle bacilli  were obtained from suspected cases of PTB patients, who were attending the Revised National Tuberculosis Control Program (RNTCP) testing center at M. M. Institute of Medical Sciences, Ambala (India). The current study included all patients, who presented with a productive cough that lasts longer than two weeks or more or the patients as instructed by the physician. However, patients who were undergoing anti-tubercular treatment (ATT) were excluded from the study. All the sputum samples used in the study were obtained for direct Acid-fast bacilli (AFB) staining at the RNTCP center. AFB smear reports were distributed to the patients after the microscopic examination. Further, all the sputum was refrigerated overnight at 4–8 °C until used. Informed consent of the patients was obtained before sputum collection. After dispatching the AFB smear report, all the sputum samples were transported to the Department of Microbiology, M. M. Institute of Medical Sciences and Research, Ambala (India) for culture.Both sputum specimens (morning and spot) collected from each patient were pooled to obtain sufficient quantity (4–6 mL) and similar quality. These mixed sputum samples were homogenized for one min using a disposable Pasteur pipette followed by vortexing of a 3 min duration to assure the equal distribution of mycobacteria. All the procedures involving specimen segregation, smear preparation, and culture were carried out in a biological safety cabinet (Class II A) . This homogenized sputum specimen was separated into three aliquots, namely; direct Auramine ‘O’ staining and other two aliquots used for culture by NALC-NaOH DDM and pancreatin-CPC DDM. n = 91) and 10% of randomly picked negative slides (n = 60) were examined by the study supervisor.For the light-emitting diode fluorescent microscopy (LED FM), direct Auramine ‘O’ smears were prepared using a 0.5 mL homogenized sputum sample on a clean glass slide. Two independent technicians under 400× magnification  microscopically examined the stained direct smears. The smear results were reported as per the guidelines published by RNTCP . To measThe second aliquot of homogenized sputum (2 mL) was subjected to NALC-NaOH DDM as described by Kent & Kubica with minor changes  . After tg) for 20 min and sediment was separated after decanting the supernatant. The sediment was re-suspended with 200 µL of DW and the resuspended pellet (0.2 mL) was cultured on two LJ culture tubes (one media with sodium pyruvate and the other with glycerol). These LJ slants were incubated  at 37 °C and checked for growth once every seven days for up to eight weeks.The homogenized sputum sample (2 mL) was transferred to Falcon tube (14 mL capacity) , added with an equal quantity of 4% pancreatin  −4% CPC  working solution. This working solution was prepared by mixing an equal quantity of 4% pancreatin and 4% CPC stock solution, which was prepared in distilled water (DW)]. Then this reaction tube was subjected to vortexing (1 min) followed by 30 min incubation (at 37 °C). After incubation, DW was added and volume brought until the brim of tube followed by thorough mixing by vortexing and inversion. Later, this tube was centrifuged (3300× M. tuberculosis (ATCC H37Rv) and M. kansasii (ATCC 12478)]. Polymerase chain reaction (PCR) (primer sequence specific for ‘IS6110’) was used to confirm the MTB isolates. The primer sequence used includes; T4- 5′-CCT GCG AGC GTA GGC GTC GG 3′ and T5-5′ CTC GTC CAG CGC CGC TTC GG 3′ with an expected band size of 123 bps [The growth of mycobacteria was presumptively identified as per guidelines published by WHO . Quality 123 bps .Diagnostic accuracies of NALC-NaOH DDM (reference methods) were calculated and compared against pancreatin-CPC DDM. The significance of differences in the sensitivities of NALC-NaOH DDM and pancreatin-CPC DDM were assessed using McNemar’s test. The significance of differences in the rate of detection of mycobacteria was analyzed using Fisher’s exact test carried out by GraphPad Prism 6 .Of 613 sputum specimens processed, direct AFB smear could detect a total of 14.85% (91/613) smear-positive cases. However, LJ detected the presence of MTB and NTM in 22.83% (140/613) and 1.63% (10/613) of the specimens, respectively when treated with NALC-NaOH DDM (reference method). In contrast, sputum samples when digested and decontaminated using pancreatin-CPC DDM, the culture positivity of MTB and NTM were 25.77% (158/613) and that of NTM 2.61% (16/613), respectively. n = 91), 60.4% (90/149) of mycobacterial isolates were grown in LJ culture after treatment with alkali-based NALC-NaOH DDM  detected twenty-five additional mycobacterial isolates in comparison with alkali-based DDM  . n = 149), and CPC (n = 174) based DDMs, 29.53% (44/149) and 27% (47/174) sputum samples were having 3+ and 2+ smear scores. These samples also showed heavy growth (3+ and 2+ growth) in LJ culture (NaOH DDM . Table 2 culture . In contn = 40), irrespective of the type of DDMs used. Alternatively, delayed growth of MTB was noted in samples with 1+ or scanty smear grades. Nevertheless, the differences between the meantime to detection of MTB (on LJ media) for CPC-based DDM was 36.23 days (SD 10.06), which was relatively less when compared to alkali-based DDM . Likewise, LJ culture showed growth of NTM with a mean detection time of 20.4 (SD 3.29) and 15.94 days (SD 3.5) for samples treated with alkali-based DDM and CPC-based DDM, respectively. p < 0.0001) to isolate mycobacterial species  of the specimens when treated with NALC-NaOH DDM in comparison with direct AFB smear 14.84% (91/613). These results were consistent with earlier works as well, in which they investigated various rapid methods for the detection of MTB in parallel with conventional LJ culture ,18.The isolation rate of NTM was considerably increased when sputum specimens were treated with pancreatin-CPC DDM  suggesting the potential of pancreatin-CPC DDM for the effective isolation of NTM as well. In the current study, the rate of contamination was found to be low for sputum samples treated with NALC-NaOH (1.8%) and pancreatin-CPC DDM (3.09%) and the differences in the contamination rate were insignificant. This minimum rate of contamination of the NALC-NaOH decontaminated samples may be because of a low concentration of NaOH. Nevertheless, the relatively low contamination rate of pancreatin-CPC DDM may be endorsed due to the bacteriostatic action of CPC, which is a quaternary ammonium compound that disrupts bacterial cell membranes  and subsequently resulting in the death of bacteria.n = 40) that possess higher smear grades regardless of the pre-treatment method used . This reaction mixture was incubated at 37 °C for 30 min. The results of the pilot study suggested that 4%concentration of both pancreatin and CPC might be effective for isolation of MTB. In this study, culture detected a significant number of MTB isolates when smear-negative samples were treated with pancreatin-CPC DDM  than those specimens when exposed to NALC-NaOH DDM . The differences between these were found to be significant . These increased false-negative results can be endorsed to the lytic property of pancreatin, which contains a mixture of lytic enzymes that could disintegrate the sputum samples to discharge the bacilli embedded in the mucus clumps and macrophages. It was also noted that the growth detection time was relatively reduced when specimens treated with pancreatin-CPC DDM as compared to those specimens that were treated with NALC-NaOH DDM  [In pancreatin-CPC DDM, pancreatin (4%) and CPC (4%) function as digestive, and decontaminating agents, respectively. The particular concentration of 4% pancreatin−4% CPC used in this study was determined after conducting a pilot study using varying concentrations of pancreatin. It was noted that overnight treatment of clinical samples with 1% CPC could decontaminate the samples effectively . HoweverNaOH DDM . This isBL MGIT) . HoweverIn summary, LJ culture showed an incremental yield in the recovery of mycobacterial isolates mainly from smear-negative sputa that were treated with pancreatin-CPC DDM than NALC-NaOH DDM treated sputa, suggesting its promising use in clinical TB laboratories.


This paper aims to experimentally investigate the effects of high volume cement replacement of blast furnace slag (BFS) on the bond, strength and durability of recycled aggregate concrete (RAC). Concrete mixtures were prepared containing 0%, 15%, 30%, 45%, 60% and 75% BFS with each of recycled aggregate and natural aggregate. Measurements of the compressive and bond strength, the resistance to chloride-ion penetration and the water permeability of concrete are reported. In addition, a microhardness test was also performed to evaluate the quality of interfacial transition zone (ITZ) in concrete. Test results of the bond strength and the compressive strength of RAC mixtures, in spite of the cement replacement amount with BFS, show that the concretes result in reduced strength when compared to natural aggregate concrete (NAC) mixtures, while the strength gains for the BFS-based concrete are higher than that of the reference mixtures without BFS at long-term ages. Incorporating BFS in concrete can inherently improve the durability properties by increasing higher resistance to chloride-ion penetration and lower water permeability. This improvement in the mechanical and durability properties of the BFS-based RAC mixture may be due to the additional pozzolanic reaction of BFS, which enhances the properties of ITZ in concrete, resulting in an improvement of the strength of concrete. In the past decades, many researchers intended to find an effective method for producing sustainable concrete with a low amount of cement or recycled aggregate. The general measure is to crush waste concrete as coarse aggregate for producing concrete, which was regarded as recycled aggregate concrete (RAC) [Cement and aggregate are the two main components in concrete. However, the procedures of their production emit much COte (RAC) ,2,3. Thete (RAC) ,5,6,7. Ite (RAC) ,9,10.For past decades, increasingly more research results of concrete with high volumes blast furnace slag (BFS) were reported, with most discussing natural aggregate concrete ,13,14,15Hence, some studies further investigated the effect of high volume blast furnace slag. Khodair  examinedMajhi  researchIn addition, the bond strength of recycled aggregate concrete is also an interesting issue. Some studies discussed the bond strength between RAC and rebar in comparison with that of ordinary concrete ,21. TheiFurthermore, other studies focused on discussing the microstructure at steel–concrete interface in reinforced concrete. Soylev  studied The abovementioned research suggests that RAC with high replacement levels of BFS may present improved durability and mechanical properties at later age. This study aims to further investigate the fresh properties, mechanical properties and durability of RAC that incorporates high replacement levels of BFS. The mechanical properties of hardened concrete were evaluated by testing the interfacial transition zone performance at the surface of aggregate and steel bars, which were measured using microhardness tests ,29.(1)Cement: Type I Portland cement obtained by Taiwan Cement Corporation Ltd., Taipei, Taiwan, with a specific gravity of 3.15. The basic properties of cement are shown in (2)Blast furnace slag (BFS): Grade 120 of ground granulated blast furnace slag obtained from Advanced-Tek Systems Co., Ltd., Taipei, Taiwan. The basic properties of BFS are shown in (3)Fine Aggregate (FA): Natural river sand with a specific gravity of 2.60 and fineness modulus of 2.40.(4)3 and maximum size of 19 mm.Coarse aggregate (CA): Crushed river stone with a specific gravity of 2.61, bulk density of 1470 kg/m(5)3 and particle sizes of 5~20 mm.Recycled coarse aggregate (RCA): Crushed waste concrete with a specific gravity of 2.26, bulk density of 1280 kg/m(6)Superplasticizer (SP): High performance water-reducing agent obtained from HI CON Chemical Admixture Taiwan Ltd., Taipei, which meets the CNS 12283 Type G with a specific gravity of 1.2 ± 0.02 and pH 7.0 ± 1.0.The mixture proportions of concrete were designed according to ACI 211.1 , basicalThe fresh properties of concrete, including slump, air content and unit weight, were simultaneously measured for each batch. Specimens for testing were cast from each mixture: a cylinder specimen of φ100 mm × 200 mm for compressive strength test, cylinder specimen of φ150 mm × 50 mm for water permeability test and cylinder specimen of φ100 mm × 50 mm for chloride-ion permeability test. For the bond strength test, cubes of 150 mm size were prepared by embedding a reinforcing bar of #7  vertically along the central axis of the specimen. A cube specimen of 50 mm × 50 mm × 50 mm in dimension with a #4  bar placed horizontally in the middle was prepared for the microhardness test. 2), α = face of angle of indenter at 136° and d = mean diagonal of indentation (mm). Generally, the hardness is correlated with the strength of material tested.The compressive strength test was performed according to ASTM C 39  at the a3 to 2314 kg/m3 decreased as the replacement ratio of BFS increased. These results indicate that the RAC mixtures prepared for test can exhibit adequate properties of fresh concrete.The measured fresh properties of concrete including slump, air content and unit weight are shown in The compressive strength of concretes measured at various ages is shown in It can be seen in Microhardness testing has been reported to be a means for characterizing the bulk paste properties in cement pastes, especially for the properties of interfacial transition zone (ITZ). The ITZ was recognized as a significant part of the microstructural system in concrete, which plays an important role in affecting the properties of concrete, such as compressive strength, tensile strength, fracture and permeability.avgμ is the average bond stress (MPa), bd is the diameter of rebar (mm) and eL is the length of embedment (mm).The bond strength of concrete obtained from the pull-out test was calculated as:avgμ  of concrete increased with the increase of compressive strength. The bond strength of BFS concretes was higher than that of the reference concrete without BFS, which increases with the increase in BFS-based content. This increase in bond strength of BFS concrete may be due to the denser and stronger ITZ at the surface of steel bars, as discussed earlier.To evaluate the long-term effect of BFS on the bond strength of concrete, the bond strength gains (in percentage) of each mixture series at 28, 56 and 91 days with respect to the 7-day bond strength are also calculated, as shown in Based on these results, the BFS may provide the effects to enhance the long-term bond strength of RAC; the rate of strength gains at later ages beyond 56 days increase with the increase in BFS content. This may be due to the fact that the pozzolanic reaction of BFS can improve the strength properties of ITZ at the surface of steel bars, resulting in an enhancement of the long-term bond strength of the BFS concretes.m1 = initial weight of specimen and m2 = specimen weight after test.The water permeability (WP) of concrete was tested using a uniaxial flow apparatus performed on cylinder specimens (φ150 mm × 50 mm) subjected to 0.29 MPa pressure for 3 h. The WP was calculated with following formula:Furthermore, the effect on the water permeability of concrete by adding BFS can also be seen from The strength development with age of the NAC and RAC mixtures presents a similar trend, in which the compressive strength of RAC series is lower than that of the corresponding NAC series, indicating that, despite the cement replacing BFS, the mixtures of RAC result in reduced strength. In addition, the strength gain at later ages for the BFS mixtures is higher than that of the reference mixture without BFS.Both of RAC and NAC mixtures incorporated with any BFS content show higher microhardness at ITZ than that of the correlated control mixture without BFS. Concrete at each age and containing more BFS presents higher microhardness at ITZ. This indicates that incorporating BFS makes the ITZ in concrete denser and stronger, especially at later ages.The bond strength of BFS concretes is higher than that for the reference concrete without BFS, which increases with the increase in BFS content. The rate of bond strength gains at long-term ages with respect to the 7-day strength increases with the increase in BFS content. This may be due to pozzolanic reaction of BFS, which enhances the strength properties of ITZ at the surface of steel bars, resulting in an improvement of the long-term bond strength of BFS concretes.Both RAC and NAC mixtures containing BFS present higher resistance to chloride ingress than that of the reference concrete without BFS, at all ages. The chloride-ion penetration value of the BFS-based concrete decreases with the increase in BFS content. Eventually, the mixture RS 75 comprising recycled aggregate and 75% BFS exhibits a pronounced resistance to chloride attack, revealing a chloride-ion penetration value of less than 1000 coulombs (very low permeability) at later ages.Incorporating BFS in concrete can inherently reduce the water permeability of concrete at all ages. Either RAC or NAC containing high volume BFS (>45%) at later ages may lead to lower water permeability, namely, superior durability to the concrete with BFS.Based on the results and findings of the experimental work for concrete with w/cm ratio in the range of 0.30 to 0.50 and with BFS content in the range of 0% to 75% by weight of the total cementitious material as cement replacement, the following conclusions can be drawn:


Escherichia coli inoculated into human-associated communities in the presence and absence of the broad and narrow spectrum antibiotics rifampicin and polymyxin B, respectively. We found strong evidence of community-level suppression of the resistant strain in the absence of antibiotics and, despite large changes in community composition and abundance following rifampicin exposure, suppression of the invading resistant strain was maintained in both antibiotic treatments. Instead, the strength of competitive suppression was more strongly associated with the source community . This suggests microbiome composition strongly influences the competitive suppression of antibiotic-resistant strains, but at least some antibiotic-associated disruption can be tolerated before competitive release is observed. A deeper understanding of this association will aid the development of ecologically-aware strategies for managing antibiotic resistance.In light of their adverse impacts on resident microbial communities, it is widely predicted that broad-spectrum antibiotics can promote the spread of resistance by releasing resistant strains from competition with other strains and species. We investigated the competitive suppression of a resistant strain of  The overuse of broad-spectrum antibiotics in clinical and agricultural settings is a key driver of the current antibiotic resistance crisis . ResearcEscherichia coli K-12 MG1655) inoculated into gut microbiome communities collected from human faecal samples. The focal strain was jointly resistant to the broad-spectrum antibiotic rifampicin  and the narrow spectrum antibiotic polymyxin B (only targets Gram-negatives). The focal strain was inoculated alongside live or sterile slurry produced using a sample from one of three healthy human donors  of a focal strain (ribed in ) into cuIn the absence of either antibiotic, focal strain density after 24 h was significantly lower in the presence of the three donor communities, indicative of strong competitive suppression Fig. . SurprisWhat makes these results particularly striking is that, consistent with previous studies , 10, 13,A limitation of this study is that we only considered the effects of two antibiotics. Nevertheless, given the scale of community perturbation observed Fig. , we can In conclusion, these results are consistent with prevailing wisdom that healthy gut communities can suppress invading strains and thereby reduce the likelihood of resistance emerging , 9, 18. Supplementary Information


This study presented evaluation of a concrete damage process by the acoustic emission (AE) technique under uniaxial multi-step compressive loading procedure combined with digital image correlation (DIC). The results showed that AE elastic wave velocity had good stress dependence in the damage process of concrete specimens with different sizes  and coarse aggregate characteristics , and the effects of specimen sizes and coarse aggregate characteristics on the stress dependence can be nearly neglected. The standard deviation of 32 AE elastic wave velocities was used as the criterion to evaluate the relative stress ratio of concrete under different damage states, and the damage process of concrete was divided into three damage stages according to this criterion. When the standard deviation is below 70, in the range of 70 to 1700, and greater than 1700, the concrete damage process is defined as steady damage process, accelerated damage process and buckling damage process, respectively. The accuracy of the presented evaluation methodology was demonstrated by comparative results with digital image correlation. The results indicate that the standard deviation of AE elastic wave velocities can potentially serve as a reliable, convenient, and non-destructive evaluation criterion of concrete damage state under uniaxial compressive loading. The durability, functionality and safety of concrete structures have aging effects, and will deteriorate to different degrees with the duration of service. A large number of engineering practices have shown that with the change in the external environment, and enhancement of the environmental stress of concrete structures beyond a certain stress level, cracks in these rock mass begin to develop, expand, and penetrate, eventually forming intricate weak surfaces and causing serious engineering problems. In order to ensure the long-term stability and economic rationality of these projects, it is necessary to conduct an effective and detailed study on the damage process of concrete structures. To estimate the health status of concrete structures in service, the in-place termly inspection of material properties, residual strength and damage degree is essential ,2,3. NonThe damage assessment of concrete materials based on acoustic emission technology was currently mostly focused on the time-domain analysis of AE characteristic parameters. The complete damage process of the materials was detected by defining the damage factor and establishing the mathematical relationship with the acoustic emission characteristic parameters. Tetsuya Suzuki  establisHowever, under the condition of compressive stress, it is a long and complicated process for concrete structures to change from initial deformation to final fracture instability. Therefore, it is of engineering significance to predict the stability of concrete structures and to ensure its safety by studying the damage process of concrete materials under compressive stress. Some studies ,31,32,333, 1630 kg/m3, and 2.84, respectively, for fine aggregate. The apparent density, accumulated density, and crushed stone value were 2.76 kg/m3, 1850 kg/m3, and 17.7%, respectively, for coarse aggregate. Fine aggregate and coarse aggregate were all cleaned by water and then dried. Continuously graded was adopted and coarse aggregate was sieved into six gradations, such as 4.75–9.5 mm, 9.5–16 mm, 16–19 mm, 19–26.5 mm, and 26.5–31.5 mm. The high-range water reducing agent with a water-reducing rate of 25% was used to maintain a consistent slump value of 180 ± 20 mm. As shown in The raw materials used in this study were Portland cement, fly ash, fine aggregate, coarse aggregate, and high-range water reducing agent. The ordinary Portland cement (PO 42.5 cement) and fly ash (Type I) meet Chinese standards. The apparent density, accumulated density, and fineness modulus were 2.65 kg/mIn this study, the loading system was a double-column bench hydraulic testing machine which is controlled by a force loading method, Micro II Express eight-channel system and DT15I-AST longitudinal wave sensors produced by Physical Acoustics Corporation of United States are used as an AE instrument, the operating frequency is in the range of 100–400 kHz, and the sampling frequency is 5 MSPS, and the detailed experimental parameters are shown in In order to obtain the characteristics of AE elastic wave velocity at different stress levels, this experiment designed a stepping load mode. The loading grads was 50 kN, and the loading rate was 1 kN/s. One loading cycle was as follows: the concrete specimen was loaded for 50 s firstly, and then the loading was kept stable for 60 s. The loading cycle was repeated until the specimen was completely damaged. During the voltage stabilization time of the AE testing system, AE elastic wave velocity was collected. The specific diagram of the loading scheme was shown in The surface deformation of the concrete specimen was measured in real time through the digital image correlation method ,38,39,40C = 1 means correlated completely, and C = 0 means irrelevant completely. The surface displacement increment of the concrete specimen is obtained by comparing two images under different loads. The horizontal displacement (u) and vertical displacement (v) are obtained by calculating the minimum correlation coefficient. Displacement and strain were measured by identifying the discrete functions of two digital gray fields. The auto sensor test (AST) was carried when the loading was kept stable, and the schematic diagram of the AE elastic wave velocity test is shown in νo), including penetrating wave velocity (νp) and surface wave velocity (νs). Penetrating wave velocity marked as red symbols is wave velocity between any two sensors located on the opposite surfaces of the concrete specimen, surface wave velocity marked as blue symbols is wave velocity between any two sensors located on the same surfaces of the concrete specimen. However, the mechanism and characteristic of AE wave propagation along the concrete specimen surface is different from that penetrating through the concrete specimen interior. Moreover, the micro-cracks firstly occurred in the concrete specimen interior. Therefore, the penetrating wave velocity more scientifically reflect the propagation characteristics of the stress wave excited by the damage source than the overall average wave velocity. In this study, the average value of AE penetrating wave velocity was defined as the AE elastic wave velocity, and the calculated equation of νp is Equation (3).One of the transmission paths of elastic wave velocity and the meaning of the overall wave velocity matrix are shown in The AE elastic wave velocity in this paper is the average value of the penetrating wave velocities from different directions in the concrete.V-0%, V-20%, V-40%, and V-60% are 4081 m/s, 4193 m/s, 4359 m/s, and 4436 m/s respectively. The initial AE elastic wave velocity of the concrete prism specimen with V-0%, V-20%, V-40%, and V-60% are 4084 m/s, 4195 m/s, 4334 m/s, and 4427 m/s, respectively. It can be found that the AE elastic wave velocity slightly increased with the increase of coarse aggregate volume fraction. In D-9.5, D-19, D-26.5, and D-31.5 were 4458 m/s, 4579 m/s, 4626 m/s, and 4651 m/s respectively. The initial AE elastic wave velocity of the concrete cube specimen with D-9.5, D-19, D-26.5, and D-31.5 were 4471 m/s, 4547 m/s, 4569 m/s, and 4587 m/s, respectively. It can be found that the AE elastic wave velocity slightly increased with the increasing of coarse aggregate maximum size. This was mainly due to the fact that elastic waves travel faster in the denser medium [The AST results of concrete specimens with different mix proportions are shown in In x represents the stress level, According to the fitting results, the relationship between AE elastic wave velocity and relative stress ratio under axial compression stress showed a good exponential function, which is given by:Furthermore, in N is the total number of the convective wave velocity (N = 32), The anisotropy of micro-cracks size and distribution can resulted from a certain degree of their preferred orientation under axial compression stress. This phenomenon led to anisotropy and discreteness of AE elastic wave velocity, and formation and development of the micro-cracks were reflected by AE elastic wave velocity. In order to better analyze the damage process of ordinary concrete, this paper uses the standard deviation of AE elastic wave velocity as the damage characteristic value. The standard deviation of AE elastic wave velocity was calculated by Equation (5).As seen in V-0%, V-20%, V-40%, and V-60% are 68.5%, 46.8%, 43.7%, and 65.1% respectively. If not otherwise specified in this chapter, these corresponding relative stress ratios are the value of the turning point in the V-0%, V-20%, V-40%, and V-60% are 62.5%, 41.6%, 40.9%, and 56.5%, respectively. In D-9.5, D-19, D-26.5, and D-31.5 are 75.0%, 72.4%, 65.1%, and 59.4%, respectively. The relative stress ratio of the concrete prism specimen with D-9.5, D-19, D-26.5, and D-31.5 are 70.8%, 61.5%, 56.5%, and 49.8%, respectively. It can be seen that the relative stress ratio is within the scope of 40.9% and 75.0% at the turning point of the damage stage I of concrete with different mix proportions and size. Otherwise, in V-0%, V-20%, V-40%, and V-60% are 0.18 mm, 0.22 mm, 0.24 mm, and 0.16 mm, respectively. The maximum horizontal strain of the concrete prism specimen with V-0%, V-20%, V-40%, and V-60% are 0.28 mm, 0.31 mm, 0.32 mm, and 0.27 mm, respectively. In D-9.5, D-19, D-26.5, and D-31.5 are 0.15 mm, 0.16 mm, 0.16 mm, and 0.18 mm, respectively. The maximum horizontal strain of the concrete prism specimen with D-9.5, D-19, D-26.5, and D-31.5 are 0.24 mm, 0.26 mm, 0.27 mm, and 0.29 mm respectively. It can be seen that the maximum horizontal strain is within the scope of 0.15 mm and 0.32 mm at the turning point of the damage stage I of concrete with different mix proportions and size. There are no obvious cracks found in the surfaces of total concrete specimens at the whole damage stage I, even at the turning point.Stage I is defined as the steady damage process of concrete with different mix proportions and specimen sizes under uniaxial compressive loading in this paper. In this stage, the standard deviation of AE elastic wave velocities changed slightly from V-0%, V-20%, V-40%, and V-60% are 94.2%, 84.3%, 81.2%, and 94.7%, respectively. If not otherwise specified in this chapter, these corresponding relative stress ratios are the value of the peak point in V-0%, V-20%, V-40%, and V-60% are 91.6%, 82.3%, 81.8%, and 91.3%, respectively. In D-9.5, D-19, D-26.5, and D-31.5 are 89.4%, 91.2%, 94.7%, and 87.2%, respectively. The relative stress ratios of the concrete prism specimen with D-9.5, D-19, D-26.5, and D-31.5 are 87.5%, 88.4%, 91.3%, and 85.7%, respectively. It can be seen that the relative stress ratio is within the scope of 81.2% and 94.7% at the peak point of the damage stage I of concrete with different mix proportions and size. Otherwise, in V-0%, V-20%, V-40%, and V-60% are 0.42 mm, 0.46 mm, 0.48 mm, and 0.39 mm, respectively. The maximum horizontal strains of the concrete prism specimen with V-0%, V-20%, V-40%, and V-60% are 0.50 mm, 0.60 mm, 0.63 mm, and 0.48 mm, respectively. In D-9.5, D-19, D-26.5, and D-31.5 are 0.33 mm, 0.34 mm, 0.39 mm, and 0.42 mm, respectively. The maximum horizontal strains of the concrete prism specimen with D-9.5, D-19, D-26.5, and D-31.5 are 0.46 mm, 0.47 mm, 0.48 mm, and 0.52 mm, respectively. It can be seen that the maximum horizontal strain is within the scope of 0.33 mm and 0.63 mm at the peak point of the damage stage II of concrete with different mix proportions and size. The micro-cracks began to occur in the surface of concrete specimens at the damage stage II, and were obviously found in the surfaces of the total concrete specimens at the peak point.The stage II is defined as the accelerated damage process of concrete with different mix proportions and specimen sizes under uniaxial compressive loading in this paper. In this stage, the standard deviation of AE elastic wave velocities began to sharply increase until to a maximum value from The stage III is defined as the buckling damage process of concrete with different mix proportions and specimen sizes under uniaxial compressive loading in this paper. In this stage, the standard deviation of AE elastic wave velocities began to sharply decrease from V-0%, V-20%, V-40%, and V-60% are 83, 139, 175, and 200, respectively. The standard deviation of AE elastic wave velocity of the concrete prism specimen, with V-0%, V-20%, V-40%, and V-60% are 73, 108, 142, and 177, respectively. It can be found that the AE elastic wave velocity slightly increased with the increase of coarse aggregate volume fraction. In D-9.5, D-19, D-26.5, and D-31.5 are 152, 190, 200, and 174 respectively. The standard deviation of AE elastic wave velocities of the concrete prism specimen with D-9.5, D-19, D-26.5, and D-31.5 are 106, 171, 177, and 152, respectively. It can be seen that the standard deviation of AE elastic velocity is within the scope of 73 and 200 at the critical point of the damage stage I of concrete with different mix proportions and size. This paper defined 70 as the waring threshold value of stage I transfer to stage II.In V-0%, V-20%, V-40%, and V-60% is 1769, 1817, 1789, and 1819, respectively. The standard deviation of AE elastic wave velocity of the concrete prism specimen with V-0%, V-20%, V-40%, and V-60% is 1714, 1846, 1827, and 1802 respectively. It can be found that the AE elastic wave velocity slightly increased with the increase of coarse aggregate volume fraction. In D-9.5, D-19, D-26.5, and D-31.5 are 1829, 1722, 1819, and 1790, respectively. The initial AE elastic wave velocity of the concrete cube specimen with D-9.5, D-19, D-26.5, and D-31.5 are 1850, 1734, 1801, and 1803, respectively. It can be seen that the standard deviation of AE elastic velocity is within the scope of 1714 and 1850 at the critical point of the damage stage II of concrete with different mix proportions and size. This paper defined 1700 as the waring threshold value of stage II transfer to stage III.In When the standard deviation of AE elastic wave velocity is in the scope of 73 and 200, the relative stress ration of concrete with different coarse aggregate characteristic and specimen size was in the scope of 40.5% and 75% at the turning point of stage I. When the standard deviation of AE elastic wave velocity was in the scope of 1714 and 1850, the relative stress ration of concrete with different coarse aggregate characteristic and specimen size was in the scope of 81.2% and 94.7% at the peak point of stage II. Therefore, this study also defined the standard deviation 70 and 1700 as the warning threshold of concrete at about 40% and 81% stress level, respectively. This definition can have a good promotion effect to the evaluation of concrete materials.(1)The AE elastic wave velocity in concrete with different mix proportion and specimen size is stress-dependent, and the relationship between AE elastic wave velocity and relative stress ratio showed a good exponential function. The effects of coarse aggregate characteristic and specimen size on the stress dependence of AE elastic wave velocity can be nearly neglected.(2)In this study, the standard deviation of 32 AE elastic wave velocities was defined as the evaluation criterion of the concrete damage process, and the whole damage process was divided into three stages by this evaluation criterion, such as a steady damage process, accelerated damage process and buckling damage process. The two key values of the standard deviation were 70 and 1700, When the standard deviation is below 70, in the range of 70 to 1700, and greater than 1700, the concrete damage process is defined as a steady damage process, accelerated damage process and buckling damage process respectively.(3)The changing history of horizontal strain verified the scientificity and reliability of this evaluation criterion. The relationship between standard deviation and relative stress ratio of the turning point and the peak point of the concrete damage process were analyzed, and the results showed that the standard deviation of AE elastic wave velocity can also be used to evaluate the stress ratio when concrete was under axial compressive loading.In this paper, the damage process of concrete under graded axial compression loading was analyzed based on the stress dependence of AE elastic wave velocity. The effects of specimen size and coarse aggregate characteristics were considered, and the conclusions can be drawn as follows:


We report a case of IgG4-RD in a patient with high IgG4 levels, low functional antibodies, and low IgM levels. He presented with bilateral orbital pseudotumors and, after initial improvement on corticosteroids, relapsed with recurrent pleural effusion and pelvic pseudotumor. He had a grossly elevated serum IgG (1905 mg/dl) with elevations in all IgG subclasses but marked elevation in IgG4 (412 mg/dl), low IgM, and low pneumococcal antibodies. Orbital mass biopsy showed polyclonal lymphocytic infiltration and increased IgG4 plasma cells. The patient was started on prednisone and tried several immunosuppressive medications including mycophenolate mofetil, methotrexate, hydroxychloroquine, and azathioprine with decrease in size of the orbital pseudotumor. During a period when the patient stopped his medications, the pseudotumor enlarged with new development of recurrent pleural effusions. He was also found to have a pelvic mass that was biopsy positive for IgG4 proliferation. This case with progression to multiorgan involvement highlights the importance of identifying patients with IgG4-related disease. In contrast to previous cases with normal-to-high IgM, the IgM was low with impaired functional antibodies. Immunoglobulin G4-related disease (IgG4-RD) is a rare relapsing-remitting fibroinflammatory disease caused by monoclonal proliferation of IgG4+ plasma cells and dense lymphoplasmacytic infiltration with reversible collagen deposition –3. It tyThe patient was a 66-year-old Caucasian male with class III obesity (BMI 42) and a history of adult-onset asthma and allergies referred by his ophthalmologist for bilateral orbital masses that showed IgG4 lymphoproliferative disease on biopsy. On the right side, the medial superior orbital mass was approximately 1.0 cm × 1.3 cm and left-sided mass was 4 mm × 4 mm. A biopsy of both right and left eyelid lesions including the bone and inferior orbital fat pad showed polyclonal lymphocytic infiltration and increased IgG4 plasma cells up to 98/HPF. The majority were T cells with a nonspecific mild increase in CD4:CD8 ratio and normal antigen expression. B cells were polyclonal with normal antigen expression. There was no immunophenotypic evidence of non-Hodgkin lymphoma. The diagnosis of IgG4 lymphoproliferative disease was given based on elevated IgG4 levels and pathologic findings, and he was referred to rheumatology. Systemic review was positive for fatigue, easy bruising and bleeding, cough, shortness of air, wheezing, hypertension, joint pain, red dry eyes, and postnasal drip. He did not smoke, denied recurrent infection other than rhinitis, and had no pertinent family history.CT of the chest showed no evidence of pulmonary parenchymal fibrosis or interstitial lung disease. Laboratory investigations at the initial visit showed elevated IgG with extremely elevated IgG4, decreased functional antibodies, and low IgM. Total IgG 1905 mg/dl (694–1618 mg/dl), IgG1 1106 mg/dl (382–929 mg/dl), IgG2 598 mg/dl (241–700 mg/dl), IgG3 98 mg/dl (22–178 mg/dl), and IgG4 412 mg/dl (4–86 mg/dl). This gives an IgG4/IgG ratio of .216 which correlates with values ≥0.2 in patients with IgG4-RD. IgA was normal at 222, and IgM was 40. His initial pneumococcal vaccination was in three years prior to presentation. Three of 14 pneumococcal antibody titers were at a protective level (>1.3 mcg/ml). Haemophilus influenza antibodies were decreased at 0.34. Angiotensin-converting enzyme (ACE) was low. Rheumatoid factor was positive at 28, and cyclic citrullinated peptide (CCP) was negative.The patient was started on prednisone 20 mg daily, and to decrease steroid need with his weight, mycophenolate mofetil 1000 mg BID was added. Mycophenolate was discontinued due to side effects of dizziness and nausea. He was dissatisfied with steroid weight gain at prednisone 20 mg daily (BMI had increased to 44.9). On this regimen, he had marked improvement in asthma symptoms and reduced size of orbital pseudotumors. To continue to try to achieve corticosteroid sparing, he briefly used methotrexate and then added hydroxychloroquine as an adjunctive treatment with no further change in tumor size, so he was unwilling to continue them. Pneumovax booster and one Prevnar booster dose were administered while the patient was off immunosuppression. An additional Prevnar booster was given while he was on low-dose prednisone. He had an increase in pneumococcal protective antibodies from 3 of 14 to 4 of 14 during treatment. When the larger right orbital pseudotumor had regressed, the patient preferred to stop taking the prednisone and declined treatment for a period of 18 months. During this time, his bilateral eye lesions returned to near baseline size before treatment. Laboratory studies at this time showed an eosinophil count of 1096 , SPEP with increased protein, decreased IgM at 20 mg/dl , IgG 3570 mg/dl , IgG4 1594 mg/dl , IgG4/IgG ratio of 0.45, ESR of 104 mm/h , and elevated CRP at 9.9 mg/dl  See . The patThe patient was unwilling to take corticosteroids again because of the efforts he had made to lose weight. He was willing to try azathioprine. He had a recurrence of left-sided pleural effusion, and repeat thoracentesis showed similar findings. He underwent pleurodesis on the left thorax. He was started on azathioprine 50 mg BID and corticosteroids, and during this period, the right orbital pseudotumor was at its smallest appearance. At this time, the patient was following with oncology and the CT/PET scan showed 3.3 cm × 1.9 cm mass in his pelvis near the left seminal vesicle as well as incidental liver lesion without PET scan uptake. Biopsy of the pelvic mass showed IgG4 stain strongly positive. Oncology started prednisone 80 mg daily with taper, and the size of the pelvic mass decreased in size to 2.1 cm × 1.1 cm. The patient continues to undergo ongoing treatment with intermittent steroids and azathioprine. Current pneumococcal antibody levels after a total of two Prevnar and two Pneumovax booster doses are 7 out of 14 protective.This patient presented with hyper IgG4-related orbital pseudotumors but, over time, developed recurrent pleural effusions and a pelvic pseudotumor with notable laboratory findings including low IgM and low functional protective antibodies.The IgG4 subclass accounts for only 3–6% of the total IgG fraction, and up to 5% of the normal healthy population may have elevated IgG4 levels , 20. IgGIn IgG4-related disease, IgM, IgA, and other IgG subclasses are frequently elevated . In contTreatment of IgG4-RD typically consists of prednisolone 0.6 mg/kg/d with gradual taper over a period of 3–6 months . PatientSeveral case studies have described incidence of immune thrombocytopenia in patients with IgG4 disease. The incidence of this finding is unknown but has been postulated to be caused by antiplatelet antibodies or other IgG subclasses of platelet antibody . This paThis case report highlights and demonstrates the relative effectiveness of steroid-sparing medications in IgG4-RD treatment, and shows a rare presentation of IgG4-RD with low IgM levels and low functional antibodies.


Infections due to resistant bacteria are associated with severe illness, increased risk for complications, hospital admissions, and higher mortality. Inappropriate use of antibiotics, which contributes to increased antibiotic resistance (ABR), is common in healthcare settings across the globe. In Cameroon, antibiotics have been reported as high as 45–70% of prescriptions. We sought to investigate the knowledge, attitudes, and perceptions regarding appropriate antibiotic use and ABR of medical doctors practicing in tertiary hospitals in Yaoundé, Cameroon.We conducted a cross-sectional survey using a 54-item self-administered questionnaire sent via email to medical doctors working in the four major tertiary hospitals of Yaoundé. The questionnaire recorded socio-demographics, perceptions on antibiotic use and ABR, sources and usefulness of education on ABR, and clinical scenarios to appraise knowledge.A total of 98/206 (48%) doctors responded. Years of experience ranged between 1 and 17 years. Most participants agreed that ABR is a problem nationwide (93%) and antibiotics are overused (96%), but only one third (32%) thought that ABR was a problem in their wards. Most respondents (65%) were confident that they use antibiotics appropriately. We found a mean knowledge score of 56% (± 14), with prescribers not influenced by patient-exerted pressure for antibiotic prescribing scoring better compared to those influenced by patients . Overall, most participants (99%) expressed interest for further education on both appropriate antibiotic use and ABR.Confidence of prescribers in their ability to appropriately use antibiotics conflicts with the low level of knowledge on antibiotic use in this group of doctors. Moreover, the opinion of the majority, that ABR is not a problem in their own backyard is in keeping with similar studies in other countries and is of significant concern. Introduction of formal antibiotic stewardship programmes in Cameroon may be a useful intervention. The threat of antibiotic resistance (ABR) is growing at an alarming rate. The Centers for Diseases Control and Prevention (CDC) report more than 2.8 million antibiotic-resistant infections in the United States each year . This isAny use of antibiotics, even appropriate, contributes to the development of resistance. Emergence of ABR is a natural phenomenon in response to selection pressure imposed by an antibiotic, which allows selection of strains able to resist the action of that antibiotic. However, inappropriate use of antibiotics, which is associated with increased antibiotic resistance, can adversely impact the clinical outcome of patients. Infections due to resistant bacteria are associated with severe disease, increased risk of complications and hospital admission and higher mortality rate , 5. InapSalmonella typhi and Klebsiella spp. [The overall goal of mitigating ABR is to preserve the effectiveness of antibiotics. Health care workers have an essential role to play in antibiotic stewardship, but their role may be jeopardized if their knowledge or practices are sub-optimal. CDC estimates that 30% (47 million antibiotics courses) of all antibiotics prescribed each year in outpatient clinics and emergency departments in the US are unnecessary . This filla spp. . If patilla spp. , 13. In lla spp. , 15. HerWe conducted a cross-sectional survey from May 2018 to February 2019, targeting all medical doctors practicing in major tertiary hospitals of Yaoundé, Cameroon, namely General Hospital (YGH), Gynaeco-Obstetric and Paediatrics Hospital (YGOPH), Central Hospital (YCH), and University Teaching Hospital (YUCH). The tertiary hospitals together employ approximatively 260 medical doctors including specialists, registrars, and general practitioners.A convenience sampling was used. An email invitation generated from Research Electronic Data Capture (REDCap) tools  hosted aSocio-demographics,Perceptions on the importance of ABR and the awareness about causes of ABR,Attitudes and practices in the choice of antibiotics and potential interventions to improve antibiotic use,Knowledge on ABR and antibiotic use rated based on ten clinical cases on: infection prevention and control (IPC), appropriate prescription of antibiotics  Gram-negative infections), duration of therapy, de-escalation, and adverse effects of antibiotics.The self-administered questionnaire comprised 54 questions and ten clinical cases structured in four sections:The questions have been made simple and unambiguous. The questionnaire was anonymous and was in English and French, the two official languages of Cameroon. The choice of the clinical cases and micro-organisms were based on the prevalence/frequency of the diseases in the selected hospitals irrespective of the wards’ specificities and are similar to the questions used in previous studies on knowledge, attitudes and practices on antibiotics use and antibiotics resistance .Electronic informed consent was obtained from each participant. All procedures were approved by both the Human Research Ethics Committee of the University of Cape Town (HREC REF: 203/2018), South Africa, and the Ethics Committee for Human Health Research in the Centre Region, Cameroon (REF: 0548/CRERSHC/2018). The study was performed in accordance with the Declaration of Helsinki.Descriptive statistics were used to characterize the total sample. Continuous variables were described using mean with standard deviation or median with interquartile range depending on the distribution of data. Proportions were calculated for categorical variables. Composite scoring of perceptions and attitudes was based on the five-point Likert-type response scales: strongly agree/agree/neutral/disagree/strongly disagree, strongly influence/influence/neutral/do not influence/do not influence at all, often/sometimes/rarely/never/not familiar, and very helpful/helpful/neutral/not helpful/not helpful at all . Likert-Of the 206 doctors invited to participate to the study, 98 (48%) responded and 66% (65/98) completed the questionnaire in its entirety. The median age was 31 years (interquartile range (IQR) 29–34) and 55% were female. The majority of respondents were residents (60%)  of respondents.The overall mean score on the knowledge questionnaire was 56% (± 14), with over a quarter 26%, 17/65) of participants scoring less than 50%. Participants scored well regarding the use of antibiotics for common infections—community acquired pneumonia (CAP) 71%, urinary tract infection (85%)—but scored poorly on antibiotic de-escalation  and duration of antibiotic prophylaxis (25%) . Moreover, perceptions on antibiotic use and ABR were not associated with knowledge. Participants who do not mainly rely on textbooks as resources for antibiotics prescribing scored better than those who do  , professional/learned societies’ guidelines , WHO  guidelines  and smart phones apps . Our results revealed that Infectious Diseases (ID) specialists are used as resources for antibiotic prescribing by only 58% (42/73) of doctors surveyed. Most respondents rely on other colleagues  and consultants  were the least utilised resource when prescribing antibiotics.During the last 12 months, respondents attended a lecture or workshop or course addressing the following topics: diagnosis of infection , dose and duration of antibiotic therapy , indications for antibiotic use , spectrum of activity of commonly used antibiotics , indications for intravenous antibiotic use  and principles of Infection Prevention and Control . Nearly all participants agreed that medical journals  and conferences  are useful resources for learning on antibiotic use and resistance. Pharmaceutical representatives were considered useful resources by 44% (31/71) of respondents. It was almost unanimously felt  that development of local guidelines would be useful in improving antibiotic use and mitigating ABR. Furthermore, almost all respondents  were of the opinion that more education on antibiotic use and resistance would be helpful.Most respondents, 93% (74/80) agreed that ABR is a significant problem in Cameroon, but only 40% (32/80) believed that it is a problem in their hospital wards. Interestingly, 54% (42/78) of doctors disagreed that poor hand hygiene is a cause for spread of antibiotic resistant bacteria Fig. .Fig. 1PeDespite acknowledgement by 96% (77/80) of participants that antibiotics are overused in Cameroon, only a third believed that antibiotics are overused in their ward Fig. . Two-thiAlmost all respondents  agreed that inappropriate antibiotic use can harm patients Fig. .The leading factors influencing antibiotic prescribing were guidelines from learned societies and WHO (100%), quality of drug and cost effectiveness ratio (99% and 96% respectively), immunosuppression and/or critical clinical status of the patient (90%) Table . InteresThis study presents the first analysis of the knowledge, attitudes, and perceptions of physician’s use of antibiotics at tertiary level hospitals in Cameroon. Awareness on antibiotic use and drivers of resistance are a critical first step to assist prescribers in using antibiotics appropriately and optimally.Participants in this study demonstrated a low level of knowledge and inaccurate perceptions on appropriate antibiotic use and ABR. These results are in keeping with previous studies in LMICs , 19. In Drivers of ABR include lack of education of HCWs, beliefs, attitudes, and knowledge of HCWs on appropriate antibiotic use and ABR among others . Most reEncouragingly, whereas a study conducted in DRC found that the majority of respondents disagreed that inappropriate use of antibiotics can harm patients, two thirds of doctors in our cohort perceived this as a threat to patients’ safety . InapproPatient expectation has been found to influence antibiotic prescription as shown in a study on antibiotic prescription for respiratory tract infections which revealed that physicians prescribe more antibiotics when they perceive a desire from the patient , 23. In The WHO reports that “globally, most prescribers receive most of their prescribing information from the pharmaceutical industry and in many countries, this is the only information they receive” . Our datThe knowledge level of the doctors in this cohort is somewhat lower than that found in similar studies conducted in DRC and USA , 30. It Limitations to this study include the small size of our cohort, due to the relatively low response rate. Although this phenomenon is inherent to web based KAP studies, it can be partly explained in our study by limited access to internet. This could limit the generalisation of our results to the entire country. As previously shown in KAP studies, the respondents in this study may have had tendency to provide ‘socially desirable’ answers. This type of studies also provides reported instead of observed practice and the interviewees might adapt their answers to the context. To minimise the potential biases, we stressed on complete respondent’s confidentiality in our survey. We have also recommended respondents to take the questionnaire individually and not as a group. We believe that studies on larger cohorts at different levels of care, and in a wider variety of HCWs are ideally needed to confirm our findings. Confirmation of these data may help inform national policies on appropriate antibiotic use and ABR in Cameroon. Further research on the most effective tools for education of HCWs with focus on increasing knowledge on ABR should be conducted.This study has highlighted gaps in the knowledge, attitudes, and perceptions toward ABR and antibiotic use of medical doctors working at the highest level of the healthcare system in Cameroon. The low level of knowledge of prescribers contrasts with their high confidence in appropriate use of antibiotics. Additionally, their non-recognition of ABR as a problem in their ward or hospital is worrisome. Establishment of local guidelines as well as antibiotic stewardship programmes and other educational tools could be a way to improve the use of antibiotics and ABR.


The magnetoelectric domains/domain walls in intrinsic multiferroics can exhibit intriguing topological nanoscale textures. These thermodynamically stabilized nano-textures are compared with nanoscale polar structures in nanostructured composite films. In addition, we show that the consideration of broken symmetries is essential to understand the macroscopic origin of multiferroicity and also to predict new multiferroicity.6 vortex lines, resulting in a topological vortex–antivortex structure, in a 2D-cut view of hexagonal RMnO3 (R = rare earths) . These multiferroics with various broken symmetries always accompany domains and domain walls. Thus, the study of the magnetoelectric properties of these domains and domain walls as well as the spatial configurations of these domains and domain walls are quintessential to understanding and utilizing bulk magnetoelectric effects in multiferroics. One important discovery in multiferroic domains/domain walls is 3D Zsee Fig.  1]. 2D . 2D 6 voscovered . It shouP) are strongly coupled, so, for instance, polarization or dielectric constant changes drastically when an applied magnetic field (H) can induce a magnetic phase transition. This phase-transition-driven magnetoelectric effect can be termed the ‘colossal magnetoelectric effect’, similar to the colossal magnetoresistance effect in ferromagnetic perovskite manganites where an applied magnetic field induces a metal–insulator transition, so electric resistance changes drastically. A large number of new MDF compounds have been discovered during the last decade. Since polarization (and magnetization (M)) is a 1D entity vector), (quasi-)1D schematics with broken symmetries can often explain the multiferroicity in most MDF materials [R = π rotation operation with the rotation axis perpendicular to the P/M direction, R = π rotation operation with the rotation axis along the P/M direction, I = space inversion, M = mirror operation with the mirror plan perpendicular to the P/M direction, M = mirror operation with the mirror plane containing the P/M direction, T = time-reversal operation. For example, {R, I, M} is the set of all broken symmetries of P, and all (quasi-)1D spin configurations on the left-hand side of Fig. R, I, M}. Thus, they do have a symmetry operational similarity  in Fig. 3 and LiCu2O2 corresponds to Fig. 4)2 and CaMn7O12 can be explained with Fig. 3CoMnO6, TbMn2O5 and orthorhombic HoMnO3 [2CoGe2O7 can be described by Fig. H only have broken {I, M}, but the left-hand-side entities with non-zero H have now broken all of {R, I, M}, so becoming SOS with P, which is consistent with e.g. the linear magnetoelectric (ME) effects in Cr2O3  [R, M, T} is the set of all broken symmetries of  M. Since any static configuration of P cannot break T, a time component has to be incorporated into the P configuration. Two examples having SOS with M are shown in Fig. M can be induced [P or M. However, it turns out that e.g. all magnets with cycloidal spin order, corresponding to Fig. P. Thus, these situations appear to resonate with the famous statement of Murray Gell-Mann: ‘Everything not forbidden is compulsory.’ In other words, when multiferroicity is allowed by the consideration of broken symmetries, the effect is often large enough, and so experimentally observable.It turns out that intrinsic multiferroicity can often be understood from the consideration of broken symmetries. Magnetic order naturally breaks time-reversal symmetry, and a spatially varying magnetic lattice, combined with a centrosymmetric crystallographic lattice above a magnetic transition temperature, can break space-inversion symmetry, leading to multiferroicity through the spin–orbit interaction, called magnetism-driven ferroelectricity (MDF). In these MDF compounds, magnetism and polarization  . It is a induced . Figure  induced  is relevIn summary, the intriguing topological structures of magnetoelectric domains/domain walls in multiferroics have been discovered and need to be further explored. In particular, the understanding of the magnetoelectric and dynamics properties of domain walls in multiferroics is at a primitive stage and needs to be further investigated. The broken-symmetry consideration with 1D entities is a strong starting point to understand multiferroicity. Furthermore, with the concept of SOS, it is rather straightforward to predict new spin textures and polarization textures that induce polarization and magnetization, respectively. Thus, this simple but powerful approach will open a new avenue to discover new multiferroic materials and phenomena.


Cilevirus groups enveloped single-stranded (+) RNA virus members of the family Kitaviridae, order Martellivirales. Proteins P15, scarcely conserved polypeptides encoded by cileviruses, have no apparent homologs in public databases. Accordingly, the open reading frames (ORFs) p15, located at the 5′-end of the viral RNA2 molecules, are considered orphan genes (ORFans). In this study, we have delved into ORFs p15 and the relatively poorly understood biochemical properties of the proteins P15 to posit their importance for viruses across the genus and theorize on their origin. We detected that the ORFs p15 are under purifying selection and that, in some viral strains, the use of synonymous codons is biased, which might be a sign of adaptation to their plant hosts. Despite the high amino acid sequence divergence, proteins P15 show the conserved motif [FY]-L-x(3)-[FL]-H-x-x-[LIV]-S-C-x-C-x(2)-C-x-G-x-C, which occurs exclusively in members of this protein family. Proteins P15 also show a common predicted 3D structure that resembles the helical scaffold of the protein ORF49 encoded by radinoviruses and the phosphoprotein C-terminal domain of mononegavirids. Based on the 3D structural similarities of P15, we suggest elements of common ancestry, conserved functionality, and relevant amino acid residues. We conclude by postulating a plausible evolutionary trajectory of ORFans p15 and the 5′-end of the RNA2 of cileviruses considering both protein fold superpositions and comparative genomic analyses with the closest kitaviruses, negeviruses, nege/kita-like viruses, and unrelated viruses that share the ecological niches of cileviruses.The genus  Orphan genes (ORFans) code for proteins with unrecognized homologs in any other species . They arKitaviridae, order Martellivirales, is a family of heterogeneous plant-infecting viruses displaying two, three, or four segments of single-stranded positive-sense RNA molecules as genomes, which have been assigned into the genera Cilevirus, Higrevirus, and Blunervirus, respectively  and p29 (putative coat protein) are in RNA 1 (≈9.0 kb); whilst the ORFs p32 (movement protein), p61, p24, and p15 are contained in the RNA2 (≈5.0 kb)   . RNA2 intructure . P24 is tructure . ORF p61wavirus) . P24 diswavirus) . ORF p15 viruses .p15 considering the genomic context in the 5′-end of the RNA2 in cileviruses. A meaningful part of the study has been founded on the comparisons of the protein folds using the principles of structure-based phylogenetic analyses.In this study, based on an integrator process comprising genomics, population genetics, usage of synonymous codons, and tridimensional (3D) structures, we elaborated a hypothesis about the conserved putative functionality of the P15 proteins across the genus. Following a chain of logical thinking, we theorize on the origin and evolution of the ORF p15 (393 nts)  .p15  and nucleotide diversity (π) ≤ 0.01  ≤ 0.01 . Accordi) ≤ 0.01 . P15 enc) ≤ 0.01   ≤ 0.01 . Transiea plants . When exrain CRD .p15 is almost 10-fold higher than among the CiLV-C isolates. Yet, as well as for CiLV-C, ORFs p15 from CiLV-C2 and PfGSV show signatures of purifying selection (ω < 1). P15 proteins of these two viruses are phylogenetically closer to each other and more distant from that in CiLV-C  sequences reveal very low identity values, approximately 14 or 20%, between the proteins from CiLV-C and PfGSV or CiLV-C2, respectively. Higher values, still moderate, approximately 55% aa sequence identity, are detected in the comparisons between P15 from CiLV-C2 and PfGSV , 2020. RCodon usage bias (CUB) refers to differences in the frequency of occurrence of synonymous codons in coding sequences . In viru1 and CAIcal2, respectively. Analyses of both ENc and RSCU of the cilevirus ORFs revealed codon usage bias. Even though the means of the ENc values of ORFs both at virus and genus levels were generally higher than 50, some viral isolates and ORFs, e.g., PfGSV_Snp1 and ORF p15, had mean values lower than 50 which are considered an indicator of skewed codon usage. Within this group, the ORF p15 of CiLV-C2_Hw displayed a distinctly low ENc value, ≈35  (To get further insight into the codon preferences of ed RCDI) . It shoued RCDI)  estimateed RCDI) . A lowerCitrus × sinensis), passion fruit (Passiflora spp.), orchid (Oncidium spp.) . For the sake of the comparisons, the analyses were performed considering both the sum of natural and experimental host plants and two subsets of plants, each comprising natural or experimental hosts. Altogether, the analysis included plants belonging to five families, including perennial woody (citrus) and perennial herbaceous (orchids) plants, short-lived evergreen perennial vine (passion fruit), and herbaceous annual (common beans and Arabidopsis) plants. Values of COUSIN and the ratio RCDI/eRCDI were visualized and compared using hierarchical clustering. The accuracy of the assessment could be potentially increased as new annotated genomes of cilevirus host plants are available.The values of COUSIN and the ratio RCDI/eRCDI were calculated using the set of host plants whose codon usage data could be directly retrieved from, or calculated using available genomic information in, public databases. Codon usage frequencies of some natural and experimental hosts of cileviruses, i.e., citrus (um spp.) , Arabidothaliana , and Phavulgaris  were retodon v44 . Coding p61 (1.28 ± 0.44), RdRp (1.19 ± 0.36), p32 (1.15 ± 0.37), and p24 (1.09 ± 0.38), whereas mean values below or near to 1 were observed for the ORFs p15 (0.89 ± 0.53) and p29 (0.93 ± 0.35)  . COUSIN al hosts . In a gl protein .RdRp and p61 bear the lowest mean values, followed in ascending order by p24, p29, and p32, and finally p15  and UniProtKB/TrEMBL8  databases retrieved 30 hits spanned in 30 sequences, all of them exclusively corresponding to the P15 proteins from CiLV-C, CiLV-C2, and PfGSV. Additionally, no hits were retrieved from a similar search but against a randomized UniProtKB/Swiss-Prot database, i.e., reversed option. According to ScanProsite, the conserved sequence motif has an approximate number of expected random matches of 6.97 × 10–08 in 100,000 sequences . Altogether, these results suggested a low probability of P15 matches by chance and, thus, highlighted the singular occurrence of the identified cysteine-rich domain in the P15 protein family.Even though a low global sequence identity of less than 25% was observed for P15 proteins, the consensus sequence obtained from a multiple sequence alignment of the cysteine-rich domain reveals a stretch of highly conserved residues organized in the sequence motif {[FY]-L-x(3)-[FL]-H-x-[LIV]-S-C-x-C-x(2)-C-x-G-x-C} . Besides6  search u9  and Q-score = 0.31 over 94 aligned residues were obtained, whereas in those from CiLV-C2 the values were RMSD = 3.83 Å and Q-score = 0.01 over 22 aligned residues. In P15 from the PfGSV isolates, the values were an overall RMSD = 4.1 Å and Q-score = 0.02 over 30 aligned residues. Detailed analysis of the 3D model for the CiLV-C_Ar02 P15 indicated that cysteine residues at positions 85 (Cys85) and 92 (Cys92) could form a disulfide bridge and consequently stabilize the four-helical bundle. Remarkably, this two-cysteine-residues pattern is also present in the conserved sequence motif across the P15 proteins. However, since the spatial localization of the two cysteines is not close enough in some 3D models, the formation of a disulfide bridge is not completely evident. Such discrepancies could ensue from the analysis of low-resolution 3D models.Among the P15 from CiLV-C isolates, an overall RMSD = 2.47 Å and The resolved crystal structures of ORF49_ HHV-8 (PDB ID: 5ipx) and ORF49 from the murine herpesvirus 68   show a fCTD) of mononegaviruses  comprises five α-helices that have an overall topology that although with different structural features, seems to be conserved with those in other rhabdoviruses, filoviruses, and paramyxoviruses   with overall RMSD = 4.0 Å and Q-score = 0.04 over 32 aligned residues  in HHV-8, which drives the expression of all lytic genes (The Poviruses . PCTD crD: 2wzl)  and rabiD: 2wzl)  with overesidues . In the ic genes . Presentic genes .p11  . The prop11  that wasp11  nor annop15 homologs based on the presence of a zinc-finger-like motif was expanded to nege/kita-like viruses and other related arthropod-infecting viruses. It also included previously ignored or poorly characterized putative ORFs. In members of the proposed subgroup Centivirus of the nege/kita-like viruses, a homolog of WhIV-8 p11 was identified in the uncharacterized Glycine dolichocarpa virus   with the Pfam motif C4-type zinc-finger of DNA polymerase delta (PF14260). Similarly, the ORF p19 in the putative centivirus Wuhan house centipede virus 1 (WHCV-1) and ORF p9 of Hubei virga-like virus 9 (HVLV-9) encode proteins with signatures of a putative zinc-finger domain  of the RNA binding superfamily (PF15247). The N-terminal of the ORF3-encoded protein of Pyrrhocoris apterus virus slightly resembles the canonical Pfam DSRM  architecture, whereas, although with low sequence similarity, the C-terminal end of this protein displays a conservative basic RNA-interacting motif. However, neither nucleotide sequences of these ORFs nor their predicted polypeptides show significant sequence identity to any element across cileviruses.Our search for supposed 1009300) . Proteinr domain , which i9. Although P11 proteins show α helix scaffolds, the arrangement of helixes is different from that observed in P15. Multiple structural alignments of 3D models by PDBeFold11 indicated that only one α-helix in P11 proteins shows structural similarity to α-helices in the P15 3D models . The lack of overall sequence or 3D structure similarity between both groups of proteins drastically reduces the probability of a common origin.To get further insight into the putative relationships between P15 and P11 proteins of WhIV-8 and GDV, their 3D structures were predicted using the I-TASSER serverp15, the genomic stretch extended up to p61 in the 5′-end of the RNA2 of cileviruses is known as the intergenic region (IR). However, this is not a proper description because rather than lacking ORFs, the IR lacks ORFs greater than 300 nucleotides. In silico tools have traditionally considered a minimum of 100 amino acids for an ORF to be annotated as a putative coding protein sequence, which has led to the inaccurate annotation of certain genomes. However, despite the detection of those small ORFs, the IRs of cileviruses show a very low density of predicted coding sequences, only 20–30%, with large non-coding stretches  , presents four regularly distributed cysteine residues and low sequence identity with motifs identified in the cytokine-induced anti-apoptosis inhibitor 1 , and PGC7/Stella/Dppa3-like domain  (In congruence with ORF y (≤45%) . With vay (≤45%) , 2020. OPF15549) .p8 overlapping the ORF p15 of CiLV-C. ORF p8 is present in every sequenced virus of the three lineages of CiLV-C   , a specigrevirus , poses a-p32-p24 . RNA2 of fitness . Alterna fitness . Howeverp15 in each of the three cilevirus species is under purifying selection, suggesting an ongoing action to conserve its nucleotide sequence, most likely precluding the change of amino acid residues and preserving function at directly selected sites  a reminiscent ancient ORF from the monopartite ancestor or (ii) its acquisition from a heterologous source by recombination, i.e., horizontal gene transfer. Although we lack evidence to exclude any of these possibilities, our approach using prediction and computational analysis of 3D protein structures has provided information on a possible external origin of P15 proteins. The scaffold of α-helixes detected in P15 shows structural resemblance with those detected in well-characterized proteins from herpesvirids and mononegavirids. Importantly, the odds of the 3D structure of P15 is the result of convergence are very low considering the small number of protein folds available  divergence from the coding sequence of a preexisting gene (ii) de novo appearance from intergenic or non-genic regions  since p15 across cileviruses can be considered alleles descendant from a common ancestor likely co-opted from another virus, this ORF should not be longer considered an orphan gene, and (ii) the markedly chimeric origin of the RNA2 genome segment, which adds further support to what appears to be a common feature of members of the family Kitaviridae (In this study, we have addressed one of the most intriguing features of the molecular biology of cileviruses: the 5′ end of the RNA2 molecule and its two most salient elements, the ORF  protein . Taken taviridae .The original contributions presented in the study are included in the article/PR-G and TP: conceptualization. PR-G, TP, CC-J, and GA: formal analysis, investigation, and methodology. JF-A: funding acquisition. TP and JF-A: resources. PR-G and TP: writing—original draft. PR-G, TP, CC-J, GA, and JF-A: writing—review and editing. All authors approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Prominence of concrete is characterized by its high mechanical properties and durability, combined with multifunctionality and aesthetic appeal. Development of alternative eco-friendly or multipurpose materials has conditioned improvements in concrete mix design to optimize concrete production speed and price, as well as carbon footprint. Artificial neural networks represent a new and efficient tool in achieving optimal concrete mixtures according to its intended function. This paper addresses concrete mix design and the application of artificial neural networks (ANNs) for self-sensing concrete. The authors review concrete mix design methods and the development of ANNs for prediction of properties for various types of concrete. Furthermore, the authors present developments and applications of ANNs for prediction of compressive strength and flexural strength of carbon nanotubes/carbon nanofibers (CNT/CNF) reinforced concrete using experimental results for the learning process. The goal is to bring the ANN approach closer to a variety of concrete researchers and possibly propose the implementation of ANNs in the civil engineering practice. Concrete is the most used construction material, primarily because of its high compressive strength and durability, but also for its impermeability and fire and corrosion resistance. Over the years, engineers have been developing different concretes for various and multiple purposes, with varieties spanning from ordinary concrete to specific types such as lightweight, high-performance , green, or nano-reinforced concrete. Since processes of hydration and hardening are irreversible, any mistake in the design of the mixture may be costly in construction stage and hazardous in the exploitation stage. Therefore, optimal mix proportions and prediction of concrete properties have been studied over the past five decades, and many different methods have been developed to this end. Furthermore, in the past decade, machine learning (ML) methods emerged as a new tool of ensuring optimal concrete mixtures, and among many ML methods, artificial neural networks (ANNs) have been fairly successful in ensuring favorable results.This paper reviews the development of ANNs for the purposes of concrete mix design and presents ANN models developed for prediction of compressive strength and flexural strength of CNT/CNF reinforced concrete. The goal of the authors is to bring the ANN approach closer to a variety of concrete behavior researchers and possibly propose the development and implementation of ANNs in mix design of nano-reinforced concrete.Concrete mix design refers only to designed mixtures and does not imply prescribed, standard, or designated mixtures of concrete. It means that the designer specifies limiting values of needed key characteristics, assuming their effect on the properties of concrete. Design in the strict sense of the word is not possible; materials are variable in several aspects and many of their properties cannot be assessed quantitatively. Concrete properties measured in the fresh state are usually workability and slump, and in the hardened state compressive strength, permeability, and durability. Overall, the 28-day compressive strength is the critical design parameter for structural concrete. Concrete mix design implies one mixture for one set of properties, and every production that requires slightly different parameters comprehends a completely new design. Consequently, the entire process is relatively long due to trial mixing and testing of every specimen. It is a time-consuming procedure that not only increases the waste of material but also the cost of concrete production.General classification includes analytical, semi-experimental, experimental, and statistical methods of concrete mix design. Analytical methods are used to reduce number of trial mixes to a minimum, rationalizing initial proportioning procedure into a systematic process based on detailed information about specific weight of components and formulae established from previously conducted testing . In geneSemi-experimental methods are based on combining the experimental models with various analytical tools such as machine learning (ML) methods. Development of more sophisticated non-parametric ML methods and growing availability of experimental datasets are opening opportunities to forecast compressive strength and other properties with higher accuracy and wider application range. This type of semi-experimental methods have shown to be useful in concrete mix design for prediction of various properties of fresh and hardened concrete.Machine learning belongs to the field of artificial intelligence, and it is used for prediction, i.e., classification that represents the prediction of the categorical value, or regression, which is the prediction of the numerical value . CertainArtificial neural networks are computational structures that are trained to learn patterns from examples. The development of ANNs is inspired by the human brain, a biological neural network functioning based on communication between neurons. The theory of connectionism was first proposed in the 1940s to simulate processing of the human brain; however, at first, the idea was abandoned for many years until contribution of several researchers led a new interest in this subject. ANNs are used in a wide variety of problems such as recalling data, classifying patterns, performing general mapping from input to output patterns, grouping similar patterns, or solving constrained optimization problems . Neural x1, x2, …, xm are the inputs, k, kb is the bias for the neuron k, function f is an activation function, and Feed-forward network topology represents dataflow from input to output units, where data processing can extend over multiple layers, but no feedback connections are present . Mathemae output .This process fits the architecture of a back-propagation algorithm. The “backpropagation learning rule” was established in 1985 as a solution to problems that were occurring with single layer or bilayer networks. It is considered a generalization of the delta rule ,43,46 foThe topic of ANNs in concrete mix design was primarily centered toward predictions of optimal mix proportions rather than predictions of the properties of concrete. Oh et al.  first diLee  showed aConversely, research work such as that of Dantas et al.  focused Several investigations were conducted from building sites to make ANN models more pragmatic and useful in realistic conditions. In situ works imply a lack of controllability of environmental conditions, which influence concrete in both a fresh and hardened state. Therefore, testing of field concrete is a more challenging task compared to laboratory, but the dataset is far more extensive and insightful. Namyong et al.  presenteAlthough most research work is focused on predicting the compressive strength, there are notable works handling other properties of concrete. Predictions of mechanical properties of hardened concrete such as flexural strength  for modiFinally, reviewing the application of ANNs for prediction of concrete properties may provide conclusions. A number of hidden layers should be kept low. More hidden layers prolong the learning process and often cause false positive result. Algorithms, usually Levenberg–Marquardt, resilient BP, BFGS quasi-Newton, and Polak–Ribiere conjugate gradient, are chosen according to the nature of the data and type of the output. Size of the dataset influences the algorithm performance and thus the total error. It has been repeatedly shown that the Levenberg–Marquardt algorithm corresponds best with a medium-sized dataset containing a few hundred data tuples. Activation functions are by default non-linear, mostly sigmoid (logistic) and hyperbolic tangent since these functions coincide with material behavior of concrete. Testing tuples must be diverse to give the best evaluation of the model, but at the same time kept within a realistic confidence interval.This work attempts to establish a working ANN model for prediction of compressive strength and flexural strength of ordinary concrete reinforced by carbon nanotubes (CNTs) or carbon nanofibers (CNFs). All models are developed, trained, and tested using Matlab Neural Fitting tool. Following, we describe the procedure of establishing optimal parameters of the ANN models for each concrete property separately and combined. The workflow follows typical schematic of extracting and collecting of the data from literature, preprocessing, and finally application of the dataset as an input for the ANN , and it Parameters describing the basis of a neural network are architecture, algorithm, and activation function. Architecture, or topology, of the ANN model refers to the number of layers and neurons within each layer. The function of a hidden layer is to detect and establish relationship between inputs and outputs. In this work, all ANN models use “shallow” architecture, meaning that there is only one hidden layer. Size of the hidden layer is problem specific and depends on the training patterns. Namely, there is no established rule for selecting the number of neurons for each hidden layer. It must be sufficiently low to ensure generalization of the network, but if it is too low, the network will not be able to learn the relationships from the data and generalize to new data ,7,81. MaThis research work uses a varied number of neurons, calculated according to Equation (3). Except for the dependency between the number of input and hidden neurons given by the literature, additional dependency is investigated to establish if there is an effect to the performance of the model.Back-propagation feed-forward multiple layer neural networks are trained with many different training algorithms, depending on the specific problem as well as the size of the network and the training dataset. The most used algorithm within a concrete mix design is the Levenberg–Marquardt algorithm due to its speed and robustness , and it Activation function represents a “mathematical gate”, which data “goes through” on its way to the next layer of the neural network. In other words, output signal of the neuron relates to input via the activation function . Choice 9; learning rate is 10−6; and 6 cross-validation checks during learning.Learning process for all ANN models in this work is provided by the Levenberg–Marquardt training algorithm with unipolar sigmoid activation function and linear transfer function. Other parameters of the model performance are maximum number of epochs at 1000; training momentum is 10A prerequisite for successful functioning of an ANN is the use of extensive and reliable dataset capable of appropriate training . Form, cMore data i.e., bigger batch size, does not necessarily lead to a better network. Although a richer dataset leads to better generalization, if the quality of the data is not at a high level, batch size itself does not make a difference for network performance.In this work, datasets represent the collection of experimental data given in the literature ,110,111.ANN models are developed and divided by their respective dataset, since the number of hidden neurons depends on the number of input neurons, which varies by the dataset. For each dataset, 12 ANN models are developed and divided into four subgroups according to the subset ratio, and each subgroup includes three ANN models with different number of hidden neurons, according to Equation (3). There are 36 ANN models in total, which are summarized in The ultimate goal of any training procedure is to minimize the mean square error (MSE) and mean absolute error (MAE) and maximize the coefficient of regression R. The iterations run until no improvement in MSE and MAE is found. Accuracy of the results is usually presented by the value of R, meaning that in case of a perfect fit between output and target value, this value would be equal to 1. In general, every phase of the network development demands a trial-and-error procedure to check suitability and stability of the network. After the initial training of the ANN models, response values R and MSE indicate the efficiency of the model. Response values for all ANN models are given in As it may be seen in Concrete mix design requires extensive knowledge of many expert issues. Inherently, obtaining concrete with appropriate parameters ensures reliable use during the prescribed exploitation period. In construction of massive structures, or commercial and residential buildings, concrete mix design assures that required parameters are achieved while keeping the costs at the necessary minimum. The ANN approach gives the possibility to freely adjust and change mix proportions according to exposure to certain materials and needed type of concrete. The construction speed and quality control may be significantly increased while decreasing the costs and carbon footprint by using ANNs to determine and predict properties of fresh and hardened concrete. Additionally, ANNs represent an appealing tool for modeling complex systems because of features such as efficiency, generalization, and simplicity. This paper assesses the predictions of compressive strength and flexural strength of CNT/CNF reinforced concrete. To this purpose, 36 models were developed using three different datasets. One dataset uses both target values, compressive and flexural strength, and the remainder have a singular property as the target value. The models were trained using Matlab Neural Fitting application. After training, validation, and testing, it may be concluded that all models show satisfactory behavior with the given topologies. In addition, all three variants of hidden neurons used here correspond to this type of neural network in achieving successful training of the network. Moreover, initial research shows that mechanical properties of CNT/CNF reinforced concrete can be successfully predicted using the described ANN models. Out of 36 models in total, models COMP_70_10_20-41, FLEX_80_5_15-16, and C+F_80_5_15-11 exhibited optimal results, most uniform error distribution, and therefore, overall most favorable behavior. The regression coefficients for training, testing, and validation stage are high and the scattering of the results is relatively small for these models. Thus, the results confirmed the correctness of the adopted models and calculations. It may be concluded that tested network topology, algorithm, and activation function give satisfactory results in assessing the problems of the mechanical properties of CNT/CNF reinforced concrete composite material. This research work shows that further research in this direction may give promising results and can move further toward developing a novel method of concrete mix design.


Antimicrobial stewardship integral to patient care. Institutions with stewardship decrease antibiotic use, cost, and antibiotic-associated infections. However, few efforts have been formally made to address discharge antimicrobial prescribing, even though many patients started on antibiotic therapy in the hospital are prescribed oral antibiotics to complete their regimens.>18 years and were discharged from the hospital with an oral antibiotic prescription. Patients discharged against medical advice, prescribed indefinite prophylactic antimicrobial therapy for legitimate reasons, or discharged to a skilled nursing facility were excluded. The retrospective group evaluated a random sample of patients discharged in 2/2020. The prospective group included patients discharged between 1/2021 – 6/2021. In the prospective group, a clinical pharmacist assessed the indication for antibiotics and pended discharge antibiotic prescriptions for physician review. Antibiotic choice and duration of therapy were based on local and national guidelines.This was an IRB approved, quasi-experimental, pre-post study. Patients were included if they were Patient Screening for Inclusion and ExclusionBreakdown of patients screened, included, and excluded for study86 (53.1%) of 162 retrospective patients from 2/2020 prior to implementation of the program demonstrated were discharged on inappropriate antimicrobial therapy with excessive duration being the principal driver for inappropriateness. In the prospective group of 64 patients, the rate of patients discharged on inappropriate antibiotics decreased to 28.1% (p=0.001). The duration of inappropriate therapy decreased from a mean of 4.6 days to 2.7 days (p=0.001). 45 (70.3%) of 64 prospective pharmacist’s interventions were accepted by providers.Study OutcomesOutcomes including overall appropriate prescribing, appropriate duration, spectrum, frequency, and dose, as well as days of inappropriate therapyLiterature demonstrates that prospective evaluation of discharge antibiotics by a clinical pharmacist is effective in improving appropriateness of discharge antibiotic prescriptions, optimizing duration of outpatient antibiotics as well as reducing unnecessarily broad-spectrum therapy. The prospective results from this study demonstrate that this innovative approach can improve outpatient oral antibiotic prescribing and provide a framework for other institutions to implement similar programs.All Authors: No reported disclosures